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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
Editorial Executive Board
Consultant Editors
Editor-In-Chief:
Bikhazi George
Assem Abdel-Razik
(Egypt)
Executive Editors
Mohamad El-Khatib
Editors
Chakib Ayoub
Marie Aouad
Ghassan Kanazi
Sahar Siddik-Sayyid
Mohamad El-Khatib
[email protected]
Bassam Barzangi
(Iraq)
Izdiyad Bedran
(Jordan)
Dhafir Al-Khudhairi
(Saudi Arabia)
Mohammad Seraj
(Saudi Arabia)
Abdul-Hamid Samarkandi
(Saudi Arabia)
Mohamad Takrouri
(Saudi Arabia)
Bourhan E. Abed
(Syria)
Mohamed Salah Ben Ammar
(Tunis)
Managing Editor Assistant Iman Jaafar
M. Ramez Salem
(USA)
Webmaster
Rabi Moukalled
Elizabeth A.M. Frost
(USA)
Secretary
Alice Demirdjian
[email protected]
Halim Habr
(USA)
Managing Editor
Founding Editor
Bernard Brandstater
Emeritus Editor-In-Chief Anis Baraka
Honorary Editors
Nicholas Greene
Musa Muallem
The Middle East Journal of Anesthesiology is a
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“For some must watch, while some must sleep”
(Hamlet-Act. III, Sc. ii)
134
Middle East Journal of Anesthesiology
Vol. 23, No. 1, February 2015
CONTENTS
editorial
«Routine» Preoxygenation
��������������������������������������������������������������������������������������������������������������������������������� Anis Baraka
5
review article
The Impact Of Endotracheal Tube Vs Laryngeal Mask Airway On The Incidence Of Postoperative
Nausea And Vomiting: A Systemic Review And Meta-Analysis
������������������������������������������������������������� Jahan Porhomayon, Sina Davari Farid, Ali A. El-Solh,
Ghazaleh Adlparvar, Nader D. Nader
9
scientific articles
Renal Protection In The Cardiac Surgery Patient: Peri-Operative Sodium Bicarbonate Infusion
(Posbi) Or Not?
��������������������������������������������������������������������Hassan H. Amhaz, Deepak Gupta, Larry Manders,
George McKelvey, Marc S. Orlewicz, Romeo N. Kaddoum
Effect Of Ultrasound-Guided Subsartorial Approach For Saphenous Nerve Block In Cases
With Saphenous Nerve Entrapment In Adductor Canal For Controlling Chronic Knee Pain
�������������������������������������������������������������������������� Arman Taheri, Maryam Hatami, Majid Dashti,
Alireza Khajehnasiri, Mahsa Ghajarzadeh
Comparison Of The Effects Of Oral Vs. Peritonsillar Infiltration Of Ketamine In Pain Reduction
After Tonsillectomy: A Randomized Clinical Trial
������������������������������������������������������������������������������������������������Afsaneh Norouzi, Abolfazl Jafari,
Hamid Reza Khoddami Vishteh, Shahin Fateh
The Impact Of Anesthetic Techniques On Cognitive Functions After Urological Surgery
17
25
29
����������������������������������������������������������������������������������������Mahtab Poor Zamany Nejat Kermany,
Mohammad Hossein Soltani, Khazar Ahmadi,
Hoora Motiee, Shermin Rubenzadeh, Vahid Nejati
Comparison Between C-Mac® Video-Laryngoscope And Macintosh Direct Laryngoscope During
Cervical Spine Immobilization
��������������������������������������������������������������������������������������������Shahir H.M. Akbar, Joanna SM Ooi
43
Effects Of Memantine On Pain In Patients With Complex Regional Pain Syndrome-A Retrospective
Study
�������������������������������������������������������Mohammad-Hazem I. Ahmad-Sabry, Gholamreza Shareghi
51
Effects Of Dexamethasone And Pheniramine Maleate On Hemodynamic And Respiratory
Parameters After Cementation In Cemented Partial Hip Prosthesis
������������������������������������������������������������������������������������������������������������������������ Abdulkadir Yektaş
55
Effect Of Preoperative Oral Pregabalin On Postoperative Pain After Mastectomy
�������������������������������������������������������������������� Mardhiah Sarah, Harnani Mansor, Choy Yin Choy
1
35
63
M.E.J. ANESTH 23 (1), 2015
Consumption Trends Of Rescue Anti-Psychotics For Delirium In Intensive Care Units (Icu
Delirium) Show Influence Of Corresponding Lunar Phase Cycles: A Retrospective Audit
Study From Academic University Hospital In The United States
������������������������������������������������������������������� Deepak Gupta, Vinay Pallekonda, Ronald Thomas,
George Mckelvey, Farhad Ghoddoussi
Ultrasound-Guided Sciaticoliteal Nerve Block: A Comparison Of Separate Tibial And Common
Peroneal Nerve Injections Versus Injecting Proximal To The Bifurcation
�������������������������������������������������������������� Alberto E. Ardon, Roy A. Greengrass, Upasna Bhuria,
Steven B. Porter, Christopher B. Robards, Kurt Blasser
Subtenon bupivacaine injection for postoperative pain relief following pediatric strabismus
surgery: A randomized controlled double blind trial
����������������������������������������������������������������������������������� Radwa H Bakr and Hesham M Abdelaziz
69
81
91
case reports
Straight To Video: Tonsillar Injury During Elective Glidescope-Assisted Pediatric Intubation
��������������������������������������������������������������������� Jason D. Rodney, Zulfiqar Ahmed, Deepak Gupta,
Maria Markakis Zestos
Percutaneous Balloon Compression Of Gasserian Ganglion For The Treatment Of Trigeminal
Neuralgia: An Experience From India
��������������������������������������������������������������������� Anurag Agarwal, Vipin Dhama, Yogesh K. Manik,
M. K. Upadhyaya, C. S. Singh, V. Rastogi
Bedside Retianed Radial Artery Catheter Removal In A Hemodynamically Unstable
Neurocritically-Ill Patient: A Case Report
����������������������������������������������������������������������������� Christa O’Hana V. San Luis, Athir H. Morad
101
105
111
Esophageal Perforation Following Orogastric Suction Catheter Insertion In An Elderly Patient
������������������������������������������������������������������Roland N. Kaddoum, Fadi Farah, Rita W. Saroufim,
Salah M. Zeineldine
117
letter to the editor
Pediatric Endotracheal Intubation
��������������������������������������������������������������������������������������������������������������������������Claude Abdallah
2
123
LIFE ON WHEELS
Triumph over the agony of pain and sadness; admission of the ways of the creator and
“happy to be alive”; optimism with brilliant accomplishments from a wheelchair and “breathing
happiness”, are but few of the accomplishments of faculties endowed on Alon P. Winnie
, Professor and Chairman of the Department of Anesthesiology of the University of Illinois.
Fig1. Dr. Winnie among his colleagues ; Dr. Baraka (far left) & Dr. Raj (far right).
In his own words, Dr. Winnie writes
« Dear Anis*…
To fulfill my promise to you, the following… Let me preface it by telling you that it was
written from the viewpoint of a rocking bed after I had been given my first wheelchair, for which I
had waited for an eternity of months while physiotherapy tried to rid me of the rigidity left behind
when the pain of the muscle spasms finally subsided… It was the middle of winter and I had a
beautiful view of the slum section of the city just behind the hospital…The first half obviously
representing the translation of my impression at night and the second during the day…
The sad white eye of this new night
Cries myriads of auto tears
That criss-cross over its many streeted face;
The freckles of which glow dimly
*
Dr. Anis Baraka, Department of Anesthesiology, American University of Beirut, Beirut, Lebanon.
MEJA 3: 240, 1972.
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M.E.J. ANESTH 23 (1), 2015
4
And disappear
One by one
As an angry lock of cloud
Slips down
And covers sad eye rendered sadder
By the loss of legs,
Yet soon
The bright orange eye of the day
Combs back the clouds
Revealing life and lives
Breathing happiness
In little gray-blue puffs
From the cigarette chimneys
As the city yawns
As a sleepy but happy to be alive yawn
And readies itself
For this new day
Of life on wheels…”
Fig 2. Dr. Alon Winnie
EDITORIAL
“ROUTINE” PREOXYGENATION
It is a fact of great clinical importance that the body oxygen stores are so small, and if
replenishment ceases, they are normally insufficient to sustain life for more than a few minutes.
Breathing oxygen causes a substantial increase in the total oxygen stores; most of the additional
oxygen is accommodated in the alveolar space (functional residual capacity) from which 80% may
be withdrawn without the PaO2 falling below the normal vale. This concept is the basis of the
preoxygenation technique1.
In 1955, Hamilton and Eastwood demonstrated that denitrogenation of the functional residual
capacity of the lung is 95% complete within 2-3 minutes, if a subject is breathing at a normal tidal
volume form a circle anesthesia system using an oxygen flow of 5 l/min2. These studies led to
the recommendation of preoxygenation as a standard practice before rapid sequence induction of
general anesthesia in patients with full stomach.
“Routine” preoxygenation has become a new “minimum standard” of care not only during
induction of anesthesia and tracheal intubation, but also during emergence from anesthesia and
tracheal extubation1.
The original American Society of Anesthesiologists (ASA) difficult airway algorithm made no
mention of preoxygenation. However, in an updated report of the ASA Task Force on “Management
of the Difficult Airway” 2003, the topic of face mask preoxygenation before initiating management
of the difficult airway was added3.
Preoxygenation before induction of anesthesia was also recommended in patients with low
functional residual capacity of the lung, associated with a high oxygen consumption. This category
includes the neonates, the pregnant and the morbidly obese patients who rapidly decrease their
oxygen saturation during apnea while breathing room air4.
Preoxygenation is also recommended in patients with decreased oxygen delivery (Cardiac
output x Hb conc x% saturation x 1.34) which include patients with low cardiac output or pulmonary
disease, as well as patients with low or abnormal hemoglobin such as methemoglobin.
Before induction of general anesthesia, preoxygenation can be achieved either by tidal volume
breathing of 100% oxygen for 3-5 minutes using an oxygen flow of 5 l/min as described by Hamilton
and Eastwood2, or by the 8 deep breaths technique for 60 seconds using an oxygen flow of 10 L/
min as described by Baraka et al5. The mean time to decrease of hemoglobin oxygen saturation
from 100% to 99% is significantly longer during the subsequent apnea following the 8-deep
breaths technique of preoxygenation than following the traditional tidal volume preoxygenation
technique5. As suggested by Benumof, the 8 deep breaths technique may be considered the best
method of preoxygenation for both efficacy and efficiency6. The high efficiency of preoxygenation
by the deep breaths technique may be attributed to a relatively larger minute volume, and/or to
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M.E.J. ANESTH 23 (1), 2015
6
Dr Baraka
possible expansion of any collapsed alveoli by the
deep breathing technique.
The beneficial effect of preoxygenation by tidal
volume or deep breathing, can be further extended
during subsequent apnea by the apneic diffusion
oxygenation7-9. The technique of ADO has been
advantageous not only in patients with a difficult
airway or pulmonary disease, but also in children, the
pregnant and the morbidly obese patients who have a
high oxygen consumption associated with a relatively
low FRC4. ADO has been also used to maintain
oxygenation during bronchoscopy7, and one-lung
ventilation10.
Apneic diffusion oxygenation (ADO) is achieved
by preoxygenation by tidal volume2, or deep breathing
technique5, to be followed by insufflations of high
flow of 100% oxygen by a catheter into the pharynx
via an open airway. During ADO, the increase in time
to hemoglobin desaturation achieved by increasing
the FIO2 from 0.9 to 1.0 is greater than that caused
by increasing the FIO2 from 0.21 to 0.99. During
ADO, CO2 is not exhaled because of the mass
movement of oxygen down the trachea. The alveolar
CO2 concentration (PACO2) shows an initial rise of
8-16 mmHg during the first minute, followed by a
subsequent fairly linear increase of about 3 mmHg/
min. Thus, the ADO can maintain oxygenation for a
prolonged period. However, the increase of PaCO2
will limit the period of apnea.
In conclusion, preoxygenation has been initially
recommended for rapid-sequence induction of
anesthesia in patients with full stomach, as well as
in patients with predicted difficult airway. However,
the technique is nowadays recommended as a routine
during induction, as well as during recovery from
general anesthesia, since difficult airway may be
unpredicted.
Preoxygenation, followed by apneic diffusion
oxygenation is indicated in patients who desaturate
rapidly during apnea such as the neonate, the obese and
the pregnant patients who have a relatively low FRC
associated with a high oxygen consumption. ADO is
also advantageous in patients with decreased oxygen
delivery such as the elderly, cardiac and pulmonary
diseased patients. The technique is also used to
maintain oxygenation during certain procedures such
as bronchoscopy, and one-lung ventilation.
“Routine” preoxygenation with 100% oxygen
is considered a “safety” measure during anesthetic
induction and emergence from anesthesia, and is
advantageous in critically-ill patients requiring airway
management. However, it must be used as an adjunct
rather than an alternative to a sequence of fundamental
precautions that minimize adverse sequelae1.
Anis Baraka, MD, FRCA (Hon)
Emeritus Professor of Anesthesiology
American University of Beirut
“ROUTINE” PREOXYGENATION
7
References
1. Baraka AS, Salem MR: Preoxygenation: In Benumof and Hagberg’s
Airway management, Third Edition 2013, Chapter 13, pp. 280-297.
2. Hamilton W, Eastwood D: A study of denitrogenation with some
inhalation anesthetic systems. Anesthesiology; 1955, 16:861-867.
3. Practice guidelines for management of difficult airway: An updated
report by the American Society of Anesthesiologists Task force
on the management of the difficult Airway. Anesthesiology; 2003,
98:1269-1277.
4. Baraka AS, Taha SK, Siddik SM et al: Supplementation of
oxygenation in morbidly obese patients using nasopharyngeal
oxygen insufflation. Anaesthesia; 2007, 62:769-773.
5. Baraka AS, Taha SK, Aouad MT, El-Khatib MF, Kawkabani
NI: Preoxygenation: Comparison of maximal breathing and tidal
volume breathing techniques. Anesthesiology; 1999, 91(3):612-616.
6. Benumof JL: Preoxygenation: Best method for both efficacy and
efficiency. Anesthesiology; 1999, 91(3):603-605.
7. Holmdahl MH: Pulmonary uptake of oxygen, acid-base metabolism,
and circulation. Acta Chir Scand; 1956, 212(supp):1-128.
8. Framery AD, Roe PG: A model to describe the folre of
oxyhemoglobin desaturation during apnea. Br J Anaesth; 1996,
76:284-291.
9. McNamara MJ, Harman JG: Hypoxemia during open airway apnea.
A computational modeling analysis. Anaesthesia; 2006, 60:741-746.
10.Baraka A, Aouad M, Taha S, El-Khatib M, et al: Apnea-induced
hemoglobin desaturation during one-lung vs two-lung ventilation.
Can J Anaesth; 2000, 47(1):58-61.
M.E.J. ANESTH 23 (1), 2015
REVIEW ARTICLE
The Impact of Endotracheal Tube vs. laryngeal Mask
Airway on the Incidence of Postoperative Nausea and
Vomiting: A Systemic Review and Meta-analysis
Jahan Porhomayon*, Sina Davari Farid** Ali A. El-Solh***,
Ghazaleh Adlparvar**** and Nader D. Nader*****
Abstract
Objective: To investigate the impact of Endotracheal tube (ETT) vs. Laryngeal Mask Airway
(LMA) on postoperative nausea and vomiting (PONV) in patients undergoing surgery with general
anesthesia.
Methods: Key words searching from databases such as Medline, Embase, and Cochrane
library provided 14 studies focusing on the use of EET vs. LMA for general anesthesia. Pooled
estimate of relative risk with 95% confidence interval using random effect model was conducted.
Results: 14 studies were selected for meta-analysis with a total of 1866 patients. 9 studies
focused on the outcome of PONV in adult patients. It showed incidence of PONV with of LMA
and ETT in adult of about 204/690 (30%) and 145/725 (20%) respectively with [Odds Ratio (OR)
= 1.69, 95% CI, 0.76-3.75, P = 0.20]. Heterogeneity was high (I2 = 87%). Five studies focused on
the outcome of PONV in pediatric patients with PONV in LMA and ETT group of 85/229 (37%)
and 72/222 (32%) respectively with (OR = 1.30, 95% CI, 0.61-2.76, P = 0.50). Heterogeneity was
moderate at (I2 = 53%). When all patients were combined heterogeneity was high at 81% with OR
= 1.56, 95% CI, 0.87-2.79, P = 0.14.
Conclusion: Risk of PONV shows an increase trend toward the use of LMA. Larger
randomized trials are needed to assess the impact of airway devices on PONV.
Keywords: Postoperative, Nausea and Vomiting, Endotracheal Tube, Laryngeal Mask
Airway.
*MD, FCCP. Associate Professor of Anesthesiology and Critical Care Medicine VA Western New York Healthcare System,
Division of Critical Care Medicine, Department of Anesthesiology, State University of New York at Buffalo School of
Medicine and Biomedical Sciences, Buffalo, New York.
**MD. Anesthesiology Research Fellow VA Western New York Healthcare System, Division of Critical Care Medicine,
Department of Anesthesiology, State University of New York at Buffalo School of Medicine and Biomedical Sciences,
Buffalo, New York.
***MD, MPH. Professor of Medicine, Anesthesiology and Preventive Medicine VA Western New York Healthcare System,
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at
Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
**** MA, BA. Research Assistant Department of Science University at Buffalo, MCC College, Rochester, New York.
***** M.D., Ph.D., FCCP. Professor of Anesthesiology, Surgery and Pathology VA Western New York Healthcare System,
Division of Cardiothoracic Anesthesia and Pain Medicine, Department of Anesthesiology, State University of New York
at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
Corresponding author: Jahan Porhomayon MD, FCCP, VA Medical Center, Rm 203C, 3495 Bailey Ave, Buffalo, NY
14215. Tel: 716 862-8707, Fax 716 862-8707. E-mail: [email protected]
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M.E.J. ANESTH 23 (1), 2015
10
Introduction
PONV remain a common problem occurring in
in 20-30% of surgical population, and can be as high
as 70-80% in the high risk population1. It increases
cost, and delays discharge, and decreases patient
satisfaction2. In this analysis, nausea is defined as
uncomfortable feeling of stomach which might lead
to the eagerness to vomit, while vomiting refers the
actual motion of throwing up.
PONV could lead to pulmonary aspiration of
gastric content and may lead to aspiration pneumonia
with potentially fatal consequences. Our current
knowledge outlines several well-established risk
factors for the occurrence of PONV3,4. These risk factors
include: patient, anesthesia and surgical risk specific
risk factors. The patient specific risk factors include,
female gender, history of PONV or motion sickness,
non-smoking status, age greater than or equal to three,
and family history of PONV in children. Anesthesia
related risk factors include volatile anesthetics, use of
Nitrous oxide, and opioid use3,5. There is also a dose
relation between volatile anesthetics and opioids.
Surgical risk factors include duration of surgery and
type of procedure, in particular strabismus correction
in children and laparoscopic procedures.
In addition to these well-established risk
factors, there are other etiologies for development
of PONV such as, the lower American society of
anesthesiology (ASA) classification, the use of
large doses of neostigmine (>2.5mg), restrictive vs.
liberal intraoperative fluid strategy, ventilation mode,
starvation nausea, heartburn, anxiety, depression,
Hepatitis C, P450 inducers/suppressors (medications
and food), migraines, and ethnicity6. However, the role
of airway devices and its impact on the incidence of
PONV remains controversial. Therefore, the following
systematic review was conducted to study the influence
of airway devices on the incidence of PONV.
Materials and Methods
We conducted databases searches from Embase,
Cochrane, Medline with the term “Laryngeal mask
AND Endotracheal tube AND Post-operative AND
Nausea AND Vomiting”. Abstracts were reviewed
Porhomay on Jahan et. al
and only prospective RCTs included7. A total of 6568
articles were identified. 5967 were excluded because
it was not related to risk factors or airway device.
601 relevant articles related to PONV risk factors
and airway device were screened. 584 were excluded
because they were either review, duplicate and nonrelevant duplications. 17 articles were assessed for
eligibility with additional 3 articles excluded due to
its retrospective nature and low quality. Finally, 14
articles included for final analysis [Figure 1].
Compared to Yu3, we included newer studies
published since, as well as pediatric studies. We also
included RCTs with the use of non-depolarizers muscle
relaxant and Neostigmine usage in the ETT group.
RCTs with regional techniques were also excluded8.
Data Extraction
Timing of PONV reporting varied among studies.
Some studies reported PONV in the post-anesthesia
Fig. 1
Endotracheal tube vs LMA for PONV
11
recovery unit (PACU) while others reported PONV
on the first postoperative day. When confronted with
multiple data points, data extracted for analysis with
earliest time for PONV was reported. This was an
effort to reduce confounding factors such as, rescue
anti-emetics given after surgery. Furthermore, PACU
treatment for PONV was not always standardized and
was often based on individual patient variables and
anesthesiologist preference. Characteristics of each
study was extracted, which included last name of first
author, publication year, patient age range, procedure
type, usage of anesthetics and prophylactic antiemetics. The following outcomes were also extracted
including the incidence of PONV for both ETT and
LMA group. After data searching and study selection,
14 studies were included in our meta-analysis. Study
characteristics and demographics were shown in Table
1. 12 studies reported postoperative vomiting as the
primary outcome and 10 reported postoperative nausea
as the primary outcome. One study did not differentiate
between nausea and vomiting. Results were shown in
Table 2.
Table 1
Studies Included
Joshi 199717
Adult ASA 1or 2; Succinylcholine or non-depolizer + Neostigmine sometimes used in ET group; Higher
overall fentanyl dose in intra-op ETT group; post-op pain management unstated
Patel 201013
Age 3-10; ProSeal LMA vs ETT; lower abdominal procedures; no opioids given intraop; caudal injection with
GA with Sevo + N2O; universal OG tube use
Klockgether 199614
Age 4-14, strabismus surgery, identical induction (Propofol, Vecuronium, Alfentanil), identical maintenance
(67% N2O, Propofol, Alfentanil). PONV incidence by 24 hours reported
Doksrod 201015
Age 3-16 tonsillectomy & adenoidectomy; prophylactic Dexamethasone used; nausea and vomiting not
reported separately
Gulati 200416
Age 1-12 ophthalmologic procedures; greater duration of surgery and more strabismus procedures in LMA
group
Hohlrieder 2007a7
Adult 18-75, standardized induction and maintenance with oral midazolam, propofol, fentanyl, and
Neostigmine in both groups. ProSeal LMA used along with ETT; Universal use OG tube placement and
decompression; No prophylactic anti-emetics
Cork199420
Adult outpatient peripheral orthopedic procedures; Non-depolarizers and Neostigmine used in both groups;
no sig differences in patient population or duration or opioids intra-op; greater morphine post-op in ET group
Hohlrieder 2007b8
Adult female 18-75 for laparoscopic gynecological surgery; iv induction after oral midazolam, ProSeal LMA
used along with ETT; Universal OG placement + Dexamethasone 4mg + Tropisetron 2mg prophylactic dose
administered
Quinn 199618
Adult 18-64; Nasal ET with Mivacurium vs. none for LMA group; no prophylactic anti-emetics
Swann 1993
Adult laparoscopic gynecological surgeries; ASA 1-2 single blinded RCT LMA vs ET. Atracurium and
Neostigmine 2.5mg given in ET group only; controlled ventilation with ETT vs intermittent manual assistance
to maintain ETCO2 in LMA group
21
Griffiths 201310
Adult ASA 1-2 Laparoscopic gynecological procedures. Single blinded RCT ProSeal LMA vs ET: same
induction; Dexamethasone prophylaxis; universal reversal with Neostigmine 2.5mg
Idrees 200019
Adult ASA 1-2 Limb surgery. Single blinded RCT ProSeal LMA vs ETT; Standardized induction +
maintenance; Dexamethasone prophylaxis;
Gul 201211
Age 1-12 strabismus surgery; ProSeal LMA vs. ETT; inhaled induction, 50% N2O, Atracurium in both groups.
Universal OG tube and gastric decompression
Porhomayon12
Adult, mostly male, undergoing general anesthesia with N2O in knee surgery
M.E.J. ANESTH 23 (1), 2015
12
Porhomay on Jahan et. al
Table 2
Outcomes on Postoperative Vomiting and Nausea
Author
Postoperative Vomiting
Postoperative Nausea
ETT
LMA
ETT
LMA
Joshi 199717
8/174 (4.6%)
15/207 (7.2%)
23/174 (13.2%)
28/207 (13.5%)
Patel 201013
1/30 (3.3%)
0/30 (0)
NR
NR
Klockgether 199614
24/50 (48%)
16/50 (32%)
14/50 (28%)
8/50 (16%)
Doksrod 201015
NR
NR
36/69 (52.2%)
37/62 (59.7%)
Gul 201211
NR
NR
4/40 (10%)
2/40 (5%)
2/30 (6.7%)
5/30 (16.7%)
NR
NR
18/100 (18%)
4/100 (4%)
45/100 (45%)
13/100 (13%)
Cork199420
1/22 (4.5%)
1/22 (4.5%)
3/22 (13.6%)
5/22 (22.7%)
Hohlrieder 2007b8
6/50 (12%)
1/50 (2%)
10/50 (20%)
2/50 (4%)
Quinn 199618
3/50 (6%)
2/50 (4%)
13/50 (26%)
9/50 (18%)
Swann 199321
4/30 (13.3%)
8/30 (26.7%)
6/30 (20%)
15/30 (50%)
Griffiths 201310
27/57 (47.4%)
28/59 (47.5%)
NR
NR
Porhomayon12
25/157 (15%)
12/157(7%)
25/157
12/157
50/3(1.6%)
50/12(4%)
NR
NR
Gulati 200416
Hohlrieder 2007a7
Idrees19
Statistical Analysis
RevMan 5.2 was used to calculate the odds
ratio for the incidence of PONV. Subgroup analysis
including only adult or pediatric patients was also
performed. I2 was used to assess heterogeneity with
a value below 30% standing for low heterogeneity, a
value between 30% and 50% standing for moderate
heterogeneity and a value above 50% standing for high
heterogeneity. Random effect model was used in all
analyses. A p value of <0.1 was significant.
Results
A total of 1899 patients were included. The
incidence of PONV with of LMA and ETT was 289/919
(31%) and 217/947 (22%) respectively. In all patients
heterogeneity was high at 81% with OR = 1.56, 95%
CI, 0.87-2.79, P = 0.14 [Figure 2, 3].
Meta-analysis of subgroups
In terms of PONV in subgroups of adults and
pediatric patients, the incidence of PONV was higher
in adults’ patients. PONV in adult with the use of LMA
and ETT was about 204/690(30%) and 145/725(20%)
respectively with (OR = 1.69, 95% CI, 0.76-3.75, P
= 0.20). In pediatric population PONV in the LMA
and the ETT group was 85/229(37%) and 72/222
(32%) respectively with (OR = 1.30, 95% CI, 0.612.76, P = 0.50). Overall, LMA was associated with
higher incidence of PONV. Statistical heterogeneity
for adult and pediatric patients was 87% and % 53
% respectively. Test for subgroup difference was not
statistically significant with p value of 0.64 and I2 = 0.
Discussion
The impact of the airway device on PONV
remains unresolved. Previous models included the
influence of airway devices on development of PONV,
Endotracheal tube vs LMA for PONV
13
Fig. 2
Study or Subgroup
1.1.1 Adult
cork
Griffiths
Hohlrieder
Hohlrieder1
Idrees
Joshi
porhomayon
quinn
swann
Subtotal (95% CI)
LMA
ETT
Events Total Events Total Weight
4
27
63
16
12
31
25
16
10
22
57
100
50
50
174
157
50
30
690
6
28
17
2
3
43
12
11
23
22
59
100
50
50
207
157
50
30
725
6.1%
8.4%
8.6%
5.8%
6.4%
9.0%
8.4%
7.9%
7.1%
68.0%
Odds Ratio
M-H, Random, 95% CI
Odds Ratio
M-H, Random, 95% CI
0.59 [0.14, 2.48]
1.00 [0.48, 2.07]
8.31 [4.29, 16.10]
11.29 [2.44, 52.38]
4.95 [1.30, 18.81]
0.83 [0.49, 1.38]
2.29 [1.11, 4.74]
1.67 [0.68, 4.08]
0.15 [0.05, 0.47]
1.69 [0.76, 3.75]
145
204
Total events
Heterogeneity: Tau² = 1.22; Chi² = 60.13, df = 8 (P < 0.00001); I² = 87%
Test for overall effect: Z = 1.29 (P = 0.20)
1.1.2 Pediatric
Doksrod
Gul
Gulati
Klockgether
Patel
Subtotal (95% CI)
36
4
6
38
1
69
40
40
50
30
229
37
4
7
24
0
62
40
40
50
30
222
8.5%
6.0%
6.9%
8.0%
2.4%
32.0%
0.74 [0.37, 1.47]
1.00 [0.23, 4.31]
0.83 [0.25, 2.74]
3.43 [1.46, 8.06]
3.10 [0.12, 79.23]
1.30 [0.61, 2.76]
72
85
Total events
Heterogeneity: Tau² = 0.36; Chi² = 8.45, df = 4 (P = 0.08); I² = 53%
Test for overall effect: Z = 0.67 (P = 0.50)
Total (95% CI)
919
947 100.0%
217
289
Total events
Heterogeneity: Tau² = 0.92; Chi² = 69.58, df = 13 (P < 0.00001); I² = 81%
Test for overall effect: Z = 1.48 (P = 0.14)
Test for subgroup differences: Chi² = 0.22, df = 1 (P = 0.64), I² = 0%
1.56 [0.87, 2.79]
0.01
0.1
1
LMA ETT
10
100
The graph favors ETT with less PONV.
but failed to show sufficient independent significance
to be included in the final models. But we continue
to see investigators including PONV as a variable
outcome difference between LMA and ETT. Two
prospective randomized control trials (RCT) by
Holhreidner reported statistically significant reduction
of PONV with the use of Pro-Seal LMA7,8. A recent
meta-analysis of RCTs in 2010 by Yu9 looked at the
risk of airway complications between the LMA and
ETT. Since the primary goal of Yu study was to look at
the airway complications, he failed to show statistical
significance in the incidence of PONV between the two
devices. Additionally, pediatric studies were excluded
due to differences in airway anatomy between adult
and children. This systematic review and meta-analysis
includes 14 total studies focusing on the incidence
of PONV comparing the different airway devices
including ETT and LMA. Overall, no statistically
significant difference was noted between airway
devices, although a trend towards higher incidence was
noted with the use of LMA group. Subgroup analysis
included only children and adult, showed similar trend
with stronger association in adult patients.
Compared with previously meta-analysis by Yu9,
we included 3 newer studies10-12 and 5 pediatric RCTs1317
. Therefore, our final analysis was more reliable. Of
the studies included, only the four by Holhreider7,8,
Quinn, Idrees and Klockgether-Radke14,18,19 showed a
M.E.J. ANESTH 23 (1), 2015
14
Porhomay on Jahan et. al
Fig. 3
0
SE(log[OR])
0.5
1
1.5
2
0.01
OR
0.1
1
10
100
Subgroups
Adult
Pediatric
statistically significant reduction in PONV with LMA.
Of note, the studies by Holhreider7 were conducted
with Pro-Seal LMA and universal oro-pharyngeal
tube placement with gastric decompression. Therefore
gastric decompression may have a role in preventing
PONV.
The study by Joshi, Swann, Doksrod and
Cork15,20,21 indicated higher PONV with the use of
ETT. One hypothesis leading to the difference in the
incidence of PONV between the airway devices may
be related to greater stimulation with the use of ETT
requiring higher doses of anesthetics and opioids3 when
compared to the LMA group6. Opioids and volatile
anesthetics have also a role in the development of
PONV with a dose dependent effect on the development
of PONV. Alteration in barometric pressure was
demonstrated by Nader et al22 when LMA was used
in comparison to ETT. Although the authors of that
article did not demonstrate a statistically significant
difference in PONV between the ETT and LMA, they
showed a higher trend of PONV in the LMA group.
This study was underpowered and additional trials are
necessary to address this hypothesis.
Limitations
Due to nature of meta-analysis, results were
analyzed from wide variety of RCTs with differing
anesthetic techniques, types of surgery, anesthesiologist
experience, various types of LMA, and time when
outcome was measurement. Heterogeneity was high
due to different anesthetic techniques23, type of surgeries
and heterogeneous population. However, with RCT
there was standardization of anesthetic techniques
between two groups to minimize confounding factors.
Those without standardization between two groups
were excluded from the trial. Despite standardization
of anesthetic techniques, there were differences in
duration of anesthesia and intra-operative opioid
usage. There were statistically significant differences
Endotracheal tube vs LMA for PONV
in patient selection as well as type of procedure within
some of the RCTs. Additionally; patient Characteristics
relevant to the risk of PONV was not always reported.
Consistent with previously performed metaanalysis9 studying the same outcome, we were able to
identify only a limited number of studies addressing
the influence of airway device on PONV. Furthermore,
many of the RCTs had small sample sizes limiting
reliability in concluding the incidence PONV between
the two groups. Furthermore, two large retrospective
studies24,25 were identified, but were not included in
the final analysis due to high degree of variability in
anesthetic techniques.
15
Conclusion
Further research and additional randomized
controlled trials are needed to precisely identify the
influence of airway device on PONV. These trials
should provide essential information for the design,
conduct, and presentation of these studies. When
comparing group, comparability should be based on
well-proven risk factors. And lastly, interpretation of
results should take into account the study hypothesis,
sources of potential bias or imprecision, and the
difficulties associated with multiplicity of analysis and
outcome.
M.E.J. ANESTH 23 (1), 2015
16
Porhomay on Jahan et. al
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SCIENTIFIC ARTICLES
Renal Protection in the Cardiac Surgery
Patient: Peri-Operative Sodium Bicarbonate
Infusion (POSBI) or Not?
Hassan H. Amhaz*, Deepak Gupta**,
Larry Manders**, George McKelvey***, Marc S. Orlewicz**
and R omeo N. K addoum **
Abstract
Background: Acute renal failure following cardiac surgery is not uncommon and carries
a high level of morbidity and mortality. The aim of our study was to determine whether perioperative sodium bicarbonate infusion (POSBI) would decrease acute kidney injury in cardiac
surgery patients and improve post-operative outcomes.
Methods: A retrospective analysis of 318 cardiac surgery patients from 2008-2011 was
performed. Clinical parameters were compared in patients receiving POSBI versus sodium
chloride. Serum creatinine levels were measured in the first five post-operative days. The primary
outcome measured was the number of patients developing post-operative renal injury. Secondary
outcomes included three-month mortality, intensive care unit and hospital length of stay.
Results: Patients given POSBI showed no significant differences compared to the normal
saline cohort in regards to increases in serum creatinine [<25% rise in Cr: 93% vs 94%; >25% rise
in Cr: 6% vs 6%; >50% rise in Cr: 1% vs 1%; >100% rise in Cr: 1% vs 0%, all with p-value >0.99].
There were fewer patients with AKIN stage 1 renal failure receiving POSBI [8% vs 28%, p = 0.02]
however there was no difference between POSBI and sodium chloride cohorts in AKIN stages
2 and 3 renal failure. Mortality, duration of hospitalization and ICU stay were not statistically
significant.
Conclusions: POSBI resulted in fewer patients developing AKIN stage 1 renal failure.
Despite this, there appears to be little benefit in the prevention of acute kidney injury after 48 hours
or mortality reduction in cardiac surgery patients.
*MD, MS.
**MD.
***PhD.
Affiliation: Department of Anesthesiology, Wayne State University, Detroit Medical Center; Detroit, Michigan, United
States.
Corresponding author: Romeo N. Kaddoum, MD. Assistant Professor; Wayne State University, Detroit Medical Center;
3990 John R, Rm 2901; 2-Hudson, Detroit, MI 48201, United States. Office: 1-313-745-7233, Fax: 1-313-993-3889. E-mail:
[email protected]
17
M.E.J. ANESTH 23 (1), 2015
18
Introduction
Acute kidney injury (AKI) in patients undergoing
cardiac surgery is a common and serious occurrence
with an incidence ranging between 3% and 50% of
patients and is associated with significant morbidity
and mortality rates as high as 38%1,2,3. Of these patients,
1% will require dialysis, with associated mortality
rates in this group as high as 60%-70%4,5,6. There
are numerous factors that contribute to postoperative
renal failure, including ischemia, drugs, generation of
reactive oxygen free radicals, hemolysis and activation
of inflammatory and complement pathways1,4,6.
Additionally, numerous independent risk factors have
been found to be predictive of post-operative AKI
following cardiac surgery4,6-10. Although some studies
have shown sodium bicarbonate to ameliorate postoperative kidney injury, its use in cardiac surgery
remains controversial. We present a retrospective
multi-centered study of 318 patients undergoing
cardiac surgery to evaluate whether peri-operative
sodium bicarbonate infusion (POSBI) would reduce
post-operative AKI.
Material and Methods
After institutional review board approval (Wayne
State University IRB committee, IRB#065611M1E),
a retrospective analysis of 318 post-cardiac surgery
patients, from two institutions within our medical
center over a four-year period (2008-2011) was
performed. Biochemical and clinical parameters
were compared in patients receiving POSBI versus
sodium chloride. Inclusion and exclusion criteria of
the study are listed in Table 1. Serum creatinine levels
were measured in the first five post-operative days in
patients who received sodium bicarbonate and those
receiving sodium chloride.
Starting in 2009, our medical center instituted
a sodium bicarbonate infusion protocol for patients
undergoing cardiac surgery due to new literature
showing possible benefit from POSBI. Previously,
patients received normal saline at a rate of 1-1.5cc/
kg/hr from the start of surgery for a total of 24 hours.
The sodium bicarbonate infusion protocol simply
added 3 Amps (150mEq) of sodium bicarbonate in 1
Romeo Kaddoum et. al
liter of D5W. The protocol was to infuse the sodium
bicarbonate at a rate of 1-1.5cc/kg/hr starting from the
beginning of surgery for a total of 24 hours as normal
saline was previously done.
