Sedation during mechanical ventilation in infants and

children: dexmedetomidine versus midazolam.

Background: We sought to compare the efficacy of midazolam versus

dexmedetomidine for sedation during mechanical ventilation in infants

and children.

Methods: We performed a prospective, randomized trial in a

pediatric intensive care unit in a tertiary care center. Infants and

children requiring mechanical ventilation underwent a continuous

infusion of either midazolam (starting dose of 0.1 mg/kg/h) or

dexmedetomidine (starting dose of either 0.25 or 0.5 [micro]g/kg/h) with

intermittent morphine, as needed. The efficacy of sedation was assessed

using the Ramsay sedation scale, pediatric intensive care unit sedation

score, and the tracheal suctioning score as well as bispectral

monitoring.

Results: There were 10 patients in each group. Sedation as assessed

by the clinical sedation scores and the bispectral index was equivalent

in the 3 groups. There were 36 morphine boluses administered to the

midazolam group versus 29 and 20 morphine boluses administered

respectively to the 0.25 and 0.5 [micro]g/kg/h dexmedetomidine groups (P

= 0.02 for midazolam versus 0.5 [micro]g/kg/h dexmedetomidine). Total

morphine use (mg/kg/24 h) was 0.74 [+ or -] 0.5, 0.55 [+ or -] 0.38, and

0.28 [+ or -] 0.12 in the midazolam and the two dexmedetomidine groups

respectively (P = not significant for midazolam versus 0.25

dexmedetomidine, P = 0.01 for midazolam versus 0.5 dexmedetomidine). In

the two dexmedetomidine groups, 5 of 6 patients who at some point had a

Ramsay score of 1 were less than 12 months of age while only 1 was more

than 12 months of age (P < 0.05).

Conclusions: At a dose of 0.25 [micro]g/kg/h, dexmedetomidine was

approximately equivalent to midazolam at 0.22 mg/kg/h. At 0.5

[micro]g/kg/h, dexmedetomidine provided more effective sedation as

demonstrated by the need for fewer bolus doses of morphine, a decrease

in the 24-hour requirements for supplemental morphine, as well as a

decrease in the total number of assessment points with a Ramsay score of

1 (inadequate sedation) and the number of patients who had a Ramsay

score of 1.

Key Words: children, dexmedetomidine, mechanical ventilation,

midazolam, morphine sulfate, sedation

**********

Sedative and analgesic agents are commonly administered to

alleviate the discomfort associated with mechanical ventilation. In

addition to humanitarian concerns, appropriate levels of sedation are

needed to prevent patient-ventilator asynchrony, thereby allowing for

effective mechanical ventilation, as well as preventing inadvertent

tracheal extubation or dislodgement of invasive vascular devices. In the

pediatric-aged patient, benzodiazepines and opioids are the agents used

most commonly to achieve these goals.

Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is

a centrally-acting, [[alpha].sub.2] agonist that is currently approved

by the U.S. Food and Drug Administration for short-term use ([less than

or equal to]24 h) to provide sedation in adults. Preliminary experience

in the adult population has demonstrated its efficacy in alleviating the

discomfort associated with mechanical ventilation. (1,2) To date,

reports regarding the use of dexmedetomidine in pediatric patients have

been anecdotal. (3,4) The current study prospectively compares the

efficacy of midazolam with two doses of dexmedetomidine (0.25 and 0.5

[micro]g/kg/h) to provide sedation during mechanical ventilation in

infants and children.

Methods

The study was approved by the Institutional Review Board of the

University of Missouri and written, informed consent was obtained from a

parent. Patients admitted to the pediatric intensive care unit who

required mechanical ventilation with an endotracheal tube were

considered eligible for inclusion. Patients with preexisting central

nervous system dysfunction or acquired conditions resulting in ongoing

dysfunction were excluded. After endotracheal intubation and before

obtaining informed consent, sedation was provided by intermittent doses

of midazolam (0.1 mg/kg/h) as needed. The patients were randomized to

receive either midazolam (starting dose of 0.1 mg/kg/h) or

dexmedetomidine (starting dose of either 0.25 or 0.5 [micro]g/kg/h).

