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MIDDLE EAST JOURNAL OF ANESTHESIOLOGY
Department of Anesthesiology
American University of Beirut Medical Center
P.O. Box 11-0236. Beirut 1107-2020, Lebanon
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Consultant Editors
Editor-In-Chief:
Ghassan Kanazi
Assem Abdel-Razik
(Egypt)
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Bassam Barzangi
(Iraq)
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Chakib Ayoub
Marie Aouad
Sahar Siddik-Sayyid
Izdiyad Bedran
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Mohammad Seraj
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Abdul-Hamid Samarkandi
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Mohamad Takrouri
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Middle East Journal of Anesthesiology
Vol. 21, No. 3, October 2011
CONTENTS
editorial
Succinylcholine “The Gold Standard” For Rapid-Sequence Induction Of Anesthesia
- Pro & Cons ��������������������������������������������������������������������������������������������������������������������������������������������������������������� Anis Baraka
323
scientific articles
Prospective, Randomized Study To Assess The Role Of Dexmedetomidine In Patients With
Supratentorial Tumors Undergoing Craniotomy Under
�������������������������������������������������������� Rabie Soliman, Amira Hassan, Amr Rashwan and Ahmed Omar
Anesthetic Challenges In Oro-Facial Cleft Repair In Ile-Ife, Nigeria
������������������������������������������������������������������ Anthony Adeneka, Aramide Faponle and Fadekemi Oginni
Comparison Between Ropivacaine 1,5 MG ML-1 Plus Fentanyl 2 MF ML-1 And Ropivacaine
1,5 MG ML-1 Plus Clonidine 1 µg ML-1 As Analgesic Solution After Anterior Cruciate
Ligament Reconstruction: A Randomized Clinical Trial
������������������������������������������������������������������������������������������������� Apostolos Kalakonas, Georgios Kotsovolis,
Omiros Chalkeidis and Christos Triantafyllou
The Influence Of Simulation-Based Physiology Labs Taught By Anesthesiologists On The
Attitudes Of First-Year Medical Studnets Towards Anesthesiology
������������������������������������������������������� Samuel Demaria, Ethan Bryson, Carol Bodian, Yury Khelemsky,
Alan Sim, Andrew Schwartz, Daniel Katz and Adam Levine
Preemptive Analgesic Effect Of Diclofenac: Experimental Study In Rats
�������������������������������������������������������������������������� Antigona Hasani, Marija Soljakova, Muharrem Jakupi
and Serpil Ustalar-Ozgen
Comparison Between Two Phenylephrine Infusion Rates With Moderate Co-Loading For The
Prevention Of Spinal Anaesthesia- Induced Hypotension During Elective Caesarean Section
����������������������������������������������������������������������������������������� Tarek Ansari, Medhat Hashem, Ahmed Hassan,
Ahmed Gamassy and Ayad Saleh
Evaluation Of An Intraoperative Algorithm Based On Near-Infrared Refracted
Spectroscopy Monitoring, In The Intraoperative Decision For Shunt Placement, In Patients
Undergoing Carotid Endarterectomy
������������������������������������������������������������������� Ioannis Zogogiannis, Christos Iatrou, Miltiadis Lazarides,
Theodossia Vogiatzaki, Mitchell Wachtel, Petros Chatzigakis and Vassilios Dimitriou
Effects Of Preoperative Oral Carbohydrates And Trace Elements On Perioperative
Nutritional Status In Elective Surgery Patients
���������������������������������������������������������������������������� Yoshimasa Oyama, Hideo Iwasaka, Keisuke Shiihara,
Satoshi Hagiwara, Nobuhiro Kubo, Yutaka Fujitomi and Takayuki Noguchi
Reduced Hemodynamic Responses To Tracheal Intubation By The Bonfils Retromolar
Fiberscope: A Randomized Controlled Study
����������������������������������������� Abdulaziz Boker, Waleed Almarakbi, Abeer Arab and Adnan Almazrooa
319
325
335
341
347
355
361
367
375
385
M.E.J. ANESTH 21 (3), 2011
eFFecT oF prophylacTic dexameThaSone on nauSea and vomiTinG aFTer laparoScopic
GynecoloGical operaTion: meTa-analySiS
cecorrected in on-line version
������������������������������������������������������������������������������������������������������� Wang Bin, HE Kai-Hua, Jiang Meng-Bi,
397
Liu Chao and Min Su,
eFFecT oF KeTamine on BiSpecTral index durinG propoFol- FenTanyl aneSTheSia: a
randomized conTrolled STudy
cecorrected in on-line version
���������������������������������������������������������������������������������Saikat Sengupta, Simantika Ghosh, Amitava Rudra,
391
P Kumar, Gaurab Maitra, Tanmoy Das
CASE REPORTS
venTilaTion diFFiculTy due To herniaTion oF inFlaTinG TuBe oF The cuFF inSide The
endoTracheal TuBe
���������������������������������������������������������������������������������������������������������������������Oya Yalcin Cok, Melih Cekinmez,
Pinar Ergenoglu and Anis Aribogan
aneSTheSia For ceSarian SecTion in preGnanT Woman WiTh acuTe inTermiTTenT porphyria
and hypoThyroidiSm
���������������������������������������������������������������������������������������������������������������������� Roberto Dumas, Elizabeth Silva,
Marco Antonio Resende, Alberto Pantoja and Antonio Celso Barros
“crime Scene inveSTiGaTion” aT an aneSTheTic cocKTail parTy WiTh aTriovenTricular
diSSociaTion
�������������������������������������������������������������������������������������������������� Christoph Schlimp and Franz Wiedermann
leFT aTrial myxoma WiTh coronary arTery diSeaSe: an unexpecTed preoperaTive FindinG
��������������������������������������������������������������������Madan Maddali, Ahmed Abduraz, Prashanth Panduranga
and Elizabeth Kurian
403
405
409
413
poST-operaTive reSpiraTory complicaTionS aFTer palaToplaSTy in a 19 monTh old Female
WiTh cornelia de lanGe Syndrome: a caSe reporT
����������������������������������������������������������������������������������������������������������������� Brooke Ingram and Elizabeth Frost
419
WhaT iF The epidural caTheTer needS To Be Fixed more Than FiFTeen cenTimeTerS aT SKin?
�������������������������������������������������������������������������������������������������������������������������������������������������������������� Vishal Uppal
423
exTreme inTraoperaTive hyperKalemia in a non dialySiS paTienT underGoinG Kidney
TranSplanTaTion
���������������������������������������������������������������������������������������������������������������� Mia Kazanjian and Steven Neustein
425
SucceSSFul TreaTmenT oF early ropivacaine ToxiciTy WiTh inTralipid in a paTienT WiTh
aTTenTion deFiciT hyperacTiviTy diSorder
����������������������������������������������������������������������������������������������������������������������������������������������������������Achir Al-Alami
427
chronic uSe oF oxyBuTynin and Spinal aneSTheSia: a caSe oF poSToperaTive urinary
reTenTion and hemaTuria
����������������������������������������������������������������������������������������������������������������������������������������������������� Adriano Hobaika
inFilTraTive anGiolipoma oF The necK
������� Abdul-Latif Hamdan, Laurice Mahfoud, Hani Rifai, Charbel Rameh and Nabil Fuleihan
431
433
cardiac arreST durinG elecTive orThopedic SurGery due To moderaTe hypoKalemia
����������������������������������������������������������������������������������������������������������������� Manuel Struck and Andreas Nowak
435
The aneSTheTic manaGemenT oF a paTienT WiTh dorFman- chanarin Syndrome
�������������������������������������������������������������������� Azize Bestas, Esef Bolat, Mustafa Bayar and Omer Erhan
437
linGual Thyroid: a rare cauSe oF diFFiculT inTuBaTion
���������������������������������������������� Maroun Ghabash, Jean-Claude Stephan, May Matta and May Helou
441
320
letter to the editor
Should Surgery Be Cancelled When Surreptitious Cocaine Use Is Discovered Before
Elective Non-Cardiac Surgery?
��������������������������������������������������������� M. Chadi Alraies, Abdul Hamid Alraiyes and Franklin Michota
445
apparatus
Automatic Endotracheal Tube Cuff Inflator And Continuous Pressure Monitor/ Controller
��������������������������������������������������������������������������������������������������Musa Muallem and Mohammad El- Khatib
321
447
M.E.J. ANESTH 21 (3), 2011
EDITORIAL
Succinylcholine “The Gold Standard”
For Rapid-Sequence Induction
Of Anesthesia
- Pro & Cons The neuromuscular effects of succinylcholine (SCh) were described1 by Bovet 1949. The
drug was introduced into clinical anesthesia in the United States by Foldes et al 1952, who stated
that “the advantages of succinylcholine as a muscular relaxant in anesthesiology far outweighed its
disadvantages”2. Even today in the 6th decade of its use, SCh, despite complications, survived as
the “gold standard” for rapid-sequence induction of anesthesia (RSI), against which other relaxants
are compared3. The drug survived, despite the reported complications, because of the unique triad
characterizing its neuromuscular block i.e. rapid onset, profound relaxation and short duration,
which makes succinylcholine the drug of choice for rapid-sequence induction (RSI) of anesthesia
in patients with full stomach, as well as the preferred relaxant for tracheal intubation in patients
with a predicted difficult airway3-5.
This characteristic triad of succinylcholine neuromuscular block can be attributed to the
rapid hydrolysis of SCh by the normal plasma cholinesterase, as well as to its depolarizing action.
In addition, the low molecular weight of SCh, and its simple molecular configuration consisting
of two acetylcholine molecules attached together may contribute to its rapid onset of action by
allowing the drug to pass directly from the blood to the endplate receptors prior to equilibration in
the extracellular fluid.
The hydrolysis of SCh by the normal plasma cholinesterase is very rapid, and the
rate of hydrolysis is proportional to the substrate concentration. This rapid hydrolysis into
succinylmonocholine and choline can allow us to use multiple ED95 doses (up to 5-10 ED95)
which result in a very rapid onset of deep neuromuscular block, without a significant increase in
the duration of action.
The depolarization mechanism of SCh can also contribute to the rapid onset of block since we
need to activate only 10-25% of the endplate receptors in order to achieve depolarization block. In
contrast, non depolarizing relaxants need to block 75-90% of the receptors (i.e. the safety margin)
in order to produce nondepolarizing neuromuscular block. Also, SCh can relax the fast-contracting
muscles such as the vocal cords and the masseters more than the nondepolarizing relaxants which
relax the slow-contracting muscles more than the fast-contracting muscles. In addition, the action
of SCh is actually endplate-muscular and not neuro-muscular block which can result in profound
muscular relaxation6.
In conclusion, SCh stood the test of time as the “Gold Standard” relaxant for rapid-sequence
induction of anesthesia because of its very rapid hydrolysis, its depolarizing mechanism of
block, as well as to its simple and low molecular weight structure which can contribute to the
triad characteristics of SCh block i.e. rapid onset, profound block and short duration of action.
However, “there is no free dinner”. The characteristics contributing to the advantages of SCh as
the “Gold Standard” for rapid sequence induction of anesthesia i.e. the very rapid hydrolysis and
323
M.E.J. ANESTH 21 (3), 2011
324
ANIS BARAKA
its depolarizing action are the same factors that result
in its side effects:
I.
The ultra-short action of SCh in the presence
of normal plasma cholinesterase can change
into a very prolonged block in the presence of
homozygote atypical cholinesterase. This will
be associated with gradual desensitization and
change of block characteristics from depolarizing
block (No tetanic fade and no post-tetanic
facilitation) into phase II block (tetanic fade and
post-tetanic facilitation).
II. The depolarizing action of Sch can result in:
1. Post operative myalgia
2.
Increase of intraocular pressure, intracranial
pressure, intragastric pressure and intra
abdominal pressure
III. The autonomic effects of SCh can result following
the initial dose in sympathomimetic side effects
such as hypertension and tachycardia. In contrast,
repeated doses of SCh may produce vagotonic
bradycardia
IV. In patients having neuromuscular disorders,
depolarization by SCh can be complicated by
serious hyperkalemia, rhabdomyolysis and
malignant hyperthermia7.
Now, is it time to say Good Bye Sux?!
It seems not yet, until we can find an
alternative non-depolarizing relaxant having similar
characteristics i.e. rapid onset, short duration and
profound neuromuscular block. However, because of
the complications that can follow administration of
SCh, I recommend the following:
1.
To avoid SCh whenever contraindicated e.g. in
patients having neuromuscular disorders
2. To use SCh only whenever indicated: e..g
RSI in patients with full stomach4,5,8, and
tracheal intubation in patients having predicted
difficult airway. In addition, SCh as a single
dose, may be indicated in procedures requiring
profound relaxation for a short duration, such as
electroconvulsive therapy, cardioversion, fracture
setting3, and relief of laryngospasm. Also, SCh
is the only relaxant which is effective following
intramuscular injection.
Anis Baraka, MD,FRCA(Hon)
Emeritus Editor-in-Chief
Middle East Journal of Anesthesiology
Department of Anesthesiology
American University of Beirut Medical Center
References
1. Bovet D: Some aspects of the relationship between chemical
constitution and curare-like activity. Annals of the New York
Academy of Science; 1951, 54:407-37.
2. Foldes FF, McNall PG, Borrego-Hinojosa JM: Succinylcholine:
a new approach to muscular relaxation in anesthesiology. New
England Journal of Medicine; 1952, 247:596-600.
3. Lee C: Good bye Suxamethonium. Anaesthesia; 2009, 64 (Supp. 1),
pp. 73-81.
4. Baraka A: Muscle relaxants for rapid-sequence induction of
anesthesia. M E J Anesth; 2004, 17(4):557-568.
5. Baraka A: Rapid onset of suxamethonium block. Br J Anaesth;
1991, 66:733.
6. Baraka A: Neuromuscular block in different species. Acta Anaesth
Scand; 1972, 16:132-139.
7. Baraka A, May J: Anesthesia and Myopathy. Current Opinion in
Anaesthesiology; 2002, 15:371-376.
8. Siddik S, Jalbout M, Baraka A: Rapid sequence induction for
cesarean section. M E J Anesth; 2004, 17(4):569-584.
scientific articles
PROSPECTIVE, RANDOMIZED STUDY TO ASSESS
THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH
SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY
UNDER GENERAL ANAESTHESIA
Rabie Nasr Soliman *, Amira Refaie Hassan*, Amr Madih Rashwan*
and A hmed M ohamed O mar *
Abstract
Background: Preliminary data on the perioperative use of dexmedetomidine in patients
undergoing craniotomy for brain tumor under general anaesthesia indicate that the intraoperative
administration of dexmedetomidine is opioid-sparing, results in less need for antihypertensive
medication, and may offer greater hemodynamic stability at incision and emergence.
Dexmedetomidine, α 2 adrenoceptor agonist used as adjuvant to anaesthetic agents. Relatively recent
studies have shown that dexmedetomidine is able to decrease circulating plasma norepinephrine
and epinephrine concentration in approximately 50%, decreases brain blood flow by directly acting
on post-synaptic α 2 receptors, decreases CSF pressure without ischemic suffering and effectively
decrease brain metabolism and intracranial pressure and also, able to decrease injury caused by
focal ischemia.
Purpose: This prospective, randomized, double-blind study was designed to assess the
perioperative effect of intraoperative infusion of dexmedetomidine in patients with supratentorial
tumors undergoing craniotomy under general anaesthesia.
Methods: Forty patients with CT- scanning proof of supratentorial tumors. The patients were
classified equally into 2 groups (twenty patients in each group). Group A: - The dexmedetomidine
was given as a bolus dose of 1 µg/kg in 20 minutes before induction of anaesthesia, followed by a
maintenance infusion of 0.4 µg/kg/hr. The infusion was discontinued when surgery ended. Group
B: - The patients received similar volumes of saline.
Results: The heart rate and mean arterial blood pressure, decreased in patients of group A
(dexmedetomidine group) more than group B (placebo group) with significant statistical difference
between the two groups (P-value <0.05). No significant statistical difference between the two
groups regarding the central venous pressure and arterial partial pressure of Carbon Dioxide
(P-value >0.05). The intraoperative end-tidal sevoflurane (%) in patients of group A less than in
patients of group B (P-value <0.05).The intracranial pressure decreased in patients of Group A
more than group B (P-value <0.05). The Glasgow coma scale (GCS) improved in patients of group
A and deteriorated in patients of Group B with significant statistical difference between the two
groups (P-value <0.05).The Total fentanyl requirements from induction to extubation of patients
*
Lecturer of anaesthesia, Department of anaesthesia and neurosurgical ICU, Faculty of medicine, Cairo University, Egypt.
E-mails: [email protected], [email protected],[email protected]
325
M.E.J. ANESTH 21 (3), 2011
326
increased in patients of group B more than in patients
of group A (P-value <0.05). The total postoperative
patients' requirements for antiemetic drugs within
the 2 hours after extubation decreased in patients
of group A more than group B (P-value <0.05). The
postoperative duration from the end of surgery to
extubation decreased significantly in patients of group
A more than group B (P-value <0.05). The total urine
output during the duration from drug administration to
extubation of patients increased in patients of group A
more than group B (P-value <0.05).
Conclusions: Continuous intraoperative infusion
of dexmedetomidine during craniotomy for supratentorial
tumors under genera‑l anaesthesia maintained the
haemodynamic stability, reduced sevoflurane and
fentanyl requirements, decreased intracranial pressure,
and improved significantly the outcomes.
Key words: Dexmedetomidine - supratentorial
Tumors - Craniotomy – Sevoflurane – Fentanyl Intracranial pressure - Neurosurgical intensive care
unit.
Introduction
The intense surgical stimuli associated with
craniotomy
frequently
engender
sympathetic
activation and marked changes in systemic arterial
pressure, CBF, and ICP. Cerebrovascular responses
may result in elevated ICP and reduction in cerebral
perfusion pressure, especially in patients with impaired
autoregulation and compromised cerebral compliance.
Perioperative hypertension in neurosurgical patients
is associated with intracranial bleeding and prolonged
hospital stay1. Thus, the prevention and control of the
hemodynamic response to nociceptive stimuli are of
utmost importance to preserve cerebral homeostasis
in neurosurgical patients. The antinociceptive,
sympatholytic, and anaesthesia-sparing effects
of α 2-agonists are well documented2,3. This
spectrum of properties would be consistent with the
important goals during neurosurgical anesthesia of
intraoperative hemodynamic stability and modulation
of intraoperative sympathetic responses to attenuate
cerebrovascular and myocardial risks and avoid
intracranial hemorrhage, and to allow immediate
neurological evaluation upon emergence4-6.
R. N. Soliman et. al
Alpha-2-Adrenoreceptors are a subgroup of
noradrenergic receptors distributed broadly within
and outside the CNS. Alpha-2-Receptors in the brain
are concentrated primarily in the pons and medulla,
areas involved in transmitting sympathetic nervous
system activation from higher brain centers to the
periphery. Stimulation of presynaptic α 2-receptors
reduces norepinephrine release, and activation of
postsynaptic α 2-receptors hyper-polarizes neural
membranes. Interaction between these receptors and
norepinephrine thus acts as an inhibitory feedback loop
in which excessive norepinephrine release actually
reduces further release of the same neurotransmitter7,8.
In the spinal cord, α 2-adrenergic receptors are
located postsynaptically in the dorsal horn, and their
stimulation inhibits nociceptive signal transmission9.
In the periphery, α 2-receptors are found on vascular
smooth muscle, in which their activation results in
vasoconstriction8. Injectable dexmedetomidine was
approved by the FDA in 1999 for use in the intensive
care unit. Since its approval and clinical use, it has been
utilized for sedation during surgery and postoperative
periods10. Dexmedetomidine (DEX) is a highly selective
α 2-adrenoreceptor agonist recently introduced to
anaesthesia practice. It produces dose-dependent
sedation, anxiolysis, and analgesia (involving spinal
and supraspinal sites) without respiratory depression3,11.
DEX enhances anaesthesia produced by other
anaesthetic drugs and decreases blood pressure by
stimulating central alpha2 and imidazoline receptors12,13.
The use of DEX in neuroanaesthesia generate a
reduction in the sympathetic tone and a decrease in
peripheral noradrenaline release reducing hypertensive
responses to neurosurgical patient stimulation during
catheterization and head pin holder application14,15.
The aim of our study to assess the perioperative effect
of dexmedetomidine in patients with supratentorial
brain tumors undergoing craniotomy under general
anaesthesia.
Patients and methods
After obtaining informed consent and approval
of local ethics and research committee, forty patients
in Kasr El-Aini hospital, Cairo University with CTscanning proof of supratentorial brain tumor were
PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH
SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA
scheduled for craniotomy under general anaesthesia.
The exclusion criteria were as follows: pregnant or
nursing woman, morbid obesity, preoperative heart
rate <45 beats/min, second or third degree AV block,
antihypertensive medication with a-methyldopa,
clonidine or other α 2-adrenergic agonist during
the 28 days before scheduled study, EF <30% sleep
problems, psychiatric diseases and renal or hepatic
diseases. The surgery in all patients of both groups
was elective.
On arrival to operating room and under local
anaesthesia, the central venous line was inserted
in subclavian vein, left radial arterial cannulation
was done and the intracranial pressure (ICP) was
monitored by ventriculostomy catheter placed by
the neurosurgeon through a burr hole into the lateral
ventricle of the brain, preoperatively under local
anaesthesia. Electronic monitoring of ICP was done by
utilizing saline-filled tubing with a pressure transducer.
The transducer should be zeroed as the same for
arterial pressure (at the external auditory meatus)
before induction of anaesthesia. The patients were
randomized into 2 groups (twenty patients in each
group). Group A; The dexmedetomidine group (The
dexmedetomidine was supplied in 2-mL ampoules of
100 µg/ml concentration (Abbott, Chicago, IL, USA),
and this volume was diluted with 98 mL of normal
saline to yield a final concentration of 2 µg/ml), the
patients were premedicated with dexmedetomidine
(1 µg/kg) in 20 minutes followed by a maintenance
infusion of 0.4 µg/kg/hr. The infusion was discontinued
when surgery ended. Group B; The placebo group, the
patients were received similar volumes of saline. All
patients should be preoxygenated, and then intravenous
thiopental (3-5mg/kg) followed by fentanyl (3-5µg/
kg) and atracurium 0.5 mg/kg as a bolus dose over
30 sec, while controlled hyperventilation with 100%
oxygen was instituted. Before intubation an additional
bolus of thiopental (2-3 mg/kg) was given. After
induction, controlled mechanical ventilation was
adjusted to maintain PaCO2 between 30 and 35 mmHg.
The anaesthesia was maintained with sevoflurane 0.5
to 3%, atracurium was administered by intravenous
infusion at a rate of 0.5 mg/kg/hr and fentanyl infusion
(1 µg/kg/hr). Bolus doses of fentanyl (1-2 µg/kg)
were given to control the increased heart rate and
systemic hypertension during surgery according to the
327
need. Fluid resuscitation and maintenance fluids were
provided with glucose free iso-osmolar crystalloid
solutions 2-3 ml/kg/hr, and replacement of blood
loss and urine output. Drugs such as corticosteroids,
diuretics (1-2 mg/kg) and mannitol (1gm/kg) were
given according to the need. The monitors used
during anaesthesia included ECG, Pulse oximetry,
non invasive blood pressure, invasive blood pressure
from left radial artery cannula, continuously core
temperature from nasopharyngeal probe, central venous
pressure from subclavian vein, end tidal CO2, endtidal concentration of sevoflurane, urine output from
urinary catheter every one hour, intracranial pressure
(ICP) and arterial blood gases (ABG were done by
AVL GRAZ OMNI 6 Modular system). Neurological
assessment was done for all patients by Glasgow coma
scale before induction of anaesthesia and after 2 hours
of extubation. At the end of surgery, all patients were
transferred to neurosurgical intensive care unit and
monitored by the same monitors used intraoperatively.
The data of patients was collected at the following
timepoints, T0: The reading before administration
of the study medication, T1: The reading after
induction of anaesthesia, T2: The reading 2 hours after
administration of study medication, T3: The reading at
the of end surgery, T4: The reading on admission to the
ICU, T5: The reading before extubation and T6: The
reading 2 hours after extubation.
The Statistical Paragraph in Material and
Methods
Data were statistically described in terms of
range; mean ± standard deviation (± SD), median,
frequencies (number of cases) and relative frequencies
(percentages) when appropriate. Comparison of
quantitative variables between the study groups was
done using Mann Whitney U test for independent
samples. For comparing categorical data, Chi square
(χ2) test was performed. Exact test was used in
stead when the expected frequency is less than 5.
A probability value (p value) less than 0.05 was
considered statistically significant. All statistical
calculations were done using computer programs
Microsoft Excel version 7 (Microsoft Corporation,
NY, USA) and SPSS (Statistical Package for the Social
M.E.J. ANESTH 21 (3), 2011
328
Science; SPSS Inc., Chicago, IL, USA) statistical
program for Microsoft Windows.
Results
There were no significant statistical differences
regarding the demographic data of patients (table 1).
The types of supratentorial brain tumors in patients
were similar as in (table 1).The heart rate (table 2 and
fig. 1) and mean arterial blood pressure (table 3 and
fig. 2) decreased in patients of group A more than in
patients of group B with significant statistical difference
between the two groups (P<0.05). Two patients of
group A and Three patients of group B were received
incremental doses of atropine(0.5 mg) and ephedrine
(5 mg) as the heart rate decreased below 50 bpm and
the mean arterial blood pressure decreased below
60mmHg (table 4). One patients of group A and four
patients of group B were associated with elevated heart
rate and mean arterial blood pressure and controlled
by incremental doses of fentanyl and esmolol in
addition to nitroglycerine infusion after opening of
the dura matter (table 4). The central venous pressure
decreased in patients of both groups, but there was
no significant statistical difference between the two
groups (table 5and figure 3). There was no significant
statistical difference between the two groups regarding
the arterial partial pressure of Carbon Dioxide (table
6 and fig. 4). The intracranial pressure decreased in
patients of group A more than group B with significant
statistical difference between the two groups (table 7
and fig. 5). The Glasgow coma scale (GCS) improved
in patients of group A and deteriorated in patients of
group B with significant statistical difference (P<0.05)
between the two groups (table 8 and fig. 6). During
extubation the conscious level was not fine in one
patient of group A and four patients of group B. There
was no significant statistical difference between the two
groups regarding duration of the surgical procedures.
Regarding the end-tidal sevoflurane % (table 9), there
was significant statistical difference between the two
groups (P<0.05). The total fentanyl requirements from
induction to extubation of patients increased in patients
of group B to control the elevated heart rate and arterial
blood pressure more than in patients of group A with
significant statistical difference (P<0.05) between the
two groups (table 9). The total postoperative patients
R. N. Soliman et. al
requirements for antiemetic drugs (metoclopramide
and ondansetron) within the 2 hours after extubation
decreased in patients of group A more than group B
with significant statistical difference (P<0.05) between
the two groups (table 89). The postoperative duration
from the end of surgery to extubation (table 9) decreased
significantly in patients of group A more than group B
with significant statistical difference between the two
groups (P-value <0.05). The total urine output during
the duration from drug administration to extubation
of patients increased in patients of group A more than
group B with significant statistical difference between
the two groups (table 9).
Table 1
Demographic data and types of supratentorial brain tumors in
patients. Values are expressed as mean (SD) or %
Item
Group A
( n= 20)
Group B
( n= 20)
P-value
Age ( year)
47.10 (13.345 ) 44.00 (14.220 )
0.579
Weight (kg)
82.10 (11.229 ) 82.80 (12.007 )
0.912
Sex (Male/Female)
9/11
12/8
40
30
Meningioma
40
45
Astrocytoma
20
25
Glioma
Group A: Dexmedetomidine group and Group B: Placebo group.
Table 2
Heart rate (bpm) in patients. Values are expressed
as mean (SD)
Item
Group A
(n = 20)
Group B
(n = 20)
P-value
T0
94.90 (6.887)
91.90 (5.859)
0.315
T1
T2
T3
T4
83.80 (5.453)†
73.60 (3.893)†
73.40 (3.777)†
73.40 (3.098)†
92.80 (2.616)+
91.50 (4.116)+
90.60 (5.016)+
90.30 (4.228)+
0.001*
0.000*
0.000*
0.000*
T5
73.60 (2.797)†
89.10 (5.493)+
0.000*
†
+
T6
73.20 (2.530)
88.80 (6.494)
0.000*
Group A: Dexmedetomidine group and Group B: Placebo group.
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU.T5: The reading before extubation. T6: The reading 2
hours after extubation.
* Statistically significant (P-value < 0.05) Group A versus
Group B.
† P<0.0.05 versus baseline.
+ Statistically insignificant (P-value >0.05).
PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH
SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA
Fig. 2
The mean arterial blood pressure (mmHg) of patients in the
two groups
Fig. 1
The heart rate of patients in the two groups
Mean arterial blood pressure of patients
Group A
Group B
T0
T1
T2
T3
T4
T5
T6
Mean arterial blood pressure
of patients ( mmHg )
Heart rate of patients ( bpm )
Heart rate of patients
100.00
90.00
80.00
70.00
60.00
50.00
40.00
30.00
20.00
10.00
0.00
Timepoints ( hours )
Table 3
Mean arterial blood pressure (mmHg) of patients. Values are
expressed as mean (SD)
Group A
Group B
(n = 20)
(n = 20)
T0
94.70 (8.957)
93.90 (8.863)
0.739
T1
90.30 (8.795)
99.70 (7.790)
0.019*
T2
86.90 (7.564)†
96.80 (5.692)+
0.003*
T3
85.00 (6.549)†
96.10 (5.195)+
0.001*
T4
85.30 (5.889)†
94.00 (4.137)+
0.002*
T5
84.00 (6.037)†
84.00 (6.037)†
0.000*
T6
83.00 (4.243)†
92.60 (3.950)+
0.000*
P-value
Group A: Dexmedetomidine group and Group B: Placebo group.
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU.T5: The reading before extubation. T6: The reading 2
hours after extubation.
* Statistically significant (P-value < 0.05) Group A versus
Group B.
† P<0.0.05 versus baseline.
+ Statistically insignificant (P-value >0.05).
Item
HR<50bpm
MAP<60 mmHg
HR>100bpm
120.00
100.00
80.00
Group A
60.00
Group B
40.00
20.00
0.00
T0
T0: baseline, T1: after induction, T2: 2 hours after administration
of study medication, T3: at the end of surgery, T4: on admission
to the ICU, T5: before extubation and T6: 2 hours after
extubation. Group A: Dexmedetomidine group and Group B:
Control group.
Item
329
T1
T2
T3
T4
T5
T6
Timepoints ( hours )
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU. T5: The reading before extubation. T6: The reading 2
hours after extubation.
Group A: Dexmedetomidine group and Group B: Placebo
group.
Table 5
Central venous pressure (mmHg) of patients. Values are
expressed as mean (SD)
Item
Group A
Group B
P-value
(n = 20)
(n = 20)
T0
13.00 (1.155)
13.10 (1.197)
0.853
T1
12.40 (0.966)
1 2.50 (1.080)
0.796+
T2
9.90 (0.876)
10.30 (1.160)
0.481+
T3
9.00 (0.812)
9.80 (0.919)
0.075+
T4
8.80 (0.915)
9.60 (0.966)
0.105+
T5
9.50 (0.962)
9.30 (0.823)
0.684+
T6
9.00 (0.972)
9.00 (0.816)
1.000+
Group A: Dexmedetomidine group and Group B: Placebo
group.
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU.T5: The reading before extubation. T6: The reading 2
hours after extubation.
+ Statistically insignificant (P-value >0.05).
Table 4
Intraoperative drugs for haemodynamic disturbances
Management
Group A (n = 20)
Group B (n = 20)
2 patients
3 patients
Atropine 0.5 mg (Incremental doses)
2 patients
3 patients
Ephedrine 5-10mg (Incremental doses)
1 patients
4 patients
- Esmolol 0.mg/kg (Incremental doses) or infusion 50-200 μg /kg/
min if needed
- Fentanyl 50-100μg(Incremental doses)
MAP>100 mmHg 1 patients
4 patients
- Nitroglycerine0/5-10 μg /kg/min after opening of dura matter or
- Fentanyl 50-100μg(Incremental doses)
Group A: Dexmedetomidine group and Group B: Placebo group.
HR: Heart rate MAP: mean arterial blood pressure.
M.E.J. ANESTH 21 (3), 2011
R. N. Soliman et. al
Fig. 3
The central venous pressure (mmHg) of patients
in the two groups
Fig. 4
The arterial partial Pressure of Carbon Dioxide PaCO2
(mmHg) of patients in the two groups
Central venous pressure of patients
Arterial partial pressure of Carbon dioxide ( PaCO2 ) of patients
14.00
12.00
10.00
8.00
Group A
6.00
Group B
4.00
2.00
0.00
T0
T1
T2
T3
T4
T5
Arterial partial pressure of
CO2 (mmHg )
Central venous pressure of
patients ( mmHg )
330
37.00
36.00
35.00
34.00
Group A
33.00
Group B
32.00
31.00
30.00
29.00
T0
T6
T1
T2
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU. T5: The reading before extubation. T6: The reading 2
hours after extubation.
Group A: Dexmedetomidine group and Group B: Placebo
group.
Table 6
Arterial partial Pressure of Carbon Dioxide
PaCO2 (mmHg) of patients. Values
are expressed as mean (SD)
Item
Group A
Group B
(n = 20)
(n = 20)
T3
T4
T5
T6
Timepoints ( hours )
Timepoints ( hours )
P-value
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication. T3: The
reading at the end of surgery. T4: The reading on admission to
the ICU. T5: The reading before extubation. T6: The reading 2
hours after extubation.
Group A: Dexmedetomidine group and Group B: Placebo
group.
Table 7
Intracranial pressure (mmHg) of patients.
Values are expressed as mean (SD)
Item
Group A
Group B
(n = 20)
(n = 20)
P-value
T0
22.30 (3.057)
22.10 (2.807)
0.739
T1
20.70 (2.669)
21.20 (2.300)
0.019
T0
35.80 (3.910) 35.50 (3.894)
0.315
T2
15.60 (1.578)
†
18.90 (1.792)
0.003*
T1
31.80 (1.687) 31.90 (1.595)
0.143+
T3
13.30 (1.636)†
17.30 (1.767)
0.001*
T2
32.80 (1.676) 33.10 (1.197)
0.089+
T4
12.40 (1.265)†
16.40 (1.897)†
0.002*
T3
34.90 (1.197) 34.80 (0.789)
0.912+
T5
11.80 (0.919)†
15.70 (1.636)†
0.000*
T4
34.90 (2.601) 35.50 (1.354)
0.529+
T6
10.80 (1.135)†
15.10 (1.792)†
0.000*
T5
36.50 (0.994) 36.30 (1.160)
0.579+
T6
35.60 (1.265) 36.10 (1.663)
0.435+
Group A = Dexmedetomidine group and Group B = Control
group.
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU.T5: The reading before extubation. T6: The reading 2
hours after extubation.
+ Statistically insignificant (P-value >0.05).
Group A: Dexmedetomidine group and Group B: Placebo
group.
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU. T5: The reading before extubation. T6: The reading 2
hours after extubation.
+ Statistically insignificant (P-value >0.05).
* Statistically significant (P-value <0.05) Group A versus Group
B.
† P<0.0.05 versus baseline.
PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH
SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA
Fig. 5
The intracranial pressure (mmHg) of patients in the two
groups
Intracranial pressure of
patients ( mmHg )
25.00
20.00
15.00
Group A
10.00
Group B
5.00
0.00
T0
T1
T2
T3
T4
T5
T6
Timepoints ( hours )
T0: The reading before administration of the study medication.
T1: The reading after induction of anaesthesia. T2: The reading
2 hours after administration of study medication.T3: The
reading at the end of surgery.T4: The reading on admission to
the ICU. T5: The reading before extubation. T6: The reading 2
hours after extubation.
Group A: Dexmedetomidine group and Group B: Placebo
group.
Table 8
Glasgow coma scale (GCS) of patients. Values are expressed
as mean (SD)
Timepoints
Group A
(n = 20)
Group B
(n = 20)
P-value
T0
12.10 (1.69)
12.20 (1.73)
1.000
T6
13.40 (1.31)
11.60 (1.34)
0.011*
Group A: Dexmedetomidine group and Group B: Placebo group.
T0: Glasgow coma scale before administration of the study
medication and T6: Glasgow coma scale 2 hours after
extubation.
* Statistically significant (P-value <0.05) Group A versus Group B.
Fig. 6
Glasgow coma scale (GCS) of patients in the two groups
Glasgow coma score ( GCS ) of patients
Glasgow coma score / 15
14.00
13.50
13.00
12.50
Group A
12.00
Group B
11.50
11.00
10.50
GCS before surgery
Table 9
Intraoperative and postoperative data. Values
are expressed as mean (SD) or %
Item
Intracranial pressure ( ICP ) of patients
GCS after surgery
Timepoints
T0: Glasgow coma scale before administration of the study
medication and T6: Glasgow coma scale 2 hours after
extubation. Group A: Dexmedetomidine group and Group B:
Placebo group.
331
Group A
(n = 20)
Group B
(n = 20)
P-value
Surgical duration
239.3 (79.25)
236.1
0.1+
(min)
(82.51)
End-tidal
1.18 (0.209)
2.18
0.001*
sevoflurane (%)
(0.477)
Total fentanyl doses
440.00
602.00
0.000*
(µg)
(42.164)
(72.847)
Patients'
50.0%
100.0%
0.016*
metoclopramide
requirement %
Patients'
30.0%
80.0%
0.035*
ondansetron
requirement %
Duration before
41.40 (6.310)
87.00
0.001*
extubation (min)
(16.533)
Total fentanyl doses
440.00
602.00
0.000*
(42.164)
(72.847)
Group A: Dexmedetomidine group and Group B: Placebo group.
* Statistically significant (P-value <0.05) Group A versus Group B.
+ Statistically insignificant (P-value >0.05).
Discussion
The concept of neuroanaesthesia includes several
principles, the haemodynamic stability perioperatively
being one of utmost importance. During surgery,
abrupt increases in arterial blood pressure may cause
bleeding or edema in the operating field. Low arterial
pressures on the other hand predispose the patients
to cerebral ischaemia, because autoregulation of the
cerebral blood flow (CBF) is often impaired near
tumors or traumatized areas1. High concentrations
of volatile anaesthetics can blunt the carbon dioxide
response and render CBF pressure passively16. The
haemodynamic responses to intracranial surgery are
most often elicited at the beginning or the end of
the procedure. Similarly, the manipulation of certain
structures within the brain may produce cardiovascular
changes. After surgery, hypertension may predispose
the patient to postoperative intracranial haematoma1.
Dexmedetomidine is a highly selective α2agonist that has been shown to have sedative, analgesic
and anaesthetic sparing effects17-22.
We investigated the effects of dexmedetomidine
in neurosurgical patients in an attempt to find a
clinically feasible combination of anaesthetics that
M.E.J. ANESTH 21 (3), 2011
332
would ensure perioperative haemodynamic stability
and fast recovery without respiratory depression.
Such combination would reduce the required volatile
anaesthetics, narcotics, sedatives and decrease the risk
of affecting cerebral autoregulation.
The present study showed that the
dexmedetomidine significantly attenuated the
haemodynamic responses to laryngoscopy, intubation,
Mayfield three-pin head holder application surgical
stimulation and extubation in patients undergoing
supratentorial surgery and to control the haemodynamic
responses in patients of the control group, higher
doses of sevoflurane, fentanyl and esmolol were used
before opening of the dura in addition to nitroglycerine
after opening of the dura. In some earlier studies,
oral
clonidine
(Alpha2-agent)
premedication
provided attenuation of the hypertensive response to
laryngoscopy, intubation and head holder application
in patients undergoing supratentorial surgery23,24. In
patients undergoing general or gynaecological surgery,
numerous studies have shown that dexmedetomidine
blunts the cardiovascular responses to intubation25-27.
Other studies shown that the haemodynamic responses
to emergence from anaesthesia and extubation are
blunted with dexmedetomidine28,29, and the centrally
mediated sympatholytic effect has continued well into
the postoperative period28.
The intracranial pressure decreased significantly
with dexmedetomidine group than in patients of the
control group as the concentration of sevoflurane
decreased and urine output increased in spite of fixed
doses of diuretics. Many studies were done by to evaluate
the effect of dexmedetomidine on the intracranial
pressure and concluded that the dexmedetomidine
decreased the intracranial pressure by the inhibition
of the hypercapnic cerebral vasodilation30, and its
potent venous vasoconstriction31. The extubation was
happened more quickly in patient of group A and was
R. N. Soliman et. al
statistically significant in comparison to the patients
in the group B. It may, however, reflect the lack
of respiratory depression of dexmedetomidine and
the uses of low doses of sevoflurane and fentanyl32.
Dexmedetomidine has been shown to have minimal
effects on respiration33,34, and ventilatory weaning
and tracheal extubation has been successfully
carried out in critically ill patients under continuing
dexmedetomidine sedation35.
The dose of fentanyl decreased significantly in
group A in comparison to group B. A study done by
Arain SR et al and Venn RM, et al who concluded
that dexmedetomidine has been shown to consistently
reduce opioid requirements by 30 to 50%36,37.
The requirement for antiemetic drugs decreased
in the group A as the doses of fentanyl and sevoflurane
were decreased in comparison to the group B or due
to the decreased intracranial pressure. A study done by
Scott F et al involving patients undergoing abdominal
hysterectomy and concluded that postoperative nausea
was reduced by 77.5% when dexmedetomidine was
employed as an intraoperative anesthetic adjuvant38.
The amount of urine increased significantly in
group A and this one of the factors that leads to decrease
in the ICP. Many studies were done and showed that the
dexmedetomidine seems to induce diuresis by ability
to reduce efferent sympathetic outflow of the renal
nerve39, in addition, dexmedetomidine has been shown
to suppress antidiuretic hormone, with a resulting
diuretic effect40, and finally, dexmedetomidine
increases secretion of atrial natriuretic peptide,
resulting in natriuresis41.
Acknowledgements
All anesthetists have the authority to read the
paper.
