Feature Review Article

Dexmedetomidine and ketamine: An effective alternative for

procedural sedation?
Joseph D. Tobias, MD
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Objectives: Although generally effective for sedation during tachycardia, hypertension, salivation, and emergence phenomena
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noninvasive procedures, dexmedetomidine as the sole agent from ketamine, whereas ketamine may prevent the bradycardia
has not been uniformly successful for invasive procedures. To and hypotension, which has been reported with dexmedetomidine.
overcome some of the pitfalls with dexmedetomidine as the sole An additional benefit is that the addition of ketamine to initiate the
agent, there are an increasing number of reports regarding its sedation process speeds the onset of sedation, thereby eliminat-
combination with ketamine. This article provides a descriptive ing the slow onset time when dexmedetomidine is the sole agent.
account of the reports from the literature regarding the use of a Although various regimens have been reported in the literature,
combination of dexmedetomidine and ketamine for procedural the most effective regimen appears to be the use of a bolus dose of
sedation. both agents, dexmedetomidine (1 μg/kg) and ketamine (1–2 mg/
Data Source: A computerized bibliographic search of the lit- kg), to initiate sedation. This can then be followed by a dexmedeto-
erature regarding dexmedetomidine and ketamine for procedural midine infusion (1–2 μg/kg/hr) with supplemental bolus doses of
sedation. ketamine (0.5–1 mg/kg) as needed.
Measurements and Main Results: The literature contains four Conclusions: The available literature except for one trial is favor-
reports with cohorts of more than ten patients with a total of 122 able regarding the utility of a combination of ketamine and dexme-
patients. Two of these studies were prospective randomized tri- detomidine for procedural sedation. Future studies with direct com-
als. Additionally, there are eight single case reports or small parisons to other regimens appear warranted for both invasive and
case series (six patients or less) with an additional 21 pediatric noninvasive procedures. (Pediatr Crit Care Med 2012; 13:423–427)
patients. When used together, dexmedetomidine may prevent the 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-
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
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-
pects of inadequate sedation. Therefore, effects are generally dose-dependent and spective evaluation of dexmedetomidine
more patients are being sedated for proce- more likely with higher doses as deeper as the sole agent during an invasive pro-
dures and the depth of sedation achieved levels of sedation/anesthesia are achieved, cedure in infants and children, Munro
is increasing in certain environments. there is significant interpatient variability et al (9) reported their experience with
Regardless of the procedure, there are regarding the potential for adverse effects dexmedetomidine during cardiac cath-
several options for the agent or agents (7). Given these concerns, the search for eterization. After oral premedication
chosen for sedation. In the general prac- alternative agents continues. with midazolam and the placement of
tice of procedural sedation, propofol is a Dexmedetomidine (Precedex; Hospira intravenous access, dexmedetomidine
frequently chosen agent because it can be Worldwide, Lake Forest, IL) exerts its was administered as a loading dose of 1
easily titrated by continuous infusion, is physiologic effects through the α2- μg/kg over 10 mins, followed by an infu-
generally effective, and allows for rapid adrenergic receptor system. Initial Food sion of 1 μg/kg/hr titrated up to 2 μg/
and Drug Administration approval in kg/hr as needed. Five of the 20 patients
the United States for the administration (25%) moved during local infiltration of
From the Departments of Anesthesiology and
Pediatrics, Nationwide Children’s Hospital and the Ohio of dexmedetomidine occurred in 1999. the groin, which did not require treat-
State University, Columbus, OH. At that time, approval was granted for ment or interfere with cannulae place-
The author has not disclosed any potential conflicts the sedation of adults during mechani- ment. Twelve (60%) patients received a
of interest. cal ventilation. Additional approval was propofol bolus during the procedure for
For information regarding this article, E-mail:
[email protected]
granted in 2009 for monitored anesthe- movement, an increasing bispectral in-
Copyright © 2012 by the Society of Critical Care sia care in adults. Although Food and dex number, or anticipation of a stimu-
Medicine and the World Federation of Pediatric Intensive Drug Administration-approved only for lus. Subsequent studies in the adult
and Critical Care Societies use in adults, dexmedetomidine con- population have similarly demonstrated
DOI: 10.1097/PCC.0b013e318238b81c tinues to be used successfully in several 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– Sedation managed effectively with both regimens. Patients
ketamine with propofol–ketamine sedation in 44 sedated with ketamine–dexmedetomidine required more
pediatric patients during cardiac catheterization 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).