After randomization, if the patient was judged to be inadequately

sedated, a bolus of either midazolam (0.1 mg/kg) or dexmedetomidine

(0.25 or 0.5 [micro]g/kg) was given before the initiation of the

infusion. The bolus dose was added to the infusion when calculating the

mean daily infusion rate of the medication (midazolam or

dexmedetomidine). After the initiation of the infusions, supplemental

sedation was provided by intermittent doses of morphine (0.08-0.1

mg/kg/h) as needed. If multiple additional doses of morphine were

required (3-4 over an 8 hour period), the midazolam infusion was

increased by 0.05 to 0.1 mg/kg/h and the dexmedetomidine infusion was

increased by 0.15 to 0.25 [micro]g/kg/h. Before increasing the infusion,

if needed, the patient was bolused with the current hourly rate over a

5-minute period. This bolus dose was included in the total daily dose of

the medication. After 24 hours on either the midazolam or the

dexmedetomidine infusions, if ongoing mechanical ventilation was still

necessary, the patient was switched to the alternative agent and the

study continued.

The quality of sedation was assessed every 2 hours using 3 clinical

sedation scales and the Bispectral Index Monitor (BIS monitor; Aspect

Medical, Newton, MA). The 3 clinical sedation scores included the Ramsay

sedation scale, the pediatric intensive care unit (PICU) sedation score,

and the tracheal suctioning score (Table 1). Heart rate and blood

pressure were recorded every 2 hours. Statistical analysis included a

nonpaired t test with a Bonferroni correction, when multiple comparisons

were used, to compare demographic data (age, weight), daily morphine

use, and hemodynamic parameters (heart rate, systolic/diastolic blood

pressure). A Wilcoxon ranked-sum test was used to analyze nonparametric

data including BIS numbers and sedation scores (Ramsay, PICU sedation

score, tracheal suction score). A two-tailed Fisher exact test was used

to compare demographic data (sex distribution), number of infusion

changes, requirement for morphine boluses, number of patients with a

Ramsay score of 1 and the total number of assessment points with a

Ramsay score of 1 between the 3 groups. All data are presented as the

mean [+ or -] SD with P

Results

There were 10 patients in each of the 3 groups (midazolam,

dexmedetomidine 0.25 [micro]g/kg/h, and dexmedetomidine 0.5

[micro]g/kg/h). There were no statistically significant differences

among patient demographics, study duration, and data collection for the

3 groups (Table 2). The mean infusion rates were 0.22 [+ or -] 0.05

mg/kg/h for the midazolam group, 0.28 [+ or -] 0.07 [micro]g/kg/h in the

0.25 dexmedetomidine group, and 0.68 [+ or -] 0.15 [micro]g/kg/h in the

0.5 dexmedetomidine group. Using the 3 sedation scores and the BIS

number, there were no differences noted between the 3 groups (Table 3).

Thirty-six morphine boluses were administered to the midazolam

group versus 29 and 20 morphine boluses administered to the 0.25 and 0.5

[micro]g/kg/h dexmedetomidine groups respectively. (P = not significant

(NS) for midazolam versus 0.25 dexmedetomidine and P = 0.02 for

midazolam versus 0.5 dexmedetomidine). Total morphine use (mg/kg/24 h)

was 0.74 [+ or -] 0.5, 0.55 [+ or -] 0.38, and 0.28 [+ or -] 0.12 in the

midazolam group and the two dexmedetomidine groups (0.25 and 0.5

[micro]g/kg/h) respectively (P = NS for midazolam versus 0.25

dexmedetomidine, P = 0.01 for midazolam versus 0.5 dexmedetomidine, and

P < 0.05 for 0.25 dexmedetomidine versus emergency root canal 0.5 dexmedetomidine). During

the course of the study, there were 15 infusion changes in the midazolam

group versus 6 and 4 infusion changes in the 0.25 and 0.5 [micro]g/kg/h

dexmedetomidine groups respectively (P = 0.06 for midazolam versus 0.25

dexmedetomidine, and P = 0.01 for midazolam versus 0.5 dexmedetomidine).

When considering those patients that were inadequately sedated as

judged by a Ramsay score of 1, this occurred at 14 assessment points in

6 of the 10 patients sedated with midazolam, at 11 assessment points in

4 of the 10 patients sedated with 0.25 [micro]g/kg/h of dexmedetomidine,

and at 5 assessment points in 2 of the 10 patients sedated with 0.5

[micro]g/kg/h of dexmedetomidine (P = NS for midazolam versus 0.25

dexmedetomidine and P = 0.052 for midazolam versus 0.5 dexmedetomidine).

In the two dexmedetomidine groups, 5 of 6 patients who at some point had

a Ramsay score of 1 were less than 12 months of age while only 1 was

more than 12 months of age (P < 0.05).

