ORIGINAL RESEARCH CONTRIBUTION
The Effect of Ketamine on Intraocular
Pressure in Pediatric Patients During
Sarah M. Halstead, MD, Sara J. Deakyne, MPH, Lalit Bajaj, MD, MPH, Robert Enzenauer, MD, MPH,
and Genie E. Roosevelt, MD, MPH
Objectives: Ketamine is one of the most commonly used procedural sedation and analgesia (PSA) agents
in pediatric emergency departments (PEDs). It is considered a very safe and reliable agent, with limited
respiratory suppression, hemodynamic effects, and adverse outcomes. However, physicians are often
reluctant to use ketamine for patients with eye injuries due to a concern that ketamine might increase
intraocular pressure (IOP). The objective was to measure IOP in previously healthy children receiving
ketamine for PSA for a reason other than eye injury.
Methods: This was a prospective noninferiority study of patients seen in an academic tertiary care chil-
dren’s hospital emergency department (ED) who required ketamine for PSA. The authors measured IOP
in the right eye as soon as possible after ketamine had been administered and then at 2.5, 5, and 10 min-
utes after ketamine had been administered.
Results: Eighty patients were enrolled (28 between 1 and 5 years of age, 26 between 6 and 10 years,
26 between 11 and 15 years); 49 (61%) were male. Procedures requiring PSA included fracture⁄disloca-
tion reduction (63%), abscess incision and drainage (16%), laceration repair (11%), dental abscess inci-
sion and drainage (6%), and other (4%). The mean total ketamine dosage was 1.6 mg⁄kg (95%
confidence interval [CI] = 1.4 to 1.7). The mean initial IOP was 17.5 mm Hg (95% CI = 16.4 to
18.6 mm Hg) and at 2.5 minutes was 18.9 mm Hg (95% CI = 17.9 to 19.9 mm Hg). The mean difference
was 1.4 mm Hg (95% CI = 0.4 to 2.4 mm Hg). Using a noninferiority margin of 2.6 mm Hg (15%), nonin-
feriority (no significant elevation in IOP) was demonstrated with 95% confidence between the first and
Conclusions: Ketamine does not significantly increase IOP in pediatric patients without eye injuries
receiving typical PSA dosages in the PED. Further study should assess its safety in patients with ocular
ACADEMIC EMERGENCY MEDICINE 2012; 19:1145–1150 ª 2012 by the Society for Academic
pressure less than 24 mm Hg.1The criteria used to define
intraocular hypertension vary between different studies,
opulation-based studies suggest that the mean
intraocular pressure (IOP) is approximately 15
mm Hg, with 97% of the population having a
although in the majority of studies the upper limit of nor-
mal lies between 22 and 26 mm Hg.2There is some
suggestion that age affects IOP measurements.3
The concern that ketamine might increase IOP stems
from animal studies,4–7human studies using multiple
ª 2012 by the Society for Academic Emergency Medicine
PII ISSN 1069-6563583
From the Department of Pediatrics, Section of Pediatric Emergency Medicine (SMH, SJD, LB, GER), and the Department of
Ophthalmology (RE), University of Colorado Denver, Children’s Hospital Colorado, Denver, CO.
Received February 21, 2012; revision received April 18, 2012; accepted May 21, 2012.
Presented at the American Academy of Pediatrics National Conference, Section of Emergency Medicine, Boston, MA, October
2011, receiving the Best Research Poster Award.
The authors thank the Pediatric Glaucoma and Cataract Family Association and the Albert Medow Eye Foundation, who provided
the grant for the Tono-Pen, as well as the Children’s Hospital Colorado Research Institute, who covered partial costs for the RAs,
for their generous support. The authors have no further disclosures or conflicts of interest to report.
Supervising Editor: Jacob Ufberg, MD.
