Feature Review Article

Dexmedetomidine and ketamine: An effective alternative for

procedural sedation?
Joseph D. Tobias, MD

Objectives: Although generally effective for sedation during
noninvasive procedures, dexmedetomidine as the sole agent
has not been uniformly successful for invasive procedures. To
overcome some of the pitfalls with dexmedetomidine as the sole
agent, there are an increasing number of reports regarding its
combination with ketamine. This article provides a descriptive
account of the reports from the literature regarding the use of a
combination of dexmedetomidine and ketamine for procedural
sedation.
Data Source: A computerized bibliographic search of the lit-
erature regarding dexmedetomidine and ketamine for procedural
sedation.
Measurements and Main Results: The literature contains four
reports with cohorts of more than ten patients with a total of 122
patients. Two of these studies were prospective randomized tri-
als. Additionally, there are eight single case reports or small
case series (six patients or less) with an additional 21 pediatric
patients. When used together, dexmedetomidine may prevent the
tachycardia, hypertension, salivation, and emergence phenomena
from ketamine, whereas ketamine may prevent the bradycardia
and hypotension, which has been reported with dexmedetomidine.
An additional benefit is that the addition of ketamine to initiate the
sedation process speeds the onset of sedation, thereby eliminat-
ing the slow onset time when dexmedetomidine is the sole agent.
Although various regimens have been reported in the literature,
the most effective regimen appears to be the use of a bolus dose of
both agents, dexmedetomidine (1 μg/kg) and ketamine (1–2 mg/
kg), to initiate sedation. This can then be followed by a dexmedeto-
midine infusion (1–2 μg/kg/hr) with supplemental bolus doses of
ketamine (0.5–1 mg/kg) as needed.
Conclusions: The available literature except for one trial is favor-
able regarding the utility of a combination of ketamine and dexme-
detomidine for procedural sedation. Future studies with direct com-
parisons to other regimens appear warranted for both invasive and
noninvasive procedures. (Pediatr Crit Care Med 2012; 13:423–427)
Key Words: dexmedetomidine; ketamine; procedural sedation

I nvasive and noninvasive procedures

remain a component in the man-
agement of children with acute and
chronic diseases. In recent years
there has been a shift in the philosophy
regarding procedural sedation given the
increasing recognition of the negative as-
pects of inadequate sedation. Therefore,
more patients are being sedated for proce-
dures and the depth of sedation achieved
is increasing in certain environments.
Regardless of the procedure, there are
several options for the agent or agents
chosen for sedation. In the general prac-
tice of procedural sedation, propofol is a
frequently chosen agent because it can be
easily titrated by continuous infusion, is
generally effective, and allows for rapid
From the Departments of Anesthesiology and
Pediatrics, Nationwide Children’s Hospital and the Ohio
State University, Columbus, OH.
The author has not disclosed any potential conflicts
of interest.
For information regarding this article, E-mail:
Joseph.Tobias@Nationwidechildrens.org
Copyright © 2012 by the Society of Critical Care
Medicine and the World Federation of Pediatric Intensive
and Critical Care Societies
DOI: 10.1097/PCC.0b013e318238b81c
awakening once the procedure is com-
pleted. However, in patients with comor-
bid respiratory or cardiovascular diseases,
there may be a relatively high incidence of
respiratory effects, including hypotension,
hypoventilation, upper airway obstruc-
tion, and apnea (1–6). Although these
effects are generally dose-dependent and
more likely with higher doses as deeper
levels of sedation/anesthesia are achieved,
there is significant interpatient variability
regarding the potential for adverse effects
(7). Given these concerns, the search for
alternative agents continues.
Dexmedetomidine (Precedex; Hospira
Worldwide, Lake Forest, IL) exerts its
physiologic effects through the α2-
adrenergic receptor system. Initial Food
and Drug Administration approval in
the United States for the administration
of dexmedetomidine occurred in 1999.
At that time, approval was granted for
the sedation of adults during mechani-
cal ventilation. Additional approval was
granted in 2009 for monitored anesthe-
sia care in adults. Although Food and
Drug Administration-approved only for
use in adults, dexmedetomidine con-
tinues to be used successfully in several
different clinical scenarios in infants and
children, including procedural sedation
(8). Although generally effective for se-
dation during noninvasive procedures,
dexmedetomidine as the sole agent has
not been uniformly successful for inva-
sive procedures (9–13). In the first pro-
spective evaluation of dexmedetomidine
as the sole agent during an invasive pro-
cedure in infants and children, Munro
et al (9) reported their experience with
dexmedetomidine during cardiac cath-
eterization. After oral premedication
with midazolam and the placement of
intravenous access, dexmedetomidine
was administered as a loading dose of 1
μg/kg over 10 mins, followed by an infu-
sion of 1 μg/kg/hr titrated up to 2 μg/
kg/hr as needed. Five of the 20 patients
(25%) moved during local infiltration of
the groin, which did not require treat-
ment or interfere with cannulae place-
ment. Twelve (60%) patients received a
propofol bolus during the procedure for
movement, an increasing bispectral in-
dex number, or anticipation of a stimu-
lus. Subsequent studies in the adult
population have similarly demonstrated
that dexmedetomidine may not be the