When evaluating hemodynamic parameters including systolic/diastolic

blood pressure and heart rate, there was no difference noted between the

3 groups in regards to systolic and diastolic blood pressure (Table 4).

Heart rates were significantly lower in the two dexmedetomidine groups

than in the midazolam group (Table 4). One patient was removed from the
study because of bradycardia (heart rate of 40-50 beats/min). Data from

this patient is not included in the current cohort of patients. The

patient was a 5 week old, 3.6 kg infant with trisomy 21 who was

concurrently receiving digoxin. No hypotension was noted and the

bradycardia resolved within 1 hour of discontinuing the dexmedetomidine

infusion. This patient has been reported previously as an isolated case

report of bradycardia during dexmedetomidine infusion. (5) No other

adverse hemodynamic effects (bradycardia or hypotension) were noted in

the study population.

Discussion

The current study provides prospective data regarding the efficacy

of dexmedetomidine for sedation during mechanical ventilation in infants

and children. We found the efficacy of 0.25 [micro]g/kg/h of

dexmedetomidine to be approximately equivalent to that of midazolam at

0.22 mg/kg/h. Although the level of sedation as assessed by the three

clinical sedation scales and the BIS number was equivalent in the 3

groups, patients receiving the higher dose of dexmedetomidine (0.5

[micro]g/kg/h) required fewer bolus doses of morphine, used less total

morphine per 24 hours, and had fewer points when a Ramsay score of 1 was

assigned, thereby demonstrating the higher dose of dexmedetomidine (0.5

[micro]g/kg/h) to be somewhat superior to midazolam.

Dexmedetomidine is the pharmacologically active dextro-isomer of

medetomidine. The [[alpha].sub.2] adrenergic agonist class of drugs can

be divided into 3 groups: imidazolines, phenylethylamines, and

oxalozepines. Both dexmedetomidine and clonidine are imidazole compounds

that exhibit a high ratio of specificity for the [[alpha].sub.2] versus

the [[alpha].sub.1] receptor. Clonidine exhibits an

[[alpha].sub.2]:[[alpha].sub.1] specificity ratio of 200:1 while that of

dexmedetomidine is 1,600:1. (6) Therefore, dexmedetomidine is considered

a full agonist at the [[alpha].sub.2] adrenergic receptor. By activation

of specific transmembrane [[alpha].sub.2] adrenergic receptors at

various locations throughout the central nervous system, dexmedetomidine

produces physiologic effects including sedation, anxiolysis, and

analgesia. These physiologic effects are mediated via stimulation of

postsynaptic [[alpha].sub.2] adrenergic receptors that activate a

pertussis toxin-sensitive guanine nucleotide regulatory protein (G

protein) resulting in inhibitory feedback and decreased activity of

adenylyl cyclase. (7,8) The subsequent reduction in cyclic adenosine

monophosphate (cAMP) and cAMP-dependent protein kinase activity causes a

predominant dephosphorylation of various species of ion channels, (9)

which modifies ion translocation and membrane conductance, resulting in

decreased neuronal activation. (10) Dexmedetomidine also activates

receptors in the medullary vasomotor center, thereby reducing

norepinephrine turnover and decreasing central sympathetic outflow

resulting in alterations in sympathetic function including a decrease in

heart rate and blood pressure. Additional effects result from the

central stimulation of parasympathetic outflow and inhibition of

sympathetic outflow from the locus caeruleus in the brainstem. The

latter effect plays a prominent role in the sedation and anxiolysis

produced by these agents as decreased noradrenergic output from the

locus caeruleus allows for increased firing of inhibitory neurons

including the [gamma]-amino butyric acid (GABA) system resulting in

sedation and anxiolysis. (11-13) Dexmedetomidine, through activation of

[[alpha].sub.2] adrenergic receptors of the dorsal horn of the spinal

cord, regulates the release of Substance P resulting in primary

analgesic effects as well as potentiation of opioid-induced analgesia.

Previous reports in adults have demonstrated dexmedetomidine to be

an effective agent for sedation and anxiolysis during mechanical

ventilation. Venn et al. evaluated the efficacy of dexmedetomidine in

119 postoperative cardiac and general surgical patients requiring

postoperative ventilation. (1) The patients were randomized to

dexmedetomidine administered as a loading dose of 1 [micro]g/kg over 10

minutes followed by an infusion of 0.7 [micro]g/kg/h or placebo. Despite

having equivalent Ramsay scores, patients receiving dexmedetomidine had

a statistically significant decrease in supplemental midazolam and

morphine requirements. Similar findings were reported by Martin et al.

in a prospective, randomized trial of 401 postsurgical patients. (2)

Aside from the current study, experience with dexmedetomidine in

pediatric-aged patients has been anecdotal. We have previously reported

our experience with dexmedetomidine in two separate cohorts of patients.