PROSPECTIVE, RANDOMIZED STUDY TO ASSESS THE ROLE OF DEXMEDETOMIDINE IN PATIENTS WITH
SUPRATENTORIAL TUMORS UNDERGOING CRANIOTOMY UNDER GENERAL ANAESTHESIA
333
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ANESTHETIC CHALLENGES IN ORO-FACIAL
CLEFT REPAIR IN ILE-IFE, Nigeria
Anthony Taiwo Adenekan*, Aramide Folayemi Faponle**,
Fadekemi Olufunmilayo Oginni***
Abstract
Background and Methods: A retrospective review of all patients with oro-facial lip defects
operated at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria over an 18 month
period was undertaken with a view to determine: the pattern of presentation; associated clinical
problems and congenital anomalies; perioperative complications; anaesthetic techniques used and
outcomes; and the determinants of outcome.
Results: Of the 80 patients treated, 74 were managed under general anaesthesia but the case
records of only 60 (81%) of these patients were available for review. The ages ranged between
3 months and 59 years. The male to female ratio was 1:1. Eighty percent of all cases studied
were cleft lip (CL) ± cleft palate (CP). Of these, 65% were left sided CL, 23% were right sided
while 12% were bilateral. All patients had ASA score 1 or 2 at the time of surgery. Halothane in
O2 induction was employed in 60% of the patients while 40% had IV induction. Intubation was
facilitated with muscle relaxant in 63.3% of these patients. Naso-tracheal intubation was performed
in 82% of all cleft palate repairs. Preoperative complications were encountered in 18% of the
patients. Associated congenital anomalies were noted in 5% of the cases. One case each of difficult
intubation and failed intubation were encountered. Intra-operative dysrrhythmia was noted in 5%
of cases; no life-threatening complication was encountered peri-operatively.
Conclusions: There is a dramatic increase in the number of patients presenting for care due
to improved awareness of the population. Peri-operative attention to detail is essential in handling
the challenges posed by the condition.
Introduction
Oro-facial cleft is a common congenital deformity with a worldwide incidence of 1 in 7-800
live births1. The actual aetiology is largely unknown2. Oro-facial cleft is associated with facial
disfigurement, feeding difficulty, and speech and dental development problems. It is accompanied
with significant psychosocial consequences. However, patients with oro-facial cleft can achieve
their ultimate potential through aesthetic and functional treatment. In recent times, surgical
treatment of patients with oro-facial cleft has been facilitated by the SmileTrain, USA globally.
This has led to an increasing number of patients presenting for care in Nigeria.
*
**
***
MBBS, DA, FWACS, Consultant, Dept. of Anaesthesia.
BSc, MBChB, FWACS, FMCA, Consultant, Dept. of Anaesthesia.
BChD, FMCDS, FWACS, Consultant, Dept. of Oral and Maxillofacial Surgery.
Correspondence to: Dr. A.T. Adenekan, Department of Anaesthesia, Obafemi Awolowo University, Ile-Ife, Nigeria. Tel:
+2348033855903, E-mail: [email protected]
335
M.E.J. ANESTH 21 (3), 2011
336
A. T. Adenekan et al.
The occurrence of these congenital defects in
Nigeria has been documented by previous reports3,4. Orofacial cleft can be repaired within the first year of life.
In limited resourced economies, many of the patients
present much later probably due to ignorance, poverty,
and limited available material and human resources5,6.
However, little is known about the anaesthetic
challenges in oro-facial cleft repair in Nigeria.
of attempts, intubation aids, outcome and analgesic
used were noted. Details of intraoperative monitoring,
critical incidents, recovery room complications,
and postoperative complications were documented.
Data were analysed using SPSS version 12.0.1 and
summarized into tables and relationships tested using
the Chi-square test at 5% level of significance.
This study was undertaken to assess: the pattern
of presentation of oro-facial cleft; associated clinical
problems and congenital anomalies; perioperative
complications; anaesthetic techniques used and
outcomes; and the determinants of outcome.
Results
Method
A retrospective review of anaesthesia for all orofacial cleft repairs performed over an 18 month period
(between January 2006 to June 2007) at the Obafemi
Awolowo University Teaching Hospital, Ile-Ife, was
undertaken. The hospital is a tertiary health facility
located in South-western Nigeria with referral from
over 200 kilometres radius.
The theatre records were reviewed to identify all
cases of oro-facial clefts operated during the period.
The case records of the patients identified were then
reviewed.
The data retrieved include demographic details
of the patients, diagnosis (including the type of cleft,
medical diagnosis, additional craniofacial deformities),
proposed surgery, preoperative packed cell volume
(PCV), pre-induction vital signs, premedication used,
anaesthetic technique, induction technique and relaxant
use for intubation. Also, the intubation route, number
Eighty patients were treated during the study
period. They were all Nigerians residing in Ile-Ife and
its environs. Of these, seventy four patients (92.5%)
were managed under general anaesthesia (GA) while
the rest (7.5%) were operated under local anaesthesia
(LA). However, the case records of only sixty patients
(81%) managed under GA were available for review at
the time of this study.
Table 1 shows the age distribution of the patients.
The ages ranged between 3 months and 59 years with
a mean of 10.08 ± 11.60 years. Majority (86.7%) of
the patients presented after the first year of life, while
7 patients (11.7%) presented after the age of 20 years.
No gender predilection was observed.
Table 1
Age and Gender Distribution of Patients
Age
1-4 Months
5-12 Months
1-10 Years
10-20 Years
>20 Years
Total
Male
No (%)
Female
No (%)
No of Pts
No (%)
%
3
2
19
3
3
30
0
3
14
9
4
30
3 (5.0)
5
33
12
7
60
5.0
8.3
55.0
20.0
11.7
100.0
Table 2
Cleft Deformity type by Gender
Type of Cleft
Gender
Side
Male
No (%)
Female
No (%)
Right
No (%)
Left
No (%)
Total (%)
Cleft lip only
17 (54.8)
14 (45.2)
7 (22.6)
24 (77.4)
31 (51.7)
Cleft lip and palate
7 (63.6)
4 (36.4)
4 (36.4)
7 (63.6)
11 (18.3)
Cleft palate alone
6 (54.5)
5 (45.5)
-
-
11 (18.3)
-
1
-
-
1 (1.7)
Bilateral Transverse
Bilateral cleft Lip
Total
-
6
-
-
6 (10)
30 (50%)
30 (50%)
11(26.2%)
31(73.8%)
60 (100)
ANESTHETIC CHALLENGES IN ORO-FACIAL CLEFT REPAIR IN ILE-IFE, Nigeria
Type of defect by gender in this series is shown
in Table 2. Isolated cleft lip, isolated cleft palate and
combined cleft lip and palate were commoner in
males than females (17: 14, 7:4, and 6:5 respectively).
Bilateral cleft lip (n = 6) and bilateral transverse cleft
lip (n = 1) observed in this series were exclusively
in females. However, the difference observed is not
statistically significant (p = 0.43).
The PCV ranged from 26-44% and mean was
32.78 ± 3.76%. Table 3 shows the pattern of distribution
of medical complications among the patients. Preoperative complications were noted in 18% of cases
(n = 11). Anaemia was the commonest, occurring in
11.7% (n = 7). One 6 month old child with cleft lip had
severe anaemia and was transfused before presentation
for anaesthesia. Others were under-nutrition (5%, n
= 3), delayed developmental milestone with growth
retardation (1.7%, n = 1), upper respiratory tract
infection (1.7%, n = 1) and chronic suppurative otitis
media (1.7%, n = 1). Besides the cleft palate patient
with chronic suppurative otitis media and another
with anaemia, the remaining patients (n = 9) were
cases of cleft lip with or without associated cleft
palate. However, there was no statistically significant
relationship between the type of oro-facial cleft and
medical complications (p = 0.88).
Table 3
Distribution of medical complications among oro-facial cleft
patients
Clinical complications
Cleft lip ±
Cleft
cleft palate
palate
Anaemia
3
1
Anaemia + Transfused before
surgery
1
-
Anaemia + Severe undernutrition
2
-
Under-nutrition
1
-
Delayed dev milestone +
growth retardation
1
-
Upper Respiratory Tract
Infection
1
-
Chronic suppurative otitis
media
-
1
Nil
41
8
Total
50
10
337
Three patients (5%) had associated congenital
abnormalities. Two of these (3.4%) were craniofacial
abnormalities while one (1.7%) was cardiovascular.
One of the patients with craniofacial abnormalities
had Wolf-Hirschhorn syndrome7 (- a one year old
girl with a combination of microcephaly, low set
ears, hypertelorism, growth retardation, delayed
developmental mile stones in addition to a right
complete cleft lip and incomplete cleft palate). The
other was a case of complete cleft palate with lower lip
pits. The third patient had congenital cardiac disease
(membranous ventricular septal defect) with left
complete cleft lip.
All patients were either ASA physical status-1
(77%) or ASA-2 (23%) at the time of surgery. Eighty
five percent had IV atropine premedication to dry
their airway; six (10%) patients who had intravenous
induction with ketamine also had IV diazepam
premedication in addition.
Induction with halothane in oxygen was
employed in 60% of the patients while 40% had
intravenous induction (thiopentone or ketamine). All
cases had endotracheal intubation with halothane ±
N2O in O2 for maintenance. Intubation was facilitated
with muscle relaxant (suxamethonium) in 63.3% of
these patients. Naso-tracheal intubation was performed
in 18% of all cases (but 82% of all cleft palate repairs).
Respiration was assisted in all patients less than 2
years old. Ketamine anaesthesia either in form of
intermittent boluses or total intravenous anaesthesia
was not employed in this case series.
One case of difficult intubation was noted
in a 5-month old boy with cleft lip. After multiple
unsuccessful attempts during the initial presentation,
he was rescheduled and successfully intubated at
representation for anaesthesia and surgery two weeks
later. Failed intubation occurred in one patient. This
was in the child with Wolf-Hirschhorn syndrome. The
patient has not been represented for anaesthesia as at
the time of this review.
Intraoperative dysrrhythmia was noted in three
(5%) of the patients. Delayed recovery was experienced
in 2 (3.4%) cases. These patients were induced with
ketamine. Postoperative complications noted were
palatal fistula in one patient and palatal fistula with bifid
uvula in another. There was no perioperative mortality.
M.E.J. ANESTH 21 (3), 2011
338
Discussion
In this review, 80 patients were treated over a 1½
year period. An earlier report from the same centre 12
years ago8 reported an average of 7 patients presenting
over 18 months or 4.4 patients per year (57 cases over
13 years period). The current report represents over
1000% increase in the number of patients presenting
for care in about 1 decade. In contrast with earlier
reports4,8 majority (86.7%) of the patients in this series
presented after the first year of life. This is particularly
unlike the findings of Ugboko et al8 where 90%
of the patients presented within the first year of life
while only 1.7% reported in adulthood. The pattern of
presentation observed in this study suggests positive
attitude towards oro-facial cleft surgeries.
There was equal number of male and female in
this review in agreement with earlier reports including
that of Sullivan among black patients in the United
States2,9. It however differs from the findings in
some other Nigerian studies5,10 which showed female
preponderance and others8,11,12 which showed male
preponderance.
Anaemia was the commonest preoperative
complications noted in this series (11.7%). Undernutrition (5%) and growth retardation with delayed
developmental milestones (1.7%) were also observed.
These are usually due to feeding problems. Cleft lip
defect interferes with lip closure and sucking while
cleft palate patients have swallowing difficulties.
Repeated infections could also be contributory
and these complications can be prevented by early
presentation and repair of the defects13.
Chronic rhinorrhoea is common in oro-facial
cleft and patients may present with recurrent upper
respiratory tract infection (URTI). Surgical repair
reduces rhinorrhoea and URTI. Therefore, the risks
of anaesthesia and adverse respiratory events should
be individually balanced against the benefits of the
surgery14. URTI was noted in 1.7% of the patients but
no adverse respiratory event was observed.
Atropine premedication can be administered to
dry the airway particularly when difficult intubation is
anticipated or ketamine induction is to be used. Difficult
laryngoscopy occurs in up to 10% of patients with
oro-facial cleft and the incidence rises in those with
A. T. Adenekan et al.
associated syndrome15. The incidence of associated
abnormalities with or without recognized syndrome
is quoted to be 10-60%16. Craniofacial abnormalities
are the most common and these may affect intubation
outcome. The only case of failed intubation encountered
was in the child with Wolf-Hirschhorn syndrome. It is
hoped that intubation outcome will be good during
representation at which time the child would have been
older. Congenital cardiac disease occurs in 5-10%
of patients with oro-facial cleft16. One (1.6%) of the
patients in this series had ventricular septal defect. The
anaesthesia was however uneventful.
Naso-tracheal intubation was used in 82% of
all cleft palate repairs in this series. This reflects the
surgeons’ preference as against oro-tracheal intubation
which is often used. Besides providing greater access
to the mouth, the risk of kinking of endotracheal tube
following application mouth gag is removed. The risk
of inadvertent extubation or endobronchial intubation
may also be less with this route. However, naso-tracheal
intubation requires greater expertise and is associated
with the risk of damage to nasal mucosa and bleeding.
Disruption of palatal repair during extubation may
also be a remote complication. The possible role of
this technique in the two cases of postoperative palatal
fistula observed out of 15 cases of palatoplasty in this
series cannot be established.
Intraoperative dysrrhythmia was noted in
three (5%) of the patients. Possible causes include
inadequate depth of anaesthesia, hypercapnia and
halothane in the presence of cathecolamines. The risk of
dysrrhythmia is much lower with the use of isoflurane,
enflurane, or desflurane. However, halothane because
of its affordability remains the primary inhalational
anaesthetics in Nigeria. Delayed recovery was
experienced in 2 patients (3.3%). This might be related
to diazepam premedication and ketamine induction
used in these cases.
Conclusion
There has been a dramatic increase in the
number of patients presenting for care particularly
adults. Increased support from donor organizations
and training of appropriate manpower will help to
clear the backlog of patients with oro-facial cleft.
ANESTHETIC CHALLENGES IN ORO-FACIAL CLEFT REPAIR IN ILE-IFE, Nigeria
Early presentation and repair may help in reducing
the incidence of preoperative complications. Airway
management challenges are not uncommon; however,
anaesthesia for oro-facial cleft repair can be given
339
relatively safely in developing countries with attention
to detail and the careful use of available facilities and
anaesthetic agents.
References
1.Hatch DJ: Airway management in cleft lip and palate. Br J Anaesth;
1996, 76:755-756.
2.Omovie EE, Shepherd JP: Cleft lip and Palate. Africa Health; 1994,
22-24.
3.Akpata O, Ojo MA, Eroje BM and Ohre O: Congenital Cleft lip,
cleft palate and lip fistulae (Van Der Woude Syndrome) in two
Nigerian families. The Saudi Dental Journal; 1995, 7:40-44.
4.Iregbulem LM: The incidence of cleft lip and palate in Nigeria. Cleft
Palate J; 1982, 19:201-204.
5.Olasoji HO, Dogo D, Obiano SK and Yawe T: Cleft lip and Palate
in North Eastern Nigeria. Nig Ot J Hosp Med; 1997, 7:209-213.
6.Paul AM, Spauwen PHM, Spronk CA and Niemeijer RPE: Cleft lip
and palate treatment in Bangladesh. European Journal of Plastic
Surgery; 2007, 29 (6):267-270.
7.Butler MG, Hayes BG, Hathaway MM and Begleiter ML: Specific
Genetic Diseases at Risk for Sedation/Anesthesia Complications.
Anesth Analg; 2000, 91:837-855.
8.Ugboko V, Owotade F, Otuyemi O and Adejuyigbe O: experience
with cleft lip and palate patients seen in a Nigerian Teaching
Hospital. Paediatric dental Journal; 1997, 7:41-44.
9.Sullivan WG: Cleft lip with and without cleft palate in Black. An
analysis of 81 patients. Plast Reconstr Surg; 1989, 84:406-408.
10.Adekeye EO: Occurrence of cleft lip and palate in Kaduna. Nigerian
Dental Journal; 1982, 3(1):19-25.
11.DeMey A, Vadoud-Seyedi J, Demol F and Govaerts M: Early
postoperative complications in primary cleft lip and palate surgery.
Eur J Plast Surg; 1997, 20:77-79.
12.Calnan JS: Recent Advances in surgery. 6th Edition. Ed Swelyn
Taylor pg 356. J and A Churchill London, 1964.
13.Tung MK, Yau CK, Lau DWC, Kwock CL, Mak ASY and Lui
WWK: Cleft lip and palate management. J Hong Kong Med Assoc;
1994, 46(4):274-281.
14.Kotur PF: Surgical repair of cleft lip and palate in children with
upper respiratory tract infection. Indian J Anaesth; 2006, 50(1):5859.
15.Gunawardana RH: Difficult laryngoscopy in cleft lip and palate
surgery. Br J Anaest; 1996, 76:757-759.
16.Rawlinson E: Anaesthesia for cleft lip and palate. Update in
Anaesthesia; 2002, 14:27-30.
M.E.J. ANESTH 21 (3), 2011
COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1
PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5 MG ML -1
PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER
ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION:
A RANDOMIZED CLINICAL TRIAL *
Kalakonas Apostolos, Kotsovolis Georgios,
Chalkeidis Omiros and Triantafyllou Christos
Abstract
Backround: Ropivacaine is commonly used as local anesthetic for postoperative analgesia
through an epidural catheter. Data show that several adjuvants influence the analgesic effect of
local anesthetic potency.
Objective: The aim of the study was to compare fentanyl and clonidine as adjuvants to 1,5
mg ml-1 ropivacaine in terms of motor blockade, pain relief and side effects.
Methods: In this single center, randomized, clinical trial, 52 patient scheduled for arthroscopic
anterior cruciate ligament reconstruction were radomly allocated in two groups. At twenty-six
patient a solution with ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 (group F) was administered
through patient controlled epidural analgesia (PCEA) as postoperative analgesia and ropivacaine
1,5 mg ml-1 plus clonidine 1 μg ml-1 (group C) was administered at the remaining twenty-six
patients. The VAS score, the Bromage scale and total solution consumption were documented and
compared between the two groups for 24 hours after the end of the operation.
Results: The mean patient control consumption of the solution was higher at group C respect
group F (p = 0,007). At the 8th hour after the operation we register a statistical significant difference
at the mean VAS score between the two groups (p<0, 05) with clonidine group achieving a higher
score. At the 8th and 12th hour clonidine group register a lower Bromage score than fentanyl group
(p<0,005 and p = 0,002).
Conclusion: Ropivacaine 1,5 mg ml-1 plus fentanyl 2 μg ml-1 administred through PCEA
compared with ropivacaine 1,5 mg ml-1 plus clonidine 1 μg ml-1 h guarantee higher quality analgesia
after ACL reconstruction.
Keywords: Ropivacaine, fentanyl, clonidine, anterior cruciate ligament.
Conflict of interest: The study has been supported solely from the departmental sources.
*
Department of Anaesthesiology 424 Teaching Military Hospital Thessaloniki, Periferiaki Odos N.Eukarpia 56421,
Greece.
Corresponding Author: Kalakonas Apostolos MD, 424 Teaching Military Hospital Thessaloniki, Periferiaki Odos
N.Eukarpia 56421, Greece. Tel: +302310381954, Fax: +302310381010. E-mail: [email protected]
341
M.E.J. ANESTH 21 (3), 2011
342
Introduction
Placement of an epidural catheter allows to
provide better postoperative analgesia for abdominal
and lower extremity surgery respect parenteral opioid
administration1. Several studies comparing PCEA
over conventional epidural continuous infusion have
found several benefits, including better analgesia and
superior patient satisfaction2.
Ropivacaine and bupivacaine are the most
common local anesthetics administrated for epidural
anlgesia. Usually adding adjuvants such opioids, a2adrenergic agonist, neostigmine, ketamine reduce side
effects of local anesthetics and increase the analgesic
propriety of the mixture3.
The aim of this study was to compare motor
blockade, pain relief, drug consumption and side
effects during patient controlled epidural analgesia
(PCEA) with ropivacaine 1,5 mg ml-1 plus fentanyl 2
μg ml-1 versus ropivacaine 1,5 mg ml-1 plus clonidine
1 μg ml-1.
Methods
After thorough explanation of the parameters of
the study 52 ASA 1-2 patients agreed to sign the consent
form and participate in our study.These patients were
scheduled for arthroscopic anterior cruciate ligament
(ACL) reconstruction. After the admission of the
patient in the operating room, adequate monitoring
for each patient was commenced. To all patients 2,8
ml of heavy bupivacaine 5 mg ml-1 was administrated
intrathecally for surgical anesthesia. We used a kit of
combined spinal epidural anesthesia and an epidural
catheter was advanced 3cm into the epidural space
for postoperative analgesia. The puncture level was
L2-L3 or L3-L4. All the patients were operated by the
same surgeon. The epidural infusion was started in the
recovery room. Every patient was randomized (sealed
and opaque envelopes) in one of the two groups. 26
patients for fentanyl (F) and 26 patients for clonidine
(C). The study solution was prepared by an anaesthesia
nurse, who was not involved in the treatment of the
patients. In group F the epidural mixture consisted of
ropivacaine 1,5 mg ml-1 plus 2 μg ml-1 fentanyl and in
group C was ropivacaine 1,5 mg ml-1 plus 1 μg ml-1
clonidine. The infusion rate postoperatively was 5ml
K. Apostolos et al.
h-1 for either solutions regulated by an electronic pump.
All the patients were instructed to self administrate
epidural bolus doses of 5 ml on demand using the same
pump. The lockout interval was 20min. An investigator
blinded to the identity of the solution visited every
patient 2, 4, 8, 12, 24 hours after the operation. At
every visit he examined the motor blockade using the
Bromage scale (modified Bromage’s score: 0 = no
motor block, 1 = hip blocked, 2 = hip and knee blocked,
3 = hip, knee and ankle blocked) and pain using VAS
score. Solution consumption, urination, hypotension,
nausea and vomiting were also recorded. If any patient
wasn’t content from the analgesic regiment (suffered
pain VAS>6) automatically was excluded from the
trial and another pain rescue regiment was started
additionally.
Statistical analysis was performed using the
SPSS 15.0. Continuous variable were evaluated with
t-test. The Mann-Whitney test was used if data were
not normally distributed. A p value less than 0, 05 was
considered statistically significant.
Results
A total of 2 patients were excluded from the
statistical analyses. Reasons for withdrawal are
presented in Table 1. There were no significant
differences between the two groups in the demographic
data. (Table 2) Hypotension and vomiting was rare.
The first urination timing between the two groups
was statistically insignificant too (Table 3). There
was a statistical difference at the mean patient control
consumption of the solution. The mean patient control
consumption of the solution was higher at group
C respect group F (p = 0,007) (Table 3). The pump
indication during the 24 hours was statistical different
except the 4th hour (p<0, 05). In fact at the 2nd hour
group F consumed more solution than group C. At the
rest measuring hours (8th, 12th, 24th) group C consumed
more (Fig. 1). At the 8th hour after the operation we
register a statistical significant difference at the mean
VAS score between the two groups (p<0, 05) with
group C achieving a higher score (Fig. 2). At the 8th
and 12th hour group C register a lower Bromage score
than group F (p<0,005 and p = 0,002 respectively)
(Table 4).
COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1 PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5
MG ML -1 PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER ANTERIOR CRUCIATE LIGAMENT
RECONSTRUCTION: A RANDOMIZED CLINICAL TRIAL
2,50
2,00
Group
Fentanyl
Clonidine
Mean VAS score
Table 1
Reason for withdrawal
Patient group
Reason for
Comment
withdrawal
Group F
Insufficient
Replace with a more dense
analgesia
epidural solution
Group C
Technical
Epidural catheter
problem
dislocation
343
1,50
1,00
Table 2
Demographic characteristics
Groups
Age
Weight
Height
BMI
Fentanyl
27,4 (4,28)
85,04 (8,43)
180 (5,66)
26,24 (2,4)
Clonidine
28,76 (4,43) 81,88 (7,68)
178,76 (5,87) 25,59 (1,73
0,50
0,00
2
4
8
12
24
Time
Values in parentheses indicate standard deviation.
* VAS score in Group 1(Fentanyl) different than 2(Clonidine) [p<0,05]
Table 3
Patient controlled local anesthetic consumption, time of first
urination and cases of hypotension and vomiting
Groups
Hypotention Vomit
PCEA
Yes
No Yes No 2h 4h 8h 12h 24h No
25 0
25 0 11 6 3
4
1
Clonidine 27,80 (26,22)* 3
22 1
24 6 7 11 1
0
0
- Values in PCEA column indicate the extra mean patientcontrolled local anesthetic consumption in addition to the base
dose (5 ml h-1) and values in parentheses indicate standard
deviation.
- Values in other columns indicate frequency.
* Statistical difference between the groups.
Fig. 1
Mean pump indication in 24 hours
150,00
Mean Pump indication
Group
Fentanyl
Clonidine
100,00
50,00
2
4
8
12
24
Time
* Pump indication in Group 1(Fentanyl) different than 2(Clonidine) [p<0,05]
Fig. 2:
VAS score of the patients
Time
Group
score
Urination
Fentanyl 13,40 (14,629) 0
0,00
Table 4
Bromage level of kinetic blockade
2
4
8
12
24
F/C
F/C
F/C
F/C
F/C
0
3/2
4/7
4/18
12/21
22/25
1
11/6
14/11
16/4
10/4
0/0
2
11/17
7/7
5/3
3/0
3/0
3
0/0
0/0
0/0
0/0
0/0
Discussion
Epidural analgesia is more effective for
postoperative pain relief respect other regiments4.
But pain relief isn’t the only goal for a successful
postoperative outcome. Other variants such as early
mobilization and fewer side effects from the analgesic
regiment are some aspects. With this study we compare
two analgesic solutions trying to achieve excellent
pain relief without any motor blockade and no side
effects. Ropivacaine is an amide local anesthetic with a
high pKa (8.1). At the same concentration ropivacaine
produce less motor block than bupivacaine5.
Opioids used epidurally, and especially fentanyl,
as adjuvant to local anesthetics reduce the dose and
side effects of both drugs and achieve better analgesia.
Opioids mediate their analgesic effect by acting at
their receptors in the substantia gelatinosa of the spinal
cord6,7. These results have been underlined by Berti et
al where a combination of ropivacaine and opioid were
M.E.J. ANESTH 21 (3), 2011
344
K. Apostolos et al.
administered epiduraly for postoperative analgesia
after anterior cruciate ligament repair8.
ml-1 fentanyl as adjuvant in epidural solutions seems to
be free of side effects too18,19,20.
Clonidine is another drug that is frequently used
as adjuvant to local anesthetics for epidural analgesia
and significantly enhances the duration of analgesia of
epidurally administered ropivacaine9. This α2 agonist
mediates its analgesic effect by activating postsynaptic
α2 receptors in the gelatinous substance of the
spinal cord, mimicking the activation of descending
inhibitory pathways10,11,12. De Kock et al have used
clonidine as the sole agent administrated epidurally for
postoperative analgesia13.
We register a higher consume from Group C than
Group F. Sides effects at both groups were statistically
insignificant. Patient comfort was higher at Group F
than Group C if we evaluate the VAS score. Even if at
Group C the legs sensibility and mobility return earlier
the greatest patient’s fear is pain. There are no similar
studies with such low ropivacaine concetration after
ACL reconstruction operation in order to compare the
postoperative analgesia and patient comfort.
Several studies had already proposed different
concentration for epidural ropivacaine. When
used alone 2 mg ml-1 seems to be the optimal
concentration14,15,16. But sometimes with excessive
motor block. Although Tetsuya et al propose 0.5 mg
ml-1 as the favorable concentration in order to reduce
local anesthetics side effect, in our study we conclude
that even in higher concentration up to 1,5 mg ml-1
ropivacaine was also free of side effects17.
Concentration of 1 μg ml-1 clonidine and 2 μg
In conclusion, we consider that ropivacaine
1,5 mg ml-1 plus fentanyl 2 μg ml-1 administred
through PCEA is safe, without side effects and can
provide excellent postoperative analgesia after ACL
reconstruction.
Acknowledgement
The study has been supported solely from
departmental sources.
COMPARISON BETWEEN ROPIVACAINE 1,5 MG ML -1 PLUS FENTANYL 2 ΜG ML -1 AND ROPIVACAINE 1,5
MG ML -1 PLUS CLONIDINE 1 ΜG ML -1 AS ANALGESIC SOLUTION AFTER ANTERIOR CRUCIATE LIGAMENT
RECONSTRUCTION: A RANDOMIZED CLINICAL TRIAL
345
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K, Tanzawa I, Kawata K, Hanawa T, Hiejima Y: Comparison of Three
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M.E.J. ANESTH 21 (3), 2011
THE INFLUENCE OF SIMULATION-BASED
PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS
ON THE ATTITUDES OF FIRST-YEAR MEDICAL
STUDENTS TOWARDS ANESTHESIOLOGY
Samuel DeMaria Jr*, Ethan O. Bryson*, Carol Bodian**,
Yury Khelemsky*, Alan J. Sim***, Andrew D. Schwartz****,
Daniel Katz**** and Adam I. Levine*****
Abstract
Background: The development of medical students’ perceptions of different medical
specialties is based on many factors and influences their career choices and appreciation of other
practitioners’ knowledge and skills. The goal of this study was to determine if participation in
a series of anesthesiologist-run, simulation-based physiology labs changed first year medical
students’ perceptions of anesthesiologists.
Methods: One hundred first-year medical students were surveyed at random three months
before completion of a simulation-based physiology lab run by anesthesiologists. All participants
received the same survey instrument, which employed a 5-point Rating Scale to rate the
appropriateness of several descriptive terms as they apply to a particular specialist or specialty. A
post-simulation survey was performed to track changes in attitudes.
Results: Response rates to the survey before and after the simulation labs were 75% and
97% (of the initial cohort responding), respectively. All students who filled out the post-simulation
surveys had been exposed to anesthesiologists in the prior three months whereas none had interacted
with surgeons in the interim. Nearly all had interacted with internal medicine specialists in that time
period. No changes in the medical students’ perceptions of surgeons or internal medicine specialists
were evident. Statistically significant changes were found for most descriptors of anesthesiologists,
with a trend towards a more favorable perception after the simulation program.
Conclusions: Using a survey instrument containing descriptors of different medical
specialists and specialties, we found an improved attitude towards anesthesiology after medical
students participated in an anesthesiologist-run simulation-based physiology lab series. Given the
importance of providing high quality medical education and attracting quality applicants to the
field, integrati‑on of anesthesiology staff into medical student courses at the non-clinical level
appears useful.
*
Assistant Professor, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY.
**
Associate Professor, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY.
*** Fellow, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY.
**** Resident, Department of Anesthesiology, Mount Sinai Medical Center, New York, NY.
*****Associate Professor and Residency Program Director, Department of Anesthesiology.
Associate Professor, Structural and Chemical Biology, Mount Sinai Medical Center, New York, NY.
Corresponding Author: Samuel DeMaria Jr., Department of Anesthesiology, One Gustave L. Levy Place, Box 1010,
New York, NY 10029. Tel: (212) 241-7475, Fax: (212) 426-2009. E-mail: [email protected]
347
M.E.J. ANESTH 21 (3), 2011
348
Disclosures: This study was funded by the
department of anesthesiology, Mount Ainai Medical
Center.
Acknowledgements
The authors wish to acknowledge the medical
students who agreed to participate in this study and
Basil Hans, PhD, of the physiology department at the
Mount Sinai School of Medicine.
Introduction
The influences on medical students’ attitudes
toward different medical specialties are varied and
have been studied extensively1,2,3,4. These attitudes may
affect medical students’ career choices as well as their
respect and appreciation of physicians in other fields
once they enter practice. Early exposure to clinicians
in the basic science years has been identified as one
factor that can alter students’ perceptions5. While
work has been done regarding patients’ perceptions
of anesthesiologists, mostly revealing pervasive
misconceptions about their roles, training and
abilities6,7,8,9 little has been done regarding students’
perceptions towards anesthesiologists.
In order to uphold the goals of the specialty and
attract high quality applicants, a good public relations
initiative is important to the field of anesthesiology.
Indeed, the American Society of Anesthesiologists
(ASA) is actively engaged in studying and improving
the profile of anesthesiologists through its newly
launched Lifeline Campaign10. While patients and
practicing clinicians of other specialties are the main
targets of this campaign, clinicians at their earliest
stages seem an equally important demographic to
address.
One way the perception of anesthesiologists
might be improved is through the active participation
of anesthesiologists in medical education during
the basic science years where their unique scope of
practice makes them particularly suited to teaching
human physiology. The use of high fidelity simulation,
in particular, allows students to meet anesthesiologists
in an environment where their knowledge and skills
can enhance the students’ educational experience. In
this setting, medical students might be surprised to see
Samuel DeMaria et al.
that anesthesiologists have an exceptional command of
physiologic and pharmacologic principles and can be
effective communicators and enthusiastic educators.
The simulation team from the Department of
Anesthesiology at the Mount Sinai Medical Center
has been conducting simulator-based physiology labs
for the Mount Sinai School of Medicine (MSSM) for
approximately fifteen years. The current course covers
the cardiovascular, respiratory and autonomic nervous
systems over three weeks and has been unchanged since
1999. Prior to this time, truncated simulations had been
performed. This course has allowed students access to
anesthesiologists early in their schooling. Indeed, it is
likely that in most institutions medical students will
at best have a mandatory 3rd year anesthesia rotation
of variable length or an elective during their 4th year
when match application deadlines have either passed
or are looming.
Anecdotally, our team has observed that students’
attitudes toward the practice of anesthesiology and
anesthesiologists seem to improve dramatically after
completing the simulation series with many students
asking to “shadow” a faculty member after the
experience. This survey was conducted to determine
whether the prevailing attitude towards anesthesiology
and anesthesiologists changed after first-year medical
students participated in a simulator–based physiology
lab conducted solely by anesthesiologists.
Materials and Methods
Study Design
After obtaining institutional review board
approval and exemption from written informed
consent from the Mount Sinai Hospital Program for the
Protection of Human Subjects, a 60-item questionnaire
was developed. The questionnaire was designed to
elicit data from first-year medical students regarding
their perceptions of anesthesiology, but other medical
specialties were included to make the purpose appear
to be one of more general interest and mask the
principle goal of the study. Also, we believed that it was
important to prove that the opposite of the study goal
was true. Namely, if no exposure occurred, we posited
that attitudes should not change. Ten descriptive terms
and three medical fields were included in the survey,
THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE
ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY
which takes approximately 5-10 minutes to complete
(Appendix 1). A 5-point rating scale was employed
so that students could rate their level of agreement
or disagreement with the applicability of an available
descriptive term to the specialists (as people) or
specialty (as a field).
Appendix 1
Survey instrument regarding perceptions of different specialists
and specialties
Please rank the appropriateness (in your honest opinion) of the
following descriptions as they apply to the typical specialist in
each field by placing the appropriate number between 1 and 5
in each box.
1 – strongly disagree
2 – disagree
3 – neither agree nor disagree
4 – agree
5 – strongly agree
Internist
Surgeon
Anesthesiologist
devoted
intelligent
compassionate
hard-working
approachable
focused
confident
dexterous/
skillful
influential/
leader
problem-solver
Please rank the appropriateness of the following descriptions
as they apply to each specialty by placing the appropriate
number between 1 and 5 in each box
1 – strongly disagree
2 – disagree
3 – neither agree nor disagree
4 – agree
5 – strongly agree
Internal
Surgery Anesthesiology
Medicine
stimulating
prestigious/
respected
hands-on
rewarding
good life style
competitive/
rigorous
patient-centered
intellectual
boring
my possible career
349
Student subjects from the Mount Sinai School of
Medicine (MSSM) class of 2012 were recruited during
a physiology lecture in November of 2008. This class
has 140 students enrolled. On the day the class was to
be surveyed, one hundred students were present. Each
student received a survey and was asked to return it to a
study group member once completed. The study group
members did not identify themselves as members
of the department of anesthesiology. Three months
later, after completing a simulation-based physiology
lab series, the 75 students who completed the initial
survey were again surveyed. In addition to the core
survey, students were asked if they had any exposure
to members of the three medical specialties before and
during the time since the initial survey. Exposure was
defined as an instructive interaction such as a didactic
or “shadowing” experience.
Simulation Course
The simulation-based physiology lab series is
an integral mandatory component of the first-year
physiology course at the MSSM. Students participate in
three different two-hour simulation-based laboratories
taught by a team of 2-3 anesthesiologists (residents
and attendings) in groups of 10-15 students per
session. The first lab covers cardiovascular physiology,
the second covers respiratory physiology and the
final session is a trauma scenario/autonomic nervous
system lesson. During these fundamental laboratories
the simulator serves as a means to demonstrate normal
and deranged physiology. In the final session, students
apply principles of basic cardiovascular and pulmonary
physiology to successfully resuscitate a simulated
hypotensive trauma patient.
Full environment simulation (FES) is staged
for each session using a METI (Medical Education
Technologies Inc.) Human Patient Simulator (HPS).
The HPS has full drug recognition capabilities and
monitoring data are displayed on a large 50-inch plasma
cell with Smartboard overlay capability (SMART
Technologies Inc.). The overlay affords the ability to
operate any Windows based (Microsoft Corporation)
program from the plasma cell or write directly on
the screen via a blackboard function. The facilitators
rapidly change the display between physiologic data
and blackboard in order to review key physiologic
M.E.J. ANESTH 21 (3), 2011
350
Samuel DeMaria et al.
concepts as the scenarios unfold. The experience
is Socratic and the students are expected to apply
physiologic concepts learned in the classroom in order
to interpret clinically relevant patient care issues. Each
scenario is stopped and started as needed to discuss
the application of classroom knowledge to the clinical
situation and to allow participants time to develop
diagnostic and therapeutic plans. Anesthesiology is not
discussed, per se, though the scenario facilitators do
introduce themselves as anesthesiologists and discuss
the relevance of basic physiologic concepts to the
practice of acute care medicine typically encountered
in the emergency room, operating room, or critical
care bay.
Statistical Analysis
Returned surveys were reviewed and data entered
in an Excel file. Categorical variables are described as
frequency and percentage, and continuous variables as
means. In order to maintain anonymity, no attempt was
made to identify the respondents by name from pre
to post surveys. The pre- and post-simulation survey
responses to each question were compared using
Wilcoxon Two-Sample Tests.
Results
Of the 100 surveys that were distributed prior
to the simulation program, a total of 75 (75%)
were returned. Seventy-three surveys (97%) were
returned in the post-simulation group by the cohort
of 75 participants. Table 1 shows the demographic
distribution of study participants.
Table 1
Participants by age and gender
Pre-Simulation Post-Simulation
(n = 75)
(n‑ = 73)
Mean Age (SD, Range)
24 (20-32)
24 (20-33)
Women (%)
45 (60)
44 (60)
Caucasian Race (%)
49(65)
49(67)
Before the simulation labs, 12% and 20% of
students had been exposed to anesthesiologists and
surgeons as teachers, respectively. Forty-three percent
of students had been exposed to physicians from
internal medicine before the labs and 95% had been
exposed by the time of the last survey. During the
period between the two surveys, 100% of the students
in the final cohort had exposure to anesthesiologists
through the physiology labs. The group had no
comparable exposure to surgeons in that time period.
The results of the surveys for specialists
(Table 2) and specialties (Table 3) are shown below.
In almost every category, the post-simulation
anesthesiology scores were significantly higher
than their pre-simulation counterparts, whereas no
significant differences were noted for the surgery or
internal medicine scores. The one negative attribute,
“boring”, decreased in the post-simulation scores. The
anesthesiology match rates for MSSM are included in
Table 4.
Table 2
Pre and post-simulation perceptions of surgeons, internists and anesthesiologists
Surgeon
Anesthesiologist
Mean score Mean score
pre-sim
post-sim
Devoted
4.2
4.3
Intelligent
4.4
4.4
Compassionate
2.9
3.0
Hard-working
4.6
4.7
Approachable
2.7
2.7
Focused
4.5
4.6
Confident
4.7
4.8
Dexterous
4.7
4.8
Influential/ leader
4.1
4.3
Problem-solver
4.0
4.2
p-value
0.60
0.48
0.94
0.35
0.99
0.64
0.42
0.37
0.13
0.30
Mean score Mean score
pre-sim
post-sim
3.6
4.0
4.2
4.5
3.1
3.6
3.7
4.1
3.4
3.9
4.2
4.3
4.1
4.4
4.1
4.5
3.4
3.8
4.0
4.4
p-value
0.018
0.024
0.002
0.02
0.0003
0.71
0.04
0.03
0.012
0.006
Internist
Mean score Mean score p-value
pre-sim
post-sim
4.3
4.3
0.98
4.2
4.2
0.62
4.3
4.3
0.69
4.3
4.1
0.18
4.3
4.3
0.77
4.2
3.9
0.06
4.1
3.9
0.15
3.7
3.6
0.42
3.7
3.6
0.48
4.4
4.5
0.46
Pre and post-simulation scores are reported as mean scores on a Likert Scale. P-values are based on Wilcoxon 2-sample test comparisons
of pre and post-simulation survey data.
THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE
ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY
351
Table 3
Pre and post-simulation perceptions of surgery, internal medicine and anesthesiology
Surgery
Anesthesiology
Internal Medicine
Mean
Mean score
p-value Mean score Mean score p-value Mean score Mean score p-value
score pre- post-sim
pre-sim
post-sim
pre-sim
post-sim
sim
Stimulating
4.2
4.3
0.89
3.2
3.9
<0.0001
3.8
3.8
0.62
Prestigious
4.7
4.8
0.61
3.7
4.0
0.046
3.3
3.3
0.91
Hands-on
4.8
4.8
0.65
3.6
4.3
<0.0001
4.0
3.8
0.29
Rewarding
4.1
4.2
0.64
3.3
3.9
0.0002
4.1
4.0
0.31
Good lifestyle
2.3
2.5
0.23
4.1
4.3
0.49
3.3
3.3
0.89
Competitive
4.7
4.7
0.64
3.9
4.3
0.03
3.2
3.1
0.34
Patient-centered
2.9
3.1
0.104
3.1
3.3
0.12
4.7
4.7
0.77
Intellectual
3.8
3.8
0.55
3.6
4.1
0.012
4.3
4.2
0.56
Boring
2.1
2.1
1.0
3.3
2.5
<0.0001
2.5
2.6
0.48
Possible career
2.7
3.0
0.17
2.2
3.1
<0.0001
3.4
3.2
0.46
Pre and post-simulation scores are reported as mean scores on a Likert Scale. P-values are based on Wilcoxon 2-sample test comparisons
of pre and post-simulation survey data.