Table 1
Study Inclusion and Exclusion Criteria*
Inclusion criteria
Exclusion criteria
Age 18-80
End Stage Renal Disease
(ESRD)
CABG +/- valve surgery,
intracardiac surgery
Emergency cardiac surgery
Redo cardiac surgery
Use of intra-aortic balloon pump
(IABP)
Pre-operative plasma
creatinine concentration
>1.3 mg/dL
Currently enrolled in another
study
NYHA class III/IV
Known blood-borne Infectious
disease
Left Ventricle EF <35%
Chronic corticosteroid therapy
* Cardiac surgery patients having one or more of the listed
criteria
To determine a sample size for the study a
Chi-squared power analysis was chosen to obtain an
alpha error probability of 0.05 and a power of 0.95.
A sample size of 300 patients (at least 150 in each
group; effect size d=0.2 small -medium) was deemed
to give the study sufficient power. Repeated Measures
Analysis of Variance (ANOVA) and T-tests (Unpaired;
two sided) were used where appropriate to measure
continuous variables between the 2 patient groups
with post hoc differences measured using the StudentNeuman-Keuls test. Comparisons between study
groups on proportional differences were examined
using a non-parametric Fisher’s Exact Chi-square test,
when applied to 2X2 tables. A p-value of <0.05 was
considered significant.
Of note, the 318 patients that were included in
our study were patients of only two cardiothoracic
surgeons who used sodium bicarbonate consistently
following the protocol implementation in 2009. Hence,
when data before 2009 was obtained for patients not
receiving POSBI we used the patients from only these
two surgeons. For this reason, the 318 cardiac surgery
patients only represent a smaller fraction of total
cardiac surgery patients at our institution. This was
done to minimize surgeon bias and to exclude surgeons
Renal Protection in the Cardiac Surgery Patient
who did not consistently use POSBI.
The primary outcome measured was the number
of patients who developed post-operative renal
injury following cardiac surgery. Kidney injury was
defined into four categories which were based on
baseline serum creatinine levels to those on the fifth
postoperative day: serum creatinine increases <25%,
an increase greater than 25%, greater than 50%, and
greater than 100% from baseline. The proportion of
kidney injury between these groups as defined by
the AKIN criteria was also compared, Table 2. Other
Characteristics
19
secondary outcomes that were measured included
intensive care unit (ICU) and hospital length of stay,
and three-month mortality rates.
Table 2
Acute Kidney Injury Network (AKIN) Classification Criteria
Classes
Serum Cr (sCr) Criteria
1
sCr increase x 1.5 - 2 (50%-100%) or sCr
increase >0.3 mg/dL from baseline
2
sCr increase x 2 - 3 (101%-200%) from baseline
3
sCr increase x 3 (>201%) or sCr >4 mg/dL with
increase >0.5 mg/dL
Table 3
Patient pre-operative characteristics
Sodium
Bicarbonate
Demographic data
Age, yr, mean (SD)
Gender
Males, n (%)
Females, n (%)
Race
African Americans, n (%)
Non - African Americans, n (%)
Comorbidities
Hypertension, n (%)
Chronic kidney disease, n (%)
Peripheral vascular disease, n (%)
Hypercholesterolemia, n (%)
Chronic obstructive pulmonary disease, n (%)
Diabetes Mellitus, n (%)
Left ventricular ejection fraction, percent (SD)
Hemodialysis, n (%)
Medications
Beta-blockers, n (%)
ACE inhibitors or angiotensin blockers, n (%)
HMG-CoA reductase inhibitor, n (%)
Pre-operative creatinine levels
Cr <1.0, n (%)
1.0 <Cr <1.3, n (%)
1.4 <Cr <1.6, n (%)
1.7 <Cr <1.9, n (%)
Cr >2, n (%)
Pre-operative Ejection Fraction (EF)
EF <15%, n (%)
15% <EF <25%, n (%)
25% <EF <35%, n (%)
35% <EF <45%, n (%)
45% <EF <55%, n (%)
EF >55%, n (%)
Sodium Chloride
p-value
62 (11)
63 (12)
0.56
0.01
119 (68)
56 (32)
77 (54)
66 (46)
118 (67)
57 (33)
103 (72)
40 (28)
158 (90)
47 (27)
28 (16)
146 (83)
57 (33)
77 (44)
49 (15)
13 (7)
133 (93)
38 (27)
40 (28)
114 (80)
39 (27)
65 (45)
49 (15)
17 (12)
0.42
>0.99
0.01
0.47
0.33
0.82
0.83
0.18
137 (78)
86 (49)
144 (82)
86 (60)
83 (58)
96 (67)
0.0005
0.12
0.003
0.17
60 (34)
68 (39)
22 (13)
3 (2)
21 (12)
56 (38)
48 (33)
11 (8)
7 (5)
23 (16)
0 (0)
16 (9)
16 (9)
21 (13)
34 (20)
90 (49)
3 (2)
11 (7)
15 (10)
21 (15)
29 (20)
73 (48)
0.39
0.47
M.E.J. ANESTH 23 (1), 2015
20
Romeo Kaddoum et. al
Results
Three hundred and eighteen patients underwent
cardiac surgery at our institutions from 2008 thru 2011.
There were 175 patients who received POSBI and 143
patients received only sodium chloride. Preoperative
patient characteristics of the study are listed in Table
3. Patient characteristics were fairly matched between
POSBI and normal saline groups with the exception
that recipients of POSBI were more likely to be male
and be on β-blockers and statins. However, more
peripheral vascular disease was seen in patients
receiving normal saline. New institutional mandates
regarding patients receiving preoperative β-blockers,
around the same time the sodium bicarbonate infusion
protocol was instituted, is a likely reason for why the
sodium bicarbonate group received more β-blockers.
Regarding the surgery type, no significant differences
were seen between groups with the exception that
more patients who underwent mitral valve repair
received POSBI. However, when considering all valve
surgeries combined, there was no significant difference
seen between the POSBI and normal saline groups.
Although aortic clamp times did not differ between
the groups, cardiopulmonary bypass (CPB) time
was slightly lower in the sodium bicarbonate group,
Table 4.
Serum creatinine levels measured on the fifth
post-operative compared to baseline were divided into
four categories: <25%, >25%, >50%, and >100%.
There were no significant differences between patients
receiving POSBI versus normal saline, Table 5. When
renal dysfunction was defined using the AKIN criteria,
creatinine levels 48 hours post-operatively compared
to baseline, patients receiving POSBI had fewer
patients with AKIN stage 1 renal failure. However, no
significant differences were observed between the two
groups in regards to AKIN stage 2 and 3, Table 6. The
Table 4
Type of surgery and patient intra-operative characteristics
Characteristics
Sodium Bicarbonate
Sodium Chloride
Cardiac surgery
p-value
0.08
Valve surgery only, n (%)
58 (33)
41 (27)
0.29
Aortic valve replacement, n (%)
25 (14)
18 (12)
0.57
Mitral valve replacement, n (%)
14 (8)
16 (10)
0.39
Mitral valve repair, n (%)
12 (7)
3 (2)
0.04
Double valve surgery, n (%)
7 (4)
4 (3)
0.52
100 (57)
80 (54)
0.56
17 (9)
22 (14)
0.16
Cardiopulmonary bypass time, mins (SD)
106 (38)
119 (57)
0.02
Aortic clamp time, mins (SD)
86 (32)
93 (52)
0.16
CABG only, n (%)
Valve and CABG surgery, n (%)
Table 5
Post-operative sCr changes in patients receiving POSBI vs Normal Saline
Sodium Bicarbonate
Normal Saline
p-value
<25% sCr Rise
163 (93%)
134 (94%)
>0.99
>25% sCr Rise
10 (6%)
8 (6%)
>0.99
>50% sCr Rise
1 (1%)
1 (1%)
>0.99
>100% sCr Rise
1 (1%)
0 (0%)
>0.99
175
143
Post-operative sCr change
Total
Renal Protection in the Cardiac Surgery Patient
21
Table 6
Post-operative AKIN stage in patients receiving POSBI vs Normal Saline
Sodium Bicarbonate
Normal Saline
p-value
148 (85%)
110 (62%)
0.09
AKIN Stage 1
14 (8%)
24 (28%)
0.02
AKIN Stage 2
7 (4%)
5 (3%)
>0.99
AKIN Stage 3
6 (3%)
4 (3%)
>0.99
175
143
Post-operative AKIN stage
Normal
Total
Table 7
Secondary outcomes measured
Secondary outcomes
Sodium Bicarbonate
p-value
Normal Saline
Mortality, n (%)
27 (15)
25 (16)
0.76
Intensive Care Unit stay, days (SD)
9.2 (8.6)
10 (9.2)
0.39
Duration of hospitalization, days (SD)
10.7 (9.9)
12 (8.7)
0.22
secondary outcomes that were measured in the study
included 30-day mortality, length of hospitalization
and ICU stay, Table 7. Our average ICU length of stay
was higher than other studies secondary to several
patients in each cohort with ICU stays longer than
one month. However, total hospital length of stay was
consistent with other published studies1. No significant
differences were seen between groups in regards to 30day mortality, length of hospitalization or ICU stay.
Discussion
Acute kidney injury (AKI) is a common and
serious complication following cardiac surgery
with an incidence ranging from 3% to 50%1,7. AKI
following cardiac surgery carries a significant cost
burden and is an independent predictor of mortality.
Pre-operative serum creatinine levels are the most
important predictive factor for post-operative AKI7,10.
Approximately 10% to 20% of patients with baseline
creatinine levels between 2mg/dL and 4mg/dL will
require dialysis and those with creatinine levels
greater than 4mg/dL will require dialysis 30% of the
time7. Patients requiring post-operative dialysis have
a mortality rate of 60-70%. To date, no treatment
including peri-operative sodium bicarbonate infusion
has been shown to be effective in preventing renal
failure after cardiac surgery1,7,9.
Only a few prospective randomized control trials
have been done to evaluate the role of sodium bicarbonate
or other adjuvant therapies (N-acetylcysteine and
fenoldopam) in the prevention of acute kidney injury
following cardiac surgery. Haase et al1, conducted
a pilot double-blinded, randomized control trial of
100 cardiac surgery patients. The patients underwent
treatment to see if POSBI can attenuate postoperative
increases in serum creatinine. Their primary outcome
was reaching a serum creatinine of >25% above
baseline within the first five postoperative days. They
found a statistical significance using bicarbonate in
patients with creatinine increases >25% however there
was no difference in patients with creatinine increases
of either >50% and >100%. There was no statistical
significance found when acute kidney injury was
defined by the AKIN criteria. No mortality benefit
was seen in patients receiving POSBI. Furthermore,
other large RCT studies looking at N-acetylcysteine,
fenoldopam and statins failed to show a clear benefit
in postoperative renal protection.
Post-operative renal failure is multifactorial:
ischemia-reperfusion injury seen from hemodynamic
instability and aortic cross clamping, low cardiac
output states, loss of pulsatile flow while on bypass,
nephrotoxic drugs, generation of reactive oxygen
free radicals, and the activation of neutrophils,
inflammatory and complement pathways7,10,11.
Furthermore, mechanical and shear forces on red blood
cells seen in cardiopulmonary bypass is associated
with levels of free hemoglobin which exceeds the
capacity of haptoglobin. Thus, longer bypass times are
M.E.J. ANESTH 23 (1), 2015
22
Romeo Kaddoum et. al
Table 8
Major Risk Factors for Developing Acute Kidney Injury
Patient Risk Factors
Surgical Risk Factors
Age
Pre-operative use of an IABP
Female
CABG, Valve or combined procedures
Pre-operative serum creatinine
CPB duration
EF <35%
Hemodilution during CPB
Insulin Dependent Diabetes Mellitus
Emergency surgery
Chronic obstructive pulmonary disease
associated with increased free hemoglobin exposure
and can theoretically worsen kidney injury. Under
acidic conditions increased free iron release from
hemoglobin occurs which catalyzes the Haber-Weiss
reaction promoting hydroxyl radical formation. The
alkalinizing effects of sodium bicarbonate on the urine
are thought to provide some degree of renal protection
due to the reduction in hydroxyl radical formation
from free iron and tubular cast formation1,7,10,11.
study showed that 1.1% of these patients had AKI after
surgery, and the mortality in this group was 63.7%. The
end result of the study was that cardiac surgery was an
independent risk factor for developing AKI, and was
associated with a high mortality rate. The rate of AKI
and AKI-related mortality could not be explained by
comorbidities alone12. In addition to cardiac surgery,
cardiopulmonary bypass itself was found to be an
independent risk factor for the development of AKI6.
Classification of renal injury, as with AKIN,
does not provide insight into the nature of the injury.
Typically, the window for therapeutic intervention has
passed once serum creatinine levels begin to rise4. As
a result, biomarkers for the early detection of renal
injury have been sought after. Neutrophil gelatinaseassociated lipocalin (NGAL), cystatin C, IL-18,
kidney injury molecule-1 (KIM-1) and many more
have all been studied1,4,7,10. Urinary NGAL levels are
virtually undetectable in patients with normal kidney
function and serve as a marker of oxidative stress.
Urinary NGAL levels greater than 100ng/mL two
hours following cardiopulmonary bypass predict acute
kidney injury (sensitivity, 82%; specificity, 90%); much
higher than other studied biomarkers1,10. In a study
by Haase et al1, the use of sodium bicarbonate does
not appear enough to thwart the acute kidney injury
seen following cardiac surgery despite a significant
attenuation in urinary NGAL.
Although there appears to be a beneficial effect
of POSBI within the literature there are several
important factors that must be considered. First, the
definition of “AKI”, an increase in serum creatinine
>25%, is quite liberal. This equates to less than a
0.1mg/dL/day increase in serum creatinine over the
first five post-operative days5. Mehta and colleagues13
convened in an international meeting to develop a
uniform system for the diagnosis and classification of
acute kidney injury, which is formally known as the
AKIN criteria, Table 2. When AKI is defined as an
increase in serum creatinine >50%, no difference is
found between POSBI and normal saline groups seen
in the prospective pilot study1,5. Regardless of stage, no
significance was found when the AKIN criteria were
used5. Although we found a lower incidence of AKIN
stage 1 renal failure in patients receiving POSBI,
it appears that by the fifth post-operative day these
benefits are no longer seen.
Several risk factors have been identified that
are associated with AKI in cardiac surgery patients,
Table 84,6-10. Chertow et al12, conducted a large cohort
study of 42,273 patients undergoing coronary artery
bypass graft (CABG) or valvular heart surgery. This
The use of sodium bicarbonate and its resulting
alkalemia is not benign. Mortality, CO2 retention and
associated hypoxia from impaired oxygen delivery are
all potential complications of POSBI5. Haase et al1,
showed considerable group differences from baseline
Renal Protection in the Cardiac Surgery Patient
to 24 hours post-operatively in plasma bicarbonate
concentration, base excess, and pH levels. Therefore,
careful monitoring of plasma pH and bicarbonate levels
would be warranted in instances where large amounts
of sodium bicarbonate are being administered.
Our study has several limitations that should be
noted. Although retrospective, pre-operative patient
characteristics between cohorts were fairly matched
however if we were to match for every characteristic
the overall numbers would be low and the study
underpowered. Additionally, we did not include
patients with new-onset hemodialysis requirements
following cardiac surgery. Numerous patients have
multiple uncontrolled comorbidities with baseline
renal dysfunction that may have contributed to the
extended ICU length of stay compared to other studies
however overall length of hospitalization remained
consistent1.
23
Conclusion
We present a retrospective multicenter study
comparing the use of POSBI to that of sodium chloride
in patients undergoing cardiac surgery to prevent postoperative renal failure. Despite a lower incidence of
patients developing AKIN stage 1 renal failure in the
POSBI cohort, the benefit does not persist through the
fifth post-operative day. With no reduction in mortality,
hospital or ICU length of stay, there currently appears
to be no benefit with the use of POSBI in cardiac
surgery patients.
Acknowledgments
Dimitrios Apostolou, MD - cardiothoracic
surgeon of patients in study
Ali Kafi, MD - cardiothoracic surgeon of patients
in study
M.E.J. ANESTH 23 (1), 2015
24
Romeo Kaddoum et. al
References
1. Haase M, Haase-Fielitz A, Bellomo R, et al: Sodium bicarbonate
to prevent increases in serum creatinine after cardiac surgery: a pilot
double-blind, randomized controlled trial. Crit Care Med; 2009, Jan;
37(1):39-47.
2. Adabag AS, Ishani A, Bloomfield HE, Ngo AK, Wilt TJ: Efficacy
of N-acetylcysteine in preventing renal injury after heart surgery:
a systematic review of randomized trials. Eur Heart J; 2009, Aug;
30(15):1910-7.
3. Liakopoulos OJ, Choi YH, Haldenwang PL, et al: Impact of
preoperative statin therapy on adverse postoperative outcomes in
patients undergoing cardiac surgery: a meta-analysis of over 30,000
patients. Eur Heart J; 2008, Jun; 29(12):1548-59.
4. Coleman MD, Shaefi S, Sladen RN: Preventing acute kidney injury
after cardiac surgery. Curr Opin Anaesthesiol; 2011, Feb; 24(1):706.
5. Weisberg L: Sodium bicarbonate for renal protection after heart
surgery: let’s wait and see. Crit Care Med; 2009, Jan; 37(1):333-4.
6. Stallwood M, Grayson A, Mills K, Scawn N: Acute renal
failure in coronary artery bypass surgery: independent effect of
cardiopulmonary bypass. Ann Thorac Surg; 2004, Mar; 77(3):96872.
7. Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A:
Acute kidney injury: a relevant complication after cardiac surgery.
Ann Thorac Surg; 2011, Oct; 92(4):1539-47. Epub 2011, Aug 27.
Review.
8. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill
WW: Acute renal failure after coronary intervention: incidence,
risk factors, and relationship to mortality. Am J Med; 1997, Nov;
103(5):368-75.
9. Ranucci M, Soro G, Barzaghi N, et al: Fenoldopam prophylaxis
of postoperative acute renal failure in high-risk cardiac surgery
patients. Ann Thorac Surg; 2004, Oct; 78(4):1332-7; discussion
1337-8.
10.Kumar A, Suneja M. Cardiopulmonary bypass-assicated acute
kidney injury. Anesthesiology; 2011, Apr; 114(4):964-70.
11.Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R:
Cardiopulmonary bypass-associated acute kidney injury: a pigment
nephropathy? Contrib Nephrol; 2007, 156:340-53.
12.Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J:
Independent association between acute renal failure and mortality
following cardiac surgery. Am J Med; 1998, Apr; 104(4):343-8.
13.Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury
Network. Acute Kidney Injury Network: report of an initiative
to improve outcomes in acute kidney injury. Crit Care; 2007,
11(2):R31.
Effect of ultrasound-guided subsartorial
approach for saphenous nerve block in
cases with saphenous nerve entrapment
in adductor canal for controlling
chronic knee pain.
Arman Taheri*, Maryam Hatami**, Majid Dashti***,
Alireza Khajehnasiri**** and Mahsa Ghajarzadeh*****
Abstract
Background: Saphenous nerve neuropathy is one of the causes of chronic pain of the knee.
Blockade of saphenous nerve under sonographich guide has been used for controlling pain
in recent years. The goal of this study was to evaluate the effect of saphenous nerve block for
controlling pain in patients with chronic knee pain.
Method: Thirty five patients with chronic knee pain referred to Amir Alam hospital during
June 2012-June 2013 were enrolled in this study. Under sonographic approach, subsartorial
blockade of saphenous nerve conducted and patients were followed up for 3 months after
treatment. Demographic data, ASA (American Society of Anesthesiologists) category, weight,
height, complications of intervention and pain scores were recorded.
Results: In 54%, the NRS was zero 30 minutes after intervention. In one patient (2.8%) all
NRSs were 0 after intervention. We observed no sensory dysfunction in enrolled cases.
Conclusion: the result of current study showed that ultrasound guided subsartorial approach
is moderately effective in blockade of saphenous nerve in cases with saphenous nerve entrapment
in adductor canal for controlling chronic knee pain.
Keywords: ultrasound-guided block, knee pain, pain management.
Introduction
Saphenous nerve is a terminal branch of the femoral nerve which innervates medial,
anteromedial, and posteromedial aspects of the lower extremity1. Saphenous nerve entrapment is
one of the causes of chronic knee pain (especially at medial site) which could mimic orthopedic
disorders of the knee or L4 radiculopathy2.
*
FIPP, Assistant professor of Anesthesiology, Iran section of World Institute of Pain Director, Chairman of Tehran
University of Medical Science Fellowship Program, Department of Anesthesia & Pain Management Amiralam Hospital,
Tehran University of Medical sciences, Tehran, Iran.
**
Pain fellowship, Department of Anesthesia & Pain Management, Tehran University of Medical Sciences, Tehran, Iran.
*** Cardiac anesthesia fellowship, department of anesthesia, Shahid rajaee hospital, Tehran University of Medical Sciences,
Tehran, Iran.
****Assistant Professor of Anesthesiology and Pain, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
*****Brain and Spinal Injury Repair Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Corresponding author: Maryam Hatami MD. E-mail: [email protected]
25
M.E.J. ANESTH 23 (1), 2015
26
Maryam Hatami et. al
Blockage of saphenous nerve could be applied
for procedures on the medial aspect of the distal leg3.
Different approaches could be applied for blockage of
saphenous nerve such as perifemoral, trans-sartorial,
block at the medial femoral condoyle, below-the-knee
field block, and blockade at the level of the medial
malleolus. Benzon et al found that trans-sartorial
approach was the best approach for complete sensory
blockade4.
located. After negative aspiration, 10 cc Bupivacaine
25% and 40 mg methyl prednisolone sulphate under
the sonography guidance were injected. Maximal NRS
was recorded after 30 minutes, one week, one month
and three months after intervention. The Numeric
Rating Scale (NRS) is a 10-point scale for patient selfreporting of pain. Zero means ‘No pain’ and 10 means
‘Worst possible pain’.
In recent years, blockade of the saphenous nerve
under the guidance of ultrasound has been considered
as an acceptable approach. Tsai et al reviewed the
medical records of 39 cases who underwent subsartorial
saphenous nerve block for lower extremity surgery
and found that this technique was successful in 77%
of cases5.
Demographic data, ASA, weight, height, and
complication of intervention were recorded.
The aim of the study is to evaluate effect of
saphenous nerve block in cases with saphenous nerve
entrapment in adductor canal for controlling chronic
knee pain.
Method and material
In this cross sectional study which conducted
between June 2012-June 2013 in Amir Alam hospital
(affiliated hospital of Tehran university of medical
sciences), patients with chronic knee pain (pain
more than 3 months), Numeric rating scale ≥7 and
tenderness in adductor canal were enrolled. Patients
with previous surgery of lower extremities, recent
trauma to the knee, consumption of anti-coagulant
agents, drug abuse, severe osteoarthritis (according to
radiologic findings), allergy to local anesthetic agents,
psychologic disorders, and active infection were
excluded.
For blockade, patients were placed in supine
position, with the lower extremity rotated externally
at the hip, and the knee slightly flexed. The midthigh area was prepped and 8-12 MHz linear probe
was placed at the proximal aspect of the leg (10 cm
proximal to medial condyle) to obtain a cross-sectional
view of the femoral artery in short-axis. The saphenous
nerve was defined as a highly hyperechoic structure
medial to femoral artery. The needle was inserted
lateral to femoral artery then proceeded to the medial
aspect of the artery where the saphenous nerve was
Official approval from ethics committee of
TUMS was obtained for the study and all the patients
gave informed consent.
Statistical analyses were performed with SPSS
software version 18.0 (Statistical Product and Service
Solutions, SSPS Inc., Chicago). Results are presented
as mean ± SDs, and frequencies. The Student’s t test
was used for continuous variables, and the Pearson x2
test with Fisher’s exact test was applied for categorical
variables. Repeated measure ANOVA was used to
compare mean NRS during study period. P value <0.05
was considered statistically significant.
Results
Thirty five cases enrolled in this study. Mean
age of all cases was 54.6 ± 12.8 years. Twenty four
cases (68.6%) were female and 11 (31.4%) were male.
Twenty there (65.7%), 9 (25.7%), and 3 (8.6%) patients
were ASA class I,II, and III respectively. Only the left
knew was affected in 9 patients (25.7%), only the right
knee was affected in 11 patients (31.4%) while both
knees were affected in 15 patients (42.9%).
Mean BMI, and pre-intervention NRS were 25.1
± 2.3 (kg/m2) and 8 ± 0.8 (7-10) respectively.
Repeated measure ANOVA showed that mean
NRS significantly decreased throughout the evaluation
time (p <0.001) (Table 1).
In nineteen patients (54%), the NRS was zero at
30 minutes after intervention (Table 2).
Only one patient (2.8%) had a NRS of 0
throughout the study period. We observed no sensory
dysfunction in in all enrolled cases.
saphenous nerve block in knee pain
27
Table 1
(mean ± SD) NRS during evaluation time
NRS before intervention
8 ± 0.8
NRS after 30
minutes
NRS after one
week
NRS after one
month
NRS after 3
months
P value
0.7 ± 0.8
1.5 ± 1.3
2.2 ± 1.8
5.2 ± 2.6
<0.001
Table 2
Success rates during follow up
Success rate
Reduction of NRS scores to 0 after 30 minutes
19 (54.3%)
Reduction of NRS scores to 0 after one week
7(20%)
Reduction of NRS scores to 0 after one month
4(11.4%)
Reduction of NRS scores to 0 after 3 months
3 (8.6%)
Discussion
The result of this study showed that ultrasoundguided sub-sartorial blockade of saphenous nerve in
cases with saphenous nerve entrapment in adductor
canal is a successful method for controlling pain during
post intervention period in patients with chronic knee
pain.
We observed that pain NRS became zero 30
minutes after intervention in 54% of cases and pain
eradicated in 2.8% of patients who suffer from chronic
knee pain. However, this success rate is lower that the
rates in previous studies.
Romanoff et al evaluated 30 patients with
saphenous nerve entrapment in adductor canal who
underwent series of nerve blockade (mean 1.9 of
blockade). They reported VAS score of 6.4 at baseline
and 2.8 at the end of the study. Eighty seven of cases
had improved at the final stage of the study6.
Their findings along with our results show that
saphenous nerve blockade in cases with saphenous
nerve entrapment in adductor canal is effective for
controlling pain.
In Tsai et al study the success rate of saphenous
nerve blockade in cases who underwent lower
extremity surgery was 77% and in Benzon et al study
the success rate was 70%4-5. In their study saphenous
nerve block was performed in conducted for patients
who were candidate for menisectomy.
In another studyby Manickam, et al, blockade
of the saphenous nerve at the distal part of adductor
canal for patients who underwent ankle or foot surgery
resulted in 100% success rate7.
The lower success rate in the current study could
be attributed due to our first experiment in doing subsartorial blockade of saphenous nerve.
During follow up we found that NRS decreased
significantly and then increased but the mean score at
the end of follow up was lower than pre intervention
score. It could show that this approach is useful for
reducing pain for a short time and it is not applicable
for eradicating pain. May be continuous blockades
or other methods such as radio frequency (RF) is
necessary for eradicating pain in cases with chronic
knee pain.
Chronic knee pain is a disabling condition
which affects quality of life of the patients and
limits daily activity8. Different underlying diseases
such as osteoarthritis, rheumatoid arthritis, bursitis,
chondromalacia patella, baker’s cyst and jumper’s
knee are among common causes of chronic knee pain.
This study has some limitations. First, the sample
size was low and the follow up period was short. Larger
studies with long follow up periods are recommended.
Conclusion: The results of the current study
showed that ultrasound guided subsartorial approach
is moderately effective in blockade of saphenous nerve
in cases with saphenous nerve entrapment in adductor
canal for controlling chronic knee pain.
M.E.J. ANESTH 23 (1), 2015
28
Maryam Hatami et. al
References
1.Horn J-L, Pitsch T, Salinas F, Benninger B: Anatomic basis to the
ultrasound-guided approach for saphenous nerve blockade. Reg
anesth pain med; 2009, 34(5):486-9.
2.Brad McKechnie D: Saphenous Nerve Entrapment Neuropathy.
Dynamic Chiropractic; May 22, 1995, 13(11):1-3.
3.Akkaya T, Ersan O, Ozkan D, Sahiner Y, Akin M, Gümüş H, et
al: Saphenous nerve block is an effective regional technique for
post-menisectomy pain. Knee Surgery, Sports Traumatology.
Arthroscopy; 2008, 16(9):855-8.
4.Benzon HT, Sharma S, Calimaran A: Comparison of the different
approaches to saphenous nerve block. Anesthesiology; 2005,
102(3):633-8.
5.Tsai PB, Karnwal A, Kakazu C, Tokhner V, Julka IS: Efficacy
of an ultrasound-guided subsartorial approach to saphenous nerve
block: a case series. Can J Anesth; 2010, 57(7):683-8.
6.Romanoff ME, Cory PC, Kalenak A, Keyser GC, Marshall WK:
Saphenous nerve entrapment at the adductor canal. Am J Sports
Med; 1989, 17(4):478-81.
7.Manickam B, Perlas A, Duggan E, Brull R, Chan VW, Ramlogan
R: Feasibility and efficacy of ultrasound-guided block of the
saphenous nerve in the adductor canal. Reg anesth pain med; 2009,
34(6):578-80.
8. Ikeuchi M, Ushida T, Izumi M, Tani T: Percutaneous Radiofrequency
Treatment for Refractory Anteromedial Pain of Osteoarthritic
Knees. Pain Med; 2011, 12(4):546-51.
9. Tsui BC, Özelsel T: Ultrasound-guided transsartorial perifemoral
artery approach for saphenous nerve block. Reg anesth pain med;
2009, 34(2):177-8.
10.Krombach J, Gray AT: Sonography for saphenous nerve block near
the adductor canal. Reg anesth pain med; 2007, 32(4):369-70.
11.Mansour N: Sub-sartorial saphenous nerve block with the aid of
nerve stimulator. Reg anesth; 1992, 18(4):266-8.
12.Bouaziz H, Benhamou D, Narchi P: A new approach for saphenous
nerve block. Reg anesth; 1996, 21(5):490.
13.Gray AT, Collins AB: Ultrasound‐Guided Saphenous Nerve Block.
Reg anesth pain med; 2003, 28(2):148.
Comparison of the effects of oral vs.
peritonsillar infiltration of ketamine
in pain reduction after tonsillectomy:
a Randomized Clinical Trial
Afsaneh Norouzi*, Abolfazl Jafari**,
Hamid Reza Khoddami Vishteh***
and S hahin Fateh ****
Abstract
Background: Although oral ketamine has been used in some cases to reduce pain in children,
the use of this drug to reduce pain after tonsillectomy has not been studied yet.
Methods: This double-blind clinical trial was conducted in 2009 in 92 children who were
aged three to nine years old, met ASA I or II criteria, and were candidate for tonsillectomy. Patients
were divided randomly into two groups. Half an hour before general anesthesia, 5 mg/kg ketamine
mixed in 2 cc/kg apple juice was given to the children in oral ketamine group and 2 cc/kg of apple
juice alone was given to the children in the peritonsillar group. After general anesthesia and three
minutes before surgery 1 cc of 0.9% normal saline in the oral group and 1cc of ketamine (0.5 mg/
kg) in the peritonsillar group was injected to the tonsil bed of patients.
Results: There was no difference between the two groups in terms of sex, age, and weight.
Duration of surgery was significantly shorter in the peritonsillar group (P <0.001) and the severity
of postoperative bleeding was significantly higher in peritonsillar group (P = 0.022). However,
postoperative bleeding recurred in 25 patients (27%) and there was no statistically significant
difference between the two groups. The level of pain in children six hours after surgery according
to CHEOPS criteria was significantly lower in the peritonsillar group (0.9 ± 0.8) than in the oral
group (2.6 ± 1) (P <0.001).
Conclusions: The finding of this study showed that, compared with the peritonsillar
infiltration of ketamine, the use of oral ketamine before general anesthesia was less effective in
reducing postoperative pain of tonsillectomy in children.
Keywords: tonsillectomy, adenotonsillectomy, postoperative pain, ketamine.
*Assistant Professor (MD), Department of Anesthesiology and Intensive Care Medicine, Arak University of Medical
Sciences, Arak, Iran.
**Assistant Professor (MD), Department of Otolaryngology, Arak University of Medical Sciences, Arak, Iran.
*** General Practitioner, Arak University of Medical Sciences, Arak, Iran.
****Assistant Professor (MD), Thoracic surgeon, Department of Surgery, Arak University of Medical Sciences, Arak, Iran.
Corresponding author: Afsaneh Norouzi, Assistant Professor (MD), Department of Anesthesiology and Intensive Care
Medicine, Arak University of Medical Sciences, Arak, Iran. Address: Valiasr hospital, Arak, Markazi province, Iran. Tel:
+989181611365, Fax: +988613137474. E-mail: [email protected], [email protected]
29
M.E.J. ANESTH 23 (1), 2015
30
Afsaneh Norouzi et. al
Introduction
Materials and Methods
Adenotonsillectomy is one of the most
common ear, nose, and throat surgeries in children
and postoperative pain is one of its important
complications. Inadequate control of postoperative
pain leads to different complications such as poor
nutrition, dehydration, sleep disorders, behavioral
changes, nausea, and vomiting1; moreover, it can
increase the length of hospitalization and consequently
increase healthcare costs2. Despite the high prevalence
of pain after tonsillectomy and adenotonsillectomy3, 4
and the presence of different analgesics and assessment
tools for measuring age-related pain5, the choice of
appropriate analgesic to be used after tonsillectomy
operation is still controversial6.
This double-blind clinical trial was conducted
in 2009 on 92 children aged three to nine years old
who were referred to Amir Kabir hospital in Arak
City. Inclusion criteria were: being aged three to nine
years old, meeting ASA I or II criteria, and candidate
for tonsillectomy surgery. Exclusion criteria were: the
presence of an underlying disease, and the presence
of contraindications to the use of ketamine including
upper airway active infection, increased intracranial
pressure, open eyes surgery, and seizures. The study
was approved by the Ethics Committee of the Arak
University of Medical Sciences.
To reduce pain after tonsillectomy in children,
different groups of drugs (oral paracetamol, opioids,
NSAIDs, and local anesthetics) have been studied.
Although paracetamol is a safe and effective analgesic,
when it is used alone it cannot achieve an appropriate
analgesic effect after tonsillectomy7. Opiates may
reduce upper airway tone, suppress the cough reflex,
cause sedation and respiratory depression (especially
in unintended outpatient surgery), and also lead to
postoperative nausea and vomiting4. Although NSAIDs
are an alternative to opioids, they may increase the risk
of postoperative bleeding and reoperation8. In addition,
local anesthetics are associated with vasoconstriction9.
N-methyl-D-aspartate (NMDA) receptors in the
dorsal horn of the spinal cord are involved in central
sensitization to painful stimuli10. Ketamine is a noncompetitive antagonist of NMDA receptors which has
analgesic effects at sub-anesthetic doses10. Safari et al
showed that the use of ketamine reduced the need for
postoperative opioids and other analgesics in children
undergoing tonsillectomy11. Intravenous injection12,
peritonsillar infiltration13, rectal14, spray at the site of
surgery15, continuous infusion16 and subcutaneous
injection11 of ketamine have been investigated for pain
reduction after tonsillectomy, too. To our knowledge,
no previous studies have evaluated the role of oral
ketamine for pain reduction after tonsillectomy.
The aim of the current study is to compare oral
ketamine to peritonsillar ketamine infiltration for pain
relief after tonsillectomy.
After explaining the procedures of the study to
parents and obtaining their informed consent, patients
who met inclusion criteria were divided randomly into
two groups. In order to double-blind study, injectable
medications were tagged using similar labels and oral
ketamine was also given to patients mixed in apple
juice by a medical student. Anesthesiologist and ENT
specialists were unaware of the patient group and used
apple juices and injectable medications for patients,
respectively. Anesthesia was started using fentanyl
and atropine as premedication and then anesthesia
was induced using sodium thiopental 6 mg/kg and
atracurium 0.5-1 mg/kg and it was sustained with
isoflurane 1%, NO2 and O2 with a ratio of 50%. All
patients were intubated and to prevent entering blood
to the throat, which is of the factors causing nausea,
gauze was placed in the throat.
Half an hour before general anesthesia, 5 mg/kg
ketamine mixed in 2 cc/kg apple juice was given to the
children in oral ketamine group and 2 cc/kg of apple
juice alone was given to the children in the peritonsillar
group. After the induction of general anesthesia and
three minutes before surgery 1 cc of normal saline
0.9% in the oral group and 1cc of ketamine (0.5 mg/
kg) in the peritonsillar group was injected to the each
tonsil bed of patients (a total of 2 cc injections for each
child). Injection was performed by an ENT specialist.
Age, sex, weight, duration of surgery,
intraoperative blood loss, postoperative bleeding (in the
recovery room), nausea, vomiting, and postoperative
bleeding recurrence six hours after surgery were
recorded by the medical student who was unaware of
Oral ketamine vs. peritonsillar infiltration in tonsillectomy
31
patient group. In order to measure the pain six hours
after surgery, Modified Scoring CHEOPS criterion
was used (Table 1). The range for this criterion is from
0 to 10 where a higher score indicates greater pain17.
order to compare the two groups, chi-square test and
Mann-Whitney U test were used. P-value less than
0.05 was considered as a significant level.
Power calculations had indicated that 46 children
would be required per group to detect a difference of
30% in facial CHEOPS pain scoring with a power of
85% and α =0.05 . SPSS 13 software was used for data
analysis. Qualitative variables were described using
frequencies and percentages and quantitative variables
were described using mean and standard deviation. In
Results
There were no differences between the two
groups in terms of sex, age, and weight (Table 2).
