Download Dexmedetomidine for Pediatric Sedation for Computed

Dexmedetomidine for Pediatric Sedation for Computed
Tomography Imaging Studies
Keira P. Mason, MD*†
Steven E. Zgleszewski, MD*
Jennifer L. Dearden, MD*
Raymond S. Dumont, MD*
Michele A. Pirich, RN, BSN†
Cynthia D. Stark, RN, CPNP†
Peggy D’Angelo, BSN, RN†
Shann MacPherson, BSN, RN†
Paulette J. Fontaine, BS†
Dexmedetomidine is a sedative with limited experience in the pediatric population.
This is the first study that prospectively evaluates the sedation profile of a
dexmedetomidine pilot program for pediatric sedation for radiological imaging
studies. In March 2005, our hospital sedation committee approved the replacement
of IV pentobarbital with dexmedetomidine as the standard of care for CT imaging.
Detailed Quality Assurance (QA) data sheets collect relevant information on each
patient, which is then logged into a computerized sedation database. After IRB
approval, all QA data was accessed. Sixty-two patients with a mean age of 2.8 years
(SD ⫽ 1.8, range 0.5–9.7) received IV (IV) dexmedetomidine administered as a 2
mcg/kg loading dose over 10 minutes, followed by repeat boluses of 2 mcg/kg
over 10 minutes until target of Ramsay Sedation Score 4 (RSS) achieved. Patients
were then maintained on 1 mcg/kg/hr infusion until imaging is completed.
Repeated-measures ANOVA indicated that compared to pre-sedation values, the
heart rate and mean arterial blood pressure decreased an average of 15% during
bolus, infusion and recovery (P ⬍ 0.01). No significant changes were observed in
respiratory rate or end-tidal CO2. Mean recovery time was 32 ⫾ 18 minutes. Based
on our pilot results, dexmedetomidine may provide a reliable and effective method
of providing sedation.
(Anesth Analg 2006;103:57–62)
Linda Connor, RN†
David Zurakowski, PhD*‡
N
eonates and infants undergoing radiological imaging studies often require sedation to minimize motion artifact. Historically, chloral hydrate and pentobarbital have been the drug of choice for pediatric
sedation in radiology departments (1– 4). Rates of
successful sedation with this medication range from
85–98% (5,6). Both pentobarbital and chloral hydrate
are medications which each have almost 100 years of
clinical experience. Because of their extended half-life,
they have been associated with prolonged recovery
times and sedation-related morbidity (7–10).
Since 1993, pentobarbital has been the mainstay of
our pediatric sedation program for diagnostic imaging
in radiology. In an effort to decrease our rate of failed
sedations, reduce our recovery room time and improve our adverse event rate, the Radiology Sedation
Committee established a pilot program using dexmedetomidine (Precedex; Hospira, Lake Forest, IL) as a
From the Departments of *Anesthesia, †Radiology, and ‡Biostatistics, Children’s Hospital Boston and Harvard Medical School, 300
Longwood Avenue, Boston, Massachusetts 02115.
Accepted for publication February 1, 2006.
Address correspondence and reprint requests to Keira P. Mason,
MD, Department of Anesthesia, Children’s Hospital Boston, 300
Longwood Avenue, Boston, MA 02115, Tel: 617-355-7737, Fax:
617-278-9237; Email: [email protected]
Copyright © 2006 International Anesthesia Research Society
DOI: 10.1213/01.ane.0000216293.16613.15
Vol. 103, No. 1, July 2006
sedation replacement to pentobarbital for CT imaging.
Dexmedetomidine is a highly selective ␣2 adrenoceptor
agonist that has sedative and analgesic effects (11). It has
limited experience in the pediatric population. There has
not been a prospective study evaluating its use for
pediatric sedation for diagnostic imaging studies. Following approval by the Radiology and Hospital Sedation Committee, we established a pilot protocol to replace pentobarbital with dexmedetomidine. This study
was designed to evaluate the efficacy and adverse event
profile of dexmedetomidine. To our knowledge, we are
the only institution which has established a dexmedetomidine sedation program for CT imaging.
