RESEARCH PAPER

Prolonged Dexmedetomidine Infusions in Critically Ill

Infants and Children
PAMELA D REITER, MOLLI PIETRAS AND *EMILY L DOBYNS

From the Department of Pharmacy, Center for Pediatric Medicine, and *Pediatric Intensive Care Unit,
Section of Critical Care Medicine, The Children’s Hospital, 13123 East 16th Ave, Denver, USA.
Correspondence to: Pamela D Reiter, Department of Pharmacy, Center for Pediatric Medicine, The Children's Hospital,
13123 East 16th Ave, Denver, USA. E-mail: reiter.pam@tchden.org
Manuscript received: July 21, 2008; Initial review: August 27, 2008; Accepted: October 4, 2008.

Objective: To present our institutional experience with (0.5-1 mcg/kg) prior to the start of the infusion. Duration of
prolonged dexmedetomidine (DEX) infusions in critically ill DEX therapy was 110 ± 83 hours (range 32-378 hours;
infants and children. median 76 hours). Rationale for adding DEX to sedation
Design: Retrospective medical chart review between regimens included: intent to extubate (n=12), intent to
January 1, 2007 and December 1, 2007. reduce benzodiazepine and opioid use (n=10), exclusive
continuous sedation (n=5) and management of drug with-
Setting: Tertiary care pediatric teaching hospital. drawal (n=2). Sedation scores remained stable during
Participants: Infants and children (up to 18 years of age) DEX therapy. Use of conventional analgesia and sedation
who received DEX for a duration greater than 24 hours. was generally reduced while receiving DEX. Initiation of
therapy was associated with a transient, yet statistically
Main Outcome Measures: DEX dosing schema and
significant reduction in HR (from 120 ± 28 bpm to 107 ± 27
rationale for use. Indices describing DEX efficacy and
bpm) (P = 0.002), but without a change in blood pressure.
tolerability including change in patient-specific sedation
scores, change in blood pressure and heart rate, and Conclusions: Prolonged DEX infusions were associated
change in conventional analgesia and sedation with a reduction in concomitant analgesia and sedation
requirements. medications. DEX was well tolerated with the exception of
heart rate, which decreased during the initiation of therapy
Results: Twenty-nine patients (age 5.32 ± 6.1 y) were
but may not represent a clinically significant reduction.
evaluated. DEX therapy was initiated at 0.36 ± 0.16 mcg/
kg/hour. One-third of patients received a loading dose Key words:Children, Dexmedetomidine, Sedation.

Published online 2009 April 1. PII: S097475590800430-1

D
exmedetomidine HCl (DEX; Precedex, duration) in adults undergoing mechanical venti-
Hospira Inc, Lake Forest Ill, USA) is a lation. Based on efficacy in adults, DEX is now
potent alpha-2-adrenergic agonist that being considered in children. Pediatric experience
imparts sedative, analgesic and with DEX has been predominately in the form of
anxiolytic effects without causing respiratory case series and small reports and has focused mainly
depression. DEX may be helpful in reducing on short term or procedural use(2-10). Little data is
traditional sedative/analgesic use while still available describing extended infusions in children
allowing for a calm, comfortable, and cooperative (11-13).
state. The pharmacologic effect of DEX is mediated
through all four known subtypes of alpha-2 Accompanying Editorial: Pages 761-762
adrenergic receptors (α2A, α2B, α2C, α2D)(1) and
currently is FDA approved as a sedative for short- We report our experience with prolonged (greater
term use (periods not exceeding 24 hours in than 24 hours) use of DEX in critically ill children

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REITER, et al. DEXMEDETOMIDINE IN CHILDREN