Table 3 shows the comparison of the characteristics of
surgeries and postoperative complications between the
two groups. Duration of surgery was ≤20 minutes in
Table 1
Modified CHEOPS scoring
Score
0
1
2
Cry
No cry
Crying, moaning
Scream
Facial
Smiling
Neutral
Grimace
Verbal
Positive statement
Negative statement
Suffering from pain, another complaint
Torso
Neutral
Variable, taut, upright
Stretched
Legs
Neutral
Kicking
Stretched, continuous move
Table 2
Comparison of demographic characteristics between groups
Oral group
(N = 46)
Peritonsillar group
(N = 46)
Male
37 (80%)
9 (20%)
Female
30 (65%)
16 (35%)
≤5 yr
9 (20%)
12 (26%)
6-7 yr
18 (39%)
11 (24%)
Sex
Age group
Weight
≥8 yr
19 (41%)
23 (50%)
≤20 Kg
18 (39%)
18 (39%)
21-24 Kg
18 (39%)
12 (26%)
≥25 Kg
10 (22%)
16 (35%)
P value
0.101
0.278
0.275
Table 3
Comparison of surgery time and side effects between groups
Surgery time
Peritonsillar group
(N = 46)
P-value
0 (0%)
19 (41%)
21-29 min
18 (39%)
7 (15%)
≥30 min
28 (61%)
20 (44%)
Mild
9 (20%)
14 (30%)
Moderate
37 (80%)
27 (59%)
0 (0%)
5 (11%)
Post-op bleeding recurrence
9 (20%)
16 (35%)
0.101
Nausea & Vomiting
0 (0%)
2 (4%)
0.153
Post-op bleeding
≤20 min
Oral group
(N = 46)
Severe
<0.001
0.022
M.E.J. ANESTH 23 (1), 2015
32
Afsaneh Norouzi et. al
19 patients (21%), 21-29 minutes in 25 patients (27%),
and ≥30 minutes in 48 patients (52%). The durations of
surgeries were significantly shorter in the peritonsillar
group than in the oral group (P <0.001). The severity of
postoperative bleeding was mild in 23 patients (25%),
moderate in 64 patients (70%), and severe in five
patients (5%); overall, the incidence of postoperative
bleeding was significantly higher in peritonsillar
group than in the oral group (P = 0.022). Postoperative
bleeding recurred in 25 patients (27%) and there was
no statistically significant difference between the two
groups. Only two patients had postoperative nausea
and vomiting, and there was no significant difference
between the two groups.
The level of pain in children six hours
after surgery according to CHEOPS criteria was
significantly lower in the peritonsillar group (0.9 ±
0.8) than in the oral group (2.6 ± 1) (P <0.001). Table
4 shows the characteristics of pain in each item. All
the children in the peritonsillar group had neutral facial
expression; however in the oral group only half the
children had neutral facial expression (P <0.001). In
the peritonsillar group, 39% of children were suffering
from pain, whereas 76% of patients in the oral group
were suffering from pain (P <0.001). The leg condition
was neutral in all children in the peritonsillar group,
while only 30% of children in the oral group had
neutral condition (P <0.001). There was no significant
difference between the two groups in terms of children
cry and their body shape (Torso).
Discussion
The findings of this study showed that, compared
with oral ketamine, the peritonsillar infiltration of
ketamine after general anesthesia and immediately
before tonsillectomy shortened the duration of
operation and reduced the severity of postoperative
pain. Although postoperative bleeding was more in the
ketamine peritonsillar group, the recurrent bleeding,
nausea, and vomiting after surgery was not significantly
different between the two groups. Thus, it seems that,
compared to peritonsillar infiltration, the use of oral
ketamine 5 mg/kg is less effective in reducing pain in
children after tonsillectomy.
Ketamine is a noncompetitive antagonist of the
NMDA receptor. These receptors are located in the
dorsal horn of the spinal cord and play an important role
in the development of central sensitization to painful
peripheral stimuli. Seemingly, hyperexcitability of the
central nervous system appears to be the cause of the
Table 4
Comparison of pain based on CHEPOS between groups
Cry
Oral group
(N = 46)
Peritonsillar group
(N = 46)
No cry
28 (61%)
36 (78%)
Crying, moaning
18 (39%)
10 (22%)
0 (0%)
0 (0%)
Scream
Facial
Verbal
Torso
Legs
Smiling
0 (0%)
0 (0%)
Neutral
23 (50%)
46 (100%)
Grimace
23 (50%)
0 (0%)
0 (0%)
16 (35%)
Negative statement
11 (24%)
12 (26%)
Suffering from pain, another complaint
35 (76%)
18 (39%)
Neutral
Positive statement
46 (100%)
46 (100%)
Variable, taut, upright
0 (0%)
0 (0%)
Stretched
0 (0%)
0 (0%)
Neutral
14 (30%)
46 (100%)
Kicking
0 (0%)
0 (0%)
32 (70%)
0 (0%)
Stretched, continuous move
P-value
0.070
<0.001
<0.001
1.000
<0.001
Oral ketamine vs. peritonsillar infiltration in tonsillectomy
wind-up phenomenon and subsequent hyperalgesia in
the place of injury18. The goal of preemptive analgesia
is to prevent the afferent impulses to the spinal cord
that is causing such a phenomenon. Hence, preemptive
analgesia may prevent pain memory in the central
nervous system and reduce the need for analgesics
in the postoperative period19. It has been shown that
ketamine’s effects on these receptors can reduce pain
in humans20.
Ketamine has been used in different ways, at
different doses and different times as an analgesic after
tonsillectomy surgery, but the reported results were
not consistent have been various. Some studies failed
to show the effect of ketamine on reducing pain after
tonsillectomy. O’Flaherty et al’s study which compared
the effects of the administration of intravenous
ketamine with that of placebo4 and Van Elstraet et al’s
study which examined the effect of ketamine on pain
after tonsillectomy in adults21 did not show a positive
effect in reducing pain after tonsillectomy. However,
other studies reported that using ketamine was
effective in reducing pain following tonsillectomy.
Murray et al showed that a low-dose of intravenous
ketamine may be effective in reducing pain after
tonsillectomy22. Marcus et al23 and Elhakim et al24
stated that the intramuscular ketamine can be used
as an alternative analgesic for tonsillectomy. Erhan
et al. reported that ketamine injection in the tonsillar
area was more effective than placebo in reducing
pain without inducing sedation or nausea25. Dal et al.
reported that intravenous or peritonsillar infiltration
of ketamine before adenotonsillectomy surgery
could reduce postoperative pain and reduce the need
for analgesics without causing any adverse effects26.
More recent studies have also suggested the effect of
ketamine on reducing pain after tonsillectomy. Sizer
et al12 showed that intravenous ketamine was effective
in reducing pain following tonsillectomy. According to
a study by Siddiqui et al. peritonsillar infiltration of
33
ketamine with doses of 0.5 or 1 mg/kg reduced pain
after tonsillectomy, compared to control13. Our study
also showed that peritonsillar infiltration of ketamine
could be a useful method for reducing pain following
tonsillectomy in children.
Although ketamine has been used via different
methods to reduce pain after tonsillectomy, oral
method, however, has not been used yet for this
purpose. Filatov et al. have compared oral ketamine
as premedication with rectal diazepam/diclofenac
in adenoidectomy surgery and reported that oral
ketamine group had slightly higher pain scores than
other group27. However, they conclude that oral
ketamine is not suitable for premedication in upper
airway surgeries27. Oral ketamine has been effective in
children for controlling pain in different cases such as
abdominal malignancy surgery, sickle cell crisis, and
chronic pains28-30. It has also been used for anesthetic
premedication in children in surgeries such as dental,
ophthalmic and minor surgeries31-33. In addition, oral
ketamine is effective in postoperative agitation in
children34. In the present study we examined the effects
of oral ketamine in reducing pain after tonsillectomy
and compared it with peritonsillar ketamine. Although
Ketamine reduced postoperative bleeding, overall
it was associated with more pain in children than
peritonsillar infiltration. Thus, it seems that oral
ketamine with a dose of 5 mg/kg is less effective in
reducing pain in children after tonsillectomy compared
to peritonsillar infiltration.
Conclusions
The finding of this study indicated that, compared
with the use of oral ketamine before tonsillectomy,
the peritonsillar infiltration of ketamine after general
anesthesia and immediately before tonsillectomy
was more effective in reducing postoperative pain in
children.
M.E.J. ANESTH 23 (1), 2015
34
Afsaneh Norouzi et. al
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A: Ketamine reduces swallowing-evoked pain after paediatric
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34.Kararmaz A, Kaya S, Turhanoglu S and Ozyilmaz MA: Oral
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The Impact of Anesthetic Techniques
on Cognitive Functions after
Urological Surgery
Mahtab Poor zamany Nejat kermany*, Mohammad Hossein Soltani**,
Khazar Ahmadi***, Hoora Motiee***, Shermin Rubenzadeh***
and Vahid N ejati ***
Abstract
Background: Postoperative cognitive dysfunction (POCD) is a well-recognized complication
of cardiac and noncardiac surgery. However, contradictory results concerning postoperative mental
function have been reported. The aim is to determine the effect of anesthetic techniques (general or
spinal) on cognitive functions using more sensitive neuropsychological tests in patients undergoing
urological surgery.
Material and Methods: A total of thirty patients were enrolled in the study and assigned to
receive either general (n=15) or spinal (n=15) anesthesia. A battery of neuropsychological tests
including Wisconsin Card Sorting Test, Iowa Gambling Task, Stroop Color-Word Test, N-back
Task and Continuous Performance Test was performed preoperatively and three days later.
Results: The two experimental groups were similar at baseline assessment of cognitive
function. Although there were no statistically significant differences between general and spinal
anesthetic groups with respect to Wisconsin Card Sorting Test and Iowa Gambling Task, a
significant intergroup difference between pre-and postoperative N-back scores was detected in
the general anesthesia group (p=0.001&p=0.004). In addition, patients within this group had
significantly higher error rates on the Stroop Color-Word (p=0.019) and Continuous Performance
Tests (p=0.045). In contrast, patients receiving spinal anesthesia exhibited little change or marginal
improvement on all subscales of the battery.
Conclusions: Our findings indicate significant decline in specific aspects of mental function
among patients who were administered general anesthesia compared with the other technique. It
seems that spinal anesthesia contributes to lower disturbance after surgery.
Key word: Anesthesia - Cognitive function - Urology.
*
Anesthesiology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences
(SBMU), Tehran, I.R. Iran.
** Urology Department of Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences (SBMU),
Tehran, I.R. Iran.
*** Neuroscience department of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, I.R. Iran. Address: No#99,
9th Boston St., Pasdaran Ave, Tehran, Iran.Tel & Fax: 0098-21-22588016 .
Corresponding author: Vahid Nejati , Urology Department of Shahid Labbafinejad Medical Center, Email : v_nejati@sbu.
ac.ir
35
M.E.J. ANESTH 23 (1), 2015
36
Introduction
Postoperative cognitive dysfunction (POCD) is
a common complication in adult patients undergoing
surgical procedures which refers to decline in variety
of neuropsychological domains such as verbal or
visual memory, executive functioning, language
comprehension, attention and concentration1. Although
primarily observed after cardiac surgery, it has also
been detected following major noncardiac surgeries2,3.
While POCD is presumed to be transient and the longterm effects are considered uncertain4,5, recent studies
suggest that the symptoms of neurocognitive change
may persist long after the operation6,7 and diminish
quality of life. Patients with POCD are more likely to
withdraw from employment and social activities that
will lead to premature dependency8,9. The ISPOCD 1
study (International Study of Post-Operative Cognitive
Dysfunction) of 1,218 elderly patients (60 yr or older)
scheduled for major noncardiac surgery showed that
cognitive impairment was present in 25.8% patients
one week after the operation and in 9.9% of them after 3
months10. Furthermore, postoperative cognitive decline
has been associated with significantly higher risks of
postoperative morbidity and mortality, particularly in
elderly11. A similar study revealed that patients with
POCD at hospital discharge were more likely to die
whitin 3 months of the discharge12. In general, the rate
of cognitive dysfunction has been positively correlated
with mortality risk. Several studies show an increased
risk of early mortality in elderly individuals with
cognitive deterioration13,14.
The etiology of POCD is likely multifactorial
with type of surgical procedure (due to differences
in duration) metabolic/endocrine stress response,
imbalance of neurotransmitter system (particularly
acetylcholine and serotonin), hypoxia and
hospitalization, all potentially playing a role15.
Advanced age, history of cerebral vascular accident
with no residual impairment, lower educational
level, evidence of cognitive dysfunction at hospital
discharge and alcohol abuse also contribute to the
pathogenesis of POCD12,16. With further identification
of preoperative risk factors for POCD, patients and
healthcare providers can be better informed before
making a decision to proceed with major surgery.
Mahtab poor zamany Nejat kermany et. al
It has been speculated that POCD risk could be
reduced by performing certain surgical procedures
under regional anesthesia. Results of a study indicated
that the maintenance of mental function in an elderly
population was better following spinal anesthesia when
compared with general anesthetic technique17. Similarly,
another report showed that the incidence of cognitive
deterioration was lower after epidural anesthesia18.
A recent study found that general anesthesia posed
a significant risk for the occurrence of early POCD
in elderly patients that could persist for 3 days after
surgery19. However, review of the existing literature
has not revealed a significant difference between the
two intraoperative anesthetic techniques20,21. The
heterogeneity of procedures used to measure cognitive
deficits and methodological inconsistencies make the
limited literature on POCD difficult to interpret22,23.
Most of these tests are subsets of test banks used to
assess the memory and intelligence of adults. The use of
more sensitive neuropsychological tests may elucidate
more prolonged damage to cognitive performance. In
addition, the majority of previous investigations have
primarily focused on elderly patients, a population with
an increased vulnerability to neurological deterioration
after exposure to anaesthesia24,25. As a result, the
cognitive effects of anesthesia and surgery in young
and middle-aged adults are poorly understood. The
objective of this study was to evaluate post-operative
mental function of patients who had undergone general
or spinal anesthesia for a urologic surgery, and to
compare the effect of these two anesthetic techniques
on mental function.
Material and Methods
From July to September 2011, 30 patients
undergoing urological surgery following either general
or spinal anesthesia were participated in the study at
Shahid Labbafinezhad Hospital. Written informed
consent was taken from all patients and university
ethics committee approved the study structure. Entry
criteria included age (24+ yr), normal mental status,
speaking and reading fluency in the Persian language
and the absence of any serious vision or hearing
impairment that would preclude neuropsychological
testing. Participants were excluded if they had any
Impact of anesthesia on cognitive function
prior history of dementia, central nervous system
disease, psychiatric disorders, alcoholism and drug
abuse. In addition, any patients with history of allergy
to anesthetic drugs were also excluded. Information
about the demographic status, medical history,
education and occupational history of the subjects
were documented.
Anesthetic techniques and agents
All patients received 5cc/kg normal saline
serum before anesthesia. In the group of patients who
underwent general anesthesia, the following agents
were used for the induction of anesthesia: Fentanyl
(2µ/kg), Midazolam (1mg), Lidocain (1.5mg/kg),
Propofol (2mg/kg) and Atracurium (0.5mg/kg). For
maintenance phase of general anesthesia, Propofol
(100-200µ/kg) and Remifentanil (0.1 µ/kg/min)
were used. Spinal Anesthesia was done by injection
of 2.5 to 3 cc bupivacaine 0.5% (Marcaine®) in the
subarachnoid space. For post-operative pain control,
intravenous pethidine (25-50 mg) was administrated in
the recovery room and Diclofenac 100mg suppository
was given in the ward as needed.
Neuropsychological Assessment
The cognitive function evaluation was performed
in an undisturbed room with only the patient and the
psychometrician present. Patients completed the tests
one day prior to surgery and at hospital discharge (three
days after the operation). The psychological measures
included Wisconsin Card Sorting Test, Stroop ColorWord Task, Continuous Performance Test, N-Back
Task and Iowa Gambling Test that were administered
in about 30 minutes. These measures primarily focus
on executive functions and memory, elaborated as
follows:
Wisconsin Card Sorting Test is commonly
regarded as “the gold standard executive function
task”26,27. Patients were asked to match response cards
to reference cards according to three dimensions of
sorting principle (color, form and number)28. Stroop
Color-Word Test estimates the patient’s ability
to concentrate and ignore distracting stimuli29.
Continuous Performance Test (CPT) requires subjects
37
to maintain vigilance and react to the presence or
absence of specific stimuli within a continuously
presented set of distracters30,31. N-Back Task is one of
the most popular experimental paradigms for studies
of working memory, in which subjects are asked to
monitor the identity or location of a set of verbal or
nonverbal stimuli and to indicate when the currently
presented stimulus is the same as the one presented in
trials previously32,33. Iowa Gambling Task evaluates
decision-making under initially ambiguous conditions.
It simulates real-life decision making by testing the
ability of subjects to learn to sacrifice immediate
rewards in favor of long-term gains34,35.
Statistical Analysis
Given the large number of dependant variables,
comparison of the cognitive function between the two
anesthesia groups was performed with multivariate
analysis of covariance (MANCOVA) using SPSS
(version 18). Follow-up tests were conducted when
warranted by multivariate results with ANOVA and
paired t-tests. Pre-test scores were considered to be
covariate variables in order to control for the practice
effect. The customary two-tailed α level of significance
was set at 0.05.
Results
Thirty patients (13 women and 17 men) were
recruited. The subjects had a mean age of 44.6
(±12.66). 36.6% subjects were classified as young
(24-39yr), 53.33% were middle-aged (40-59) and 10%
were elderly (60-65). General anesthesia was used in
15 patients (50%), and the remaining subjects received
spinal anesthesia.
The baseline characteristics of the patients included
in the study are listed in table 1. Data analysis revealed
that the two groups did not differ in preoperative scores.
However, statistically significant differences were
observed when postoperative scores were compared
with the baseline levels. Results indicated significant
association between general anesthetic technique and
damage to particular domains of cognitive functions.
Although subtests of the Wisconsin Card Sorting Test
and Iowa Gambling Task did not change significantly
M.E.J. ANESTH 23 (1), 2015
38
Mahtab poor zamany Nejat kermany et. al
between the two groups, separate univariate analysis
and paired t-test showed that patients were more
likely to have worse 1-and 2-back test performance
after general anesthesia (p=0.001& p=0.004). These
patients also had significantly higher omission error
score on the Continuous Performance Task (p=0.045)
and considerable error rates on the 3rd part of the
Stroop Color-Word Test (p=0.019). It is worth noting
that patients receiving spinal anesthesia showed
little change or slight improvement on all subscales
of the battery. The mean pre-and postoperative
neuropsychological test scores are exhibited in
Table 2.
Discussion
This study is one of the few investigations of
postoperative cognitive function that includes younger
population. In the current study, we used some of
the most popular neuropsychological tasks to assess
executive functions. Comparison of the two arms of
the study was based on MANCOVA which provided
more statistical power. Our data revealed that general
anesthesia was associated with weaker performance in
the memory and concentration domains. These results
are in accordance with the findings of Chung et al,
who found that patients receiving general anesthesia
performed worse on digit-symbol substitution for 2-3
days after surgery36. Herbert and colleagues also noted
that choice reaction time was impaired for 36hours
after administration of general anesthesia37. Findings
of another study indicated that general anesthesia
patients perceived residual impairment of their
cognitive faculties after 3 days38.
Previous research addressing the role of anesthesia
on cognitive deterioration has yielded conflicting
results. The absence of a consistency regarding the
operational definition of POCD may contribute to
this issue. Our findings are inconsistent with the
vast majority of existing evidence demonstrating no
significant difference between intraoperative regional
and general anesthesia in preserving postoperative
Table 1
General characteristics of the patients, compared in two groups (general vs. spinal anesthesia.)
General
Anesthesia
Spinal Anesthesia
Total
P value
46.9
42.26
44.6
0.614
24-39 (Young)
6
5
11
0.120
40-59 (Middle-aged)
8
8
16
60 and above (Elderly)
1
2
3
Male
7
10
17
Female
8
5
13
Less than High school
4
7
11
High School
6
4
10
More than High school
5
4
9
Lithotripsy
4
1
5
Intravesical injection
1
2
3
Radical Nephrectomy
2
0
2
Varicocelectomy
2
3
5
Bladder Stone Removal
2
2
4
TUL
1
5
6
TURT
1
2
3
Mean Age
Age Groups
Sex
Education
Type of
surgery
0.211
0.340
0.151
Impact of anesthesia on cognitive function
39
Table 2
Pre-and postoperative (at hospital discharge) test results
Preoperative
Postoperative
General
Spinal
General
Spinal
(n-15)
(n-15)
(n-15)
(n-15)
Achieved Clusters
1.66±0.61
1.60±0.63
1.66±0.72
2.00±0.84
Number of Total Errors
37.93±6.39
38.2±5.79
37.53±6.01
36.26±7.53
Perseverative Errors
15.46±3.62
14.86±2.13
14.8±3.66
12.00±
Iowa Gambling Task
25.20±2.48
23.53±3.29
26.20±1.97
23.46±3.99
1-back
19.93±6.71
16.26±6.30
16.20±5.99*
17.73±6.41
2-back
8.13±3.29
8.73±3.97
5.60±2.55*
10.33±3.90
Omission Error
16.06±8.67
16.33±8.10
19.20±7.93*
13.60±6.56
Commission Error
1.064±0.51
1.157±0.94
1.11±0.35
1.151±0.56
Hit Reaction Time
0.548±0.06
0.562±0.04
0.606±0.1
0.541±0.05
Error Rates 1
1.33±0.97
1.40±0.82
1.60±1.88
0.66±0.61
Reaction Time 1
0.46±0.45
0.33 ±0.37
0.42±0.54
0.25±0.32
Error Rates 2
0.53±0.74
0.53±0.63
2.13±1.95
0.26±0.59
Reaction Time 2
0.34±0.55
0.27±0.34
0.79±0.81
0.22±0.46
Error Rates 3
17.40±7.91
19.33±7.006
22.06±6.94*
16.60±6.99
Reaction Time 3
1.85±0.93
1.34±0.55
2.11±0.91
1.53±0.61
Wisconsin Card Sorting Test
N-Back Task
Continuous Performance Test
Stroop Color-Word Task
Values are given as mean±SE. “*” mark indicates significant difference in the assigned group before and after the operation.
cognitive function. For instance, in a prospective,
randomized study, Williams-Russo et al, compared
the effect of epidural versus general anesthesia
on the incidence of POCD in patients undergoing
elective unilateral total knee replacement and found
no significant difference postoperatively20. In another
randomized trial, no significant differences were found
in the postoperative mental abilities between patients
who received general, regional or combined anesthetic
techniques39. O’Hara et al, observed no clinically
important impacts on major outcomes in patients
who were administered general or spinal anesthetic
techniques after the hip surgery40. In a systematic
review, Wu et al, found that intraoperative neuraxial
anesthesia does not decrease the incidence of POCD
when compared with general anaesthesia41.
Detection of POCD requires two crucial
elements: a sensitive battery of tests and controlling for
the practice effect. We used some of the well-known
psychological measurements to determine more subtle
defects. The enhancement observed in this trial cannot
be attributed to practice effect. In as much as, pretest
scores were considered as covariate variables.
There may be several factors that might have a
negative impact on cognitive function after general
anesthesia. Some agents that are used to induce and
maintain anesthesia may deteriorate cognition and
memory10. In addition, there may be a possibility of
hemodynamic instability, hypoxia and stress induced
response due to prolonged intubation; the factors that
are not commonly related to regional anesthesia15.
M.E.J. ANESTH 23 (1), 2015
40
This study was limited by two major factors.
Firstly, patients were not allocated randomly to the
general or spinal anesthesia groups. Secondly, we
were unable to include a control group of healthy
volunteers matched with the experimental groups in
the present study. Hospitalized patients not undergoing
surgery or any other intervention were also considered
as a better control group, but a sufficient sample size
for comparison could not be attained due to lack
of participation. Our findings should therefore be
interpreted with caution. A more extensive study with
follow-up testing is required to determine the precise
profile of the postoperative cognitive impairment.
In conclusion, our results suggest a linkage
between general anesthesia and weaker postoperative
Mahtab poor zamany Nejat kermany et. al
mental function. Local anesthesia might have an
advantage over general anesthesia in terms of
neuropsychological functioning.
Acknowledgments
The authors thank the hospital staff and patients
for taking part in this study. Their assistance was
essential for data collection and the coordination of the
research protocol.
Conflict of interest:
The authors have no conflict of interest.
Impact of anesthesia on cognitive function
41
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Comparison between C-MAC ® video-laryngoscope
and Macintosh direct laryngoscope during
cervical spine immobilization
Shahir HM Akbar* and Joanna SM Ooi**
Abstract
Background: Video-laryngoscopes have gained popularity in the recent years and have
shown definite advantages over the conventional Macintosh direct laryngoscopes. However, there
is still insufficient evidence comparing the C-MAC® with the Macintosh for patients during manual
inline stabilization (MILS).
Methods: This prospective, randomized, single blind study was carried out to compare
tracheal intubation using the C-MAC® video-laryngoscope and Macintosh laryngoscope in
patients during MILS. Ninety consented patients, without features of difficult airway, who required
general anesthesia and tracheal intubation were recruited. Intubation was performed with either
the C-MAC® video-laryngoscope or the Macintosh laryngoscope by one single investigator
experienced with both devices. Various parameters which included Cormack and Lehane score,
time to intubate, intubation attempts, optimization maneuvers, complications and hemodynamic
changes were recorded over the initial period of 5 minutes.
Results: C-MAC® video-laryngoscope performed significantly better with lower Cormack
and Lehane grades, shorter time to intubate of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds (p=0.001) and
needed less optimization maneuvers. There were no significant differences seen in the intubation
attempts, complications or hemodynamic status of the patients with either device.
Conclusion: The C-MAC® video-laryngoscope was superior to the Macintosh laryngoscope
for patients requiring intubation when manual inline neck stabilization was applied.
Keywords: C-MAC® laryngoscope, Macintosh laryngoscope, intubation, neck immobilization,
manual inline stabilization.
Introduction
Securing the airway with tracheal intubation in a patient suspected or known to have
a cervical spine injury has always been a challenge regardless of whether it is conducted in a
controlled operating room environment, in a busy critical zone of the emergency department or
in an out-of-hospital setting. This has been recognized since the early 1950’s and by the early
1980’s the standard of care to overcome this scenario was to use the time tested formulae of direct
laryngoscopy with tracheal intubation using manual inline stabilization (MILS)1 with a Macintosh
laryngoscope. MILS is a maneuver that ensures a neutral alignment and motionless cervical spine
* MBBS, Master in Medicine (Anesthesiology).
** MD, Master in Medicine (Anesthesiology).
Corresponding author: Professor Dr. Joanna Su Min Ooi. Address: Department of Anesthesiology and Intensive Care,
University Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur,
Malaysia. Tel: +0193207265, Fax: +60391456585. E-mail: [email protected]
43
M.E.J. ANESTH 23 (1), 2015
44
during the intubation process and is carried out by a
healthcare personnel who places a hand on each side
of the patients neck with fingers pressed on each
mastoid process and the hands then pressed firmly
into the operating table2. While the practice of MILS
was considered to be the standard care with regards to
prevention or worsening of any neurological morbidity,
it has been found that MILS produced significantly
worse laryngoscopy view upon direct laryngoscopy for
tracheal intubation3-5. The delay in or a failed tracheal
intubation could potentially result in hypoxia leading
to worse outcomes and is a leading cause of morbidity
and mortality for patients in both the operative setting
and in an emergency situation5,6.
With due consideration to the above, advances
in technology have provided alternatives to the
conventional Macintosh laryngoscope to perform
direct laryngoscopy during a MILS scenario.
Considerable development has occurred especially
in the field of indirect laryngoscopy using videoassisted techniques producing devices such as
the Glidescope® (Saturn Biomedical System
Inc., Burnbaby, Canada) and the Airwayscope®
laryngoscope (Pentax Corporation, Tokyo, Japan).
These new devices have been shown to have
definite advantages over the conventional Macintosh
direct laryngoscopy in scenarios where MILS was
applied. These included better glottic visualization,
less optimizing maneuvers needed for a successful
intubation and more favorable hemodynamic profiles
during the intubation itself7-10.
The C-MAC® (Karl Storz, Tuttlingen, Germany),
a portable video-laryngoscope is unique as it offers an
original Macintosh blade shape with an approximately
80° angle of view and practically eliminated fogging
of the camera11. Owing to its similar design to the
Macintosh blade, there would not be very much of a
learning curve to using it by most anesthetic doctors.
An initial study showed great promises in it being able
to obtain good view of the glottis on the first attempt
in all patients12. At this point of time the question of
whether any video-laryngoscope is definitely better in
MILS is yet to be answered convincingly3.
The aim of this study was to compare
laryngoscopic views (based on Cormack and Lehane
grading) during tracheal intubation when using either
J.Su Min Ooi et. al
the C-MAC® video-laryngoscope or the Macintosh
laryngoscope during MILS. The time taken to intubate
(seconds), number of intubation attempts, optimization
maneuvers required, complications encountered and
the changes in hemodynamic parameters of the patients
being intubated were also compared.
Methods
This study design was based on a prospective,
randomised, single-blinded clinical trial that was done
following approval of the Dissertation Committee
of the Department of Anesthesiology and Intensive
Care, Universiti Kebangsaan Malaysia Medical Center
(UKMMC) and the Research Ethics Committee of
UKMMC (Research No. FF-024-2011).
After obtaining written informed consent, ninety
patients between 18 and 60 years of age with American
Society of Anesthesiology (ASA) physical status I or II,
scheduled for elective surgery under general anesthesia
that required tracheal intubation were enrolled in the
study. Those patients who had features of difficult
airway (e.g. Mallampati grade >III, thyromental
distance <6cm or a Body Mass Index >35kg/m2),
pregnant or had other conditions associated with an
increased risk of pulmonary aspiration were excluded
from the study. Likewise patients who had pre-existing
cervical neck pathologies, hypertensive individuals
and those with allergies or contraindications to
medications used for general anesthesia were excluded
as well.
The selected patients were then randomised
into two arms. Group 1 patients were intubated with
the C-MAC® video-laryngoscope whereas patients in
Group 2 were intubated with the Macintosh (MAC)
laryngoscope. This randomisation process was done
using ‘Random Numbers Tables’ that were computer
generated.
In the operating room, all patients received
a standardized general anesthetic. Both groups
of patients were started on IV fluid of Lactated
Ringer’s solution. Induction of anesthesia with the
administration of 100% oxygen at 6 liters/min, IV
fentanyl (2 mcg/kg) and IV propofol (up to 2 mg/kg)
was carried out to induce unconsciousness defined
as loss of eyelash reflex. Subsequently manual
C-MAC® video-laryngoscope during manual inline stabilization
ventilation was initiated with sevoflurane (2.0%) in
oxygen as test ventilation, before administration of IV
rocuronium (0.6 mg/kg) as a muscle relaxant. Standard
anesthetic monitoring which included ECG, noninvasive blood pressure (NIBP), oxygen saturation
(SpO2), end tidal carbon dioxide (EtCO2) and a multigas analyzer were provided to both groups of patients.
After full muscle relaxation was confirmed with a
nerve stimulator, the patient’s neck was immobilized
utilizing MILS technique. The MILS was performed
by another medical officer who stood at the right side
of the patient caudal to the intubator and the patient’s
airway. The assistant placed a hand on each side of the
patient’s neck with fingers pressed on each mastoid
process and the hands were then pressed firmly into
the operating table ensuring neutral alignment and a
motionless cervical spine as described in Advanced
Trauma Life Support2.
Intubation was then performed with one of the two
devices (both with blade #3) as per the group that the
patient was in . A tracheal tube size #7.5 - 8 for males
and #7 - 7.5 for females was used. Once the vocal cords
were visualized they were graded using the Cormack
and Lehane (CL) grading. After successful tracheal
intubation in all patients, mechanical ventilation was
commenced for the duration of the procedure with
anesthesia being maintained with sevoflurane (1.0
MAC) and air-oxygen mixture (FiO2 0.5).
In each group, tracheal intubation was considered
a failure if it could not be established with three attempts,
within three minutes or desaturation of SpO2 <92%. In
the event of such an incident, MILS was abandoned
and intubation was performed using the Macintosh
blade with optimal patient head and neck positioning.
Any additional instruments to aid intubation were used
if deemed necessary. All intubations were performed
by the investigator SH, an anesthetic trainee whose
previous experience includes >30 intubations with the
C-MAC® and more than 5 years frequent use of the
Macintosh laryngoscope.
Data collected included CL score, time to intubate
in seconds (defined as when either of the blades was
inserted beyond the lip until first appearance of the
capnograph waveform) and number of intubation
attempts. In addition, the nature of optimisation
maneuvers done such as the use of a gum elastic
45
bougie (GEB), external laryngeal manipulation (ELM)
or presence of a second assistant were also recorded.
Complications including fogging of lens, local trauma
(mucosal/lip/dental), hypoxia (SpO2 <92%) and failed
intubation were recorded. Recording of the patient’s
baseline mean arterial pressure (MAP) and heart
rate (HR) along with repeat recordings at fixed one
minute time intervals for 5 minutes were done. No
other medications were administered, or procedures
performed during the 5-minute data collection period
after tracheal intubation. Subsequent management was
left to the discretion of the anesthetist providing care
for the patient.
The sample size was obtained using the computer
software: “Power and Sample Size Calculations
Version 3.0.14, January 2009” otherwise known as PS2.
(http://bisotat.mc.vanderbilt.edu/powersamplesize ).
The alpha error was set at 5% (p<0.05) and a beta error
of 20% (power = 0.8). The p0 was set at 0.2 from a
previous study with the Macintosh laryngoscope using
MILS where 20% of patients obtained CL grade 1
views9. Since the C-MAC® video-laryngoscope has not
been studied previously in this manner, the probability
of obtaining a CL grade 1 view was estimated as
50% from a preliminary study12. Thus the p1 was
set at 0.5 and the results calculated using the sample
size software as discussed previously. The sample
size required was found to be 38 patients, which was
rounded up to 40 patients on each arm. A dropout rate
of 10% was factored in to give a sample size of 45
patients in each arm and thus a total sample size of 90
patients.
Data analysis was done using Chi-square test for
non-parametric data and Student’s t-test for parametric
data. A p value of less than 0.05 was considered as
statistically significant. All analysis was performed
using SPSS for Windows (version 12.0, Chicago, IL).
Results
A total of 90 patients were enrolled into the
study with 45 patients in each group. There were no
significant differences in the patient characteristics
such as age, gender, ASA physical status, BMI and
Mallampati grades between the two groups as shown
in Table 1.
M.E.J. ANESTH 23 (1), 2015
46
J.Su Min Ooi et. al
Table 1
Demographic and patient characteristics. Values expressed as
Mean ± SD or number (%)
Gender
32.7 ± 6.8*
38.8 ± 8.9
1
44 (97.8)
39 (86.7)
2
1 (2.2)
4 (8.9)
3
0
2 (4.4)
13 (28.9)
None
38 (84.4)**
27 (60.0)
25 (55.6)
22 (48.9)
GEB
3 (6.7)
1 (2.2)
20 (44.4)
23 (51.1)
ELM
3 (6.7)
14 (31.1)
ELM + GEB
1 (2.2)
3 (6.7)
Second
assistant
0
0
Blade size
change
0
0
Failed
intubation
0
2 (4.4)
Lip trauma
0
1 (2.2)
Esophageal
intubation
0
0
Dental
trauma
0
0
SpO2<92%
0
0
40.8 ± 15.1
41.6 ± 14.8
Female
22 (48.9)
24 (53.3)
Male
23 (51.1)
21 (46.7)
26.2 ± 4.7
26.9 ± 3.7
I
30 (66.7)
32 (71.1)
II
15 (33.3)
I
II
BMI (kg/m )
Mallampati
MAC
(n=45)
MAC
(n = 45)
2
ASA
C-MAC®
(n=45)
C-MAC®
(n = 45)
Age (years)
Table 2
Intubation characteristics. Values are expressed as Mean ± SD
or numbers (%)
The CL grade was significantly better in Group
1 using the C-MAC® producing a CL Grade I for
67% of the study population compared to Group 2
with only 38% of the sample having CL Grade I as
shown in FIGURE 1 (p <0.05). None of the patients
in Group 1 had CL Grade IV whereas there was one
patient in Group 2 with CL grading of IV. The majority
of patients intubated with the MAC (56%) were found
to have a CL Grade of II. The CL grading correlated
well with the time to intubate (TTI) which was found
to be significantly shorter in Group 1 with a mean time
of 32.7 ± 6.8 vs. 38.8 ± 8.9 seconds for Group 2 (p =
0.001) as shown in Table 2.
The number of intubation attempts required
in the two groups however was found to be not
significantly different. The majority of patients in both
Fig. 1
Cormack and Lehane grades
obtained in the two groups
* p <0.05
TTI ( seconds)
Intubation
attempts
Optimization
maneuvers
Complications
* p = 0.01, ** p <0.05.
C-MAC® video-laryngoscope during manual inline stabilization
groups were able to be intubated in the first attempt.
Optimisation maneuvers were found to be commonly
required for patients in Group 2 with 31% of them
requiring ELM and 7% required both ELM and GEB.
In contrast 84% of Group 1 patients required no such
measures for successful tracheal intubation and only
7% of patients needed the help of either a GEB or
ELM (p =0.01).
There were no reported complications in patients
from Group 1. In Group 2, there were two cases of
failed intubation and one case of minor lip trauma.
However on statistical analysis these results were
not significant. Additionally, there was no occurrence
of oxygen desaturation or esophageal intubation
encountered on both the study arms. On a side note,
we experienced fogging occurring in 11% of the cases
on the C-MAC® arm but this was not severe enough to
impair the performance of the device. This was likely
47
due to the presence of a built in software system that
initiates pre-warming of the optical system by the
camera light12.
Both groups had similar trends of MAP and HR
over the 5-minute data collection period as shown in
Figures 2 and 3. There were no recorded increases of
more than 20% of their respective baseline values of
these two parameters. However at one point of time
(T +1: one minute post intubation) Group 2 had a
higher MAP of 93.5 ± 16.0 vs. 86.9 ± 10.4 mmHg for
Group 1(p<0.05). The rest of the data points were not
statistically different between the groups.