METHODS
Database
In December 1993, the Children’s Hospital Radiology Sedation Committee was established to create
sedation guidelines for the department of Radiology
and to monitor staff credentialing and quality assurance. The radiology nursing staff collects and records
specific information on each sedation. This information is transcribed to a computerized database (FileMakerPro, version 2.1; Claris, Cupertino, CA) by a
single designated staff member. The database contains
information on patient demographics, medical diagnosis, time of examination, duration of fasting status,
type of examination performed as well as the date of
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the study, medications and dosages (micrograms per
kilogram body weight) administered, patient’s American Society of Anesthesiologists (ASA) physical status
classification, (12) adverse and paradoxical events,
time required to sedate and recover, and failed
sedations.
Within 24 hours of the sedation, a radiology nurse
attempts to contact all patients (or their parents) who
were sedated. Satisfaction and delayed adverse events
are recorded at this time. All adverse events are
reviewed at monthly meetings of the Radiology Sedation Committee. Current protocols are routinely reviewed and modified and new protocols are frequently piloted in efforts to improve sedation practice.
An Unplanned Admission: An unexpected admission to the hospital overnight as a direct result of
an adverse event directly related to the sedation.
A Gastrointestinal Side Effect: Vomiting, aspiration or diarrhea occurring within 24 hours of the
administration of sedation.
An Allergic Reaction: Unexplained rash or allergic
symptoms that develop within 24 hours of receiving sedation.
The Time To Achieve Sedation: Time in minutes
from initial administration of sedative to achievement of adequate sedation of the patient.
Definition of Terms
All adverse events and specific demographics related
to the patient and the sedation are entered into the
computerized database. Adverse events are classified
according to acuity and placed in different categories: A,
B and C. Category A encompasses the most serious
events which include need for resuscitation, cardiovascular complications, decrease in oxygen saturation, aspiration, allergic reaction, and the use of reversal agent.
Grade B: prolonged sedation (greater than 3 hours
recovery time), vomiting, unplanned admission, and
paradoxical reaction. Grade C: failed sedation, awakens
before procedure over, greater than 3 IV attempts.
The definition of each adverse event and demographic data-point is defined below (7):
A Failed Sedation: Inadequate sedation subsequent to receiving the maximum allowable dosages per the sedation protocol or inability to
complete the planned procedure secondary to
unacceptable motion artifact.
A Prolonged Sedation: Inability to meet discharge
criteria 3 hours following ingestion of the sedative
or failure to return to baseline mental and behavioral status within 24 hours of receiving sedation.
Decrease in Oxygen Saturation: Sustained decrease in oxygen saturation of greater than 5%
from baseline for more than 1 minute, despite
facemask oxygen delivery of 6 L/minute, head
repositioning, suctioning and physical stimulation.
A Need for Resuscitation: Decline in the patient’s
respiratory rate and oxygen saturation that requires resuscitative efforts which include positive
pressure ventilation, cardiopulmonary resuscitation or the use of medications which reverse the
sedation.
A Cardiovascular Complication: Sustained (⬎5
minute) decrease (⬎20%) in the patient’s mean
arterial pressure with or without a decrease in
heart rate below the lower limit of the normal
range for the patient’s age.
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Dexmedetomidine Sedation for Pediatrics
Paradoxical Reaction: a rage, irritability or agitation that was not present prior to sedation.
Duration of Sedation: Total duration of sedation
defined as the time from which the initial sedative
is administered to the point at which the last dose
of sedation is received.
Imaging Time: Time duration of entire imaging
study from initiation of scan to radiologist confirming completion of successful CT study.
Sounds awkward.
Recovery Time: Time in minutes from last dose of
sedation to point at which patient meets discharge
criteria from the recovery room.
Sedation Protocol
Prior to administering sedation, all sedation candidates are evaluated by a radiology nurse in order to
determine whether the child has any medical conditions that would disqualify this patient from sedation.