Table 4
Comparison of anesthesiology match rates of medical students
at MSSM++ and nationwide
Year
MSSM (%)
National (%)*
1991+
6.9
6.3
1992+
9.2
6.5
1993
3.9
5.8
1994
4.3
4.9
1995**
1.5
2.9
1996**
0.7
1.2
1997+
2.5
1.7
1998+
4.1
2.6
1999**
2.3
2.8
2000+
5.9
3.7
2001
1.8
4.7
2002+
6.7
5.9
2003+
14.5
6.0
2004
4.6
5.8
2005+
8.7
5.9
2006+
9.9
6.5
2007+
12.3
6.3
2008+
7.3
6.5
2009+
10.9
6.7
+ Greater percentage placement than national average.
* Derived from National Residency Matching Program website:
www.nrmp.org/index.html
++ Mount Sinai School of Medicine.
** The cardiovascular lab was introduced in 1995, the
respiratory lab in 1996 and the complete course in 1999.
Discussion
Misconceptions of anesthesiology are common
amongst other medical specialists and patients6,7,8,9.
Similar inaccurate perceptions amongst medical
students may deter them from choosing anesthesiology
as a specialty or cause them to have an inaccurate
opinion of anesthesiologists as professional colleagues
in the future. It makes implicit sense that resources
invested by members of academic anesthesiology
departments in the form of medical student teaching
might help improve the attitudes of these budding
clinicians towards the field. This is important not just
for recruitment of strong applicants to the field, but for
strong professional relationships amongst practitioners
which are based on mutual respect and appreciation of
each others’ roles and abilities. This, ultimately, fosters
the teamwork which is so important to safe medical
care.
In this study, we showed that exposure of firstyear medical students to anesthesiology resident and
attending physicians in a series of simulation-based
physiology labs improved their attitudes towards the
field. Exposure to internal medicine specialists in
a more traditional setting (lectures and shadowing
opportunities) did not have a similar effect on attitudes.
In particular, marked positive improvements (p<0.001)
were found for the following domains: “approachable”,
“stimulating”, “hands-on”, “rewarding”, “boring” and
“my possible career”. None of the students surveyed
had been exposed to surgeons and their views of
these clinicians did not change. This is important in
corroborating the data gathered for anesthesiology, as
no change would be expected if no exposure occurred.
Most had been exposed to practitioners from internal
medicine through lectures and shadowing experiences,
yet their overall attitudes did not change significantly.
M.E.J. ANESTH 21 (3), 2011
352
It is possible that attitudes towards internal medicine
did not change because expectations of that field were
more in line with reality.
While our results are limited by several factors
(e.g., relatively low initial response rate, p-values not
adjusted for the influence of doing many significance
tests in a survey-based design) the trends we
observed are compelling. It is possible that although
we attempted to feign that anesthesiology was the
principal study subject we were unsuccessful in doing
so. This may have led participants to give favorable
ratings to anesthesiologists once the course facilitators
were identified as such. Additionally, the results of
this study may be heavily influenced by selection bias
since those more interested in the simulation labs or
in anesthesiology may have been more likely to return
the surveys. Indeed, the study was done for one course
and one class by one group at only one medical school.
Also, a lack of subject identifier use means that no
individual shifts in attitude could be determined and
this negatively impacts the statistical significance
of our data. It is also impossible to tell whether the
observed shift in attitudes towards anesthesiologists
was due to faculty skill or the educational environment.
The current design does not allow the necessary
comparisons to identify the sources of the change or
the relative weight of either factor. Future work should
be done to more effectively determine the importance
of faculty skill versus environment in improving
attitudes.
We are currently investigating whether this
change in perception is sustained or manifests as
a higher number of students ultimately pursuing
anesthesiology as a career. Each year, the simulation
labs are rated very highly by students. In this most
recent cycle, 98.5% of students (138 completers of
140 total students) rated the course as “excellent” and
all respondents agreed that the course should continue
Samuel DeMaria et al.
to be integrated into the physiology curriculum. The
course in its current form was first introduced in 1999
and effects, if any, would be expected from 2002 to
present assuming normal graduation pathways. We
have accordingly seen a significant percentage of the
graduating class entering anesthesiology since the
introduction of the complete course, with rates higher
than the national average in 7 out of the past 8 years
(Table 4). However, this is a correlation not based
on rigorous data gathering and is certainly the result
of many confounding factors. Other than this brief
exposure to anesthesiologists in the first year, students
have a 1-week mandatory clerkship in their 3rd year.
We believe that respect for anesthesiologists fostered
in students’ first year simulation course may result
in students entering this brief clerkship with positive
expectations and that this potentially explains the high
rate of placement in anesthesia programs.
We propose it is crucial for anesthesiologists
to maintain a strong presence in the basic science
curriculum to enrich the educational experience of
students and potentially foster interest in and respect
for the specialty. Most simulation centers are run by
or have anesthesiologists on staff. The simulated
environment allows students to learn basic science in a
unique way and also see anesthesiologists “in action”
and dynamically applying basic physiologic concepts to
patient care. In this fashion, students get a high quality
educational experience and gain an appreciation of the
knowledge and scope of practice of anesthesiologists.
Anesthesiologists should therefore take a more active
role in the education of medical students at even the
earliest stages. In this fashion, simulation serves not
just as a powerful educational tool, but a recruiting tool
as well.
This effect may be true for other specialties as
well, such as nursing, emergency medicine and critical
care.
THE INFLUENCE OF SIMULATION-BASED PHYSIOLOGY LABS TAUGHT BY ANESTHESIOLOGISTS ON THE
ATTITUDES OF FIRST-YEAR MEDICAL STUDENTS TOWARDS ANESTHESIOLOGY
353
References:
1. Levin KJ, Friedman CP, Scott PV: Anesthesiology and the
graduating medical student: a national survey. Anesth Analg; 1979,
58(3):201-7.
2. Samra SK, Davis W, Pandit SK, Cohen PJ: The effect of a clinical
clerkship on attitudes of medical students toward anesthesiology. J
Med Educ; 1983, 58(8):641-7.
3. Henderson E, Berlin A, Fuller J: Attitude of medical students
towards general practice and general practitioners. Br J Gen Pract;
2002, 52(478):359-63.
4. Hauer KE, Durning SJ, Kernan WN et al: Factors associated with
medical students' career choices regarding internal medicine. JAMA;
2008, 300:1154-1164.
5. Grayson MS, Klein M, Franke KB: Impact of a first-year primary
care experience on residency choice. J Gen Intern Med; 2001,
16(12):860-3.
6. Klafta JM, Roizen MF: Current understanding of patients’ attitudes
toward and preparation for anesthesia: a review. Anesth Analg; 1996,
83:1314-21.
7. Ho RY, Wong DT: Anesthesiology: the misunderstood occupation!
Can J Anaesth; 2005, 52(2):208-9.
8. Garcia-Sanchez MJ, Prieto-Cuelar M, Galdo-Abadin JR,
Palacio-Rodriguez MA: Can we change the patient’s image of
the anesthesiologist? (Spanish). Rev Esp Anestesiol Reanim; 1996,
43:204-7.
9. Huang Y, Yang K, Ren H, Luo A: A survey of elective surgical
patients’ attitudes toward anesthesia in PUMC hospital. Chin Med
Sci J; 2002, 17:77-80.
10.http://lifelinetomodernmedicine.com/ accessed September 30, 2009.
M.E.J. ANESTH 21 (3), 2011
PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC:
EXPERIMENTAL STUDY IN RATS
Antigona S. Hasani*, Marija Soljakova**, Muharrem H. Jakupi***
and S erpil Z. U stalar -O zgen ****
Abstract
Background: Preemptive analgesia is an antinociceptive treatment that prevents central
sensitization. Antinociceptive effects of diclofenac are well-known. The aim of this study was to
investigate preemptive analgesic effects of intraperitoneally administrated diclofenac, before and
after acute and inflammatory induced pain in rat model.
Methods: Forty eight male Sprague Dawley rats were included in the study. The rats are
divided in five groups (n = 8 per each group); Group A, diclofenac at 10 mg/kg given ip, 30 min
before the nociceptive stimulus realized with hot plate test; Group B, diclofenac at 10 mg/kg given
ip, 5 min after the nociceptive stimulus, realized with hot plate test; Group C, diclofenac at 10
mg/kg given ip, 30 min before the nociceptive stimulus realized with formalin test, and; Group D,
diclofenac at 10 mg/kg given ip, 5 min after the nociceptive stimulus, realized with formalin test.
Saline was used as a control. Paw movements in response to induced pain with hot plate test and
formalin test were measured during 60 minutes.
Results: Preemptive analgesic effect was significant in both groups when diclofenac was
administrated before the pain stimuli (P<0.01 and P<0.001). The significant decrease in paw
movements started in 15 min after pain stimuli in group A and in 25 min, in group C.
Conclusion: Intraperitoneally administered diclofenac had preemptive analgesic effects on
acute thermal, and inflammatory induced pain in rats. Our results contain the preemptive analgesic
effect of systematically administrated diclofenac.
Keywords: diclofenac, preemptive analgesia, hot plate test, formalin test.
Introduction
Preemptive analgesia suggests that the application of analgesic in prior to proceeding of
noxious stimuli prevent the sensibility of the central nervous system, which provokes the pain. Pain
associated with tissue damage results in prolonged modulation of the somatosensory system, with
increased responsiveness of both peripheral and central pain pathways1. Experimental evidence
proposes that to ‘prevent’ or ‘preempt’ the noxious input to the CNS, may be more effective than
treatment. The idea of preemptive analgesia was first introduced into clinical practice by Crile
*
Assistant Professor, Department of Anesthesiology & Reanimation, University Clinical Centre of Kosovo, Pristina,
Kosovo.
**
Professor, Department of Anesthesiology & Reanimation, Medical Faculty”Sv. Kiril Metodij” Skopje, Macedonia.
*** Professor, Institute of Clinical Pharmacology, Medical Faculty, Pristina, Kosovo.
**** Assistant Professor, Department of Anesthesiology & Reanimation, Ozel Acibadem Universitesi, Istanbul, Turkey.
Corresponding Author: Dr. Antigona Hasani, Department of Anesthesiology & Reanimation, University Clinical Centre
of Kosovo, Pristina, Kosovo; Address: Arberia, rr. Zagrebit no. 5, 10000 Pristina, KOSOVO. Tel: 0037744402781, Fax:
+38138243838, E-mail: [email protected]
355
M.E.J. ANESTH 21 (3), 2011
356
Antigona S. Hasani et al.
in 19132 and further developed by Wall3 and Woolf4.
The definition of preemptive analgesia was formed
by Kissin5. According to him, preemptive analgesia
is “treatment that prevents establishment of central
sensitization caused by incisional and inflammatory
injuries; it starts before incision and covers both the
period of surgery and the initial postoperative period.
Preemptive analgesia prevents pathologic pain that
is different from physiologic pain”, which means:
prevention or reversal of central and peripheral
sensitization.
Diclofenac sodium, 2-[(2,6-dichlorophenyl)
amino] benzene acetic acid, is a non-steroidal antiinflammatory drug (NSAID), with an approximate
relative COX-1⁄COX-2 specificity ratio of one6.
NSAIDs inhibit the cyclo-oxygenase enzymes (COX),
and decrease peripheral and central prostaglandin
production. To reduce the inflammation that
accompanies tissue injury, decreasing prostaglandin
production attenuates the response of the peripheral and
central components of the nervous system to noxious
stimuli and reduce the pain occurred in response to
following noxious stimuli7. These properties would
seem to make NSAIDs ideal drugs to use in a preemptive approach.
Preemptive analgesic effect of diclofenac is
discussed in many studies, but the results are still
controversy8-14.
In the present study the preemptive analgesic
properties of systemically administered diclofenac
sodium were investigated in a rat model of acute and
inflammatory pain.
Materials and Methods
After Institutional Ethics Committee approval, 48
male (8 for each group) Sprague Dawley rats, weighing
250-300g (60-70 days after birth), were included in the
study. The animals were housed in a cage at 20-25ºC
under diurnal light condition and allowed to access
food and water ad libitum. All experiment was done
in accordance with the Guide for the Care and Use of
Laboratory Animals published by the United States
National Institutes of Health (NIH Publication No. 8023, revised 1996).
Diclofenac
sodium
(Proanalysis-Merck,
Germany) was dissolved in normal saline to achieve
solutions of 10 mg/kg for intraperitoneally (ip)
administration. The total injected volume was adjusted
to 10 ml/kg in each rat. Diclofenac was used for ip
injection at 1-ml syringe with a 23-G needle.
The rats are divided in five groups;
Group A, diclofenac at 10 mg/kg given ip, 30 min
before the nociceptive stimulus realized with hot plate
test;
Group B, diclofenac at 10 mg/kg given ip, 5 min
after the nociceptive stimulus, realized with hot plate
test;
Group C, diclofenac at 10 mg/kg given ip, 30 min
before the nociceptive stimulus realized with formalin
test, and;
Group D, diclofenac at 10 mg/kg given ip, 5 min
after the nociceptive stimulus, realized with formalin
test.
Saline group, (1ml/kg), normal saline given ip,
was used as a control.
The acute thermal pain was realized with hot
plate test. The hot plate test was performed at 55ºC on
the paw of each rat. Animals were placed on the heated
smooth surface and observations began and continued
for the next 60 minutes (Fig. 1a. and 1b). To prevent
the tissue injury the rats were removed from the hot
plate test after 30 sec. Hot plate tests were performed
10 min before or 30 min after ip drug injection, and
repeated every 10 min during 60 min.
Fig. 1a
Hot plate test
PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC: EXPERIMENTAL STUDY IN RATS
Fig. 1b
Paw movements
357
catatonic excitement and flaccidity) were observed in
animals during the study.
Statistical analysis was performed using SPSS
version 15. Data are expressed as the mean ± SD or
95% confidence interval (CI). The experimental groups
were compared by the nonparametric Kruskal-Wallis
test. Multiple comparisons after the Kruskal-Wallis
test were performed using the two-tailed Dunn test. A
P value less than 0.05 were considered significant.
Results
Fig. 1c
Formalin test
Preemptive analgesic effect, in groups before and
after diclofenac sodium administration, was shown
in hot plate test with significant decrease in paw
movements in group A, when diclofenac sodium was
administrated before the pain stimuli with hot plate test
(P<0.01) (Fig. 2).
Fig. 2
Paw movements after ip administration of diclofenac before
and after the pain stimuli and control group in hot plate test.
Data are presented as mean ± SD. * significant difference
The formalin test, model of inflammatory pain,
was performed ten minutes after drug administration.
Fifty microlitres of 10% formalin was injected
subcutaneously into the dorsal surface of the right hind
paw with a 30-G needle (Fig. 1c). Immediately after
injection, the rat was placed in an open surface, and their
paw response was observed at ten minutes intervals for
a period of one hour. The number of movements was
counted for one minute. Two phases were observed:
phase 1 for the first six minutes after injection; and
phase 2 beginning after about ten minutes.
The paw movements were measured every
10 minutes during 60 minutes. A nociceptive score
was determined by measuring the 4 behavioural
categories: 0, the position and posture of the hind paw
is indistinguishable from the contralateral paw; 1, the
paw has little or no weight placed on it; 2, the paw is
elevated and is not in contact with any surface; 3, the
paw is licked, bitten or shaken.
Significant decrease of paw movements was
shown in formalin test as well, in groups before
administration of diclofenac sodium (group C)
(P<0.001) (Fig. 3).
Fig. 3
Paw movements after ip administration of diclofenac before
and after the pain stimuli and control group, with formalin test.
Data are presented as mean ± SD. * significant difference
Behavioral side effects (agitation, allodinia,
M.E.J. ANESTH 21 (3), 2011
358
Antinociceptive effects in the hot plate test, group
before (group A) started in 15 min after diclofenac
administration and continue to decrease during
followed 60 minutes. In the formalin test group before
(group C) significantly increased paw movements,
antinociceptive effects continue to decrease in 25 min
and up to 60 min.
Diclofenac decrease the number of paw
movement in both phases of formalin test, in group C
(P<0.05).
Antinociceptive
effects
of
diclofenac
administrated before pain stimuli were higher in
group C, than the corresponding group A (P<0.01 vs.
P<0.001, respectively) (Fig. 4).
Fig. 4
Paw movements after ip administration of diclofenac before
and after the pain stimuli and control group,
in hot plate test and formalin test. Data are presented as mean
± SD. * significant difference
Antigona S. Hasani et al.
In our study, we used before versus after design;
we applied diclofenac before and after pain stimuli.
It is evident that pain processing may be reduced
by preadministration of various agents (e.g. opioids,
local anesthetics, NSAID etc.) leading to the concept
of preemptive analgesia. Due to their mode of action,
competing with arachidonic acid for binding to
cyclo-oxygenase and decreasing the formation of
prostaglandins, treatment with NSAIDs should be
started as early as possible. The treatment should
be initiated before the input of nociceptive stimuli;
however, the clinical value of this technique remains
still uncertain15.
Instrumentation of the uterus and Fallopian
tubes during laparoscopy or surgery leads to
prostaglandin release and, the prostaglandins
released play a role in pain following laparoscopy16.
Inhibition of prostaglandin production by the NSAIDs
both peripherally and centrally should, therefore,
decrease postoperative discomfort and reduce opioid
requirement17.
Woolf and colleagues showed no difference with
preoperative diclofenac from postoperative diclofenac
in patients undergoing laparoscopic tubal ligation18.
Both before and after ip administration of
diclofenac decrease the number of paw movements
after pain stimuli performed by hot plate or formalin,
in comparison with control saline group (P<0.001)
(Fig. 2, 3, 4).
No behavioural side effects were observed in any
animal.
Discussion
In this recent study, we demonstrated that
intraperitoneally administered diclofenac had
preemptive analgesic effects in the hot plate test and
formalin test in rats.
Preemptive analgesia can reduce both the acute
and inflammatory pain and in this way can reduce
peripheral and central sensitization.
However, Buggy et al. and Gillberg et al.
demonstrate
that
preoperative
administration
of ketorolac, piroxicam and diclofenac did
reduce postoperative pain in patients undergoing
laparoscopy19,20. Our findings support these results as
well.
There are two systematic reviews published in
recent years; one of them supports the clinical value
of preemptive analgesia, whereas the other one is
the opposite. Firstly, Moiniche et al21 published a
systematic review of 80 studies, with 3761 patients,
based on before versus after design. They show that
the trials of single-dose epidural analgesia resulted
with an improvement in pain control in 7 of 11 studies,
but that validity and clinical relevance of the effect of
epidural analgesia were uncertain. They concluded
that the preemptive use of analgesics is not resulted in
better postoperative pain relief. However, three years
later, Ong et al. in their review analyzed 66 studies with
data from 3261 patients and concluded that preemptive
epidural analgesia, preemptive local wound infiltration
and NSAID administration improve postoperative
PREEMPTIVE ANALGESIC EFFECT OF DICLOFENAC: EXPERIMENTAL STUDY IN RATS
pain scores22. Comparing the two reviews, Ong et al.
suggested that 10 additional new trials from 2001–
2003, not included in the review by Moiniche et al.
Our study shows that ip administered diclofenac
has preemptive and antinociceptive effects in acute
thermal and inflammatory induced pain.
The hot plate test evaluates supraspinal
antinociceptive effects, and it reflects activity in
thermally sensitive afferent fibers and activity of Aδ
and C fibers25.
Responses in the formalin test are mediated by
both the spinal and supraspinal sites. The phase 1
response of the formalin test is caused by the direct
stimulation of nociceptors by formalin or tissue
damage, and is thought to be an acute pain reaction.
This reflects activity that is prominent in Aβ, Aδ and
high-threshold C nociceptor afferent fibers. The phase
2 response is caused by inflammation after formalin
injection and central sensitization related to C activity.
It reflects activity in mechanically insensitive afferent
fibers and activity of Aδ and C fibers26.
Sensory fibers respond to physical and chemical
stimuli producing mediators with origin from tissue
injury and inflammation. These inflammatory mediators
activate or sensitize afferent fibers, and the neural
impulses originated from nociceptors are transmitted
via peripheral nerves to the spinal cord and with cranial
nerves to cranial nerve ganglia. Prostaglandins are
among the most important mediators of inflammatory
pain. During inflammation prostaglandin formation is
induced by COX enzymes. NSAIDs block COX enzymes
production and produce analgesia27.
Studies have highlight that NSAIDs do not
increase the pain threshold in animal model such as
tail-flick and hotplate tests, but they normalize the pain
behavior, which is observed after tissue injury and
inflammation mechanism28,29. However, diclofenac
359
cause dose dependant analgesia. The ED50 values for
diclofenac are 7.20 mg/kg (3.95 ± 13.30)30. We assume
that the inadequate administered doses of drug may
decrease the concentration in peripheral nociceptive
terminals and antinociceptive response may fail.
The intraperitoneally administrated dose of
diclofenac sodium, in our study, was 10 mg/kg, the
optimal dose to cause antinociceptive response in rats.
The analgesic action of NSAIDs is generally
considered to be related to an inhibition of the
enzyme cyclo-oxygenase and to involve a peripheral
site of action. Recent studies have demonstrated the
central antinociceptive mechanism of action of the
NSAIDs31-36.
Bjorkman studied the site and nature of the
antinociceptive effect of diclofenac and paracetamol
in the central nervous system. He observed the
antinociceptive effect of diclofenac engage with
central nervous component in different areas of central
nervous system30.
Herrero and colleagues31 studied the central
antinociceptive effect of NSAID ketoprofen in two
experiment models in rats and conclude that ketoprofen
has central while peripheral analgesic activity.
The present results suggest that intraperitoneally
administered diclofenac has few effects at the level
of the spinal cord and antinociceptive effects in the
periphery and the brain.
However the available preoperative trials of
preemptive NSAID use have modest or unclear
results and it may be due to controversy associated
with the definition of preemptive analgesia. Even
though, NSAIDs may have an ability to induce a
preemptive analgesic effect. Our study suggests how
the preoperative use of diclofenac was more effective.
It is expected that NSAIDs will play an increasing role
in preemptive analgesia and pain relief in general.
M.E.J. ANESTH 21 (3), 2011
360
Antigona S. Hasani et al.
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Comparison between two phenylephrine
infusion rates with moderate
co-loading for the prevention
of spinal anaeshtesia- induced
hypotension during elective
*
caesarean section
Tarek Ansari, Medhat M. Hashem, Ahmed A. Hassan,
Ahmed Gamassy and Ayad Saleh
Abstract
Background: Phenylephrine induces maternal bradycardia in 50% of mothers when used
for prevention and treatment of spinal anaesthesia-induced hypotension during caesarean delivery.
Rapid fluid administration immediately after initiation of the spinal block (co-loading) may have
a vasopressor sparing effect. The aim of this study was to evaluate the hypothesis that when
using rapid crystalloid co-loading, an infusion of 50 mcg/minute of PE could be as effective as
100 mcg/minute in preventing maternal hypotension but with minimal maternal bradycardia and
an acceptable fetal outcome.
Methods: 117 mothers scheduled for elective caesarean section were recruited in this
randomized controlled trial. Co-loading with 10 ml/kg of Hartmann’s solution started immediately
after a standard spinal anaesthesia. Parturients were then randomly allocated into two groups.
Group 50 (n = 54) received phenylephrine infusion at 50 μg/min, and group 100 (n = 63) 100 μg/
min. Rescue phenylephrine boluses (50 mcg) were administered if needed to maintain systolic
blood pressure between 80-100% of its baseline values.
Results: Systolic blood pressure was not different between mothers in both groups during the
study period. All neonatal Apgar scores at 1 minute were ≥7 and at 5 minutes were ≥ 9. No mother
had umbilical arterial pH <7.2. Umbilical arterial and venous blood gas and acid base values were
not different between both groups except the umbilical arterial PCO2 that was significantly higher
in group 100. There were more frequent episodes of maternal bradycardia in Group 100 than in
Group 50 (eleven and one parturients respectively). There was no difference in the incidence of
nausea and vomiting in both groups.
Conclusion: In combination with rapid co-loading, an infusion rate of 50 µg/min of PE is as
adequate as 100 µg/min in prevention of spinal anaesthesia-induced hypotension during elective
caesarean section. Both infusions are associated with a similar neonatal outcome. PE infusion of
50 µg/min is associated with significantly less maternal bradycardia than 100 µg/min.
Keywords: Phenylephrine, Spinal Aneasthesia, Caesarean section, Hypotension, Co-loading.
*
Department of Anaesthesia, Corniche Hospital, Abu Dhabi, United Arab Emirates.
Corresponding Author: Dr Medhat M. Hashem, Consultant Anaesthetist, North East London NHS Treatment Centre,
King George Hospital,Barley Lane, Ilford, Essex, IG3 8YY, UK. Tel +(44) 08450524175, Fax: +(44) 02085984605.
E-mail: [email protected]
361
M.E.J. ANESTH 21 (3), 2011
362
Introduction
During elective caesarean section, maternal
hypotension is the most frequent complication of
spinal anaesthesia with an incidence approaching
100%1. Among its multifactorial aetiology is profound
vasodilatation secondary to complete sympathetic
denervation that is often accentuated by a variable
degree of aortocaval compression. Many strategies
are currently used to minimize hypotension including
maternal left tilt, leg wrappings2, sympathomimetic
drugs3, and intravenous fluid loading whether before
(pre-loading)4 or with (co-loading) induction of spinal
anaesthesia. Co-loading may be more effective than
preloading in terms of reducing the dose of vasopressor
prior to delivery5.
Recent work suggests that prophylactic
continuous infusion of the <alpha>-adrenergic
agonist phenylephrine (PE) is superior to ephedrine
in prevention of spinal anaesthesia induced
hypotension. Major postulated benefits are a
reduction in the incidence of nausea and vomiting,
and less fetal acidosis6,7. But when PE was used on its
own to maintain maternal systolic blood pressure at
100% of baseline, the incidence of hypotension was
still 29%8. A Cochrane systematic review concluded
that no one method on its own is effective, and
that combining more than one measure should be
investigated9.
PE induces bradycardia in up to 50% of mothers,
in a dose-related manner, via a secondary baroreceptor
response to induced-hypertension11. The aim of the
study was to evaluate the hypothesis that when using
rapid crystalloid co-loading, PE infusion of 50 mcg/
minute could be as effective as 100 mcg/minute in
preventing maternal hypotension with similar foetal
outcome but with minimal maternal bradycardia.
Methods
Following Corniche hospital Ethics Committee
approval (Abu Dhabi United Arab Emirates) and
informed written consent, 117 mothers scheduled for
elective caesarean section were recruited. All mothers
had normal singleton pregnancy at 37 week gestation
or more. Exclusion criteria were American Society of
Tarek Ansari et al.
Anaesthetists (ASA) Class 3 or more, height <150 or
>180 cm, or body mass <60 or >100 kg, pre-eclampsia,
known fetal abnormality, or any contraindication to
spinal anaesthesia.
Oral ranitidine (150 mg) was given on the
evening before and the morning of surgery. In the
preparation room, oral sodium citrate 0.3 M (30 ml)
was given. Three measurements of non-invasive
blood pressure at one minute interval were taken after
the mothers were allowed a 5 minute rest period in the
supine position with left lateral tilt. The average of the
3 readings of systolic blood pressure (SBP) was used
as a baseline.
Following skin infiltration with 2% lidocaine,
a 16G IV catheter was inserted and intravenous fluid
was started at a minimal rate to keep the vein open.
Mothers were randomized into Group 50 (PE 50 µg/
ml) or Group 100 (PE 100 µg /ml) using closed
similar envelops labeled with either of the two
designated concentration of PE. An anaesthetist, who
was not involved in the case management, prepared
a 20 ml syringe for PE infusion with the designated
concentration. Both the patient and the anaesthetist in
charge of the case were blinded to the concentration of
PE in the syringe.
In the operating theatre, after the skin was
infiltrated with 2% lidocaine, subarachnoid injection
of 3 ml (15 mg) hyperbaric bupivacaine 0.5% and
preservative-free fentanyl 20 µg was performed in the
sitting position using a 26G atraumatic spinal needle
(RapidTM, Portex, UK) at the L3-4 or L4-5 interspace.
With the operating table leveled, mothers were
positioned supine with left lateral tilt and 2 pillows
supporting the head and shoulders. Monitoring
consisted of a continuous 3 lead electrocardiograph,
noninvasive blood pressure measurement every
minute, and pulse oximetry. Intraoperative
haemodynamic data, from the time of induction of
spinal anaesthesia until the delivery of the baby, were
downloaded from the monitor (IntelliVue MP70,
Phillips Medical Ltd, Germany) for off-line analysis.
Five minutes after induction of anaesthesia, the upper
sensory level of anaesthesia was assessed using loss
of cold stimulus discrimination. Oxygen (5 L/min)
by a clear facemask was given only if pulse oximetry
reading was less than 95%.
Comparison between two phenylephrine infusion rates with moderate co-loading for the
prevention of spinal anaeshtesia- induced hypotension during elective caesarean section
Immediately after spinal anaesthesia, both
PE infusion and co-loading were commenced. An
intravenous bolus of warm Hartmann's solution
(10 ml/kg) was administered as rapidly as possible,
with the aid of a pressure bag inflated at 200 mmHg,
followed by a reduction of the rate to a minimal flow.
PE infusion was commenced at a rate of 60 ml/h for
the first three minutes and stopped if SBP was greater
than 120% of the baseline. After the first three minutes,
the infusion was continued at the same rate if SBP
was between 80-100% of baseline, until the time of
delivery. PE infusion was discontinued if the SBP was
more than 100% of the baseline value. A rescue dose
of PE (50 µg) was given if blood pressure decreased
to below 80% of the baseline for two consecutive
readings despite PE infusion. If bradycardia (heart
rate <50/min) developed without hypotension, PE
infusion was discontinued for one minute. Intravenous
glycopyrronium (200 µg) was used to treat bradycardia
associated with hypotension (SBP<80% of baseline).
After delivery, an intravenous bolus of oxytocin (5 IU)
was slowly administered. Apgar score was assessed
at 1 and 5 minutes after delivery by the attending
paediatrician, who was unaware of the dose of PE used.
With the umbilical cord double clamped, umbilical
venous and arterial blood samples were drawn for gas
and acid base analysis.
The primary outcome of the study was the
incidence of maternal hypotension, defined as a drop
in SBP to less than 80% of baseline. The incidence of
hypotension was 29% in a previous study8. A priori
363
sample size of 58 mothers in each group was deemed
sufficient to detect a 5% difference (α = 0.05, β = 0.8).
Another 10% was added to compensate for drop outs.
Secondary outcomes were maternal bradycardia, the
total dose of PE used pre-delivery, the incidence of
nausea and vomiting, Apgar scores at 1 and 5 minutes,
and umbilical arterial and venous blood gases and base
deficits. Normally distributed numerical data were
described in terms of mean and standard deviation and
compared using unpaired t-test and one way ANOVA.
Non-normally distributed data were compared using
Mann-Whitney test. Categorical data were analysed
using Chi square and Fischer Exact tests where
appropriate. Statistical analysis was performed using
SPSS 14.0 for windows (Statistical Package for Social
Sciences). Statistical significance was assumed at a P
value of <0.05.
Results
One hundred and twenty eight mothers were
originally enrolled in this trial with eleven dropouts
due to different reasons. Two mothers had inadequate
block and subarachnoid injection was repeated. Trial
design was not strictly followed in four mothers. Five
umbilical blood gas results had technical problems.
One hundred and seventeen full-term parturients
undergoing elective caesarean section completed the
study. None of them complained of intraoperative
pain nor was intraoperative supplementation with
analgesics or sedatives required (Table 1).
Table 1
Mothers’ characteristics, block height and surgical times in both groups
Group 50
(n = 54)
Group 100
(n = 63)
P
Age (years)
32.7 (4.6)
32.8 (5.3)
0.92
Weight (Kg)
74.0 (9.1)
75.5 (9.9)
0.41
Height (cm)
158.4 (4.8)
159.0 (6.6)
0.56
Gestational age (weeks)
38.4 (1.0)
38.2 (0.9)
0.26
T4 (T2-T6)
T4 (T2-T6)
1.0
Induction to delivery time (minutes)
14.5 (2.7)
14.0 (3.5)
0.35
Uterine incision to delivery time (seconds)
65.5 (36.9)
72.0 (55.8)
0.47
Block height at 5 minutes (dermatome)
All values are mean (SD) except block height: median (range).
M.E.J. ANESTH 21 (3), 2011
364
Tarek Ansari et al.
Table 2
Intraoperative haemodynamic data and side effects
Group 50
(n = 54)
Incidence of hypotension (systolic blood pressure less than 80% of
8 (14.8)
baseline)
Incidence of hypertension (systolic blood pressure more than 120%)
2 (3.7)
Phenylephrine dose used (micrograms)
546.9 (211.3)
Number of mothers that received at least one rescue dose of
7 (12.9)
phenylephrine
Incidence of bradycardia (heart rate less than 50/min)
1 (1.8 %)
Number of mothers that received glycopyrronium
0
Co-loading volume (ml)
759 (95)
Incidence of nausea and vomiting
3 (5.5)
Values are number (%) except phenylephrine dose and co-loading volume: mean (SD).
* denotes a significant difference (p<0.05).
Intraoperative haemodynamic data and side
effects are shown in table 2. Systolic blood pressure
was not different statistically at any time during the
study period (Fig. 1).
Fig. 1
Mean systolic blood pressure in both groups
None of the neonates in both groups had an
umbilical artery pH <7.2 (Table 3). All neonatal Apgar
scores at 1 minute were ≥7 and at 5 minutes were ≥9.
P
Group 100
(n = 63)
3 (4.7)
0.12
10 (15.8)
913.5 (361.4)
1 (1.5)
0.063
<0.001*
0.023*
11 (17.4 %)
1 (1.5 %)
775 (107)
1 (1.5)
0.005*
0.46
0.39
0.33
All umbilical arterial and venous blood gas values were
not different between neonates in both groups except
the umbilical arterial PCO2 that was significantly
higher in neonates in group 100 (p<0.05).
Discussion
In this trial, we found that when using rapid
crystalloid co-loading, PE infusion of 50 mcg/min
would maintain SBP at near normal values, similar
to PE infusion of 100 mcg/min that was suggested in
previous trial.10 This trial failed to detect a difference in
the incidence of hypotension although it was powered to
detect it. Also, there was no difference in the incidence
of hypertensive episodes between both groups. Blood
pressure was measured non-invasively every minute in
this study. Invasive arterial blood pressure monitoring
would have been more sensitive but it lacks clinical
justification. There was no significant difference in
Table 3
Neonatal outcome in both groups
Group 50
(n = 54)
Group 100
(n = 63)
P
7.31 (0.04)
52.5 (6.7)
13.8 (5.0)
-0.15 (2.5)
7.30 (0.04)
55.4 (7.1)
12.7 (5.4)
0.26 (1.9)
0.14
0.02*
0.24
0.26
7.36 (0.03)
43.1 (4.2)
23.8 (5.5)
-1.5 (1.6)
7.35 (0.03)
44.4 (5.2)
24.4 (6.1)
-1.3 (1.6)
0.29
0.13
0.64
0.29
Umbilical arterial blood gases
pH
PCO2 (mmHg)
PO2 (mmHg)
Base excess (mmol Litre-1)
Umbilical venous blood gases
pH
PCO2 (mmHg)
PO2 (mmHg)
Base excess (mmol Litre-1)
Values are mean (SD), * denotes a significant difference (p<0.05).
Comparison between two phenylephrine infusion rates with moderate co-loading for the
prevention of spinal anaeshtesia- induced hypotension during elective caesarean section
the incidence of nausea and vomiting between both
groups.
Crystalloid preloading before spinal anaesthesia
for caesarean section, as a sole measure, is not effective
in preventing hypotension12. This is probably due to
its rapid redistribution and the stimulation of atrial
natriuretic peptide secretion that lead to peripheral
vasodilatation and diuresis13. Starting fluid loading
immediately after induction of spinal anaesthesia (coloading) is a more rational approach as intravascular
volume expansion coincides with sympathetic
blockade-associated
vasodilatation5,14.
Rapid
crystalloid co-loading with 20 ml/kg was associated
with less ephedrine requirement than with preloading
suggesting that co-loading has a vasopressor-sparing
effect5. In non-obstetric patients, co-loading, with
12 ml/kg, was associated with a significant increase
in cardiac output as compared to preloading and
no loading, with no difference in the incidence of
hypotension15.
In a recent Cochrane systematic review, no
conclusions were reached with respect to the optimum
intravenous fluid loading volume9. In this trial, coloading relied on a body weight-based moderate
volume of Hartmann’s solution (10 ml/kg). This
moderate co-loading would minimize any deleterious
effect of sudden intravascular volume expansion. This
volume was used previously in a similar study16. To
achieve an optimum response to co-loading, the preset
Hartmann's volume was infused as rapidly as possible,
aided with a pressure bag inflated at 200 mmHg,
through a standard 16 gauge venous catheter. Gravity
was the driving force in previous co-loading trials5,10.
Further studies are needed to quantify the vasopressorsparing effect of different co-loading volumes.
All vasopressors share the same adverse effects
that include anaphylaxis, hypertension and cardiac
dysrhythmia17. There is also a potential for impaired
utero-placental perfusion secondary to vasoconstriction.
Among the currently used vasopressors, PE is gaining
popularity in preventing spinal anaesthesia-induced
hypotension in mothers undergoing caesarean section.
Contrary to previous beliefs, it is now suggested that
maintaining utero-placental perfusion pressure by PE
outweigh its potential utero-placental vasoconstriction
effect18. This is evident by higher UApH in mothers
365
receiving PE as compared to ephedrine19.
Although some studies showed that PE was not
associated with maternal or foetal morbidity, the high
incidence of maternal bradycardia is still a concern20.
The recommended infusion dose of PE ranges from
30 to 180 mcg/min. according to blood pressure
response21. This wide dose range may precipitate
high plasma concentrations that might precipitate
hypertension and bradydysrhythmia. Ventricular
bigeminy was previously reported in a mother having
a caesarean section under spinal anaesthesia while
receiving PE boluses of 100 μg/min22. We believe that
a user-friendly infusion regimen that can be adopted
easily even by less experienced practitioners is needed.
PE infusion protocol in this study was simple. PE
infusion (60 ml/h) commenced immediately after
subarachnoid injection for 3 minutes. After 3 minutes,
the anaesthetist will either discontinue or continue PE
infusion at the same rate to maintain maternal SBP
within 20% of its baseline. If maternal SBP dropped
below 80% of baseline, PE infusion will restart at the
same rate (60 ml/h).
In this trial, only one mother in group 50
developed one or more episodes of sinus bradycardia
(1.8%) as compared to eleven mothers in group 100
(17.4%). The difference was highly significant (p =
0.005). The incidence of bradycardia in group 100 is
comparable to that of Ngan kee et al, 16.9% when used
a similar dose of PE10. Two different mechanisms could
instigate sinus bradycardia during spinal anaesthesia;
sympathetic cardiac denervation and baroreceptor
response to PE induced hypertension. In this trial,
the technique of spinal anaesthesia was the same in
all mothers. The dose of bupivacaine used (15 mg)
was within the recommended dose range18,23. As there
was no detectable difference in block height between
both groups, we can assume that the difference in
the incidence of sinus bradycardia is attributed to the
significant difference between the doses of PE. In this
trial, glycopyrrolate was given if bradycardia persists
despite PE discontinuation or if bradycardia was
associated with hypotension. There was no difference
in the use of glycopyrrolate between both groups as
apparently discontinuation of PE infusion promptly
eliminated sinus bradycardia.
All babies in both groups had an Apgar score
M.E.J. ANESTH 21 (3), 2011
366
of >7 at one minute and >9 at 5 minutes. The UA pH
was ≥7.3 for all babies in both groups. There was no
statistical significant difference between both groups’
UA and UV blood gas and acid-base values except
UA PCO2. The UA PCO2 was significantly higher
in group 100 as compared to group 50. Although the
difference in UA PCO2 was statistically significant,
it was not clinically relevant. It was previously
suggested that a higher UA PCO2 might indicate
foetal respiratory acidaemia secondary to acute uteroplacental insufficiency24. We believe that any attempt
Tarek Ansari et al.
to associate this with the higher dose of PE (100 mcg/
minute) would be speculative.
We conclude that, in combination with rapid
co-loading, an infusion rate of 50 µg/min of PE is
as adequate as 100 µg/min in prevention of spinal
anaesthesia-induced hypotension during elective
caesarean section. PE infusion of 50 µg/min is
associated with significantly less maternal bradycardia
than 100 µg/min. Both infusions are associated with a
similar neonatal outcome.
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EVALUATION OF AN INTRAOPERATIVE
ALGORITHM BASED ON NEAR-INFRARED
REFRACTED SPECTROSCOPY MONITORING, IN
THE INTRAOPERATIVE DECISION FOR SHUNT
PLACEMENT, IN PATIENTS UNDERGOING CAROTID
ENDARTERECTOMY
Ioannis D. Zogogiannis*, Christos A. Iatrou**,
Miltiadis K. Lazarides***, Theodossia D. Vogiatzaki****,
Mitchell S. Wachtel*****, Petros K. Chatzigakis******
and Vassilios K. D imitriou *******
Abstract
Background: We evaluated whether the use of an intraoperative algorithm based on
cerebral oximetry with near-infrared refracted spectroscopy (NIRS) monitoring, could aid in the
intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy (CEA).
Methods: In this prospective, randomized, controlled study were included 253 patients who
underwent CEA under general anesthesia. They were randomly allocated in Group A (n = 83) using
NIRS monitoring and the suggested algorithm, Group B (n = 84) using NIRS monitoring without
the algorithm and Group C (n = 86) who served as controls. Shunt placement criterion for Group
A and B was 20% drop in ipsilateral regional saturation from the baseline value recorded before
surgery. Primary endpoint of the study was to evaluate the use of the intraoperative algorithm
based on NIRS monitoring, in the intraoperative decision for shunt placement, in patients
undergoing carotid endarterectomy. Additionally, we examined whether this might affect the rate
of postoperative neurologic deficits.