(3,4) The first series included four patients in whom dexmedetomidine

was used to provide sedation during mechanical ventilation, as an

adjunctive agent intraoperatively for controlled hypotension during

posterior spinal fusion, and for procedural sedation during upper

gastrointestinal endoscopy. The second series included five patients in

additional clinical scenarios including sedation during spontaneous

ventilation in a toddler with status asthmaticus, in the management of

substance withdrawal (tobacco, cannabinoids, and ethanol) in an

adolescent after complex cardiothoracic surgery, and in the

postanesthesia arena for the control of shivering and emergence

delirium. Although anecdotal, these two series demonstrated that

dexmedetomidine was effective in all of these clinical scenarios, except

for procedural sedation during upper gastrointestinal endoscopy, and was

free of significant adverse effects.

As with many of the agents currently used for sedation in the

intensive care unit population, there is a potential for adverse

cardiorespiratory effects with dexmedetomidine. In the study of Venn et

al, (1) 18 of 66 patients that received dexmedetomidine developed

adverse hemodynamic effects that included either hypotension (mean

arterial pressure less than 60 mm Hg or a greater than 30% decrease from

baseline) or bradycardia (heart rate less than 50 beats/min). In 11 of

these 18 patients, the hemodynamic effects occurred during the bolus

infusion. Talke et al (14) noted similar hemodynamic effects in a cohort

of adult patients after vascular surgery. Although only 1 of 22 patients

experienced hypotension, they also noted one patient who developed a 5

to 10 sinus pause after anesthetic induction with thiopental and

fentanyl suggesting that there may be a synergistic vagotonic effect of

dexmedetomidine with other agents. In their perioperative study, Peden

et al (15) noted a similar episode of sinus pause as well as episodes of

bradycardia when dexmedetomidine was combined with propofol, and altered

their protocol to include the administration of an anti-cholinergic

agent. Given their experience and that reported in the literature, they

recommended the administration of anticholinergic agent to patients less

than 40 years of age.

In our study population, the baseline heart rate was significantly

lower in both of the dexmedetomidine groups when compared with

midazolam; as noted previously, one patient who was concurrently

receiving digoxin developed clinically significant bradycardia (heart

rate 40-50 beats/min), which necessitated discontinuation of the

dexmedetomidine. Although no episodes of hypotension were noted, given

the potential adverse effects of dexmedetomidine on cardiac output as

demonstrated by the study of Bloor et al. in healthy, adult volunteers,

(16) close monitoring of cardiovascular function is suggested until a

larger experience with this agent in pediatric-aged patients is

accumulated.

Similarly, there is the potential for adverse effects from

dexmedetomidine on respiratory function. As all of the patients in the

current study were receiving mechanical ventilation, no attempt was made

to discern the potential effects of dexmedetomidine on ventilatory

function in the current cohort of patients. Although several of the

previous studies in adults have demonstrated the feasibility of weaning of ventilatory support with
tracheal extubation while receiving a
dexmedetomidine infusion, other studies have clearly demonstrated

potential deleterious ventilatory effects from dexmedetomidine. (17,18)

After the administration of 2 [micro]g/kg of dexmedetomidine, Belleville

et al. demonstrated a rightward shift and down-sloping of the C[O.sub.2]

response curve in healthy male volunteers. (17) They also noted a

decreased ventilatory response to an end-tidal C[O.sub.2] of 55 mm Hg

during carbon dioxide challenge.

Conclusion

In summary, we present preliminary experience with dexmedetomidine

in pediatric-aged patients. At a dose of 0.25 [micro]g/kg/h,

dexmedetomidine was approximately equivalent to midazolam at 0.22

mg/kg/h. A higher infusion rate of 0.5 [micro]g/kg/h provided more

effective sedation as demonstrated by the need for fewer bolus doses of

morphine, a decrease in the 24-hour requirements for supplemental

morphine as well as a decrease in the number of Ramsay scores of 1 and

the number of patients who had a Ramsay score of 1. Overall,

dexmedetomidine was less effective in patients less than 12 months of

age as 5 of the 6 patients who received a Ramsay score of 1 during

dexmedetomidine administration (either 0.25 or 0.5 [micro]g/kg/h) were

less than 12 months of age.