Specifically, in its Sedation Policies and Guidelines,
the Radiology sedation committee has established a
list of medical conditions that would contraindicate a
child from receiving dexmedetomidine sedation
(Table 1). Our Sedation Policies and Guidelines incorporate and expound on those recommended by the
American Academy of Pediatrics (13,14). The nurse
collects and documents the patient’s past medical,
surgical, sedation and anesthetic history. A physical
examination, review of systems and review of pertinent laboratory data is recorded along with the current medications, allergies and fasting status. The
supervising anesthesiologist confirms the findings
prior to obtaining informed consent for the sedation.
Although all pentobarbital sedation at our institution has been administered by a radiology nurse with
physician (radiologist or anesthesiologist) oversight,
for this pilot program all dexmedetomidine was administered by an anesthesiologist. Although dexmedetomidine is considered a sedative and theoretically
only requires a pulse oximeter and blood pressure
ANESTHESIA & ANALGESIA
Table 1. Medical Conditions That Contraindicate
Dexmedetomidine
Active, uncontrolled gastroesophageal reflux
Active, uncontrolled vomiting
Current (or within the past 3 mo) history of apnea
requiring an apnea monitor
Active, current respiratory issues that are different
from the baseline status (pneumonia, exacerbation
of asthma, bronchiolitis, respiratory synctitial virus
Unstable cardiac status (life-threatening arrhythmias,
abnormal cardiac anatomy, significant cardiac
dysfunction
Craniofacial anomally, which could make it difficult
to effectively establish a mask airway for positive
pressure ventilation if needed
Current use of digoxin, beta blockers, or calcium
channel blockers
Moya Moya disease
Non-onset stroke
Children’s Hospital, Boston, Radiology sedation guidelines, 2005.
monitor as required by American Academy of Pediatrics, we elected to do full monitoring, as if the child
was undergoing a general anesthetic.
After evaluating different dosage regimens, the
Radiology Sedation Committee established by consensus a protocol for dexmedetomidine administration.
The protocol specifies that all children have a baseline
set of vital signs prior to sedation which include MAP,
oxygen saturation, heart rate and respiratory rate. An
initial loading dose of 2 mcg/kg IV dexmedetomidine
is administered over a 10 minute period. Patients are
monitored initially with pulse oximetry. As the level
of sedation increases, additional monitors are added
in conjunction with the patient’s tolerance. Typically,
the child does not tolerate nasal prong capnography
and insufflation of the non-invasive blood pressure
cuff until there is a Ramsay Sedation Score (RSS) 4
(15). A RSS 4 or RSS 5 is a clinically derived scoring
system that is generally accepted as an adequate
sedation depth to tolerate diagnostic imaging studies.
After the initial loading dose, the sedation score is
assessed, usually by confirming tolerance of blood
pressure measurement or nasal prongs. If RSS 4 has
been achieved, and the CT scan is not yet completed,
the maintenance infusion of 1 mcg/kg/hr is initiated
until completion of study. However, if RSS 4 has not
been achieved with the initial load, a repeat bolus of
2 mcg/kg over 10 minutes is administered. If the RSS
4 is achieved following this 2nd bolus, an infusion of
1 mcg/kg/hr is immediately started. At a RSS 4, all
patients are fully monitored as if undergoing a general
anesthetic. Specifically, pulse oximetry, capnometry,
respiratory rate, blood pressure, heart rate and electrocardiogram are followed and documented at
5-minute intervals throughout the procedure. Regardless of sedation level, all children complete the initial
loading dose. The CT imaging study is initiated as
soon as the desired level of sedation has been
achieved, sometimes even during the initial or repeat
loading dose.
Vol. 103, No. 1, July 2006
Following the procedure, the patient is transported
to the radiology recovery room where a nurse monitors and records the identical vital signs every 5
minutes until discharge criteria are met.
Record Review
After Institutional Review Board approval, the prospectively gathered data was reviewed to compare
outcome variables for all children who underwent CT
imaging and received as standard of care dexmedetomidine per established protocol outlined above. All
patients (parents) signed written, informed consent
for the sedation. A total of 62 patients were sedated
between March 15 and June 1, 2005. Outcome data
were acquired from Quality Assurance forms which
included time to sedation, recovery time, amount of
medication (mcg/kg) administered, vital signs, failed
sedations and adverse events.