Discussion
From this study, we found that using the C-MAC®
video-laryngoscope would be of benefit in patients with
Fig. 2
Changes in MAP during
tracheal intubation. Values are
expressed as Mean ± SD
* p <0.05
Fig. 3
Changes in mean heart
rate following tracheal
intubation. Values are
expressed as Mean ± SD
M.E.J. ANESTH 23 (1), 2015
48
MILS due to its superiority in various aspects compared
to the Macintosh laryngoscope. The C-MAC® was
able to obtain better CL scores with a majority of
them being CL Grade I without requiring additional
optimization maneuvers. The Macintosh laryngoscope
on the other hand had majority of CL II grades. Poor
laryngoscope views in the setting of MILS is a known
factor that will complicate intubation in this group of
patients1. The limited neck movement from the MILS
made direct laryngoscopy become more challenging
mainly due to difficulties in aligning the oral,
pharyngeal and laryngeal axis which was required for
a successful tracheal intubation10. In order to overcome
this situation, having an indirect laryngoscope such
as the C-MAC® with a camera mounted on the blade
capturing live images and projecting them onto a video
screen dramatically reduces the line of sight required
which in turn resulted in the much improved CL scores
as seen occurring in our study. This advantage was also
noted by McElwain and Laffey where 35 % of patients
intubated with the C-MAC® had a CL Grade 1 vs. the
Macintosh which produced CL Grade 1 in 19% of their
study sample10.
The mean difference of 18 seconds reduction
in TTI for the C-MAC® obtained in our study may
initially seem unremarkable at its face value especially
since the lengthened period of apnea for the Macintosh
group was not associated with desaturation or other
hemodynamic changes. However, in an emergency
airway management situation where the patient is
at risk of hypoxia, any reduction in the TTI could
be a very crucial factor. In a similar study the TTI
recorded however was longer although insignificantly
for the C-MAC® [TTI of 27secs IQR 18, 47] vs.
Macintosh [TTI of 23 sec IQR 14, 47]10. A point to
note in that study was that the measurement of TTI
was not standardized. The investigators measured the
TTI from the time the laryngoscope blade passed the
lips up till they visualized the ETT passing the vocal
cords and in cases where the ETT was not visualized,
the appearance of capnograph tracing was taken as
the end point. In our study the TTI was standardized
and recorded for all intubations from the time the
laryngoscope blade passed the lips till the appearance
of the capnograph.
J.Su Min Ooi et. al
Using the C-MAC® also resulted in less need
for additional optimization maneuvers compared to
the Macintosh Group. In our study we found that the
Macintosh group required the use of ELM in 61% of
patients which was similarly seen in other studies as
well9,10. The main reason behind this was because of
the need for the intubator to obtain a best line of sight
by aligning the intubation axis as has been discussed
earlier. This however is not needed when using the
C-MAC® as the vocal cords are readily visualized due
to the blade mounted camera and 80° angle of view12.
During the course of our intubations, we did not require
a change in blade size or use of second assistant for
either of the groups and blade size #3 was used for
both devices.
Patients from both groups had no significant
complications. Oxygenation was well maintained
despite the variation in intubation times due to the
process of preoxygenation that was conducted in
our study. There may possibly have been hypoxemia
if this crucial step was omitted highlighting once
again its importance especially in emergency airway
management. The lack of significant airway trauma
in both groups as observed in our study arise possibly
because of the similar shape and structure of the two
laryngoscope blades that results in similar mechanical
forces and movements during intubation when using
either of the devices. These similarities in the low
occurrence of airway trauma was also observed in
other studies as well10,13.
There are a few limitations that can be identified
in our study. Firstly, it is not possible to blind
the investigator about the device being used. The
performance of the device is highly dependent on the
capabilities of the operator. However due to the overall
similar design of the two blades this would be quite
unlikely to affect performance markedly. Nevertheless
all the intubations were carried out by a single
investigator (SH) so that the variability in technique
and operator bias could be minimized. The other issue
lies with the subjectivity of the CL scoring. Once again
by utilizing a single operator we hope that this can be
overcome as well.
One important factor to keep in mind is that
this study was conducted on adequately fasted,
pre-oxygenated patients with no difficult airway
C-MAC® video-laryngoscope during manual inline stabilization
management anticipated. These patients underwent
elective surgery exclusively. Thus the situation would
be expected to be very different in the post-trauma
patients presenting to the emergency department or
operating room for emergency airway management.
Further well planned studies will be required to assess
how the C-MAC® performs in these situations.
49
Conclusion
In conclusion, our study demonstrated that
the C-MAC® video-laryngoscope was superior for
patients being intubated during manual inline neck
stabilization when compared to the standard Macintosh
laryngoscope.
M.E.J. ANESTH 23 (1), 2015
50
J.Su Min Ooi et. al
References
1. Manoach S, Paladino L: Manual In-Line Stabilisation For Acute
Airway Management Of Suspected Cervical Spine Injury: Historical
Review And Current Questions. Ann Emerg Med; 50:236-45 2007.
2. Committee on Trauma, American College of Surgeons. ATLS:
Advanced Trauma Life Support Program for Doctors (8th ed.).
Chicago: American College of Surgeons, 2008.
3. Calder I and Pearce A: Core Topics in Airway Management.
9780521111881. 2nd Edition. 248. Cambridge; Cambridge
University Press, 2010.
4. Nolan JP, Wilson ME: Orotracheal intubation in patients with
potential cervical spine injuries. An indication for the gum elastic
bougie. Anesthesia; 1993, 48:630-3.
5. Heath KJ: The effect of laryngoscopy of different cervical spine
immobilisation techniques. Anesthesia; 1994, 49:843-5.
6. Mort TC: Emergency tracheal intubation: complications associated
with repeated laryngoscopy attempts. Anaesth Analg; 2004, 99:60713.
7. SUN DA, WARRINER CB, PARSONS DG, et al: The Glidescope®
video-laryngoscope: randomised clinical trial in 200 patients. Br J
Anaesth; 2005, 95:381-4.
8. Enomoto Y, Asai T, Arai T, et al: Pentax-AWS®, a new video-
laryngoscope, is more effective than the Macintosh laryngoscope
for tracheal intubation in patients with restricted neck movements: a
randomised comparitive study. Br J Anaesth; 2008, 100:544-8.
9. Malik MA, Maharaj CH, Harte BH, et al: Comparison of
Macintosh, Trueview EVO2®, Glidescope®, and Airwayscope®
laryngoscope use in patients with cervical spine immobilisation. Br
J Anaesth; 2008, 101:723-30.
10.Mcelwain J and Laffey JG: Comparison of the C-MAC®, Airtraq®,
and Macintosh laryngoscopes in patients undergoing tracheal
intubation with cervical spine immobilisation. Br J Anaesth; 2011,
107(2):258-264.
11.Thierbach A, Piepho T: Emergency Airway Management. Tuttlingen,
Germany: Endo PressTM 2009.
12.Cavus MD, Kieckhaefer J, Doerges V, et al: The C-MAC® videolaryngoscope: first experiences with a new device for videolaryngoscopy guided intubation. Anaesth Analg; 2010, 110:473-7.
13.Maharaj CH, Buckley E, Harte BH, et al: Endotracheal
intubation in patients with cervical spine immobilisation. A
comparison of Macintosh and Airtraq laryngoscope®. Br J
Anaesth; 2007, 107:53-9.
Effects of Memantine on Pain in Patients
with Complex Regional Pain Syndrome-A
Retrospective Study
Mohammad-Hazem Ahmad-Sabry*
and G holamreza S hareghi **
Abstract
Introduction: Memantine was discovered in 1968 and is used as a treatment for Alzheimer’s
disease. We evaluated the use of memantine to treat complex regional pain syndrome in this
retrospective study.
Patients and methods: 56 patients with CRPS, who were treated with trial of memantine for
at least two months with 40mg QHS from 2007 until 2009.
Results: 34 females and 22 male patients. Age-46.0+/-9.7 years. Number of years with
CRPS-9.24 ± 5.7 years. Mean age-46.0+/-9.7 years. Memantine was started at 5 or 10mg QHS,
before being increased by 5 or 10mg every 4-7 days, as tolerated, to a maximumdose of 40mg60mg, as tolerated. In all, 13 patients showed complete remission from CRPS with VAS 0 and the
disappearance of allodynea for at least nine months after the use of memantine. In addition, 18
patients showed partial improvement of VAS and allodynea. Eight patients showed no improvement
even after continuous use of memantine at a dose of 40mg QHS for two months. Seven patients
could not take more than 5mg of memantine per day and had to stop it due to side effects. In terms
of subjective improvement in short-term memory, nine patients showed much improvement, 14
patients showed some improvement, three patients showed no changes and one patient didnot
answer the questionnaire. Regarding subjective feelings of a having better quality of life, 17 patient
answered yes, three did not feel any changes, six could not give an answer and two did not fill out
the questionnaire.
Conclusions: Memantine is a promising option for the treatment of CRPS. A randomised
controlled study is needed to evaluate its efficacy*.
Introduction
Bowsher (1991) found that neuropathic pain affected 25-50% of chronic pain patients in
most pain clinics1. Richards (1967) reported the history of CRPS and its terminology2. Although
previous descriptions were of single cases, Weir Mitchell, Morehouse and Keen (1864) first
described the condition in full in the book “Gunshot Wounds and other Injuries of Nerves”. The
* MB, ChB MSc FRCPC MD ABPM.
** MD, PhD, DABIPP.
Department of Anesthesia and Surgical Intensive Care, Alexandria Faculty of Medicine, Alexandria University, Alexandria,
Egypt, Advanced Pain Therapeutics of Knoxville, Knoxville, TN, USA.
Correspondence author: Mohammad-Hazem I. Ahmad-Sabry MB, ChB MSc FRCPC MD ABPM, Alexandria Faculty of
Medicine, Khartoum Square, Shalalat, Alexandria, EGYPT, 21111. Tel: +2016-271-8827 or +203-487-0509, Fax: +203-4842236. Email:[email protected]
51
M.E.J. ANESTH 23 (1), 2015
52
Ahmad-Sabry et. al
authors described the condition as a burning pain,
which Weir Mitchell later described as causalgiain
1872 in the Merck Manual for Health Professionals3.
Thomas and Grossberg explained the multimodal
therapies and treatments used for Alzheimer’s disease,
including memantine which was discovered 19684.
Siniset al. (2007) published his preliminary
report on the use of memantine in complex regional
pain syndrome with promising results5. Scheleyet al.’s
(2007) experiment with memantine in patients with
phantom limb pain, in combination with continuous
brachial plexus blocks, showed a decrease in phantom
pain up for to six months6. However, treating CRPS
remains an off-label use for memantine. In this study,
we evaluated the use of memantine in patients with
complex regional pain syndrome.
hallucinations, wild dreams, and psychotic ideations
were the frequent complaints while on memantine.
The mean age of the participants was 46.0 ±
9.7 years. The average number of years since the
participants’ diagnoses of CRPSwas9.24 ± 5.7 years.
Memantine was started at 5 or 10mg QHS, before
being increased by 5 or 10mg every 4-7 days, as
tolerated, up to a maximum level of 40mg, or 60mg
if a better response was achieved with no side effects.
No changes were made in any of the patients’ current
poly-pharmacy treatment plans for CRPS during the
experiment until the patients asked for to stop or
decrease their non-experimentalmedications.
Before the starting memantine, all of our patients
had been taking a large variety of CRPS treatments
including:
Several diagnostic/therapeutic sympathetic
blocks (all patients), and/or continuous sympathetic
blocks (if possible, some patients).
Patients and methods
We reviewed the charts of patients with diagnosed
with CRPS that were treated in our clinic from 2007
until 2009. In all, 56 CRPS patients (52 CRPS I, four
CRPS II) were treated with memantine, including 34
females and 22 males. Retrospective, open label data
and results were gathered from treating our patients
during at least two years of follow-up after beginning
memantine. All patients consented to the off label use
of memantine for the treatment of CRPS.
Table 2
Paired Samples Statistics
Std. Error
Mean
Std.
Deviation
N
Mean
.20065
1.40456
49
8.1633
VASB
0.44134
3.08937
49
3.5510
VASA
.29776
2.08432
49
7.7755
Burn B
.41853
2.92973
49
3.7143
Burn A
Table 1
Patient Demographics
Percentage
Frequency
42.9
21
Male
57.1
28
Female
100.0
49
Total
Patients received a minimum dose of 40mg/day60mg/day, as long as a better response was achieved
with no side effects. Seven patients were excluded from
the study because they did not tolerate a memantine
dose of even 5 mg a day. Five of the seven patients had
already been diagnosed with bipolar affective disorder
at least two years prior to their CRPS diagnosis
and were on antipsychotic medications and mood
stabilisers prior to receiving the memantine. Severe
A number of months of proper physical therapy.
Psychological therapy, if needed.
Extensive poly-pharmacy therapy: membrane
stabilisers, NSAIDS, anti-depressants, muscle
relaxants, alpha-2 agonists, alpha-1 antagonists,
steroids, opioids and/or biphosphonats.
A few had intrathecal delivery systems ([opioids/
baclofen/clonidine/local anaesthetic] combinations).
A few had epidural Dorsal Column Stimulation
for pain modulation.
A few had a combination of treatments five and
six.
Each patient was encouraged to maximise
participation in daily living activities.
Effects of Memantine on Pain in Patients with Complex Regional Pain Syndrome-A
Retrospective Study
All patients received a monthly evaluation for
signs of changes in:
Allodynia
Burning pain
Short-term memory loss
Anger level
Normalcy in everyday life
To assess for burning pain, the following
assessments were used:
•
•
•
•
•
1) Quantitative Visual Analog Scale (VAS) before and
after six months on the full dose of memantine.
2)Quantifying the number of exaggerated burning
attacks per month on the primary CRPS extremity
(patients voted to call these “a 10/10 Fire Storm”).
Allodynia was assessed according to the
following:
1) Percentage of decrease of the disgusting unpleasing
feelingsrelated tosoft touch of the skin of the area
affected by CRPS.
2)For the patients that enjoyed taking a shower prior
to the development of CRPS,the time spent in the
shower from before and after six months on memantine.
To assess for CRPS-related migraine headaches, a
quantitative decrease in the numberof migraine attacks/
monthbefore and after six months on memantine was
examined.
We followed the patients for at least two years
after the start of the memantine.
Results
In all, 56 patients were enrolled in the study,
and ultimately, seven were excluded, as they did not
tolerate the memantine. Of the patients that were
excluded, six were females and one was male. Five
of the seven patients had been already diagnosed
with bipolar affective disorder at least two years prior
to the CRPS diagnosis, and were on antipsychotic
medications and mood stabilisers prior to beginning
memantine. Severe hallucinations, wild dreams, and
psychotic ideations were the frequent complaints
related to side effects while on memantine. Out of the
49 patients that continued to use memantine, 21 were
male (42.9%) and 27 were female (57.1%).
53
The mean VAS was 8.1633 (SD: 1.40456) before
the use of memantine and 3.5510 (SD: 3.08937)
after the use of memantine, which was statistically
significant at p <0.001. Those that responded positively
to the memantine did not ask for any increase in other
pain medications, and instead, asked for the dosages
of the other medications to be decreased. The mean
burning pain was 7.7755 (SD: 2.08432) before the
use of memantine and 3.7143 (SD: 2.92973) after the
use of memantine, which was statistically significant
at p <0.000. Out of 49 patients, 13 (26.5%) showed
a complete disappearance of the pain, burning and
allodynea.
Discussion
Memantine is a drug with the ability to block
NMDA receptors in the brain. Juliato Piovesan et al.
(2008) suggested that memantine was much more
potent inhibitor of central and peripheral sensitisation
than were non-NMDA antagonists7. Park et al. (2012)
tested the drug on trigeminal pain in rats8. Belozertseva
and Bespalov (1998), as well as Popik and Kozela
(1999), showed that memantine could attenuate the
tolerance to morphine in animal models9,10. Davidson
and Carlton’s (1998) experiment demonstrated that the
local use of memantine in attenuating pain in animal
modelswas comparable to the use of dexmethorphan
and ketamine11. Eisenberg et al. (1998) failed to find
clinical benefits of using memantine for post-herpetic
neuralgia when using doses of 10-20mg/day12.
Nikolajsen et al. (2000), in a randomised cross-over
study,could not find any difference when using 20mg/
day of memantine after amputation or nerve injury
surgery13. Siniset al. (2007) published preliminary
results in human patients with CRPSthat had good
responsesto the medication when using 20 mg/day5.
Scheleyet al. (2007) found a decrease in the medication
requirements, as well as in the phantom limb pain, when
using memantine at doses of 20-30mg/day compared
to those people that did not use the drug6. Grande et
al. reported the use of memantine with small doses
of ketamine for opioid tolerant oncology patients,
demonstrating less opioid consumption at memantine
doses of 20mg a day, and recommended more studies
be done in this area14. Thomas and Grossberg (2009)
M.E.J. ANESTH 23 (1), 2015
54
recommended the use of memantine for Alzheimer’s
disease and other neuropsychiatric diseases due toits
level of safety4. Olivan-Blázquezet al. (2014) found
promising results for memantine use at doses of 20g/
day when used for fibromyalgia15.
We used the memantine in our practice for
resistant cases of CRPS and used largerdoses than
what was recommended for use in patients with
Alzheimer’s disease (40mg/day), which could be why
other studies results did not show the same benefits.
Also, in our study, the pathology was different than in
Ahmad-Sabry et. al
the other studies, which might also contribute to the
conflicting results. Our study was limited in the lack
of randomisation with a controlled group that used
aplacebo. However, in our study, we compared the
same patient before and after the use of memantine,
using the patients’ data before the treatment as the
control. We concluded that memantine is effective and
is a promising option for the treatment of CRPS. More
studies are needed using blinding, randomisation and
possibly placebo procedures.
References
*. Partially published as an abstract presentation in the 8th Congress of
European Federation of IASP Chapter (EFIC) October 9-12, 2013 in
Florence, Italy.
1. Bowsher D: (1991) Neurogenic pain syndromes and their
management. Brit Med Bull; 1991, (47):644-666.
2. Richards RL: (1967) The term causalgia. Medical History; 11(1):8690.
3. Russell K, Portenoy: (Feb 2012) Neuropathic pain. Merck Manual
for Healthcare Professionals.
4. Thomas S, Grossberg T: (2009) Memantine: A review of studies
into its safety and efficacy in treating Alzheimer’s disease and other
dementias. ClinInterv Aging; 4:367-377.
5. Sinis N, Birbaumer N, Gustin S, Schwarz A, Bredanger S, Becher
ST, Unertl K, Schaller HE, Haerle M: (2007) Memantine
treatment of CRPS, A preliminary report of 6 cases. Clin J Pain;
23:237-243.
6. Scheley M, Topfner S, Wiech K, Schaller H, Konrad C, Schmelz
M, Birbaumer N: (2007) Continuous brachial plexus blockade
in combination with the NMDA receptor antagonist memantine
prevents phantom pain in acute traumatic upper limb amputees. Eur
J Pain; 2007, Apr: 11(3):299-308. Epub 2006 May 22.
7. Piovesan EJ, Randunz V, Utiumi M, Lange MC, Kowacs PA,
Mulinari RA, Oshinsky M, Vital M, Sereniki A, Fernandes AF,
Silva LL, Werneck LC: (2008) Influence of NMDA and non-NMDA
antagonists on acute and inflammatory pain in the Trigeminal
territory. Arq Neuropsiquiatr; 66(4):837-843.
8. Park J, Suh J, Shin H, Park G: (2012) Influence of memantine
on nociceptive responses of the trigeminocervical complex after
formalin injection. Cephlalgia; 2012 Mar, 32(4):308-16.
9. Belozertseva I, Bespalov A: (1998) Effects of NMDA receptor
channel blockers, dizocilpine and memantine, on the development of
opiate analgesic tolerance induced by repeated morphine exposures
or social defeats in mice. Nauyn Schmiedergs Arch Pharmacol;
358(2):270-4.
10.Popik P, Kozela E: (1999) Clinically available NMDA antagonist,
memantine, attenuates tolerance to analgesic effects of morphine in
a mouse tail flick test. Pol J Pharmacol; 1999 May-Jun, 51(3):22331.
11.Davidson E, Carlton S: (1998) Intraplantar injection of dextrorphan,
ketamine or memantine attenuates formalin-induced behaviors.
Brain Res;1998 Feb, 23:785(1):136-42.
12.Eisenberg E, Kleiser A, Dortort A, Haim T, Yarnitsky D: (1998)
The NMDA (N-methyl-D-aspartate) receptor antagonist memantine
in the treatment of postherpetic neuralgia: A double-blind, placebocontrolled study. Eur J Pain; 2(4):321-327.
Nikolajsen L, Gottrup H, Kristensen A, Jensen T: (2000) 13.
Memantine (a N-Methyl-D-Aspartate receptor antagonist) in
the treatment of neuropathic pain after amputation or surgery:
A randomized, double-blinded, cross-overstudy. Anesth Analg;
91:960-6.
14.Grande L, O’Donnell B, Fitzgibbon D, Terman G: (2008) Ultralow dose ketamine and memantine treatment for pain in an opioidtolerant oncology patient. Anesth Analg; 107:1380-3.
15.Olivan-Blázquez B, Herrera-Mercadal P, Puebla-Guedea M,
Pérez-Yus MC, Andrés E, Fayed N, López-Del-Hoyo Y, Magallon
R, Roca M, Garcia-Campayo J: (2014) Efficacy of memantine in the
treatment of fibromyalgia: A double-blind, randomised, controlled
trial with 6-month follow-up. Pain; 2014 Dec, 155(12):2517-25.
Effects of dexamethasone and pheniramine
maleate on hemodynamic and
respiratory parameters after
cementation in cemented partial
hip prosthesis
Abdulkadir Yektaş*, Funda Gümüş*, Tolga Totoz*,
Nurten Gül*, Kerem Erkalp* and Ayşin Alagöl*
Summary
Purpose: To prevent hemodynamic and respiratory changes that are likely to occur during
cementation in partial hip prosthesis by prophylactic use of pheniramine maleate and dexamethasone.
Methods and Materials: The study included 40 patients aged between 60 and 85 years with an
American Society of Anesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis.
Just after spinal anesthesia, 4 mL normal saline was pushed in patients in Group S, whereas 45.5
mg pheniramine maleate and 8 mg dexamethasone mixture was pushed intravenously in a total
volume of 4mL in patients in Group PD.
Results: Amounts of atropine and adrenaline administered after cementation were significantly
higher in Group S than in Group PD (P <0.05). There was a significant difference between SpO2
values before and after cementation in Group S; SpO2 value was lower after cementation (P <0.05)
except for 1. min after cementation. SpO2 value increased 1 min after cementation (P = 0.031)
Conclusion: Prophylactic use of pheniramine maleate and dexamethasone in partial hip
prosthesis led to an increase in SpO2 value and a decrease in the utilization of adrenaline and
atropine after cementation.
Keywords: Methylmethacrylate, partial hip prosthesis, bone cement implantation syndrome,
pheniramine maleate, dexamethasone.
Introduction
Partial hip arthroplasty is usually performed in elderly population in whom concomitant
diseases may enhance the likelihood of a more progressive BCIS (Bone Cement Implantation
Syndrome). BCIS is the most important cause of intraoperative morbidity and mortality in patients
undergoing cemented hip arthroplasty, and rarely, hypoxia and confusion may be encountered in
the postoperative period. Intraoperative mortality rate is 0.43 % for cemented partial hip prosthesis
in patients with or without femur fracture1. Although the etiology and pathophysiology of BCIS
have not been understood clearly, few mechanisms including monomer-mediated model, embolic
model, histamine release and hypersensitivity, complement activation, and multimodal model
*Anesthesiology and Reanimation Clinic, Bagcilar Training and Research Hospital, Istanbul, TURKEY.
Corresponding author: Abdulkadir Yektas. Address: Bagcilar Egitim ve Arastirma Hastanesi Anesteziyoloji ve
Reanimasyon Klinigi 34200 Bagcilar, Istanbul, TURKEY, Tel: + 90 505 388 18 84, Fax: + 90 212 488 69 63. E-mail:
[email protected]
55
M.E.J. ANESTH 23 (1), 2015
56
have been suggested. In a study, blockade of histamine
receptors by clemastine and cimetidine (H1 and H2
antagonists) was reported to have protective effects3.
Pheniramine maleate is an H1 receptor antagonist.
H1 receptor antagonists have been successfully used
before drug infusion to prevent and for acute treatment
of type I hypersensitivity9. Dexamethasone is a
synthetic glucocorticosteroid. In animal studies, this
glucocorticosteroid has been demonstrated to inhibit
airway eosinophilia in the presence of antigen by
inhibiting interleukin-5 synthesis and to be successfully
used for the prophylaxis of type I hypersensitivity
reaction10,11.
The aim of the present study is to assess the
effect of pheniramine maleate and dexamethasone on
incidence of hypotension, bradycardia and hypercarbia
associated with BCIS.
Methods and Materials
After obtaining approval from the Ethical
Committee of Bağcılar Training and Research
Hospital and written informed consents of the patients,
40 patients aged between 60 and 85 years with an
American Society of Anesthesiologists (ASA) grade
of II-III who underwent partial hip prosthesis with
cement due to femur neck fracture under spinal
anesthesia were included in the study. The present
study was designed as a prospective, randomized and
double-blinded study.
Data of the patients regarding age, height, weight,
gender, concomitant diseases, medications, smoking
status, ASA classification and surgery duration of
surgery were recorded.
Patients with allergic diseases, those using antiallergic medications or corticosteroids, who have
deep venous thrombosis and lower extremity venous
insufficiency, those with cardiac disease likely to cause
atrial fibrillation or thromboembolism, or paraplegiahemiplegia, who were immobile before fracture (i.e.,
bedridden patients), those with previous cardiac
surgery, and those having a contraindication for
regional anesthesia were excluded from the study.
The patients did not receive any premedication.
The patients were positioned with the hip that would be
A.Yektas et. al
operated being on top, and an 18 G intravenous canula
was placed into a pheripherial vein in the dorsal aspect
of the hand opposite to the surgery side and 0.9% NaCl
was administreted at a rate of 10 mL kg-1 h-1 for first
hour and than 5 mL kg-1 h-1. In order to obtain blood
sample for blood gas analysis, an intra-arterial catheter
was inserted into the radial artery of the arm on the
surgery side via a 20-gauge intravenous catheter, and it
was washed with heparinized fluid and closed using a
three-way tap. The patients were administrated oxygen
at a rate of 2 L/min through a free oxygen mask which
was fixed hole in any side of the free oxygen mask in
which the free end of end-tidal CO2 (ET-CO2) line. All
patients underwent electrocardiography, non-invasive
arterial blood pressure measurement, peripheral pulse
oximetry and end-tidal CO2 monitoring. All patients
underwent spinal anesthesia. Patients in both groups
were positioned laterally with the leg that would be
operated being on top, and spinal anesthesia was
performed via a 27-gauge Quincke-type needle after
performing
cutaneous-subcutaneous
infiltration
anesthesia using 2 mL of 2% lidocaine through L4L5 space. After observing cerebrospinal fluid (CSF)
outflow, 1 mL (5 mg) isobaric bupivacaine and 25 µg
(0.5 mL) fentanyl were administered in a total volume
of 1.5 mL. Spinal anesthesia was performed by a
specialist in both groups. The patients in whom spinal
anesthesia was unsuccessful three times were excluded
from the study. Then the patient were randomly divided
into the following two groups using sealed envelopes:
1) Group S (n = 20) patients were administrated 4 mL
of normal saline, 2) Group PD (n = 20) patients were
administrated 45.5 mg pheniramine maleate and 8 mg
dexamethasone. Prior to spinal anesthesia, basal values
of arterial blood pressure, heart rate, oxygen saturation
by pulse oximeter (SpO2), end-tidal CO2 (ETCO2), and
blood gases were recorded. Pre-prepared syringes were
used; thus, both the anesthesiologist and the patient
were blinded to the content.
Cephazoline sodium 1 g was administered
iv approximately 30 to 60 min prior to surgery for
prophylaxis.
Values of arterial blood pressure, heart rate,
SpO2, end-tidal CO2, and blood gases were recorded
for all patients prior to surgical procedure and at 10min intervals until the first minute before cementation.
Dexamethasone & pheniramine in hip prosthesis
57
Amount of bleeding, amount of crystalloid
administered by IV route, and, if used, doses of
atropine and adrenaline were also recorded until the
first minute before cementation. Those parameters
were recorded at 1-min intervals in the first 5 min after
cementation and then every 5 minutes. Measurements
were discontinued at the 25th min after cementation.
Amount of administered crystalloid throughout the
surgical procedure and amount of bleeding were
recorded. Arterial blood gases were analyzed before
spinal anesthesia, just before cementation, and at the
10th and 25th min after cementation.
of bleeding throughout surgery before and after
cementation, amount of crystalloid, amount of atropine
and adrenaline were compared between the groups by
an independent-t test.. Data analyses were performed
using the Statistical Package for the Social Sciences
(SPSS, Inc. Chicago, IL, USA) version 11.5. A P value
<0.05 was considered statistically significant.
A 5 µg adrenalin was pushed via venous route
in the following conditions: 1) a decrease in mean
blood pressure more than 30% of the initial value until
cementation, 2) after cementation, a more than 30%
decrease in the blood pressure value measured before
cementation. In case of a decrease in heart rate below
50 beats/min, 0.5 mg atropine was injected. Patients
in whom amount of bleeding before cementation
exceeded 400 mL were excluded from the study
(bleeding before cementation exceeded 400 mL in any
of the patients), and blood loss was replaced by normal
saline.
When the surgical procedure was completed and
following postoperative observation, patients with a
modified Aldrete score of ≥9 were transferred to the
clinic.
Statistical Analysis
Based on a preliminary study performed in 10
patients, we estimated that a sample size of 20 patients
in each group would be sufficient with a 5% error and
a statistical power of 80% assuming that the mean
arterial pressure on the 25th min would be 92 ± 15
mmHg in Group PD and 85 ± 15 mmHg in Group S.
Descriptive statistics of data were expressed as
mean ± standard deviation. Normal distribution of
variables was tested by Kolmogorov Smirnov test.
Comparison of data regarding age, height, weight,
gender, type of surgery, duration of surgery, time
elapsed from spinal anesthesia to cementation, and
ASA grades were performed using the Chi square
test. Heart rate, arterial blood pressure values, SpO2,
end-tidal CO2 and blood gas measurements, amount
Results
Distributions of age, weight, height, type of
surgery, duration of surgery, duration of cementation,
ASA grades and gender in the study groups are
presented in Table 1. There were no statistically
significant differences between the groups in terms of
age, weight, height, type of surgery, duration of surgery,
duration of cementation, ASA grade and gender.
Table 1
Distribution of age, weight, height, type of surgery, duration
of surgery, duration of cementation, the American Society of
Anesthesiologists grades and gender in the study groups. Data
are presented as mean ± SD
Group S
(n = 20)
Group PD
(n = 20)
P
Age (years)
80.50 ± 7.05
76.85 ± 9.31
0.198
Weight (kg)
70.75 ± 11.14
70.60 ± 10.45
0.989
Height (cm)
168.45 ± 8.40
166.35 ± 5.65
0.462
Duration of
surgery (min)
79.30 ± 27.29
84.55 ± 18.01
0.579
Duration of
cementation
(min)
61.60 ± 22.87
64.35 ± 10.55
0.968
ASA (II/III)
14/6
13/7
0.708
Gender
(F/M)
11/9
12/8
0.061
SD: standard deviation; ASA: the American Society of
Anesthesiologists; F: female; M: male
Doses of atropine and adrenaline and the amounts
of intravenous fluid and bleeding in the study groups
are presented in Table 2. The dose of adrenaline used
M.E.J. ANESTH 23 (1), 2015
58
A.Yektas et. al
Table 2
Distribution of amounts of atropine, adrenaline, and intravenous fluid, and the amount of bleeding in the study groups. Numbers are
presented as mean ± SD.
Group S
(n = 20)
Group PD
(n = 20)
P
Adrenaline after cementation (µg)
4.50 ± 11.34
0.75 ± 1.83
0.022
Atropine after cementation (mg)
0.25 ± 0.91
0.00 ± 0.00
0.014
Intravenous crystalloid before cementation (mL)
560.50 ± 206.33
480.00 ± 176.51
0.345
Intravenous crystalloid
surgical procedure (mL)
890.00 ± 282.65
827.50 ± 181.71
0.274
Amount of bleeding before cementation (mL)
184.25 ± 96.99
158.75 ± 77.01
0.243
Total amount of bleeding (mL)
228.75 ± 118.73
211.00 ± 77.50
0.059
administered
throughout
SD: standard deviation
after cementation was significantly higher in Group S
than in Group PD (P = 0.022). The dose of atropine
used after cementation was significantly higher in
Group S than in Group PD (P = 0.014).
pH (P = 0.102), PaCO2 (P = 0.063), PaO2 (P = 0.175) and
end-tidal CO2 values (P = 0.448) and 25th min pH (P =
0.193), PaCO2 (P = 0.186), PaO2 (P = 0.084) and endtidal CO2 values (P = 0.054) min after cementation.
Comparison of the study groups in terms of
systolic diastolic and mean arterial pressures, heart rate
and SpO2 before and after cementation are presented
in Table 3. There were no statistically significant
differences between the groups in terms of systolic/
diastolic and mean arterial pressure, heart rate and
SpO2. Heart rate increased significantly 2 min after
cementation in Group PD when compared to before (p
= 0.008) (Table 3).
One patient in Group S developed cardiopulmonary
arrest at the 1st min after cementation and accepted as
dead after performing cardiopulmonary resuscitation
(CPR) for 45 min. Blood gas values and end-tidal CO2
values of this case was not consistent with pulmonary
embolus.
In Group S, SpO2 increased 1 min after
cementation (P = 0.031), and were significantly lower
at the rest of all times when compared to the value
before cementation (P = 0.003, P = 0.003, P <0.001,
P = 0.003, P = 0.001, P = 0.001, P = 0.001, P = 0.004,
respectively) (Table 3).
There were no significant differences between
Group S and Group PD in terms of PH (P = 0.168),
partial arterial carbon dioxide pressure (PACO2) (P =
0.067), partial arterial oxygen pressure (PAO2) (P =
0.056) and end-tidal CO2 values before cementation
and at the 10th (P = 0.067) and 25th (P = 0.152) min
after cementation.
In addition, there were no significant differences
in both groups in terms of pH, PaCO2, PaO2 and endtidal CO2 values before cementation, and at the 10th min
All patients were transferred to the clinic after
observing postoperatively in recovery room for 2
hours and then all patients were discharged. None
of the patients developed postoperative hypoxia or
confusion.
Discussion
Respiratory and cardiovascular changes during
partial hip replacement seriously affect the prognosis
of patients. These changes exist in a wide spectrum of
disorders ranging from temporary hypoxia to cardiac
rhythm disorders and even cardiac arrest12,13.
Several mechanisms have been suggested in
the etiology and pathophysiology of BCIS including
monomer-mediated model, embolic model, histamine
release and hypersensitivity, complement activation,
and multimodal model2. A study has shown that
implantation of methacrylic bone cement into the femur
may increase plasma histamine level by more than 1
ng/mL. Temperate histamine release may cause severe,
97.2 ± 2.4
97.5 ± 2.8
S
PD
84.4 ± 18.7
76.4 ± 13.0
S
PD
85.4 ± 21.8
93.8 ± 20.7
S
PD
71.8 ± 16.5
PD
76.4 ± 21.0
S
96.3 ± 2.9
97.8 ± 2.8
87.1 ± 21.8
79.4 ± 18.9
81.7 ± 16.9
83.1 ± 22.1
69.8 ± 15.6
69.9 ± 17.7
125.6 ± 22.1 124.0 ± 26.0
137.4 ± 27.0 127.2 ± 28.3
1.min
PD
S
Before C
95.9 ± 3.2
92.6 ± 21.9*
95.1 ± 24.5*
76.1 ± 23.9
81.7 ± 16.9
88.3 ± 20.7
67.0 ± 14.3
73.6 ± 17.4
118.8 ± 27.6
128.2 ± 24.4
2.min
96.0 ± 3.0
92.1 ± 21.9*
86.9 ± 22.2
75.7 ± 24.0
78.9 ± 17.4
87.9 ± 25.3
67.8 ± 13.6
74.3 ± 21.8
121.1 ± 22.9
127.2 ± 25.9
3.min
5.min
10.min
87.6 ± 19.3
74.4 ± 23.1
81.9 ± 15.8
89.5 ± 20.6
68.0 ± 13.6
74.0 ± 20.1
87.3 ± 17.9
75.1 ± 25.7
87.7 ± 15.8
91.8 ± 26.3
70.9 ± 12.4
74.2 ± 21.4
95.8 ± 2.8
95.9 ± 2.8
95.6 ± 2.9
92.2 ± 21.9* 92.7 ± 21.9* 92.7 ± 21.9*
88.3 ± 18.7
74.7 ± 24.6
79.5 ± 16.2
91.6 ± 27.2
67.9 ± 15.4
74.3 ± 23.1
122.1 ± 22.7 119.9 ± 34.1 132.8 ± 20.3
130.3 ± 28.3 131.5 ± 25.5 135.3 ± 24.3
4.min
87.1 ± 17.5
87.41 ± 7.9
93.4 ± 9.8
95.5 ± 3.3
96.0 ± 2.6
92.7 ± 22.0*
81.5 ± 27.5
85.2 ± 19.9
84.4 ± 13.9
81.2 ± 27.2
92.4 ± 25.3
68.4 ± 12.1
69.1 ± 11.6
89.9 ± 18.5
70.6 ± 20.8
72.2 ± 19.01
92.2 ± 21.9* 92.5 ± 21.9*
88.4 ± 20.3
79.7 ± 25.1
90.8 ± 14.9
93.2 ± 26.1
70.7 ± 11.8
72.9 ± 21.4
131.6 ± 22.2
134.6 ± 23.5 131.6 ± 23.9
25.min
133.6 ± 26.1
20.min
130.2 ± 28.4 135.1 ± 24.1
15.min
SAP: Systolic Arterial Pressure; DAP: Diastolic Arterial Pressure; MAP: Mean Arterial Pressure; HR: Heart Rate; SpO2: Peripheral Oxygen Saturation; Group; S: Saline; Group; PD:
pheniramine maleate-dexamethasone; Before C: Before cementation.
