ORIGINAL ARTICLE
Ketamine and Atropine for Pediatric Sedation
A Prospective Double-Blind Randomized Controlled Trial
Payman Asadi, MD,* Hamed-Basir Ghafouri, MD, Mohammadreza Yasinzadeh, MD,
Seid Mohamad Hosseini Kasnavieh, MD, and Ehsan Modirian, MD, MPH
Introduction: Sedation in children can be a challenge for emergency
physicians, which demands for selecting an effective medication with few
complications and good analgesic effects. This study has been performed
to evaluate the adverse effects of ketamine while using either atropine or
placebo in emergency departments.
Methods: This is a prospective randomized controlled trial involving
200 patients with age ranging between 2 and 15 years, who need a painful
procedure. Participants randomly were divided into 2 groups both treated
by ketamine (1 mg/kg intravenously administered); group 1 received ex-
cessive intravenous atropine (0.01 mg/kg), whereas distilled water was
given to group 2 as placebo. Adverse effects and duration of the treat-
ments were recorded.
Results: From March to September 2010, 200 of 218 eligible patients
were enrolled. The mean (SD) age of patients in the intervention group
was 7.0 (3.6) years that showed no statistical difference with the control
group (age range, 2Y15 years; mean, 7.1 [3.8] years). The mean proce-
dure and sedation time between the intervention and placebo groups
were not significantly different (P = 0.919 and 0.783, respectively). Sev-
eral differences between the intervention and placebo groups were noted
including nausea and vomiting, but only the difference in hypersalivation
was statistically significant (12% vs 28%). Low oxygen saturation was re-
ported only in 2% of the participants, whereas none of the children experi-
enced apnea or laryngospasm during the sedation process.
Conclusions: Atropine added to ketamine significantly reduces hyper-
salivation without producing any adverse effects on the procedure dura-
tion or success rate.
Key Words: sedation, ketamine, atropine
(Pediatr Emer Care 2013;29: 136Y139)
S edation in children can be a challenge for physicians work
in emergency departments. A child exposed to any kind of
trauma can feel the pain to the same level as an adult, whereas
unfamiliar and frightening environment of the emergency de-
partment can lead to more anxiety and pain.1 This fact neces-
sitates selecting an effective drug with few complications and
good analgesic effects. The physician must determine the ap-
propriate medications for sedation according to any particular
procedure to minimize the childs emotional and physical dis-
comforts and provide a safe and effective treatment.
From the *Poursina Hospital, Guilan University of Medical Sciences,
Rasht; and Hazrat Rasoul Akram Hospital, Tehran University of Med-
ical Sciences, Tehran, Iran.
Disclosure: No financial support was received except for that provided by
Tehran University of Medical Sciences.
Reprints: Hamed-Basir Ghafouri, MD, Department of Emergency Medicine,
Rasul Akram Hospital, Niayesh St, Sattarkahn Ave, Tehran University
of Medical Sciences, Tehran, Iran (e-mail: h-basirghafouri@
sina.tums.ac.ir).
Copyright * 2013 by Lippincott Williams & Wilkins
ISSN: 0749-5161
136 www.pec-online.com
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Ketamine is a phencyclidine derivative for procedural se-
dation.2 It is a dissociative agent allowing potent sedation, an-
algesia, and amnesia during painful procedures with minimal
respiratory depression.3,4 The safe and effective use of keta-
mine for sedation in children undergoing procedures such as
fracture reduction and wound management in emergency depart-
ments has been described.1,5 Typical indications for ketamine use
are short, painful procedures and examinations likely to produce
excessive emotional disturbance.6 Ketamine is effective either as
a sole agent or in combination with a benzodiazepine for brief
painful procedures in children.3 Intravenously administered, a dose
of 0.5 to 1.0 mg/kg will produce light sedation in a child for ap-
proximately 10 minutes.7
Ketamine can sedate the child with preserving the airway
tone and reflexes, maintenance of spontaneous respiration, and
relative cardiovascular stability.8 The adverse effects of keta-
mine include nausea, vomiting, recovery agitation, hallucinations,
double vision, random movements, myoclonus or increased mus-
cle tone, transient rash, and hypersalivation1,9,10 Laryngospasm,
respiratory depression, and apnea are not usually seen except in
very high doses.11Y13
Increased oral secretions and hypersalivation resulted from
using ketamine is one of the most common adverse events seen
in previous studies with rare airway compromise.10 There are
numerous reports with controversial results about using adjunc-
tive anticholinergics such as atropine or glycopyrrolate along
with ketamine to limit excessive mucosal secretions,14,15 but it
has not always been found to be effective in the emergency de-
partment setting.14,16 This prospective double-blind randomized
controlled trial has been performed to assess ketamine adverse
effects when using either atropine or placebo in the emergency
department.
METHODS
Objectives
In this study, we evaluated the effects of atropine as a con-
junct therapy with ketamine and assessed its potential effects on
reducing hypersalivation, the most important adverse effect of
ketamine, and its subsequent airway compromise.
Participants
From March to September 2010, data from 218 healthy
children with a physical status score of I or II (American So-
ciety of Anesthesiologists), aged between 2 and 15 years, who
needed procedural sedation and analgesia (PSA) for any pain-
ful procedures in the emergency department were eligible for
participation in the study. Eighteen of these patients were not