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Koruk et al (17) Prospective randomized trial comparing dexmedetomidine– Sedation was equally effective in both groups. Times for
ketamine with midazolam-ketamine in 50 pediatric eye-opening, verbal response, and cooperation were
patients for extracorporeal shock wave lithotripsy decreased in the dexmedetomidine–ketamine group.
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The incidence of nausea and vomiting was lower with

dexmedetomidine–ketamine (4.7% vs. 32%).
Mester et al (18) Retrospective case series using dexmedetomidine and No patients responded to infiltration of the groin
ketamine for sedation during cardiac catheterization. No with local anesthetic and placement of the arterial
comparative group was included. The cohort included 16 and venous cannulae. Three patients required a
children ranging in age from 16 mos to 15 yrs 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.
McVey and Tobias (19) Retrospective case series using dexmedetomidine and The lumbar puncture for the performance of spinal
ketamine for sedation during lumbar puncture for spinal anesthesia was tolerated in all of the patients. One
anesthesia. No comparative group was included. The patient required a decrease of the dexmedetomidine
study cohort included 12 children ranging in age from 2 infusion for bradycardia. One patient required a fluid
to 9 yrs 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. administered. Although limited in superior. Patients sedated with dexme-
Jalowiecki et al (10) reported that dex- number when compared to reports us- detomidine–ketamine required more ket-
medetomidine was ineffective during ing only dexmedetomidine, there have amine (2.03 ± 1.33 vs. 1.25 ± 0.67 mg/kg/
colonoscopy in adults and was associ- been several reports in the literature hr; p < .01) and more frequently required
ated with a high incidence of adverse regarding the use of a dexmedetomi- supplemental doses of ketamine (10/22
effects, including a prolonged delay in dine–ketamine combination for proce- patients vs. 4/22 patients). Additionally,
discharge times. The authors closed the dural sedation in the pediatric population the recovery time was longer with dex-
study before completion (12). Similar (Table 1) (16–19). Two of these reports medetomidine and ketamine (median
issues were encountered when compar- have been prospective randomized trials time, 45 vs. 20 mins; p = .01). No clini-
ing dexmedetomidine with midazolam with a comparison to another sedation cally significant differences in the hemo-
for monitored anesthesia care in adults regimen (16, 17). Tosun et al (16) com- dynamic or respiratory status were noted
during cataract surgery (13). pared a procedural sedation regimen that between the two groups.
In specific clinical scenarios, the included dexmedetomidine and ketamine Koruk et al (17) prospectively com-
response to failures with usual doses (1–2 with one that combined propofol and pared sedation using dexmedetomidine
μg/kg) has been to switch to or to add al- ketamine. The study cohort included 44 and ketamine to a regimen using mid-
ternative agents or to increase the dose children, ranging in age from 4 months azolam and ketamine during extracor-
of dexmedetomidine (14, 15). However, to 16 yrs, with acyanotic congenital heart poreal shock wave lithotripsy in a cohort
when such dose escalations are attempt- disease undergoing cardiac catheteriza- of 50 pediatric patients who ranged in
ed, a higher incidence of hemodynamic tion. Ketamine (1 mg/kg) and dexmedeto- age from 2 to 15 yrs. Patients received
effects such as bradycardia and hypoten- midine (1 μg/kg) were administered over either a bolus dose of dexmedetomidine
sion has been noted. Given these issues, 10 mins, followed by infusions of dexme- (1 μg/kg over 10 mins) and ketamine
the addition of a second agent to dexme- detomidine at 0.7 μg/kg/hr and ketamine (1 mg/kg) or a bolus dose of midazolam
detomidine rather than dose escalations at 1 mg/kg/hr. In the other arm of the (0.05 mg/kg) and ketamine (1 mg/kg).