Results: When compared with Group A, Group B and Group C had 3.7 times (99% c.i 1.59.5) and 70.6 times (99% c.i. 15-724.3) respectively, greater likelihood of having a shunt placed.
When compared with Group B, Group C had 19.4 times (99% c.i. 4.3-191.2) greater likelihood
of having a shunt placed. Regarding the rate of postoperative neurologic deficits no significant
difference was found between the three groups.
Conclusions: The use of a specific algorithm based on NIRS monitoring, in patients
undergoing CEA, may aid in the intraoperative decision for shunt placement.
*
**
Consultant Anesthetist, «G Gennimatas» General Hospital of Athens, Greece.
Associate Professor of Anesthesia, Department of Anesthesia, Democritus University of Thrace Medical School,
Greece.
***
Professor of Vascular Surgery, Medical School, Democritus University of Thrace, Greece.
****
Assistant Professor of Anesthesia, Medical School, Democritus University of Thrace, Greece.
***** Associate Professor, Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
****** Consultant Vascular Surgeon, Department of Vascular Surgery, «G Gennimatas» General Hospital of Athens, Greece.
******* Associate Professor of Anesthesia, Head of Department of Anesthesia, «G Gennimatas» General Hospital of Athens,
Greece.
Corresponding Author: Vassilios K Dimitriou, Associate Professor of Anesthesia, Head of Department of Anesthesia,
«G Gennimatas» General Hospital of Athens, 154 Mesogion Avenue, 11527 Athens, Greece. Fax: +302132032212.
E-mail address: [email protected]
367
M.E.J. ANESTH 21 (3), 2011
368
Keywords: Carotid endarterectomy,
monitoring, cerebral oximetry.
I. D. Zogogiannis et al.
shunt,
Financial competing interests
- We have not received financial support
(reimbursements, fees, funding, or grants) from
an organization that may in any way gain or lose
financially from the publication of this manuscript.
- We do not have any other financial competing
interests.
Introduction
Hypoperfusion during carotid endarterectomy
(CEA) due to clamping of the internal carotid artery
may result in cerebral ischemia or further aggravate
a preexisting brain damage1-4. The complications
reported in the NASCET and ECST studies, included
a 5.8% and 7.5% major stroke rate and 2.1% and
3.2% mortality rate, respectively1,3. Previous studies
have showed the risks for postoperative neurologic
deficits during common carotid artery (CCA) cross
clamping and embolic events due to vascular surgical
manipulations5,6. Vascular surgeons estimate the
risk adequacy of the collateral flow by measuring
the stump pressure7-10. Recently, the introduction of
cerebral Near-Infrared Refracted Spectroscopy (NIRS)
monitoring has been associated with shorter recovery
and hospital stay in noncardiac surgery11 and with a
decrease in major organ dysfunction after cardiac
surgery12. Furthermore, Denault et al. have suggested
an algorithm based on NIRS monitoring to optimize
cerebral oxygenation during surgery13. However, there
are not extensive studies for the intraoperative use
of NIRS and/or NIRS based intraoperative strategies
during carotid endarterectomy. In this prospective
study, we evaluated whether the use of an intraoperative
algorithm based on NIRS monitoring, could aid the
intraoperative decision for shunt placement, in patients
undergoing carotid endarterectomy.
Methods
This prospective, controlled, randomized
study was conducted in two Greek institutions from
December 2007 to January 2010, and included 253
patients American Society of Anesthesiologists
physical status II-III, aged 42-82 years who underwent
carotid endarterectomy. The study was in conformation
with the principles outlined in the Declaration of
Helsinki and was approved by the Institutional Ethics
Committee. The criteria for carotid endarterectomy
were symptomatic carotid artery stenosis greater than
70% and asymptomatic carotid artery stenosis greater
than 80% with coexisting risk factors14. The degree of
stenosis was evaluated by means of vascular ultrasound
and invasive angiography. Preoperatively, all patients
underwent a complete clinical neurologic evaluation
followed by a brain computed tomography (CT) scan.
Anesthetic management was standardized.
Anesthesia was induced with fentanyl and propofol.
Neuromuscular blockade was achieved with
cisatracurium. Maintenance was with remifentanil
infusion, sevoflurane in oxygen and nitrous oxide.
Heparin 100U/kg was administered five minutes before
carotid cross clamping (CCC). Stump pressure was
measured using a transducer system connected to 22G
catheter. Thirty minutes before emergence morphine
was administered for postoperative analgesia.
Standard monitoring in all patients included
electrocardiography (ECG), end tidal carbon dioxide
(EtCO2), invasive blood pressure (IBP) and pulse
oximetry (SpO2). Patients were randomly allocated by
using closed envelopes into three groups. In the first
and second group (group A and group B respectively),
in addition to the above mentioned monitoring, cerebral
oximetry with near-infrared refracted spectroscopy
(INVOS 4100, Somanetics Inc., Troy MI) was used.
Patients in the third group (Group C) underwent
routine CEA without INVOS monitoring and served
as control group. In groups A and B, the cerebral
oximetry sensors (rSO2) were placed on the forehead
over the eyebrows monitoring the ipsilateral and
contralateral hemispheres. Baseline rSO2 values were
obtained before induction and without any medication
administered and from that point continuous recording
every 10 seconds was established. Cerebral oximetry
changes were recorded when the patient entered the
operating room without any medication (T1), 2min
before CCC (T2), 2min after CCC (T3), 2min after
end of patching during reperfusion (T4), 10min after
reperfusion (T5) and after emergence (T6). The change
from the baseline (ΔrSO2) taken before induction
EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY
MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING
CAROTID ENDARTERECTOMY
was recorded in percentage. The rSO2 values were
recorded as averages. A 20% drop from the baseline
was considered as a cutoff value for ischaemia and
the surgeon was notified. This value has been well
established from previous studies15-17. During the
above time points vital signs (MAP, HR, EtCO2) were
recorded in all patients. Patients in group A were
managed according to the algorithm developed by
Denault et al13 for patients undergoing cardiac surgery,
which was adjusted for patients undergoing carotid
surgery by our team (Fig. 1). On the other hand, in
patients of group B cerebral oximetry values were
recorded but anesthesia management was not based
upon the aforementioned algorithm. Patients who
exhibited new neurologic deficits postoperatively that
persisted for more than 24 hours underwent a followup brain CT scan.
Fig. 1
The suggested intraoperative algorithm based on cerebral
oximetry with near-infrared refracted spectroscopy
369
Primary end point of the study was to evaluate
whether the use of the intraoperative algorithm based
on NIRS monitoring might affect the intraoperative
decision for shunt placement, in patients undergoing
carotid endarterectomy. Additionally, the possible effect
of the above algorithm upon the rate of postoperative
short-term neurologic deficits was examined.
Statistical Analysis
Categorical variables were evaluated by twotailed Fisher exact tests, with odds ratio estimates for
2 x 2 tables being conditional maximum likelihood
estimates. Continuous variables were evaluated by twotailed Welch's t tests, with natural logarithms of ratios
being taken. Because three statistical assessments were
performed for many variables, alpha was adjusted such
that null hypotheses were rejected when P < 0.5/3 ≈
0.015. Power analysis was performed with Power
And PrecisionTM (Biostat, Inc., Englewood, NJ). Other
statistical analyses were performed on R2.10.1 (R
Development Core Team (2009). R: A language and
environment for statistical computing. R Foundation
for Statistical Computing, Vienna, Austria. ISBN
3-900051-07-0, URL http://www.R-project.org).
All remaining analyses had results that might
have been due to chance (P > 0.015, for each analysis);
power analysis revealed all would have been able to
detect moderate sized differences. Seventy patients per
patient group detects as significant moderately-sized
differences for χ² tests of 2 x 2 contingency tables and
two-tailed t tests in 81% of studies with alpha = 0.01.
Table 1
Demographic and clinical characteristics
Group A
Group B
Group C
(n = 83)
(n = 84)
(n = 86)
P-values
Fisher exact test, two-tailed
A vs B
A vs C
B vs C
Gender (M/F)
57/26
68/16
Mean (range)
60/26
0.20
0.87
0.12
Age (yrs)
BMI (kg/m2)
69.1 (50-82)
27.7 (23.1-33.1)
68.3 (48-80)
26.9 (21.5-33.8)
N (%)
68.4 (48-81)
28.2 (22-33.1)
0.28
0.15
0.28
0.31
0.40
0.0057
Hyperlipidemia
Hypertension
Diabetes mellitus
Coronary artery disease
42/83 (50.6%)
45/83 (54.2%)
21/83 (25.3%)
32/83 (38.5%)
41/84 (48.8%)
47/84 (55.9%)
21/84 (25%)
31/84 (36.9%)
40/86 (46.5%)
46/86 (53.4%)
24/86 (27.9%)
33/86 (38.3%)
0.71
0.68
0.87
0.7
0.3
0.85
0.7
0.75
0.56
0.65
0.71
0.7
Hemodialysis
4/83 (4.8%)
5/84 (5.9%)
5/86 (5.8%)
0.85
0.88
0.88
M.E.J. ANESTH 21 (3), 2011
370
I. D. Zogogiannis et al.
Table 2
Preoperative neurologic status
Group A
Group B
Group C
(n = 83)
(n = 84)
(n = 86)
Asymptomatic
56/83 (67.4%)
56/84 (66.7%)
58/86 (67.4%)
Symptomatic
27/83 (32.5%)
27/84 (32.1%)
27/86 (31.3%)
Stroke
11/83 (13.2%)
13/84 (15.4%)
14/86 (16.2%)
TIAs
9/83 (10.8%)
10/84 (11.9%)
10/86 (11.6%)
Amaurosis fugax
7/83 (8.4%)
5/84 (5.9%)
4/86 (4.6%)
Differences between groups were not statistically significant (Fisher’s test), TIAs: Transient Ischemic Attacks.
Results
Patients were randomly allocated to three groups:
group A (n = 83) and group B (n = 84) in which NIRS
monitoring was applied and group C (n = 86) in
which only standard anesthesia monitoring was used
(control group). There were no differences between
groups with respect to demographic and clinical
characteristics (Table 1). There were not statistically
significant differences in the preoperative neurologic
status between the three groups (Table 2).
Table 3 shows data from the monitoring of
intraoperative vital signs. MAP values taken two
minutes after the opening of the CCA (T4) were
decreased in all groups as compared to values taken two
minutes before CCA cross clamp (T2). Chronological
alterations in MAP between the above two time points
(MAP T4/T2 ratios) were significantly increased in
both groups A and B as compared to controls, which
means that accordingly there was a smaller amount of
reduction in MAP values in groups A and B as compared
to controls (Table 3). EtCO2 values taken two minutes
after the opening of the CCA (T4) were increased
in groups A and B, while decreased in controls, as
compared to values taken two minutes before CCA
cross clamp (T2) (Table 3). Finally, chronological
alterations in rSO2 values between two minutes after
CCA cross clamp and two minutes before CCA cross
clamp, as described by the rsO2 T3/T2 ratio, showed
an increase of the above ratio in group A as compared
to group B (Table 3).
Table 4 describes significant differences
concerning shunt placement that were recorded
between groups. Specifically, patients in groups B and
C exhibited 3.7 times (99% c.i 1.5 - 9.5) and 70.6 times
Table 3
Intraoperative monitoring data
Group A
(n = 83)
MAP T3/T2
MAP T4/T2
0.85 (0.6-1.14)
0.86 (0.58-1.2)
Group B
Group C
(n = 84)
(n = 86)
Log mean (range)
0.87 (0.54-1.2)
0.83 (0.65-1.1)
0.96 (0.74-1.4)
0.78 (0.57-1.35)
P-values
Welch's t test, two-tailed, on logs
A vs B
A vs C
B vs C
0.57
0.31
0.11
< 0.001
0.002
< 0.001
MAP T5/T2
0.81 (0.6-1.27)
0.92 (0.65-1.3)
0.77 (0.6-1.04)
< 0.001
0.07
< 0.001
HR T3/T2
0.97 (0.68-1.9)
1.0 (0.66-1.5)
0.96 (0.65-1.5)
0.39
0.76
0.20
HR T4/T2
1.01 (0.75-1.7)
1.03 (0.57-1.5)
0.98 (0.6-1.5)
0.50
0.46
0.19
HR T5/T2
1.01 (0.75-1.5)
1.0 (0.60-1.5)
1.04 (0.8-1.6)
0.85
0.36
0.30
etCO2 T3/T2
1.03 (0.90-1.2)
1.01 (0.92-1.1)
0.95 (0.8-1.2)
0.015
< 0.001
< 0.001
etCO2 T4/T2
1.05 (0.94-1.4)
1.02 (0.92-1.1)
0.93 (0.8–1.0)
0.006
< 0.001
< 0.001
etCO2 T5/T2
1.03 (0.9-1.3)
1.03 (0.97-1.1)
0.90 (0.8–1.0)
0.87
< 0.001
< 0.001
rSO2 T3/T2
0.91 (0.73-1.1)
0.85 (0.6-1.1)
§
< 0.001
§
§
rSO2 T4/T2
1.04 (0.9-1.2)
1.02 (0.82-1.2)
§
0.11
§
§
rSO2 T5/T2
1.04 (0.9-1.2)
1.03 (0.83-1.2)
§
0.43
§ §
MAP: mean arterial pressure, HR: heart rate etCO2: end-tidal carbon dioxide, rSO2: cerebral oximeter measured regional hemoglobin
saturation in cerebral tissue ipsilateral to the operated carotid artery. MAP, HR, et CO2 and rSO2 ratios reference ratios of measurements
taken at different time points: T2 - two minutes before common carotid artery cross clamp; T3 - two minutes after common carotid
artery cross clamp; T4 - two minutes after opening common carotid artery; T5 - ten minutes after opening common carotid artery. §
rSO2 values were not recorded in the control group.
EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY
MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING
CAROTID ENDARTERECTOMY
(99% c.i. 15 - 724.3), respectively, greater likelihood
of having a shunt placed, as compared with patients in
group A. When compared with Group B, Group C had
19. 4 times (99% c.i. 4.3 - 191.2) greater likelihood of
having a shunt placed.
Table 4
Intraoperative shunt placement
Shunt
Not placed
Placed
p-value
Fisher's exact test
Group C 0 (0%)
86 (100%)
<0.001
Group A 60 (72.3%)
23 (27.7%)
<0.001
Group B 34 (40.5%)
50 (59.5%)
<0.001
There were no significant differences between
the three groups regarding postoperative neurologic
deficits (Table 5). Thirty two out of the total 253
patients (12.6%) experienced neurologic deficits
postoperatively and only 13 out of the total 253
patients (5.1%) suffered a permanent deficit confirmed
by a CT scan as an ischemic region. Finally, seven
out of the total 253 patients (2.7%), (group A n = 1,
group B n = 2 and group C n = 4) exhibited evidence
of cardiovascular ischemia, as assessed by clinical and
laboratory examinations; while 2 out of the total 253
patients (0.8%), one in group B and one in group C,
expired due to cardiovascular events, postoperatively.
Table 5
Postoperative neurologic deficits between groups
Neurologic
deficit
Group A
Group B
Group C
No
73 (87.9%) 73 (86.9%) 75 (87.3%)
Yes
10 (12.1%) 11 (13.1%) 11 (12.7%)
P-value
Fisher's
exact test
0.89
Discussion
We demonstrated that the use of an intraoperative
algorithm based on NIRS monitoring, in patients
undergoing carotid endarterectomy, may aid in the
intraoperative decision for shunt placement. The latter
during carotid endarterectomy is a surgical practice
that may minimize the risk of perioperative cerebral
ischemia18. However, definite benefits from this
intraoperative practice have not been published yet.
Additionally, there is no consensus whether routine
shunting is superior to selective shunting during
carotid endarterectomy19.
The present data suggested that in patients in whom
371
an intraoperative algorithm based on NIRS monitoring
was used (group A), the rate of shunt placement was
reduced as compared to patients in whom even though
NIRS monitoring was applied the specific algorithm
was not utilized (group B). Additionally, no significant
differences between the three groups concerning the
rate of postoperative neurologic deficits were recorded.
Postoperatively, 12.6% of patients presented with new
neurologic deficits, and only 5.1% of patients were
diagnosed with permanent deficits. These findings are
in agreement with the NASCET and ECST studies1,2.
During surgery the identification of possible
hypoperfusion may aid in the intraoperative decision
for the necessity of shunt placement. Intraoperative
stroke accounts for 15–20% of the perioperative
strokes, due to hypoperfusion during cross-clamping
or thromboembolism20,21. Intraoperative neurological
deficit is most often associated with carotid artery
dissection or clamp release (83%) and only rarely
(17%) with cross-clamping22.
Mental status evaluation during carotid crossclamping in the awake patient remains the gold
standard with which other methods of monitoring
should be compared23,24. Monitoring of the conscious
patient provides a unique opportunity to determine
the time of onset of a neurological deficit and to
deduce the likely cause25,26. In patients under general
anesthesia monitoring with electroencephalography
(EEG) is oftentimes applied27, however this method
can not reliably detect cerebral ischaemia and therefore
provide a clear guide to shunting. Recent data reported
a 82% rate of shunting in patients who underwent
CEA under general anesthesia28, which is significantly
higher compared with the 28.4% recorded rate in our
patients in whom the specific intraoperative algorithm
based on NIRS monitoring was used.
Cerebral
oximetry
with
near-infrared
spectroscopy (NIRS) allows for continuous monitoring
of changes in cerebral oxygenation (rSO2) through
adhesive sensors on the patients’ forehead16,29,30. NIRS
was evaluated under regional anesthesia in patients
undergoing CEA by previous studies (16, 31). In these
studies rSO2 values showed an intersubject variability
in the pre-clamp period. Specifically, Samra et al16
considered a decrease in rSO2 of 20%, or an absolute
reading of less than 50%, as indicative of cerebral
M.E.J. ANESTH 21 (3), 2011
372
I. D. Zogogiannis et al.
ischaemia, resulting in a false-negative rate of 2.6%
and a false-positive rate of 66.7%. Roberts et al31 used
a decrease of ≥ 27% in rSO2 as indication for a shunt
and had no false-negative or false-positive results in
45 patients. A possible explanation was the shorter
duration of cross-clamping, and it was demonstrated
that permanent sequelae result from a combination of
both the magnitude and duration of ischaemia31.
the study groups postoperatively. Therefore placement
of shunt may not be of the major criteria to avoid
neurological complications. It may be the patient's
integrity of circle of Willis and collateral circulation
to compensate the acute ischemia during carotid cross
clamp. From this point of view cerebral oximetry
with near-infrared spectroscopy may be a useful and
effective monitoring.
Our study implemented the use of NIRS
monitoring along with a series of interventions such
as intraoperative adjustments of MAP, CO2, FiO2 and
pertinent modifications in the depth of anesthesia in
order to provide a safe guide for shunting.
Our study exhibits several limitations. First,
embolic insult is a significant factor in determining
patient outcome and no published studies have
demonstrated that NIRS can detect emboli. On the other
hand, neither EEG nor SEP can detect emboli and even
the usage of transcranial Doppler is rather problematic
in detecting emboli32-34. Additionally, NIRS is highly
regional in nature and monitoring is limited to a small
but critical area of the watershed between the middle
and anterior cerebral arteries territories.
In the present study a 20% drop in rSO2 was used
as a cutoff value indicative of cerebral ischemia, which
is comparable to previous reports16,31. Interestingly, we
found that chronological alterations in between and
two minutes before CCA cross clamp, as described
by the rsO2 T3/T2 ratio, showed an increase of the
above ratio in group A as compared to group B. Hence,
two minutes after CCA cross clamp rSO2 values
were increased in group A as compared to group B.
This might be attributed to the fact that intraoperative
adjustments of MAP, CO2, FiO2 and pertinent
modifications in the depth of anesthesia, according to
the suggested algorithm, were applied only in patients
of group A. However, no significant differences in the
rate of new neurologic deficits were recorded between
Conclusions
We found that the use of an intraoperative
algorithm based on NIRS monitoring, in patients
undergoing carotid endarterectomy, may aid in the
intraoperative decision for shunt placement. However,
no significant effect of the above method upon the rate
of postoperative neurologic deficits was observed.
EVALUATION OF AN INTRAOPERATIVE ALGORITHM BASED ON NEAR-INFRARED REFRACTED SPECTROSCOPY
MONITORING, IN THE INTRAOPERATIVE DECISION FOR SHUNT PLACEMENT, IN PATIENTS UNDERGOING
CAROTID ENDARTERECTOMY
373
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M.E.J. ANESTH 21 (3), 2011
Effects of preoperative oral carbohydrates
and trace elements on perioperative
nutritional status in elective
surgery patients
Yoshimasa Oyama*, Hideo Iwasaka*, Keisuke Shiihara*,
Satoshi Hagiwara*, Nobuhiro Kubo**, Yutaka Fujitomi***,
Takayuki Noguchi*
Abstract
Purpose: In order to enhance postoperative recovery, preoperative consumption of carbohydrate
(CHO) drinks has been used to suppress metabolic fluctuations. Trace elements such as zinc and
copper are known to play an important role in postoperative recovery. Here, we examined the
effects of preoperatively consuming a CHO drink containing zinc and copper.
Methods: Subjects were 122 elective surgery patients divided into two groups (overnight
fasting and CHO groups); each group was further divided into morning or afternoon surgery
groups. Subjects in the CHO group consumed 300 mL of a CHO drink the night before surgery,
followed by 200 ml before morning surgery or 700 ml before afternoon surgery (≥2 hours before
anesthesia induction). Blood levels of glucose, nonesterified fatty acids (NEFA), retinol-binding
protein, zinc, and copper were determined.
Results: One subject in the CHO group was excluded after refusing the drink. There
were no adverse effects from the CHO drink. NEFA levels increased in the fasting groups.
Although zinc levels increased in the CHO group immediately after anesthesia induction, no group
differences were observed the day after surgery.
Conclusion: Preoperative consumption of a CHO drink containing trace elements suppressed
preoperative metabolic fluctuations without complications and prevented trace element deficiency.
Further beneficial effects during the perioperative period can be expected by adding trace elements
to CHO supplements.
*
**
***
M.D. Ph.D, Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita,
Japan.
M.D, Ph.D, Department of Surgery, Oita Kouseiren Tsurumi Hospital, Oita, Japan.
M.D., Ph.D, Department of Breast Surgery, Oita Kouseiren Tsurumi Hospital, Oita, Japan.
Corresponding Author: Yoshimasa Oyama M.D, Department of Anesthesiology and Intensive Care Medicine, Oita
University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita 879-5593, Japan. Tel: +81-97-586-5943,
Fax: + 81-97-586-5949. E-mail: [email protected]
375
M.E.J. ANESTH 21 (3), 2011
376
Introduction
In the last decade, the customary practice of
overnight fasting before elective surgery has been
reconsidered, and a shorter fasting time has been
advised. Intake of water, black coffee, tea, or fruit
juice without pulp up to 2 to 3 h before anesthesia
induction does not increase the risk of pulmonary
aspiration and is recommended by anesthesiology
societies in many countries1-4. However, while thirst,
unfitness, and malaise prior to surgery can be improved
by preoperative intake of such drinks5, metabolism is
unchanged because the drinks contain few calories. In
recent years, preoperative management has focused
on maintaining physiologic function and enhancing
postoperative recovery. The Enhanced Recovery After
Surgery (ERAS) critical care protocol recommends
the preoperative consumption of a carbohydrate
(CHO) drink6, which helps maintain the nutritional
state and suppress catabolism due to surgical stress7.
Furthermore, it has been reported to enhance recovery
and reduce the duration of hospitalization8.
Many nutrients are important for postoperative
recovery, including the trace elements zinc (Zn) and
copper (Cu), which are important in wound healing.
Zn is required by enzymes involved in cell division
and proliferation, and Cu is required for initiate the
cross-linking of elastin and collagen9,10. Surgical stress
increases Zn and Cu consumption11, increases their
excretion in urine and discharge through drains12-14,
and causes their direct loss by bleeding. Moreover,
the demand for these elements increases during
the postoperative assimilation phase, resulting in
perioperative Zn and Cu deficiencies. Low preoperative
concentrations of Zn have been observed in patients
with delayed postoperative wound healing15, and
satisfactory outcomes have been obtained for burn
patients by early administration of trace elements16.
However, studies evaluating the effects of preoperative
supplementation of trace elements in elective surgery
patients have not been reported.
In order to evaluate the nutritional state resulting
from preoperative nutrition management, a dynamic
index capable of detecting subtle changes is needed.
Generally, a protein with a short half-life is used for
this purpose. Among such proteins, retinol-binding
protein (RBP) is considered a good indicator of
Y. Oyama et al.
daily nutritional changes17, and is well-suited for
evaluating nutritional states that may be influenced by
preoperative nutrition management.
Preoperative oral CHO administration is used
effectively throughout Europe and the United States.
However, conventional overnight fasting is still
used as standard practice in some nations18,19.
The aim of this study was to evaluate the effects
of an 18% CHO drink containing trace elements on
preoperative nutritional state and trace element levels
as compared with a conventional fasting protocol.
Methods
This study was conducted between May and
August 2009. The study protocol was approved by
the Medical Ethics Committee of Oita Kouseiren
Tsurumi Hospital, and was carried out in accordance
with the Helsinki Declaration. For all subjects, we
provided a full explanation of the aims and methods
of the study and obtained their informed consent.
Patients
Subjects were 122 elective surgery patients.
Selection criteria were: scheduled surgery; age, 20-89
years; body mass index (BMI), 18-35; and American
Society of Anesthesiologists (ASA) physical status (PS)
classification, 1-3. Exclusion criteria were: diabetes,
abnormal glucose tolerance, upper gastrointestinal
disease (gastroesophageal reflux, hiatal hernia), ileus,
use of drugs that cause delayed gastric emptying, and
patients that needed to begin fasting two days before
surgery. One subject in the CHO consumption group
refused the CHO drink after we obtained consent, and
was therefore excluded.
Patients were divided into two groups according
to the period of study: 1) The first 2-month period
involved the conventional overnight fasting protocol
at this hospital (fasting group, n = 61); 2) the next
2-month period used the new protocol of preoperative
CHO drink supplementation (CHO group, n = 60).
Both groups were further divided into morning
surgery (AM group, 9:30-10:00 surgery suite entry)
and afternoon surgery (PM group, 14:00-16:00 surgery
suite entry). Patient characteristics are shown in
Table 1.
Effects of preoperative oral carbohydrates and trace elements on perioperative
nutritional status in elective surgery patients
377
Table 1
Patient characteristics and demographic data
AM fasting
PM fasting
AM CHO
PM CHO
n = 26
n = 35
n = 27
n = 33
9/17
17/18
7/20
15/18
Age (y)
62 ± 11
61 ± 18
59 ± 12
61 ± 15
Height (cm)
157 ± 9
159 ± 9
159 ± 9
157 ± 9
Weight (kg)
BMI (kg/m2)
59 ± 12
60 ± 12
61 ± 10
58 ± 9
24 ± 4
24 ± 4
24 ± 3
24 ± 3
ASA (I/II/III)
4/22/0
5/29/1
6/20/1
7/25/1
Sex (M/F)
178 ± 81#
Duration of surgery (min)
132 ± 64
135 ± 60
132 ± 72
Data are presented as absolute numbers or mean ± SD. CHO = carbohydrate, M = male, F = female, BMI = body mass index, ASA
#
= classification of illness according to the American Society of Anesthesiology. P <0.05 vs. PM fasting, AM CHO, and PM CHO
groups (ANOVA).
Study protocol
For all patient groups, the final meal before
surgery was at 18:00. The fasting group began their
fast at 21:00 on the night before surgery. The CHO
group ingested a CHO drink (IsocalTM, Arginaid®
drink, Nestle) the CHO drink and then waited
2-3 hours before surgery: AM surgery group
(300 ml from 21:00 throughout the night before
surgery and 200 ml from 6:30 to 7:30 on the day
of surgery), and PM surgery group (300 ml from
21:00 throughout the night before surgery, and on
the day of surgery, 200 ml from 6:30 to 7:30, 300 ml
from 9:00 to 10:00, and 200 ml from 11:00 to 12:00)
(Fig. 1). The contents of the Arginaid® drink are shown
in Table 2. In the fasting group, intravenous crystalloid
fluid solution without sugar was initiated at 9:00
for morning and afternoon surgeries. In the CHO
group, intravenous crystalloid fluid solution without
sugar was initiated at 9:00 for morning surgeries and
13:00 for afternoon surgeries. Blood samples for
measuring blood glucose, nonesterified fatty acid
(NEFA), RBP, Zn, Cu, blood urea nitrogen (BUN),
and creatinine were collected immediately after
anesthesia induction, and blood samples for Zn and
Cu measurements were also collected the following
morning. To assess patient discomfort before surgery,
we asked questions regarding thirst, hunger, and
anxiety using a questionnaire immediately after they
entered the surgery suite. Responses were given using
a 5-point Likert scale (1: not at all, 2: hardly, 3: neither,
4: somewhat, 5: very much).
Fig. 1
Timeline of perioperative carbohydrate (CHO) drink
consumption
Table 2
Contents of the preoperative carbohydrate drink suppleent
(ISOCAL® Arginaid® drink)
Typical contents per 100 ml
Carbohydrates
18 g
Protein
2g
L-arginine
2g
Phosphorus
18 mg
Zinc
8 mg
Copper
0.8 mg
Anesthesia and surgery
No premedication was administered, and
patients walked into the surgery suite. If there were
no contraindications, patients received an epidural
catheter at an appropriate location before general
anesthesia in thoracic surgery, orthopedic surgery
of the lower limbs, or urinary tract surgery. Epidural
anesthesia was initiated before general anesthesia
with mepivacaine. When combined with epidural
anesthesia, general anesthesia was induced with
propofol (2 mg/kg) and vecuronium (0.1 mg/kg),
M.E.J. ANESTH 21 (3), 2011
378
and maintained by sevoflurane (1%3%-). When not
combined with epidural anesthesia, general anesthesia
was induced with propofol (1.5 mg/kg), vecuronium
(0.1 mg/kg), and remifentanil (0.5 µg/kg/min);
sevoflurane (1%-3%) and remifentanil (0.2-0.5 µg/
kg/min) were used for maintenance. Heart rate and
blood pressure were recorded at the following time
periods: immediately before anesthesia induction,
and 1, 2, and 5 minutes after anesthesia induction.
The anesthesiologist maintained normovolemia
throughout the surgery and gave a single injection of
ephedrine (4 mg) as a vasopressor to maintain mean
systolic blood pressure at 60-70 mmHg. When
the target blood pressure could not be maintained,
the anesthesiologist initiated continuous infusion of
dopamine (2-5 µg/kg/min).
Assessment of gastric content volume
To determine residual gastric content, a doublelumen gastric tube was inserted immediately after
anesthesia induction. Insertion into the stomach was
confirmed by auscultation and aspiration. The gastric
tube was moved several times, and gastric juice was
aspirated at several locations. The amount of gastric
juice was then measured.
Biochemical analysis
Blood glucose levels were measured immediately
after collection by the glucose oxidase method
using a blood gas analyzer (ABL-555, Radiometer,
Copenhagen, Denmark). Blood samples for measuring
NEFA, RBP, Zn, Cu, BUN, and creatinine were
centrifuged immediately after collection and stored at
-20˚C until analysis.
NEFA levels were determined by enzymatic
methods (SRL, Tokyo, Japan), and RBP levels were
determined with nephelometric methods (SRL, Tokyo,
Japan). Serum BUN (urease-glutamate dehydrogenase
method), creatinine (sarcosine oxidase-peroxidase
method), Zn (5-Br-PAPS colorimetric method;
reference range118-66 µg/dl), and Cu (3,5-DiBrPAESA colorimetric method; reference range 71-132
µg/dl) were determined by an automated analyzer
(TBA-200FR; Toshiba Medical Systems, Tokyo,
Japan) and commercial kits (Shino-Test, Tokyo, Japan
for creatinine, Zn, and Cu; SYSMEX, Hyogo, Japan
for BUN).
Y. Oyama et al.
Statistical analysis
Parametric data are expressed as mean ± standard
deviation (SD); group differences were determined by
one-way ANOVA or Student’s t-test, and differences
in repeated measurements by Fisher’s protective leastsquares difference and paired samples t-test.
Nonparametric data are expressed as medians
and quartiles; group differences were determined by
the Kruskal-Wallis test and differences in repeated
measurements by the Mann-Whitney U-test. P <0.05
was considered significant. Statistical analysis was
carried out with StatView for Windows, version 5.0
(SAS Institute Inc.).
Results
Demographic data
Of the 122 elective surgery patients, one subject
in the CHO group refused the CHO drink after we
obtained consent and was thus excluded; 121 subjects
completed the study. There were no differences in
patient characteristics before surgery; however, surgery
duration for the AM fasting group was longer than that
of the other patient groups (Table 1).
The types of surgery performed are shown in
Table 3. Thoracic surgeries were lobectomies and
partial lobectomies, breast surgeries were mastectomies
and breast preservations, gastrointestinal surgeries
were laparoscopic cholecystectomies, plastic surgeries
were body surface surgeries, orthopedic surgeries
were joint replacement and spinal surgeries as well
as osteosynthesis of broken limbs, and urinary tract
surgeries were prostatectomies and bladder removal.
Given the hospital’s surgery schedule, no orthopedic
or urinary surgeries were performed in the morning
(AM) surgery groups.
Table 3
Surgical procedures
AM fasting PM fasting AM CHO PM CHO
n =26
n =35
n =27
n =33
Thoracic, n
Breast, n
Digestive, n
Urologic, n
Plastic surgery, n
Orthopedic, n
CHO = carbohydrate.
8
11
4
0
3
0
2
6
3
5
8
11
8
7
5
0
7
0
2
8
2
5
9
7
Effects of preoperative oral carbohydrates and trace elements on perioperative
nutritional status in elective surgery patients
379
Table 4
Preoperative patient characteristics
AM fasting
n =26
Glucose (mg/dl)
PM fasting
n =35
102 ±14
93 ±11
AM CHO
n =27
PM CHO
n =33
104 ±16
105 ±11
§§
#
475 ±278
**
589 ±357 ††
NEFA (µEq/L)
679 ±237
927 ±317
RBP (mg/dl)
4.1 ±1.4
3.7 ±1.1
3.8 ±0.9
5.0 ±6.6
BUN (mg/dl)
15 ±7
14 ±4
14 ±3
16 ±4
Creatinine (mg/dl)
0.8 ±0.4
0.7 ±0.2
0.7 ±0.1
0.8 ±0.2
Data are presented as mean ± SD. CHO = carbohydrate, NEFA = nonesterified fatty acids, RBP = retinol binding protein. §§P
<0.01 vs. AM fasting, AM CHO, and PM CHO groups; #P <0.05 vs. AM fasting; **P <0.01 vs. AM fasting; † †P <0.01 vs. PM fasting.
Preoperative fasting duration was 751 ± 6 min
for AM fasting and 1013 ± 13 min for PM fasting.
The time from final CHO drink consumption to
anesthesia was 201 ± 4 min for the AM CHO group
and 209 ± 11 min for the PM CHO group. In the
CHO groups, the time from the final meal excluding
drink consumption was 754 ± 9 min for AM CHO and
1023 ± 15 min for the PM CHO group, which did
not differ significantly from fasting durations in the
fasting groups.
Effects of CHO consumption on preoperative
biochemical data
As shown in Table 4, blood glucose levels
immediately after anesthesia induction were lower in
the PM fasting group than in other patient groups.
However, NEFA increased more in the PM fasting
group (927 ± 54 µEq/L) than the AM fasting group
(679 ± 46 µEq/L; P = 0.022), and was lower in
the AM CHO group (475 ± 54 µEq/L) than the AM
fasting group (679 ± 46 µEq/L; P = 0.016). Likewise,
there was a significant decline in the PM CHO group
(589 ± 62 µEq/L) compared with the PM fasting
group (927 ± 54 µEq/L; P <0.001). In contrast, RBP,
BUN, and creatinine levels did not differ among
patient groups.
Effects of CHO on serum trace element levels
Table 5 shows that, immediately after anesthesia
induction, serum levels of Zn were higher in the
CHO groups than in the fasting groups (AM fasting vs.
AM CHO: 67 ± 2 μg/dl vs. 105 ± 4 μg/dl, P <0.001;
PM fasting vs. PM CHO: 69 ± 2 μg/dl vs.100 ± 4
μg/dl, P <0.001). However, on postoperative day 1, Zn
levels had decreased in the CHO groups and were not
significantly different from the fasting groups.
Serum levels of Cu did not differ among
groups immediately after anesthesia induction or on
postoperative day 1. However, in the CHO group, Cu
levels on postoperative day 1 were lower than those
observed immediately after anesthesia induction.
Table 5
Trace elements
AM fasted
PM fasted
AM CHO
PM CHO
n =26
n =35
n =27
n =33
67 ± 9
69 ± 10
105 ± 19**
62 ±10 ##
59 ±15 ##
65 ±10 ##
65 ±21 ##
96 ±16
96 ±17
93 ±16 #
96 ±15
102 ±23
95 ±21 ##
Zn (μg/dl)
Anesthesia induction
Day 1
Cu (μg/dl)
Anesthesia induction
Day 1
Data are presented as mean ± SD. CHO = carbohydrate.
anesthesia induction; ##P <0.01 vs. anesthesia induction.
95 ±14
**
P <0.01 versus AM fasting;
96 ±16
††
100 ±
†
21†
P <0.01 vs. PM fasting; ## P <0.01 vs.
M.E.J. ANESTH 21 (3), 2011
380
Effects of CHO on preoperative discomfort
Answers to the questionnaire evaluating thirst,
hunger, and anxiety before anesthesia induction did
not differ significantly among groups (Table 6).
Effects of CHO on perioperative clinical
data
Heart rate and blood pressure at each time
periods did not differ significantly across groups.
At 1, 2, and 5 minutes after anesthesia induction,
heart rate and blood pressure were lower than those
observed immediately before anesthesia induction
(Table 7). During the anesthesia induction period,
inotrope requirements did not differ across groups.
For PM surgeries, preoperative intravenous fluid
replacement was lower in the CHO groups than the
fasting groups due to protocol differences; however, no
differences in intravenous fluid replacement amounts
were observed among patient groups during surgery.
We did not observe a single case of pulmonary
aspiration or other adverse event associated with
CHO drink consumption. Mean gastric juice volumes
immediately after anesthesia induction were low,
and did not differ among groups (Table 8). Maximum
volumes of gastric juice were 83 ml (AM fasting), 60
ml (PM fasting), 71 ml (AM CHO), and 33 ml (PM
CHO).
Discussion
The present study shows that preoperative
supplementation of a CHO drink containing trace
elements suppresses preoperative increases in NEFA
levels and decreases in Zn levels. The CHO drink
was a hypertonic solution containing protein and trace
elements; therefore, gastric retention time may have
been prolonged compared with that of an isotonic
CHO drink. Henriksen et al. reported that preoperative
supplementation with a drink containing 12.5% CHO
and 3.5% protein did not increase gastric juice
volume. Likewise, we did not observe increased gastric
juice volume or pulmonary aspiration, demonstrating
the safety of this perioperative protocol.
The CHO group took more water during the
preoperative period than did the fasting group.
However, during the anesthesia induction period, heart
Y. Oyama et al.
rate and blood pressure did not differ significantly
across groups, indicating that the balance of bodily
fluids did not differ significantly. We also observed no
group-dependent differences in intraoperative fluid
volume or urinary volume. These observations may
indicate that dehydration caused by overnight fasting
as well as that caused by CHO drink replacement is
within a normal range of homeostasis, and is mainly
regulated by renal function.
In the CHO groups, preoperative NEFA levels
were low compared to those of the fasting groups
due to lipolysis suppression, which is consistent with
previous reports by Soope et al. and Henriksen et
al.7,20. Elevated NEFA levels suppress phosphoinositide
3-kinase in muscle cells, thereby lowering glucose
uptake and promoting insulin resistance21. Accordingly,
glucose oxidation and nonoxidative glucose disposal
have been prevented by intravenous administration of
lipids to healthy adults22. Preoperative consumption of
a CHO drink has also been shown to attenuate insulin
resistance23, possibly by reducing NEFA levels.
RBP changes were not observed in the present
study. The half-life of RBP is 10 to 20 h, suggesting
that RBP would respond to subtle differences in the
nutritional state caused by brief perioperative fasting
or CHO drink consumption. Fasting times were 12 to
17 h, which may have been too short to be captured
by RBP changes. Deteriorating renal function can also
increase RBP [24], but no differences in renal function
were observed in the study.
Wound repair is an important postoperative
process, and delayed wound healing is a serious
problem. The trace elements Zn and Cu are important
in wound healing. Zn is essential for cell division
and proliferation, and demand for Zn increases after
surgery. In a state of deficiency, Zn is supplied by
bone, muscle, and the liver, which generally store Zn.
In the present study, we observed that preoperative
serum Zn concentrations were decreased to the lower
end of the reference range in the fasting groups, which
reflects the notion that serum Zn is taken from storage.