enrolled because of refusal by parents or unavailability of the
investigators at the time of the patients presentation to the
emergency department. The remaining 200 patients were al-
located to drug or placebo groups by using blinded random-
ized blocks (Fig. 1).
Pediatric Emergency Care & Volume 29, Number 2, February 2013
Pediatric Emergency Care & Volume 29, Number 2, February 2013
FIGURE 1. Description of patient enrollment and randomization.
Sample Size
To detect a 20% difference in incidence of hypersalivation,15
at the 5% significance level with 90% power, we required approx-
imately 88 patients per treatment group. As we encountered more
patients during our study period, we enrolled 218 patients to gain
more power, using convenience sampling method and evaluated
200 children (3Y16 years) who did not meet the exclusion criteria.
Exclusion Criteria
Patients with history of asthma or psychosis, upper airway
tract infections or abnormalities, cardiovascular diseases or hy-
pertension, head injury with loss of consciousness, vomiting or
abnormal conscious level, increased intraocular pressure or in-
tracranial pressure, thyroid disease, and porphyria were excluded.17
Ethics
A written informed consent was obtained from the parents
of all the participants. This study was approved by the relevant
human research ethics committees.
Presedation Evaluation
A presedation evaluation was performed for all patients to
recognize the appropriate participants. Patients information
including an accurate body weight was recorded. The monitor-
ing and airway management equipment was prepared. Physical
examination including vital signs (heart rate, respiratory rate,
pulse oximetry, and blood pressure) was performed and docu-
mented. Situations that indicated a difficult airway management
or underlying disorders were noted.
Intervention and Data Collection
The intervention group received 1 mg/kg intravenously ad-
ministered ketamine and 0.01 mg/kg atropine, whereas the con-
trol group received 1 mg/kg ketamine along with distilled water.
Age, sex, body weight, type of procedure, time of sedation,
any medical emergency interventions, and physicians satisfac-
tion from the sedation process and adverse effects of the inter-
vention were fully recorded by a blinded investigator (a physician)
through complete observation and examination of the signs or
symptoms of the patients after drug injection.
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Ketamine and Atropine for Pediatric Sedation
Any nausea (tendency to vomit) or any grade of vomiting,
muscle spasm, rash, unusual movement, or tachycardia observed
by the investigator were recorded as adverse effects. Apnea (ces-
sation of spontaneous breath for 910 seconds), low oxygen satu-
ration (G90%) and hypersalivation (90 mL of saliva), as well as
occurrence of emergent phenomenon (obvious unpleasant dreams
and inconsolable crying)15 were also recorded. Increased salivation
was recorded based on the estimated volume of patients excessive
salivation. Physicians judgment (the one who was responsible for
PSA) was the main criterion to determine whether a patient re-
quired suction.
Patients were carefully monitored during sedation proce-
dure by pulse oximetry, electrocardiogram, and ETCO2 monitor
(when available). Other equipments such as oxygen, bag-mask
ventilation, laryngoscope, endotracheal tubes, and suction cathe-
ters were in immediate access in case of emergency.
Discharge Criteria
Monitoring was continued after the procedure until the child
met the criteria for safe discharge. These consisted airway pa-
tency and stable cardiovascular function, easy arousability with
intact protective reflexes, ability to talk (if age appropriate), abil-
ity to sit, stand or walk unaided (if age appropriate), and ade-
quate hydration with management of any nausea, vomiting, or
pain.7,18,19 A full explanation and advice sheet was provided
to the supervising parent.
Randomization
Although evaluations were completed for all patients and
confirmed that a patient can be included in the study, the par-
ticipants randomly allocated to control or intervention groups
using 50 blocks of cards; each block contained 4 closed enve-
lopes to assign 2 participants to each group. This assured that
the sequence was concealed until interventions were assigned.
The envelopes were opened by the nurse who was responsible
for drug injection to consign the participants to their groups. All
data including the times were recorded by a blinded observer.
Blinding
The researcher who recorded the data, the physician who
was responsible for PSA, and the one who analyzed the data
were blinded to the intervention process. The nurse who opened
the envelope and assigned the patient to one of the groups and
the physician who performed the procedure were not blinded.
Statistical Methods
Categorical data were presented as frequencies, percent-
ages, and odds ratios with 95% confidence limits reported to
compare adverse effects of each treatment group. Mean time
measurements were compared by using independent t test in
both groups. Fisher exact test or W2 tests were applied to com-
pare the treatment groups. All recorded data were statistically
analyzed using SPSS version 17 (SPSS Inc, Chicago, IL).
All P values were reported based on 2-sided tests and
compared with a significance level of 5%.
RESULTS
Participants
Among the total 218 eligible patients, 200 participants
were enrolled and allocated to the study groups. The pro-
cedures performed using ketamine/atropine and ketamine/
placebo (Fig. 1). All data recorded by a blind researcher were
analyzed by a blind statistician.
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Asadi et al Pediatric Emergency Care & Volume 29, Number 2, February 2013