and attempt to characterize indications, dosing intention was to describe data regarding mechanical
schema, use of as needed sedation, hemodynamic ventilation requirements and attempts at extubation.
effects and clinical sedation scores associated with The use and titration of DEX was completely at the
this therapy. discretion of the medical team and the decision to
extubate was based on assessment by the unit
METHODS intensivist. Hemodynamic variables (blood pressure
[mmHg] and heart rate [beats per minute; bpm])
This was a retrospective chart review of all infants were documented before and during DEX infusions.
and children (up to 18 years of age) who received All medical record charting at TCH is electronic and
DEX for greater than 24 hours in duration between patient-specific variables from bedside monitors are
January 1, 2007 and December 1, 2007. Patients downloaded hourly. Since all subjects had
were identified from the pharmacy database continuous monitoring of hemodynamic variables,
(Epic Hyperspace (Epic Rx) Systems we averaged patient-specific data every 12 hours
Cooperation®) at The Children’s Hospital (TCH), during DEX therapy. We elected to categorize
Denver, Colorado. This study protocol was reviewed patients based on unit location (cardiac, pediatric or
and approved by the Colorado Multiple Institutional neonatal ICU) because each unit is directed by
Review Board and informed parent/subject consent separate and distinct medical teams, and the physio-
was waived. logy and diagnoses of patients are uniquely tied to
Data collection included patient demographics their location, This location classification then
and indices related to DEX efficacy and tolerability. allowed for comparison of prescribing practices
Primary outcomes included DEX dosing schema between physician groups and comparison of
(initial dose, maximum dose and duration), efficacy and tolerability of DEX based on major
indication/rationale for DEX use, change in patient- underlying disease state(s).
specific sedations scores, change in hemodynamic Data are presented as mean ± standard deviation
parameters (systolic and diastolic blood pressure, (SD) or percentage where appropriate. Median data
and heart rate) and number of conventional as are reported if significant skewness was detected. A
needed sedation doses required before, during and two-tailed, paired t-test of means was performed to
after DEX therapy. The number of “as needed” determine statistical change in hemodynamic
sedation doses required during DEX therapy was variables. A P value less than 0.05 was considered
calculated by adding the number of doses required statistical significant for any given measure.
per patient per day and then taking the mean of that
number. Adequacy of sedation was assessed using a RESULTS
numerical scoring system developed and validated
at the Penn State Children’s Hospital for A total of 40 patients received DEX during the study
mechanically ventilated children(14). This scoring period. Eleven patients (n=7, PICU patients; n=4,
system allows the medical team to designate a CICU patients) were excluded because they received
patient-specific sedation goal. The bedside nurse DEX for less than 24 hours duration, leaving 29
then assigns a sedation score based on the behavior patients (n=14, PICU; n=15, CICU) for analysis.
of the ventilated child. Currently, only the Pediatric Mean age of study population was 5.32±6.1 years
Intensive Care (PICU) uses this numerical tool in with a range of 0.42-18 years. Patients in the CICU
their mechanically ventilated patients. Sedation was subgroup were younger than patients in the PICU
scored multiple times throughout the day and was subgroup (3.2±5.6 yrs vs 7.6±5.9 yrs, respectively).
averaged over 12-hr periods for our analysis. There were more males (59%) than females in the
study group. Ninety-three percent of patients were
The daily dose of DEX (mcg/kg/hour) was mechanically ventilated at the start of DEX therapy
calculated by averaging the 24-hr dosing (86% in PICU and 100% in CICU). The 2 patients
requirement of each patient. Because DEX is often who were spontaneously breathing at the initiation of
used to aid in successful extubation, our secondary DEX were adolescents (13 yrs and 15 yrs) and had a

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REITER, et al. DEXMEDETOMIDINE IN CHILDREN

diagnosis of sepsis and Steven’s Johnson syndrome, and CICU (0.67±0.32 mcg/kg/hr). The mean
respectively. duration of DEX therapy was 110±83 hours (range:
32-378 hours; median=76 hours) and was twice as
The primary diagnoses of the study population long in the PICU patients (149±102 hrs) as compared
were heterogeneous, and included correction/ to the CICU patients (72.6±34.6 hrs). Overall,
palliation of a congenital heart defect (n=10), sixteen patients (55%) had their DEX infusion
respiratory failure requiring mechanical ventilation slowly tapered downward as therapy was ending.
for reasons other than pneumonia (n=9), trauma The decision to taper the DEX infusion was directed
(n=3), respiratory failure requiring mechanical by the medical team and was equally likely in the
ventilation for pneumonia (n=3), sepsis (n=2) and CICU and PICU subgroups. In general, the taper
post-operative heart transplant (n=2). The rationale lasted from 1-4 days in duration and typically repre-
for adding DEX to sedation regimens included: sented 25-50% dose reductions per day. Of the 14
intent to transition towards extubation (n=12), intent patients who received DEX therapy for longer than
to reduce benzodiazepine and opioid dosing (n=10), 72 hours, we observed a taper in 13 (93%). When
exclusive continuous sedation (n=5) and manage- DEX was used as the exclusive continuous sedation
ment of drug withdrawal (n=2). agent (n=5 patients), the mean dose ranged from 0.3-
0.48 mcg/kg/hr and none of the patients received a
DEX Dosing. The decision to use a loading dose was loading dose. The mean duration of DEX therapy in
at the discretion of the prescribing physician. While those patients was 89 hours (range 32-168 hrs).
our institution provides general dosing recommen-
dations of 0.3-0.7 mcg/kg/hour as a continuous Sedation. The majority of patients were receiving
infusion dose, the medical team was responsible for baseline sedation medications prior to the initiation
all dose titrations. DEX therapy was initiated at a of DEX with a combination of continuous infusion
mean dose of 0.36±0.16 mcg/kg/hour (range: 0.1- midazolam (n=16), intermittent midazolam or lora-
0.75). Figure 1 illustrates the mean daily DEX dose zepam (n=19), continuous infusion opioid (n=22),
requirements (mcg/kg/hour). One-third of patients intermittent opioid (n=20) or chloral hydrate (n=14).
(8/29) received a loading dose (0.5-1 mcg/kg) prior During DEX therapy, sedation scores were recorded
to the start of the continuous infusion (4/14 PICU in all twelve of the mechanically ventilated PICU
patients and 4/15 CICU patients). When daily patients. On average, patients were maintained at a
infusion doses were averaged, the maximum dose sedation level between 2 and 3 during the first 192
was 0.65±0.34 mcg/kg/hour (range: 0.2-1.5), with hours (8 days) of therapy and then decreased to a
similar values in the PICU (0.61±0.37 mcg/kg/hr) sedation level of 1-2 for the remaining days of
therapy. This represents a trend toward more wakeful
state in those patients receiving therapy beyond 8
days.
Additional as needed doses of sedation were
recorded the day prior to starting DEX therapy,
during the DEX infusion and then again the day after
DEX therapy was discontinued. Patients received a
variety of medications which included benzodiaze-
pines (midazolam, lorazepam), opioids (fentanyl,
morphine, hydromorphone) and chloral hydrate.
Overall, the number of as needed doses was higher
during DEX therapy compared to before and after,
and this trend remained evident in the subgroup of
FIG.1 Mean daily dexmedetomidine (DEX) dose (mcg/kg/hr) patients who received DEX as exclusive continuous
over time (solid line) and number of patients receiving DEX sedation (Table I). Despite an increase in as needed
infusions (open bars) per day. doses, the overall amount of sedation (continuous