However, surgical stress increases Zn demand11 as well
as depletes it through draining12-14 and bleeding. Thus,
Zn deficiencies are likely during the perioperative
period. In contrast, we observed higher serum Zn
concentrations in the CHO groups. This suggests
Effects of preoperative oral carbohydrates and trace elements on perioperative
nutritional status in elective surgery patients
381
Table 6
Preoperative discomfort evaluated by 5-point Likert scale
AM fasting
n = 26
PM fasting
n = 35
AM CHO
n = 27
PM CHO
n = 33
Thirst
2.5 (0.5-4.5)
3 (1-5)
2 (0-4)
2 (0.75-3.25)
Hunger
2.5 (0.5-4.5)
4 (2-6)
3 (1-5)
3 (1-5)
Anxiety
2 (1-3)
2 (1-3)
1 (0-2)
2 (1-3)
Data are presented as median (interquartile range: 25 -75 percentiles) CHO = carbohydrate.
th
th
Table 7
Time course of changes in heart rate, blood pressure during anesthesia induction
HR (beats/min)
SBP (mmHg)
DBP (mmHg)
T0
T1
T2
T5
T0
T1
T2
T5
T0
T1
T2
T5
AM-fasted
71
±
18
61
±
19*
58
±
18*
55
±
16*
133
±
21
91
±
21*
80
±
19*
75
±
16*
73
±
12
48
±
10*
43
±
11*
40
±
10*
PM-fasted
71
±
12
63
±
13*
59
±
11*
57
±
13*
144
±
21
103
±
20*
91
±
19*
82
±
18*
77
±
11
56
±
11*
50
±
11*
45
±
9*
AM-CHO
70
±
14
61
±
15*
58
±
14*
57
±
12*
123
±
18
90
±
17*
82
±
15*
76
±
15*
70
±
11
50
±
10*
45
±
10*
42
±
9*
PM-CHO
71
±
13
62
±
12*
59
±
12*
58
±
12*
140
±
24
95
±
23*
86
±
17*
83
±
18*
75
±
15
53
±
13*
45
±
13*
45
±
13*
Data are presented as mean ± SD. CHO = carbohydrate, HR = Heat rate, SBP = systolic blood pressure, DBP = diastolic blood
pressure, T0 = immediate before anesthesia induction, T1 = 1 min after anesthesia induction, T2 = 2 min after anesthesia induction, T5
= 5min after anesthesia induction. *P <0.05 vs. T0.
Table 8
Perioperative clinical data
AM fasting
n = 26
PM fasting
n = 35
AM-CHO
n = 27
Preoperative fluid (ml)
161 ± 49
357 ± 159
140 ± 52
191 ± 96
Intraoperative fluid (ml)
1082 ± 493
1237 ± 629
798 ± 290
1130 ± 936
Blood loss (ml)
91 ± 136
172 ± 253
46 ± 64
138 ± 253
Urine (ml)
395 ± 318
303 ± 289
281 ± 175
194 ± 133
12 ± 22
11 ± 16
13 ± 18
10 ± 12
Gastric fluid volume (ml)
Data are presented as mean ± SD. CHO = carbohydrate.
PM-CHO
n = 33
**
**
P <0.01 vs. PM fasting.
M.E.J. ANESTH 21 (3), 2011
382
that ingesting a CHO drink with trace elements may
maintain not only serum Zn concentrations, but also
its storage in bone, muscle, and the liver, which may
help increase Zn demand during the perioperative
period. We observed lower Zn concentrations the
day after surgery in all groups, but group-related
differences did not exist. We did not administer
any trace elements postoperatively, as this yields a
decrease in Zn concentrations, as demonstrated in the
fasting groups immediately after anesthesia induction.
Acute stress induces metallothionein, which has a
strong affinity for Zn25 and redistributes Zn to the
liver and other tissues for protein synthesis, thereby
reducing serum Zn levels26. Zorrilla et al. reported
that low preoperative serum Zn concentrations were
predictive of delayed wound healing following total
hip replacement15. Maintaining preoperative serum Zn
concentrations may help redistribute Zn to the wound,
which improves wound healing.
Many metalloenzymes contain copper that reacts
with oxygen. In particular, monoamine oxidase and
lysyl oxidase are necessary for cross-linking elastin
and collagen in wound healing5,6. In the present study,
we observed postoperative changes in Cu levels in the
PM surgery group. Berger et al. reported that trauma
causes little change in Cu concentration, and that
recovery is fast10. Our findings are consistent with
those results.
Although differences in thirst, hunger, or anxiety
before anesthesia induction were not significant,
preoperative CHO drink supplementation appeared
to slightly reduce patient discomfort. Using a visual
analog scale, Hausel et al. reported that thirst and
hunger were reduced by preoperative consumption
of a CHO drink5. Shorter fasting times can reduce
discomfort associated with a surgical procedure; thus
preoperative drink supplementation can mitigate, even
if only slightly, the stress experienced by patients
before surgery.
Y. Oyama et al.
In the present study, patients received the
preoperative drink containing 18% CHO, amino acids,
and trace elements. All patients tolerated the drink
well. Preoperative consumption of a drink containing
12.5% CHO has been reported to suppress surgical
stress-induced catabolism, thereby attenuating insulin
resistance23. Furthermore, this treatment enhanced
postoperative recovery and shortened hospital stays8.
Preoperative consumption of a drink containing 18%
CHO, such as the one used in the present study, may
also enhance postoperative recovery.
Given that this study was carried out at a
single facility, there are a number of limitations. By
grouping subjects according to morning or afternoon
surgery, seasonal fluctuations in metabolism may have
influenced the results. In addition, the postoperative
observation period was short, so the long-term effects of
CHO consumption (days hospitalized, wound healing)
were not assessed. To confirm our findings, long-term
studies at multiple institutions will be needed.
In conclusion, compared to conventional
preoperative fasting, preoperative consumption of
a CHO drink containing trace elements suppressed
preoperative metabolic fluctuations without causing
adverse effects, and trace element deficiency
was circumvented. Further, the drink appears to
reduce patient anxiety. Additional benefits during
the perioperative period can be expected by adding
trace elements to the preoperative CHO drink
supplementation protocol.
Acknowlegements
The authors thank nurse Kenji Maeda, nureses
at Oita Kouseiren Turumi Hospital and laboratory
technicians Tugio Kudo and Tomonori Waki for their
excellent nursing and technical assistance, dietitian
Megumi Maruo for invaluable help.
Effects of preoperative oral carbohydrates and trace elements on perioperative
nutritional status in elective surgery patients
383
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M.E.J. ANESTH 21 (3), 2011
REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL
INTUBATION BY THE BONFILS RETROMOLAR
FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY
Waleed A. Almarakbi**, Abeer A. Arab***
and A dnan A. A lmazrooa ****
Abdulaziz Boker*,
Abstract
The Bonfils retromolar intubation fiberscope is a rigid endoscope designed to enable glottic
visualization and facilitate intubation under endoscopic vision. Theoretically, avoiding direct-vision
laryngoscopy and thus could produce less stimulation during intubation than the conventional
direct laryngoscopic procedure. This prospective randomized study was designed to compare the
effect of tracheal intubation with direct vision laryngoscopy (Macintosh blade) and the Bonfils
retromolar intubation fiberscope on the hemodynamic responses in ASA I patients. Forty patients
scheduled for elective surgery and requiring endotracheal intubation were randomly allocated to
one of two groups according to the intubating tool under sevoflurane nitrous oxide Anaesthesia (n =
20 each). The retromolar group received tracheal intubation with the Bonfils retromolar fiberscope,
while the direct laryngoscopy group received tracheal intubation by the direct vision laryngoscope
(Macintosh blade). Heart rate and arterial blood pressure (systolic BP, diastolic BP, mean ABP)
were recorded before induction of Anaesthesia, 3 minutes after induction of Anaesthesia (before
intubation) and 5 successive recordings at one-minute interval after intubation. All the systolic BP,
diastolic Bp, mean ABP and heart rate values in the direct laryngoscopy group were significantly
higher in the 5 successive minutes after intubation in comparison with the retromolar group (P
= 0.00). This might be attributed to the gentle intubating technique, by the Bonfils retromolar
fiberscope, which allows quick endotracheal intubation without manipulations of the base of the
tongue or epiglottis.
Financial Support/Conflict of interest
Authors have no commercial association with financial involvement that might pose a conflict
of interest in connection with the results of the submitted article.
The study was supported by the department of Anesthesia, King Abdulaziz University,
Jeddah, Saudi Arabia. No other source of funding to disclose.
*
MBBS, Med, FRCPC, Assistant Professor, Consultant, Department of Anesthesia & Critical Care, Chairman, Medical
Education Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
** MD, Department of Anesthesiology and Intensive Care Medicine, Ain Shams University, Cairo, Egypt.
*** MBBS, FRCPC, Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University Hospital,
Jeddah, Saudi Arabia.
**** FFA, CPE, Associate Professor, Consultant, Department of Anesthesia and Critical Care, Vice President, King Abdulaziz
University, Jeddah, Saudi Arabia.
Corresponding Author: Dr. Abdulaziz Boker, Department of Anesthesia & Critical Care, Chairman, Medical Education
Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. P. O. Box Address: P. O. Box: 80215,
Jeddah 21589, Tel/Fax: +96626408335. E-mail: [email protected]
385
M.E.J. ANESTH 21 (3), 2011
386
A. Boker et al.
Introduction
Tracheal intubation via direct laryngoscopy
produces a marked stress response1. Although
these hemodynamic responses are short lived and
tolerated by most of the patients, they might provoke
detrimental effect, on the coronary and cerebral
circulation particularly in high-risk patients2. Several
pharmacological agents have been suggested to
attenuate these stress responses to laryngoscopic
intubation such as the use of variety of anesthetic
agents, sympatholytics, vasodilators, local anesthetics
and magnesium3,4,5,6,7.
In principle, tracheal intubation techniques that
avoid or minimize oropharyngeal stimulation might
attenuate the hemodynamic stress response. However,
published studies have provided little or conflicting
evidence for an attenuated response for a variety of
non-laryngoscopic intubation devices8,9,10,11,12.
Bonfils retromolar intubation fiberscope (Karl
Storz, Gmb and Co, KG, TuttLingen, Germany) is 3.55.0mm optical stylet that allows a retromolar approach
to the larynx. It is designed to position a 6.5mm I.D.
or larger endotracheal tube directly between the vocal
cords into the trachea with minimal or no manipulation
of the epiglottis which is richly innervated13. The aim
of this study was to compare the effect of tracheal
intubation with direct vision laryngoscopy (Macintosh
blade) and the Bonfils retromolar fiberscope on the
hemodynamic responses in American Society of
Anesthesiologist (ASA) physical status I patients.
Materials and Methods
After obtaining approval from our institutional
research committee and informed consent from
each patient, forty, ASA I patients scheduled for,
less than two hours, elective surgery requiring
tracheal intubation were solicited in this prospective,
randomized, unblinded study.
Exclusion criteria were age <18 yr or >60 yr old,
history gastroesophageal reflux, a history of difficult
intubation or intercisal distance <3 cm, patients in
whom tracheal intubation time was more than 30
seconds or the oropharyngeal (Guedel) airway was
used to facilitate face-mask ventilation.
All patients were premedicated with diazepam
5mg PO and ranitidine 150mg PO 2 hrs before
induction of Anaesthesia. Also, Mallampati score,
thyromental, and sternomental distances were
measured and recorded. In the pre-induction room,
an IV cannula was inserted with infusion of lactated
ringer at a rate of 15 mL.kg-1.hr- throughout the
operation. In the operating room, patients received
standard anesthetic monitors, including noninvasive
blood pressure, electrocardiogram lead II, and pulse
oximeter (Zeus, Drager, Germany). Heart rate, systolic
blood pressure (SBP), diastolic blood pressure (DBP)
and mean arterial blood pressure (MAP) were recorded
as baseline values.
Anaesthesia was induced with xylocaine 0.5 mg/
kg with venous retention for 30 seconds to minimize
propofol pain, propofol 3mg/kg IV, and cisatracrium
0.1 mg/kg IV. Anaesthesia was then maintained with
sevoflurane 2% in oxygen and nitrous oxide 50%.
After 3 minutes of manual ventilation, arterial
blood pressure (SBP, DBP, MAP), heart rate, end tidal
CO2 and sevoflurane concentrations were recorded.
Both the Bonfils retromolar fiberscope and direct
laryngoscope (Macintosh Blade) were ready to use on
the anesthetic tray. Patients were assigned on a random
number basis (using the sealed envelope method) into
2 groups: Group D, (n = 20) in which intubation was
done by the direct vision laryngoscopy with Macintosh
blade (Karl Storz, Germany) no.3 or 4 for female
patients and no. 4 or 5 for male patients while in Group
R, (n = 20) patients were intubated by the Bonfils
retromolar fiberscope (Karl Storz, Gmb and Co, KG,
TuttLingen, Germany). Cuffed Portex tracheal tubes
(SIMS Portex, Inc., Keene NH) with internal diameter
of 7 mm for female patients and 8mm for male patients
were used after lubrication by K-Y Jelly.
As soon as the trachea was intubated and
confirmed by positive end tidal CO2, arterial blood
pressure (SBP, DBP MAP) and heart rate were recorded
for 5 successive recordings at one-minute interval.
The intubation time was recorded from the time
the device passed into the oropharynx to the time of
reconnection of the ventilator tubing system to the
endotracheal tube. A single anesthetist experienced
with the direct larygoscopy and the Bonfils retromolar
fiberscope techniques performed all tracheal
intubations. The Cromack and Lehane14 grade without
REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL INTUBATION BY THE BONFILS RETROMOLAR
FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY
external laryngeal pressure was recorded in Group
D. Intraoperative complications were recorded by an
unblinded observer e.g. mucosal injury (blood detected
on the intubation device after use), dental injury and
lip injury.
387
significant changes among the groups as regards MAP
or heart rate (P = 0.00) (Graph 1, 2).
Graph 1
Heart Rate Changes at Different Phases of
Induction of Anesthesia
Also, postoperative sore throat was assessed 12
hrs after surgery by using the visual analogue scale that
ranges from zero (no Pain) to ten (the worst imaginable
pain).
Statistical Analysis
Statistical analyses were performed with the
Stat View SE Package (Abacus Concepts, CA, USA)
on a Power Macintosh 7200 (Apple Computer Inc.,
CA, USA). Patients’ characteristics were compared
using student’s-t-test. Between group differences
were compared using analysis of variance (ANOVA)
for factors. If significant differences were observed,
Scheffe F was used for post hoc analysis. Data are
presented as mean (SD). P<0.05 was considered
statistically significant.
Results
There were no significant differences between
the two groups in terms of age, sex, weight, or height
(table 1). End tidal CO2 and sevoflurane concentrations
immediately before intubation were also similar
between the two groups (table 1).
Table 1
Patients Demographic Data, Airway Assessment and
Intubation Data
Group D: Direct Laryngoscopy group, Group R: Retromolar
group.
* P<0.05.
Graph 2
Mean Arterial Blood Pressure Changes at Different
Phases of Induction of Anesthesia
Group D: Direct Laryngoscopy group, Group R: Retromolar
group.
* P<0.05.
Both MAP and heart rate values in Group D were
significantly higher in the 5 successive minutes after
intubation in comparison with Group R (P = 0.00)
(Graph 1, 2). As regards the intubation time, it was
significantly higher in Group D than Group R (P =
0.00) (table1).
In Group D, one case was recorded to have
mucosal injury and another one for lip injury while no
cases were recorded for intraoperative complications
in Group R (table 2). Regarding the post-operative
sore throat, it was significantly higher in Group D than
Group R (P = 0.00) (table 2).
Table 2
Intra and Postoperative complications
Group D: Direct Laryngoscopy group, Group R: Retromolar
group.
* P<0.05
Before induction, there were no significant
differences between the two groups as regards MAP
and heart rate (Graph 1, 2). Furthermore, after induction
and immediately before intubation, there were no
Group D: Direct Laryngoscopy group, Group R: Retromolar
group, VAS: visual analogue scale (0-10).
* P<0.05.
M.E.J. ANESTH 21 (3), 2011
388
Discussion
This prospective study showed that tracheal
intubation by Bonfils retromolar fiberscope produced
lower level of hemodynamic responses in healthy
patients. As an Anesthesiologist become more curious
to use the new tools available, which are helping in
management of the difficult airway, Bonfils retromolar
intubation fiberscope is one of these new instruments
that recently introduced to daily anesthetic practice
as it permits clear visualization of the glottic area.
Additionally, it has a unique option of direct oxygen
insufflation through a side-port that disperses the
secretions, prevents fogging of the view and allows
oxygenation in cases of difficult ventilation during the
intubation trials.
Also, it facilitates tracheal intubation in trauma
patients with immobilized cervical spine15 and being
introduced through the retromolar space, it prevents
teeth damage in vulnerable patients as caused by the
direct vision laryngoscope.
Only few studies were done to evaluate the Bonfils
retromolar fiberscope as intubating tool16,17,18,19,20.
Orotracheal intubation using the direct vision
laryngoscopy needs elevation of the epiglottis for
laryngeal exposure. In order to elevate the epiglottis
and to put the glottic aperature in one axis with the
anesthetist eye, a forward and upward movement
of the laryngoscope blade exerted along the axis
of the laryngoscope handle, which may results in
hemodynamic response21.
In our study we anticipated that orotracheal
intubation through a gentle intubating technique
using the Bonfils retromolar fiberscope would cause
less hemodynamic responses. The study showed a
significant increase in heart rate, SBP, DBP and MAP in
the direct laryngoscopy group when compared with the
retromolar group (P<0.005) in the 5 successive minutes
after intubation. During orotracheal intubation using
the direct vision laryngoscopy sympathetic activation
occurs due to two possible causes; the direct contact
of the blade to the tongue especially the posterior
third and the vallecula with a force to elevate the
epiglottis, while the second cause is the introduction of
the endotracheal tube in the trachea. In our study, the
hemodynamic responses were lower in the retromolar
A. Boker et al.
group as one of the causes of sympathetic activation
is minimized which is the oropharyngeal stimulation.
The introduction of the retromolar fiberscope into
the oropharynx is under vision, through a camera
connected to the fiberscope and a screen, which
gives us the opportunity to direct the endotracheal
tube into the larynx with minimal or no contact with
the epiglottis. Furthermore, in order to make a clear
passage in the oropharynx for introduction of the
retromolar fiberscope, upward chin lift is achieved by
grasping the jaw with the anesthetist thumb and index
finger to separate the tongue and epiglottis away from
the posterior pharyngeal wall.
Shinji et al22 showed that hemodynamic changes
are likely to occur because of direct tracheal irritation
rather that direct stimulation of the larynx in their study,
which contained 3 groups, the light wand group received
tracheal intubation with Trachlight®, the laryngoscope
intubation group received tracheal intubation with a
direct vision laryngoscope (Macintosh blade), and the
laryngoscope alone group received the laryngoscope
alone without intubation. The maximum heart rate and
systolic blood pressure were significantly higher in both
Trachlight® and Macintosh laryngoscope group than
those in the laryngoscope alone group. On the contrary,
the study of Hirabayashi et al11 showed non-significant
changes in mean arterial blood pressure and heart rate
to tracheal intubation with using either the light wand
or the Macintosh laryngoscope. They attributed the
cause of similarity in hemodynamic response of the
light wand group to Macintosh laryngoscope group
to the technique for light wand intubation in which
the jaw is grasped and lifted upward using the thumb
and index finger of the intubator’s hand to facilitate
passage of the endotracheal tube to the larynx, which
considered by them a sufficient stimulus to cause
circulatory responses. We concur that chin lift stimulus
may cause stress response but, in our opinion, not to
the same degree as the Macintosh blade laryngoscope
does. Although we used a similar technique of chin lift,
the difference lies in using the retromolar fiberscope
instead of the light wand. The light wand technique
is a blind one in which the endotracheal tube may
touch the tongue base, vallecula, epiglottis or the
piriform fossa during the introduction trials. That
may be an added cause to the chin lift to increase the
hemodynamic response. Alternatively, the retromolar
REDUCED HEMODYNAMIC RESPONSES TO TRACHEAL INTUBATION BY THE BONFILS RETROMOLAR
FIBERSCOPE: A RANDOMIZED CONTROLLED STUDY
fiberscope introduces the endotracheal tube to the
larynx under vision to avoid touching and stimulating
the oropharyngeal structures with subsequent
minimization of the circulatory responses.
However, Nishikawa et al23 showed in their
study attenuated hemodynamic changes in the light
wand technique in comparison to the laryngoscopic
technique.
In their study, they had different anesthetic
technique as induction of general Anaesthesia was
by fentanyl 2 mcg/kg followed after 3 minutes by IV
propofol and vecronium. Fentanyl could attenuate
the hemodynamic responses associated with tracheal
intubation24,25,26.
Prolongation of the duration of intubation has
been reported to increase hemodynamic changes after
tracheal intubation27. Nishikawa et al28 concluded that
tracheal intubation using a light wand is more effective
than flexible fiberoptic intubation in attenuating
hemodynamic changes after tracheal intubation in
normotensive elderly patients. They attributed the
cause to the rapidity of intubation; the intubation times
in the light wand group were significantly shorter that
those in the fiberoptic group. In our study, the intubation
time was significantly shorter in the retromolar group
(P<0.05) thus, sharing in causes of attenuation of the
hemodynamic responses during intubation with the
Bonfils retromolar fiberscope. Another contributing
factor in the hemodynamic response to direct vision
laryngoscopy using the Macintosh blade is the degree
of force applied to elevate the tongue base and
epiglottis as revealed by the study of McCoy et al29
in which the stress response was less marked with the
use of McCoy blade than the Macintosh blade due to
reduction of force necessary to obtain clear view of
the larynx by the McCoy blade. Hassan et al30 reported
that, by activating proprioceptors, direct laryngoscopy
389
induces stress responses proportional to the intensity
of the stimulus exerted against the base of the
tongue. Therefore, the retromolar group in our study
experienced lower hemodynamic responses than the
direct laryngoscopy group as there was not any force
applied to the base of the tongue or epiglottis during
introduction of the Bonfils Fiberscope towards the
larynx which also was reflected on the lower incidence
of sore throat (VAS = 1.5 ± 0.5) than in the direct
laryngoscope group (VAS = 4.8 ± 0.8) (P<0.05).
Our study has limitations.
First, it lacks the double blinding, which is not
practical to do. Second, only normotensive patients
were included in this study so hemodynamic responses
to tracheal intubation by the Bonfils fiberscope
in hypertensive patients could not be predicted.
Collectively, we recommend a further study to evaluate
the hemodynamic effect of intubation by the Bonfils
fiberscope in hypertensive patients.
Third, patients anticipated to have difficult
intubation and whom intubation time exceeds 30
seconds were excluded from the study. Consequently,
we could not assess the hemodynamic responses
in repeated trials and prolonged intubation times.
Finally, we measured the hemodynamic parameters as
an indicator for stress response to intubation without
measuring the serum catecholamine levels as it is of
high cost and also, the study of Michal et al31 concluded
that catecholamine levels do not correlate with the
hemodynamic changes during their comparative study
between the direct vision laryngoscopy and fiberoptic
bronchoscopy as regards the stress response.
In summary, tracheal intubation by the Bonfils
retromolar fiberscope caused hemodynamic responses
significantly lower than tracheal intubation by the
direct laryngoscope (Macintosh blade) in ASA I
patients.
M.E.J. ANESTH 21 (3), 2011
390
A. Boker et al.
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25.Martin DE, Rosenberg H, Aukburg SJ et al: Low-dose fentanyl
blunts circulatory responses to tracheal intubation. Anesth Analg;
1982, 61:680-4.
26.KO SH, Kim DC, Han YJ, Song HS: Small dose fentanyl: optimal
time of injection for blunting the circulatory responses to tracheal
intubation. Anesth Analg; 1998, 86:658-61.
27.Stoelting RK: Circulating changes during direct laryngoscopy and
tracheal intubation: influence of duration of laryngoscopy with and
without prior Lidocaine. Anesthesiology; 1977, 47:381-3.
28.Nishikawa,Kohki, Kawamata, Mikito, Namiki and Akiyoshi: Light
wand intubation is associated with less hemodynamic changes
than fiberoptic intubation in normotensive, but not in hypertensive
patients over the age of 60. Can J Anesth; 2001, 48:1148-53.
29.McCoy EP, Mirakhur RK and McCloskey BV: A comparison of the
stress response to laryngoscopy. Anaesthesia; 1995, 50:943-946.
30.Hassan HG, El-Sharkawy TY, Renck H et al: Hemodynamic
and catecholamine responses to laryngoscopy with and without
endotracheal intubation. Acta Anesthesiol Scand; 1991, 35:442-7.
31.Mochal B, Avishai Z, Avital G, Sophie L, Beno R. Hemodynamic
and catecholamine response to tracheal intubation: direct
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Clinical Anaesthesia; 2003, 15:123-136.
EFFECT OF KETAMINE ON BISPECTRAL INDEX
DURING PROPOFOL - FENTANYL ANESTHESIA: A
*
RANDOMIZED CONTROLLED STUDY
Saikat Sengupta, Simantika Ghosh, Amitava Rudra,
Palash Kumar, Gaurab Maitra, Tanmoy Das
Abstract
Background: The Bispectral Index (BIS) helps in the assessment of the depth of hypnosis.
N-methyl-D-aspartic acid antagonist, ketamine, has been used in various doses to decrease
postoperative morphine consumption. The purpose of our study was to compare the effects of two
different doses (0.5 mg/kg and 0.2 mg/kg) of ketamine on BIS values.
Methods: Forty-five ASA I or II patients undergoing general anesthesia were included in this
double-blind, prospective, control trial and randomly allocated into three groups. After induction
of anesthesia and tracheal intubation, a propofol infusion was started and titrated to attain BIS
values of around 40. After five minutes of stable BIS values and in the absence of any surgical
stimulus, patients received either 0.5 mg/kg of ketamine (Group K1) or 0.2 mg/kg of ketamine
(Group K2) or normal saline (Group N) as bolus intravenously. BIS values were recorded for the
next 15 minutes, at five-minutes interval.
Results: Mean BIS values were significantly increased in Group K1 (63.5) while Group K2
(42.0) failed to show any significant rise. BIS values in Group K2 were comparable to those in
Group N.
Conclusion: Thus, under stable propofol anesthesia, a bolus of ketamine 0.5 mg/kg increases
BIS values while ketamine 0.2 mg/kg does not.
Introduction
Ketamine is an intravenous anesthetic with analgesic properties in subanesthetic doses. It is a
non-competitive antagonist of the N-methyl - D - aspartic acid (NMDA) receptor that participates
in excitatory neurotransmission in the central nervous system. Although analgesia produced by
ketamine alone does not seem to be equivalent to that produced by opioid analgesics1-4, ketamine can
prevent the development of opioid tolerance via NMDA receptors5-8 (Fig. 1). Opioid tolerance is a
major concern when postoperative pain requires large doses of opioids, such as in major abdominal
and thoracic surgeries and in cancer patients with chronic opioid intake. In such patients, Ketamine
has proved to be a useful adjuvant for the management of pain9-11.
*
Department of Anesthesiology, Perioperative Medicine and Pain, Apollo Gleneagles Hospitals.
Corresponding Author: Saikat Sengupta, MD DNB MNAMS, Senior Consultant & Academic Coordinator,
Department of Anesthesiology, Perioperative Medicine and Pain, Apollo Gleneagles Hospitals, 58, Canal Circular Road,
Kolkata-700058. Tel: +91 9830179539. E-mail:[email protected]
391
M.E.J. ANESTH 21 (3), 2011
392
S. Sengupta et al.
Fig. 1
Pain pathway and action of Ketamine
Strong pain
Opioids
µ receptors
Ketamine
NMDA receptors
Increased glutanate
synaptic effectiveness
range of ketamine doses (between 0.15 and 1 mg/Kg)
used intravenously16-18. We undertook this study to
determine the dose of ketamine which would provide
analgesia but be devoid of its paradoxical effects on
BIS. Specifically, the study aims to compare the effect
of ketamine on BIS when given at two different doses
as i.v. bolus: 0.2 mg/Kg and 0.5mg/Kg.
Hyperexcitability of dorsal root neurons
Methods
• Central Sensitization
• Wind-up phenomenon
• Pain memory
Among the three components of the triad of
anesthesia (hypnosis, areflexia, analgesia) hypnosis
is perhaps the most difficult to measure and monitor.
The importance of measuring hypnosis or depth of
anesthesia lies in the prevention of awareness, which
can be a very unpleasant experience and result in
tragic consequences for both the patient and the
anesthesiologist. Several non-continuous clinical
scales for describing sedation levels in adults have
been devised, such as the Observer’s Assessment of
Alertness and Sedation (OAAS) and the Ramsay Scales.
However, these have proved inadequate in measuring
the depth of anesthesia and have paved the way for
processed EEG monitors. ECG monitors provide a
continuous measure that encompasses the full range of
sedation levels measured by the discontinuous scales.
In October 1996, the Food and Drug Administration
(Rockville, MD) approved the Bispectral Index (BIS)
monitor (Aspect Medical Systems, Newton, MA) as an
accepted measure of the hypnotic effect of anesthetics
and sedative drugs12. BIS was derived by empirically
estimating the EEG parameters that best predicted
OAAS measurements and may be described as a
“probability of state” measure, reflecting the complex
nature of consciousness13. Today, BIS is widely used
to monitor the hypnotic component of anesthesia and
guide the administration of volatile and intravenous
anesthetics.
Several studies have reported an increase in BIS
values, despite a deepening level of hypnosis when
ketamine 0.5 mg/Kg is administered as a rapid bolus
during general anesthesia14-15. Perioperative use of
ketamine for acute postoperative pain involves a wide
After approval from the Institutional Review
Board, and obtaining written informed consent, 45
patients, ASA I or II, aged 18-65 years, posted for
surgeries under general anesthesia were enrolled in
this prospective, double-blind, randomized control
trial. Selection criteria included the absence of any
neurological or psychiatric disease, obesity and arterial
hypertension, as well as complete abstinence from
illicit drugs and alcohol.
Upon arrival in the operating theatre, noninvasive blood pressure monitoring, continuous
electrocardiography and pulse oximetry were instituted
in all patients. BIS was monitored using a Quatro TM
sensor applied appropriately to the patient’s forehead.
Premedication consisted of midazolam 0.02 mg/
Kg and glycopyrrolate 0.04 mg/Kg. General anesthesia
was induced with propofol titrated to attain a BIS
value just below 40 and fentanyl 2 µg/Kg. Tracheal
intubation was facilitated with rocuronium 0.6 mg/
Kg and maintenance of anesthesia was achieved
with propofol infusion titrated to attain BIS values
below 40 and air in oxygen (50% inspired fraction).
The propofol infusion was continuously titrated to
maintain stable BIS of ~ 40. After 5 minutes of stable
BIS and in the absence of any surgical or noxious
stimulus, patients received randomly (using closed
enveloped technique), in double-blind fashion either a
bolus of ketamine 0.5 mg/Kg diluted to 5 ml (Group
K1; n = 15) or ketamine 0.2 mg/Kg diluted to 5 ml
(Group K2; n = 15) or normal saline 5 ml (Group
N; n = 15) (Fig. 2). The solution was prepared by an
independent anesthesiologist unaware of the study
protocol. Non-invasive arterial pressure, heart rate,
pulse oximetry, end tidal CO2 and BIS values were
recorded automatically, before the start of the drug
administration until the end of the study period of 15
minutes in the absence of any surgical stimulation.
EFFECT OF KETAMINE ON BISPECTRAL INDEX DURING PROPOFOL - FENTANYL ANESTHESIA: A DOMIZED
CONTROLLED STUDY
Fig. 2
Study Methodology
5 minutes of stable BIS + Absence of any
surgical or noxious stimulus
393
Kg) although Group K2 (ketamine 0.2 mg/Kg) showed
no such increase (Table 2) (Fig. 4). Vital parameters,
however, did not vary significantly among the groups.
Fig. 4
Graphical Representation of study results
Closed Envelope Technique
I.V. Bolus
of ketamine
0.5 mg/Kg
I.V. Bolus
of ketamine
0.2 mg/Kg
I.V. Bolus
of normal
saline 5 ml
Group K1
n =15
Group K2
n =15
Group N
n =15
Results
SPSS software version 11.5 was used for
statistical analysis. Power analysis yielded a sample
size of 43 when the confidence level was fixed as 95%
to achieve an α error of 0.05 and a β error of 0.2. On
analysis of demographic data using Chi-square test, no
statistically significant differences were noted among
the 3 study groups (Table 1). BIS values were expressed
as mean (SD) and analyzed using two-way analysis of
variance (ANOVA). Compared to the control group
(normal saline 5 ml), statistically significant increase in
BIS values was noted in Group K1 (ketamine 0.5 mg/
Discussion
Review of relevant literature showed that doses of
ketamine administered perioperatively varied almost
seven-fold, from 0.15 to 1 mg/Kg i.v. No consensus
seems to be present on a specific and systematic
administration regimen of ketamine in the context of
its preemptive anti-hyperalgesic effects.
Table 1
Demographic Characteristics of Study Sample
K1
K2
N
0.5 mg/kg
0.2 mg/kg
Normal saline
15
45 ± 2*
8 (53.3)*
15
44 ± 2#
7 (46.7)#
15
43 ± 4
8 (53.3)
K1
K2
N
0.5 mg/kg
0.2 mg/kg
Normal saline
0 Min (Baseline)
58.4 (3.5)
59.0 (1.69)
60.3 (1.49)
5 Mins (After Induction)
41.2 (3.99)
40.9 (1.66)
41.5 (1.60)
No. of Patients
Age (Yrs.)
Males (Nos.) (%)
* P value > 0.05 compared to N.
# P value > 0.05 compared to N.
10 Mins (After Stabilization of BIS)
15 Mins (5 Mins after Bolus)
* P value < 0.05 compared to N.
# P value > 0.05 compared to N.
420
Table 2
BIS Values as Mean (SD)
40.2 (0.77)
40.2 (0.77)
40.1 (0.80)
63.5 (2.03)*
42.0 (0.75)#
40.8 (1.01)
M.E.J. ANESTH 21 (3), 2011
394
In 1969, Corssen et al19 reported that ketamine
1 mg/Kg increases the activity of the EEG spectrum.
In more recent studies, ketamine shifted the alpha
peak of bicoherence induced by propofol to higher
frequencies, but did not block their formation20-22.
Hirota et al23 showed that a bolus of ketamine 0.4
mg/Kg significantly increases the BIS values during
propofol-fentanyl anesthesia. Vereecke et al15 showed
the same effects on the BIS after a bolus injection of
ketamine 0.4 mg/Kg followed by a continuous infusion
of 1 mg/Kg/h. During sevoflurane anesthesia, Hans et
al14 showed that a bolus of 0.5 mg/Kg ketamine also
significantly increases the BIS values. Lauretti and
Azevedo24 have demonstrated the efficacy of 0.2 mg/
Kg of ketamine on the decrease of rescue analgesic
drug requirement for postoperative pain therapy after
vaginoplasty. Faraoni et al25 showed that under stable
propofol and remifentanil TCI anesthesia, a slow bolus
infusion of ketamine 0.2 mg/Kg administered over a
5 min period did not increase the BIS value over the
next 15 min.
With such a wide spectrum of used doses, we
decided to evaluate the effect of two different doses of
ketamine on BIS values – 0.5 mg/Kg and 0.2 mg/Kg.
Although 0.5mg/Kg of ketamine has been proved to
increase BIS values when given as an i.v bolus under
sevoflurane anesthesia14, 0.2 mg/Kg of ketamine has
been shown to have no effects on BIS when given
as an infusion over 5 minutes25. Does this hold true
when 0.2 mg/Kg ketamine is administered as a bolus?
Can the use of a propofol infusion for maintenance of
anesthesia alter the effects of 0.5mg/Kg of ketamine
on BIS? We sought the answers to these questions
through our study. The results of our study corroborate
the findings of Hans et al14 as well as Faraoni et al25
in that a bolus of 0.5 mg/Kg of ketamine significantly
increases BIS values but 0.2 mg/Kg does not, inspite
of differences in the study protocol. Faraoni et al25 have
used propofol and remifentanil TCI anesthesia while
we have used propofol infusion titrated according to
BIS alongwith fentanyl. Ketamine was administered as
a bolus in our study but Faraoni et al25 administered a
slow bolus infusion over a 5 min period.
The hypnotic effect of ketamine is characterized
by a dissociative mechanism and an increase in Ө
activity of EEG. The increase in BIS in response to
ketamine is paradoxical in that the level of anesthesia
S. Sengupta et al.
is deepened by the administration of an additional
anesthetic agent. Thus, BIS must be considered
to reflect cortical activity rather than the level of
consciousness26.
Ketamine administered in patients anaesthetized
with GABAergic agents that depress cortical activity,
induces a change in the EEG pattern towards higher
frequencies and desynchronisation (Fig. 3). This
modification is reflected in an increase in BIS and
has no relationship with the depth of anesthesia.
Anesthesiologists unaware of this paradox will
inadvertently administer additional hypnotic agents in
order to decrease BIS values, ultimately landing the
patient in an over dose of hypnotic agents which may
have profound effects on the perioperative outcome.
Once aware, the anesthesiologist will use his clinical
skills to determine the depth of anesthesia and thus
refrain from chasing the BIS values and causing an
over dose of hypnotic agents and better perioperative
outcomes.
Fig. 3
Ketamine and its effect on BIS
GABAergic AGENTS + KETAMINE
EEG
DESYNCHRONIZATION
↑ FREQUENCY
↑ BIS VALUES
UNRELATED TO ANAESTHETIC DEPTH
The reason of increase in BIS values with a
low dose of ketamine remains unclear. We also did
not evaluate the effects of ketamine on postoperative
analgesia, 24 hour morphine consumption or on the
incidence of PONV.
In conclusion, a bolus dose of ketamine 0.2
mg/Kg does not affect BIS values during propofol
anesthesia whereas higher doses of 0.5 mg/kg increase
BIS values despite a deepening level of anesthesia.
This increase modifies the relationship between BIS
and the hypnotic component of anesthesia. Ignoring
this effect could lead to inadvertent over dose of
hypnotic agents and thus calls for increased awareness
EFFECT OF KETAMINE ON BISPECTRAL INDEX DURING PROPOFOL - FENTANYL ANESTHESIA: A DOMIZED
CONTROLLED STUDY
395
among anesthesiologists.
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M.E.J. ANESTH 21 (3), 2011
Effect of prophylactic dexamethasone on
nausea and vomiting after laparoscopic
gynecological operation: meta-analysis
Jiang
Wang Bin*, HE Kai-Hua**,
Meng-Bi*, LIU Chao* and MIN Su**
Abstract
Keywords: dexamethasone; postoperative nausea and vomiting; laparoscopic gynecological
operation; meta-analysis
Background: Sex of female and laraproscopic surgery are both risk factors related to
postoperative nausea and vomiting, and dexamethasone is used as anti-emetic in some operations.
A meta-analysis of randomized trials was performed to determine the effect of prophylactic
dexamethasone administration on postoperative nausea and vomiting, pain and complications in
patients undergoing laparoscopic gynecological operation.
Methods: A systematic literature search was conducted to identify all randomized clinical
trials. The primary outcome was the incidence and severity of postoperative nausea and vomiting.
The secondary outcomes include postoperative pain and complications.
Results: Totally 1801 patients were enrolled in 11 eligible randomized trials comparing effect
of prophylactic dexamethasone administration on postoperative nausea and vomiting with placebo.
The pooled incidence of nausea, vomiting, nausea and vomiting, and rescue anti-emetic was
significantly lower in dexamethasone group than placebo group during post-anesthesia care unit
(10.5% vs 18.2%, OR 0.51, 95% CI 0.31-0.84; 6.5% vs 17.1%, OR 0.31, 95% CI 0.17-0.56; 17.0%
vs 35.4%, OR 0.33, 95% CI 0.21-0.50; 6.7% vs 23.3%, OR 0.22, 95% CI 0.10-0.49, P<0.00001)
and within the first postoperative 24 hours (25.2% vs 40.3%, OR 0.46, 95% CI 0.32-0.66; 14.4%
vs 36.6%, OR 0.27, 95% CI 0.19-0.40; 33.0% vs 69.0%, OR 0.18, 95% CI 0.13-0.26; 21.0% vs
51.1%, OR 0.26, 95% CI 0.16-0.41, P<0.00001). No significant difference was found about the
incidence of rescue analgesia between dexamethasone group and placebo group (48.5% vs 56.4%,
OR 0.68, 95% CI 0.40-1.18, P=0.17).
Conclusion: Prophylactic dexamethasone administration decreases the incidence of nausea
and vomiting after laparoscopic gynecological operations during post-anesthesia care unit and
within the first postoperative 24 hours. (286 words)
Postoperative nausea and vomiting are the most common complications after anesthesia and
surgery, and both sex of female and type of laparoscopic operation are risk factors1. It is certain of
a remarkably high incidence after laparoscopic gynecological surgery, which is reported as nearly
70% within the first postoperative 24 hours2. It is very important to find an effective treatment to
alleviate postoperative nausea and vomiting.
*
**
PhD, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Professor, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016,
China.
Correspondence to: MIN Su, Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University,
Chongqing 400016, China (Tel: 86-023-89011068. Fax: 86-023-89011068. E-mail: [email protected]).
397
M.E.J. ANESTH 21 (3), 2011
398
Wang Bin et al.
Dexamethasone was first used as an antiemetic in patients receiving chemotherapy for
cancer treatment by a central mechanism involving
endogenous prostaglandin and opioid production3,4.
And then some trials showed that dexamethasone
alone or combination with traditional anti-emetics
may decrease the incidence and severity of
postoperative nausea and vomiting5,6. Furthermore,
perioperative dexamethasone administration may
decrease postoperative pain by modulationg the
systemic physiologic response in favor of antiinflammatory mediators. Researchers have reviewed
the pathophysiologic effects and clinical implications
of perioperative dexamethasone administration, but
the variability in surgical procedures has precluded
definitive conclusions regarding the effectiveness of
dexamethasone5.
The outcome of interest included the incidence
and severity of postoperative nausea and vomiting,
and one or more of pain, postoperative complications.
The incidence and severity of postoperative nausea
and vomiting were evaluated using these four
variables: the incidence of (1) nausea, (2) vomiting,
(3) PONV (nausea + vomiting), and (4) rescue
anti-emetic used. And retching was considered as
vomiting. Furthermore, the incidence and severity of
postoperative nausea and vomiting included two time
interval: during post-anesthesia care unit (PACU) and
within the first postoperative 24 hours. Postoperative
pain was assessed as the incidence of rescue analgesia.
The present meta-analysis was conducted to
determine the effect of prophylactic dexamethasone
administration on postoperative nausea and
vomiting, pain, and complications after laparoscopic
gynecological operation.
Studies were selected and data were extracted
independently by two reviewers. Disagreements were
resolved by consensus. We referred to the guidelines
of the Cochrane handbook for systematic reviews of
interventions 4.2 for our meta-analysis.
Methods
Statistical methods
Criteria for study selection
Randomized clinical trials that investigate
effect of prophylactic dexamethasone administration
on postoperative nausea and vomiting in patients
undergoing laparoscopic gynecological operations
were included.