TABLE 1. Baseline Demographic Characteristics TABLE 3. Adverse Effects and Therapeutic Interventions

Significance 95%
Atropine Placebo (2-Tailed) Atropine Placebo Odds Confidence
Age, mean 7.0 (3.6) 7.1 (3.8) 0.932* (100) (100) Ratio* Interval
(SD), y Adverse effects
Sex, male, 65 (65) 72 (72) 0.287 Nausea 15 20 0.71 0.34Y1.47
n (%) Vomiting 7 11 0.62 0.23Y1.62
Weight, mean 23.2 (8.0) 23.0 (9.8) 0.887* Muscle spasm 5 4 1.26 0.3321Y4.784
(SD), kg
Emergent 5 4 1.26 0.3321Y4.784
Procedure time, 9.0 (3.4) 9.2 (4.1) 0.919* phenomenon
mean (SD), min
Unusual 12 8 1.56 0.6191Y3.9113
Sedation time, 37.3 (6.8) 37.6 (7.6) 0.783* movement
mean (SD), min
Rash 8 5 1.63 0.5324Y5.0164
*Independent t test. Tachycardia 6 2 2.82 0.6876Y11.5586
W test.
2
Apnea 0 0 0 V
Low oxygen 2 2 1 V
saturation
Baseline Data Hypersalivation 12 28 0.37 0.1852Y0.738
Baseline demographic characteristics of the patients are Interventions
shown in Table 1. Characteristics were similar in both groups: Suction 4 21 0.21 0.0923Y0.4914
mean (SD) age of the patients in the intervention group was 7.0 Bag-mask 2 2 1 V
(3.6) years (range, 2Y14 years), which showed no statistically ventilation
difference with the control group (age range, 2Y15 years; mean, Intubation 0 0 0 V
7.1 [3.8] years). The difference between the sex and weight of Physical 11 9 1.25 0.4963Y3.1354
the participants in both groups was not statistically significant. containment
The mean (SD) procedure time in the intervention group was Other drugs 10 8 1.27 0.4852Y3.3505
9.0 (3.4) minutes, and the mean (SD) sedation time was 37.3 *Odds for atropine relative to placebo.
(6.8) minutes, which were comparable with the control group with
P G 0.01.
the mean (SD) time of 9.2 (4.1) minutes and 37.6 (7.6) minutes,
respectively.
The intervention and placebo groups were similar in medi-
cal procedures. Wound management, joint reduction, and fractures more among treatment group rather than controls (12% vs 2%,
were the procedures that required performing sedation (Table 2). respectively), all procedures were successfully completed (Table 2).