There is no statistical difference between groups (P >0.05)
* P <0.05 when compared with Before Cementation.
SpO2
HR
MAP
DAP
SAP
Group
Table 3
Systolic, Diastolic and Mean Arterial Pressure, Heart Rate and Peripheral Oxygen Saturation (Mean ± SD)
Dexamethasone & pheniramine in hip prosthesis
59
M.E.J. ANESTH 23 (1), 2015
60
sometimes fatal, cardiovascular complications in very
old patients in case they have signs of hypovolemia or
cardiac diseases3.
Cardiac problems defined to date have been
mostly about wall motion and rhythm disorders, with
no remarkable changes in heart rate14,15. We also found
no significant difference between heart rates before
and after cementation; heart rate at the 2nd min after
cementation was higher than before cementation only
in Group PD. In Group S, as compared with before
cementation, heart rate decreased by 0.40% at the 2nd
min, 1% at the 3rd min, 2.5% at the 4th min and 3.1% at
the 5th min, but thereafter returned to the normal values.
The dose of atropine administered was significantly
higher in Group S than in Group PD. However, as
heart rate was recorded with 5-min intervals, such
decrements in HR were not reflected in the statistical
analysis. In Group PD, an increase in the heart rate was
observed by 12.73% at the 2nd min (P <0.05), 3% at the
3rd min, 4.62% at the 4th min and 3.79% at the 5th min.
Potential causes of hypotension, one of the
parameters of BCIS, include histamine release and
type I hypersensitivity reaction, or hemodynamic
impairment caused by pulmonary air or by fat
embolism and reflex mechanisms responsive to
this16,17. An experimental study has demonstrated that
methylmethacrylate monomers influence intracellular
and extracellular calcium mobilization, resulting
in direct relaxation in venous and arterial smooth
muscles18,19. Nevertheless, this hypothesis has not
been verified by in vivo animal experiments and it
has been determined that plasma methylmethacrylate
concentration after cemented hip arthroplasty is lower
than the concentration that is likely to cause pulmonary
or cardiovascular effects20,21. A clinical study evaluating
plasma concentrations revealed that maximum levels
of serum methylmethacrylate was measured 30 s after
cementation and this was thought to cause a decrease
in arterial blood pressure20. Another study compared
non-cemented hip arthroplasty with cemented hip
arthroplasty using transesophageal echocardiography
and demonstrated a higher embolic load in the cemented
hip arthroplasty group22. The authors concluded
that, embolism might also cause hypotension due to
increase in pulmonary arterial pressure together with
decrease in right ventricular function23. In the present
A.Yektas et. al
study, there were no significant differences between
the groups in terms of the amounts of crystalloid
and bleeding before cementation and throughout the
surgical procedure.
The amount of adrenaline administered in Group
S was significantly higher than that administered in
Group PD; however, as blood pressure was measured
at specific time intervals, such variations in blood
pressure had no impact on the statistical outcomes.
A patient in Group S developed hypotensive
bradycardic arrest at the 1st min after cementation,
which was not responsive to CPR. There were no
significant differences in PaO2, pH, PaCO2 and endtidal CO2 values of this patient before cementation and
during CPR performed after cementation; this ruled
out the possibility of massive embolism.
In the present study, despite oxygen provided
through a free oxygen mask at a rate of 2 L/min in
both groups, there was a significant difference between
SpO2 values before and after cementation in Group S.
An increase by 0.25% at the 1st min after cementation
and a decrease by 7.1% at the 2nd min after cementation
were observed, and this decrease continued until the
end of surgery in the same manner. Various studies
have demonstrated hypoxia development during
hip and knee arthroplasty24,25. This has been thought
to result from pulmonary embolism or pulmonary
vasoconstriction due to cement toxicity21,26. In the
present study, there was no significant difference
between SpO2 values before and after cementation
in Group PD; this suggests that dexamethasone and
pheniramine maleate prevented bronchospasm resulted
from pulmonary vasoconstriction caused by cement
toxicity and pulmonary embolism. Studies performed
after observation of intraoperative deaths occurred
during cemented arthroplasty have demonstrated the
presence of bone marrow embolism, fat embolism and
bone embolism and methylmethacrylate particles in the
lungs27,28,29. Medulla residue may cause embolism in the
lungs, heart or paradoxically in the brain and coronary
arteries30,31. This suggests that hypotension occurs
due to characteristic hypoxia and right ventricular
dysfunction as the consequence of pulmonary
embolism21. However, a definite correlation could not
be established in the literature between the degree of
embolism detected by performing transesophageal
Dexamethasone & pheniramine in hip prosthesis
echocardiography and the severity of hypoxia22.
It has been reported that blood cement monomer
levels do not reach high concentrations that likely can
cause toxicity in human32, in which both mechanisms
are considered to play a role. Among anaphylatoxins,
C3a and C5a are potent mediators that lead to
vasoconstriction and bronchoconstriction33. The
levels of C3a and C5a have been observed to increase
in cemented hemiarthoplasties by complement
activation33. In human studies, high dose (2g)
methylprednisolone have been demonstrated to reduce
hypoxia and complement activation. The decreases
in anaphylatoxin release and oxygen saturation are
reduced by methylprednisolone33. However, whether
methylmethacrylate particles or embolus material
causes complement activation is not clear. Complement
61
levels were not studied in the present study. We
thought that complement activation might have been
prevented by dexamethasone, due to the less decrease
in hemodynamic values-although no statistically
difference was found, but clinically important-1 min
after cementation and lack of desaturation in Group PD
In conclusion, the dose of adrenaline and atropine
used after cementation was significantly lower and,
SpO2 values were stable after cementation in Group PD;
on the other hand, in Group S, SpO2 values decreased
after cementation, except for 1. min after cementation.
SpO2 value increased 1 min after cementation.
This suggests that prophylactic administration
of pheniramine maleate and dexamethasone may
minimize the clinical symptoms of BCIS.
M.E.J. ANESTH 23 (1), 2015
62
A.Yektas et. al
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without cement. J Bone Joint Surg Am; 1993, 75:581-587.
32.Bengtson A, Larsson M, Gammer W, Heideman M: Anaphylatoxin
release in association with methylmethacrylate fixation of hip
prostheses. J Bone Joint Surg Am; 1987, 69:46-49.
33.Gammer W, Bengtson A, Heideman M: Inhibition of complement
activation by high-dose corticosteroids in total hip arthroplasty. Clin
Orthop Relat Res; 1998, 236:205-209.
Effect of preoperative oral pregabalin
on postoperative pain after mastectomy
Mardhiah Sarah Harnani Mansor
and C hoy Y in C hoy **
Abstract
Background: This was a randomized, double-blinded clinical trial to study the effects of a
single oral dose of pregabalin 150 mg in postoperative pain management after mastectomy.
Methods: Design: forty nine patients ASA I or II, aged between 20-60 years, scheduled for
mastectomy with or without axillary lymph nodes dissection (ALND) were recruited into this
study. They were randomized into two groups, placebo (n = 24) or pregabalin (n = 25) receiving
either oral pregabalin 150 mg or placebo when called to operation theatre (OT). The assessment
of pain score were performed at recovery, 2, 4, 6 and 24 hours postoperatively at rest and on
movement, using the verbal numeral rating score (VNRS).
Results: VNRS scores for pain at rest were lower in the pregabalin group at 2 (p = 0.024),
4 (p = 0.006) and 6 (p = 0.003) hours postoperatively, and also at 4 (p = 0.005) and 6 (p = 0.016)
hours postoperatively on movement compared to the placebo group. Incidences of dizziness were
common, however, side effects such as nausea and vomiting, headache, somnolence and visual
disturbance were low and comparable in both groups.
Conclusion: a single dose of 150 mg pregabalin given preoperatively compared to placebo
significantly reduced postoperative pain scores after mastectomy.
Keywords: pregabalin, postoperative pain, mastectomy, opioid.
Introduction
Preventive analgesia is a treatment approach that aims to reduce the development of central
sensitization in the postoperative period by reducing peripheral nociceptive input into the central
nervous system, thus reducing postoperative pain and analgesics consumption. The concept of
preventive analgesia includes multimodal antinociceptive techniques with analgesics that exceed
the expected duration of action and also attenuate peripheral or central hypersensitivity2,3,4.
Effective methods include systemic NSAIDs, single dose epidural analgesia, systemic NMDA
receptor antagonists, systemic opioids and local anaesthetic infiltration. Gabapentin and pregabalin
have been proven to be effective medications in serving these purposes.
Pregabalin was originally developed as an antiepileptic drug with an improved pharmacological
profile when compared to that of its predecessor gabapentin5. Although gabapentin and pregabalin
were first identified as useful in the treatment for neuropathic pain, recent reviews showed that
they reduced postoperative acute pain and analgesic consumption as well. Gabapentin has been
shown to be an effective analgesic for tonsillectomy, mastectomy and knee arthroplasty6,7,8,
*
Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre.
Corresponding author: Choy Yin Choy, e-mail: [email protected]
63
M.E.J. ANESTH 23 (1), 2015
64
however pregabalin appears to be a better option when
compared with gabapentin as it has better analgesic
efficacy and an improved pharmacokinetic profile9.
Pregabalin and gabapentin bind to the α2δ sub-unit
of pre-synaptic voltage-gated calcium channels in
the spinal cord and brain1,2,3,4,5. By altering calcium
currents, it reduces or modulates the release of several
excitatory neurotransmitters including glutamate,
norepinephrine, substance P and calcitonin generelated peptide, producing inhibitory modulation of
‘over-excited’ neurons and returning them to a normal
state.
One advantage of pregabalin in clinical use is
that it has higher bioavailability when giving orally
with linear pharmacokinetics property compared to
gabapentin. It is rapidly and extensively absorbed after
oral dosing in the fasting state with maximal plasma
concentration occurring within 1 hour after single or
multiple doses9. Absorption of gabapentin is limited
by saturable, active and dose dependent transport in
gastrointestinal tract but absorption of pregabalin is not
saturable, resulting in a linear pharmacokinetic profile
with bioavalability exceeding 90% and independent
of dose3,5. In recent years, pregabalin has been
introduced as an adjunct in multimodal management
of postoperative analgesia in many studies because of
its favourable pharmacokinetics10-15.
The aim of this study was to compare the effect
of single-dose 150 mg oral pregabalin to placebo on
postoperative pain after mastectomy for breast cancer.
Methods
This randomized, double-blinded clinical trial
was done following approval of the Dissertation
Committee of the Department of Anaesthesiology
and Intensive Care, Universiti Kebangsaan Malaysia
Medical Centre (UKMMC) and the Research Ethics
Committee of UKMMC (Research No. FF–444-2012).
Forty nine, ASA I or II patients, aged 20 to 60 years
who were scheduled for elective mastectomy with or
without axillary lymph nodes dissection (ALND) were
included in the study. Informed and written consent
was obtained from all patients during preoperative
anaesthetic assessment a day before surgery.
Exclusion criteria included, known contraindication to
Mardhiah Sarah Harnani Mansor and Choy Yin Choy
medication use in the study, patients with chronic pain
or on daily intake of analgesic and impaired kidney
function (creatinine level >80 µmol/L). Patients were
randomized using computer-generated randomized
numbers to receive either pregabalin (Lyrica®) or
placebo (vitamin B complex). Information regarding
the study and the verbal numerical rating scale (VNRS)
range from 0 – 10 was explained to the patients. On the
day of surgery, all patients were given premedication
of oral midazolam 7.5 mg with either oral pregabalin
150 mg (in 2 tablets) or oral vitamin B complex (in 2
tablets) one hour before being sent to operating room.
Patients were instructed to close their eyes before
given the test drug to swallow.
In the operation theatre, basic monitoring
included electrocardiogram (ECG), oxygen saturation
(SpO2) and non invasive blood pressure (NIBP).
General anesthesia was induced with IV propofol
1.5 – 2.5 mg/kg and IV fentanyl. After the patient
was adequately anaesthetized, a supraglottic airway
device was inserted. Anaesthesia was maintained with
sevoflurane in 50% O2 / 50% air mixture maintaining
minimum alveolar concentration (MAC) of 0.8–1.0.
Intraoperatively, patients were given IV morphine 0.1–
0.2 mg/kg as an analgesic. Additional IV parecoxib 40
mg was given at the time of skin suturing. Adequate
local anesthetic infiltration of levobupivacaine up to 2
mg/kg was given by the surgeon at the incision site.
Pain was assessed by independent observer in
the recovery area, 2, 4, 6 and 24 hours postoperatively
using the VNRS at rest and on movement. In the
ward, all patients received oral etoricoxib 120 mg
daily with oral paracetamol 1g every 6 hours as a
standard analgesic. If the pain score was rated 5 or
more, intravenous tramadol 50 mg was given as a
rescue medication. Any incidence of side effects such
as nausea, vomiting, headache, somnolence, dizziness
and visual disturbance were documented.
Based on previous study13, with the power of
0.8, alpha value of 0.05 and dropout rate of 10%, the
sample size calculated was 60. Statistical analysis
and calculations was performed using SPSS for
Windows Version 12.0. VNRS pain score and amount
of intraoperative morphine used were analysed using
Mann-Whitney U-test. Categorical variables such
as number of patients needed rescue analgesic and
Effect of preoperative oral pregabalin on postoperative pain after mastectomy
65
Table 1
Demographic data values are expressed as mean± SD or number(percentage)
Age
Placebo
(n=24)
Pregabalin
(n=25)
52.0 ± 8.4
51.5 ± 9.6
Weight (kg)
62.4 ± 8.0
60.2 ± 5.0
Height (cm)
156.9 ± 3.0
156.2 ± 2.8
Race
Malay
Chinese
Indian
12 (50)
8 (33.3)
4 (16.7)
17 (68)
5 (20)
3 (12)
ASA
I
II
12 (50)
12 (50)
15 (60)
10 (40)
Type of operation
Mastectomy
Mastectomy with ALND
6 (25)
18 (75)
6 (24)
19 (76)
* p value = 0.024. “ p value = 0.006. ‘ p value = 0.003.
incidence of side effects were evaluated with X2 test or
Fischer’s exact test. A p value of <0.05 was considered
statistically significant.
Results
Forty nine patients were recruited in this study
in which 24 patients were in the placebo group and
25 patients were in the pregabalin group. There were
no statistical differences with regards to age, weight,
height, race, ASA and type of operation (Table 1).
Figure 1 showed VNRS at rest in pregabalin
group compared to placebo. There were statistically
significant differences at 2, 4 and 6 hours
postoperatively.
Figure 2 showed VNRS on movement in
Fig. 1
postoperative VNRS.
values are expressed
as mea
* p value = 0.024. “ p value = 0.006. ‘ p value = 0.003.
M.E.J. ANESTH 23 (1), 2015
66
Mardhiah Sarah Harnani Mansor and Choy Yin Choy
Fig. 2
postoperative
VNRS. values
are expressed as
mean
* p value = 0.005. “ p value = 0.016.
pregabalin group compared to placebo. There were
statistically significant differences at 4 and 6 hours
postoperatively.
There was no statistically significant difference
in the mean intraoperative morphine consumption in
both placebo group and pregabalin group.
Six patients from the placebo group and three
patients in the pregabalin group needed tramadol as
a rescue drug postoperatively, however the difference
was statistically not significant. There was no
difference in postoperative oral analgesic consumption
for both groups.
Adverse effects postoperatively in both groups,
which was statistically not significant are presented in
table 2.
There was no documented incidence of
somnolence or visual disturbances in any of the
patients.
Table 2
Incidence of side effects
Placebo
n = 24
Pregabalin
n = 25
Nausea/vomiting
17
19
Headache
8
7
Dizziness
9
16
Discussion
In this current study, we found that preoperative
single dose of oral pregabalin 150 mg was effective
in reducing both the resting and on movement
postoperative pain in patients undergoing mastectomy
with or without ALND. Spreng et al, showed a
reduction of postoperative pain at rest and morphine
consumption from 4 up to 24 hours postoperatively
after lumbar discectomy with a single dose of oral
pregabalin 150 mg10. In another study, Agarwal et
al used a single dose of oral pregabalin 150 mg and
effectively reduced postoperative pain and fentanyl
consumption in patients undergoing laparoscopic
cholecystectomy up to 24 hours11. Jokela et al used
oral pregabalin 150 mg preoperative for day-case
gynecological laparoscopic surgery and had better
analgesia during the early recovery but not sustained up
to 24 hours12. A study by Kim et al where mastectomy
patients received oral pregabalin 75 mg twice a day
showed that there was reduced postoperative pain and
analgesic consumption respectively13. That study also
showed the ability of divided doses of pregabalin to
reduced pain after 48 hours up to 1 week after surgery.
Ittichaikulthol et al used a higher dose of oral
pregabalin 300 mg preoperatively and showed
reduction of pain scores and morphine consumption
Effect of preoperative oral pregabalin on postoperative pain after mastectomy
for abdominal hysterectomy with or without salphingooophorectomy up to 24 hours post operatively14.
However a study by Paech et al using a lower dose
of oral pregabalin 100 mg preoperatively was unable
to reduce acute pain or improve recovery after minor
gynecological surgery15. Most of these studies also
showed comparable rescue analgesic needed similar
with the current study.
A meta analysis on efficacy of pregabalin in
acute postoperative pain by Zhang et al concluded
that postoperative opioid consumption and opioid
related side effects were reduced but pain scores were
not reduced. These conflicting results could possibly
be due to differences in dosage, dosing regimen, type
of surgery, the use of other analgesic regimes such as
opioid or non opioids, different anesthetic technique
and surgical procedure16.
Most studies showed pregabalin to be well
tolerated and associated with dose dependent
adverse effects that are mild to moderate and usually
transient11-15. Different doses of pregabalin have been
used in the literature and doses ranging from 75 mg
to 300 mg11-17. It has been shown that higher doses
67
are associated with increased frequencies of side
effects. The common adverse effects of pregabalin are
nausea and vomiting, visual disturbances, headache,
dizziness and somnolence. Most of the studies showed
no significant adverse effects when a lower dose of
pregabalin was used10-14. Nausea and vomiting were
the common side effects in the current study followed
by headache and dizziness. There were no documented
side effects of somnolence or visual disturbances.
There are a few limitations in study. The pain
score was assessed immediately in the postoperative
period in the recovery area which makes it difficult to
assess the effects of pregabalin at that point of time.
Another confounding factor is the use of IV tramadol
as a rescue drug which may affect the assessment
of pain score postoperatively and incidence of side
effects.
Conclusion
In conclusion, single dose of 150 mg pregabalin
given preoperatively compared to placebo significantly
reduced the postoperative pain scores after mastectomy.
M.E.J. ANESTH 23 (1), 2015
68
Mardhiah Sarah Harnani Mansor and Choy Yin Choy
References
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early postsurgical pain: current evidence and future directions.
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pregabalin on postoperative pain and preoperative anxiety in patients
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W, Putarawuthicai P and Rungphet S: Effects of pregabalin on
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Consumption Trends of Rescue Anti-Psychotics for
Delirium in Intensive Care Units (ICU Delirium) show
influence of Corresponding Lunar Phase Cycles:
A Retrospective Audit Study from Academic
University Hospital in the United States
Deepak Gupta**, Vinay Pallekonda*, Ronald Thomas**,
George Mckelvey** and Farhad Ghoddoussi**
Abstract
Background: The etiology of delirium in intensive care units (ICU) is usually multi-factorial.
There is common “myth” that lunar phases affect human body especially human brains (and minds).
Objective: In the absence of any pre-existing studies in ICU patients, the current retrospective
study was planned to investigate whether lunar phases play any role in ICU delirium by assessing
if lunar phases correlate with prevalence of ICU delirium as judged by the corresponding
consumptions of rescue anti-psychotics used for delirium in ICU.
Materials and Methods: After institutional review board approval with waived consent,
the daily census of ICU patients from the administrative records was accessed at an academic
university’s Non-Cancer Hospital in a Metropolitan City of United States. Thereafter, the ICU
pharmacy’s electronic database was accessed to obtain data on the use of haloperidol and quetiapine
over the two time periods for patients aged 18 years or above. Subsequently the data was analyzed
for whether the consumption of haloperidol or quetiapine followed any trends corresponding to the
lunar phase cycles.
Results: A total of 5382 pharmacy records of haloperidol equivalent administrations
were analyzed for this study. The cumulative prevalence of incidents of haloperidol equivalent
administrations peaked around the full moon period and troughed around the new moon period.
As compared to male patients, female patients followed much more uniform trends of haloperidol
equivalent administrations’ incidents which peaked around the full moon period and troughed
around the new moon period. Further sub-analysis of 70-lunar cycles across the various solar
months of the total 68-month study period revealed that haloperidol equivalent administrations’
incidents peaked around the full moon periods during the months of November-December and
around the new moon periods during the month of July which all are interestingly the major holiday
months (a potential confounding factor) in the United States.
Conclusion: Consumption trends of rescue anti-psychotics for ICU delirium revealed an
influence by lunar phase cycles particularly that of full moon periods on female patients in the ICU.
Introduction
* *MD.
**PhD.
Corresponding author: Vinay Pallekonda MD, Department of Anesthesiology, Wayne State University, School of Medicine.
Box No 162, 3990 John R, Detroit, MI 48201. Tel: 313-745-7233, Facsimile: 313-993-3889. E-mail: [email protected]
69
M.E.J. ANESTH 23 (1), 2015
70
Critically ill patients in the Intensive Care Units
(ICUs) frequently experience delirium which is an
acute reversible dysfunction of the brain. The etiology
of ICU delirium is usually multi-factorial1. There is
common “myth” that lunar phases affect human body
especially human brains (and minds). This “myth”
has often been studied in various scenarios including
automobile accidents and injury accidents2, suicides3,
peri-operative blood loss4, clustering of seizures5,
mental status changes in schizophrenics6, and human
and animal behavior and physiology7. The results of
these studies reveal much ambiguity of the issue due to
poorly understood underlying mechanisms; and hence
results of various studies have either supported5-7 or
refuted2-4 this norm/”myth” altogether. The common
thread of this “myth” is that as lunar phases affect the
oceans (tidal forces), these phases may affect the human
body because it is composed of 70% water (fluids) that
may result in “human tidal waves” generated by lunar
influences8.
Based on this background and in the absence
of any pre-existing studies in the ICU patients, the
current retrospective study was planned to investigate
whether lunar phases have any role in ICU delirium
by assessing if lunar phases correlate with prevalence
of ICU delirium as judged by the corresponding
consumptions of rescue anti-psychotic medications
used for delirium in ICU.
Materials and Methods
After institutional review board approval with
waived consent, the daily census of ICU patients from
the administrative records was accessed at an academic
university’s Non-Cancer Hospital in a Metropolitan
City of United States. Thereafter, the ICU pharmacy’s
electronic database was accessed to obtain data on the
use of haloperidol and quetiapine over the two time
periods for patients aged 18 years or above. Haloperidol
and quetiapine are the two rescue anti-psychotic
medications primarily used to manage ICU delirium
in our hospital. The two time periods analyzed in this
study were: 2008-2012 (five year period before the
standardized protocol for ICU delirium was instituted
in our hospital) and March 2013-October 2013 (eight
month period after the standardized protocol for ICU
Gupta Deepak et. al
delirium was instituted in our hospital). Since March
2013, our hospital’s standardized protocol for ICU
delirium include (a) daily screening for delirium with
Intensive Care Delirium Screening Checklist (ICDSC)
to recognize patients with positive ICDSC scores ≥4
followed by (b) their initial non-pharmacological
management with sleep promotion, ambient noise
reductions during night-time, early and aggressive
ambulation, and circadian rhythm cycle promotion,
and thereafter reserving (c) pharmacological treatment
for intractable cases in form of haloperidol 2.5mg
every 6hrs as needed intravenous boluses (maximum
single dose 5mg and maximum daily dose 40mg)
or quetiapine 25-50mg by mouth every 12hrs
(maximum dose 200mg every 12hrs) besides ensuring
maximization of pain management strategies and
minimization of benzodiazepine use among the ICU
delirium patients.
Subsequently, the day-to-day lunar phases
(from new moon to first quarter to full moon to third
quarter) for these time periods were accessed from
the freely available public domain web-address http://
www.timeanddate.com/calendar/moonphases.html.
Thereafter, the daily prevalence of ICU delirium was
adjudged by recording the daily percentage of ICU
patients who had received haloperidol or quetiapine.
Subsequently, the data was analyzed for whether the
incidents of haloperidol or quetiapine administrations
followed any medication consumption trends
corresponding to the lunar phase cycles (any timesensitive-trends across the 29-plus days of a standard
lunar cycle as described in Table 1). Additionally, the
data was compared for patients’ age and sex, and their
actual haloperidol/quetiapine usage. For uniformity
during comparisons, all anti-psychotic usage was
equated to per mg oral haloperidol equivalents as per
the below-mentioned explanations for bio-equivalence.
Using a multiplication factor of 1.6, intravenous
haloperidol dose was converted to oral haloperidol
equivalent as per the recommendations of the freely
available public domain web-address http://www.
globalrph.com/haloperidol_dilution.htm.
Similarly,
9
although Woods (2003) advised using a conversion
of 75mg quetiapine as equivalent to 2mg oral
haloperidol, Andreasen et al (2010)10 described the
changing arena of patients’ requirements for very
Rescue anti-psychotics for delirium in ICU
71
Table 1
Nomenclature of Lunar Phases for the Study
Popular
Nomenclature
Popular Explanation
Nomenclature for Explanation for This Study
This Study
New Moon
Time when 0% Visible Moon
New Moon Period
First Quarter
Time after New Moon when 50% NOT STUDIED
Moon becomes Visible
NOT APPLICABLE
Full Moon
Time when 100% Visible Moon
24-hr period in either direction of Full
Moon’s Time (Total 48-hr Period)
Last Quarter
(also known as Third
Quarter)
Time after Full Moon when 50% Moon NOT STUDIED
remains Visible
NOT APPLICABLE
Waxing Crescent
Over 7-8 days when Moon becomes Lunar Phase 1
Visible from 0% to 50%
Time Zone from New Moon’s Time to First
Quarter’s Time
Waxing Gibbous
Over 7-8 days when Moon becomes Lunar Phase 2
Visible from 50% to 100%
Time Zone from First Quarter’s Time to
Full Moon’s Time
Waning Gibbous
Over 7-8 days when Moon looses Lunar Phase 3
Visibility from 100% to 50%
Time Zone from Full Moon’s Time to Last
Quarter’s Time
Waning Crescent
Over 7-8 days when Moon looses Lunar Phase 4
Visibility from 50% to 0%
Time Zone from Last Quarter’s Time to
New Moon’s Time
high doses of quetiapine for efficacy and hence
calculated and recommended the changed equivalent
doses as 151.97mg quetiapine equivalent to 2 mg oral
haloperidol. Therefore, for our retrospective study, we
followed the latest 2010 recommendations and used 76
mg quetiapine per mg oral haloperidol equivalent for
study results analysis.
For statistical analysis, ANOVA (Analysis of
Variance) tests (Repeated measures 2 way ANOVA
treatment) were used to compare the continuous data.
Fisher exact test and Chi square analysis were used to
compare categorical data. For post-hoc analyses, the
Student Newman-Keuls test was used. P-values <0.05
were considered statistically significant.
Results
As described in the CONSORT Diagram (Figure
1), a total of 5382 pharmacy records of haloperidol
equivalent administrations were analyzed for this study
(4734 administrations during 2008-2012 period and
648 administrations during 8-month period in 2013).
The time-trends analysis for these administrations
Full Moon Period
24-hr period in either direction of New
Moon’s Time (Total 48-hr Period)
were tabulated based on a minimally modified popular
nomenclature of lunar phases (Table 1) where the
focus was comparisons between new moon period vs.
full moon period; and inter-phase comparisons among
the four lunar phases. As shown in Table 2, although
there were variations for ICU delirium incidence
among lunar cycles with the widest values ranging
from one-in-four ICU patients to one-in-nine ICU
patients receiving haloperidol equivalents (P <0.001),
most commonly every 5th or 6th ICU patient based on
daily ICU census was receiving haloperidol equivalent
during 2008-2013 combined period irrespective of
lunar cycle phase. However, the cumulative prevalence
of incidents of haloperidol equivalent administrations
(Table 2; Figure 2) were significantly different in both
study periods (2008-2012 and 8-month 2013) wherein
the incidents of haloperidol equivalent administrations
peaked around the full moon period and troughed
around the new moon period. There was a significant
difference between the incidents of haloperidol
equivalent administrations based on the patients’
sex (Table 3; Figure 3) wherein as compared to male
patients, female patients followed much more uniform
M.E.J. ANESTH 23 (1), 2015
72
Gupta Deepak et. al
Table 2
At any given time-point, each instance of haloperidol equivalent administration was representative as following
LUNAR PERIOD
Percentage Incidence
of Haloperidol
Equivalent
Administration per
Daily Census
Incidence of
Haloperidol
Equivalent
Administration per
Daily Census On
Average
P Value
(F-Test)
COMBINED 2008-2013
Cumulative Prevalence
of Incidents of
Haloperidol Equivalent
Administrations
P Value
(F-Test)
COMBINED 2008-2013
New Moon Period
16.7% ±16.6%
1-in-6 Patients
0.88
n=337
Full Moon Period
16.9% ±14.7%
1-in-6 Patients
Lunar Phase 1
18.3% ±18.3%
1-in-5 Patients
Lunar Phase 2
17.6% ±16.2%
1-in-6 Patients
n=1453
Lunar Phase 3
17.5% ±14.5%
1-in-6 Patients
n=1427
Lunar Phase 4
18.7% ±19.2%
1-in-5 Patients
n=1308
0.006
n=412
0.18
2008-2012
n=1194
<0.001*
2008-2012
New Moon Period
16.1% ±15.0%
1-in-6 Patients
<0.001
n=309
Full Moon Period
17.8% ±15.4%
1-in-6 Patients
New Moon Period
23.8% ±28.3%
1-in-4 Patients
n=28
Full Moon Period
10.7% ±5.2%
1-in-9 Patients
n=51
0.03
n=361
2013
2013
2008-2012
0.008
2008-2012
Lunar Phase 1
18.8% ±18.6%
1-in-5 Patients
Lunar Phase 2
18.3% ±17.1%
1-in-5 Patients
n=1269
Lunar Phase 3
17.9% ±15.0%
1-in-6 Patients
n=1248
Lunar Phase 4
19.6% ±20.0%
1-in-5 Patients
n=1166
2013
0.16
n=1051
<0.001*
2013
Lunar Phase 1
14.1% ±15.1%
1-in-7 Patients
n=143
Lunar Phase 2
12.9% ±6.1%
1-in-8 Patients
n=184
Lunar Phase 3
14.6% ±9.1%
1-in-7 Patients
n=179
Lunar Phase 4
11.8% ±6.5%
1-in-8 Patients
n=142
0.02*
*All pair-wise post-hoc comparisons are significantly different (P<0.05) when compared to their expected frequencies
trends of haloperidol equivalent administrations’
incidents which peaked around the full moon period
and troughed around the new moon period during both
study periods (2008-2012 and 8-month 2013). On
further analysis of the actual administered haloperidol
mg equivalent doses, the statistical significance for
differences in the administered doses across lunar
cycle phases were only observed when the patientdoses were compared across the combined 2008-2013
period (Table 4: section B); and even though there was
a statistical significance, the average clinical doses
were 0.6-0.7 haloperidol mg equivalent per daily
ICU census across all the lunar cycle phases (Table
4: section B). Further sub-analysis of 70-lunar cycles
across the various solar months of the total 68-month
study period (Figure 4) revealed that haloperidol
equivalent administrations’ incidents peaked around
the full moon periods during the months of NovemberDecember and around the new moon periods during
the month of July; however, interestingly, the actual
administered haloperidol mg equivalent average doses
were highest around the new moon periods during the
months of November-December.
Rescue anti-psychotics for delirium in ICU
73
Fig 1
CONSORT Diagram
Discussion
To summarize the key points of the study results:
(a) ICU delirium events, as adjudged by haloperidol
equivalent administrations’ incidents, occurred on an
average in approximately 20% of ICU patients daily
at our hospital during 2008-2013; (b) ICU delirium
events peaked around full moon; (c) ICU delirium
events trended similarly across the lunar cycles during
pre-standardized protocol time period (2008-2012) as
well as during post-standardized protocol time period
(2013); (d) as compared to male patients, ICU delirium
events in female patients more uniformly followed
lunar cycle trends; (e) after removing patients’ age as
confounding factor, haloperidol mg equivalent doses’
trends were statistically different (though differences
were clinically inconspicuous) in relation to lunar
cycle phases; and (f) ICU delirium events happening in
relation to lunar cycle phases were more common in the
solar months of July, November and December which
are interestingly the major holiday months (a potential
confounding factor) in the United States besides July
being first month-in-training for new resident/fellow
ICU physicians and November-December being
severe winter weather months in our Metropolitan city.
The moon and its effects on animal and human
M.E.J. ANESTH 23 (1), 2015
74
Gupta Deepak et. al
Table 3
Demographics of Patients who received Haloperidol Equivalent Administrations
LUNAR PERIOD
Age (Mean ±SD)
in years
P Value
(F-Test)
Cumulative Prevalence
of Incidents of
Haloperidol Equivalent
Administrations
Gender Distribution of
Incidents of Haloperidol
Equivalent Administrations
P Value
(F-Test)
COMBINED 2008-2013
New Moon Period
57.8 ±13.5
Full Moon Period
59.1 ±14.2
Lunar Phase 1
58.3 ±13.7
Lunar Phase 2
0.2
n=337
Females 39%
Males 61%
n=412
Females 54%
Males 46%
n=1194
Females 43%
Males 57%
57.6 ±15.2
n=1453
Females 50%
Males 50%
Lunar Phase 3
57.5 ±13.7
n=1427
Females 51%
Males 49%
Lunar Phase 4
58.5 ±13.8
n=1308
Females 45%
Males 55%
n=309
Females 39% Males 61%
n=361
Females 53%
Males 47%
n=28
Females 50%
Males 50%
n=51
Females 63%
Males 37%
n=1051
Females 41%
Males 59%
0.15
<0.001
<0.001
2008-2012
New Moon Period
57.2 ±13.5
Full Moon Period
59.0 ±14.0
0.09
<0.001
2013
New Moon Period
65.0 ±11.6
Full Moon Period
60.1 ±16.0
0.16
0.34
2008-2012
Lunar Phase 1
57.9 ±13.6
0.09
Lunar Phase 2
56.9 ±15.3
n=1269
Females 48%
Males 52%
Lunar Phase 3
57.4 ±13.9
n=1248
Females 49%
Males 51%
Lunar Phase 4
58.2 ±14.1
n=1166
Females 45%
Males 55%
n=143
Females 57%
Males 43%
<0.001
2013
Lunar Phase 1
61.3 ±14.5
0.009
Lunar Phase 2
62.9 ±13.5
n=184
Females 60% Males 40%
Lunar Phase 3
58.4 ±12.6
n=179
Females 63% Males 37%
Lunar Phase 4
61.2 ±10.5
n=142
Females 47%
Males 53%
0.03
Rescue anti-psychotics for delirium in ICU
75
Table 4
Haloperidol mg Equivalent-Strength Administration Dose Per Daily Intensive Care Unit Census
Lunar Period
Characteristic that Acted as
Confounding Factor/Covariate
Study Period 2008-2012
A
Number of
Administrations (n)
New
Period
Moon 309
Haloperidol mg
Equivalent (Mean
±SD)
P Value
(F-Test)
Study Period 2013
Number of
Administrations (n)
Haloperidol mg
Equivalent (Mean
±SD)
0.6 ±1.0
28
0.4 ±0.7
Full
Moon Period
361
0.6 ±0.7
51
0.4 ±0.4
Lunar Phase 1
1051
0.6 ±0.9
143
0.4 ±0.6
Lunar Phase 2
1269
0.6 ±1.0
184
0.4 ±0.5
Lunar Phase 3
1248
0.6 ±0.8
179
0.5 ±0.6
Lunar Phase 4
1166
0.7 ±1.1
142
0.4 ±0.7
Patient’s Age as Co-Variate
B
Number of Administrations (n)
New
Period
Moon 337
Haloperidol mg Equivalent (Mean ±SD)
0.6 ±1.0
Full
Moon Period
412
0.6 ±0.7
Lunar Phase 1
1194
0.6 ±0.9
Lunar Phase 2
1453
0.6 ±0.9
Lunar Phase 3
1427
0.6 ±0.8
Lunar Phase 4
1308
0.7 ±1.1
Patient’s Sex: Female
C
Number of
Administrations (n)
Haloperidol mg
Equivalent (Mean
±SD)
0.85
0.27
P Value
(F-Test)
0.006
0.001
Patient’s Sex: Male
Number of
Administrations (n)
Haloperidol mg
Equivalent (Mean
±SD)
New
Period
Moon 133
0.4 ±0.5
204
0.6 ±1.2
Full
Period
Moon 223
0.5 ±0.7
189
0.6 ±0.7
Lunar Phase 1
509
0.5 ±0.8
685
0.6 ±0.9
Lunar Phase 2
721
0.6 ±0.9
732
0.6 ±1.0
Lunar Phase 3
728
0.6 ±0.8
699
0.6 ±0.8
Lunar Phase 4
591
0.6 ±0.9
717
0.7 ±1.2
P Value
(F-Test)
0.17
0.74
M.E.J. ANESTH 23 (1), 2015
76
Fig. 2
Graphical Presentation of
Haloperidol Equivalent
Administrations’ Incidents
across the Whole Study Period:
New Moon vs. Full Moon AND
Lunar Phases 1-4 (Comparative
P-Values reported in Table 2)
Fig. 3
Graphical Presentation of
Haloperidol Equivalent
Administrations’ Incidents’
Distribution per Patients’ Sex/
Gender: New Moon vs. Full
Moon AND Lunar Phases 1-4
(Comparative P-Values reported
in Table 3)
Gupta Deepak et. al
Rescue anti-psychotics for delirium in ICU
77
Fig. 4
Graphical Presentation of
Haloperidol Equivalent
Administrations’ Incidents across
the 68-Solar Month Study Period:
New Moon vs. Full Moon (F-Test
P-Value <0.001 for Overall
Solar Month Trends’ Effect) AND
Lunar Phases 1-4 (F-Test P-Value
<0.001 for Overall Solar Month
Trends’ Effect)
behavior have fascinated mankind since ancient times.