Data sources and search strategy
We carried out this meta-analysis in accordance
with the standard protocol recommended by the quality
of reporting of meta-analyses group and the guidelines
of Cochrane handbook of systematic reviews of
interventions 4.2. We searched Pubmed, EMBASE,
ISI Web of Science and the Cochrane Central Register
of Controlled Trials for randomized trials investigate
impact of prophylactic dexamethasone administration
on postoperative nausea and vomiting in patients
undergoing laparoscopic gynecological operations. We
included following terms: laparoscopic, gynecological
operation, steroid, dexamethasone, nausea, vomiting.
Searches were restricted to the period from January 1,
1998 to December 31, 2009 and language of English.
Classification of outcome and definitions
Data abstraction and assessment of quality
Binary outcomes from individual studies were
analyzed according to the Mantel–Haenszel model to
compute individual odds ratios (ORs) with pertinent
95% confidence intervals (CIs), and a pooled summary
effect estimate was calculated by means of fixed
effect. Statistical heterogeneity and inconsistency was
measured using, respectively, Cochran Q tests and I2
values. Computations were performed with SPSS 11.0
(SPSS, Chicago, IL) and RevMan 4.2 (a freeware
available from The Cochrane Collaboration). All P
values were two-sided, and P<0.05 was considered as
statistically significant.
Results
Description of included studies
Overall
11
randomized
double-blind
7-17
investigate effect of prophylactic
clinical trials
dexamethasone administration on postoperative nausea
and vomiting in patients undergoing laparoscopic
gynecological operations were identified, in which
1801 patients were involved, and all belonged to
Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic
gynecological operation: meta-analysis
399
Table 1
Prophylactic dexamethasone administration
Trial
Dexamethasone administration
Rescue-antimetic
Rescue analgesia
Chu
dexamethasone 5 mg, iv
15 min after induction
Ondansetron 4 mg iv
Ketorolac 30 mg iv
Fujii
Dexamethasone 4 mg/8 mg, iv
At end of the sugery
Not mentioned
50 mg indomethacin rectally
Michael
Dexamethasone 4 mg/2mg, iv
At end of the sugery
Prochlorperazine 12.5 mg iv, followed by Not mentioned
droperidol 1 mg iv as necessary
Yuksek
Dexamethasone 8 mg, iv
2 min before induction
Metroclopramide 10 mg, iv
3 mg morphine first, and 50 μg
fentanyl repeated if necessary
Maddali
Dexamethasone 8 mg, iv
2 min before induction
Not mentioned
Not mentioned
Lee
Dexamethasone 8 mg, iv
2 min before induction
Metoclopramide 10 mg, iv
Ketorolac 15 mg iv
Eliana
Dexamethasone 8 mg, iv
2 min before induction
Ondansteron 4 mg iv
Tramadol 50 mg iv
Huang
Dexamethasone 5 mg, iv
After tracheal intubation
Ondansteron 4 mg iv
Not mentioned
wang
Dexamethasone 10 mg, iv
at induction
Ondansteron 4 mg iv
Not mentioned
Rajeeva
Dexamethasone 8 mg, iv
after induction
Metoclopramide 0.15 mg/kg, iv
75mg diclofenac im
Rothenberg
Dexamethasone 0.017 mg/kg, iv, Not mentioned
just prior to abdominal incision
Ketorolac 30-60 mg iv, then
morphine 1-2 mg iv if necessary
ASA(America Society of Anethesiologists) grade I or
II. Laparoscopic operations included tubal ligation,
myonectomy, hysterectomy, salpingo-oophorectomy,
oophorocysterctomy and diagnostic laparoscopy.
All of the studies administered a single dose of
dexamethasone intravenously, with the timing of
administration ranging from immediately before
anesthesia induction to the end of the surgery (Table
Fig. 1
Forest plot for the comparison of incidence of nausea,
vomiting, PONV, and need for rescue anti-emetic during
PACU between dexamethasone group and placebo group.
Fig 2
Forest plot for the comparison of incidence of nausea,
vomiting, PONV, and need for rescue anti-emetic within 24 h
between dexamethasone group and placebo group.
M.E.J. ANESTH 21 (3), 2011
400
Wang Bin et al.
Table 2
Baseline characteristics of patients
Trial
Chu
n
372
Age (y) *
Weight (kg)*
43.1(4.7)
57.2(9.2)
MS
(%)
17
Previous
PONV (%)
7
Smoker
(%)
----
To (min)*
91.9(24.8)
Ta (min)*
114.5(29.0)
Fujii
90
35.6(6.4)
53.0(7.0)
0
0
27
85.3(33.1)
123.0(34.6)
Michael
614
32.5(6.3)
64.0(6.8)
----
16
38
---
40.0(18,1)
Yuksek
60
31.1(5.2)
61.9(7.3)
0
----
----
57.3(10.6)
71.7(16.4)
Maddali
120
29.1(7.2)
62.8(12.6)
----
-----
----
62.9(24.6)
----
Lee
164
39.3(8.0)
56.9(6.8)
0
0
0
113.8(23.0)
137.9(21.9)
Eliana
40
30.5(6.5)
60.5(10.1)
0
0
----
62.0(37.7)
88.5(37.6)
Huang
115
34.0(6.4)
55.0(7.7)
0
0
----
42.0(12.2)
65.0(17.3)
wang
81
33.0(6.2)
55.0(8.1)
---
----
----
44.0(11.8)
66.5(17.3)
Rajeeva
51
28.7(4.8)
49.8(6.7)
0
0
Rothenberg
94
32.0(5.5)
66.1(7.8)
12
8
* mean(sd); MS: motion sickness; To: time of operation; Ta: time of anesthesia
1). All the studies measured incidence of postoperative
nausea and vomiting, and a substantial proportion
measured pain. Not enough reported complications,
health-related quality of life or hospital length of
stay to allow us to pool the results. The baseline
characteristics revealed a relatively young and healthy
population, and a relatively short time of anesthesia
and operation (Table 2).
Effect of prophylactic dexamethasone
administration on postoperative nausea and
vomiting
The incidence of nausea, vomiting, PONV, and
need for rescue anti-emetic was significantly lower in
dexamethasone group than in placebo group during
PACU (10.5% vs 18.2%, OR 0.51, 95% CI 0.31-0.84;
6.5% vs 17.1%, OR 0.31, 95% CI 0.17-0.56; 17.0% vs
35.4%, OR 0.33, 95% CI 0.21-0.50; 6.7% vs 23.3%,
OR 0.22, 95% CI 0.10-0.49, P<0.00001) (Fig. 1)
and within the first postoperative 24 hours (25.2% vs
40.3%, OR 0.46, 95% CI 0.32-0.66; 14.4% vs 36.6%,
OR 0.27, 95% CI 0.19-0.40; 33.0% vs 69.0%, OR 0.18,
95% CI 0.13-0.26; 21.0% vs 51.1%, OR 0.26, 95% CI
0.16-0.41, P<0.00001) (Fig. 2).
Effect of prophylactic dexamethasone
administration on postoperative pain
The incidence of rescue analgesia in
dexamethasone group was lower than in placebo group
----
28.7(4.0)
----
----
41.8(12.7)
----
(48.5% vs 56.4%, P=0.17), which suggest a trend
toward less need for rescue analgesia in dexamethasone
group although the CI was wide (OR 0.68, 95% CI,
0.40-1.18) (Fig. 3).
Discussion
This meta analysis identified 11 randomized
and double-blind trials, which investigate the effect
of prophylactic dexamethasone administration
on postoperative nausea and vomiting in patients
undergoing laparoscopic gynecological operations.
Although the trials varied with different other antiemetics, every trial compared dexamethasone
with placebo, and presented data for us to pool the
results. The pooled results showed that prophylactic
dexamethasone administration decreased incidence and
severity of postoperative nausea and vomiting during
PACU and within the first postoperative 24 hours.
Fig. 3
Forest plot for the comparison of rescue analgesics between
dexamethasone group and placebo group.
Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic
gynecological operation: meta-analysis
Prophylactic dexamethasone was administered at
different time, varied from 2 minutes before induction
to at the end of the operation. Most trials administered
dexamethasone soon before or after induction, while
just one trial prior to the abdominal incision, and
two at the end of the surgery. The optimal timing of
dexamethasone administration is still unclear because
there was no significant difference between trials with
different time of administration.
8 mg or more dexamethasone was administered
in 8 trials, and 5 mg or less dexamethasone was
administerd in 3 trials. Any dose can decrease
incidence and severity of postoperative nausea and
vomiting compared with placebo. 8 mg or more
dexamethasone was more effective than 5 mg or less
on prevention PONV (32% vs 38%). And so 8 mg or
more dexamethasone was suggested.
This meta-analysis showed lower incidence
of rescue analgesia in dexamethasone group than in
placebo group, but the difference was not significantly,
which was not consistent with other studies18. With
repeated reading the trials, all the trials paid more
attention to postoperative nausea and vomiting, while
only a few trials investigated pain simultaneously, and
so a relatively less data about pain could be collected.
Another aspect should be taken account that 354
401
patients underwent diagnostic laparoscopic operation,
which was minimal invasive and hardly induced pain.
And so it was sure that there was a trend a less need for
rescue analgesia in dexamethasone group.
All the trials did not report serious adverse events
after prophylactic dexamethasone administration,
which
suggested
its
safety.
Furthermore,
dexamethasone was very cheap compared with other
types of anti-emetics. That is to say, dexamethasone is
both safe and economic drug to prevent postoperative
nausea and vomiting.
Certainly, there are several limitations in this
meta-analysis. First, it suffers from inherent limitations
of any analysis of aggregate data from published
reports to lump study ourcomes rather than data from
individual patients. Second, the conclusion of our metaanalysis can not be confined to all patients undergoing
laparoscopic gynecological operations, since all the
trials excluded obese patients. In fact, there are more
and more obese patients. At the same time, our metaanalysis just included trials reported in English.
In conclusion, prophylactic dexamethasone
decreases the incidence of nausea and vomiting after
laparoscopic gynecological operations during PACU
and within the first postoperative 24 hours.
M.E.J. ANESTH 21 (3), 2011
402
Wang Bin et al.
Reference
1. Fujii Y: Postoperative nausea and vomiting and their sex differences.
Masui; 2009, 58:59-66.
2. McKeen DM, Arellano R, O'Connell C: Supplemental oxygen does
not prevent postoperative nausea and vomiting after gynecological
laparoscopy. Can J Anaesth; 2009, 56:651-7.
3. Aapro MS, Alberts DS: Dexamethasone as an antiemetic in patients
treated with cisplatin. N Engl J Med; 1981, 305:520.
4. Callery MP: Preoperative steroids for laparoscopic surgery. Ann
Surg; 2003, 238:661-662.
5. Holte K, Kehlet H: Perioperative single-dose glucocorticoid
administration: pathophysiologic effects and clinical implications.
J Am Coll Surg; 2002, 195:694-712.
6. Fujii Y, Nakayama M: Dexamethasone for the reduction of
postoperative nausea and vomiting and analgesic requirements after
middle ear surgery in adult Japanese patients. Methods Find Exp
Clin Pharmacol; 2009, 31:337-40.
7. Chin-Chen Chu, Ja-Ping Shieh, Jann-Inn Tzeng, Jen-Yin Chen, Yi
Lee, Shung-Tai Ho, et al: The prophylactic effect of haloperidol
plus dexamethasone on postoperative nausea and vomiting in
patients undergoing laparoscopically assisted vaginal hysterectomy.
Anesth Analg; 2008, 106:1402-1406.
8. Y Fujii, M Nakayama: Dexamethasone for reduction of nausea,
vomiting and analgesic use after gynecological laparoscopic surgery.
Inter J Gyn and Obst; 2008, 100:27–30.
9. Michael J Paech, Matthew WM Rucklidge, Jennifer Lain, Philip
H: Dodd, Emma-Jane Bennett, Dorota A. Doherty. Ondansetron
and dexamethasone dose combinations for prophylaxis against
postoperative nausea and vomiting. Anesth Analg; 2007, 104:808814.
10.MS Yuksek, HA Alici, AF Erdem, M Cesur: Comparison of
prophylactic anti-emetic effects of ondansetron and dexamethasone
in women undergoing day-case gynaecological laparoscopic
surgery. J Inte Med Res; 2003, 31:481-488.
11.Maddali MM, Mathew J, Fahr J, Zarroug AW: Postoperative
nausea and vomiting in diagnostic gynaecological laparoscopic
procedures: comparison of the efficacy of the combination of
dexamethasone and metoclopramide with that of dexamethasone
and ondansetron. J Postgrad Med; 2003, 49:302-306.
12.Yi Lee, Hsien-Yong Lai, Pei-Chin Lin, Shen-Jer Huang, YouhSheng Lin: Dexamethasone prevents postoperative nausea and
vomiting more effectively in women with motion sickness. Can J
Anesth; 2003, 50:232–237.
13.Eliana Marisa Ganem, Fernanda B Fukushima, Daniela S
Medeirosda Silva, Giane Nakamura, Yara Marcondes Machado
Castiglia, Pedro Thadeu Galvão Vianna: Efficacy of propofol and
propofol plus dexamethasone in controlling postoperative nausea
and vomiting of gynecologic laparoscopy. Rev Bras Anestesiol;
2002, 52:394-401.
14.Jeng-Chai Huang, Ja-Ping Shieh, Chao-Shun Tang, Jann-Inn
Tzeng, Koung-Shing Chu, Jhi-Joung Wang: Postoperative nausea
and vomiting after ambulatory laparoscopic surgery. Can J Anesth;
2001, 48:973-977.
15.JJ Wang, ST Ho, HS Liu, CM Ho: Prophylactic antiemetic effect
of dexamethasone in women undergoing ambulatory laparoscopic
surgery. Br J Anesth; 2000, 84:459-462.
16.V Rajeeva, N Bhardwaj, YK Batra, LK Dhaliwal: Comparison of
ondansetron with ondansetron and dexamethasone in prevention of
PONV in diagnostic laparoscopy. Can J Anesth; 1999, 46:40-44.
17.DM Rothenbergr, J Mccarthyc, C Peng, DA Normoyle: Nausea
and vomiting after dexamethasone versus droperidol following
outpatient laparoscopy with a propof ol-based general anesthetic.
Acfn Aizaesfkesiol Scand; 1998, 42:637-642.
18.Korb K, Scherer M, Chenot JF: Steroids as adjuvant therapy for
acute pharyngitis in ambulatory patients: a systematic review. Ann
Fam Med; 2010, 8:58-63.
VENTILATION DIFFICULTY DUE TO HERNIATION
OF INFLATING TUBE OF THE CUFF INSIDE THE
**
ENDOTRACHEAL TUBE
Oya Yalcin Cok, Melih Cekinmez, Pinar Ergenoglu
and A nis A ribogan
The complications due to airway equipments remain to be one of the most challenging
situations for the anesthesiologists. Any part of an endotracheal tube may cause a risk when it leads
to an obstruction in the airway. Here, we present an increased airway pressure due to herniation of
inflating tube of the cuff inside an armored (wire reinforced) endotracheal tube during neurosurgery
in prone position.
A 34 years old, female patient was scheduled for 6th thoracic vertebraectomy and bilateral
transpedinculer fixation after vertebrae fracture and dislocation. The patient was intubated
uneventfully with an armoured tube (I.D. 7.5 mm, O.D. 17 mm, Mallinckrodt, St. Louis, USA).
The tube level was checked by auscultation and taped at 19 cm. The initial airway pressure was
between 14 - 16 cm H2O with a tidal volume of 450 ml and 11 breaths/min. The anesthesia was
maintained by isoflurane and nitrous oxide/O2 (50%/50%). The endotracheal tube checked again for
an unintentional malpositioning of the tube after prone positioning and confirmed by auscultation
and airway pressure which remained between 18 and 20 cm H2O. After two hours, air leakage was
suspected from the tube and the cuff was inflated with 1 ml of air and the leakage was ended. Airway
pressure started to rise during rod placement after transpedinculer screws insertion at the 3rd hour,
and the neurosurgeons were informed about the problem assuming that the rise in airway pressure
might be related to the surgical procedure as the manipulations due to the reduction for obtaining
thoracic lordosis could be the cause of increased airway pressure. We tried to aspirate through the
endotracheal tube with a 14 Ch aspiration catheter. However, we couldn’t insert the catheter more
than 5 cm inside the tube. The manual ventilation was started until suturation since the airway
pressure and PaCO2 peaked at 60 cm H2O and 70 mmHg, respectively. After a rapid closure of the
surgical site, the patient positioned supine, however airway pressure still remained high and the
suctioning was impossible. When we inspected inside the tube, we noticed a transparent projection
obstructing ½ of the inner diameter of the endotracheal tube (Fig. 1). Immediately, we removed
the obstructed tube and replaced it with a standard 7.5 mm tube. The airway pressure returned into
normal and increase in PaCO2 resolved quickly. The patient was extubated uneventfully.
*
* Baskent University, Faculty of Medicine, Ankara, Turkey.
Corresponding Author: Dr. Oya Yalcin Cok, Baskent University, Department of Anesthesiology and Reanimation,
Adana Research and Education Center, Yuregir Adana/Turkey. Tel: +90 322 3272727-1469, Fax: +90 322 3271274.
E-mail: [email protected]
403
M.E.J. ANESTH 21 (3), 2011
404
Oya Yalcin Cok et al.
Fig. 1
The photograph of the obstruction inside the
endotracheal tube
Nitrous oxide may diffuse into the potential
spaces in the structure of armoured tubes as they
are manufactured in layers3. This may cause a layer
separation leading to an obstructing projection inside
the tube.4 However, in our case, the obstructing
projection was originated from inflating tube of
the cuff (Fig. 2). Inflating the tube cuff during the
operation exacerbated the obstruction as the pressure
was increased both because of the diffused nitrous
oxide and additional air volume. We observed that
deflating the pilot balloon and the cuff resolved the
obstruction after we replaced it with a new tube. It is
important to emphasize that this was not inspected in
the routine examination of the tube before intubation.
We suggest that armoured tubes may require a more
careful examination as they are more likely to cause
unusual complications.
Fig. 2
Diagram of the herniation of
inflating tube of the cuff
References
1. Yapici D, Atici S, Birbicer H, Oral U: Manufacturing defect in
an endotracheal tube connector: risk of foreign body aspiration. J
Anesth; 2008, 22:333-4.
2. Gettelman TA, Morris GN: Endotracheal tube failure: undetected
by routine testing. Anesth Analg; 1995, 81:1313.
3. Hansen D, Dopjans D, Syben R: [Obstruction of a spiral anesthesia
tube in a pediatric circuit system]. Anaesthesist; 1995, 44:884-6.
4. Kopp KH, Wehmer H: [Nitrous oxide induced intraluminal tube
obstruction during endotracheal intubation with armored tubes
(author's transl)]. Anaesthesist; 1981, 30:577-9.
ANESTHESIA FOR CESARIAN SECTION IN
PREGNANT WOMAN WITH ACUTE INTERMITTENT
PORPHYRIA AND HYPOTHYROIDISM
- Case Report* -
Roberto P. Dumas, Elizabeth F. V. Silva,
Marco Antonio C. Resende, Alberto V. Pantoja
and A ntonio C elso G. S. B arros F.
Abstract
Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder¹ affecting
the production of heme, the oxygen-binding prosthetic group of hemoglobin². It is characterized
by a deficiency of the enzyme hydroxymethylbilane synthase; without this cytoplasmic enzyme,
heme synthesis cannot finish, and the metabolite porphobilinogen accumulates in the cytoplasm³.
Some additional factors must also be present such as drugs, hormones, dietary changes, infections
diseases and surgery that trigger the appearance of symptoms, which include neurological disorders,
abdominal pain, constipation, and muscle weakness. We present a perioperative course of a pregnant
woman with porphyria in association with hypothyroidism and its anesthetic management.
Case Report
A 30 yr-old, 67 Kg female woman was admitted with history of 42 weeks of gestational age
and proposal to hold an emergency cesarean section for cephalo-pelvic disproportion.
Past medical history included diagnosis of AIP (without sequelae and with no history of acute
crisis of last 2 years) and hypothyroidism with hormone replacement to 75 mcg of levothyroxine
daily. His airway classification was Mallampati 2 and her ASA status was PIIE.
After completion of the venipuncture with an 18G catheter and monitoring with ECG, NIBP,
pulse oximetry and urine output hourly, carried spinal anesthesia with the patient in the left lateral
position with a 27G Quincke tip and, by median, L3-L4 interspace and injection of 12 mg of heavy
bupivacaine combined with 50 mcg of morphine. At the fifth minute of the blockade, the sensory
level was at T4. After the birth of male fetus (Apgar 9/10), was administered 10 IU of oxytocin.
The volume replacement was given with 500 ml of dextrose 5% and 1000 ml of Ringer's lactate;
had diuresis of 150 ml during the procedure. The patient remained stable throughout the procedure,
which lasted about 75 minutes.
*
Dept. of Surgery. Hospital Universitário Antônio Pedro – Universidade Federal Fluminense.
Corresponding Author: Antonio Celso G. S. Barros F, Dept. of Surgery. Hospital Universitário Antônio Pedro – Universidade
Federal Fluminense. Rua Marquês de Paraná, 303. Centro. Niterói-RJ. CEP 24220-300. Tel: 55-21-26299000 Ramal 9090.
E-mail: [email protected]
405
M.E.J. ANESTH 21 (3), 2011
406
R. P. Dumas et al.
Discussion
The AIP management includes high-carbohydrate
diet; in severe attacks, a glucose 10% infusion is
recommended, which may aid in recovery. Infection
is one of the causes of attacks and requires treatment.
Pain is extremely severe and almost always requires
the use of analgesic drugs and should be treated early
as medically possible.
Nausea and vomiting can be severe. Hematin
and heme arginate are the drugs of choice and need
to be given very early in an attack to be effective.
They are not curative drugs, but can shorten attacks
and reduce the intensity of an attack. Patients with a
history of acute porphyria are recommended to wear
an identification at all times in case they develop
severe symptoms, a result of which may be that they
cannot explain to healthcare professionals about their
condition and the fact that some drugs are absolutely
contraindicated.
An attack of acute intermittent porphyria may
be precipitated by one of the "four Ms": medication,
menstruation, malnutrition, maladies. If drugs have
caused the attack, discontinuing the offending
substances is essential. Patients that experience
frequent attacks can develop chronic neuropathic pain.
This is thought to be due to axonal nerve deterioration
in affected areas of the nervous system. Depression
and seizures often accompanies the disease and is best
dealt with by treating the offending symptoms and, the
judicious use of anti-depressants and anti-convulsant
drugs. Most seizure medications exacerbate this
condition. Urine from a person experiencing an acute
attack may be red or "port wine" in color because of
the presence of porphyrins.
In obstetrics, the main factors triggering the acute
crisis of porphyria are hyperemesis gravidarum, fasting
pre and post-operative, hormonal changes, infections,
surgery and anesthesia. The anesthetic management
must include a careful selection of drugs, hydration
with glucose solution, diet-based carbohydrates,
prophylaxis of bronchial aspiration and evaluation
of liver function. Regional anesthesia is preferred,
because they are many unknown and unsafe anesthetic
drugs, which can be seen in the Table 1. However,
regional anesthesia should be avoided in cases where
there is a neurological injury suspect or indefinite.
Worsening of porphyria during pregnancy may
be between 50% and 90%, with maternal mortality
ranging from 2% to 40%, fetal mortality from 13%
to 40%. In conclusion, AIP and its association
with hypothyroidism in a pregnant patient can be
catastrophic. The main complicating factors in this
case are the association of exposure to surgical stress,
drugs and anesthetic procedure itself.
Table 1
Common Used Anesthetic Drugs Classification
DRUGS
SAFE
UNKNOWN
UNSAFE
HYPNOTICS
Midazolam, Propofol, Lorazepam
Ketamin, Diazepam
Barbiturates, Etomidate
INHANALATED
Nitrous Oxide, Desflurane
Isoflurane, Halothane, Sevoflurane
Enflurane
OPIOIDS
Fentanyl, Morfine
Alfentanyl, Sufentanyl
MUSCLE RELAXANTS
Succinylcholine, Vecuronium
Atracurium, Pancuronium
LOCAL ANESTHETICS
Bupivacaine
Lidocaine
ANOTHER DRUGS
Neoestigmine
Steroids
ANESTHESIA FOR CESARIAN SECTION IN PREGNANT WOMAN WITH ACUTE INTERMITTENT PORPHYRIA
AND HYPOTHYROIDISM
407
References
1. Whatley SD, Roberts AG, Llewellyn DH, Bennet CP, Garret
C, Elder GH: "Non-erythroid form of acute intermittent porphyria
caused by promoter and frameshift mutations distant from the
coding sequence of exon 1 of the HMBS gene". Hum Genet; 2000,
107(3):243-8.
2. Baker S and Taylor B: Anaesthesia is also risky in patients with
porphyria. BMJ; 2006, 321:1023-1023.
3. Aarsand AK, Petersen PH, Sandberg S: “Estimation and
application of biological variation of urinary delta-aminolevulinic
acid and porphobilinogen in healthy individuals and in patients with
acute intermittent porphyria". Clinical Chemistry; 2006, 52(4):650656.
4. JAMES MFM and HIFT RJ.: Porphyrias. Br J Anaesthesia; 2000,
85:143-153.
5. Jensen NF, Fiddler DS, Striepe V: Anesthetic considerations in
porphyrias. Anesth Analg; 1995, 80:591-599.
6. Yamashita AM, Gozzani JL: Anestesia em Obstetrícia. 2 Edição.
São Paulo. Editora Atheneu, 2007.
7. James WD, Berger TG et al: Andrews' Diseases of the Skin:
Clinical Dermatology. Saunders Elsevier, 2006.
8.American Porphyria Foundation. "About Porphyria: Acute
Intermittent Porhyria", 2007.
9. Marcucci L: PathCards. Baltimore, MD: Lippincott Willians &
Wilkins, 2004, pp. 105-106.
M.E.J. ANESTH 21 (3), 2011
“CRIME SCENE INVESTIGATION” AT AN ANESTHETIC
COCKTAIL PARTY WITH ATRIOVENTRICULAR
DISSOCIATION
Christoph J. Schlimp*
and
Franz J. Wiedermann**
Abstract
A healthy 21-year old female patient received midazolam, propofol, fentanyl, rocuronium,
nitrous oxide in oxygen, ranitidine, diclofenac, neostigmine and glycopyrrolate during the
anesthetic process for elective knee arthroscopy and developed a complete AV dissociation with
a P-wave frequency of 40 and a “small” QRS-complex frequency of 55 beats/min. Based on this
typical case of poly-pragmatic anesthetic drug administration causing a complete atrioventricular
dissociation in a young healthy patient we will discuss the possible pharmacodynamic mechanisms
of all used drugs with regard to the cardiac conduction system.
Keywords: atrioventricular heart block, general anesthesia, midazolam, fentanyl, propofol,
ranitidine, neostigmine, rocuronium, glycopyrrolate, nitrous oxide.
Financial support and conflict of interest: None.
Introduction
Poly-pragmatic drug administration during balanced anesthesia is commonly used to reduce
high doses and side effects of one drug or to antagonize (side) effects of other drugs. Typically
used poly-pragmatic anesthetic drug administrations are e.g. different hypnotics: benzodiazepines
for pre-medication, barbiturates for induction and a volatile anesthetic for sustaining anesthesia; or
e.g. different opioids: fentanyl for induction of anesthesia, remifentanyl for accurate controllable
analgesia during the operation and a less potent agent like morphin or piritramid for postoperative analgesia. In addition to hypnotics and opiods, neuromuscular blocking agents and their
antagonist (acetyl-cholinesterase inhibitor again combined with its own vegetative antagonist: an
anticholinergic) are commonly used. Histaminic H2-receptor antagonists are also often administered
to minimize gastric volume and for gastric protection in combination with non-steroidal anti
inflammatory drugs. However, the advantages of this poly-pragmatic drug administration may lead
to difficult allocation of possible side effects due to the higher potential of drug interaction. Based
on a “crime scene” of a complete atrioventricular (AV) dissociation after administration of nine
different drugs in a young healthy patient we will investigate and discuss the scene and review the
possible pharmacodynamic mechanisms of all used drugs with regard to its influence on the AV
conduction system.
*
**
Dept. of Anesthesiology and Critical Care Medicine, Trauma Hospital Klagenfurt, Austria.
Associate Professor. Dept. of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, Austria.
Corresponding Author: Dr. Christoph Schlimp, Department of Anesthesiology and Critical Care Medicine, Trauma
Hospital Klagenfurt, Waidmannsdorferstrasse 35, A-9021 Klagenfurt, Austria. Tel: +43-463-5890-1035, Fax: +43-4635890-1038. E-mail: [email protected]
409
M.E.J. ANESTH 21 (3), 2011
410
“Crime Scene”
A 21-year-old woman, 65 kg and 168 cm, ASA
status I, presented for an elective knee arthroscopy of
about 45 min anesthesia. Medical history and physical
examination were without pathological findings, the
patient took no medication, and preoperative routine
laboratory results were within the normal range. The
following drugs were given to the patient during
the anesthetic process: midazolam (7.5 mg orally),
propofol (200 mg bolus + 400 mg/h), fentanyl (0.15
mg), rocuronium (25 mg), nitrous oxide (66%) in
oxygen (33%), ranitidine (50 mg), diclofenac (75mg),
neostigmine (3.2 mg) and glycopyrrolate (0.6 mg).
Suddenly the monitoring ECG showed a complete
AV dissociation, with a P-wave frequency of 40 and
a “small” QRS-complex frequency of 55 beats/min,
hemodynamical stable and resolving during emergence.
C.S.I. “Crime Scene Investigation”
Investigator: At the scene currently under
investigation, we saw the appearance of a complete AV
dissociation during anesthesia. Nine drugs (midazolam,
fentanyl, propofol, rocuronium, nitrous oxide,
ranitidine, diclofenac, neostigmine, glycopyrrolate)
have been spotted on the scene. Which drug used has
the potential to elicit AV dissociation?
Anesthesia Expert: Midazolam was reported to
have a dose-dependent depressing effect on the AV
node in isolated guinea pig hearts1. Fentanyl is known
to have central vagal effects and might probably posses
direct depressing effects on the AV conduction2. Clinical
evaluation of cardiac electrophysiological effects of
midazolam combined with fentanyl, however, did not
show significant changes in the electrophysiological
variables3.
Propofol’s mechanism of action on the AV
conduction system is not completely known and
literature is quite dissolute on this topic. Propofol
is supposed to have a central vagotonic and/or
sympatholytic mechanism4 and was held responsible for
the occurrence of a second degree AV Mobitz I block5-7
reversible by anticholinergic drug administration. In a
child, a single bolus of propofol elicited a complete
AV block, but this child was suffering from Ondine’s
curse, characterized by a generalized disorder of
autonomic function8. The combination of propofol and
neostigmine in a patient also caused a complete heart
block9. In all of the cases described above, the AV block
was thought to be caused by a vagotonic (cholinergic)
mechanism. Recently, propofol was associated with
antiarrhythmic properties in the cardiac conduction
system10, but the indirect vagotonic or direct influence
of propofol on the electrophysiological properties of
the heart are controversial and may depend on the
species investigated and the specific conditions of
study. The negative dromotropic effects of propofol
in the isolated guinea pig heart were suggested to be
mediated by muscarinic M2-receptors11, an idea which
would be supported by a study that found no direct
effect of propofol on the canine cardiac conduction
system under autonomic blockade12. This is in contrast
with the results of a study of isolated rabbit hearts,
in which under complete autonomic blockade at
clinically relevant propofol doses, a direct frequencydependent effect on the AV node was found13. A study
in closed chest pigs showed that propofol causes a
dose-related depression of the sinus node and the
His-Purkinje system but has no effect on the AV node
function14 whereas studies in isolated guinea pig heart
revealed dose-or frequency-dependent AV nodal
effects of propofol1,15. On the cellular level, propofol
suppressed directly the sodium, calcium and potassium
currents in rabbit heart myocytes16. However, clinical
studies have shown that propofol does not affect the
effective refractory periods of the AV node in patients
with Wolff-Parkinson-White syndrome17 and children
undergoing radiofrequency ablation18.
Ranitidine blocks histaminic H2-receptors and
inhibits the G-protein mediated rise in cyclic adenosine
monophosphate, and thus decreases the heart rate.
Furthermore, by blocking competitively H2-receptors,
free histamine molecules can now activate more H1receptors leading to a G-protein- mediated rise in
calcium decreasing cardiac dromotropy. Extremely
rare cardiovascular side effects are reported to occur
especially after rapid infusion19, and it has been
mentioned in association with AV block20,21.
Neostigmine, a peripheral acetyl-cholinesterase
inhibitor is strongly parasympathomimetic by
increasing the acetyl-cholin concentration also at
the muscarinic M2-receptor in the heart, Therefore,
neostigmine was reported to cause AV conduction
411
depression in several cases9,22-24.
Investigator: What effects do the other drugs
exert on the cardiac conduction system?
Anesthesia Expert: Glycopyrrolate, a peripheral
blocking drug at the muscarinic M2-receptor in the
heart, enhances parasympatholytic effects and therefore
is a cardiac conduction-stimulatory agent. Rocuronium
is also known to have weak parasympatholytic
activity25. Nitrous oxide was mentioned in a case of
AV dissociation with AV junctional rhythm26 but its
influence on the heart’s automaticity and conduction
is not easy to define and might rather be a change
in sympathetic nervous activity27. Diclofenac is not
known to have any direct impact on cardiac arrhythmia,
besides the possible hyperkalemia after non-steroidal
anti-inflammatory drug-induced renal dysfunction28.
Investigator: What do you think was the
combined effect of all these drugs and which drug
should be held most responsible regarding the onset of
AV dissociation in this patient?
Anesthesia Expert: Probably minor complices
on the scene but inevitably present in almost all
anesthetic scenes were midazolam and fentanyl. Due
to its previously discussed properties, propofol is a
very interesting possible culprit present during the
whole act. Another potential offender present and
to be considered is ranitidine. All these drugs were
finally toped up with neostigmine. We have previously
discussed, that midazolam, fentanyl, propofol,
ranitidine and neostigmine have all depressing effects
on the AV conduction and may therefore conclude
in the first place that their combination might have
elicited this AV dissociation.
Timing of the appearance of neostigmine
shortly before the onset of the AV dissociation
would also suggest that it played the major role
in this act. Furthermore, due to the well known
parasympathomimetic effect of neostigmine to induce
bradycardia, it is usually combined with glycopyrrolate
a parasympatholytic. Some would now advocate that
the simplest explanation for the heart block in this
patient is a relatively high dose of neostigmine and
a relatively low dose of glycopyrrolate. Rocuronium
that has weak vagolytic side effects was apparently not
much of a help to support glycopyrrolate in this case.
We do, however, not know whether a higher dose of
glycopyrrolate would have made any difference in the
occurrence of the AV dissociation and can conclude
that midazolam, fentanyl, propofol and ranitidine had
at least a very high potential for enhancing this side
effect of neostigmine.
Investigator: Well, then is there anything, that
could have prevented AV dissociation?
Anesthesia Expert: With regard to this patient,
it is of interest that post-operative evaluation of preoperative existing electrocardiography (ECG) showed
a borderline AV block grade I with a PQ interval of
212 ms.
Pre-operative consideration of this fact would
probably have changed the poly-pragmatic drug
administration in this case, but routine ECG evaluation
in young patients is not common and its outcome and
cost effectiveness with regard to the prevention of such
adverse events would be subject to further discussion
and investigation? However its knowledge might lead
to a more critical use of the previously discussed agents
in such patients. Furthermore, routine use of intraoperative relaxometry might help to reduce or avoid
the routine use of acetyl-cholinesterase inhibitors and
their mentioned side effects. Routine use of ranitidine
in every patient should be carefully considered and
restricted to especially indicated cases. Maybe, where
possible, regional anesthesia would be preferable
reducing drug interaction and its potential to cause AV
dissociation in such patients.
Final pleading
The combination of many drugs routinely used
during general anesthesia may have caused the complete
AV dissociation in this scene. It appears that the
cardiac conduction-stimulatory agent glycopyrrolate
was not effective enough to compensate for the cardiac
conduction-depression, provoked by the cumulative
drug interaction due to combination of midazolam,
fentanyl, propofol, ranitidine and neostigmine.
Anesthetists should be aware of the cardiac conduction
side effects of routinely used drug cocktails and should
adapt poly-pragmatic drug administration with regard
to possible AV conduction abnormalities evident
on available ECGs even in young healthy patients.
Current poly-pragmatic drug administration should be
generally reconsidered.
M.E.J. ANESTH 21 (3), 2011
412
References
1. Stowe DF, Bosnjak ZJ, Kampine JP: Comparison of etomidate,
ketamine, midazolam, propofol, and thiopental on function and
metabolism of isolated hearts. Anesth Analg; 1992, 74:547-58.
2. Bovill JG, Sebel PS, Stanley TH: Opioid analgesics in anesthesia:
with special reference to their use in cardiovascular anesthesia.
Anesthesiology; 1984, 61:731-55.
3. Lau W, Kovoor P, Ross DL: Cardiac electrophysiologic effects of
midazolam combined with fentanyl. Am J Cardiol; 1993, 72:177-82.
4. Cullen PM, Turtle M, Prys-Roberts C, Way WL, Dye J: Effect of
propofol anesthesia on baroreflex activity in humans. Anesth Analg;
1987, 66:1115-20.
5. Ganansia MF, Francois TP, Ormezzano X, Pinaud ML, Lepage
JY: Atrioventricular Mobitz I block during propofol anesthesia for
laparoscopic tubal ligation. Anesth Analg; 1989, 69:524-5.
6. Elhairy A, Seguier JC, Sinda P: Auriculo-ventricular conduction
disorder following a continuous administration of propofol. Apropos
of a case. Cah Anesthesiol; 1992, 40:417-9.
7.El Hairy M: Mobitz I atrioventricular block during propofol
anesthesia. Ann Fr Anesth Reanim; 1993, 12:606.
8. Sochala C, Deenen D, Ville A, Govaerts MJ: Heart block following
propofol in a child. Paediatr Anaesth; 1999, 9:349-51.
9. James MF, Reyneke CJ, Whiffler K: Heart block following
propofol: a case report. Br J Anaesth; 1989, 62:213-5.
10.Kannan S, Sherwood N: Termination of supraventricular tachycardia
by propofol. Br J Anaesth; 2002, 88:874-5.
11.Alphin RS, Martens JR, Dennis DM: Frequency-dependent effects
of propofol on atrioventricular nodal conduction in guinea pig
isolated heart. Mechanism and potential antidysrhythmic properties.
Anesthesiology; 1995, 83:382-4; discussion 24A.
12.Ikeno S, Akazawa S, Shimizu R et al: Propofol does not affect the
canine cardiac conduction system under autonomic blockade. Can J
Anaesth; 1999, 46:148-53.
13.Wu MH, Su MJ, Sun SS: Age-related propofol effects on
electrophysiological properties of isolated hearts. Anesth Analg;
1997, 84:964-71.
14.Pires LA, Huang SK, Wagshal AB, Kulkarni RS:
Electrophysiological effects of propofol on the normal cardiac
conduction system. Cardiology; 1996, 87:319-24.
15.Napolitano CA, Raatikainen MJ, Martens JR, Dennis DM: Effects
of intravenous anesthetics on atrial wavelength and atrioventricular
nodal conduction in guinea pig heart. Potential antidysrhythmic
properties and clinical implications. Anesthesiology; 1996, 85:393402.
16.Wu MH, Su MJ, Sun SS: Comparative direct electrophysiological
effects of propofol on the conduction system and ionic channels of
rabbit hearts. Br J Pharm; 1997, 121:617-24.
17.Sharpe MD, Dobkowski WB, Murkin JM, Klein G, Yee R:
Propofol has no direct effect on sinoatrial node function or on
normal atrioventricular and accessory pathway conduction in WolffParkinson-White syndrome during alfentanil/midazolam anesthesia.
Anesthesiology; 1995, 82:888-95.
18.Lavoie J, Walsh EP, Burrows FA, Laussen P, Lulu JA, Hansen DD:
Effects of propofol or isoflurane anesthesia on cardiac conduction
in children undergoing radiofrequency catheter ablation for
tachydysrhythmias. Anesthesiology; 1995, 82:884-7.
19.Vial T, Goubier C, Bergeret A, Cabrera F, Evreux JC, Descotes J:
Side effects of ranitidine. Drug Saf; 1991, 6:94-117.
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block in a young duodenal ulcer patient treated with a standard oral
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of ranitidine. Can J Anaesth; 1999, 46:776-8.
22.Lonsdale M, Stuart J: Complete heart block following
glycopyrrolate/neostigmine mixture. Anaesthesia; 1989, 44:448449.
23.Tanaka H, Murata K, Sera A, Horibe M, Izumi H, Tsuchiya T:
Conversion to 2nd degree from 1st degree atrioventricular (AV)
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24.Webb MD: Type I second-degree AV block after neostigmine
administration in a child with renal failure. Anesth Prog; 1995,
42:21-2.
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patients, paralysed with vecuronium. Br J Anaesth; 1997, 78:586-7.
26.Roizen FR, Plummer GO, Lichtor JL: Nitrous oxide and
Dysrhythmias. Anesthesiology; 1987, 66:427-31.
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JP: Effects of nitrous oxide on contractile function and metabolism
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28.Alva JP, Kotian G: Diclofenac induced renal dysfunction presenting
as cardiac arrhythmia. J Assoc Physicians India; 2001, 49:749-52.
LEFT ATRIAL MYXOMA WITH CORONARY
ARTERY DISEASE: AN UNEXPECTED
PREOPERATIVE FINDING
- Case Report -
Madan Mohan Maddali*, Ahmed Mohammed Abduraz**,
Prashanth Panduranga*** and Elizabeth Kurian****
Abstract
We describe the case of a 54-year-old man with no symptoms of a cardiac disease who, in the
preoperative assessment for eye surgery was diagnosed to have a left atrial myxoma coupled with
coronary artery disease. After thorough investigations, the patient underwent resection of the left
atrial tumor and coronary artery bypass grafting with a succesful outcome. The histopathological
examination revealed a myxoma. This case report highlights the importance of preoperative
evaluation in patients with unsuspected coexisting cardiac diseases, treatment options and the
anesthetic concerns.