Statistical Analysis
Continuous variables including age, weight, dose,
heart rate, respiratory rate, mean arterial pressure,
end-tidal carbon dioxide, as well as the times to
sedation and discharge were tested to assess whether
they followed a Gaussian-shaped distribution and no
significant skewness or non-normality was detected.
Therefore, these variables are expressed in terms of
the mean and standard deviation and changes in the
vital measurements from baseline were evaluated
using repeated-measures analysis of variance
(ANOVA) (16). Adverse events are reported as percentages with 95% confidence intervals as determined
by the normal approximation, A power analysis indicated that a minimum sample size of 60 patients
would provide estimation of the true adverse event
rate to within 5% with a confidence level of 95%
(version 5.0, nQuery Advisor, Statistical Solutions,
Cork, Ireland). Finally, multiple logistic regression
analysis was applied to determine if any demographic
or procedural variables were associated with adverse
events during sedation (17). Statistical analysis was
performed using the SPSS software package (version
12.0, SPSS Inc., Chicago, IL). Two-tailed values of P ⬍
0.05 were considered statistically significant.
RESULTS
Sixty-two children received dexmedetomidine per
above delineated protocol for CT imaging (34 males
and 28 females) with a mean age of 2.8 years (SD ⫽
1.8, range 6 months–9.7). Patients’ weight averaged
14.6 ⫾ 5.1 kg. The majority of examinations consisted
of imaging the head and/or neck (66%), abdomen
(18%), and thorax or spine (13%). 32% were ASA I and
58% were ASA II. The demographics of the study
group are presented in Table 2.
Among the 62 patients, the mean loading dose of
dexmedetomidine was 2.2 mcg/kg. Per protocol, all
patients completed the 2 mcg/kg loading dose over 10
minutes. 52 patients sedated to RSS4 with the loading
© 2006 International Anesthesia Research Society
59
Table 2. Demographics of the Patients Undergoing Sedation
for Computed Tomography Imaging (n ⫽ 62)
Age (yr)
Weight (kg)
Male
Female
Type of examination
Head or neck
Thorax or spine
Abdomen
Hip
ASA physical status
I
II
III
Total loading dose (␮g/kg)*
2.8 ⫾ 1.8 (0.5–9.7)
14.6 ⫾ 5.1 (8.0–
32.9)
34 (55%)
28 (45%)
41 (66%)
8 (13%)
11 (18%)
2 (3%)
20 (32%)
36 (58%)
6 (10%)
2.2 ⫾ 0.6 (2–4)
Values are mean ⫾ sd (range) or number (%).
Loading dose: initial dose (2 ␮g/kg) ⫹ second bolus (if needed) to achieve Ramsey sedation
score ⫽ 4. Ten patients had a second bolus of 2 ␮g/kg.
dose only. Of these patients, 6 children were able to
complete the CT imaging study during the loading
dose. Ten patients (16%) required a second bolus (1–2
mcg/kg). A total of 56 patients (90%) required the
maintenance infusion of 1 mcg/kg/hr following the
loading dose (⫾ 2nd bolus).
Pre-sedation mean values of heart rate and respiratory rate for the entire cohort were 115 ⫾ 19 (range
80 –164) and 24 ⫾ 4 (range 16-34), respectively.
Repeated-measures ANOVA indicated that compared
to pre-sedation, heart rate decreased during bolus,
infusion, and in recovery (P ⬍ 0.01). Mean decline in
HR from baseline (pre-sedation) to recovery was 15%
(SD ⫽ 10%). 70% of the patients exhibited a decrease
in heart rate of between 5–25%. As shown in Table 3,
ten patients (16%) developed sinus arrhythmias (SA)
during either the bolus or infusion. Despite the sinus
arrhythmia, all patients demonstrated hemodynamic
stability. All SA resolved prior to completion of the
study and lasted for no longer than 2–3 minutes. There
were no incidences of SA in the recovery room. No
significant changes were observed in respiratory rate
(Fig. 1). Pre-sedation mean values of MAP for the
entire cohort averaged 80 ⫾ 12 mm Hg (range 60 –102).