Similarly, the medical profession has not been naive
or immune to these discussions. Thakur and Sharma
(1984)8 observed that crime rates in three different
cities in India during 1978-1982 increased threefold
from new moon period to full moon period; and the
authors explained this effect secondary to “human tidal
waves” in human physiology as similar to gravitational
effects of moon on the oceans. However, Laverty and
Kelly (1998)2 reviewed a nine-year period with almost
300,000 accidents and observed periodic changes
secondary to calendar changes and season changes but
no relationship was apparent in relation to lunar cycle
phases including full moon period.
Barr (2000)6 revisited the historical aspect of term
“lunacy” wherein during pre-modern times, mentally
ill patients were supposedly displaying behavior
changes in accordance to the changes in moon (“lunar”)
phases. Among 100 patients who were followed for
two-and-half years, Barr6 observed significant changes
during full moon period in the schizophrenic patients
as compared to the non-schizophrenic patients; and
concluded that further investigations were required
to validate the findings. Zimecki (2006)7 further
expanded these discussion by reviewing the lunar
phase effects on the animal kingdom in regards to
phylogenesis, fishes’ fertility cycles, hormonal level
changes in birds, sensory system of rats, and human
reproduction. Zimecki7 tried to explain lunar effects
on animal physiology as due to possible induction
of changes in electromagnetic milieu around animals
due to the periodic changes in the moon. Around
same time, Polychronopoulos et al (2006)5 reported
neurology emergency department experience over
five year-period that as compared to 21.4% epileptic
seizures that occurred during new moon period, 34.2%
epileptic seizures occurred during full moon period.
They re-iterated5 the possibility of epileptic seizures
induction secondary to deprived sleep behavior during
the full moon periods as an evolutionary learned
behavior in response to increased night-time ambient
light during the full moon period.
Recently, Voracek et al (2008)3 reviewed over
65,000 suicides in Austria from 1970-2006. They
M.E.J. ANESTH 23 (1), 2015
78
did not find any significant difference in completed
suicides’ incidence between new moon period vs. full
moon period, and the completed suicides’ incidence was
equally divided among the four lunar phases. Voracek
et al (2008)3 suggested that as compared to their almost
four-decade long study period, other researchers’ short
duration study periods can be the reason for other
studies reporting lunar effects on human behavior
events because they themselves also observed new
moon as well as full moon sporadically affecting
completed suicide rates during a few individual years
among their cumulative 37-year long study period.
Similarly, Schuld et al (2011)4 questioned the idea of
patients scheduling their elective major surgeries in
accordance to avoid lunar phases like full moon period
because their analysis of emergency surgeries’ tenyear data revealed absence of statistical significance in
regards to any differences in peri-operative blood loss
and complications when measured in concurrence to
lunar phases.
The limitations of our study are that (a) it is a
retrospective analysis, (b) it measured primarily the
action (rescue anti-psychotics use) and assumed the
corresponding cause (ICU delirium), (c) it puts forth
only our observations but does not provide evidence for
the interpretation how (if any) lunar phases affect ICU
Gupta Deepak et. al
delirium, and (d) it does not differentiate the effects
of lunar phases (if any) on the ICU delirium patients
vs. their medical care providers who had diagnosed
ICU delirium and decided to administer haloperidol
equivalents.
Conclusion
In summary, consumption trends of rescue antipsychotics for ICU delirium revealed an influence
by lunar phase cycles particularly that of full moon
periods on female patients in the ICU.
Acknowledgement
The authors are deeply indebted to the appreciative
efforts of Ms. Connie Tourangeau, Pharmacist, and
Mr. Xavier Bell, Field Engineer, Department of
Pharmacy, Harper Hospital, Detroit Medical Center,
Detroit, Michigan, United States in regards to their
retrospective enlisting of the ICU patients according
to the medications that they had received per their
databases. The authors are also grateful to Ms Sapna
Parmar, Information Systems Division Application
Staff, for her help in enlisting daily ICU patients’
census data for our retrospective study period.
Rescue anti-psychotics for delirium in ICU
79
References
1. Banh HL: Management of delirium in adult critically ill patients: an
overview. J Pharm Pharm Sci; 2012, 15:499-509.
2. Laverty WH, Kelly IW: Cyclical calendar and lunar patterns in
automobile property accidents and injury accidents. Percept Mot
Skills; 1998, 86:299-302.
3. Voracek M, Loibl LM, Kapusta ND, Niederkrotenthaler T,
Dervic K, Sonneck G: Not carried away by a moonlight shadow:
no evidence for associations between suicide occurrence and lunar
phase among more than 65,000 suicide cases in Austria, 1970-2006.
Wien Klin Wochenschr; 2008, 120:343-349.
4. Schuld J, Slotta JE, Schuld S, Kollmar O, Schilling MK, Richter
S: Popular belief meets surgical reality: impact of lunar phases,
Friday the 13th and zodiac signs on emergency operations and
intraoperative blood loss. World J Surg; 2011, 35:1945-1949.
5. Polychronopoulos P, Argyriou AA, Sirrou V, Huliara V, Aplada
M, Gourzis P, Economou A, Terzis E, Chroni E: Lunar phases
and seizure occurrence: just an ancient legend? Neurology; 2006,
66:1442-1443.
6. Barr W: Lunacy revisited. The influence of the moon on mental
health and quality of life. J Psychosoc Nurs Ment Health Serv; 2000,
38:28-35.
7. Zimecki M: The lunar cycle: effects on human and animal behavior
and physiology. Postepy Hig Med Dosw (Online); 2006, 60: 1-7.
8. Thakur CP, Sharma D: Full moon and crime. Br Med J (Clin Res
Ed); 1984, 289:1789-1791.
9. Woods SW: Chlorpromazine equivalent doses for the newer atypical
antipsychotics. J Clin Psychiatry; 2003, 64:663-667.
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Antipsychotic dose equivalents and dose-years: a standardized
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M.E.J. ANESTH 23 (1), 2015
The Use of Paravertebral Blockade for
Analgesia after Anterior-Approach
Total Hip Arthroplasty.
Alberto E. Ardon* MD MPH, Roy A. Greengrass*
MD, Upasna Bhuria* MBBS,
Steven B. Porter* MD, Christopher B. Robards*
MD and Kurt Blasser** MD
Abstract
Background: Anterior approaches for total hip arthroplasty (ATHA) are becoming
increasingly popular. We postulated that the use of PVB of the T12, L1, and L2 roots would provide
adequate analgesia for ATHA while allowing motor sparing.
Methods: The medical records of 20 patients undergoing primary ATHA were reviewed.
T12, L1 and L2 paravertebral blockade was accomplished with 3-4ml of 1% ropivacaine with
epinephrine 1:200,000 and 0.5mg/ml of preservative-free dexamethasone per level. Primary
outcomes were mean opioid consumption in intravenous morphine equivalents and worst recorded
visual analog scale (VAS) pain scores during postoperative days 0 to 2 (POD 0 to 2).
Results: Mean opioid consumption was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on
POD2. Median worst VAS scores were 2 for all time intervals except POD 0, which had a median
value of 0. All patients had full hip motor strength the evening of POD0. 19 patients were able to
ambulate the afternoon of POD1.
Conclusion: T12-L2 PVB, when utilized as part of a multimodal analgesic regimen, results
in moderate opioid consumption, low VAS scores, preservation of hip motor function, and may be
an effective regional anesthesia technique for ATHA.
Keywords: Paravertebral blockade1, anterior total hip arthroplasty, multimodal analgesia,
opioid consumption.
Introduction
Anterior approaches for total hip arthroplasty are becoming increasingly popular due to
advantages of less muscle trauma, resulting in enhanced convalescence1.
*Department of Anesthesiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224.
**Department of Orthopedic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224.
Corresponding author: Alberto E. Ardon, Department of Anesthesiology, Mayo Clinic, Jacksonville, FL 4500 San Pablo
Road, Jacksonville, FL 32224. Tel: 904-766-0738; 225-773-4407, Fax: 904-956-3332. E-mail: [email protected]
Present academic appointment and address: Assistant Professor, University of Florida-Jacksonville, 2nd Floor, Clinical
Center, Department of Anesthesiology, 655 West 8th Street, C72, Jacksonville, FL 32209. Tel: 904-244-4195; 225-7734407, Fax: 904-244-4908. E-mail [email protected]; [email protected]
1. PVB: paravertebral blockade.
ATHA: anterior total hip arthroplasty.
POD: postoperative day.
VAS: visual analog scale.
81
M.E.J. ANESTH 23 (1), 2015
82
Unfortunately, similar to posterior approaches,
anterior total hip arthroplasty (ATHA) is associated
with significant pain requiring moderate to large doses
of opioids with attendant side effects. Multimodal
analgesia including regional analgesic techniques such
as posterior lumbar plexus block (psoas compartment
block) have been utilized to treat the pain of total hip
arthroplasty with encouraging results2. However, the
motor weakness associated with psoas compartment
block may limit ambulation and decrease effective
physiotherapy, possibly increasing the risk of falls3. It
is felt by many surgeons that motor sparing analgesic
techniques would be of benefit to patients.
While opioids are commonly used for
postoperative analgesia in hip arthroplasty patients, the
use of these medications is associated with a significant
negative side effect profile that includes nausea and
vomiting, respiratory depression, prolonged recovery
room stay, increased healthcare burden, and decreased
patient satisfaction4. Consequently, the use of a
regional anesthetic technique as a part of a multimodal
analgesic plan aimed at reducing postoperative opioid
consumption would be advantageous.
The paravertebral block (PVB) is a block of
the mixed nerve soon after it exits the intervertebral
foramen5. It provides intense unilateral analgesia of
long duration and has become the primary anesthetic
for many applications6,7. We postulated that the use
of PVB of the T12, L1 and L2 roots would provide
adequate analgesia for ATHA while allowing motor
sparing. In this study we present our initial expanded
case series of 20 patients who received PVB for ATHA.
Methods
The Institutional Review Board (IRB) approved
this study. From June 2013 to February 2014, the
medical records of 20 patients undergoing primary
ATHA were reviewed. No patient had preoperative
motor deficit or opioid consumption requiring longacting opioids.
After a preoperative interview, informed consent
for both surgical anesthesia and peripheral nerve
blockade was obtained by an anesthesiologist. All
blocks were performed in the preoperative area in a
sterile fashion after placement of American Society of
Alberto Ardon et. al
Anesthesiologists standard monitors and verification of
patient identity and laterality of the procedure. Sedation
was at the discretion of the attending anesthesiologist,
and included sedative doses of midazolam, fentanyl,
ketamine, and/or propofol.
For PVB placement, patients were positioned
in the sitting position. The T12, L1 and L2 spinous
processes were identified in the sitting position either
by counting from the L4 spinous process at the level
of iliac crest and/or from the T7 spinous process
at the level of lower border of the scapulae. Needle
entry points were marked 2.5 cm lateral to the spinous
process as described previously by Greengrass et
al5. After skin infiltration with 2% lidocaine with
epinephrine 1:200,000 at the marked sites, a sterile
22 G, 10 cm Tuohy needle (B Braun, Melsungen,
DE) was introduced perpendicular to the skin until
the transverse process was contacted. The needle was
then redirected in a caudad direction and advanced
1-1.5 cm. After negative aspiration, 3-4 ml of 1%
ropivacaine with epinephrine 1:200,000 and 0.5mg/ml
of preservative free dexamethasone were injected per
level. Injections were repeated at the other two levels.
Sensory deficit in the distribution of T12, L1 and L2
dermatomes were confirmed with ice testing prior to
surgical anesthesia. Absence of motor blockade upon
hip flexion, assessed with the modified Bromage scale,
was also confirmed preoperatively. The modified
Bromage scale is defined as follows: 1 = unable to
move foot or knee; 2 = able to move foot only; 3 =
just able to move knee; 4 = full flexion of knee; 5 = no
detectable weakness of hip flexion while supine. One
patient required an additional injection at all levels to
establish appropriate sensory deficit.
Surgical anesthesia was achieved with an
intrathecal injection of 12.5 to 13mg of preservativefree isobaric 0.5% bupivacaine. The same surgeon
performed all surgeries utilizing a modified SmithPeterson anterior approach. No patients had
intraoperative complications. At the discretion of the
surgeon, patients received an intra-articular injection
consisting of morphine 10mg, ketorolac 30mg, and
epinephrine 200mcg. Daily opioid and non-opioid
analgesic consumption, visual analog scale (VAS) pain
scores, and length-of-stay data were extracted from the
electronic medical record.
Paravertebral block for hip arthroplasty
83
Table 1
Patient characteristics
Pt ID
Age
ASA
Sex
Operative Side
Consistent Preoperative
opioid, if any
Day of Discharge
1
82
2
64
3
F
Right
No
POD 3
2
M
Right
No
POD 2
3
72
3
F
Right
No
POD 3
4
56
1
M
Right
No
POD 2
5
74
3
M
Left
No
POD 3
6
76
2
F
Left
No
POD 3
7
81
3
M
Left
No
POD 3
8
65
2
M
Left
Oxycodone
POD 3
9
72
2
M
Right
No
POD 2
10
71
2
M
Left
No
POD 3
11
69
2
M
Left
Oxycodone
POD 2
12
61
2
F
Right
No
POD 2
13
77
2
M
Left
No
POD 3
14
91
3
M
Right
No
POD 3
15
67
2
F
Left
No
POD 3
16
70
2
F
Right
No
POD 3
17
64
2
F
Right
Hydrocodone
POD 3
18
70
3
M
Right
No
POD 3
19
72
3
M
Left
No
POD 3
20
83
3
M
Left
No
POD 2
Postoperatively, patients received scheduled
intravenous acetaminophen every 6 hours for the first
24 hours, and thereafter on an as-needed basis. All
patients received oral celecoxib 200mg twice daily.
Primary Outcomes
Mean opioid consumption in intravenous morphine
equivalents during the time intervals of postoperative
day 0 (POD 0, defined as the period of time from surgical incision until 07:00 on postoperative day 1), postoperative day 1 (POD 1, defined as 07:00 until 07:00
on POD2), and postoperative day 2 (POD 2, defined as
.)07:00 on POD2 until 18:00
Worst recorded visual analog scale (VAS) pain scores,
rated from 0 - 10, during time intervals from POD 0
.to 2
Secondary Outcomes
Secondary outcomes included maximum opioid
consumption, non-opioid analgesic consumption,
ability to ambulate, and distance ambulated.
Results
Patient characteristics are shown in Table 1.
A total of 20 patients were included, all of whom
received a spinal anesthetic. Mean operative time
was 78 minutes. Three patients had documented
preoperative opioid consumption with short-acting
agents. However, none of these patients consumed
more than 30mg of oral morphine equivalents per day.
The remaining patients denied use of preoperative
opioids. No patients developed complications from
the paravertebral blocks while hospitalized. No falls
M.E.J. ANESTH 23 (1), 2015
84
Alberto Ardon et. al
Table 2
Opioid consumption in IV morphine equivalents (mg)
Patient ID
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Mean
Median
POD 0
4
10
10
15
0
5
12
10
9
0
10
10
5.3
3.3
20.3
10
21.7
16.7
0
0
8.4
9.5
POD 1
12
10
10
10
15
33.3
42.3
20
11.3
20
15
25
4
13.3
18.3
15
36.7
10
0
0
16.6
15
POD 2
9
5
5
10
0
30
15.6
15
5
15
10
10
13.3
7.5
5.3
10
30
0
0
0
9.8
9.5
Table 3
Visual analog pain scores
Patient ID
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
n/a: not recorded
secondary to lack of record
or patient discharge
Worst VAS
POD 0 to
19:00
0
0
5
0
0
0
2
0
0
0
5
4
0
6
4
2.5
6
0
0
0
Worst VAS
POD 0-1
overnight
0
4
2
8
1
7
2
4
0
3
5
2
2
5
2
2
4
6
0
0
Worst VAS
POD 1 AM
Worst VAS
POD 1 PM
0
2
0
3
0
3
2
1
0
3
2
3
2
3
2
0
6
2
0
0
0
2
0
3
n/a
1
0
2
0
2
2
3
0
3
3
2
4
0
0
0
Worst VAS
POD 1-2
overnight
0
4
0
3
3
5
7
2
0
2
2
1
0
3
3
0
5
4
0
1
Worst VAS
POD 2 AM
Worst VAS
POD 2 PM
2
2
2
2
0.5
0
0
2
0
2
5
1
0
0
2
0
4
2
1
2
2
n/a
3
n/a
1
4
4
0
2
2
4
n/a
n/a
0
3
1.5
3
2
0
n/a
Paravertebral block for hip arthroplasty
occurred during hospitalization. Six patients were
discharged on POD 2.
Opioid consumption in IV morphine equivalents
by patient is shown in Table 2. Mean opioid consumption
was 8.4mg on POD0, 16.6mg on POD1, and 9.8mg on
POD2. Median opioid consumption was 9.5mg, 15mg,
and 9.5mg for POD0, POD1, and POD2, respectively.
Maximum opioid consumption was 21.7mg on POD0,
42.3mg on POD1, and 30mg on POD2. The three
patients with documented preoperative opioid use had
postoperative opioid consumption greater than the
median on POD 0, 1 and 2.
Worst VAS scores recorded for each patient are
shown in Table 3; values ranged from 0 to 8. Median
worst VAS scores, shown in Table 4, were 2 for all
time intervals except POD0, which had a median value
of 0.
Table 4
Median worst visual analog pain scores (minimum, maximum)
POD0 to 19:00
0 (0,6)
POD 0-1 overnight
2 (0,8)
POD1 AM
2 (0,6)
POD1 PM
2 (0,4)
POD 1-2 overnight
2 (0,7)
POD2 AM
2 (0,5)
POD2 PM
2 (0,4)
Regarding non-opioid analgesics, median
acetaminophen and celecoxib doses are shown in Table
5. Median acetaminophen dose was highest on POD 0
(4000mg), while median celecoxib dose was higher on
POD1 and POD2 (400mg).
Table 5
Median acetaminophen and celecoxib consumption among
patients (mg)
Acetaminophen Consumption
POD 0
4000
POD 1
2650
POD 2
1000
Celecoxib Consumption
POD 0
200
POD 1
400
POD 2
400
85
All patients had modified Bromage scores of 5
the evening of POD 0; 2 patients were able to ambulate
at that time. On the morning of POD 1, 15 patients
were able to ambulate, while 19 were able to do so by
that afternoon (Table 6). Median distances ambulated
on the morning and afternoon of POD1 were 30 feet
and 80 feet, respectively.
Table 6
Ambulation among study patients, with distance ambulated in
feet [median (range)]
# of patients ambulated POD0
2
# of patients ambulated POD1 AM
15
# of patients ambulated POD1 PM
19
Distance ambulated POD1 AM
30 (1, 500)
Distance ambulated POD1 PM
80 (5, 980)
Discussion
Although the concept of the paravertebral
block (PVB) originated in the early 20th century, its
popularity has waxed and waned. Recently, a renewed
interest in the technique has developed, as it has been
found to be an effective analgesic technique that
minimizes hemodynamic compromise8,9. The injection
of local anesthetic in the paravertebral space blocks
conduction in the dorsal and ventral rami of the exiting
spinal nerve root. Paravertebral blockade also inhibits
conduction through the sympathetic chain, resulting
in only a unilateral sympathectomy. At the levels of
thoracic vertebrae, the paravertebral space is a wedge
shaped space defined anterolaterally by the parietal
pleura, posteriorly by the superior costotransverse
ligament, and medially by the vertebral, vertebral
disk, and intervertebral foramina. The superior and
inferior borders are provided by the heads of the ribs.
In the lumbar vertebrae, the inter-transverse ligament
provides the posterior border of the paravertebral space.
As explained by Greengrass et al, the paravertebral
space provides an area where exiting spinal nerves are
not tightly enveloped by fascia, possibly facilitating
nerve blockade5.
Paravertebral blockade is commonly used
for breast surgery, video-assisted thoracic surgery,
minimally invasive cardiac surgery, herniorrhaphy, and
hand-assisted laparoscopic nephrectomy7,8,9. To our
M.E.J. ANESTH 23 (1), 2015
86
knowledge, use of this analgesic technique in anteriorapproach hip arthroplasty has not been described
in the literature. While the use of PVB was reported
by Bogoch and colleagues in 2002 for postoperative
analgesia following total hip and knee arthroplasty,
the technique described suggests a psoas compartment
blockade, not a true paravertebral block, as the initial
needle approach was made 4cm lateral to the spinous
process rather than 2.5cm10. Lee et al reported excellent
analgesia in two patients who patients received L1/
L2 paravertebral blocks along with local anesthetic
infiltration of the joint for hip arthroscopy11. Wardhan
and colleagues described continuous L2 paravertebral
blockade to be slightly inferior to a lumbar plexus
catheter when comparing opioid consumption in
posterior approach total hip arthroplasty patients, with
no motor strength advantage12. However, patients in
that study received 15ml of local anesthetic during
placement of the paravertebral catheter. Injection of a
large amount of local anesthetic in the paravertebral
space may result in epidural and/or unpredictable
spread5,13,14. In one radiographic study, 25% of patients
who received 20ml injectate at a single paravertebral
level had epidural spread evident on MRI13. Thus,
observed weakness in PVB patients after a large
volume injection could be secondary to neuraxial or
extensive paravertebral spread of local anesthetics.
In our current study, we have limited the injectate
to a maximum of 4ml per level, which we believe
minimizes the risk of these complications. In our case
series, no patient had a modified Bromage score less
than 5 the evening of POD 0. Additionally, no patient
was noted by physical therapy as having significant
ipsilateral lower extremity weakness that prevented
full participation in physical activity.
Studies addressing opioid consumption among
patients who undergo anterior approach total hip
arthroplasty are limited. In a prospective study by
Barrett et al, ATHA patients consumed a mean of
32.2mg, 50.7mg, and 33.7mg IV morphine equivalents
on POD 0, 1 and 2, respectively15. Another study by
Restrepo describes POD0, POD1, and POD2 mean
intravenous morphine consumption as 11.2mg,
13.9mg, and 6.82mg, respectively. However, patients
in this study received intrathecal morphine as part of
their analgesic plan, thus our results are not directly
comparable1. Additionally, the risk of postoperative
Alberto Ardon et. al
respiratory depression after an intrathecal opioid
injection is unnecessary when non-opioid modalities
are available. Bogoch et al’s study which used a
single-injection lumbar plexus block showed an opioid
consumption of 18.7mg of morphine equivalents in the
first 8 hours after surgery, which is significantly higher
than our results10. Some studies contend that there is
little difference in opioid consumption or pain scores
when comparing an anterior approach hip arthroplasty
to a classic posterior approach. Rodriguez et al found
no difference in either metric when comparing the
two surgical methods16. Even with a lumbar plexus
catheter in place, opioid consumption may be high in
the classic posterior approach. For example, Wilson
et al documented a mean opioid consumption of
54.67mg of IV morphine equivalents in the first 24
hours after THA, even with a properly functioning
lumbar plexus catheter17. If indeed little difference in
opioid consumption exists between the two surgical
techniques, our results suggest that multimodal
analgesia including a PVB at T12-L2 may decrease
opioid consumption significantly in ATHA patients.
During the time intervals studied, all median
VAS scores were 2 or less. Reports of perioperative
VAS scores for the ATHA patient population are
limited. One study described mean POD 0, 1, and 2
VAS scores to be (4.2 ± 1.4), (4.0 ± 1.0) and (3.8 ±
1.1), respectively15. The low median VAS scores in our
study, combined with moderate opioid consumption,
are thus encouraging.
The potential efficacy of paravertebral blockade
in this study may be explained on anatomic grounds.
First, the cutaneous analgesia provided by paravertebral
blocks at T12, L1 and L2 is suited for coverage of the
surgical incision. Second, as described by Wetheimer
in 1952, the peripheral nerve innervation of the hip
joint is provided by the obturator nerve, femoral nerve,
and branches of the sacral plexus18. The spinal nerves at
the levels of T12, L1 and L2 provide sensory fibers to
the iliohypogastric, ilioinguinal, genitofemoral, lateral
femoral cutaneous, femoral and obturator nerves.
Thus, a significant proportion of the sensory fibers
to the hip joint are affected by T12-L2 paravertebral
blockade. Lastly, the bony innervation of the hip
joint may indeed be affected by this paravertebral
approach. Although osteotomal anatomy of the hip
Paravertebral block for hip arthroplasty
joint is much less well defined, Brown and colleagues
describe L2 as providing innervation to the medial
midshaft femur, iliac crest, and anterior superior iliac
spine; L3 provides innervation to the femoral neck and
acetabulum19. In our study we did not conduct an L3
block so as to decrease the total anesthetic dose and
minimize the risk of motor block. Based on our results,
separate blockade of L3 may indeed not be required for
adequate analgesia after ATHA. Femoral nerve fibers
arise from L2, L3, and L4 nerve roots. Blockade with
moderate volume only at L2, while giving sensory
block in that dermatomal distribution and having
limited caudal spread, may allow full motor function
of the femoral nerve. We recognize, however, that until
further studies delineating osteotomal hip innervation
are conducted, the exact contribution of PVB analgesia
to the hip joint may not be well defined.
The patients in this case series received both
acetaminophen and celecoxib as part of a multimodal
approach to postoperative analgesia. Acetaminophen
use was highest on POD0-1, which may have
contributed to the low opioid consumption and very
low median worst VAS of zero. Likewise, twice-daily
celecoxib administration may also have contributed
to decreasing the total opioid consumption among
these patients. While the exact contribution of
acetaminophen and celecoxib in reducing opioid
requirements in these anterior hip arthroplasty patients
is not known, previous studies in total knee and
posterior-lateral approach hip arthroplasty suggest that
multimodal analgesia reduces opioid burden20,21. The
low overall pain scores and opioid consumption in this
case series certainly suggest that the use of multimodal
analgesia may contribute to the analgesic efficacy of
paravertebral blockade.
All but two of the study patients were able to
participate in physical therapy to some degree by the
evening of their surgical day. The two patients who
did not were limited by a late discharge from the
recovery room, as they were both mid-afternoon cases.
By the morning of POD1, 15 of the 20 patients were
able to ambulate. Median distance ambulated during
the morning physical therapy session was 30 feet. By
the afternoon of postoperative day 1, 19 patients were
ambulating, with a median distance of 80 feet. These
results, when considered in the context of low median
87
VAS scores on POD1, suggest that paravertebral
blockade may provide significant analgesia to facilitate
ambulation during the first 24 hours after surgery.
As mentioned previously, 13 patients received
intraarticular morphine, ketorolac and epinephrine.
The evidence supporting the use of these medications
within the articular space without local anesthetic,
however, is not robust. While some studies do suggest
that the use of intraarticular local anesthetic may
enhance postoperative analgesia22,23,24, the analgesic
properties of intra-articular morphine or epinephrine
without local anesthetic are yet to be supported
by data. To our knowledge, there are no studies
regarding the analgesic properties of sole epinephrine
when injected into an articulation. Regarding opioids,
one murine-model study suggests that subcutaneous
administration of morphine may have some analgesic
properties at the site of injection, but these effects
have not been validated in the intra-articular space
in humans25. Another study in patients undergoing
knee surgery showed no difference in postoperative
opioid consumption when morphine is added to intraarticular bupivacaine in the presence of a femoral
nerve block26. The efficacy of ketorolac when injected
into a joint without local anesthetic has also not been
studied extensively. One small study by Vintar et
al studied the impact of 10mg ketorolac on an ondemand intraarticular bolus of 25mg ropivacaine
and 2mg morphine available every 60 minutes.
Patients who received intraarticular ketorolac had
decreased opioid use 24 hours postoperatively27.
However, another study showed that patients who
only received intraarticular ketorolac had higher
pain scores and shorter time to first analgesic request
compared to patients who only received intraarticular
bupivacaine28. In our study, when patients who did
not receive this intra-articular injection are analyzed
separately, mean and median opioid consumption are
similar to those of the overall cohort (Table 7). Thus,
given these results and the paucity of evidence for
the efficacy of this intra-articular mixture, we do not
believe this modality affected our primary outcome.
However, as shown in Table 8, median worst VAS
scores did seem to be slightly higher in those patients.
Thus, we realize that the theoretical possibility
of a combined analgesic effect cannot entirely be
discounted.
M.E.J. ANESTH 23 (1), 2015
88
Alberto Ardon et. al
Table 7
Mean and median opioid consumption in mg IV morphine
equivalents, patients who did not receive intra-articular
injection
Mean
Median
POD 0
8.96
10
POD 1
12.43
10
POD 2
7.04
5
Table 8
Median visual analog pain scores (minimum, maximum),
patients who did not receive intra-articular injection
POD0 to 19:00
0 (0,5)
POD 0-1 overnight
5 (0,9)
POD1 AM
0 (0,3)
POD1 PM
2 (0,6)
POD 1-2 overnight
4 (0,6)
POD2 AM
5 (0,8)
POD2 PM
6 (0,7)
The limitations in our case series include the
retrospective nature of the study, the small number of
patients, and the lack of randomization. Additionally,
the VAS scores were recorded by ward nursing staff
per regular protocol, without mention of activity status
during the patient’s self-assessment of pain. However,
since we have collected the worst recorded VAS
rather than the entire range of pain scores, we hope to
capture as many VAS scores associated with activity
as possible. We also recognize that while appropriate
sensory deficit was confirmed preoperatively, the
duration of this sensory deficit was not documented.
Thus, we can only speculate on the exact duration
of the paravertebral block. Given the steady level of
opioid requirements throughout postoperative day 2,
though, we suspect that the analgesia associated with
nerve blockade continued to some degree during this
time period.
Conclusion
T12 through L2 paravertebral blockade, when
utilized as part of a multimodal pain management plan,
results in low VAS scores, preservation of hip motor
function, moderate opioid consumption, and may be
an effective analgesic modality for patients undergoing
anterior approach total hip arthroplasty. The outcomes
of our retrospective case series are encouraging.
Prospective studies are warranted.
Paravertebral block for hip arthroplasty
89
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M.E.J. ANESTH 23 (1), 2015
Subtenon bupivacaine injection for postoperative
pain relief following pediatric strabismus surgery:
A randomized controlled double blind trial
Radwa H Bakr** and Hesham M Abdelaziz*
Abstract
Background: Strabismus surgery in children is often associated with undesirable intraoperative
and postoperative side effects including pain, postoperative nausea and vomiting (PONV), and
occulocardiac reflex (OCR). Systemic analgesics have side effects and are contraindicated in some
cases. We hypothesized that the preoperative subtenon injection of bupivacaine would reduce
postoperative pain and the incidence of side effects adverse effects.
Methods: Sixty children (2 to 6 years of age, ASA status I to II) were randomized to receive
either subtenon bupivacaine 0.5% or a saline injection before the beginning of surgery in a doubleblind manner. Pain scores using the Face, Legs, Cry, Activity, and Consolability (FLACC) scale,
incidence of OCR and PONV, requirement of additional systemic analgesia, and time to discharge
from the recovery room were compared.
Results: The pain scores were significantly lower in the subtenon bupivacaine group at 0 min
(p = 0.0056) and at 30 min (p = 0.013). There was no significant difference between the two groups
at the other time intervals. There was a significant reduction in the incidence of occulocardiac
reflex and the incidence of vomiting in the subtenon bupivacaine group. Eight of the 27 patients
in the subtenon bupivacaine group required additional systemic analgesia compared to 19 of 29
controls. The time to discharge from recovery room was lower in the subtenon bupivacaine group.
Conclusion: These data provide some evidence that a preoperative subtenon block with
bupivacaine combined with general anesthesia allows efficient control of postoperative pain as
well as a reduction in the incidence of OCR and PONV in young children undergoing strabismus
surgery.
Keywords: Bupivacaine, Pain, Pediatrics, Strabismus surgery, Subtenon anesthesia.
Introduction
Following strabismus surgery children often experience severe discomfort and are unable
to open the operated eye. The surgical manipulation of the medial rectus muscle causes severe
bradycardia because of the occulocardiac reflex1. The postoperative period is marked by frequent
obvious discomfort, caused by a high frequency of postoperative nausea and vomiting and pain.
Pain after strabismus correction is thought to be in the conjunctival area, but Tenon’s capsule, sclera,
and stretched muscles may also contribute to its intensity1. This pain represents a source of distress
to the child and the parents. Different modalities of treatment have been proposed and found to
be variably effective. Opioids are helpful but carry the risk of nausea, vomiting, and drowsiness.
*
MD.
Department of anesthesia and intensive care, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
∗
91
M.E.J. ANESTH 23 (1), 2015
92
Non-steroidal anti-inflammatory drugs (NSAIDs)
remain controversial in small children. The side effects
of these agents are particularly undesirable in the
ambulatory surgery setting or are contraindicated in
many children. Regional anesthesia has been proposed
for management of postoperative pain following
strabismus surgery. Topical amethocaine 1% drops
and subconjunctival infiltration with bupivacaine
0.5% administered at the conclusion of strabismus
surgery have been shown to be effective in reducing
postoperative pain2,3,4. Retrobulbur and peribulbar
block have been explored in children with varying
degrees of success5. Among the different techniques,
the subtenon eye block is widely used for anterior and
posterior segment surgery in adults. A small quantity
of local anesthetic is injected in the subtenon space
by use of a smooth cannula after surgical incision
of the conjunctiva. This technique ensures adequate
postoperative analgesia in adults6,7 although it has not
been sufficiently explored when used before the start
of surgery in children.
We performed a prospective, randomized,
double-blind, controlled study to determine the efficacy
of subtenon’s bupivacaine injection at reducing
postoperative pain, the incidence of postoperative
complications, and the requirements of postoperative
analgesics in pediatric patients undergoing strabismus
surgery.
Patients and Methods
Approval to perform the study was granted by the
Institutional Review Board. Informed written consent
was obtained from the parents prior to their children’s
enrollment in the study. Sixty children aged 2-6 years
of age with ASA status I to II scheduled for primary
surgical correction of unilateral or bilateral strabismus
were included in the study. Patients were randomly
allocated to one of 2 equal groups. The inclusion
criteria were: age 6 years or under, unilateral or bilateral
surgery, primary surgery or reoperation, horizontal,
vertical, or oblique muscle surgery. Exclusion criteria
were: known drug sensitivity or body weight less than
8 kg.
A standard anesthetic protocol was used for all
children included in the studyMidazolam (0.3 mg/kg)
Radwa Bakr et. al
and atropine (10 μg/kg) were given rectally 30 minutes
before anesthesia. EMLA (eutectic mixture of local
anesthetics) cream was applied 30 min before anesthesia
over two potential venipuncture sites. Induction was
by sevoflurane inhalation and maintenance was by
spontaneous ventilation of sevoflurane in oxygen and
nitrous oxide via laryngeal mask airway. Intraoperative
analgesia was in the form of rectal paracetamol 20
mg/kg. Patients were monitored intraoperatively by
electrocardiography, pulse oximetry, noninvasive
blood pressure, and end-tidal CO2 measurements.
Heart rate and blood pressure were recorded before
induction and every 5 minutes during anesthesia and
surgery until the end of the procedure. After induction,
bupivacaine 0.5% or a placebo saline solution were
slowly injected in the subtenon space with a curved,
blunt 25-mm 20 gauge cannula introduced through
a small conjunctival and subtenon limbal aperture.
The dose of bupivacine was titrated according to the
child’s body weight to ensure a subtoxic dose of less
than 2.5 mg/kg. The efficacy of the block was judged
satisfactory if the pupil was widely dilated and fixed,
thus confirming ciliary ganglion blockade.
The anesthesiologist, surgeon, and nurses were
blinded to the nature of the injected solution. All
operations were performed by the same surgeon.
Surgery was started 5 minutes after the subtenon
injection. The surgical protocol was standardized; for
surgery on the vertical rectus muscles the conjunctiva
was opened over the insertion. The inferior oblique was
approached via limbal peritomy if surgery on the lateral
rectus was also being performed, or via a circumferential
conjunctival incision 10 mm from the limbus if not. The
conjunctiva was closed with 6-0 or smaller Vicryl®.
All patients received 1 drop of amethocaine 1% onto
the operated eye at the conclusion of surgery. After
emergence from anesthesia patients were transferred
to the recovery ward. On arrival in the recovery room,
the patient›s behavior was assessed by a nurse who
was not aware of the nature of the solution injected in
the subtenon space. The pain scale used for assessment
was the Face, Legs, Activity, Cry, Consolability scale
(FLACC)8 (Table 1). This behavioral pain assessment
scale is widely accepted as a method of assessment
for pain in children by direct observation. The scale
consists of 5 categories. Each category is scored on a
0-2 scale, which results in a total score of 0-10. A score
Subtenon bupivacaine for pediatric strabismus surgery
93
Table 1
FLACC (face, legs, activity, cry, consolability) scale
Face
Legs
0
1
2
No particular expression
or smile
Occasional grimace or frown,
withdrawn, disinterested
Frequent to constant frown,
clenched jaw, quivering chin
0
1
2
Normal position or relaxed
Uneasy, restless, tense
Kicking or legs drawn up
Activity
Cry
Consolability
Lying quietly, normal position, Squirming, shifting back and forth,
moves easily
tense
Arched, rigid or jerking
0
1
2
No cry (awake or asleep)
Moans or whimpers
Crying steadily, screams or sobs,
frequent complaint
0
1
2
Content, relaxed
Reassured by touch
Difficult to console or comfort
The FLACC scale can be used in children up to 7 years and in children with cognitive impairment. Each of the five categories (faces,
legs, activity, cry, consolability) is scored 0-2, and the scores are added to yield a total from 0 to 10. Each section above is scored and
a total obtained.
of 0 means relaxed and comfortable, 1-3 indicates
mild discomfort, 4-6 indicates moderate pain, and
7-10 indicates severe discomfort or pain or both.