Address for correspondence and reprints: Genie Roosevelt, MD, MPH; e-mail: firstname.lastname@example.org.
anesthetics concurrently,8and studies using much larger
dosages of ketamine9than one would typically use for
procedural sedation and analgesia (PSA). However, other
studies report no significant increase.10,11Blumberg
et al.12concluded that ketamine might have advantages
over gas anesthetics for obtaining IOP measurements in
children as ketamine neither increased nor decreased
IOP from baseline measurements. Our objective was to
measure IOP in previously healthy pediatric patients
receiving ketamine PSA in the pediatric emergency
department (PED) to evaluate if ketamine may be consid-
ered as a PSA agent for patients with eye injuries.
We performed a prospective noninferiority study mea-
suring IOP in pediatric patients receiving ketamine PSA
for a complaint other than an eye injury (e.g., fracture
or dislocation reduction, laceration repair, abscess inci-
sion and drainage) in an urban tertiary care PED. This
study was approved by the institutional review board.
Written informed consent was obtained from the
parent or guardian of all patients enrolled in the study;
written assent was obtained from all patients 7 years of
age and older. An Investigational New Drug (IND)
application was approved to use proparacaine hydro-
chloride ophthalmic solution 0.5% drops as it is not
approved by the U.S. Food and Drug Administration
for use in children (IND No. 107557).
Study Setting and Population
Study subjects were recruited from patients between
1 and 15 years of age who had an American Society of
Anesthesiologists physical status classification of 1⁄1E
or 2⁄2E. After the parent or guardian consented to
ketamine PSA, each was approached to participate in
the study. To control for potential IOP differences by
age, subjects were recruited in the following age
blocks: 1 to 5, 6 to 10, and 11 to 15 years.
Patients were excluded from the study if they had a
history of glaucoma or any other eye condition. Patients
with a latex allergy were excluded, as the cover tips for
the tonometer contain latex. Patients with an allergy to
ester-type local anesthetics such as benzocaine, buta-
caine, tetracaine, or proparacaine were excluded as we
used proparacaine hydrochloride ophthalmic solution
After patient enrollment, one to two drops of the local
placed in the right eye immediately prior to PSA. IOP
was measured with the Tono-Pen XL (Reichert Technol-
ogies, Buffalo, NY), an accurate handheld applanation
tonometer,13,14in the right eye as soon as possible after
ketamine had been administered and then at 2.5, 5, and
10 minutes after initial ketamine administration. IOP
was measured by pediatric emergency medicine attend-
ing physicians and fellows who were trained on the
Tono-Pen XL by a pediatric ophthalmologist. Tono-Pen
readings were considered acceptable if the reliability
measure was 5 or 10% (i.e., the standard deviation of
the measurements was 10% or less of the measure-
ment). The same physician obtained all measurements
for a given patient. The ketamine was administered
intravenously (IV) by the treating attending physician,
who was not the same physician measuring IOP. The
dosage and timing of the ketamine administration, as
well as all the administration of other medications,
were left to the treating physician’s discretion.
Demographic and clinical variables, including age, sex,
weight, procedure performed, other medications given,
recorded onto a standardized data collection sheet. Pulse
and blood pressure were recorded at the same intervals
as the IOP measurements by research associates.
The primary outcome measure was the mean difference
in IOP between the initial and 2.5-minute measurements
with a noninferiority margin of 15%. The secondary
outcome measure was the change in IOP over the
10-minute study period.
The Kruskal-Wallis test was used to compare total dos-
ages of ketamine between the three age groups as the
distribution was nonparametric. The mean difference
with 95% confidence intervals (CIs) of the initial IOP
and the 2.5-minute IOP measurement were used to
evaluate noninferiority. Linear regression was per-
between total ketamine dosage and IOP at 10 minutes
controlling for baseline IOP measurements. Repeated-
measures analysis of variance (ANOVA) was performed
to analyze IOP trends during the study period control-
ling for age and initial heart rate as a proxy for discom-
fort. Sample size calculations were performed a priori
with a power of 0.9 and a = 0.05. Using a noninferiority
design with a clinically significant margin of noninferi-
ority of 15% between the initial and 2.5-minute mea-
surements, 26 patients would be required for each of
the three age groups (1 to 5, 6 to 10, 11 to 15 years) for
a total study population of 78. The noninferiority mar-
gin of 15% was chosen by a pediatric ophthalmologist
(RE) as a clinically relevant difference. Data were ana-
lyzed using SAS 9.2 (SAS Institute Inc., Cary, NC).