Pediatr Crit Care Med 2012 Vol. 13, No. 4 423

Table 1. Large case series regarding dexmedetomidine–ketamine for procedural sedation in infants and children

Author Type of Study and Cohort Size Outcomes

Tosun et al (16) Prospective randomized trial comparing dexmedetomidine–
ketamine with propofol–ketamine sedation in 44
pediatric patients during cardiac catheterization
Koruk et al (17) Prospective randomized trial comparing dexmedetomidine–
ketamine with midazolam-ketamine in 50 pediatric
patients for extracorporeal shock wave lithotripsy
Mester et al (18) Retrospective case series using dexmedetomidine and
ketamine for sedation during cardiac catheterization. No
comparative group was included. The cohort included 16
children ranging in age from 16 mos to 15 yrs
McVey and Tobias (19) Retrospective case series using dexmedetomidine and
ketamine for sedation during lumbar puncture for spinal
anesthesia. No comparative group was included. The
study cohort included 12 children ranging in age from 2
to 9 yrs
Sedation managed effectively with both regimens. Patients
sedated with ketamine–dexmedetomidine required more
ketamine (2.03 ± 1.33 vs. 1.25 ± 0.67 mg/kg/hr;
p < .01), more frequently required supplemental doses
of ketamine (10 of 22 patients vs. 4 of 22 patients), and
had a longer recovery time (median time of 45 vs. 20
mins; p = .01).
Sedation was equally effective in both groups. Times for
eye-opening, verbal response, and cooperation were
decreased in the dexmedetomidine–ketamine group.
The incidence of nausea and vomiting was lower with
dexmedetomidine–ketamine (4.7% vs. 32%).
No patients responded to infiltration of the groin
with local anesthetic and placement of the arterial
and venous cannulae. Three patients required a
supplemental dose of ketamine. In two patients, the
dexmedetomidine infusion was decreased because of
heart rate changes. Two patients had development
of upper airway obstruction that responded to
repositioning of the airway.
The lumbar puncture for the performance of spinal
anesthesia was tolerated in all of the patients. One
patient required a decrease of the dexmedetomidine
infusion for bradycardia. One patient required a fluid
bolus for blood pressure of 68/38 mm Hg. Two patients
had upper airway obstruction that resolved with
repositioning of the airway.