Outcomes Adverse Events

Applying ketamine (with or without atropine) led to good Adverse events recorded during the study procedure are
sedation, and most of the procedures were done with complete listed in Table 3. Nausea, vomiting, and hypersalivation were
cooperation of the patient or with minimal crying or movements. the complications that were reported less in the intervention
Although crying with thrashing movements was significantly seen group compared with the control. Only hypersalivation showed
a significant decrease among the patients who received atropine
(12% vs 28%) (Table 4). The odds ratio of 0.37 (95% confi-
TABLE 2. Procedures and Tolerance dence interval, 0.18Y0.74) proved that hypersalivation would
Atropine, Placebo, Significance reduce under atropine treatment compared with placebo. Pa-
% % (2-tailed)* tients in intervention group who received atropine showed sig-
nificantly less salivation than those in the control group; hence,
Tolerance less suction was needed (4/12 among treatment group and 21/28
Cooperative 54 58 0.021 among the controls). It should be noted that physicians judg-
Some movement 34 40 ment on airway complications was the most important point of
or crying view to perform suctioning for a patient, independent of the
Crying with thrashing 12 2 amount of saliva. Other adverse effects such as abnormal
movements
Unable to complete 0 0
procedure TABLE 4. Estimated Volume of Patients Excessive Salivation
Procedure
Fracture 11 16 0.357 Excessive Salivation, mL* Atropine, % Placebo, %
Reduction 47 38 0 88 72
Wound management 42 46 G5 7 15
*W2 test. 5Y10 4 10

Stable fractures requiring only splinting or casting. 910 1 3

Fractures or dislocations requiring closed reduction. *W2; asymptotic significance (2-sided) = 0.097.

138 www.pec-online.com * 2013 Lippincott Williams & Wilkins

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Pediatric Emergency Care & Volume 29, Number 2, February 2013
movements, rash, muscular spasm, and tachycardia were seen
more frequently in the intervention group, none of which was
statistically significant (Table 3). Low oxygen saturation was
reported only in 2% of the participants, whereas none of the
children experienced apnea or laryngospasm during the sedation
process.
DISCUSSION
Despite inconsistent data that adjunctive anticholinergics
can reduce the amount of oral secretions, lower tolerance by the
children is another important adverse effect of using atropine.
It can restrict its use along with ketamine for pediatric seda-
tion. Children who received atropine showed more crying with
thrashing movements than the patients in the placebo group.
Although using atropine causes more muscle spasm, emergent
phenomenon, unusual movement, and transient rash among the
patients, these are not significant.
Prolonged sedation and failure to sedate adequately for the
procedures are common problems in pediatric practice.1 It seems
that using atropine along with ketamine do not affect the seda-
tion time (37.3 [6.8] in intervention group vs 37.6 [7.6] in placebo
group), but considering sufficient sedation, adverse effects of
ketamine such as muscle spasms, unusual muscle movements, or
myoclonus are aggravated by atropine. These findings are in
contrast to what Brown et al16 reported in their observational
study that at the doses used for ketamine sedation in children,
when adjunctive atropine is omitted, excessive salivation is un-
common. Our data show that even in atropine group, hyper-
salivation is not rare and 12% of the subjects would experience
hypersalivation; this is as high as reported by McGlone et al9 who
used intramuscular ketamine along with atropine. Our conclusion
is consistent with the data of Heinz et al,15 whose randomized,
double-blinded trial of 83 emergency department pediatric pa-
tients resulted in significantly less hypersalivation (11% vs 31%,
P = 0.03) and also less emesis with atropine (9% vs 26%), which
is due to its anticholinergic and mild antiemetic properties.
However, they believed that routine use of atropine for prophy-
laxis should not be encouraged. It seems that using atropine re-
duces the need for suctioning of the secretions along with
reduction of nausea and vomiting. It also has no effect on other
complications of ketamine.
Low oxygen saturation was reported only in 2% of the par-
ticipants without any difference between the groups. None of the
children twisted to apnea or laryngospasm. Our study showed no
efficacy in reducing airway complications except for hypersaliva-
tion, which supports the conclusion of previous studies suggesting
that coadministered anticholinergics should not be routinely used
during ketamine sedation.14,15
Limitations
Failure to blind the nurse who assigned the groups and the
physician who was responsible for the procedure as well as
failure to perform long-term follow-up of all patients after the
procedure were our most important limitations.
CONCLUSIONS
Adding atropine to ketamine significantly reduces hyper-
salivation without producing any adverse effects on the pro-
cedure success rate or duration. We recommend further studies
to confirm the effects of atropine as adjunct for ketamine se-
dation in children at emergency departments.
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Ketamine and Atropine for Pediatric Sedation
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