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REITER, et al. DEXMEDETOMIDINE IN CHILDREN

TABLE I COMPARISON OF SEDATION REQUIREMENTS sedation plus as needed sedation) was generally
BETWEEN STUDY AND DEXMEDETOMIDINE GROUPS reduced during DEX therapy. Of the patients who
Sedation requirement Entire DEX as were receiving continuous opioid and BZD therapy
according to DEX study exclusive when DEX was initiated, 54% (n=11) and 45%
therapy (n=5) continuous (n=11) were able to completely discontinue their
sedation continuous opioid and BZD infusions during DEX
(n=5) therapy, respectively. Another 18% (n=4) and 4.5%
Number of needed BZD doses/day per patient (n=1), respectively, were able to reduce their
continuous infusion requirements by more than 50%.
1 d before initiation 1.8±2.3 1.3±0.9
Six patients (4 opioid patients and 2 BZD patients)
During DEX therapy 2.2±1.7 1.9±1.3 required an increase in infusion doses even after
1 d following discontinuation 0.9±1.2 1.3±1.3 starting DEX therapy.
Number of needed opioid doses/day per patient
Hemodynamic effects. Systolic and diastolic blood
1 d before DEX initiation 2.2±2.4 1.8±2.4
pressures, along with heart rate (HR), were
During DEX therapy 2.6±1.3 1.3±0.7 documented hourly and then averaged over 12-hour
1 d following discontinuation 0.9±1.4 1.5±3 periods during DEX therapy. Overall, patients
Number of chloral hydrate doses/day per patient appeared to tolerate DEX initiation well (Fig. 2). At
day 4, there appears to be a reduction in both systolic
1 d before DEX initiation 0.8±1 0.4±0.5
and diastolic pressures in the CICU subgroup, but
During DEX therapy 1±1.24 1.3±1.9 this represents the exit of older patients and re-
1 d following discontinuation 0.8±1.3 1±1.4 calibration of means to reflect a younger group of
* All data presented as mean ± SD. Dose of sedation requirement
remaining subjects. A transient, yet statistically
was calculated by adding the number of doses required per significant decrease in HR was associated with the
patient per day and then taking the mean of that number; d-day. first 24 hours of DEX therapy. Baseline (24 hrs prior

FIG. 2 Mean heart rate (circle) systolic (triangle) and diastolic (square) blood pressure of study group (pediatric intensive care
subject = solid markers and cardiac intensive care subjects = open markers). Each marker represents a 12-hour block of time.
Dotted line represents start of DEX infusion and first 12-hour blood pressure measurement on therapy.