optimal agent for painful procedures.
Jalowiecki et al (10) reported that dex-
medetomidine was ineffective during
colonoscopy in adults and was associ-
ated with a high incidence of adverse
effects, including a prolonged delay in
discharge times. The authors closed the
study before completion (12). Similar
issues were encountered when compar-
ing dexmedetomidine with midazolam
for monitored anesthesia care in adults
during cataract surgery (13).
In specific clinical scenarios, the
response to failures with usual doses (1–2
μg/kg) has been to switch to or to add al-
ternative agents or to increase the dose
of dexmedetomidine (14, 15). However,
when such dose escalations are attempt-
ed, a higher incidence of hemodynamic
effects such as bradycardia and hypoten-
sion has been noted. Given these issues,
the addition of a second agent to dexme-
detomidine rather than dose escalations
may be the preferred option.
Procedural Sedation With Dexmedeto-
midine and Ketamine. Issues of concern
when considering dexmedetomidine as
an agent for procedural sedation include
a long onset time, limited analgesic ef-
fect, and the potential for hemodynamic
effects, including bradycardia and hypo-
tension, especially when larger doses are
administered. Although limited in
number when compared to reports us-
ing only dexmedetomidine, there have
been several reports in the literature
regarding the use of a dexmedetomi-
dine–ketamine combination for proce-
dural sedation in the pediatric population
(Table 1) (16–19). Two of these reports
have been prospective randomized trials
with a comparison to another sedation
regimen (16, 17). Tosun et al (16) com-
pared a procedural sedation regimen that
included dexmedetomidine and ketamine
with one that combined propofol and
ketamine. The study cohort included 44
children, ranging in age from 4 months
to 16 yrs, with acyanotic congenital heart
disease undergoing cardiac catheteriza-
tion. Ketamine (1 mg/kg) and dexmedeto-
midine (1 μg/kg) were administered over
10 mins, followed by infusions of dexme-
detomidine at 0.7 μg/kg/hr and ketamine
at 1 mg/kg/hr. In the other arm of the
study, propofol (1 mg/kg) and ketamine
(1 mg/kg) were administered as the load-
ing dose, followed by a propofol infusion
at 100 μg/kg/hr and ketamine at 1 mg/kg/
hr. In both arms of the study, supplemen-
tal bolus doses of ketamine (1 mg/kg)
were available as needed. Although seda-
tion was effective with both regimens,
the propofol–ketamine combination was
superior. Patients sedated with dexme-
detomidine–ketamine required more ket-
amine (2.03 ± 1.33 vs. 1.25 ± 0.67 mg/kg/
hr; p < .01) and more frequently required
supplemental doses of ketamine (10/22
patients vs. 4/22 patients). Additionally,
the recovery time was longer with dex-
medetomidine and ketamine (median
time, 45 vs. 20 mins; p = .01). No clini-
cally significant differences in the hemo-
dynamic or respiratory status were noted
between the two groups.
Koruk et al (17) prospectively com-
pared sedation using dexmedetomidine
and ketamine to a regimen using mid-
azolam and ketamine during extracor-
poreal shock wave lithotripsy in a cohort
of 50 pediatric patients who ranged in
age from 2 to 15 yrs. Patients received
either a bolus dose of dexmedetomidine
(1 μg/kg over 10 mins) and ketamine
(1 mg/kg) or a bolus dose of midazolam
(0.05 mg/kg) and ketamine (1 mg/kg).
Patients were then observed by an anes-
thesiologist who was blinded to which
medications they had received. Sedation
was equally effective in both groups with-
out clinically significant changes in the
hemodynamic and respiratory param-
eters. Although there was no difference
in the time to achieve an Aldrete score
of 8, the times for eye opening, verbal

424 Pediatr Crit Care Med 2012 Vol. 13, No. 4

Table 2. Small case series and isolated case reports regarding dexmedetomidine–ketamine for procedural sedation

Author Type of Study and Cohort Size Dosing Regimen for Dexmedetomidine and Ketamine Outcomes