may be the preferred option. study, propofol (1 mg/kg) and ketamine Patients were then observed by an anes-
Procedural Sedation With Dexmedeto- (1 mg/kg) were administered as the load- thesiologist who was blinded to which
midine and Ketamine. Issues of concern ing dose, followed by a propofol infusion medications they had received. Sedation
when considering dexmedetomidine as at 100 μg/kg/hr and ketamine at 1 mg/kg/ was equally effective in both groups with-
an agent for procedural sedation include hr. In both arms of the study, supplemen- out clinically significant changes in the
a long onset time, limited analgesic ef- tal bolus doses of ketamine (1 mg/kg) hemodynamic and respiratory param-
fect, and the potential for hemodynamic were available as needed. Although seda- eters. Although there was no difference
effects, including bradycardia and hypo- tion was effective with both regimens, in the time to achieve an Aldrete score
tension, especially when larger doses are the propofol–ketamine combination was 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 The bolus dose of both agents was repeated to surgical procedure was completed
5, 6, and 10 mos) with a history achieve a Ramsay sedation scale score of 4. This was without difficulty. No clinically
of ongoing or recent acute viral followed by a dexmedetomidine infusion at 0.7–1 significant change in hemodynamic or
upper respiratory infections and μg/kg/hr, titrated to maintain a Ramsay sedation respiratory status was noted
congenital heart disease scale score of 4 during the surgery
Barton et al (22) Procedural sedation in six infants Dexmedetomidine was administered at an average Effective sedation was achieved and the
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(age 3 d to 29 mos) with dose of 1.5 μg/kg (range, 1–3 μg/kg). Three of the procedure was completed without
congenital heart disease 6 patients (50%) required bolus doses of ketamine incident. No clinically significant
(0.3–0.5 mg/kg) because of movement during the change in hemodynamic or respiratory
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procedure status was noted

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 be used so that the exact point of
during a magnetic resonance maintained by a dexmedetomidine infusion (1 μg/ airway obstruction could be identified.
imaging scan for evaluation of kg/hr). One patient required a repeat of the bolus Effective sedation was achieved
sleep apnea doses of ketamine and dexmedetomidine and an with no significant respiratory or
increase of the dexmedetomidine infusion to hemodynamic effects. A brief episode
2 μg/kg/hr 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
Irvani and Wald (24) 6-yr-old girl with Treacher A bolus dose of dexmedetomidine 1 μg/kg was Effective sedation for fiberoptic
Collins syndrome and severe followed by a continuous infusion at 1 μg/kg/hr. intubation while maintaining
micrognathia Once a Ramsay sedation scale score of 5 (sluggish spontaneous ventilation
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
Mahmoud et al (25) 4-yr-old, 20-kg boy with a large A loading dose of dexmedetomidine (2 μg/kg) and Successful completion of the procedure
mediastinal mass and tracheal ketamine (0.5 mg/kg) were administered. Propofol that included biopsy of the anterior
compression (1 mg/kg) was administered to facilitate mediastinal mass, lumbar puncture,
placement of an laryngeal mask airway. The and bone marrow aspiration.
anesthetic was maintained with a dexmedetomidine Spontaneous ventilation was
infusion at 2 μg/kg/hr) and ketamine boluses to a maintained throughout the procedure.