Pain assessment was performed after the removal of
the laryngeal mask, and then at 30 min intervals until
discharge from the recovery ward. Children with a
FLACC score equal to or higher than 4 were given 20
mg/kg rectal paracetamol. The following parameters
were collected in the recovery room: Pain scores, at 0
min, 30 min, 1hr, 2hrs, 3hrs, incidence of occurrence of
Occulo-cardiac reflex (indicated by a sudden decrease
of the heart rate higher than 20% and concomitant with
muscular traction), incidence of postoperative nausea
and vomiting, number of patients requiring additional
systemic analgesia, and the mean time to first analgesia.
Statistical analysis was done using SPSS (version
14.0, SPSS Inc., Chicago, IL, USA). Continuous
data, such as age, weight, anesthetic duration, time
to discharge from the recovery ward and time to eye
opening, were expressed as mean and SD and were
analyzed using Student’s t-test. A chi-squared test was
performed for the comparison between qualitative
variables. A Mann-Whitney U test allowed intergroup
comparison between quantitative variables. A P value
< 0.05 was considered as significant. Results were
expressed as mean ± SD. Confidence intervals of 95%
are provided for statistically significant results.
Results
Fifty six children completed the study. One child
in the control group and three in the treatment group
were excluded after recruitment due to incomplete
data. 46 (82.0%) underwent unilateral and 10 (18.0%)
underwent bilateral surgery. 45 operations (81.1%) were
primary procedures and 11 (18.9%) were reoperations.
27 children (48.6%) were randomized to the treatment
group and 29 (51.4%) were randomized to the control
group. The groups were similar with regards to age,
weight, sex, proportions having bilateral surgery or
reoperations, and number of muscles operated upon
(Table 2).
The pain scores at each time interval are
summarized in Table (3). The treatment group
experienced significantly less pain than the control at
the 0-h observation (P = 0.005) and at 30 min (P =
0.013). There was no significant difference between
the two groups at the other time intervals. There was
a significant reduction in the incidence of occurrence
of occulocardiac reflex that required a temporary
interruption of traction on the muscles and the
injection of atropine in the study group (5 patients)
compared to (11 patients) in the control group. The
incidence of nausea was not significantly decreased in
the study group (3 patients compared to 4 patients in
M.E.J. ANESTH 23 (1), 2015
94
Radwa Bakr et. al
Table 2
Patient characteristics: Data is presented as mean ± SD
Subtenon Group
(N = 27) Mean (SD)
Control Group
(N = 29) Mean (SD)
P-value
Age (years)
3.27 ± 1.69
3.37 ± 1.71
0.38
Weight (kg)
17.6 ± 3.6
17.9 ± 3.9
0.54
12:15
11:18
0.62
Sex ratio (male: female)
ASA I:II
18:1
18:1
1
Unilateral: Bilateral surgery
22:5
24:5
0.9
Primary surgery: reoperations
21:6
22:8
0.69
Number of operated muscles
2.2 ± 0.8
2.2 ± 0.8
1
Length of the operation
35.5 ± 10
36 ± 10.2
0.63
the control group); however, the incidence of vomiting
was significantly lower in the study group (6 patients)
than the control group (10 patients) (Table 4). Eight
of the 27 patients in the subtenons group required
additional systemic analgesia (30%) compared to 19
of 29 controls (65%). This difference was borderline
with regards to statistical significance (P = 0.052). The
median time to first analgesia was 2hrs 45min in the
control group compared to 1 hour in the study group
(Table 5). The length of stay in the recovery room
was reduced to a significant degree in the bupivacaine
group; two hours after the removal of the LMA, 22
of 29 children recruited in the control group were still
present in the recovery room in contrast to 4 of the 27
children in the study group.
Discussion
Strabismus surgery in children is frequently
performed as an outpatient procedure. A large
proportion of children experience clinically significant
pain after strabismus surgery9. Additionally, Pediatric
strabismus surgery often leads to postoperative
behavioral problems during the recovery period as a
result of pain, visual disturbances, nausea and vomiting,
and separation from parents. A study demonstrated
that altered behavior was encountered on emergence
in 44% of operated children, and that 20% of them
exhibited complex symptoms simulating delirium10.
Symptoms such as PONV and pain are the
main cause of delayed discharge, contact with the
hospital after discharge, and hospital readmission after
outpatient surgery for these children11.
Pain after strabismus surgery may be caused by
sectioning and traction exerted on the extraoccular
muscles. Many strategies have been proposed for
treatment of the pain experienced by these children.
Topical analgesia using drops containing a NSAID
was efficient in some studies12, but not effective in
others13,14.
Table 3
Summary of pain scores, Mean ± SD
Subtenon Group
(N = 27)
Control Group
(N = 29)
P-value
0 min
1.77 ± 1.12
3.41 ± 1.12
0.005
30 min
1.66 ± 1
3.17 ± 1.04
0.013
1 hr.
2.11 ± 0.89
2.14 ± 0.1
0.91
2 hrs.
2.55 ± 0.89
2.86 ± 1.41
0.57
3 hrs.
3.04 ± 1.4
2.72 ± 1.47
0.38
Subtenon bupivacaine for pediatric strabismus surgery
95
Table 4
Incidence of side effects: Data is presented as n(%)
Subtenon Group (N = 27)
Control Group (N = 29)
P-value
OCR
5 (18%)
11 (38%)
0.003
Incidence of nausea
3 (11%)
4 (14%)
0.575
Incidence of vomiting
6 (22%)
10 (34%)
0.048
Opioid analgesia is frequently used to reduce
postoperative pain after strabismus surgery; however,
these drugs often cause nausea, vomiting, and
drowsiness. A study showed that opioid analgesia is
associated with more prolonged recovery times after
anesthesia, a longer stay in hospital, and delayed return
to normal activity when compared to other analgesics15.
Intravenous NSAID such as ketorolac have been
shown to be as effective as morphine and pethidine for
the relief of pain after strabismus surgery in children,
and with a lower incidence of postoperative nausea
and vomiting16,17.
Other studies showed that systemic NSAIDs
such as ketoprofen were efficient in reducing pain
after strabismus surgery in children when compared to
placebo18,19.
On the other hand certain NSAIDs such as
ibuprofen and simple analgesics such as paracetamol
were shown to be less effective20.
Asthma occurs in 30% to 40% of children, 20%
of those are sensitive to aspirin and other NSAIDs21,22.
In addition, reactions to NSAIDs include urticaria,
angioedema, rhinitis23, and exacerbation of asthma
or bronchospasm24-27, which may be fatal28. These
side effects occur after administration in common
ophthalmic procedures and have been shown to occur
with NSAIDs such as ibuprofen, diclofenac, and
ketorolac28. Therefore the use of NSAIDs may not be
appropriate for many children undergoing strabismus
surgery.
Different techniques of regional anesthesia
combined with general anesthesia have been proposed
for the young child undergoing strabismus surgery. In
addition to controlling postoperative pain, it has been
suggested that suppression of the trigeminal reflex by
regional anesthesia may correlate with a decrease in
the incidence of vomiting29.
These techniques have yielded conflicting
reports. Postoperative topical tetracaine compared
with topical saline in pediatric strabismus surgery was
shown to provide a short-lived but significantly better
pain relief as judged by both pain score and analgesic
requirement30.
Topical amethocaine 1% drops and subconjunctival
infiltration with bupivacaine 0.5% administered at the
conclusion of strabismus surgery have been shown to
be equally effective in reducing postoperative pain31,
although another study did not show any additional
analgesic effect of either of these interventions when
compared to placebo32. Similarly, a study showed that
the subconjunctival injection of bupivacaine 0.5% as
compared with a placebo decreased postoperative pain
scores in 36 young children. Another study compared
subconjunctival bupivacaine to topical tetracaine in
children undergoing squint surgery, with both giving
effective analgesia.
Table 5
Requirements of additional systemic analgesia
Number of patients requiring additional
systemic analgesia n (%)
Median time to first analgesia
Subtenon Group (N = 27)
Control Group (N = 29)
P-value
8 (30%)
19 (65%).
0.052
2 hours 45 minutes
1 hour
0.05
M.E.J. ANESTH 23 (1), 2015
96
However, some investigators found no
difference in pain score after pediatric squint
surgery using postoperative topical saline, topical
tetracaine or subconjunctival bupivacaine. Although
subconjunctival local anesthetics have had some
success in the relief of postoperative pain, the source
of pain after strabismus surgery is believed to be
receptors in tenon’s fascia and muscle tendons as well
as conjunctival receptors.
Regional blocks have also been explored in
children. Retrobulbar anesthesia by the administration
of 2 mL of bupivacaine 0.5% before surgery was as
effective as a subconjunctival injection given after the
operation in 10 children5. However the block reduced
the incidence of OCR from 60% (control group) to 4%
in children3. Similarly, a study proved that peribulbar
block (0.3 mL/kg of a bupivacaine 0.5% and lidocaine
2% mixture) reduced postoperative pain in 25 children
5 to 14 years of age to a significant degree; two thirds
of these children were operated on for strabismus33,34.
The authors also reported a major reduction in the
incidence of occulocardiac reflex and postoperative
nausea and vomiting compared with the control group
treated with pethidine35,36.
However, when comparing different eye blocks
in children, subtenon anesthesia seems to offer some
advantages over retrobulbar or peribulbar blocks in
pediatric strabismus surgery; All these techniques
require the cooperation of patients by asking them
to move their eyes laterally to exclude perforation
of the globe or nerve injury during the procedure37.
Small children are unable to cooperate in this way,
which leads to performance of the block under general
anesthesia, with poor clinical control.
Thus, in the current study, we elected to perform
subtenon anesthesia in pediatric patients undergoing
squint surgery. Subtenon’s anesthesia results in
excellent anesthesia and akinesia and is widely used
for adult anterior and posterior segment surgery38. The
anesthetic agent is delivered into the subtenon’s space
posterior to the globe’s equator using a blunt cannula
inserted through a conjunctival incision, usually
located in the inferonasal quadrant. The drug spreads
rapidly through the subtenon’s space and anesthetizes
the long and short ciliary nerves as they pierce Tenon’s
capsule around the optic nerve39.
Radwa Bakr et. al
These nerves carry sensory fibers from the sclera,
cornea, and uveal tract. Spread of the drug into the
muscle sheaths and eyelids results in anesthesia of
these structures40.
The surgery is then started through the same
conjunctival incision which allows access to extraocular
muscles. Therefore, application of anesthetics is no
more invasive than the operation itself. Moreover,
the required volume of local anesthetics to provide
adequate analgesia is less important and limits the risks
of damage caused by rapid injection or myotoxicity
from the anesthetic solution.
Complications after subtenons anesthesia are
uncommon but orbital hemorrhage41, extraocular
muscle injury42,43, and globe perforation with scissors
during dissection of the subtenons space44 have all
been reported. There is also a risk of damage to
structures crossing the subtenons space during rapid
or high volume injection, and of myotoxicity from
the anesthetic agent, but neither of these has yet been
reported after subtenons administration. This was fully
explained to parents at the time of consent. There were
no complications resulting from subtenon injection in
this study.
We chose to administer the block preoperatively
rather than postoperatively since regional blocks
are associated with fewer episodes of bradycardia
and hypertension intraoperatively caused by the
occulocardiac reflex which results from the traction
on the extraoccular muscles45, this was evident in our
study where a significant difference in the occurrence
of occulocardiac reflex was observed.
Preoperative administration also offered the
advantage of facilitation of surgical dissection and
delivery of a controlled volume. The administration of
local anesthetic, postoperatively is usually associated
with protrusion of Tenon fascia and leakage of
anesthetic through the incision. The administration
of a preoperative subtenon block did not result in any
surgical difficulty from tissue distortion.
In this study we looked at the administration
of a long acting anesthetic; bupivacaine has an onset
of action of approximately 20 min45, preoperative
administration ensures analgesic effectiveness as the
general anesthetic wears off. We, found significant
reduction in postoperative pain score as measured by
Subtenon bupivacaine for pediatric strabismus surgery
the FLACC score.
Similar results have been obtained in a randomized
controlled trial that investigated the postoperative use
of sub-Tenon lignocaine in 111 children undergoing
squint surgery. Pain was reduced significantly in the
first hour after surgery, but thereafter there was no
effect46. Lignocaine is a shorter-acting anesthetic with
a duration of 1-2h when given as a sub-Tenon block,
while the effect of bupivacaine lasts for 3-3.5h45.
Our findings are also similar to those obtained
by Steib et al. who explored the preoperative
administration of bupivacaine in 40 children the
authors found a significant reduction in pain scores in
the study group. The incidence of occulocardiac reflex
and postoperative nausea and vomiting were also
reduced in the study group47.
On the other hand, in a study by Morris et al the
authors used preoperative levobupivacaine to perform
subtenon block in 27 children undergoing strabismus
surgery and found no significant reduction in pain
scores in the study group49. However, their study had
several limitations; a placebo was not used in the
control group, and not all patients received exactly the
same general anesthetic agents or additional analgesia
these two factors may have influenced the results
obtained by these investigators. These factors were
avoided in our study which may explain our favorable
results. However, the results obtained by these authors
matched previous results obtained by Carden et al33.
97
No data in the literature suggests the optimal
volume to inject in the pediatric population. Use of a
large volume to produce akinesia is not essential, as
general anesthesia is always used with young children,
which allows satisfactory operating conditions by
itself49-52.
A significant reduction in PONV was observed
in our study during the recovery period. This
undesirable effect after strabismus surgery is caused
by pain, traction of the muscles, and perioperative
use of opioids. A similar reduction in PONV was also
encountered in the study conducted by Steib et al47.
In conclusion, a preoperative subtenon block
with bupivacaine combined with general anesthesia
allowed efficient control of postoperative pain as well
as a reduction in the incidence of OCR and PONV
in young children undergoing strabismus surgery.
We recommend that further studies be conducted to
determine the optimal volume to inject in the subtenon
space and to compare different local anesthetics.
Acknowledgements
The authors sincerely acknowledge the support of
the Ain Shams University Ophthalmology Department
in supporting this anesthesiology research. The authors
also acknowledge the efforts of Mr. Deepak Gupta in
the statistical calculations and analysis.
M.E.J. ANESTH 23 (1), 2015
98
Radwa Bakr et. al
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M.E.J. ANESTH 23 (1), 2015
CASE REPORTS
Straight to Video: Tonsillar Injury During
Elective GlideScope Ò-Assisted
Pediatric Intubation
Jason D. Rodney*, Zulfiqar Ahmed*, Deepak Gupta*,
and M aria M arkakis Z estos *
Abstract
Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy
may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) can
be very helpful but it does not come without risks. In this case report, we report an unfavorable
outcome of VL in a pediatric patient with adenotonsillar hypertrophy.
Introduction
Airway management in pediatric patients presenting for tonsillectomy and adenoidectomy
may prove challenging given the enlarged upper airway structures. Video Laryngoscopy (VL) as a
modality of airway instrumentation has the potential to facilitate an unobstructed view of the vocal
cords in situations where the oral, pharyngeal and laryngeal axes are difficult to align. Such may
be the case due to body habitus, trauma or neoplasm, among other indications. For this reason,
VL is an important tool in the anesthesiologist’s armamentarium. It has been suggested that VL
has earned a place high up in an algorithm for dealing with a difficult airway, particularly in a
“can’t intubate/can’t ventilate” patient scenario1-4. VL may also be considered in patients where
minimizing the force required during laryngoscopy is desirable such as a patient with loose teeth.
Even though VL can be very helpful, it does not come without risks. There have been numerous
case reports describing injury to various oropharyngeal structures. Hereby, we report an unfavorable
outcome of VL in a pediatric patient with adenotonsillar hypertrophy undergoing tonsillectomy
and adenoidectomy.
Case Presentation
A 6-year old female with comorbidities of sickle cell disease and a history of numerous
blood transfusions presented for elective tonsillectomy-adenoidectomy due to obstructive sleep
apnea. Preoperative airway examination revealed Mallampati Class I with full range of neck
*MD.
Corresponding author: Maria Markakis Zestos, MD, Chief of Anesthesiology, Children’s Hospital of Michigan, Associate
Professor, Wayne State University, 3901 Beaubien St, Suite 3B-17, Detroit Michigan 48201, United States. Office: 1-313745-5535, Fax: 1-313-745-5448. E-mail: [email protected]
101
M.E.J. ANESTH 23 (1), 2015
102
and jaw mobility, adequate thyro-mental distance,
and as expected, enlarged tonsils. In addition to
tonsillar hypertrophy, it was noted that the patient
had loose upper incisors about which the parent was
very concerned. The anesthesia team decided to use
GlideScopeÒ Cobalt AVL for endotracheal intubation
in an effort to avoid inadvertent pressure or traction on
the loose teeth.
After the induction of anesthesia, endotracheal
intubation was attempted by the anesthesiology
resident with the GlideScopeÒ. A Cormack Lehane
grade I laryngoscopic view was easily achieved with
a size 2 GlideScopeÒ blade. A 6.0 internal diameter
(ID) oral RAE endotracheal tube, without stylet, was
unsuccessfully introduced to the oropharynx. The
rigid GlideRiteÒ stylet was not used during the initial
attempts to pass the endotracheal tube because when
inserted into the endotracheal tube, the tip of the stylet
protruded beyond the end of the oral RAE endotracheal
tube. The RAE endotracheal tube of ID 6.0 mm was
removed, and it was noted that blood was present on
the tip of the endotracheal tube.
Mask ventilation was resumed with oxygen
and sevoflurane and at this time, it was much more
difficult to manually ventilate than during induction
despite head-tilt-chin-lift and jaw thrust maneuvers.
A subsequent attempt at VL by the supervising
anesthesiologist revealed that the tonsils were almost
completely obstructing the laryngoscopic view. Further
attempts at intubation were withheld, and assistance
was sought from the otorhinolaryngology surgical
team due to the apparent injury to the enlarged tonsils
during the initial intubation attempt.
The examination by the otorhinolaryngologist
revealed Brodsky Grade 4+ tonsils with one
partially detached tonsil having minimal mucosal
bleeding. Endotracheal intubation was achieved by
an attending physician with a Miller 2 blade with no
observable effect to the loose teeth. At this time, the
decision was made to proceed with the tonsillectomyadenoidectomy as planned. After discussion with the
concerned parent, the loose tooth was removed by the
attending dentist. The remainder of the peri-operative
course was unremarkable.
J.Rodney et. al
Discussion
Even though VL has been shown to improve the
ability of novices to obtain laryngeal exposure when
compared to Direct Laryngoscopy (DL) in adults5,
there is evidence for and against ease of use with
respect to pediatric patients. Fonte et al6 demonstrated
that pediatric residents, who were unfamiliar with VL,
failed at tracheal intubations at a higher rate while
using VL than when performing DL with a Miller
blade in pediatric patients with a normal airway or
tongue edema. Ilies et al7 found no difference between
an attending physician’s and an experienced resident’s
ability to obtain an improved view of vocal cords using
VL after DL. Despite a perceived disadvantage to using
VL for tracheal intubation by novices, it has been shown
that in the hands of experienced anesthesiologists,
VL does improve the ability to successfully intubate
pediatric patients8-10. VL may prove to be a useful tool
in obtaining laryngeal exposure, but there have been
numerous reports of injury to various oropharyngeal
structures in adults including abrasion, perforation
and laceration of tonsils, palatopharyngeal wall,
lingual nerve as well as dental injury11-18. It has been
suggested that both the blind insertion and pathway
of the endotracheal tube and the rigid stylet may be
contributing factors to oropharyngeal injury during
VL19-20.
Although the decision for airway instrument
choice was ultimately influenced by the patient’s
dentition rather than a perceived difficult airway (even
though the loose tooth was eventually removed by a
dentist), this case shows one instance wherein use of
GlidescopeÒ for pediatric endotracheal intubation may
have contributed to more harm than good. Even if the
rigid stylet is not used to facilitate intubation, there is
an inherent risk of oropharyngeal injury when using
the video laryngoscope due to the inability to visualize
the endotracheal tube passing from the opening of the
mouth to the point where it enters the field of focus of
the camera lens.
The GlidescopeÒ has become a popular tool
among peri-operative, critical care and emergency
room care providers. Few would dispute that it
has earned a place in the American Society of
Anesthesiologists’ Difficult Airway Algorithm21 which
Injury with GlideScope pediatric intubation
states that providers managing difficult airway should
give appropriate considerations to the comparative
benefits vs. workability potential of options including
VL as the initial intubation attempt3. In the presence of
a known pharyngeal mass it may be worth considering
DL, flexible fiberoptic (FFO) bronchoscope or a
combination of VL and FFO used in conjunction as
described by Weissbrod and Merati22. We would
also recommend caution when using the video
laryngoscope for educational purposes. Although VL
may facilitate both trainer and trainee to visualize the
vocal cords in pediatric patients, its use may increase
103
the risk of oropharyngeal injury or failed intubation in
inexperienced hands.
Conclusion
In summary, operators’ tendency to direct and
focus their attention ‘Straight To Video’ in VL should
be cautioned against in order to avoid potential
oropharyngeal injuries along the route of blind
insertion of the endotracheal tube from the angle of the
mouth until it becomes visible on the screen of the VL.
M.E.J. ANESTH 23 (1), 2015
104
J.Rodney et. al
References
1. Caldiroli D, Cortellazzi P: A new difficult airway management
algorithm based upon the El Ganzouri Risk Index and GlideScope®
videolaryngoscope: a new look for intubation? Minerva Anestesiol;
2011, 77:1011-1017.
2. Frova G: Do videolaryngoscopes have a new role in the SIAARTI
difficult airway management algorithm? Minerva Anestesiol; 2010,
76:637-640.
3. Saxena S: The ASA difficult airway algorithm: is it time to include
video laryngoscopy and discourage blind and multiple intubation
attempts in the nonemergency pathway? Anesth Analg; 2009,
108:1052.
4. Weiss M, Engelhardt T: Proposal for the management of the
unexpected difficult pediatric airway. Paediatr Anaesth; 2010,
20:454-464.
5. Cooper RM, Pacey JA, Bishop MJ, Mccluskey SA: Early clinical
experience with a new videolaryngoscope (GlideScope) in 728
patients. Can J Anaesth; 2005, 52:191-198.
6. Fonte M, Oulego-Erroz I, Nadkarni L, Sánchez-Santos L,
Iglesias-Vásquez A, Rodríguez-Núñez A: A randomized comparison
of the GlideScope videolaryngoscope to the standard laryngoscopy
for intubation by pediatric residents in simulated easy and difficult
infant airway scenarios. Pediatr Emerg Care; 2011, 27:398-402.
7. Ilies C, Fudickar A, Thee C, Dütschke P, Hanss R, Doerges V, Bein
B: Airway management in pediatric patients using the Glidescope
Cobalt®: a feasibility study. Minerva Anestesiol; 2012, 78:10191025.
8. Kim JT, Na HS, Bae JY, Kim DW, Kim HS, Kim CS, Kim SD:
GlideScope video laryngoscope: a randomized clinical trial in 203
paediatric patients. Br J Anaesth; 2008, 101:531-534.
9. Redel A, Karademir F, Schlitterlau A, Frommer M, Scholtz
LU, Kranke P, Kehl F, Roewer N, Lange M: Validation of the
GlideScope video laryngoscope in pediatric patients. Paediatr
Anaesth; 2009, 19:667-671.
10.Xue FS, Liu HP, Liu JH, Liao X, Zhang YM: Facilitating
endotracheal intubation using the GlideScope video laryngoscope in
children with difficult airways. Paediatr Anaesth; 2009, 19:918-919.
11.Cross P, Cytryn J, Cheng KK: Perforation of the soft palate using
the GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:588589.
12.Cooper RM: Complications associated with the use of the
GlideScope videolaryngoscope. Can J Anaesth; 2007, 54:54-57.
13.Choo MK, Yeo VS, See JJ: Another complication associated with
videolaryngoscopy. Can J Anaesth; 2007, 54:322-324.
14.Chin KJ, Arango MF, Paez AF, Turkstra TP: Palatal injury
associated with the GlideScope. Anaesth Intensive Care; 2007,
35:449-450.
15.Malik AM, Frogel JK: Anterior tonsillar pillar perforation during
GlideScope video laryngoscopy. Anesth Analg; 2007, 104:16101611.
16.Vincent RD JR, Wimberly MP, Brockwell RC, Magnuson JS: Soft
palate perforation during orotracheal intubation facilitated by the
GlideScope videolaryngoscope. J Clin Anesth; 2007, 19:619-621.
17.Hsu WT, Tsao SL, Chen KY, Chou WK: Penetrating injury of
the palatoglossal arch associated with use of the GlideScope
videolaryngoscope in a flame burn patient. Acta Anaesthesiol
Taiwan; 2008, 46:39-41.
18.Leong WL, Lim Y, Sia AT: Palatopharyngeal wall perforation during
Glidescope intubation. Anaesth Intensive Care; 2008, 36:870-874.
19.Dupanovic M: Maneuvers to prevent oropharyngeal injury during
orotracheal intubation with the GlideScope video laryngoscope. J
Clin Anesth; 2010, 22:152-154.
20.Magboul MM, Joel S: The video laryngoscopes blind spots and
possible lingual nerve injury by the Gliderite rigid stylet-case
presentation and review of literature. Middle East J Anesthesiol;
2010, 20:857-860.
21.Apfelbaum JL, Hagberg CA, Caplan RA, Blitt CD, Connis RT,
Nickinovich DG, Hagberg CA, Caplan RA, Benumof JL, Berry
FA, Blitt CD, Bode RH, Cheney FW, Connis RT, Guidry OF,
Nickinovich DG, Ovassapian A: American Society of
Anesthesiologists Task Force on Management of
the Difficult Airway: Practice guidelines for management
of the difficult airway: an updated report by the American Society
of Anesthesiologists Task Force on Management of the Difficult
Airway. Anesthesiology; 2013, 118:251-270.
22.Weissbrod PA, Merati AL: Reducing injury during video-assisted
endotracheal intubation: the “smart stylet” concept. Laryngoscope;
2011, 121:2391-2393.
Percutaneous Balloon Compression of
Gasserian Ganglion for the treatment
of Trigeminal Neuralgia: An
Experience from India
Dr. Anurag Agarwal*, Dr. Vipin Dhama**, Dr. Yogesh K. Manik**,
Dr. M. K. Upadhyaya**, Dr. C. S. Singh**and Dr. V. Rastogi**
Abstract
Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in
the dermatomal distribution area of trigeminal nerve. Percutaneous balloon compression (PBC)
of Gasserian ganglion is an effective, comparatively cheaper and simple therapeutic modality
for treatment of TN. Compression secondary to PBC selectively injures the large myelinated
A-alfa (afferent) fibers that mediate light touch and does not affect A-delta and C-fibres, which
carry pain sensation. Balloon compression reduces the sensory neuronal input, thus turning off
the trigger to the neuropathic trigeminal pain. In this current case series, we are sharing our
experience with PBC of Gasserian Ganglion for the treatment of idiopathic TN in our patients at
an academic university-based medical institution in India. During the period of August 2012 to
October 2013, a total of twelve PBCs of Gasserian Ganglion were performed in eleven patients
suffering from idiopathic TN. There were nine female patients and two male patients with the
age range of 35-70years (median age: 54years). In all patients cannulation of foramen ovale was
done successfully in the first attempt. In eight out of eleven(72.7%) patients ideal ‘Pear-shaped’
balloon visualization could be achieved. In the remaining three patients (27.3%), inflated balloon
was ‘Bullet-shaped’. In one patient final placement of Fogarty balloon was not satisfactory
and it ruptured during inflation. This case was deferred for one week when it was completed
successfully with ‘Pear-shaped’ balloon inflation. During the follow up period of 1-13 months,
there have been no recurrences of TN. Eight out of eleven patients (72.7%) are completely off
medicines (carbamazepine and baclofen) and other two patients are stable on very low doses
of carbamazepine. All patients have reported marked improvement in quality of life. This case
series shows that percutaneous balloon compression is a useful minimally invasive intervention
for the treatment of trigeminal neuralgia.
Introduction
Trigeminal neuralgia (TN) is characterized by unilateral, lancinating, paroxysmal pain in
the dermatomal distribution area of trigeminal nerve1. According to International Headache
Society (IHS) and International Association for Study of Pain (IASP) trigeminal neuralgia is
*MD, PDCC.
**MD.
Corresponding author:Anurag Agarwal, MD, PDCC, Pain Specialist & Associate Professor, Dept. of Anesthesiology &
Pain Medicine, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India. Tel: 00-91-73889-70385. E-mail
ID: [email protected]
105
M.E.J. ANESTH 23 (1), 2015
106
painful, unilateral affliction of face, characterized by
brief, electric shock like pain limited to one or more
divisions of trigeminal nerve, commonly evoked by
trivial stimuli like shaving, talking, washing of face
but may also occur spontaneously with abrupt onset
and termination2. Exact cause of TN is not known, and
multiple treatment options are available but there is no
ideal treatment available for all patients3. Severity of
pain can result in poor health and deterioration of dayto-day functional status4,5. According to IHS, TN can
be classified as classical or idiopathic and symptomatic
or secondary6,7. In 2003, Burchiel classified TN on
the basis of clinical features: Type 1 TN which is
predominantly episodic and sharp; and Type 2 TN
which is constant, dull, and burning in nature8.
The American Academy of Neurology (AAN)
and the European Federation of Neurological
Societies (EFNS) Guidelines on TN treatment (2008)
recommend medical treatment with carbamazepine
and oxcarbazepine or lamotrigine and baclofen as
first option for TN7. In patients refractory to medical
treatment or in whom side effects of medications are
intolerable, other surgical treatments are recommended.
Various modalities of surgical treatment are possible,
from major intracranial operation to minimally
invasive percutaneous techniques. Because of the
achievable longest duration of pain relief, microvascular decompression (MVD) is recommended as
the first option, but it is a major intracranial operation,
which may not be suitable for older, debilitated
patients. MVD is also complicated with the risk of
major neurological morbidity and mortality. Due to
their minimally invasive nature and possibility to
repeat, percutaneous procedures are widely used for
the surgical treatment of TN, mostly in the patients
who are not eligible for MVD, are not willing to
have MVD or are refractory to previous surgical
treatments. One of these procedures is percutaneous
balloon compression (PBC) of Gasserian ganglion
which was first introduced by Mullan and Lichtor in
19839.
PBC is an effective, comparatively cheaper and
simple therapeutic modality for treatment of TN.
Compression secondary to PBC selectively injures the
large myelinated A-alfa (afferent) fibers that mediate
light touch and does not affect A-delta and C-fibres,
Anurag agarwal et. al
which carry pain sensation. Balloon compression
reduces the sensory neuronal input, thus turning off
the trigger to the neuropathic trigeminal pain. PBC is
not as selective for pain originating from a particular
trigeminal division as radiofrequency thermocoagulation (RFTC) is10,11.
In this current case series, we are sharing our
experience with PBC of Gasserian ganglion for
the treatment of idiopathic TN in our patients at an
academic university-based medical institution in India.
Case Series
During the period of August 2012 to October
2013, a total of twelve PBCs of Gasserian Ganglion
were performed in the Department of Anesthesiology
and Pain Medicine at Lala Lajpat Rai Memorial
Medical College, Meerut, India in eleven patients
suffering from idiopathic TN. There were nine female
patients and two male patients with the age range of
35-70years (median age: 54years). All the patients
were suffering from Burchiel Type 1 TN with the
classical features of idiopathic TN i.e., electric shocklike lancinting pain in the territory of trigeminal
nerve (CN V). Two patients had involvement of
both maxillary (V2) and mandibular (V3) divisions of
Cranial Nerve V; three patients had involvement of
V2 division only and remaining six patients had TN
alongV3 division only. The duration of the disease
ranged from 2.5-12 years. Only three patients could
undergo a magnetic resonance imaging because of
financial constraints; all other patients were screened
for any intra-cranial pathology by computerized
tomography scanning. None of our patients had
bilateral TN; five patients had involvement of right
side CN V and six patients had left-sided involvement.
All patients had been treated with carbamazepine and
baclofen as part of failed medical management prior
to PBC. One patient had already undergone retrogasserian glycerol rhizotomy, which provided pain
relief for only five months. One patient underwent
PBC on two occasions secondary to non-satisfactory
placement of balloon inside the Meckel’s cave
followed by rupture of balloon and venous bleeding.
The case was deferred and performed again after one
week with satisfactory results.
Compression in Gasserian ganglion in trigeminal neuralgia
Procedural Details of PBC: All the procedures
were performed under conscious sedation using two
dimensional C-arm fluoroscopic guidance. Patients
were placed in supine position with slight extension
of neck. C-arm fluoroscope was aligned to take a
‘Modified sub-mental view’, in which foramen ovale
was visualized between mandible on the lateral side
and maxilla on the medial side (Figure 1). In this
view, a 14-gauge cannula with blunt trocar was used
to enter the foramen ovale to reach the Meckel’s cave
where the Gasserian ganglion is situated (Figure
2). Once entry was confirmed in the Meckel’s cave,
lateral view was obtained wherein 4-Fr Fogarty
catheter was gently threaded in to the Meckel’s
cave up to the clivus. After confirmation of correct
position of the balloon in anterio-posterior and lateral
views, Fogarty balloon was inflated with 0.8-1 ml
of water soluble contrast dye (Omnipaque-240, GE
Healthcare) for 1.5-3minutes. After completion of
the intervention, Fogarty balloon was deflated and
removed along with the cannula; and manual digital
pressure was applied for five minutes against the
maxilla to stop any bleeding and cerebrospinal fluid
drainage. A small dressing was applied on the skin
puncture site and patients were transferred to postanesthesia care unit for observation. After regaining
full consciousness, patients were examined for relief
in pain, facial sensation and corneal reflex; and, after
two to four hours, patients were discharged home on
oral antibiotics and non-steroidal anti-inflammatory
drugs (NSAIDs).
Fig. 1
Submental View showing Foramen Ovale
107
Fig. 2
Modified Submental View with cannula in Foramen ovale
Procedural Results of PBC: In all patients
cannulation of foramen ovale was done successfully in
the first attempt. In eight out of eleven(72.7%) patients
ideal ‘Pear-shaped’ balloon visualization could be
achieved (Figures 3-4). In the remaining three patients
(27.3%), inflated balloon was ‘Bullet-shaped’. In one
patient final placement of Fogarty balloon was not
satisfactory and it ruptured during inflation. This case
was deferred for one week when it was completed
successfully with ‘Pear-shaped’ balloon inflation. In
one patient, venous bleeding was detected on removal
of trocar from cannula that ceased after placement of
Fogarty catheter and successful PBC. In another patient,
who had not been pre-medicated with atropine, there
was sudden asystole on entering in to the foramen ovale,
which responded to Inj. atropine 1.2mg intravenous
bolus with no post-operative sequelae. In all other
patients, no episode of major bradycardia occurred due
to pre-medication with atropine 0.4mg intravenously.
All patients had complete relief of neuralgic pain in the
immediate post-operative period. In nine out of eleven
patients (81.81 %), there was mild to moderate facial
hypoesthesia, which was more prominent with longer
compression-duration (3 minutes vs. 1.5 minutes).
This hypoesthesia improved within 6-8 weeks and did
not cause appreciable discomfort to these patients. Five
out of eleven patients (45.4%) complained about mild
facial dysesthesias (continuous burning sensation in
CN V distribution), which improved in 6-8 weeks with
the use of neuro-modulatory drugs such as pregabalin.
One patient complained of malocclusion of mandible
and difficulty in chewing on the operated side, which
M.E.J. ANESTH 23 (1), 2015
108
Anurag agarwal et. al
Fig. 3
Ideal Pear shaped balloon in Lateral View
Fig. 4
Anterio-Posterior view with Pear shaped balloon
Discussion
also improved in four weeks without any treatment.
Four out of eleven (36.36%) patients revealed mild to
moderate asymptomatic masseteric weakness on postoperative physical examination that also improved in
4-6 weeks. None of the patients had loss of corneal
reflex and/or anesthesia dolorosa. In two out of eleven
(18.2%) patients, there was eruption of herpes labialis
on the ipsilateral side, which was treated with anti-viral
drugs with resolution of the lesions within two weeks.
All patients complained of temporal headache in the
immediate post-operative period, which improved in
24-48 hrs with the use of NSAIDs and ice fomentation.
None of the patients had any major complication such as
corneal ulcer, 4th or 6th cranial nerve palsy, meningitis
or death. During the follow up period of 1-13 months,
there have been no recurrences of TN. Eight out of
eleven patients (72.7%) are completely off medicines
(carbamazepine and baclofen) and other two patients
are stable on very low doses of carbamazepine. All
patients have reported marked improvement in quality
of life.
Minimally invasive pain interventions have
found a niche among the available treatments for many
intractable, chronic painful conditions such as TN.
PBC has been found to be an effective intervention in
many studies3,6,10,12. PBC has an advantage of sparing
the corneal reflex over other percutaneous methods. It
has a unique mechanism of action of selective injury
to large myelinated A-alfa and A-beta fibers and
relative sparing of small, unmyelinated C-fibers and
poorly myelinated A-delta fibers13. So it may be the
best technique for addressing ophthalmic division (V1)
pain of TN6 and this observation has been confirmed
by Brown et al12.
Initially PBC was advocated for older age
group and for those who were unfit for major surgical
procedure. Now it has been found useful even in
many young patients, especially those who do not
have any evidence of vascular malformation and/or
are unwilling to undergo major surgery. Strojnik and
Smigoc9 and Natrajan14 have used this technique in
patients with aberrant basilar artery as well as in young
patients. In our study, there was a female patients
preponderance, most patients were of advanced age
and there was almost equal distribution of right side
vs. left side involvement, although some authors have
found preponderance of right sided involvement9.