Bozdogan et al (21) Sedation during caudal anesthesia Bolus dose of ketamine (1 mg/kg) dexmedetomidine. Caudal epidural block was achieved and
in three high-risk infants (ages
5, 6, and 10 mos) with a history
of ongoing or recent acute viral
upper respiratory infections and
congenital heart disease
Barton et al (22) Procedural sedation in six infants Dexmedetomidine was administered at an average
(age 3 d to 29 mos) with
congenital heart disease
Luscri and Case series of three children with Sedation was initiated with a bolus dose of ketamine The scan required that no artificial airway
Tobias (23) trisomy 21 who required sedation (1 mg/kg) and dexmedetomidine (1 μg/kg) and
during a magnetic resonance
imaging scan for evaluation of
sleep apnea
Irvani and Wald (24) 6-yr-old girl with Treacher
Collins syndrome and severe
micrognathia
Mahmoud et al (25) 4-yr-old, 20-kg boy with a large
mediastinal mass and tracheal
compression
Munro et al (26) 12-yr-old, 31-kg boy with
pulmonary hypertension
Rozmiarek et al (27) 21-yr-old, 43-kg man with
Duchenne muscular dystrophy
with compromised cardiac and
respiratory function
Corridore et al (28) A 3-yr-old, 14-kg girl with a
mediastinal mass and tracheal
compression
The bolus dose of both agents was repeated to
achieve a Ramsay sedation scale score of 4. This was without difficulty. No clinically
followed by a dexmedetomidine infusion at 0.7–1
μg/kg/hr, titrated to maintain a Ramsay sedation
scale score of 4 during the surgery
dose of 1.5 μg/kg (range, 1–3 μg/kg). Three of the
6 patients (50%) required bolus doses of ketamine
(0.3–0.5 mg/kg) because of movement during the
procedure
maintained by a dexmedetomidine infusion (1 μg/
kg/hr). One patient required a repeat of the bolus
doses of ketamine and dexmedetomidine and an
increase of the dexmedetomidine infusion to
2 μg/kg/hr
A bolus dose of dexmedetomidine 1 μg/kg was
followed by a continuous infusion at 1 μg/kg/hr.
Once a Ramsay sedation scale score of 5 (sluggish
response to glabellar tap) was achieved, three
incremental doses of ketamine (0.25 mg/kg) were
administered until there was no response to a
glabellar tap
A loading dose of dexmedetomidine (2 μg/kg) and
ketamine (0.5 mg/kg) were administered. Propofol
(1 mg/kg) was administered to facilitate
placement of an laryngeal mask airway. The
anesthetic was maintained with a dexmedetomidine Spontaneous ventilation was
infusion at 2 μg/kg/hr) and ketamine boluses to a
total dose of 30 mg
Premedication with midazolam (2 mg) and ketamine Effective sedation during cardiac
(15 mg) followed by dexmedetomidine (1 μg/
kg) and an additional dose of ketamine (15 mg).
Dexmedetomidine infusion at 1 μg/kg/hr during
the procedure and at 0.5 μg/kg/hr for 2 hrs after
the procedure
Dexmedetomidine was administered as a loading
dose of 1 μg/kg along with ketamine (20 mg). This
was followed by a dexmedetomidine infusion at
1 μg/kg/hr. An additional 10 mg of ketamine was
administered during the procedure
Dexmedetomidine (1 μg/kg) and ketamine (1 mg/
kg) were administered over 5 mins followed by
a dexmedetomidine infusion at 0.5 μg/kg/min.
Additional doses of ketamine (0.3–0.5 mg/kg) were
administered every 30–45 mins as needed based on
the patient’s response to the procedure
surgical procedure was completed
significant change in hemodynamic or
respiratory status was noted
Effective sedation was achieved and the
procedure was completed without
incident. No clinically significant
change in hemodynamic or respiratory
status was noted
be used so that the exact point of
airway obstruction could be identified.
Effective sedation was achieved
with no significant respiratory or
hemodynamic effects. A brief episode
of upper airway obstruction occurred
in one patient, which responded to
repositioning of the airway. All three
patients had mild hypercarbia with
maximum ETco2 of 49, 53,
and 52 mm Hg
Effective sedation for fiberoptic
intubation while maintaining
spontaneous ventilation
Successful completion of the procedure
that included biopsy of the anterior
mediastinal mass, lumbar puncture,
and bone marrow aspiration.
maintained throughout the procedure.
catheterization
Effective sedation for bone marrow and
biopsy
Effective sedation for the 135-min
procedure that included biopsy of a
large anterior cervical lymph node
and placement of a percutaneous
intravenous central catheter

response, and cooperation were dec-
reased in the dexmedetomidine–­ketamine
group. Additionally, the incidence of nau-
sea and vomiting was significantly lower
with dexmedetomidine–ketamine com-
pared with midazolam–ketamine (4.7%
vs. 32%).
Two other large case series provide us
with retrospective information regarding
the combination of dexmedetomidine and
ketamine for procedural sedation without
a comparative group (18, 19). Mester et al
(18) retrospectively reviewed the use of
dexmedetomidine and ketamine for
sedation during cardiac catheterization in
16 children with congenital heart disease,
ranging in age from 16 months to 15 yrs
old. A bolus dose of ketamine (2 mg/kg)
and dexmedetomidine (1 μg/kg) mixed
in a single syringe was administered over
3 mins, followed by a continuous infusion