Keywords: Myxoma; heart atria left; Myxoma/surgery; Coronary Disease/surgery.
Atrial myxomas are the most common benign primary tumours of the heart and sudden deaths
probably related to coronary embolization have been described1,2. This report is unusual on account
of a rarely described concomitant presence of a left atrial {LA} myxoma with coronary artery
disease [CAD] in an otherwise asymptomatic patient. The objective of this report is to highlight
the importance of a through preoperative evaluation in the diagnosis of cardiac ailments even in
asymptomatic patients. In addition, this report draws attention to conundrums like:
a)
Could the CAD be secondary to embolization from the LA myxoma
b)
What are the therapeutic options? When should coronary artery bypass surgery [CABG] be
performed and
c)
What are the anesthetic challenges?
Case History
A large LA mass was incidentally found during a transthoracic echocardiography [TTE]
examination when an asymptomatic 54 year old man with electrocardiogram [ECG] changes was
undergoing a routine preoperative cardiological assessment for eye surgery. He was a diabetic with
sedentary habits and belonged to ASA class III physical status [BMI >30]. All his hematological
*
Senior Consultant in Anesthesia,Royal Hospital, Muscat, Sultanate of Oman.
** Senior Specialist in Cardiology, Royal Hospital, Muscat, Sultanate of Oman.
*** Senior Specialist in Anesthesia, Royal Hospital, Muscat, Sultanate of Oman.
****Resident in Anesthesia, Oman Medical Specialty Board, Sultanate of Oman.
Address for correspondence: Dr. Madan Mohan Maddali, Senior Consultant in Anesthesia, Royal Hospital, P.B. No:
1331, P.C: 111, Seeb, Muscat, Sultanate of Oman. Tel/Fax: 00 968 24499759. E-mail: [email protected]
413
M.E.J. ANESTH 21 (3), 2011
414
and biochemical markers were within normal limits
except that he had dyslipedemia as well as an elevated
fibrinogen level {4.31g/L[normal: 1.5 to 4.2]}.
ECG showed a sinus rhythm with left axis
deviation, left ventricular hypertrophy with strain and
a QS pattern in III,AVF. Chest radiography showed
cardiomegaly with minimal left basal effusion.
Transesophageal echocardiography (TEE) confirmed a
large LA mass [5 cm x 3.5 cm] attached to fossa ovalis
with specks of calcification. The mass was prolapsing
into mitral valve during diastole [Fig. 1] and the mitral
valve was normal. LA appendage had no thrombus but
there was a 4 mm layered atheroma in the descending
aorta.
Considering patients age, diabetic status, ECG
showing old inferior wall myocardial infarction (MI)
pattern and left ventricular dysfunction, a coronary
angiography was performed which demonstrated an
isolated 70% occlusion of the left anterior descending
[LAD] artery.
Under general anesthesia with standard ASA
monitoring intraoperative TEE guidance, the patient
underwent resection of the LA mass and coronary
artery bypass grafting with an anastomosis between
the left internal mammary artery and the LAD artery
on cardiopulmonary bypass [CPB]. Tables 1 and 2
show perioperative hemodynamic data and blood gas
Fig. 1
Transesophageal
echocardiography in long-axis
view showing a large left atrial
myxoma attached
at fossa ovalis and prolapsing
into left ventricle during
diastole
M. M. Maddali et al.
parameters. The postoperative course was uneventful.
The specimen weighed 47 grams (gms) and on
histopathological analysis confirmed the diagnosis of
a myxoma.
Discussion
Fifty percent of all primary cardiac tumors
are myxomas with a majority arising in the LA3,4.
Approximately 10% of patients with atrial myxomas
may be completely asymptomatic1. Most often
a thorough preoperative evaluation detects the
underlying pathology in these asymptomatic patients
when they undergo incidental non cardiac or cardiac
surgery. Awareness of the clinical signs and symptoms
produced by myxomas is essential to raise the suspicion
of their presence.
Atrial myxomas can produce obstructive,
constitutional, and embolic symptoms when they
weigh greater than 70 gms5. As the myxoma in our
patient weighed less probably he was asymptomatic.
Obstruction of mitral valve can mimic mitral
stenosis6. Systemic manifestations like weight loss,
arthralgias, fever, anemia etc might occur before
obstructive or embolic events and might be due to
microembolism or due to the triggering of immunologic
responses by tumor fragmentation7.
LEFT ATRIAL MYXOMA WITH CORONARY ARTERY DISEASE: AN UNEXPECTED PREOPERATIVE FINDING
415
Table 1
Perioperative hemodynamic parameters
8:00
8:30
8:30 am 9:00 am
PAP [mm Hg]
9:00
9:30
am
9:30
-10:00
am
10:30
-11:00
am
11:30
12:00
am
11:00
-11:30
am
12:00
12:30
am
25/15
26/14
CVP [mm Hg]
8
7
7
ETCO2[mm Hg]
32
32
34
SaO2
100
100
100
150/80
100/65
105/ 65
Arterial Blood
pressure[mm Hg]
10:00
-10:30
am
8
9
34
34
100
100
100
125/55
125/ 60
105/ 50
CPB
Started at 9:42 am
Ended at 11:10 am
Table 2
Blood gas analysis values of arterial and mixed venous blood
Arterial Blood Gas /
Electrolytes
arterial sample
[8:42am]
venous
sample
[9:40am]
venous
sample
[10:30am]
arterial
sample
[10:32am]
venous sample
[10:56am]
venous
sample
[11:35am]
PH
(7.35 - 7.45)
7.548
7.435
7.404
7.431
7.375
7.460
PCO2
mmHg
35.6
38.5
38.4
36.4
39.2
36.4
PO2
mmHg
174.7
41.7
47.5
190.9
42.6
37.3
HCO3 std mmol/L
23.5
23.8
23.4
23.2
22.1
21.9
tCO2 mmol/L
19.9
24.4
24.6
23.4
23.6
21.3
Base Excess
-1.3
-0.4
-1.1
-1.5
-2.5
-2.7
Na+
(135.0 - 148.0mmol/L)
134.6
135.5
136.8
138.6
135.2
139.7
K+
(3.5 – 5.3 mmol/L)
3.14
3.14
4.36
4.34
4.2
3.48
Ca++
(1.13 – 1.32mmol/L)
0.8
0.8
1.11
1.10
1.11
0.94
Cl(98 – 106 mmol/L)
106
101
107
107
107
105
Anion Gap [mmol/L]
12.5
14.3
4.7
5.6
6.0
10.7
Screening for myxomas should involve a thorough
history, physical examination and echocardiography
[TTE: 95% sensitivity, TEE: 100% sensitivity]8.
The age at presentation and the symptoms of
atrial myxomas and CAD can be similar. At times,
the two lesions coexist as seen in our patient. A high
index of suspicion remains the key element in making
a combined diagnosis9.
Is the CAD in this patient secondary to
embolization from the myxoma or a coexisting condition
secondary to atherosclerosis or both? Coronary artery
embolization, albeit a lethal complication of atrial
myxomas, is extremely rare [0.6%]10. The low rates
might be because emboli are less likely to enter the
coronary arteries11. There is a tendency for embolism
into the right coronary artery due to its conducive
M.E.J. ANESTH 21 (3), 2011
416
position.
Villous or polypoidal myxomas are fragile and
embolize easily12. Tumors with an irregular and friable
surface have a higher incidence of embolization7.
Even though, the myxoma in this patient was not
villous, it could have been the source of right coronary
artery embolization with subsequent recanalization.
This was seen as QS waves in the inferior wall leads in
the ECG as well as an akinetic segment on TTE. But,
coronary angiography that was performed a few days
later revealed a normal right coronary artery suggesting
a possible recanalization. The rate of recanalization is
high for coronary embolism from myxomas13,14,15. We
believe that the CAD in this patient was due to both
atherosclerotic disease as well as due to a previous
tumour emboli.
As regards the therapeutic options, in cases of
atrial myxoma presenting with acute MI, coronary
angiography is mandatory12. Thrombolytic therapy
usually is not recommended for patients with cardiac
myxomas and MI, because of the risk of tumor
embolisation16,17.
Following diagnosis of an atrial myxoma,
immediate operative removal is advisable. Patients
with associated CAD should undergo CABG during
tumor removal. If the excision of the myxoma is to
be delayed in patients with atrial myxoma and MI, it
would be advisable to repeat coronary angiography
M. M. Maddali et al.
immediately before the operation, because of the
tendency for spontaneous recanalization.
The anesthetic concerns for patients with a LA
myxoma are similar to those with mitral stenosis.
Occasionally, atrial fibrillation might warrant heart rate
control with pharmacologic therapy perioperatively.
Postural hypotension can occur due to prolapse of
the tumor mass into a valve orifice. Entrapment of
the myxoma in the mitral valve during the course of
anesthesia can result in a cardiac arrest. Placing the
patient in the right lateral decubitus position with a
head down tilt and vigorously shaking the chest might
aid in dislodging the tumor from the mitral valve18.
In conclusion, patients with atrial myxoma
are either asymptomatic or often present with non
specific symptoms that are often overlooked in the
absence of a supporting cardiac history. This makes
an early diagnosis challenging. Although atrial
myxomas are very rare, their presence should be
considered, particularly in young patients without
cardiac risk factors who present with either acute or
old MI. Echocardiography is a reliable diagnostic tool
that helps in the differential diagnosis and decisionmaking. Surgery should not be delayed in patients
with polypoid-type LA myxomas because of the high
incidence of embolism. For patients aged above 40 years
and without cardiovascular risk factors, it is advisable
to perform coronary angiography preoperatively to
identify the presence of a concomitant CAD.
LEFT ATRIAL MYXOMA WITH CORONARY ARTERY DISEASE: AN UNEXPECTED PREOPERATIVE FINDING
417
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of coronary angiography in myxoma patients: a 14-year experience
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M.E.J. ANESTH 21 (3), 2011
POST-OPERATIVE RESPIRATORY COMPLICATIONS
AFTER PALATOPLASTY IN A 19 MONTH OLD FEMALE
WITH CORNELIA DE LANGE SYNDROME
- A Case Report -
Brooke Ingram*, Elizabeth AM Frost
Abstract
Cornelia De Lange syndrome is a rare genetically heterogeneous and sporadic syndrome, with
an estimated prevalence of 1 in 10,000 to 30,000. The disorder may present many complications
during anesthesia due to cardiac, gastrointestinal and airway anomalies. We report a case of an
ex premature toddler presenting for repair of a cleft palate. Postoperatively she had respiratory
distress, successfully treated by the anesthetic care team Causes for the complication are discussed.
Case Report
A 19 month old former 34-week gestational age female with a history of Cornelia De Lange
Syndrome presented for closure of a cleft palate. Additional past medical history was significant for
reflux disease treated by Nissen fundoplication, failure to thrive managed with G-tube placement,
and hearing loss for which she had undergone left myringotomy tube placement. Previous anesthetic
records indicated she was easily ventilated with an oral airway but a Grade 3 view was achieved
during prior intubation attempts with a Miller 1 blade. On examination, with a deep bite, her lower
front incisors bit into her malformed palate.
Induction of anesthesia was achieved with sevoflurane and nitrous oxide in oxygen. A WIS
blade 1.0 revealed an anterior airway with a grade 3 view which improved to a grade 2 view with
cricoid pressure. The first attempt to pass a 4.0 endotracheal tube failed. The next attempt with a
3.5 cuffed tube was successful. Intravenous access was secured. Anesthesia was maintained with
isoflurane in oxygen plus intermittent fentanyl. At the conclusion of surgery, the patient’s mouth
and gastric tube were suctioned; she was moving spontaneously. The trachea was extubated and
she was given blow-by oxygen. Her oxygen saturation remained satisfactory for approximately
five minutes. She was then moved to her hospital bed at which time acute desaturation to the 60s
occurred. The patient was moved back to the OR table and ventilated with 100% inspired oxygen.
She remained otherwise hemodynamically stable. Dexamethasone 4 mg and glycopyrrolate
30 mcg were given in addition to albuterol nebulization. An oral airway was placed with the
surgeon’s approval and mask ventilation with continuous positive pressure reestablished. No upper
airway obstruction or swelling could be observed, but auscultation of her lungs revealed rhonchi
bilaterally. After approximately one hour, the inspired oxygen was decreased from 100% with
assisted ventilation to blow-by oxygen. At time of transport, she remained hemodynamically stable
*
Department of Anesthesiology, Mount Sinai Medical Center, New York, NY.
Contact information: E-mail: [email protected], [email protected]. Phone: (212) 241-1518, Fax: (212) 4262009.
419
M.E.J. ANESTH 21 (3), 2011
420
with oxygen saturations above 92%. Over the next few
hours, the oxygen saturation improved to 99%. There
were no further episodes of desaturation. Chest X-ray
was clear. She was discharged to home after 3 days.
B. Ingram & E. A. Frost
autosomal dominant.
Discussion
Cornelia de Lange syndrome (CdLS) was first
documented by Brachman in 19161 and later by a
Dutch pediatrician, Cornelia de Lange in 19332,3. The
syndrome consists of multiple congenital anomalies
resulting in a distinctive facial appearance, prenatal
and postnatal growth deficiency (95%), feeding
difficulties (reflux in 90%), psychomotor delay,
behavioral problems, and associated malformations
that mainly involve the upper extremities (80% have
clinodactyly, bradydactyly or olidactylyl). Congenital
heart disease occurs in 20-30% and hearing loss in
60%4,5. The most diagnostic aspect of the disease are
the facial characteristics which include: confluent
eyebrows, long curly eyelashes, low anterior and
posterior hairline, underdeveloped orbital arches,
well-defined arched eyebrows (as though they had
been penciled), long philtrum, thin lip, depressed nasal
bridge, high arched/cleft palate, and micrognathia
(Fig. 1). A gene responsible for CdLS-NIPBL on
chromosome 5-was discovered in 2004 jointly by
researchers at the Children’s Hospital of Philadelphia,
USA and researchers at Newcastle University, UK6,7.
In 2006, a second gene-SMCIA on the X chromosonewas found by Italian scientists. A third gene
discovery was announced in 2007. The gene SMC3
is on chromosone 10 and was also discovered by the
research team in Philadelphia. The latter two genes
seem to correlate with a milder form of the syndrome.
NIPBL and SMC3 have autosomal dominance and
SMCIA, an X linked dominant pattern of inheritance.
All genes are involved in sister chromatid cohesion.
There is no known cure but the syndrome can be
managed by treating associated clinical symptoms.
Sixty six percent of CdLS individuals die during the
first year of life. Mortality occurs primarily from
aspiration in infancy and from infection and bowel
obstruction there after4,5. However, some children
live until adulthood.The vast majority of cases are
due to spontaneous mutations, although the defected
gene can be inherited from either parent, making it
Anesthetic concerns include high risk of
aspiration, upper airway obstruction and difficult
intubation, unpredictable response to drugs due to
endocrine disorders and renal failure, and adverse
effects of pulmonary hypertension or congenital cardiac
anomalies. Pulmonary hypoplasia also predisposes the
patient to respiratory infection post operatively.
The etiology of our patient’s postoperative
respiratory distress was probably multifactorial.
She may have had undiagnosed sleep apnea and
thus was extremely susceptible to sedatives. There
may also have been residual effects of prematurity
as she remained very small for her age at the time
of surgery. Opioid-induced respiratory depression
and residual inhalational anesthetic effects are other
possibilities. As prolonged surgery was performed
in the area, postoperative edema of the oropharynx
may also have had some additive effect. Most likely,
it was a combination of these factors. The importance
of close communication between all members of the
perioperative team and careful monitoring of vital
signs, especially oxygenation, is emphasized. These
patients should not be candidates for day care surgery
or anesthetic management in an out patient facility,
including a dental office.
In an attempt to identify patients and learn more
about the syndrome, the Cornelia de Lange Syndrome
(CdLS) Foundation was established as a nonprofit,
family support organization based in Connecticut,
USA. It provides materials for public education and
information. In addition to Reaching Out, a bi-monthly
newsletter, the Foundation produces and distributes
POST-OPERATIVE RESPIRATORY COMPLICATIONS AFTER PALATOPLASTY IN A 19 MONTH OLD FEMALE
WITH CORNELIA DE LANGE SYNDROME
several other publications on the syndrome, as well as
a video The foudation can be reached at info@cdlsusa.
421
org Ph:001 860-676-8166 860-676-8255 Toll-Free
Support Lines: 800-753-2357 (United States)
References
1.Brachmann, W: Ein Fall von symmetrischer Monodaktylie durch
Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen,
sowie anderen Abnormitaeten (Zwerghaftigkeit, Halsrippen,
Behaarung) (A case of symmetrical monodactyly, representing
ulnar deficiency, with symmetrical antecubital webbing and other
abnormalities, (dwarfism, cervical ribs, hirsutism)). Jahrbuch fuer
Kinderheilkunde und physische Erziehung; 1916, 84:225-235.
2. de Lange, C: Sur un type nouveau de degenerescence (typus
Amstelodamensis). Arch. Med. Enfants; 1933, 36:713-719.
3.http://www.whonamedit.com/synd.cfm/1080.html
4.Deardorff M, Yaeger D, and I Krantz: "Cornelia de Lange
Syndrome". National Center for Biotechnology Information; 2006.
Available at: www.ncbi.nlm.nih.gov.
5.Parker, P: Cornelia de Lange Syndrome-A Bibliography and
Dictionary for Physicians, Patients, and Genome Researchers.
ICON Group International; 2007.
6.Krantz ID, McCallum J, DeScipio C, et al (2004): "Cornelia de
Lange syndrome is caused by mutations in NIPBL, the human
homolog of Drosophila melanogaster Nipped-B". Nat. Genet;
36(6):631-5. doi:10.1038/ng1364. PMID 15146186.
7.Tonkin E, Wang TJ, Lisgo S, Bamshad MJ, Strachan T (2004):
"NIPBL, encoding a homolog of fungal Scc2-type sister chromatid
cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange
syndrome". Nat. Genet. 36(6):636–641. doi:10.1038/ng1364. PMID
15146185.
M.E.J. ANESTH 21 (3), 2011
WHAT IF THE EPIDURAL CATHETER NEEDS
TO BE FIXED MORE THAN FIFTEEN
CENTIMETRES AT SKIN?
Vishal Uppal*
Epidural catheters inserted 8 cm within the epidural space are more likely to result in
intravenous cannulation and unilateral block1. Epidural catheters inserted 2 or 4 cm within the
epidural space are more likely to be dislodged than epidural catheters inserted 6 or 8 cm.1 Obese
patients are at particular risk of epidural catheter displacement2. It is recommended that epidural
catheters should be inserted 5 or 6 cm into the epidural space when prolonged labour or caesarean
delivery is likely1,3. Epidural catheters do not have cm markings between 15 and 20 cm marks. I
would like to report an inconvenient situation caused by absence of these markings and a method of
dealing with it. A 26 year old, morbidly obese primigravida requested an epidural in the first stage
of labour. Her booking BMI and body weight were recorded as 66 kg.m-2 and 175 kg respectively.
After failing to reach epidural space with a standard 10.5 cm, 18 gauge Portex Epidural needle, a
Portex extra length (13.5 cm) Tuohy needle was used. On the fourth attempt, the epidural space
was located using loss of resistance to saline technique with the Tuohy needle at 11 cm to skin.
An 18 gauge epidural catheter was inserted via the Tuohy needle beyond the 20 cm mark and the
Tuohy needle was withdrawn with care. I intended to leave the epidural catheter 6 cm into the
epidural space to minimise risk of catheter dislodgement. This implied that the epidural catheter
would need to be 17 cm at the skin. But, as mentioned earlier, there are no cm marking on epidural
catheter between 15 and 20 cm marks. However, Portex extra length Tuohy needles have markings
every cm starting from the tip of the needle. So, I used the Tuohy needle markings to measure 3
cm from 20 cm mark on the epidural catheter. Using the Tuohy as a guide, I pulled the epidural
catheter out from 20 cm to 17 cm at skin for fixation. The parturient had a good bilateral epidural
block for labour analgesia. The same epidural catheter was later used to provide successful regional
anaesthesia for an emergency caesarean delivery. I have described a simple and accurate method
of measuring catheter length if the epidural catheter needs to be fixed more than 15 cm at skin.
However, care must be taken not to shear the catheter with the tip of the epidural needle while
measurement.
From the Department of Anaesthesia, Princess Royal Maternity Hospital, Glasgow, UK.
*
DA, FRCA, Speciality Registar in Anaesthesia, Glasgow Royal Infirmary, Glasgow, UK
Correspondence to: Dr. Vishal Uppal, FRCA, Speciality Registar in Anaesthesia, Princess Royal Maternity Hospital,
Glasgow Royal Infirmary, Glasgow, UK. Tel: +44 01412114620, Fax: +44 01412111191. E-mail: drvishal76@rediffmail.
com
423
M.E.J. ANESTH 21 (3), 2011
424
V. Uppal
References
1.D'Angelo R, Berkebile BL, Gerancher JC: Prospective examination
of epidural catheter insertion. Anesthesiology; 1996, 84:88-93.
2.Hamilton CL, Riley ET, Cohen SE : Changes in the position of
epidural catheters associated with patient movement. Anesthesiology;
1997, 86:778-84.
3.Beilin Y, Bernstein HH, Zucker-Pinchoff B: The optimal distance
that a multiorifice epidural catheter should be threaded into the
epidural space. Anesth Analg; 1995, 81:301-4.
EXTREME INTRAOPERATIVE HYPERKALEMIA
IN A NON DIALYSIS PATIENT UNDERGOING
KIDNEY TRANSPLANTATION
Mia Kazanjian
and
Steven M. Neustein**
Abstract
The majority of patients who present for kidney transplantation have end stage renal disease
and are on dialysis. Those patients are known to be at risk for the development of hyperkalemia.
A patient who has not required dialysis, and with stable potassium levels would not be expected to
acutely develop intraoperative hyperkalemia. Presented here is an unusual case in which a 61-yearold man with chronic renal disease but no history of dialysis developed severe intraoperative
hyperkalemia during a renal transplant.
Case Report
A 61-year-old man with end stage renal disease secondary to polycystic kidney disease
presented for right sided living unrelated renal transplant. Past medical history was also significant
for hypertension and hyperlipidemia, and past surgical history revealed bilateral cataract repair.
The patient had no history of dialysis. Home medications included atenolol, enalopril, and
simvastatin. Physical examination revealed a well developed, well nourished man weighing
78 kg and measuring 176 cm; it was otherwise unremarkable. Preoperative EKG was normal.
Preoperative comprehensive metabolic panel revealed a BUN of 70 mg/dl, a creatinine of 5.3 mg/
dl, and a potassium of 5.1 mEq/L. Review of past potassium levels revealed a level of 5.4 mEq/L
5 days prior to surgery, and an earlier level of 5.5mEq/L. He had nothing per orem (NPO) after
midnight on the night prior to surgery.
In the operating room, standard American Society of Anesthesiologists monitors were applied
to the patient. Initial vital signs included heart rate of 52 beats/min with normal sinus rhythm
and blood pressure of 135/88 mmHg. Following induction of general anesthesia with 2 mg of
midazolam, 200 mg of propofol, 200 mcg of fentanyl, and 10 mg of vecuronium, an endotracheal
was placed and anesthesia was maintained with desflurane. An arterial line was placed following
the induction of anesthesia, and an arterial blood gas (ABG) shortly after the start of surgery
revealed pH 7.28, paCO2 39 mmHg, paO2 284 mmHg, bicarbonate 18 mEq/L, glucose 94 mg/dL,
and potassium 7.5 mEq/L. The electrocardiogram (ECG) revealed peak T waves. Repeat arterial
blood gas confirmed elevated potassium at 7.4 mEq/L. Fifty mEq of sodium bicarbonate was
given, followed by 25 g of dextrose, 1000 mg of CaCl2, and 10 units of regular insulin. When a
subsequent ABG showed potassium 6.9 mEq/L and 244 mg/dL of glucose, 1000 mg of CaCl2 and
5 units of regular insulin were given. The next ABG taken 30 minutes later showed potassium =
5.2 mEq/L and glucose = 87 mg/dL, after which 12.5 g of dextrose was infused. Subsequent ABGs
during the procedure revealed potassium levels <5 mEq/L and glucose levels in the 50s to 80s,
Corresponding Author: Steven M. Neustein, Associate Professor of Anesthesiology Mount Sinai Medical Center, 1 Gustave L.
Levy Place, Box 1010, Dept. of Anesthesiology, New York, NY 10029-6574 Tel: (212) 241-7467, Fax: 212-426-2009. E-mail:
[email protected]
425
M.E.J. ANESTH 21 (3), 2011
426
prompting a total of 37.5 g of dextrose to be given.
The peaked T waves resolved as the potassium level
became normalized. Two L of .9% NaCl, and 4 L of
45% NaCl, each with 75 mEq of bicarbonate, were
administered intravenously (IV). Urine output was
2800cc.
The kidney was transplanted successfully into
the right iliac fossa with minimal blood loss. Total
surgery time was 5 hours 9 minutes. Postoperative
potassium level was 3.8 mEq/L. For the remainder of
the hospital stay, it remained <5 mEq/L. The patient
made an uneventful recovery, the transplanted kidney
functioned well with consistently adequate urine
output, and he was discharged home on POD 3.
Discussion
This case is of particular interest in that the
patient had no history of dialysis and had a record of
past stable potassium levels in the range of low to mid
5 mEqs/L. Cases of intraoperative hyperkalemia may
be attributable to RBC transfusions, extensive muscle
dissection, metabolic acidosis, use of angiotensin
receptor blockers (ARBs) or angiotensin converting
enzyme (ACE) inhibitors, use of succinylcholine, and
propofol infusion syndrome (1-3). In our patient with
chronic renal disease, there is not a clear explanation
for the acute and dramatic rise in potassium during
this procedure. He did not receive any blood during
the procedure, there was limited muscle dissection,
and there was no propofol infusion. There was no
potassium in the intravenous fluid at any time. Possible
M. Kazanjian and S. M. Neustein
causes for his hyperkalemia include consequence of
intraoperative metabolic acidosis which was apparent
by the low bicarbonate level, administration of
enalapril prior to surgery, and coincidental worsening
of renal failure. It could have possibly been related to
the ingestion of foods containing potassium, and then
subsequent dehydration from the standard maintenance
of NPO status preoperatively.
Patients with a history of chronic renal failure,
especially those on ACEIs/ARBs, should be routinely
monitored for potassium and creatinine levels.
Raebel et al2 analyzed the characteristics of patients
on ACEIs/ARBs that were predictive of compliance
with routine potassium and creatinine monitoring.
They found that risk factors of older age, comorbid
chronic renal disease, heart failure, or diabetes, recent
hospitalization, higher number of outpatient visits,
and therapy with diuretics, potassium supplements, or
digoxin increased the likelihood of monitoring.
Intraoperative treatment relied on administration
of medications to actively lower potassium; this entailed
giving sodium bicarbonate, insulin, and calcium. In
addition, switch of fluids to 45% NaCl with sodium
bicarbonate after diagnosis of hyperkalemia sought to
prevent further rise in potassium by providing alkaline
IV fluid instead acidic fluid. With continual insulin
boluses, glucose levels were monitored to avoid
hypoglycemia. In all kidney transplantation cases,
the electrolyte levels should be assessed on the day of
surgery. An arterial line should be placed and levels
sampled intraoperatively in order to assess for acute
changes and monitor treatments.
References
1. Mali AR, Patil VP, Pramesh CS, Mistry RC: “Hyperkalemia during
surgery: is it an early warning of propofol infusion syndrome?”
Journal of Anesthesia; 2009, 23:421-423.
2. Raebel MA, McClure DL, Simon SR, Chan KA, Feldstein A,
Andrade SE, Lafata JE, Roblin D, Davis RL, Gunter MJ, Platt R:
“Laboratory monitoring of potassium and creatinine in ambulatory
patients receiving angiotensin converting enzyme inhibitors and
angiotensin receptor blockers”. pharmacoepidemiology and drug
safety; 2007, 16:55-64.
3. Suzuki S, Kashiwagi G, Nakasone Y, Tomioka A, Saito S: “Case
of unexpected intraoperative hyperkalemia”. Masui; 2009, Aug,
58(8):1014-6.
SUCCESSFUL TREATMENT OF EARLY
ROPIVACAINE TOXICITY WITH INTRALIPID
IN A PATIENT WITH ATTENTION
DEFICIT HYPERACTIVITY DISORDER
Achir A. Al-Alami*
Case Report
A 16 year old male underwent right shoulder arthroscopy and Bankart procedure. The patient
weighed 58 Kg and had a BMI of 19.6. He had a history of attention deficit hyperactive disorder
(ADHD) treated with atomoxetine, a newer drug that works by selectively inhibiting the re-uptake
of norepinephrine (1). We planned for a general endotracheal anesthetic with interscalene block
for postoperative analgesia. Monitors were applied in the preoperative block room including:
ECG, non-invasive blood pressure, and pulse oximeter. Nasal oxygen was administered at 2 L/
min. Sedation was provided with 2 mg of midazolam IV. The patient was positioned in right lateral
decubitus. After sterile preparation of the skin with chlorhexidine, a high frequency US probe 1215 Hz (HD 11 XE, Phillips, Bothell, WA, USA) was used to localize the brachial plexus roots. A
nerve stimulator was set at 0.4 mA with a frequency of 2 Hz and 0.3 ms. Skin and subcutaneous
tissue anesthesia was obtained with injection of 3 ml of 1% lidocaine. Using a posterior approach,
the interscalene block was performed in plane, using a 90 mm 21 guage nerve stimulator needle
(Arrow, StimuQuik, Reading, PA, USA). The C6 root stimulation was confirmed with a biceps
twitch, and 20 ml of 0.75% ropivacaine was injected after negative aspiration and negative test
dose (D5W with 1:200,000 epinephrine, 3 ml). The C5 root stimulation was confirmed with a brisk
deltoid twitch, and 20 ml of 0.75% ropivacaine was injected after negative aspiration and negative
test dose. A total of 40 ml of 0.75% ropivacaine was given.
Ten minutes after the block, the patient became slightly confused, reported visual
hallucinations (purple spots), and was noted to have slower and slightly slurred speech. He also
had an intention tremor in his left arm when asked to move it, but no obvious tremor at rest. Cranial
nerves 2-12 were grossly intact, but he did have some non-coordinated tremor in his tongue on
protrusion. His respiratory rate increased to 25. His heart rate steadily increased from 75 to 156
bpm over 5-7 minutes. He remained in sinus rhythm. His blood pressure increased from 112/62
to 140/80. Suspecting ropivacaine toxicity, we infused 1.5 mg/kg Intralipid 20% (Fresenius Kabi,
Uppsala, Sweden) as a bolus over 4-5 minutes. His heart rate and breathing declined rapidly. We
then administered 0.5 mg midazolam IV. Intralipid infusion was continued at 0.25 mg/kg/min over
3 hours. After 20-30 minutes of observation, his motor twitching ceased, his speech became more
coherent, and his hallucinations were gone. He had a full motor and sensory block of the operative
arm. He was taken to the operating room and underwent an uneventful general anesthetic with
endotracheal intubation. He was maintained on propofol (150-200 mcg/kg/min) and sevoflurane
1.2% in air: oxygen mixture of 1:1.
*
Correspondence: Achir A Al-Alami, Regional Anesthesia Fellow, University of Iowa Hospital and Clinics, 200 Hawkins
Dr, Iowa City, IA, 52242, USA. E-mail: [email protected]
427
M.E.J. ANESTH 21 (3), 2011
428
The postoperative course was uneventful; he
reported minimal pain in his elbow. He had some
recollections of the events, including remembering the
purple spots he had seen. A month after the surgery the
patient was called and he reported that he was doing
well.
Discussion
Ropivacaine has been shown to be a safe longacting local anesthetic. In both animal studies and case
reports, investigators have shown that ropivacaine
cardiac toxicity is more responsive to standard ACLS
recommended resuscitation procedures in comparison
with other local anesthetics2,3. The estimated incidence
of ropivacaine-induced toxic events is 6-8 in 1000,000
patients4. The manufacturer’s maximum recommended
dose of ropivacaine (300 mg) for brachial plexus
blockade is not evidence based5,6. Total dose is an
important consideration, but we must weigh it against
other factors such as the pharmacokinetics of the drug,
block site, patient characteristics and drug interactions.
Used collectively, these considerations provide the
greatest margin of safety against local anesthetic
toxicity6,7.
In our case, direct intravascular injection
is unlikely as the block was performed under
visualization with ultrasound, there was no blood
visualized after aspiration, the HR did not change with
test dose, and signs and symptoms of local anesthetic
toxicity occurred10 minutes after completion of the
block. We believe that the observed symptoms were
the result of ongoing systemic absorption of the drug.
The administered dose of ropivacaine was 5.3 mg/
kg which can be considered in the toxic range for a
brachial plexus block (4-8 mg/kg)7-12. Other factors
may have played a role in the development of toxicity
Achir A. Al-Alami
in our patient. These include the high vascularity
associated with the interscalene approach, the lean
body mass of the patient and potentially his ADHD
diagnosis. There is a bidirectional relationship
between ADHD and epilepsy. In one study children
diagnosed with ADHD have been shown to have
greater incidence of EEG abnormalities in comparison
to general population (6.1% vs 3.5%). In another study
of children with ADHD, 30.1% of them were found
to have pathological EEG findings13,14. If we consider
that his ADHD was a contributing factor to the
development of CNS symptoms, the cardiovascular
and respiratory symptoms we observed may have
been due to sympathetic stimulation from global CNS
excitation15. It is also likely that these symptoms can
be explained as direct cardiac toxicity resulting from
the excessive local anesthetic in the blood.
There have been two reported cases of early
CNS symptoms induced by local anesthetic toxicity
successfully treated by lipid infusion16,17. Our case
highlights the concept that early administration of
Intralipid for treatment of local anesthetic-induced
early CNS toxicity prior to development of seizure
and cardiac arrest is a safe and viable option for
anesthesiologists. Our case also highlights the diversity
of symptoms that may be present in patients with local
anesthetic toxicity. These symptoms may be different
or masked in populations with ongoing mental disease
or in those taking pharmaceuticals for those diseases.
The patient’s BMI, associated co-morbidities
and type of block are important in determining local
anesthetic dosage. Furthermore, we found Intralipid
infusion was safe and successful in reversing
local anesthetic-induced early CNS and cardiac
abnormalities when administered early prior to the
development of seizure and cardiac arrest.
SUCCESSFUL TREATMENT OF EARLY ROPIVACAINE TOXICITY WITH INTRALIPID IN A PATIENT WITH
ATTENTION DEFICIT HYPERACTIVITY DISORDER
429
References
1. Chang K, Nayar D, Howe M, Rana M: Atomoxetine as an adjunct
therapy in the treatment of co-morbid attention-deficit/hyperactivity
disorder in children and adolescents with bipolar I or II disorder. J
Child Adolesc Psychopharmacol; 2009, 19 (5):547-51.
2. Finucane BT: Ropivacaine cardiac toxicity-not as troublesome as
bupivacaine. Can J Anesth; 2005, 52(5):449-53.
3. Ohmura S, Kawada M, Ohta T et al: systemic toxicity and
resuscitation in bupivacaine, levobupivacaine, or ropivacaineinfused rats. Anesth Analg; 2001, 93:743-48.
4. Periodic safety update report: Naropin, Astra Zeneca; 2000, May,
17.
5. Hickey R, Blanchard J, Hoffman J, Sjovall J, Ramamurthy
S: Plasma concentrations of ropivacaine given with or without
epinephrine for brachial plexus block. Can J Anaesth; 1990, 37:87882.
6. Rosenberg H, Veering B, Urmey WF: Maximum recommended
doses of local anaesthtics: A multifactorial concept. Region Anesth
Pain Med; 2004, 29(6):546-75.
7. Spofford C, Menhusen MJ: Possible Bupropion interaction with
ropivacaine: setting the stage for seizure? Region Anesth Pain Med;
2008, 33(2):193.
8. Eldejam JJ, Gros T, Viel E, Mazoit JX, Bassoul B: Ropivacaine
overdose and systemic toxicity. Anaesth Intensive care; 2000,
28:705-7.
9. Satsumae T, Tanaka M, Saito S, Inomata S: Convulsions after
ropivacaine 300 mg for brachial plexus block. Br J Anaesth; 2008,
101(6):860-2.
10.Litz RJ, Popp M, Stehr SN, Koch T: Successful resuscitation of a
ptient with ropivacaine-induced asystole after axillary plexus block
using lipid infusion. Anaesthesia; 2006, 61:800-01.
11.Mardirosoff C, Dumont I: Conculsions after the administration
of high dose ropivacaine following an interscalene block. Can J
Anaesth; 2000, 47:1263.
12.Ala-Kokko TI, Löppönen A, Alahuhta S: Two instances of central
nervous system toxicity in the same patient following repeated
ropivacaine-induced brachial plexus block. Acta Anaesth Scand;
2000, 44:623-26.
13.Wernicke JF, Chilcott Holdridge KC, Jin L, Edison T, Zhang S,
Bangs ME, Allen AJ, Ball S, Dunn D: Seizure risk in patients with
attention-deficit-hyeractivity disorder treated with atomoxetine. Dev
med child neurol; 2007, 49:498-502.
14.Hamoda HM, Guild DJ, Gumlak S, Travers BH, GonzalezHeydrich J: Association between attention-deficit/hyperactivity
disorder and epilepsy in pediatric populations. Expert rev neurother;
2009, 9(12):1747-54.
15.Sevcencu C, Struijk JJ: Autonomic alterations and cardiac changes
in epilepsy. Epilepsia; 2010, Jan, 7.
16.Spence AG: Lipid reversal of central nervous system symptoms of
Bupivacaine toxicity. Anesthesiology; 2007, 107:516-7.
17.Esponet AJ, Emmerston MT: The successful use of Intralipid for
treatment of local anesthetic-induced central nervous system
toxicity. Clin J Pain; 2009, 25(9):808-809.
M.E.J. ANESTH 21 (3), 2011
CHRONIC USE OF OXYBUTYNIN AND SPINAL
ANESTHESIA: A CASE OF POSTOPERATIVE URINARY
RETENTION AND HEMATURIA
Adriano BS Hobaika*
Overactive bladder is a disorder characterized by micturition urgency with or without incontinence and with an increased urinary frequency and nocturia. Oxybutynin is the most common
medication used in the treatment owing to having more tolerable side effects1. This drug has not
been described as a risk factor to develop postoperative urinary retention.
Male, 61 years old, 84 kg and using simvastatin in order to control hypercholesterolemia and
oxybutynin to control overactive bladder. Preoperative examinations were normal. He was scheduled to varicectomy of the lower limbs on outpatient basis. Spinal anesthesia (L3/L4 interspace)
with bupivacaine, 12.5 mg plus intrathecal fentanyl, 15 mcg was administered in addition to an
intravenous sedation with midazolam and sufentanyl. Intravenous saline (2000 ml) and ephedrine
(15 mg) was administered in order to treat hypotension during a two-hour procedure. Seven hours
after the end of the procedure, the patient complained of a strong pelvic pain, dysuria, hematuria
and clot elimination. He also presented a very painful urinary retention on palpation. There was
an immediate symptom relief when bladder catheter was used and blood clots were seen in urine.
The catheter was withdrawn and the patient was discharged on the following day, urinating with no
problems but with a slight hematuria.
Oxybutynin acts as an anticholinergic agent with an antimuscarinic action and, particularly,
an antispasmodic action in the vesical smooth muscle. As a consequence, there is an increased vesical capacity, reduced micturition frequency and inhibition of the initial micturition stimulus. In an
experimental model, urinary frequency was reduced in a situation of induced-hemorrhagic cystitis
and there was a remarkable decrease in the detrusor muscle contraction strength when compared
to the normal control2.
Intrathecal opioid administration causes urinary retention via µ- and/or δ-receptors3. In an
animal model, cholinomimetic agents and α-adrenergic agonists aggravate the increase of morphine-induced intravesical pressure4.
This patient, possibly, presented urinary retention arising out of the additive association of
two pathophysiological mechanisms. Bladder distension may have caused an increase of the intravesical pressure which led to the rupture of vessels from the bladder or prostate with hematuria.
In a recent review, Baldini et al recommends that surgical outpatients with low risk for post-operative urinary retention can be sent home without voiding5. According to these authors, the
patient of this case is classified as a high risk patient.
In surgical outpatients using oxybutynin, it should be considered the non-administration of
opioids in the neuroaxis. Moreover, it seems prudent to wait them for voiding before home discharge.
*
Master of Science in Medicine, Co-responsible for the Anesthesiology Teaching and Training Center Santa Casa de
Belo Horizonte, Staff anesthesiologist of Mater Dei Hospital.
Adress: Rua Des. Jorge Fontana, 336/1701, Belvedere. Phone: 31-55-92134969. [email protected]
431
M.E.J. ANESTH 21 (3), 2011
432
A. BS Hobaika
References
1. Abrams P, Andersson KE: Muscarinic receptor antagonists for
overactive bladder. BJU Int; 2007, 100:987-1006.
2. Mizuma EK, Takeshita MS, Suaid HJ, Martins ACP, Tucci JR S,
Cologna AJ, Gonçalves MA: Efeito do cloridrato de oxibutinina na hiperatividade vesical conseqüente a cistite hemorrágica.
Acta Cir Bras; 2003, 18 suppl, 24-27.
3. Dray A: Epidural opiates and urinary retention: New models
provide new insights. Anesthesiology; 1988, 68:323-324.
4. Durant PAC, Yaksh TL: Drug effects on urinary bladder tone
during spinal morphine-induced inhibition of the micturition reflex in unanesthetized rats. Anesthesiology; 1988, 68:325-334.
5. Baldini G, Bagry H, Aprikian A, Carli F: Postoperative Urinary
Retention: Anesthetic and Perioperative Considerations. Anesthesiology; 2009, 110:1139-1157.