Repeated-measures ANOVA indicated that compared
Figure 1. Heart rate and respiratory rate throughout the
sedation time course in all patients. Repeated-measures
ANOVA revealed a statistically significant change (P ⬍ 0.01)
in heart rate but no change in respiratory rate after baseline.
Asterisks denote significant changes relative to pre-sedation
levels.
to pre-sedation, MAP decreased during infusion and
recovery (P ⬍ 0.01). Similar to the change in HR, the
average decline in MAP from baseline to recovery was
15% (SD ⫽ 15%) with about 70% of patients showing
a decline between 1–30%. No significant changes were
observed in end-tidal CO2 levels (Fig. 2). No supplemental oxygen was delivered during the sedation.
There were no significant drops (ⱖ5%) in oxygen
saturation. Despite the drop in blood pressure and
heart rate, all changes were still within the clinical
range of normal (ⱖ5 percentile for age).
Dexmedetomidine had a mean time to sedation of
approximately 10 ⫾ 2 minutes and a sedation duration, which averaged 21 minutes (range 10 –37 minutes). Duration of CT imaging averaged just over 8
Table 3. Performance Characteristics of Dexmedetomidine,
Electrocardiogram Findings, and Adverse Events During
Sedation and in the Recovery Room
Performance results (min)
Time to achieve sedation
Duration of sedation
CT imaging time
Recovery Time
ECG findings*
Duration sedation
Adverse events
Duration sedation
Duration recovery
Delayed (24 h)
9.9 ⫾ 2.4 (6–20)
21.0 ⫾ 5.5 (10–37)
8.1 ⫾ 4.3 (2–20)
31.8 ⫾ 18.0 (5–75)
10 (16.1)
5 (8.1)
3 (4.8)
2 (3.2)
Values are mean ⫾ SD (range) or number (%).
*All sinus arrhythmia occurred during initial loading bolus or maintenance infusion.
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Dexmedetomidine Sedation for Pediatrics
Figure 2. MAP and end-tidal carbon dioxide at various time
points from pre-sedation to recovery. End-tidal CO2 was not
measured prior to sedation. Repeated-measures ANOVA
indicated that relative to pre-sedation baseline levels, mean
BP declined significantly during infusion and continued to
be lower than baseline during recovery (P ⬍ 0.01). However
patients remained within the normal range. No significant
changes were observed from bolus to infusion and recovery
with respect to end-tidal CO2. Asterisks denote significant
changes relative to pre-sedation levels.
ANESTHESIA & ANALGESIA
minutes (range 2–20 minutes). Mean recovery time
was nearly 32 ⫾ 18 minutes (Table 2). Performance
characteristics of dexmedetomidine for the study
group are shown in Table 2.
There were no Type A adverse events in this study.
All adverse events were Type B and occurred during
sedation (n ⫽ 5) or in the recovery room (n ⫽ 3).
Irritability, agitation, and vomiting were the most
common Type B occurrences (Table 3). Two children
became increasingly agitated during the loading dose.
After more than 5 minutes of extreme agitation during
the loading dose, at the anesthesiologist’s discretion,
an alternate means of sedation was chosen (propofol
for one child and pentobarbital for another). A total
adverse event rate of 8.1% was observed during
sedation and 4.8% during recovery. Only two delayed
events occurred at 24 hours (event rate ⫽ 3.2%) and
these were both irritability.
Multiple logistic regression analysis was conducted
to assess whether demographics, procedural, or sedation variables were associated with adverse events
during sedation. Age, weight, gender, type of examination, and dose of dexmedetomidine were not found
to be significant predictors of adverse events during
sedation (all P ⬎ 0.10).
At 24 hour follow-up, all parents were contacted
and given a scale of approval rating that included very
satisfied, satisfied, neutral and dissatisfied. Most parents expressed a high degree of satisfaction with the
use of dexmedetomidine: 98% indicated that they
were either satisfied (n ⫽ 44) or very satisfied (n ⫽ 17).