Pediatr Crit Care Med 2012 Vol. 13, No. 4 425

of dexmedetomidine at 2 μg/kg/hr for
the initial 30 mins and then 1 μg/kg/hr
for the duration of the case. No patient
responded to infiltration of the groin and
placement of the arterial and venous can-
nulae for cardiac catheterization. Three
patients required a supplemental dose of
ketamine (1 mg/kg). In two of these pa-
tients, the bolus dose of ketamine was ad-
ministered before changing the vascular
cannulae in the middle of the procedure.
In two patients, the dexmedetomidine
infusion was decreased from 2 to 1 μg/
kg/hr at 12–15 mins instead of 30 mins
because of a decrease in heart rate. Two
patients had development of upper airway
obstruction that responded to reposition-
ing of the airway. No central apnea was
noted. Although the Paco2 was ≥45 mm
Hg in seven patients, the maximum value
was 48 mm Hg.
More recently, McVey and Tobias (19)
described their experience using these
agents during lumbar puncture for spi-
nal anesthesia in 12 pediatric patients.
The dosing regimen was the same as
that reported by Mester et al. The lum-
bar puncture for the performance of spi-
nal anesthesia was tolerated in all of the
patients without movement or the need
for supplemental agent. The heart rate
decrease was ≥20% from baseline in 5
of 12 patients, although only one patient
required intervention with an early de-
crease of the dexmedetomidine infusion.
One patient had a blood pressure decrease
of 20% from baseline. This patient had
fasted for over 10 hrs before surgery and
had a low blood pressure reading of 68/38
mm Hg that responded to a fluid bolus of
10 mL/kg. Upper airway obstruction in
two patients resolved with repositioning
of the airway.
Additional information regarding the
potential utility of a dexmedetomidine–
ketamine combination is provided by
Zor et al (20) in their study of 24 adults
undergoing burn dressing changes. A sec-
ondary outcome of the study was to find
the most effective means of limiting the
adverse effects related to the administra-
tion of ketamine. Twenty-four adults were
randomized into one of three groups.
Group 1 received ketamine (2 mg/kg),
group 2 received tramadol (1 mg/kg) fol-
lowed 30 mins later by ketamine (2 mg/
kg) and dexmedetomidine (1 μg/kg),
whereas group 3 received tramadol (1 mg/
kg) followed 30 mins later by ketamine
(2 mg/kg) and midazolam (0.05 mg/kg).
The authors reported improved analge-
sia and a decreased incidence of adverse
426
effects, including emergence phenomena
and hallucinations related to ketamine in
patients who received dexmedetomidine
(group 2).
Additional anecdotal experience in
small retrospective case series or individ-
ual case reports have consistently dem-
onstrated the utility of dexmedetomidine
in conjunction with ketamine for proce-
dures in which a deep level of sedation is
required while maintaining spontaneous
respiration (Table 2) (21–28). Several of
these reports have included patients with
significant comorbid conditions, includ-
ing pulmonary hypertension, upper air-
way obstruction with sleep apnea, tracheal
compression from a mediastinal mass,
congenital heart disease, as well as com-
promised cardiac and respiratory func-
tion. These reports, which have included
a total of 21 pediatric patients, demon-
strate that a dexmedetomidine–ketamine
combination effectively achieves the de-
sired level of sedation while minimizing
the potential for adverse effects.
CONCLUSION
Given its limited analgesic effects,
dexmedetomidine does not appear to be
the ideal agent for painful procedures.
However, anecdotal experience and a
few large series from the literature dem-
onstrate the utility of a combination of
dexmedetomidine with ketamine for pro-
cedural sedation. When used together,
dexmedetomidine may limit the tachy-
cardia, hypertension, salivation, and
emergence phenomena from ketamine,
whereas ketamine may prevent the bra-
dycardia and hypotension that has been
reported with dexmedetomidine (20, 29,
30). Additionally, the addition of ketamine
to dexmedetomidine to initiate the seda-
tion process speeds the onset of seda-
tion and eliminates the slow onset time
when dexmedetomidine is used as the
sole agent with the loading dose adminis-
tered over 10 mins. When used in such a
scenario, the two agents can be coadmin-
istered from a single syringe. Although
various regimens have been reported in
the literature, the most effective regimen
appears to be the use of a bolus dose of
both agents, dexmedetomidine (1 μg/kg)
and ketamine (1–2 mg/kg), to initiate
sedation. This can then be followed by a
dexmedetomidine infusion (1–2 μg/kg/
hr) with supplemental bolus doses of ket-
amine (0.5–1 mg/kg) as needed. Although
still relatively preliminary, the current
literature supports the potential utility of
the combination of ketamine and dexme-
detomidine for procedural sedation, even
in patients with compromised respiratory
or cardiac function. When compared with
other agents used for procedural sedation,
these two agents have limited effects on
ventilatory function when compared with
other more commonly used agents (4,
31). Future studies may take one of two
directions. Because there are no direct
comparisons of dexmedetomidine as the
sole agent for sedation vs. a dexmedeto-
midine–ketamine combination, this may
be one venue. If the dexmedetomidine–
ketamine combination is superior, then
direct comparisons to other commonly
used regimens (propofol) appear war-
ranted for both invasive and noninvasive
procedures. Given the increased cost of
a dexmedetomidine regimen, whenever
such studies are performed, attention to
the cost-benefits ratio including man-
power issues of recovery times should be
included.
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