INFILTRATIVE ANGIOLIPOMA
OF THE NECK
Abdul-Latif Hamdan*, Laurice Mahfoud**, Hani Rifai**,
Charbel Rameh**, Nabil Fuleihan*
Introduction
Lipomas are the most common mesenchymal tumors of the body. They can occur in any
soft tissue ranging from subcutaneous fat to the parosteal areas adjacent to bone. They are usually
asymptomatic masses easily diagnosed on radiological imaging1. Angiolipoma is a variant of lipoma
with proliferation of its vascular component. These tumors occur on the trunk and extremities of
young adults with the forearm being the most common site of involvement. Documented sites
of occurrence in the head and neck region include cheek, palate, neck, jaw, nose, eyelid, parotid,
tongue, paranasal sinuses and parapharynx. Only 4 cases have been described in the neck, with
75% of these being infiltrative2. We would like to present the fifth case of infiltrative angiolipoma
of the neck.
Case presentation
A 23y old male patient, previously healthy, presented with a four month history of a slowly
growing, painless neck mass that was not associated with skin changes, fever, recent infection or
trauma. No history of contact with patients with tuberculosis. Physical examination revealed a well
circumscribed soft left postero-lateral neck mass, 5 × 5 cm, non tender and non pulsatile. Patient had
normal muscle power in his upper extremities and normal pulses. A fine needle aspiration revealed
an acellular specimen. Magnetic resonance imaging of the head and neck showed a heterogeneous
5 × 4 × 4 cm, well-circumscribed mass with a prominent vascular component, underneath the
trapezius and longus colli muscles. The mass enhanced on T1 and T2 weighted images. The
patient underwent resection of the posterior neck mass through a cervical approach incision. Intraoperatively the mass was found to be infiltrating the adjacent muscles. Histopathologic examination
revealed proliferation of small mostly capillary sized vessels and adipose tissue between muscle
fibers In a pseudo-infiltrative type (Fig. 1). The diagnosis was consistent with angiolipoma of the
neck the infiltrative type.
Discussion
Lipomas occur in regions such as back and shoulders, with the head and neck region being
rarely the site of origin. Histologically, they are classified into five categories; 1) lipoma; 2)
hybernoma; 3) heterotopic lipoma; 4) lipomatoses syndrome; and 5) histologic variants of lipoma
* MD, FACS, Clinical Associate Professor, Otolaryngology Department, American University of Beirut Medical CenterLebanon.
** MD, Resident, Otolaryngology Department, American University of Beirut Medical Center-Lebanon.
Corresponding Author: Abdul-latif Hamdan, MD, FACS, Clinical Associate Professor, Otolaryngology Department,
American University of Beirut Medical Center-Lebanon, Tel/Fax: 961-1746660, P.O. Box: 110236 Beirut-Lebanon. E-mail:
[email protected], [email protected]
433
M.E.J. ANESTH 21 (3), 2011
434
Abdul-Latif Hamdan
Fig. 1
H&E staining (X100 magnification) shows proliferation of small mostly capillary sized vessels and adipose tissue between muscle
fibers in a pseudo-infiltrative type. The vessels have plump nuclei with well formed lumina. Mitotic figures are not seen. There is no
atypia. Findings are constant with angiolipoma
such as angiolipoma. Angiolipomas constitute 6%17% of all lipomas with only 20 cases being reported
in the literature. They are suspected whenever the
lesion becomes painful or tender and at times leading
to muscular pain and or neural deficits. This is more
common when the tumor is infiltrative and lacks an
identifiable capsule, as in our case3,4. Histopathologic
characteristics of angiolipomas include 1) gross
evidence of tumor formation; 2) microscopic evidence
of more than 50% of mature lipocytes in the tumor and
3) microscopic evidence of angiomatous proliferation.
These were the findings in our case. Because of their
extensive vascular component and their tendency
to locally recur, they have often been classified
under benign vascular lesions such as intramuscular
hemangiomas. The differential diagnosis includes
hemangioma, lymphangioma, kaposi’s sarcoma and
angiosarcoma. Liposarcomas can be differentiated by the
presence of embryonal adipose tissue, pleomorphism,
increased number of mitosis and metastasis1,2. The
non fatty vascular component of angiolipomas makes
these tumors radiologically distinct with Magnetic
resonance imaging (MRI) being the most sensitive
imaging technique. These tumors tend to show high
signal intensity on T1-weighted sequences and T2weighted fast spin echo-MRI sequences. Analyzing the
nonfatty regions of these atypical lipomas invariably
provides the clue for distinguishing them from well
differentiated liposarcomas. These later tend to have
thick nodular septa that enhance variably on contrast
enhancement images. These findings were not present
in our case. MRI is also used for the assessment of the
neighboring structures and the extent of infiltration3-5.
Treatment consists of complete surgical excision. In
the infiltrative type, wider resection that includes the
adjacent involved soft tissues is recommended in view
of the high incidence of local recurrence. Adjuvant
radiation therapy may be recommended in cases of
incomplete resection.
References
1.Alvi A, Garner C, Thomas W: Angiolipoma of the head and neck. J
Otolaryngol; 1998, 27:100-3.
2.Ozer E, Shuller D: Angiolipoma of the neck. Otolaryngol Head
Neck Surg; 2006, 135:643-644.
3.Enzinger FM, Weiss SW: Benign lipomatous tumors. In: Enzinger
FM, Weiss SW. eds. Soft tissue tumors. 3rd Edition. St. Louis: Mosby;
1995, 381-430.
4.Munk PL, Lee MJ, Janzen DL, et al: Lipoma and liposarcoma:
evaluation using CT and MR imaging. AJR Am J Roentgenol; 1997,
169:589-94.
5.Kim JY, Park JM, Lim GY, et al: Atypical benign lipomatous tumors
in the soft tissue: Radiographic and pathologic correlation. J Comp
Assisted Tomography; 2002, 26(6):1063-1068.
CARDIAC ARREST DURING ELECTIVE
ORTHOPEDIC SURGERY DUE TO
MODERATE HYPOKALEMIA
Manuel F. Struck*, Andreas Nowak*
Abstract
We report the case of a perioperative cardiac arrest (ventricular fibrillation) of a patient
undergoing elective orthopedic surgery due to moderate hypokalemia (serum potassium 2,8 mmol/l),
whereas preoperative levels were normal. He was successfully resuscitated without neurological
deficits and underwent postoperative intensive care monitoring. In times of increasing populations
of elderly people presenting with considerable co-morbidity, clinicians should be aware of possible
rapid changes of electrolyte levels resulting in perioperative cardiac arrhythmia.
Introduction
Perioperative cardiac arrhythmias are common complications, which, in most cases, do not
affect hemodynamic stability and not always require antiarrhythmic therapy. Life-threatening
arrhythmias with a sudden and unexpected onset during non-cardiac surgery are rare1. Electrolyte
imbalances such as a low serum potassium level may be one possible underlying cause2. This
condition is commonly defined as moderate (3-2.5 mmol/l) or severe hypokalemia (<2.5 mmol/l).
Reasons for a hypokalemia in the perioperative setting may be previous medication, hypoglycemia
(transcellular shift of potassium from serum into cells), and renal or gastrointestinal losses.
Case Report
We report the case of a 71-year-old man with a medical history of arterial hypertension,
arterial obstructive disease, both without medication, borderline diabetes mellitus, treated with
dietary measures, hypercholesterolemia, treated with simvastatin, alcohol and nicotine use, and no
allergies. He was scheduled for amputation of his left lower thigh due to necrotic erysipelas and
osteomyelitis for which he had been treated with clindamycin and levofloxacin. Further medication
included palladon for pain therapy. Preoperative examination showed a 72 kg, 178 cm man. Noninvasive blood pressure was 143/85 mmHg, heart rate was 78/min and ECG revealed no cardiac
pathology. Preoperative laboratory values included hemoglobin (Hb) of 5.8 mmol/l and serum
potassium of 3.9 mmol/l.
The patient underwent anesthetic induction and endotracheal intubation with intravenous
sufentanil (40 µg), propofol (100 mg) and rocuronium (50 mg) after implementation of standard
monitoring. He was started on intravenous ketamine via infusion pump (5 mg/h) and received a
bolus application of 25 mg for postoperative pain therapy. Anesthesia was maintained with 40%
*
MD, Department of Anesthesiology, Friedrichstadt Hospital, Dresden, Germany.
Correspondence: Manuel Florian Struck, Department of Anesthesiology, Friedrichstadt Hospital, Dresden, Germany,
Friedrichstr. 41, 01067 Dresden, Germany. Phone: 0049(0)3514801170, Fax: 0049(0)3514801179. E-mail: manuelstruck@
web.de
435
M.E.J. ANESTH 21 (3), 2011
436
oxygen, 60% air, and sevoflurane (0.7-1.3% endtidal concentration). Surgery then commenced and
was uneventful. An arterial blood sample to assess
the blood loss revealed anemia (Hb 5.0 mmol/l)
and moderate hypokalemia (serum potassium 2.9
mmol/l).
About one minute later, the ECG monitor alarmed
and displayed an artefact-like pattern that frequently
occurs when surgeons use electrocoagulation devices,
whereas this was not the case. The immediate check
of the ECG electrodes revealed no mislocation,
and the palpation of both carotid arteries revealed
pulselessness. Surgery was abandoned, and chest
compressions were performed immediately. The
first defibrillation had no effect, whereas the second
resulted in asystole. After total administration of
2 mg adrenaline (aliquots of 1 mg each), return of
spontaneous circulation (ROSC) was evident by
palpable pulses of both carotid arteries and the ECG
showed a heart rate of 87/min. The first available BP
was 160/90 mmHg. The time from onset of ventricular
fibrillation to ROSC was 9 minutes. Surgery was than
completed, and the patient was transferred to the
intensive care unit, where he received correction of
hypokalemia and anemia.
He was successfully weaned off the ventilator
and.extubated 4 hours after ROSC. Subsequent
neurological examination revealed no deficits.
Laboratory measures, ECG, echocardiography and
chest radiography did not show evidence of cardiac
ischemia, valvular pathology or pulmonary embolism.
After three further days of monitoring, the patient was
discharged to the regular ward.
M. F. Struck & A. Nowak
Discussion
In this patient, there was no high-risk medication
for a hypokalemia such as diuretics or insulin, whereas
his antibiotic medication have rarely been reported to
cause electrolyte imbalances2.
Other possible causes for a perioperative cardiac
arrest may be iatrogenic by anesthetic agents or
insufficient pain therapy.
However, the analysis of five prospective cohort
studies, covering 6253 non-cardiac surgery patients,
revealed postoperative cardiac arrhythmia in 7.84%3.
The occurrence of atrial fibrillation was by far the most
frequent type of arrhythmia (4.41%), whereas VF was
a very rare complication (0.02%).
In another large review, the overall frequency of
perioperative cardiac arrest was 4,3 per 10.0004. Most
arrests were not due to anesthesia-related causes, and
most patients experiencing anesthesia-related arrest
survived to hospital discharge.
Conclusion
We conclude that ventricular fibrillation and
cardiac arrest may suddenly occur perioperatively
probably due to unrecognized moderate electrolyte
imbalances even patients presenting with a lower
risk profile. In a future demography of increasing age
and morbidity it may hardly be possible to identify
this kind of risk factor in any patients scheduled for
surgery. Therefore, clinicians may be confronted
more frequently with similar complications requiring
appropriate attention and immediate response measures
for successful management.
References
1.Thompson A, Balser JR: Perioperative cardiac arrhythmias. Br J
Anaesth; 2004, 93:86-94.
2.Alfonzo AV, Isles C, Geddes C, Deighan C: Potassium disordersclinical spectrum and emergency management. Resuscitation; 2006,
70:10-25.
3.Walsh SR, Tang T, Wijewardena C, Yarham SI, Boyle JR, Gaunt
ME: Postoperative arrythmias in general surgical patients. Ann R
Coll Surg Engl; 2007, 89:91-95.
4.Sprung J, Warner ME, Contreras MG, Schroeder DR, Beighley
CM, Wilson GA, Warner DO: Predictors of survival following
cardiac arrest in patients undergoing noncardiac surgery: a study of
518,294 patients at a tertiary referral center. Anesthesiology; 2003,
99:259-269.
THE ANESTHETIC MANAGEMENT OF A PATIENT
WITH DORFMAN-CHANARIN SYNDROME
Azize Beştaş*,
Esef Bolat**, Mustafa K. Bayar***,
Ömer L. Erhan***
Abstract
Dorfman-Chanarin syndrome (DCS), which is also known as neutral lipid storage disease, is
a rare autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma.
Since the Dorfman-Chanarin syndrome is a multisystemic disease the choice of drugs and the
conduct of anesthesia in these patients are important. Preoperative evaluation should be performed
in detail and anesthetic method and drugs to be used should be chosen carefully in accordance with
affected system, overall state of patient and characteristics of the operation, in order to decrease
perioperative morbidity rates in these patients. We report the anesthetic management of a child
with DCS operated for correction of strabismus under general anesthesia.
Keywords: Dorfman-Chanarin syndrome, anesthesia.
Introduction
Dorfman-Chanarin syndrome (DCS), which is also known as neutral lipid storage disease, is
a rare autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma1.
Peripheral blood smears showing lipid vacuoles in neutrophils (Jordans’ anomaly) in patients with
ichthyosis leads to the diagnosis2. Other organ systems, such as liver, muscle, central nervous
system, ears and eyes are frequently involved1,3. Therefore, patients with DCS may present
anesthetic challenges to the anesthesiologist. To our best knowledge, there is no information
available on the anesthetic management of a patient with DCS. Here, we report the anesthetic
management of a child with DCS operated for correction of strabismus under general anesthesia.
Case Report
A 5-year-old, 18 Kg, 108 cm (at 25th-50th percentiles) girl with DCS was scheduled for elective
strabismus surgery. Review of the previous medical records revealed that the patient had presented
with ichthyosis since birth. At age 16 months, she had demonstrated hepatomegaly, hepatosteatosis,
elevated liver enzymes, renal parenchymal hypertrophy and motor-mental retardation. After
observing the peripheral blood smears showing lipid vacuoles in neutrophils (Jordans’ anomaly)
she had been diagnosed with DCS. The patient’s preoperative physical examination revealed
*
**
***
Associate Professor, Firat University School of Medicine Department of Anesthesiology and Reanimation, 23119-ELAZIG,
TURKEY.
Assistant Professor, Bozok University School of Medicine Department of Anesthesiology and Reanimation, YOZGAT,
TURKEY
Professor, Firat University School of Medicine Department of Anesthesiology and Reanimation, 23119-ELAZIG,
TURKEY.
Corresponding Author: Dr. Azize BESTAS, Fırat Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimation AD, 23119
Elazıg-TURKEY, Tel: +90 532 3402332, Fax: +90 424 2388096. E-mail: [email protected]; [email protected]
437
M.E.J. ANESTH 21 (3), 2011
438
generalized squamatous skin lesions and horizontal
strabismus in the right eye. The liver was palpable
to 2 cm below the costal margin, smooth and firm,
but the spleen was not palpable. She also had slight
motor-mental retardation. Other systemic examination
was normal. Results of laboratory studies showed a
normal blood count, lipid profile, serum electrolytes,
urea, creatinine, total protein, albumin, globulin, total
bilirubin, direct bilirubin, indirect bilirubin, glucose,
prothrombin time, activated partial thromboplastin
time, INR and urinanalysis. The liver functions
were deranged with elevated enzymes [serum
aspartate aminotransferase (AST): 122 U/L, alanine
aminotransferase (ALT): 145 U/L, alkaline phosphate
(ALP): 312 U/L, gammaglutamyl transferase (GGT):
36 U/L]. The muscle enzyme, serum creatine
phosphokinase (CPK) has also been increased (CPK:
722 U/L). However, there were no myopathy evidence
clinically and she was electromyographically normal.
Ultrasound of the abdomen showed hepatomegaly with
grade II hepatosteatosis, splenomegaly and bilateral
grade I renal parenchymal hypertrophy. A chest x-ray
showed a normal heart size, and clear lung fields. Liver
biopsy showed 80% fatty changes, minimal portal
fibrosis with mixed type inflammatory infiltrates. Skin
biopsy revealed marked hyperkeratosis and sporadic
acanthosis. The peripheral blood smear showed lipid
vacuoles in the cytoplasm of leucocytes consistent
with Jordans’ anomaly, characteristic of DCS. Lipid
vacuoles were also found in cells of the myeloid
series in bone marrow smear. The patient received no
preoperative medication.
In the operating room, electrocardiography, heart
rate, non-invasive arterial blood pressure, temperature,
pulse oximetry and end-tidal (ET) CO2 were monitored.
In addition, neuromuscular function was monitored by
using a peripheral nerve stimulator (TOF Watch SX
Monitor, Organon, Oss. Holland). Heating blanket was
used and room temperature was kept at normal limits,
in case of a possibility of hypothermia development.
Anesthesia was induced with sevoflurane in 50%
nitrous oxide (N2O) and oxygen (O2). After induction
of anesthesia, intravenous access was established
and TOF Watch SX Monitor was calibrated. Then,
endotracheal intubation was performed easily without
using muscle relaxants, at the first attempt. Following
tracheal intubation, anesthesia was maintained with
A. Beştaş et al.
isoflurane 1.0-1.5% in a combination of 50% N2O
and O2. Ventilation was controlled mechanically and
was adjusted to maintain an ET CO2 at 30-40 mmHg.
Muscle relaxants were not used, since the patient
had not moved during surgical operation, which was
completed in 50 minutes, and the operation had been
performed easily. After stopping the administration
of anesthetic agents the patient waked up rapidly,
began to breathe spontaneously; she could raise her
head and grasp forcefully. Her trachea was extubated
uneventfully.
In recovery room, patient was evaluated
with “Modified Aldrete Scoring System”. When
her Modified Aldrete Score reached to 10 she
was transported from recovery room to the ward.
Patient’s hemodynamic variables, SpO2 and body
temperature were within normal limits both during
the operation and in recovery room. There were no
differences in laboratory values on the second day
postoperatively compared with preoperatively. The
patient was discharged successfully on the third day
postoperatively.
Discussion
Since the Dorfman-Chanarin syndrome is a
multisystemic disease the choice of drugs and the
conduct of anesthesia in these patients are important.
Extracutaneous manifestations variably include fatty
liver, myopathy, cataracts, hearing impairment, mental
retardation and a variety of neurologic symptoms1,3,4.
In this presented case, the perioperative anesthetic care
has been performed by considering the ichthyosis,
hepatosteatosis, hepatic disfunction and raised serum
CPK, present in the patient.
There is a tendency to increased skin fragility
in the ichthyotic patients, therefore adhesive pads
or electrodes can cause trauma during application
or removal. However, the fixation of endotracheal
tube and ECG monitor electrodes to the skin was
well tolerated by the patient. It is very important to
maintain normothermia during surgery, because
patients with ichthyosis have risk of developing
inadvertent hypothermia during anesthesia5. Using of
heating blanket and at normal room temperature, the
intraoperative body temperature of the patient could be
maintained at a normal level during operation.
THE ANESTHETIC MANAGEMENT OF A PATIENT WITH DORFMAN-CHANARIN SYNDROME
Patients with liver disease are at risk for
perioperative morbidity and mortality. General
anesthesia can reduce total hepatic blood flow and
hence can increase the present parenchymal damage6.
Therefore drugs decreasing the hepatic blood flow,
hypotension and hypercapnia should be avoided.
Isoflurane and desflurane may be the most appropriate
for use in patients with liver disease, as they seem to
decrease liver blood flow less than the other volatiles,
and have a low degree of metabolism7. In the present
case, we preferred isoflurane in maintenance of
anesthesia, stabilized the hemodynamic variably and
adjusted the ventilation to maintain normocapnia.
Besides, since hepatic dysfunction affects the
distribution, metabolism and excretion of anesthetic
drugs8, drug doses and dosing schedules should be set
accordingly. The coagulopathy, associated with liver
disease, may cause bleeding of friable nasopharyngeal
structures, such as application of an endotracheal tube.
Abnormally high levels of serum CPK can be
reflect an occult myopathy9. Patients with myopathy
are very sensitive to paralyzing agents. If a muscle
relaxant had been required in these patients, a shortacting non-depolarizing muscle relaxant should be
administered carefully, using small incremental doses
and under close monitoring of neuromuscular function,
since some reports have described prolonged effect
439
of neuromuscular blocking agents in patients with
myopathy10,11. Furthermore, use of succinylcholine
should also be avoided because of risk of severe
hyperkalemia development or malign hyperthermia12.
Although she is clinically and electromyographically
normal, we monitored the neuromuscular function,
since serum CPK level was high in our case. We did
not use muscle relaxants for endotracheal intubation,
since sevoflurane could provide sufficient muscle
relaxation. Moreover, we did not use neuromuscular
blocking agents during surgery, because the surgical
operation did not require further muscle relaxation and
the patient was sufficiently anesthetized with volatil
anesthetic agent. Although strabismus correction
in children is associated with a high incidence of
postoperative nausea and vomiting (PONV) without
prophylactic antiemetic medication13 PONV was not
occurred in our patient.
Anesthesia for these patients should be carried
out carefully, because DCS is a multisystemic lipid
storage disease. Preoperative evaluation should be
performed in detail and anesthetic method and drugs
to be used should be chosen carefully in accordance
with affected system, overall state of patient and
characteristics of the operation, in order to decrease
perioperative morbidity rates in these patients.
M.E.J. ANESTH 21 (3), 2011
440
A. Beştaş et al.
References
1. CIesek S, Hadem J, Manns MP, FIscher J, Strassburg CP: A
rare cause of nonalcoholic fatty liver disease. Annals of Internal
Medicine; 2006, 145:154-155.
2. Rozenszajn L, Klajman A, Yaffe D, EfratI P: Jordans’ anomaly in
white blood cells. Report of case Blood; 1966, 28:258-265.
3. Akiyama M, Sawamura D, Nomura Y, Sugawara M, Shimizu H:
Truncation of CGI-58 protein causes malformation of lamellar
granules resulting in ichthyosis in Dorfman-Chanarin Syndrome.
The Journal of Investigative Dermatology; 2003, 121:1029-1034.
4. Chanarın I, Patel A, Slavın G, Wılls EJ, Andrews TM, Stewart G:
Neutral-lipid storage disease: A new disorder of lipid metabolism.
British Medical Journal; 1975, 1:553-555.
5. Kubota R, Miyake N, Nakayama H, ArIta H, Hanaoka K: Anesthetic
management of a patient with non-bullous congenital ichthyosiform
erythroderma. Masui; 2003, 52:1332-1334.
6. Keegan MT, Plevak DJ: Preoperative assessment of the patient
with liver disease. American Journal of Gastroenterology; 2005,
100:2116-2127.
7. Green DW, Ashley EMC: The choice of inhalation anaesthesia for
major abdominal surgery in children with liver disease. Paediatric
Anaesthesia; 2002, 12:665-673.
8. Hanje AJ, Patel T: Preoperative evaluation of patients with liver
disease. Nature Clinical Practice Gastroenterology & Hepatology;
2007, 4:266-276.
9. Isaacs H, Barlow MB: Malignant hyperpyrexia during anaesthesia:
possible association with subclinical myopathy. British Medical
Journal; 1970, 1:275-277.
10.Schmidt J, Muenster T, Wick S, Forst J, Schmitt HJ: Onset and
duration of mivacurium-induced neuromuscular block in patients
with Duchenne muscular dystrophy. British Journal of Anaesthesia;
2005, 95:769-772.
11.Wick S, Muenster T, Schmidt J, Forst J, Schmitt HJ: Onset and
duration of rocuronium-induced neuromuscular blockade in patients
with Duchenne muscular dystrophy. Anesthesiology; 2005, 102:915919.
12.Sullivan M, Thompson WK, Hill GD: Succinylcholine-induced
cardiac arrest in children with undiagnosed myopathy. Canadian
Journal of Anaesthesia; 1994, 4:497-501.
13.Kuhn I, Scheıfler G, Wıssıng H: Incidence of nausea and vomiting in
children after strabismus surgery following desflurane anaesthesia.
Paediatric Anaesthesia; 1999, 9:521-526.
LINGUAL THYROID: A RARE CAUSE
OF DIFFICULT INTUBATION
Maroun Badwi Ghabash*, Jean-Claude M. Stephan**,
May Semaan Matta*** and May Radi Helou****
Abstract
This case report is about a patient with an oropharyngeal mass presenting to our hospital for
biopsy under general anesthesia. Because of the great risk of failure of mask ventilation and direct
laryngoscopy, an awake fiberoptic intubation was performed successfully. The biopsy revealed a
thyroid tissue leading to the diagnosis of ectopic lingual thyroid.
Introduction
Managing a patient with difficult airway is among the most challenging and stressful tasks
in anesthesia1. The inability to provide adequate ventilation and to perform tracheal intubation is
associated with major morbidity and mortality2.
Lingual thyroid, first described in 1869 by Hickman3, is located at the base of the tongue
between the circumvallate papillae and epiglottis. This ectopic variation has an incidence
of 1:1000004. Its position and size may cause obstruction of the laryngeal pathway leading to
ventilation and intubation difficulties with a potential dramatic risk of hemorrhage during attempts
of intubation.
This case report describes the successful management of a patient with symptomatic lingual
thyroid undergoing surgery under general anesthesia.
Case Report
A 42-year-old woman presented to our hospital for biopsy of an oropharyngeal mass under
general anesthesia. The pre-operative anesthetic evaluation revealed a patient with 55 Kg body
weight, 155 cm height, non-smoker, with a negative past medical and surgical history, and
absence of weight loss; She was only complaining of dyspnea and dysphonia. Airway examination
for difficult intubation was insignificant; Normal mobility of the neck, Mallampati score of 1,
thyromental distance of 6 cm, mouth opening of 4 cm and inability of visualization of the mass.
Pre-operative investigation included normal hematology tests, coagulation profile, chemistry,
TSH, free T3 and T4 and a normal chest X-ray. A CT-scan of the neck showed an evidence of a large
well defined 5 cm heterogeneous mass lesion at the base of the tongue extending to the oropharynx
*
MD, Anesthesiologist, Chairman of Anesthesia, Haddad Hospital for the Rosary Sisters Gemayze-Beirut-lebanon, chargé
d’enseignement at the Lebanese University-Medical School.
**
MD, Third Year Resident of Anesthesia, Department of Anesthesia Lebanese University-Medical School.
*** MD, Anesthesiologist, Haddad Hospital for the Rosary Sisters Gemayze-Beirut-Lebanon.
**** MD, Anesthesiologist, Chairman of Anesthesia and ICU Department at the Lebanese University-Medical School.
Corresponding Author: Maroun Ghabash, MD, Anesthesiologist, Chairman of Anesthesia, Haddad hospital for the
Rosary Sisters, Gemayze, Beirut-Lebanon. Tel: 03-451882, E-mail:[email protected]
441
M.E.J. ANESTH 21 (3), 2011
442
and causing marked narrowing of the oropharyngeal
airway mainly on the left side (Fig. 1).
M. B. Ghabash et al.
Fig. 2
The mass as visualized by the fiberscope
Fig. 1
The mass at the base of the tongue as visualized by the scan
Embryology
The patient had been explained about the hazards
of intubation in her case and that an awake fiberoptic
intubation will be performed. No premedication was
given preoperatively.
In the induction room, a standard monitoring
was applied on the patient and an intravenous access
was established. A solution of lidocaine 5% and
phenylephrine nasal was sprayed in both nostrils. The
fiberscope, Olympus P40, lubricated and threaded
through the lumen of an ETT size 6.5, was inserted
in the right nostril and was navigated into the oral
pharynx. The mass was visualized (Fig. 2) and was
completely obscuring the epiglottis and the larynx. The
fiberscope was guided through a narrow passage on the
right side of the lesion then was flexed anteriorly to
enter between the vocal cords into the trachea. Once
reaching the carina, the ETT was railroaded over the
fiberscope. Intubation was reconfirmed by the presence
of EtCO2 and anesthesia was induced with propofol
and was maintained with rocuronuim, sevoflurane and
remifentanyl. Surgery underwent uneventfully and the
patient was extubated.
Embryologically, the thyroid gland develops as
an endodermal diverticulum between the first and the
second pharyngeal pouches. At the seventh week of
embryonic life, it passes from the base of the tongue
in front of the hyoid bone to settle ultimately anterior
to the trachea. Incomplete caudal migration of the
gland may lead to lingual thyroid as a developmental
anomaly5. The etiology of this embryonic defect is not
yet understood, but maternal antibodies against thyroid
antigens have been incriminated6.
Discussion
Management of the difficult airway in the general
surgical population has been widely studied, and
several algorithms have been established7. However,
the incidence of difficult ventilation and endotracheal
intubation in lingual thyroid surgery has rarely been
reported.
Clinically, the lingual thyroid presents as a pink
and firm mass at the base of the tongue. Most of the
cases are asymptomatic, but frequently encountered
symptoms are due to mass effect: dysphonia,
dysphagia, lump in throat sensation, dyspnea, chronic
cough and bleeding. Surgical intervention is indicated
LINGUAL THYROID: A RARE CAUSE OF DIFFICULT INTUBATION
in symptomatic cases or as prophylactic due to the risk
of malignant transformation. Lingual thyroid surgery
under general anesthesia is a risky challenge due to its
location, size and bleeding tendency.
This paper presents the case of an expected
difficult airway due to a symptomatic mass sized
5cm in the oropharynx (Figure 1). The approach to
the airway was based on two targets. The first was
to keep a spontaneous breathing: we avoided the use
of sedative drugs that can cause apnea and posterior
displacement of the soft palate, base of the tongue or
epiglottis; thus majoring the already narrowed pharynx
by the mass leading to difficulty and inability of mask
443
ventilation. In addition, any attempt to insert a guedel
airway, LMA, or fast track can easily injure the fragile
tissue leading to bleeding with a fatal outcome.
The second target was to visualize the vocal cord
and to intubate the patient under direct vision without
traumatizing the surrounding tissue. On the other hand,
performing a direct classical laryngoscopy can also
cause hemorrhage and catastrophic compromise of the
airway.
As a result, an awake fiberoptic intubation was
the only choice to successfully secure the airway in
this case.
References
1. Kheterpal S, Martin L, Shanks A and Tremper K: Prediction and
outcomes of impossible mask ventilation. Anesthesiology; 2009,
110:891-7.
2. Caplan R, Posner K, Ward R and Cheney F: Adverse respiratory
events in anesthesia: a closed claims analysis. Anesthesiology; 1990,
72:828-33.
3. Hickman W: Congenital tumor of the base of the tongue, pressing
down the epiglottis on the larynx and causing the death by
suffocation sixteen hours after birth. Trans pathology Soc London;
1869, 20:160-63.
4. Douglas P and Baker A: Lingual thyroid. Br J Oral Maxillofac
Surg; 32:123-4.
5. Abdallah-Matta M, Dubarry P, Pessy J and Caron P: Lingual
thyroid and hyperthyroidism: a new case and review of the literature.
J Endocrinol Invest Mar; 2002, 25(3):264-7.
6. Van Der Gaag R, Drexhage H and Dussault J: Role of maternal
immunoglobulins blocking TSH induced thyroid growth in sporadic
forms of congenital hypothyroidism. Lancet; 1985, 1:1246-50.
7. American Society of Anesthesiologists Task Force of Management
of Difficult Airway.Practice guidelines for management of the
difficult airway. Anesthesiology; 2003, 98:1269-77.
M.E.J. ANESTH 21 (3), 2011
SHOULD SURGERY BE CANCELLED
WHEN SURREPTITIOUS COCAINE USE
IS DISCOVERED BEFORE ELECTIVE
NON-CARDIAC SURGERY?
M. Chadi Alraies MD FACP*, Abdul Hamid Alraiyes MD**,
Franklin Michota MD FACP*
Answer: Patients presenting for elective non-cardiac surgery requiring general anesthesia
who test positive for cocaine but are asymptomatic and clinically nontoxic are at no greater risk
for surgical complications than cocaine-free patients. Routine cancellation of surgery for these
patients is unwarranted. Such patients need careful preoperative history and physical examination
along with screening electrocardiogram (ECG) looking for QT prolongation. Patients who display
signs of acute cocaine intoxication or those with a prolonged QT interval will need to have
elective surgery delayed. However, there is paucity in literature and no guidelines supporting this
practice and clinician practicing perioperative medicine and anesthesia should be vigilant till more
prospective studies are done to support this practice.
Discussion
One of the goals of the preoperative evaluation is to ensure that the surgical patient is optimized
for the stress of surgery. In the patient with a history of cocaine use, it is reasonable to avoid the
combined stress of acute cocaine exposure and surgery; however, postponing surgery well beyond
the time cocaine is physiologically active may be unnecessary and cause a delay in patient care.
Cocaine blocks the reuptake of norepinephrine, dopamine, and serotonin at the synaptic
junctions producing an excess of transmitter at the postsynaptic receptor sites1. Signs include an
increase in systolic, diastolic and mean arterial blood pressure, heart rate, body temperature and the
potential for coronary artery vasospasm and arrhythmias. Cocaine toxicity is a clinical diagnosis,
as signs of toxicity do not correlate well to measured blood concentrations of cocaine2,3. The most
reliable supporting evidence for cocaine toxicity is a confirmed history of active use4.
Many cocaine abusers are not going to admit to it5. Patients with surreptitious cocaine abuse
may manifest feelings of excitation, report weight loss, anxiety, requests for sedatives and pain
medicine and complain of digestive problems. Cocaine abusers should be asked for timing, amount,
route of cocaine in the last 24 hours, and length of addiction6.
Cocaine users are known to experience a higher cardiac related mortality associated with
arrhythmia and coronary artery disease7. The mechanism for the induction of these arrhythmias is
a combination of coronary artery vasospasm and cocaine-induced sodium and potassium channel
blockade that causes lengthening of the QTc interval as well8.
*
**
MD, Cleveland Clinic, Cleveland, Ohio, USA.
MD, Tulane University, New Orleans, Luisiana, USA.
Corresponding author: Clinical Assistant Professor of Medicine, Cleveland Clinic Lemer College of Medicine of Case
Western Reserve University, Staff, Department of Hospital Medicine, Institute of Medicine, Cleveland Clinic, 9500
Euclid Ave. A13, Cleveland, OH 44195, Office: (216) 445-1472, Fax: (216) 445-1767. E-mail: [email protected]
445
M.E.J. ANESTH 21 (3), 2011
446
Cocaine has a short half-life in plasma (30-90
minutes) and is rapidly hydrolysed into metabolites
by plasma and liver esterases9. Cocaine metabolites
pose no cocaine-like stimulation effects and have
long half-life which is responsible for positive urine
testing for 6 to 14 days after cocaine ingestion. As a
result, urine tests for cocaine are poor markers of acute
intoxication, but may reflect surreptitious cocaine
abuse in the past10,11.
The cancellation of surgery among patients who
screen positive for cocaine use is a common practice
in many surgical centers. However, there is paucity in
literature studying the management of these patients
going for urgent or elective surgery. We found two
studies that addressed this issue. Ryb GE et al12,
studied cocaine-positive patients (n = 465) undergoing
surgery and compared those patients with recent (<24
hours) cocaine use vs. patients who did not use cocaine
M. C. Alraies et al.
immediately before injury (>24 hours). Outcomes were
similar for mortality (3% vs. 4%), infectious (18%
and 19%) and neurologic (2% vs. 1%) complications.
Another study investigated the role of screening ECG
as a safety protocol among patients going for elective
surgery (N =13)40 . No significant differences in
episodes of ST segment elevation/depression >1 mm,
recovery room stay, intraoperative body temperature,
duration of anesthesia and total anesthesia/analgesic
dose, were found when compared with controls that
did not have a positive cocaine urine test. We should
be careful in interpreting these two studies giving the
small sample size.
In summary, surreptitious perioperative cocaine
use does occur. Patients with a normal ECG and
without clinical signs of cocaine toxicity may proceed
safely with surgery. However, larger prospective
studies are needed to support this practice.
References
1.Ritz MC: Cocaine inhibition of ligand binding at dopamine,
norepinephrine and serotonin transporters: a structure-activity study.
Life Sci; 1990, 46:635-45.
2.Karch SB: Relating cocaine blood concentrations to toxicity: an
autopsy study of 99 cases. J Forensic Sci; 1998, 43:41-45.
3.Karch SB: Cocaine cardiovascular toxicity. South Med J; 2005,
98:794-799.
4.Stephens BG: National Association of Medical Examiners Position
Paper on the Certification of Cocaine-related Deaths. Am J Forensic
Med Pathol; 2004, 25:11-13.
5.Skerman JH: The cocaine-using patient: perioperative concerns.
Middle East J anesthesiol; 2005 Feb, 18(1):107-22.
6.Frost EA: Preanesthetic assessment of the of the drug abuse patient.
Anesthesiology Clinics of North America; 1990, 8:829-841.
7.Bauman JL: Cocaine related sudden cardiac death: a hypothesis
correlating basic science and clinical observations. J Clin
Pharmacol; 1994, 34:902-11.
8.Kimura S: Early after depolarizations and triggered activity induced
by cocaine. Circulation; 1992, 85:2227-35.
9.Cheng D: Perioperative care of the cocaine-abusing patient. Can J
Anaesth; 1994, 41:10, pp. 883-7.
10.Jatlow PI: Drug abuse profile: cocaine. Clin Chem; 1987,
33:66B-71B.
11.Brownlow HA, Pappachan J: Pathophysiology of cocaine abuse.
Eur J Anaesthesiol; 2003, 19:395-414.
12.Ryb GE, Cooper C: Outcomes of cocaine-positive trauma patients
undergoing surgery on the first day after admission; 2008 Oct,
65(4):809-12.
13.Hill GE: General anesthesia for the cocaine abusing patient. Is it
safe? Br J Anaesth; 2006, 97:654-657.
AUTOMATIC ENDOTRACHEAL TUBE CUFF
INFLATOR AND CONTINUOUS PRESSURE
MONITOR/CONTROLLER
Musa Muallem*, Mohamad F. El-Khatib**
Background
Endotracheal tube cuff pressure over 30 cm of water has been found to occur in about 50%
of cases where cuff inflation was performed without monitoring, using pilot balloon palpation,
minimal leak, or minimal occlusive volume techniques1. The incidence of post operative respiratory
complications such as cough, sore throat, hoarseness, blood-streaked expectoration, and even
tracheal stenosis is increased with increase of cuff pressure over 30 cm of water2. Mandatory
continuous monitoring and control of the endotracheal tube cuff pressure have been recommended
to minimize such complication.
Anesthesiologists continue to ignore the above important recommendation in many
institutions because they do not have easy access to devices that monitor and control cuff pressure,
and because continuous intracuff pressure control and measurement using a device are not yet
mandate or standard of care for anesthesia practice. Intermittent checking of the cuff pressure
during anesthesia is not good enough and has a very poor compliance. Ideally, the cuff pressure
should be monitored and controlled at the required level continuously and automatically without
concern from the anesthesiologist.
This situation prompted us to design and develop cuff inflator and cuff pressure monitor/
regulator that is simple and practical.
Description of the apparatus
The cuff inflator/monitor is operated by an oxygen line from the auxiliary outlet of the
anesthesia machine at a pressure of 50 psi. The oxygen line is connected to the inlet of a Butane
gas reducing valve available commercially in the market and which operate at an inlet pressure
of five bars and an outlet pressure variable from 15 to 45 cm of water. This reducing valve fits
the requirements of a reducing valve suitable for building a cuff inflator monitor/controller. The
oxygen comes out from the Butane reducing valve at a maximum pressure of 45 cm of water and
can be further reduced to 15 cm of water by the valve pressure controlling knob.
The oxygen from the reducing valve outlet is connected by plastic tubings to:
1- Outlet nipple that connect through an oxygen plastic tube, via a luer tap at the distal end,
to the ET tube cuff pilot balloon (Fig. 1, 2).
*
Emeritus Professor.
**Professor.
Department of Anesthesiology, American University of Beirut Medical Center, Beirut 1107-2020 Lebanon.
Correspondence to: Dr. Mohamad El-Khatib. E-mail: [email protected]
447
M.E.J. ANESTH 21 (3), 2011
448
M. Muallem & M. F. El-Khatib
Fig 1
Schematic Diagram
the valve outlet plastic tube to reduce the oxygen flow
rate to a minimum, yet enough to inflate the cuff in
few seconds. While the venting needle valve and the
outlet to the tube cuff are closed, the outlet pressure of
the Butane reducing valve is set at 45 cm H2O, by the
valve controlling pressure knob or by a screw driver.
Then the venting needle valve knob is turned to open
and pressure set at 30 cm H2O. When the cuff inflator/
controller is connected to the tube cuff, the cuff will
be inflated instantly and its pressure is maintained
constant at 30 cm of water or as set by the user.
The pressure of the cuff can be increased or
decreased by the needle valve that increases or
decreases the gas vented out, as each case may require,
and depending on the inflating pressure required to
inflate the lung. Usually the cuff pressure is set at 30
cm of water or slightly higher than the lung inflating
pressure required.
Fig 2
Back view
The cuff inflator/controller described above
(Fig. 3) has been used successfully for many years
in the department of anesthesiology at the American
University of Beirut Medical center during anesthesia
and in chronically intubated and ventilated patients,
without complications or failure, provided all
connections are tight with no leaks.
Fig 3
Front View
2- Airway pressure gauge graduated from 0 to 60
cm H2O (figure 1, 2).
3- Needle valve that is vented to atmosphere.
A brass insert with a very small hole is placed in
AUTOMATIC ENDOTRACHEAL TUBE CUFF INFLATOR AND CONTINUOUS PRESSURE
MONITOR/CONTROLLER
449
References
1.Kim Z Rokamp, Niels H Secher, Ann M Moller and Henning B
Nielsen: Tracheal tube and laryngeal mask cuff pressure during
anaesthesia-Mandatory monitoring is in need. BMC Anesthesiology;
2010, 10:20doi:10.1186/1471-2253-10-20.
2.Liu J, Zhang X, Gong W, Li S, Wang F, Fu S, Zhang M, Hang Y:
Correlations between controlled endotracheal tube cuff pressure and
post procedural complications: a multicenter study. Anesth Analg;
2010 Nov, 111(5):1133-7. Epub 2010 Aug 24.
M.E.J. ANESTH 21 (3), 2011
GUIDELINES FOR AUTHORS
The Middle East of Anesthesiology publishes original
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M.E.J. ANESTH 21 (3), 2011
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