Eighty patients were enrolled between February 2010
and May 2011: 28 between 1 and 5 years of age, 26
between 6 and 10 years, and 26 between 11 and
15 years; 49 (61%) were male (Table 1). The most com-
monly performed procedure during the study was frac-
ture⁄dislocation reduction, although abscess incision
and drainage and laceration repair were more common
in the youngest age group. Other procedures included
gynecologicexam and oral foreign body removal
(Table 1). The mean total ketamine dosage administered
IV was 1.6 mg⁄kg (95% CI = 1.4 to 1.7). The dosage did
not differ based on the age of the patient (p = 0.44).
Other medications received by patients during their
PED course included glycopyrolate, midazolam, and
ondansetron. Glycopyrolate was the most commonly
Halstead et al.•EFFECT OF KETAMINE ON IOP IN CHILDREN
used other medication (11%), primarily in the youngest
age group. Other less frequently administered medica-
tions included methylene blue and lidocaine cream
The mean initial IOP was 17.5 mm Hg (95% CI = 16.4
to 18.6 mm Hg), and at 2.5 minutes was 18.9 mm Hg
(95% CI = 17.9 to 19.9 mm Hg). The mean difference
was 1.4 mm Hg (95% CI = 0.4 to 2.4 mm Hg). Using a
noninferiority margin of 2.6 mm Hg (15%), noninferiority
(no significant elevation in IOP) was demonstrated with
95% confidence between the first and second readings.
The mean difference between initial and 2.5 minutes for
the 1-to 5-year-oldgroup
CI = )0.4 to 3.3 mm Hg), for the 6- to 10-year-old group
was 2.0 (95% CI = 0.7 to 3.3 mm Hg), and for 11- to 15-
year-old group was 0.7 (95% CI = )1.5 to 3.0). Patient-
level analysis was included in by-subject plots for the
three different age groups (Figures 1–3). There was no
evidence of a dose–response relationship between IOP
at 10 minutes and total ketamine dosage in mg⁄kg con-
trolling for the baseline IOP measurement (p = 0.15).
There was a statistical difference in IOP over the 10-
was 1.4 mm Hg(95%
minute study period controlling for age and initial heart
rate using repeated measures
ANOVA(p < 0.01;
We found that ketamine did not significantly increase
IOP in pediatric patients undergoing PSA. Although we
saw a statistically significant trend in IOP during the
study period, we do not believe that this finding is clini-
cally significant given the small changes seen in IOP
(<2.5 mm Hg). Small, transient elevations in IOP in this
range are not even considered clinically significant for
patients with glaucoma, as diurnal fluctuations of IOP
to this degree are anticipated.15,16These findings are
important because ketamine has not been traditionally
used in the PED for PSA for ophthalmic exams in pedi-
atric patients with eye injuries due to concerns that
ketamine might increase IOP. The strengths of our
study include stratification by age to ensure the inclu-
sion of younger children, a noninferiority design with
sample size calculations, and dosage of ketamine typical
Demographic Characteristics, Procedures Performed, and Medication Administration
Variable Overall (n = 80) 1–5 yr (n = 28)6–10 yr (n = 26) 11–15 yr (n = 26)
Male, n (%)
Procedures, n (%)
Abscess incision and drainage
Dental abscess incision and drainage⁄tooth extraction
Mean total dosage of ketamine, mg⁄kg (95% CI)
Other medications, n (%)
49 (61) 16 (57)15 (58) 18 (69)
Figure 1. IOP measurements (mm Hg) in patients aged 1 to 5 years.
ACADEMIC EMERGENCY MEDICINE•October 2012, Vol. 19, No. 10•www.aemj.org
for PSA usage in the PED (i.e., 1–2 mg⁄kg IV). In addi-
tion, we saw no evidence of a dose–response relation-
ship between ketamine dosage and IOP.