Only 1 parent was neutral and none indicated
dissatisfaction.
DISCUSSION
In 1993, the Department of Radiology established a
computerized database for all sedations. This database
has enabled the Radiology Sedation Committee to
perform quality assurance, review outcome data and
evaluate modifications of the sedation protocols. By
conducting pilot studies with alternative sedation
techniques (8,9) and analyzing the results efficiently
with this database, we have been able to establish new
protocols and improve existing ones (18). The committee represents a collaboration between members of the
Departments of Anesthesia and Radiology.
Recent literature looked at 16,467 sedations, and
found a total of 58 cases of oxygen desaturation,
representing an overall incidence of 0.35%. There were
2 cases of pulmonary aspiration (incidence of 0.01%),
10 sedations which required airway resuscitation (incidence of 0.06%) and a failed sedation rate of ⬍1%
(10). Other authors report a 2.9% incidence of hypoxemia and a 7% failed sedation rate (19). Clearly, some
of the medications (fentanyl, pentobarbital, midazolam, droperidol, morphine, chloral hydrate) that are
currently being used for sedation are long acting and
potential respiratory depressants. There is a growing
interest in ␣2 agonists for sedation and analgesia.
Vol. 103, No. 1, July 2006
Dexmedetomidine has a short half-life of 1.5–3 hours
after IV dosing (20,21). This is a significantly shorter
half-life than that of pentobarbital and chloral hydrate.
A short-half life could make dexmedetomidine easier
to titrate, quicker to recover from and potentially
associated with less prolonged sedation related adverse events.
Another significant advantage of dexmedetomidine
is that in adults, it provides sedation and analgesia
with no accompanying change in resting ventilation
when administered within clinical dosing guidelines
(22–24). Some feel that dexmedetomidine actually
mimics some aspects of natural sleep (22). It has been
shown to produce dose-dependent decreases in blood
pressure and heart rate as a result of its alpha2 agonist
effect on the sympathetic ganglia with resulting sympatholytic effects (25,26). An additional advantage of
dexmedetomidine is that antagonists to ␣2 agonists
exist and could potentially provide for a quick reversal of the hemodynamic or sedative effects (27).
There is limited prospective literature in children.
The majority of publications are case reports and
series describing dexmedetomidine for sedation of
children who are ventilated, detoxifying from opioids
and benzodiazepines, failing traditional sedation techniques for MRI imaging, or undergoing an awake
craniotomy (28 –31). Dexmedetomidine has been
found to cause potentially life threatening cardiovascular complications in some adults and children
(23,27,32–34). Currently, it is approved by the Food
and Drug Administration (FDA) for use as a sedative
for adults on ventilators. Under the FDA it is limited
to use as a continuous IV infusion for no more than 24
hours. It does not have FDA approval in the pediatric
population.
We have shown that dexmedetomidine may provide a reliable and effective method of providing
sedation to children undergoing diagnostic imaging
studies. We found no effect on baseline respiration as
evidenced by respiratory rate and end-tidal CO2 values. The decreases in heart rate and blood pressure
were still clinically acceptable for this pediatric population. However, until larger studies confirm hemodynamic stability of dexmedetomidine in the pediatric
population, we would recommend full monitoring.
Developing a standard protocol for dexmedetomidine
administration that would guarantee high success
with minimal adverse events will require further
clinical trials. A limitation of this study is its small
sample size of 62 patients. We powered the study to
estimate the true adverse event rate to within 5% with
a high level of statistical confidence (i.e., 95%). Greater
precision regarding the true adverse event rate would
have required considerably more patients. Therefore,
our results need to be interpreted with caution regarding safety since data from a larger prospective study
are needed to establish assurance of dexmedetomidine
safety in pediatric CT imaging.
© 2006 International Anesthesia Research Society
61
In conclusion, in the setting of an organized, appropriately staffed and monitored sedation program,
dexmedetomidine may be an appropriate agent for
sedation of infants undergoing CT imaging
procedures.
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