In all our patients, modified Mullan’s technique
was used9,11 for PBC. Though ‘Pear-shaped’ balloon is
considered to be the best in some studies9,10,15,16,17, this
shape was achieved in only eight out of eleven patients
in our series but we did not find any differences in
the outcome, possibly due to shorter follow-up in our
study (1-13 months). Same can be true in regards to the
compression-duration wherein practitioners have used
compression time ranging from 1-20 minutes; some
authors have reported correlation between the duration
of compression and duration of pain relief but with
longer duration of compression, more complications
like facial dysesthesias9,15,18have been reported.
Compression in Gasserian ganglion in trigeminal neuralgia
109
Because there is no consensus on the optimal duration
of compression during PBC, in our practice we have
used the compression times of 1.5 minutes and 3
minutes; and we have found that although the pain
relief was complete with both compression-duration,
incidence and magnitude of facial hypoesthesia and
dysesthesia was more in patients who had received
compression for longer duration.
operative sequelae. Therefore, it is our suggestion to
ensure premedication with atropine prior to penetration
of foramen ovale before all percutaneous procedures
including PBC. Though review of medical literature
elicits rare incidences of anesthesia dolorosa, intracranial fistula formation and cranial nerve injury,
corneal ulceration and death during PBC, we did not
encounter any such adverse effect.
Prolonged masticatory weakness due to
masseter-pterygoid weakness has been reported
after PBC11,15. We also encountered malocclusion
on ipsilateral jaw in one patient and mild masseteric
weakness in four patients, which was not bothersome
to the patients because pre-procedure, they were
not chewing from that side any way due to the
precipitation of their neuralgic pain. In all patients,
this weakness completely recovered in 4-6 weeks
without any intervention. In all patients in our series,
complete relief from neuralgic pain was observed,
which is similar to other studies9,11,14. Autonomic
changes such as bradycardia and hypotension have
been reported on entering the foramen ovale in more
than 50% of cases14,19 which was not observed in
our series because of pre-medication with atropine.
Though no mortality has been reported during PBC
in the literature, Natrajan had reported an incidence
of intra-operative myocardial infarction which was
managed successfully14. We also encountered a case
of sudden asystole on foramen ovale penetration in a
patient who was not given atropine pre-operatively in
spite of our policy. It was recognized immediately due
to continuous electrocardiography and was managed
successfully with rescue dose of atropine with no post-
Recurrence of pain after successful PBC and
initial pain relief has been reported very widely in the
literature, Baabor and Perez-Limonte20had reported
15% recurrence after 3 years, and Skirving and Dan17
had reported 31.9% recurrence in 20-years duration.
In our moderate follow-up period of 1-13 months, we
have not found any recurrence so far.
The major limitations in the present study were
retrospective nature of the case series, small number
of patients (n=11) and short duration of follow-up
(1-13months).
Conclusion
This case series shows that percutaneous
balloon compression of Gasserian ganglion is a useful
minimally invasive intervention for the treatment of
trigeminal neuralgia. If performed appropriately with
the help of anatomical landmarks and radiological
guidance, it is a low risk procedure with high success
rate. Due to very low incidence of corneal anesthesia
and anesthesia dolorosa, we recommend PBC as
first choice among percutaneous interventions for
TN especially involving V1division as well as in
multidivisional pain.
M.E.J. ANESTH 23 (1), 2015
110
Anurag agarwal et. al
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15.Kouzounias K, Schechtmann G, Lind G, Winter J, Linderoth
B:Factors that influence outcome of percutaneous balloon
compression in the treatment of trigeminal neuralgia. Neurosurgery;
2010, 67:925-934.
16.Park SS, Lee MK, Kim JW, Jung JY, Kim IS, Ghang CG:Percutaneous
Balloon Compression of Trigeminal Ganglion for the Treatment
of Idiopathic Trigeminal Neuralgia: Experience in 50 Patients. J
Korean NeurosurgSoc; 2008, 43:186-189.
17.Skirving DJ, Dan NG:A 20-year review of percutaneous balloon
compression of the trigeminal ganglion. Journal of Neurosurgery;
2001, 94:913-917.
18.Lichtor T, Mullan JF: A 10-year follow-up review of percutaneous
microcompression of the trigeminal ganglion. J Neurosurg; 1990,
72:49- 54.
19.Brown JA, Preul MC: Trigeminal ganglion compression for
trigeminal neuralgia: experience in 22 patients and review of the
literature. J Neurosurg; 1989, 70:900-904.
20.Baabor MG, Perez-Limonte L: Percutaneous balloon
compression of the gasserian ganglion for the treatment of
trigeminal neuralgia: personal experience of 206 patients.
ActaNeurochirurgicaSupplementum; 2011, 108:251-254.
Bedside retained radial artery catheter removal
in a hemodynamically unstable neurocritically-ill
patient: a case report.
Christa O’Hana V. San Luis* and Athir H. Morad*
Abstract
Radial artery insertion is a common procedure in intensive care units. We describe a case of a
critically-ill 73-year-old man in the neurocritical care unit with a subarachnoid hemorrhage whose
radial arterial catheter tip was transected from the main line and was successfully managed with
bedside retrieval of the catheter.
Introduction
Radial artery insertion is usually done in the neurocritical care unit (NCCU) for the purposes
of blood pressure monitoring and arterial blood sampling. Several complications are known such
as temporary occlusion, thrombosis, pseudoaneurysm formation, hematoma formation, abscess,
cellulitis, median nerve involvement and air embolism. Retained radial artery catheter is rare but
has been reported in literature. Several causes have been mentioned such as accidental transection,
repeated catheterization and repeated wrist movements. Several modalities have been mentioned
to confirm the location of the arterial catheter as well as different methods to remove the catheter.
We describe a case of a 73-year-old man who presented with aneurysmal subarachnoid
hemorrhage due to an anterior communicating aneurysm and underwent aneurysmal clipping. His
course was complicated by cardiopulmonary instability. On his first post-operative day, the radial
arterial catheter tip on his left wrist was fractured from the main line as it was being removed. He
then underwent a bedside vascular exploration and removal of the foreign body. We also present a
review and summary of the available literature regarding retained radial catheters and the available
modes of image confirmation and options for treatment.
Case
A 73-year-old man was admitted in our Neurosciences critical care unit (NCCU) for an
aneurysmal subarachnoid hemorrhage (ASAH), Hunt and Hess 3, Modified Fischer Scale 3. He
underwent aneurysmal clipping after a four vessel angiogram revealed a 3-millimeter irregular
and superiorly projecting anterior communicating artery aneurysm. Post-operatively day 1, he was
very agitated and his left radial arterial catheter was discontinued due to very poor waveform. As it
was being pulled out, the nurse noticed that the long portion of the distal cannula was not there. It
was highly suspected that it was still in the vessel. Pulses and perfusion distally were adequate. A
*M.D, Department of Anesthesia and Critical Care Medicine, Division of Neurosciences critical care, Johns Hopkins
University School of Medicine Baltimore, MD 21287, USA.
Corresponding author: Christa O’Hana V. San Luis, M.D, 600 N Wolfe Street, Phipps 455, Baltimore, MD, 21287. Tel:
(949)8780490, Fax: (410)6147903. [email protected]
111
M.E.J. ANESTH 23 (1), 2015
112
stat portable 3-view X-ray of the wrist and hand done
visualized a 4cm catheter fragment in the anterolateral
soft tissue aspect of the distal forearm proximal to
the left wrist (Figure 1). A vascular surgery consult
was placed and surgical removal and exploration was
planned the following day. His family was informed of
the incident and consented for the procedure. On the
day of the planned exploration, the patient had acute
respiratory failure further complicated by an asystolic
event. He was immediately resuscitated and was started
on norepinephrine, dopamine, epinephrine to maintain
his mean arterial pressure. The surgical procedure
was postponed due to hemodynamic instability. Three
days after, it was deemed that due to the patient’s
continued hemodynamic instability, he was not a good
surgical candidate to transport to the operating room.
The bedside exploration of the left radial artery and
the removal of the distal catheter tip were then done
with local anesthesia under ultrasound guidance. The
incision was made at the top of the radial artery on
the left forearm. The catheter was identified right at
the entry site of the radial artery. DeBakey pickups
were used to extract the catheter out of the radial
artery (Figure 2). The radial artery was found to be
thrombosed at that location. Dopplers were performed
after the procedure to assure adequate pulses and
perfusion distally. The procedure was tolerated well
and perfusion was maintained throughout the hospital
stay.
Fig. 1
Plain left hand and wrist x-ray. Panel A is the PA (posteroanterior) view. Panel B is the lateral view. Encircled in red is
the retained radial artery catheter fragment
Christa San Luis et. al
Fig. 2
Proximal part of the radial arterial catheter without the
retained distal catheter tip
Discussion
The radial arterial line for this patient was for
strict blood pressure monitoring which is one of the
most common reasons for its placement1,2. The reason
for the radial artery catheter breakdown in this patient
is unclear. Several reasons for this type of breakdown
have been reported in the past including accidental
transection while separating the arterial line from
the intravenous line3, possible damage to the catheter
sheath due to repeated catheterization attempts4,
transection while suturing5, shearing off of the cannula
due to repeated wrist movement postoperatively during
recovery6-8, reinsertion of the stylet needle9, accidental
cutting during suture removal10,11 and dressing
removal12. In our case, our suspicion is that the patient
was probably moving his wrist repeatedly during his
post-operative agitation. Prompt vascular surgery
consult for possible exploration is very important to
prevent the possibility of distal embolization and distal
migration with thrombosis. There is also a possibility
of proximal migration4 and the use of ultrasound to
confirm the location of the catheter preoperatively
is recommended. Described by Aslam et al.1, this
proximal migration, although unlikely, may occur
because of arterial spasm distally. Several imaging
modalities may be used to confirm the location of the
retained fragment (Table 1). In this patient, the most
rapid way to confirm the imaging late at night was
a plain radiograph. With the vascular surgery team
Bedside retained radial artery catheter removal
113
Table 1
Summary of causes, diagnostic imaging and approach to removal of retained radial artery catheters
(CT = computed tomography, OR = operating room)
Source
Patient
characteristic
Cause of cannula transection
Diagnostic
procedure for
confirmation
Consulting service/
Procedure for removal
7.5 MHz highfrequency
ultrasonography,
3-D CT
Plastic surgery/OR Surgical
exploration and removal of
fragment by microforceps
Outcome
Recovered, no
residual sequelae
Moon et al.3
69 y.o.,
Male
Accidental
transection by scissors while
separating intravenous and arterial
catheter
Lee SY
et al.4
69 y.o.,
Male
Wrist CT
Reinsertion may have damaged
the catheter sheath, manufacturing
defect of angiocatheter is
suggested
Service not mentioned/OR
surgical exploration and
removal of fragment
Ho KS
et al.6
20 y.o.,
Female
Repeated wrist movement
Not mentioned
Vascular surgery/OR surgical
exploration under local
anesthesia
Aslam M
et al.1
63 y.o.,
Female
Not mentioned
ultrasound
Vascular surgery/OR surgical
exploration under local
anesthesia
Shah U.S.
et al.5
72 y.o.,
Female
Transected while securing the
arterial catheter with suture.
none
Vascular surgery/OR surgical
exploration simultaneous with
planned indicated surgery
Bengezi OA
et al.7
58 y.o., Male
Hypothesized to be repeated
flushing and manipulation created
a vulnerable point along the
catheter length
Plain X-ray of
wrist and hand
with ultrasound
confirmation
pre- and
intraoperatively
Vascular surgery/OR surgical
exploration with arteriotomy
Kim IS
et al.9
74 y.o., Male
Portable X-ray
Reinsertion of stylet needle
through the embedded catheter
sheath intraoperatively for pleural
decortication
Recovered
Unclear if vascular surgery
involved/OR Exploration and uneventful
removal during scheduled
primary surgery
Moody C
et al.10
Unknown
elderly
Accidental cutting of the plastic
cannula
Ultrasound
imaging pre-and
intraoperatively
Surgical team involved/OR
exploration with arteriotomy
and removal of catheter
Recovered
uneventful
Ferguson E et
al.11
62 y.o., Male
Accidental cutting of catheter
fragment
Portable X-ray
Vascular surgery/OR
arteriotomy and removal of
catheter
Uneventful
Mayne D and
Kharwar F8
64 y.o., Male
Repeated flexion and extension
Portable X-ray
Unclear if vascular surgery
involved/Unclear if OR
Exploration and removal or
bedside
Uneventful
Hamid
et al.12
unknown
Accidental transection with
dressing removal
Sonosite, X-ray
Percutaneous approach using
a snare
Some spasm
on angiography
however no
complications after
removal
Recovered, no
residual sequelae
Excellent flow with
good capillary refill
in all fingers.
M.E.J. ANESTH 23 (1), 2015
114
on board, they were able to perform their bedside
ultrasound localization both preoperatively and during
the surgery itself. Ideally, patients are taken to the
operating room for surgical exploration and removal
of the fragment with generally good outcome (Table
1). However that is not always possible as in our case.
The patient was hemodynamically unstable and was
unable to tolerate repeated position changes even just
for transportation. However, as soon as the patient
was deemed able to tolerate the surgical exploration
at bedside, it was immediately arranged and another
ultrasound was performed preoperatively. The
procedure was performed in our NCCU.
Retained radial artery catheter is rare but has been
reported. Clinicians should be aware of the various
Christa San Luis et. al
mechanisms by which the catheter may be transected
so precautions can be observed. Appropriate wrist
stabilization, careful suture placement and removal and
avoidance of multiple stylet needle reinsertion are the
suggested ways to prevent this complication. Prompt
confirmation of the location of the retained fragment
is indicated with simultaneous vascular surgery
consultation for timely exploration and removal.
Intraoperative confirmation of the catheter may be
needed. If the patient is unable to tolerate transport
to the operating room, it is feasible to perform the
procedure at bedside. To the authors’ knowledge this
is the first report of a bedside surgical exploration for a
retained radial arterial catheter in a hemodynamically
unstable patient.
Bedside retained radial artery catheter removal
115
References
1. Aslam M, Sarker B, Bhattacharya V: A Rare Complication of
Radial Artery Cannulation. J Med Ultrasound; 2012, 20(3):183-185.
2. Scheer BV, Perel A and Pfeiffer U: Clinical review: Complications
and risk factors of peripheral arterial catheters used for
haemodynamic monitoring in anaesthesia and intensive care
medicine. Crit Care; 2002, 6(3):199-204.
3. Moon S, Gong J, Kim J, Lee KC, K HY, Choi EK and Lee MJ: A
retained catheter fragment in radial artery caused by accidental
catheter transection during arterial catheter removal. J Anesth; 2012,
26:625-626.
4. Lee S, Na H, Kim M, Kim C, Jeon Y, Hwang J and Do S: A Sheared
catheter fragment in the wrist after arterial cannulation attempt-a
case report. Korean J Crit Care Med; 2010, 25:118-21.
5. Shah US, Downing R and Davis I: An iatrogenic arterial foreign
body. Br J Anaesth; 1996, 77:430-431.
6. Ho KS, Chia KH and Teh LY: An unusual complication of radial
artery cannulation and its management: a case report. J Oral
Maxillofac Surg; 2003, 61:955-7.
7. Bengezi OA, Dalcin A, Al-Thani H and Bain J: Unusual
complication of radial artery cannulation. Can J Plast Surg; 2003,
11(4): 213-215.
8. Mayne D and Kharwar F: Another complication of radial artery
cannulation. Anaesthesia; 1997 Jan, 52(1):89-90.
9. Kim IS, Shin HK and Dae YK: Iatrogenic catheter sheath shearing
during radial artery cannulation. Korean J Anesthesiol; 2013 Dec,
65(6 Suppl):S12-S13.
10.Moody C, Bhimarasetty C and Deshmukh S: Ultrasound guided
location and removal of retained arterial cannula fragment.
Anesthesia; 2009 Mar, 64(3):338-9.
11.Ferguson E, Baumgartner P and Hamilton M: Accidental
transection of radical artery cannula. Anaesth and Intensive Care;
2005 Feb, 33(1):142-3.
12.Hamid UI, Collins A, McConkey C and Sidhu P: Accidental
transection of a radial artery cannula. BMJ Case Reports; 2012,
doi:10.1136/bcr-2012-006753.
M.E.J. ANESTH 23 (1), 2015
Esophageal perforation following
orogastric suction catheter insertion
in an elderly patient
Roland N. Kaddoum*, Fadi Farah**, Rita W. Saroufim***
and S alah M. Z eineldine ****
Abstract
Esophageal rupture has been described following iatrogenic manipulation. In this report,
we present an elderly lady admitted to the operative theater for laparoscopic cholecystectomy.
Multiple intra-operative attempts to place a flexible orogastric tube were unsuccessful because of
failure to advance.
Post-operatively, the patient developed sepsis and a right pleural effusion. She was transferred
to the Intensive Care Unit and she was treated with antibiotics. Radiologic evaluation confirmed
an esophago-pleural fistula. Surgical repair was urgently performed for closure of fistula and lung
decortication. The patient recovered and was discharged home.
Introduction
Esophageal perforation is a serious complication of procedures performed on or around the
esophagus and is mainly iatrogenic1,2. Esophageal perforation is most frequently encountered during
endoscopic procedures3 but also during nasogastric tube placement4-9, endotracheal intubation10-14,
stricture dilation15,16 and during the use of oesophageal bougies17. This complication has a poor
prognosis with inadequate management3.
While providing anesthesia to surgical patients, anesthesists frequently insert esophageal
dilators, nasogastric tubes or orogastric tubes/suction catheters. Such interventions may cause
trauma to soft tissue structures. We describe a case of esophageal perforation secondary to the
orogastric insertion of a simple 14 french suction catheter used routinely to deflate the stomach
during laparoscopic cholecystectomy. To our knowledge, this is the first case report describing
esophageal perforation following the insertion of a flexible orogastric 14Fr suction catheter in an
adult patient undergoing laparoscopic cholecystectomy.
*
MD, Assistant Professor of Anesthesiology, American University of Beirut Medical Center, Department of Anesthesiology,
Beirut, Lebanon (Riad Solh 1107-2020).
** MD, Anesthesiology resident, Formerly of: American University of Beirut Medical Center, Department of Anesthesiology,
Beirut Lebanon (Riad Solh 1107-2020). Current Department: St. Elizabeth's Medical Center, Department of Anesthesiology,
Critical Care and Pain Medicine, 736 Cambridge Street, #213, Brighton, MA 02135.
***Medicine III student, Bachelor degree in Biology, American University of Beirut Medical Center, Department of
Anesthesiology, Beirut, Lebanon (Riad Solh 1107-2020).
****MD, Assistant Professor of Clinical Medicine, American University of Beirut Medical Center, Department of Internal
Medicine, Beirut, Lebanon (Riad Solh 1107-2020).
Corresponding author: Salah M. Zeineldine, MD, Assistant Professor of Clinical Medicine, American University of Beirut
Medical Center, Department of Internal Medicine, Beirut, Lebanon (Riad Solh 1107-2020). Tel: +961-1-350 000 x 4706,
Fax: +961-1-744 489. E-mail: [email protected]
117
M.E.J. ANESTH 23 (1), 2015
118
Roland Kaddoum et. al
Case Report
was uneventful. The patient was transferred to the
recovery room. She was fully awake and asymptomatic.
A 79 year old, 70 kg lady known hypertensive
and dyslipidemic presented for laparoscopic
cholecystectomy and intraoperative cholangiogram
secondary to an acute cholecystitis. The patient denied
any symptoms or history of dysphagia, odynophagia,
gatroesophageal reflux or chest pain. Difficult
intubation was anticipated due to short neck and a
glidescope assisted intubation was planned.
On post-op day one, the patient complained
of dry cough and dyspnea after her first meal. On
physical exam, she had scattered wheezes and right
field crakles. She was afebrile. Chest X ray (CXR)
revealed opacification on the right lower and right
middle fields. A diagnosis of pulmonary aspiration
was suspected and Solumedrol, Combivent, pulmicort
and Tazocin were started. The CXR improved in the
afternoon. However, clinically the patient was getting
worse the following day with progressive desaturation
down to 90% and became hypotensive with systolic
pressure of 80 mmHg. The patient was transferred
to the intensive care unit and Tazocin was shifted
to broad spectrum antibiotic coverage consisting of
Meropenem, Levofloxacin and Metronidazole. The
patient symptoms improved, however the cough and
wheezes persisted. A CT chest was done on post op
day 7 revealing an air pocket posterior to the carina
in continuity with the right lower lobe. A diagnosis
of esophageo-pleural fistula in the lower esophagus
was suspected and was confirmed with Gastrograffin
swallow. On post-op day 9, a thoracotomy for right
lung decortication and closure of fistula was performed.
The patient was kept intubated and extubation was
done on the following day. Antibiotics were continued
for 14 days post-op. The radiological findings on CXR
resolved on post-op day 17.
In the operating room, after lung denitrogenation
with 100% oxygen, rapid sequence induction was
performed using lidocaine 100 mg (1.5 mg/kg),
propofol 140 mg (2 mg/kg) and succinylcholine 100
mg (1.5 mg/kg) intravenously. No bag ventilation
was performed. The trachea was intubated by an
endotracheal tube (ETT) size 8.0 using the Glidesscope
and a 10Fr intubating stylet (Unomedical). Several
attempts to insert a well lubricated 14 Fr suction
catheter failed (Bicakcilar, suction catheter w/
vakon connector ideal tip 4.7 mm x 600mm). The
catheter would not advance even with an index finger
inserted in the patient mouth guiding the catheter
into the pharynx. After multiple attempts using the
laryngoscope to have better visualization, the insertion
of the orogastric tube was not successful. During
the procedure, the surgeon noted that the stomach
was inflated and insisted on the placement of an
orogastric tube to suction the stomach. We elected
then to place an ETT size 7.0 that we advanced in the
esophagus and inserted the orogastric tube through it.
The advancement of the catheter would always stop
at the same level as previously tried with or without
the laryngoscope attempts. The resistance upon the
insertion of the catheter was encountered at a distance
of about 25 cm from the lips. No forceful maneuvers
were performed and no blood was recovered over the
suction catheter. We decided to abort the placement of
the orogastric tube and the surgeon was advised so. His
concern was a fully inflated stomach that he is showing
us on the video camera. We explained that placement
of orogastric tube was difficult, and will treat his
concern by extubating the trachea when the patient is
fully awake.
After the surgical procedure ended, extubation
A repeated gastrograffin swallow was performed
on post-op day 20 showing an outpouching at the
level of the fistula but no leak. Another gastrograffin
swallow was performed on post-op day 27 showed no
leak.
The patient was discharged from the hospital on
post-op day 33.
Discussion
Perforation of the esophagus due to
instrumentation in the adult is a rare yet potentially
devastating event associated with high morbidity and
mortality3. The mortality has decreased from 38.7%
in the 1970s to 8.3% today18. The leading cause of
Esophageal perforation in laparoscopy
esophageal perforation is mainly iatrogenic with
perforations at the thoracic level being the highest19.
Most of perforations occur during instrumentation
of the esophagus i.e. endoscopy procedures,
transesophageal echocardiography, esophageal varices
sclrerotherapy, stricture dilatation, using relatively
large stiff probes (endoscope, TEE probe, SengstakenBlakemore (SB) tube, bougie). Several risk factors
have been described for esophageal perforation such
as pre-existing esophageal abnormalities (carcinoma,
stricture, diverticuli)20 and cervical osteophytes21.
Esophagogastroduodenoscopy
was
the
most
commonly litigated procedure, followed by intubation
and Nissen fundoplication22. But there have been few
reported cases of iatrogenic esophageal perforations
by a flexible nasogastric tube occurring mainly in
neonates or infants4-6,9,23.
In our patient the perforation occurred
after multiple attempts at inserting the orogastric
suction catheter where the obstruction was faced
at 25cm distal to the lips. The most common areas
of instrumental esophageal perforation are the
relatively narrow portions at the distal esophagus.
The perforation is complicated by an inflammatory
process and communication with the pleura in 80% of
the cases24. The thin mediastinal pleura is ruptured by
the inflammatory process, producing contamination
of the pleural space and a pleural effusion. Then,
gastric contents and fluids are drawn into the pleural
space by the negative intrathoracic pressure resulting
in further inflammation and fluid sequestration,
hypovolemia, and the early appearance of tachycardia
and systemic sepsis. In our patient the CXR revealed
opacifications which reflect consolidation of the lungs
that is due to an accumulation of fluids that is most
probably edema and inflammation. This explains the
scattered wheezes and crackles that were heard on
post op day one. In addition, esophageal perforation
allows bacteria, usually polymicrobia flora to spread
into the mediastinum and subphrenic space leading
to mediastinitis18,25-27. This explains the septic picture
of our patient that was revealed by hypotension and
progressive oxygen desaturation.
Literature showed a better outcome with primary
surgical closure if diagnosed in less than 24 hours.
119
However if delayed diagnosis beyond 48h was made,
no patient with esophageal perforation should be
deprived from surgical repair28. Mortality is decreased
in surgical repair versus conservative treatment29, for
that reason, our patient underwent thoracotomy for
fistula closure and repair of esophageal tear.
In any patient with a recent history of esophageal
instrumentation, the diagnosis of esophageal injury
should be suspected in the presence of any of the
symptoms encountered by our patient. Also, the
absence of gastric content on naso/orogastric tube or
the presence of blood on the catheter elicit a possible
diagnosis of perforation. Nevertheless blood was not
noted on the suction catheter in our case.
For the first 24 hours following the laparoscopic
cholecystectomy, our patient’s only complain was pain
over the incision and a mild shoulder pain attributed to
the laparoscopic procedure. This pain was controlled
by analgesics. She denied any complain or history
of dysphagia, odynophagia, dysphonia or dyspnea.
However, after her first meal she complained of
sudden dry cough and severe dyspnea. Taking into
consideration the fact that the patient was extubated
with a distended stomach, pulmonary aspiration was
the most probable diagnosis.
It was the persistence of the cough and dyspnea
and the worsening of these symptoms following
meals, along with a problematic naso/orogastric tube
insertion that made the suspiscion of esophageal
perforation high. Because of the failure of insertion of
the orogastric catheter and the occurrence of resistance
at 25 cm from the lips, an intrathoracic esophageal
injury in our case was suspected. The CT chest showed
an air pocket adjacent to the carina in continuity with
the right lower lobe. This prompted us to perform
esophagogram to confirm the diagnosis of esophageal
perforation.
The presence of underlying esophageal pathology
could explain the difficulty in advancing the orogastric
tube. As anesthesiologists we are the experts in inserting
orogastric tubes or suction catheters, a maneuver that
we perform almost every day in our practice. The
advancement of the catheter was impossible past 25cm
of the lips despite so many attempts. This could be
M.E.J. ANESTH 23 (1), 2015
120
explained by a pre-existing esophageal pouch that the
patient is unaware of or by an osteophytic compression
of the esophagus due to the patient age, which made
the advancement of the catheter impossible. Forcing
the catheter insertion through multiple attempts lead
to the perforation. On another note, the deviation from
our current practice of inserting a suction catheter
through an ETT placed in the esophagus is a very rare
maneuver that we perform in extreme situations. This
also could be the reason of the perforation.
Roland Kaddoum et. al
Conclusion
The lesson taken from this case report is not to
force the advancement of an orogastric/nasogstric
suction catheter especially when different techniques
and multiple attempts fail. The other lesson taken is
to have a very high threshold inserting an ETT in the
esophagus to facilitate the suction catheter insertion
by advancing the catheter through the ETT since this
could also be a risk factor for esophageal perforation.
Esophageal perforation in laparoscopy
121
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Desenvolvimento Pesquisa em Cirurgia; 2013, 28(4):266-71.
M.E.J. ANESTH 23 (1), 2015
LETTER TO THE EDITOR
Pediatric Endotracheal Intubation
Claude Abdallah*
Dear Editor,
I have read with interest the manuscript: ”Simulation training in endotracheal intubation in a
pediatric residency” M. E. J. Anesth 22(5) 2014, by Drs. Sharara-Chami, Taher, Kaddoum, Tamim
and Charafeddine. The authors are to be congratulated for taking the time to analyze and publish
the study, the discussion highlights interesting points.
Tracheal intubation in pediatric patients is an essential tool in anesthesiology, traditionally
acquired in a clinical setting. Factors related to the patient such as the age of the patient and the
level of experience of the trainee may be determinant factors in the decision of the anesthesiologist
to make a first attempt at tracheal intubation. Learning curves exist for practical skills and despite
useful tools to monitor the learning process; competency is difficult to assess by the anesthesiologist
in the absence of adequate exposure with the trainee or a previous documentation of the level of
execution of involved skills. Literature review shows the advantage of preparing trainees outside
the operating room so that clinical training opportunities can be used most effectively when they
arise. Scientific reports documenting the effects of simulation training on learning and updating
knowledge about airway management showed improvement in decision-making, communication
capabilities1-4 and a better learning of crisis management and endotracheal intubation5. Residents
achieve proficiency levels in a smaller number of elapsed days of training and in a smaller number
of trials in the operating room6. Simulation would represent also an additional tool for assessing
the performance of procedures in anesthesia, such as rapid sequence induction, since it represents
more clearly behaviors used in clinical practice than is possible to demonstrate using evaluation
by questionnaires7. This may be particularly interesting since theoretical lectures and standard
mannequin-based driven workshops have shown to improve overall theoretical knowledge but not
to translate to practical skill during realistic mannequin-based simulations8.
As discussed by the authors, future studies pertaining to documentation of the trainee’s
perspective when faced with a pediatric tracheal intubation with teaching of pediatric endotracheal
intubation with and without simulation training would be useful to perform.
*
MD, MSc, Children’s National Medical Centre, Division of Anesthesiology, 111 Michigan Ave. NW, Washington DC, 20010
USA, (202) 476-2407. E-mail: [email protected]
123
M.E.J. ANESTH 23 (1), 2015
124
Claude Abdallah
References
1. Russo SG, Eich C, Barwing J, Nickel EA, Braun U, Graf BM,
Timmermann A: Self-reported changes in attitude and behaviour
after attending a simulation-aided airway management course. J
Clin Anesth; 2007, 19:517-22.
2. Schaefer JJ 3rd: Simulators and difficult airway management skills.
Paediatr Anaesth; 2004, 14:28-37.
3. Owen H, Plummer JL: Improving learning of a clinical skill: the first
year’s experience of teaching endotracheal intubation in a clinical
simulation facility. Med Educ; 2002, 36:635-42.
4. Rowe R, Cohen RA: An evaluation of a virtual reality airway
simulator. Anesth Analg; 2002, 95:62-6.
5. Ti LK, Tan GM, Khoo SG, Chen FG: The impact of experiential
learning on NUS medical students: our experience with task trainers
and human-patient simulation. Ann Acad Med Singapore; 2006,
35:619-23.
6. Abrahamson S, Denson JS, Wolf RM: Effectiveness of a simulator
in training anesthesiology residents. Qual Saf Health Care; 2004,
13:395-7.
7. Zausig YA, Bayer Y, Hacke N Sinner B, Zink W, Grube C,
Graf BM: Simulation as an additional tool for investigating the
performance of standard operating procedures in anaesthesia. Br J
Anaesth; 2007, 99:673-8.
8. Wiel E, Lebuffe G, Erb C Assez N, Menu H, Facon A, Goldstein P:
Mannequin-based simulation to evaluate difficult intubation training
for emergency physicians. Ann Fr Anesth Reanim; 2009, 28:542-8.
Erratum
The correct spelling name of the first author of the Letter-to-Editor entitled
“Anesthetic management of a patient after functional hemispherectomy using
bilateral bispectral index monitoring” and published in the October 2014 issue
of the Middle East Journal of Anesthesiology (pp. 627-628) is “Shinichiro
Kira” and not “Shinichiri Kira”.
125
M.E.J. ANESTH 23 (1), 2015
GUIDELINES FOR AUTHORS
The Middle East of Anesthesiology publishes original
work in the fields of anesthesiology, intensive care, pain, and
emergency medicine. This includes clinical or laboratory
investigations, review articles, case reports and letters to the
Editor.
Submission of manuscripts:
The Middle East Journal of Anesthesiology accepts
electronic submission of manuscripts as an e-mail attachment
only.
Manuscripts must
attachment to:
be
submitted
via
email
Editor-In-Chief,
Department of Anesthesiology,
American University of Beirut Medical Center
Beirut, Lebanon
E-mail: [email protected]
Human Subjects
Manuscripts describing investigations performed in
humans must state that the study was approved by the appropriate
Institutional Review Board and written informed consent was
obtained from all patients or parents of minors.
Language:
Articles are published in English.
Manuscript Preparation
Manuscript format required:
Double-spaced lines
Wide margins (1.5 inches or 3.8 cm)
Page numbers start on title page
Word count should reflect text only (excluding abstract,
references, figures and tables).
Editorial
1500
Abstract
250 (General articles)
100 (Case Reports)
Clinical or laboratory investigations:
The following structured format is required:
1. Cover Letter
7. Discussion
2. Title page
8. Acknowledgements
3. Abstract
9. References
4. Introduction
10. Tables
5. Methods
11. Figures
6. Results
1. Cover Letter
Manuscripts must be accompanied by a cover letter,
signed by all authors and stating that:
- All authors have contributed intellectually to the
manuscript and the manuscript has been read and
approved by all the authors.
- The manuscript has not been published, simultaneously
submitted or accepted for publication elsewhere.
2. Title Page
Starts at page 1 and includes:
- A concise and informative title (preferably less than 15
words). Authors should include all information in the
title that will make electronic retrieval of the article both
sensitive and specific.
- Authors listing: first name, middle initial and last name
with a superscript denoting the academic degrees as
footprints.
- The name of the department(s) and institutions(s) to
which the work should be attributed.
- The name, address, telephone, fax numbers and e-mail
address of the corresponding author.
- Disclose sources of financial support (grants, equipment,
drug etc…).
- Conflict of interest: disclosure of any financial
relationships between authors and commercial interests
with a vested interest in the outcome of the study.
- A running head, around 40 characters.
- Word count of the text only (excluding abstract,
acknowledgements, figure legends and references).
Review article
4000
Original article
3000
Case Reports
800
3. Abstract
Letter to Editor
500
Abstract should follow the title page. It should be
structured with background, methods, results and conclusion.
M.E.J. ANESTH 22 (6), 2014
It should state, the specific purpose of the research or
hypotheses tested by the study, basic procedures, main findings
and principal conclusions.
Provide separate word count for the abstract.
4. Introduction
Provide the nature of the problem and its significance.
State the specific purpose or research objectives or hypothesis
tested. Provide only directly pertinent references and do not
include data or conclusions from the work being reported.
5. Methods
A. Selection and description of participants:
- Describe selection of participants (including controls)
clearly, including eligibility and exclusion criteria.
B. Technical information:
-Identify the methods, apparatus (give the
manufacturer’s name and address in parentheses),
and procedure in sufficient detail to allow others
to reproduce the results. Give references to
established methods. Provide references and brief
descriptions for methods that have been published.
Identify precisely all drugs and chemicals used,
including generic names(s), dose(s) ands routes(s)
of administration.
C. Statistics-describe statistical methods with enough
detail to enable a knowledgeable reader with access to
the original date to verify the reported results. Define
statistical terms, abbreviations and most symbols.
Specify the computer software used. Provide a power
analysis for the study.
6. Results
Present your results in logical sequence in the text, tables
and illustrations, giving the main or most important findings
first. Do not repeat all the data in the tables or illustrations
in the text: emphasize or summarize only the most important
observations. Extra or supplementary materials and technical
details can be placed in an appendix.
7. Discussion
Emphasize the new and important findings of the study
and the conclusions that may be drawn.
Do not repeat in details data or other information given
in the Introduction or the Results sections. For experimental
studies, it is useful to begin the discussion by summarizing
briefly the main findings, then explore possible mechanisms or
explanations for these findings, compare and contrast the results
with other relevant studies. State the limitations of the study,
and explore the implications of the findings for future research
and for clinical practice. Link the conclusions with the goals of
the study, but avoid unjustified statements and conclusions not
adequately supported by the data.
8. Acknowledgements
They should be brief. Individuals named must be given
the opportunity to read the paper and approve their inclusion in
the acknowledgments.
9. References
- References should be indicated by Arabic numerals in
the text in the form of superscript and listed at the end
of the paper in the order of their appearance. Please be
accurate, giving the names of all authors and initials, the
exact title, the correct abbreviation of the journal, year of
publication, volume number and page numbers.
- The titles of journals should be abbreviated according
to the style used in the list of Journals Indexed for
MEDLINE.
Example: (1) from a journal (2) from a book.
1.SHAWW: AND ROOT B: Brachial plexus anesthesia
Comparatives study of agents and techniques. Am. J.
Surg.; 1951, 81:407.
2. ROBINSON JS: Modern Trends in Anaesthesia, Evans
and Gray Ch. 8, Butterworth Pub. Co., London 1967.
10. Tables
Tables capture information concisely and display it
efficiently: They also provide information at any desired level
of details and precision. Including data in tables rather than text
frequently makes it possible to reduce the length of the text.
- Type or print each table with double spacing on a separate
sheet of paper.
- Number tables consecutively in the order of their first
citation in the text.
- Supply a brief title for each.
- Place explanatory matter in footnotes, not in the
heading.
- Explain all nonstandard abbreviations in footnotes.
- Identify statistical measures of variations, such as
standard deviation and standard error of the mean.
11. Figures
- Figures should be submitted in JPEG or TIFF format
with a minimum of 150 DPI in resolution.
- Colored data if requested by author is chargeable.
- If a figure has been published previously, acknowledge
the original source and submit written permission from
the copyrights holder to produce the figure.
Abbreviations and symbols:
- Use only standard abbreviations.
- Avoid abbreviations in the title of the manuscript.
-The spelled-out abbreviations followed by the
abbreviation in parenthesis should be used in first
mention.
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