Our study agrees with a recently published manu-
script that there are no clinically meaningful associa-
tions of ketamine with IOP at typical PSA dosages.17
Although Drayna et al.17found no statistically signifi-
cant changes of mean IOP between baseline and any
time point during their study period, there were only
25 patients enrolled in their study. In our study of
80 patients, we found a statistically significant differ-
ence that a smaller study would be unlikely to observe
due to sample size considerations. One of the advanta-
ges of repeated-measures ANOVA analysis is its power
to detect statistically significant differences. To date,
our study is the largest examining the relationship
between IOP and ketamine in pediatric patients.
Previous studies that showed a relationship between
IOP and ketamine used intramuscular (IM) ketamine in
the operating room (OR) in larger dosages (e.g.,
5–10 mg⁄kg) than one would typically use for PSA.8,9,12
The typical range for IM dosing of ketamine for PSA is
Figure 2. IOP measurements (mm Hg) in patients aged 6 to 10 years.
Figure 3. IOP measurements (mm Hg) in patients aged 11 to 15 years.
Mean IOP Measurements (mm Hg)
Age Group (yr) Initial IOP (95% CI)2.5-minute IOP (95% CI)5-minute IOP (95% CI) 10-minute IOP (95% CI)
Halstead et al.•EFFECT OF KETAMINE ON IOP IN CHILDREN
2 to 4 mg⁄kg. The standard initial dose of IV ketamine
for PSA is 1 mg⁄kg and usually no more than 2 mg⁄kg
total IV dosage is required. In addition, these studies
included patients who were scheduled for ophthalmic
procedures, suggesting the presence of some type of
prior ocular pathology.8,9,12These studies performed in
the OR are also confounded by the administration of
different medications such as atropine, pentobarbital,
meperidine, methohexital, and inhaled anesthetics.8,9,12
Physicians should use caution when extrapolating data
from different patient care settings, including different
types of patients and different dosages of medications,
to their patients and practice location.
We specifically included pediatric patients in the age
group of 1 to 5 years as there is a paucity of data
regarding the relationship between IOP and ketamine
in this age range. The youngest patient enrolled in the
study by Drayna et al. was 7 years of age.17Nagdeve
et al.8studied patients in the 1- to 6-year-old age group,
but their study was performed in the OR after receiving
halothane for induction. Inhaled anesthetics have been
shown to reduce IOP so their results are not generaliz-
able to patients receiving PSA in the pediatric ED.12We
thought it was important to include this age group as
they are the pediatric patients most likely to require
PSA for thorough ophthalmic exams. Reassuringly,
the IOP in this age group did not show a clinically
Limitations to our study included that IOP measure-
ments were obtained by multiple providers who were
unfamiliar with the Tono-Pen XL prior to the study,
likely resulting in greater variability in the measure-
ments than would be expected if there were fewer
observers. Our study may be underpowered, as our
sample size calculations assumed less variability in the
measurement of IOP. We measured IOP as soon as pos-
sible after ketamine administration, which was most
difficult in the younger patients. Therefore, the initial
IOP measurement may have included some effect of the
ketamine, resulting in an underestimation of the true
difference between the initial and 2.5-minute measure-
ments. We were not able to measure IOP continuously,
so could have potentially missed clinically important
spikes in IOP between measurements. We measured
IOP in patients without eye injuries so cannot comment
on ketamine’s effect on IOP in the presence of an eye
injury. Potential confounders included other medica-
tions administered during the study period such as gly-
copyrolate and midazolam. We also did not control for
the type of procedure performed, which may have con-
founded the relationship between ketamine and IOP
due to the varying levels of discomfort with different
Ketamine does not significantly increase intraocular
pressure in pediatric patients without eye injuries
receiving typical procedural sedation and analgesia
dosages in the pediatric ED. Further study should
assess its safety in patients with ocular injury.
The authors thank Drs. Ryan Caltagirone, Julia Fuzak, Joseph Gru-
benhoff, Amanda Greene, Sam Wang, and Keith Weisz for their
help measuring IOP in study patients. They also thank their
research associates, Sarah Baumbach, Korie Burroughs, and
Kendra Kocher, for patient enrollment and data collection.
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Halstead et al.•EFFECT OF KETAMINE ON IOP IN CHILDREN