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REITER, et al. DEXMEDETOMIDINE IN CHILDREN

to DEX initiation) HR was 120±28 bpm and to extubation in an effort to minimize the risk of
decreased to 107±27 bpm 24 hour post DEX respiratory depression. In 34% of patients, DEX was
initiation (P=0.002). This association was consistent initiated with the intent to reduce/spare
in both the CICU and PICU subgroups. Since rapid benzodiazepine and opioid requirements. Overall,
intravenous infusion or bolus dosing of DEX has the use of as needed sedation actually increased
been associated with a higher risk of hemodynamic during DEX therapy, but this was most likely due to
instability(1), we separately analyzed those patients the fact that the majority of patients were able to
(n=8) who received a bolus dose of 0.5-1 mcg/kg completely stop or substantially reduce their
prior to starting continuous therapy. However, we concomitant opioid and BZD infusions during this
did not find the same association. Systolic, diastolic same period. Thus, the total amount of opioid and
and HR values remained stable from 12 hours prior BZD could be reduced during DEX therapy.
to DEX therapy to 24 hours after DEX initiation Nevertheless, there was a small subgroup of children
(P= 0.56, P=0.56, P=0.78, respectively). in the present study that required an increase in
overall sedation, despite the addition of DEX.
Extubation rates. Twelve patients were started on
DEX therapy considering possible extubation while Changes in blood pressure and HR (bradycardia)
15 mechanically ventilated patients were started on have previously been reported in patients receiving
DEX for other indications. When we excluded DEX, especially when a loading dose is pres-
chronically ventilated children with tracheostomy cribed(3,15-17). DEX initiation was not associated
from analysis (n=3) and compared extubation rates with any significant change in blood pressure.
between these two groups, more patients in the However, DEX was associated with a statistically
intent-to-extubate group failed their first extubation significant reduction in HR, with a mean HR
attempt (30% failure, n=3/10) compared to the rest reduction of 13 bpm from baseline (24 hours prior to
of the study patients (7% failure, n=1/14). These DEX) to 24 hours after the initiation of DEX. This
rates are comparable to our overall extubation failure drop in HR may represent an important hemo-
rate of 6%. Of the patients who failed their first dynamic effect of DEX or may correspond to
extubation attempt after starting DEX (n=4), 3 improved sedation with less agitation. Arguably, a
patients were from the PICU and 1 was from the mean HR reduction of 13 bpm may not denote a
CICU and two of the patients had a primary clinically significant decrease. We did not observe
diagnosis of pulmonary hypertension. Of the 23 the same impact on HR in the small group of patients
patients who were acutely mechanically ventilated, 6 (n=8) who received a DEX loading dose prior to the
(26%) were extubated within 72 hours of starting initiation of a continuous infusion. One plausible
DEX, with 3 patients in the intent-to-extubate group explanation for this lack of effect may be selection
and 3 in the “other indications” group. Overall, bias. It is possible that those patients who received a
patients were mechanically ventilated 1.6±8.7 day DEX bolus were deemed more hemodynamically
(range; 8 to 35 days) after stopping DEX therapy, stable by the medical team and hence judged as
which illustrates that some patients were better candidates for a bolus, compared to the rest of
successfully extubated prior to the discontinuation the study group.
of DEX.
DEX is an appealing agent to use in patients close
DISCUSSION to extubation because of its relative lack of
respiratory drive depression. Therefore, we analyzed
We report the use of prolonged DEX infusions in the association of extubation failure/success and the
infants and children at doses of 0.1-1.5 mcg/kg/hour rational of DEX initiation. We observed a higher
for 110±83 hours (range: 32-378 hours). Overall, extubation failure rate (30%) in those patients
concomitant opioid and benzodiaze-pine therapy specifically started on DEX with the intent to
was reduced and DEX was generally well tolerated. extubate, compared to the rest of the study group
In most patients (41%), DEX was initiated as an requiring mechanical ventilation (7% failure rate). A
adjunctive to conventional sedation in patients close possible explanation for the higher failure rate in the

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REITER, et al. DEXMEDETOMIDINE IN CHILDREN

WHAT IS ALREADY KNOWN?

• Dexmedetomidine has short-term efficacy and tolerability in infants and children and has sedative, analgesic
and anxiolytic effects, without causing respiratory depression.

WHAT THIS STUDY ADDS?

• Dexmedetomidine infusions in infants and children for 110 ± 83 hours were associated with an overall reduction
in concomitant opioid and benzodiazepine therapy but associated with fall in heart rate during the first 24 hour
of therapy.

intent-to extubate group may be due to the higher best candidate for DEX, controlled prospective and
proportion of PICU patients in that group (60%) blinded trials must be performed.
compared to the rest of the study group (50%). The
Contributors: PDR was responsible for the study idea,
PICU patient population is generally more diverse in
design and data analysis. MP collected and co-analyzed
terms of pulmonary pathology while the CICU group
all data and reviewed the manuscript. ELD reviewed and
tends to be more homogenous and extubates quickly edited the manuscript; provided key insight to ICU
during the post-operative period. Additionally, the management issues; contributed important data
CICU physician group uses a ventilator weaning interpretation and intellectual content. All authors
protocol, unlike the PICU physician group. This approved the final content of the manuscript.
weaning protocol may aid in assessing patient Funding: None.
readiness for extubation. However, one can not Competing interests: None stated.
overlook the possibility that the use of DEX may
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