total dose of 30 mg
Munro et al (26) 12-yr-old, 31-kg boy with Premedication with midazolam (2 mg) and ketamine Effective sedation during cardiac
pulmonary hypertension (15 mg) followed by dexmedetomidine (1 μg/ catheterization
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
Rozmiarek et al (27) 21-yr-old, 43-kg man with Dexmedetomidine was administered as a loading Effective sedation for bone marrow and
Duchenne muscular dystrophy dose of 1 μg/kg along with ketamine (20 mg). This biopsy
with compromised cardiac and was followed by a dexmedetomidine infusion at
respiratory function 1 μg/kg/hr. An additional 10 mg of ketamine was
administered during the procedure
Corridore et al (28) A 3-yr-old, 14-kg girl with a Dexmedetomidine (1 μg/kg) and ketamine (1 mg/ Effective sedation for the 135-min
mediastinal mass and tracheal kg) were administered over 5 mins followed by procedure that included biopsy of a
compression a dexmedetomidine infusion at 0.5 μg/kg/min. large anterior cervical lymph node
Additional doses of ketamine (0.3–0.5 mg/kg) were and placement of a percutaneous
administered every 30–45 mins as needed based on intravenous central catheter
the patient’s response to the procedure

response, and cooperation were dec- Two other large case series provide us sedation during cardiac catheterization in
reased in the dexmedetomidine–­ketamine with retrospective information regarding 16 children with congenital heart disease,
group. Additionally, the incidence of nau- the combination of dexmedetomidine and ranging in age from 16 months to 15 yrs
sea and vomiting was significantly lower ketamine for procedural sedation without old. A bolus dose of ketamine (2 mg/kg)
with dexmedetomidine–ketamine com- a comparative group (18, 19). Mester et al and dexmedetomidine (1 μg/kg) mixed
pared with midazolam–ketamine (4.7% (18) retrospectively reviewed the use of in a single syringe was administered over
vs. 32%). dexmedetomidine and ketamine for 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 effects, including emergence phenomena the combination of ketamine and dexme-
the initial 30 mins and then 1 μg/kg/hr and hallucinations related to ketamine in detomidine for procedural sedation, even
for the duration of the case. No patient patients who received dexmedetomidine in patients with compromised respiratory
responded to infiltration of the groin and (group 2). or cardiac function. When compared with
placement of the arterial and venous can- Additional anecdotal experience in other agents used for procedural sedation,
nulae for cardiac catheterization. Three small retrospective case series or individ- these two agents have limited effects on
patients required a supplemental dose of ual case reports have consistently dem- ventilatory function when compared with
ketamine (1 mg/kg). In two of these pa- onstrated the utility of dexmedetomidine other more commonly used agents (4,
tients, the bolus dose of ketamine was ad- in conjunction with ketamine for proce- 31). Future studies may take one of two
ministered before changing the vascular dures in which a deep level of sedation is directions. Because there are no direct
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cannulae in the middle of the procedure. required while maintaining spontaneous comparisons of dexmedetomidine as the
In two patients, the dexmedetomidine respiration (Table 2) (21–28). Several of sole agent for sedation vs. a dexmedeto-
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infusion was decreased from 2 to 1 μg/ these reports have included patients with midine–ketamine combination, this may
kg/hr at 12–15 mins instead of 30 mins significant comorbid conditions, includ- be one venue. If the dexmedetomidine–
because of a decrease in heart rate. Two ing pulmonary hypertension, upper air- ketamine combination is superior, then
patients had development of upper airway way obstruction with sleep apnea, tracheal direct comparisons to other commonly
obstruction that responded to reposition- compression from a mediastinal mass, used regimens (propofol) appear war-
ing of the airway. No central apnea was congenital heart disease, as well as com- ranted for both invasive and noninvasive
noted. Although the Paco2 was ≥45 mm promised cardiac and respiratory func- procedures. Given the increased cost of
Hg in seven patients, the maximum value tion. These reports, which have included a dexmedetomidine regimen, whenever
was 48 mm Hg. a total of 21 pediatric patients, demon- such studies are performed, attention to
More recently, McVey and Tobias (19) strate that a dexmedetomidine–ketamine the cost-benefits ratio including man-
described their experience using these combination effectively achieves the de- power issues of recovery times should be
agents during lumbar puncture for spi- sired level of sedation while minimizing included.
nal anesthesia in 12 pediatric patients. the potential for adverse effects.
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