Table 1. Clinical sedation scales used for the study

Ramsay score

1 = Anxious, agitated, restless

2 = Eyes open, cooperative, oriented, tranquil

3 = Responds (opens eyes) only to command, light touch, normal tone of

voice

4 = Brisk response to light glabellar tap or loud noise/voice

5 = Sluggish response to light glabellar tap or loud noise/voice

6 = No response to light glabellar tap or loud noise/voice

PICU sedation score

1 = Awake, alert

2 = Occasionally drowsy, easy to arouse

3 = Frequently drowsy, easy to arouse

4 = Somnolent

Tracheal suctioning score

1 = Patient is restless or distressed when not disturbed

2 = Patient is awake and moving, but not distressed if left alone

3 = Movement only with nursing care, major limb movement/distress with

tracheal suctioning

4 = Cough, grimace or minor limb movement with suctioning

5 = No response to tracheal suctioning

Table 2. Demographic data of the three groups

midazolam dexmedetomidine 0.25 dexmedetomidine 0.5

Age (months) 36 [+ or -] 34 44 [+ or -] 54 39 [+ or -] 44
Weight 19 [+ or -] 20 22 [+ or -] 27 21 [+ or -] 24

Gender (M/F) 6/4 7/3 7/3

Infusion

duration

(h) 22 [+ or -] 8 21 [+ or -] 10 22 [+ or -] 9

Table 3. BIS number and clinical sedation scores of the three groups (a)

midazolam dexmedetomidine dexmedetomidine

0.25 0.5

BIS number 57 [+ or -] 8 51 [+ or -] 12 60 [+ or -] 10

Ramsay score 3.6 [+ or -] 0.9 3.7 [+ or -] 1.1 3.5 [+ or -] 0.8

PICU sedation

score 2.9 [+ or -] 1.2 3.1 [+ or -] 0.9 2.9 [+ or -] 1.1

Tracheal

suction score 3.5 [+ or -] 1.2 3.2 [+ or -] 1.4 3.5 [+ or -] 1.3

(a) BIS, bispectral index score.

Table 4. Hemodynamic parameters of the three groups (a)

midazolam dexmedetomidine dexmedetomidine

0.25 0.5

Systolic BP (mm Hg) 94 [+ or -] 22 88 [+ or -] 31 96 [+ or -] 26

Diastolic BP (mm Hg) 46 [+ or -] 16 52 [+ or -] 19 49 [+ or -] 21

Heart rate (beats/

min) 142 [+ or -] 36 122 [+ or -] 31 112 [+ or -] 26

(a) BP, blood pressure.

Accepted August 29, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9705-0451

References

1. Venn RM, Bradshaw CJ, Spencer R, et al. Preliminary UK

experience of dexmedetomidine, a novel agent for postoperative sedation

in the intensive care unit. Anaesthesia 1999;54:1136-1142.

2. Martin E, Ramsay G, Mantz J, et al. The role of the

[[alpha].sub.2] adrenoceptor agonist dexmedetomidine in post-surgical

sedation. J Intensive Care Med 2003;18:29-41.

3. Tobias JD, Berkenbosch JW. Initial experience with

dexmedetomidine in paediatric-aged patients. Paediatr Anaesth

2002;12:171-175.

4. Tobias JD, Berkenbosch JW, Russo P. Additional experience with

dexmedetomidine in pediatric patients. South Med J 2003;96:871-875.

5. Berkenbosch JW, Tobias JD. Development of bradycardia during

sedation with dexmedetomidine in an infant concurrently receiving

digoxin. Pediatr Crit Care Med 2003;4:203-205.

6. Virtanen R, Savola JM, Saano V, et al. Characterization of the

selectivity, specificity and potency of medetomidine as an

[[alpha].sub.2] adrenoceptor agonist. Eur J Pharmacol 1988;150:9-14.

7. Correa-Sales C, Reid K, Maze M. Pertussis toxin-mediated

ribosylation of G proteins blocks the hypnotic response to an

[[alpha].sub.2]-agonist in the locus coeruleus of the rat. Pharmacol

Biochem Behav 1992;43:723-727.

8. Correa-Sales C, Nacif-Coelho C, Reid K, et al. Inhibition of

adenylate cyclase in the locus coeruleus mediates the hypnotic response

to an [[alpha].sub.2] agonist in the rat. J Pharmacol Exp Ther

1992;263:1046-1049.

9. Nacif-Coelho C, Correa-Sales C, Chang LL, et al. Perturbation of

ion channel conductance alters the hypnotic response to the

[[alpha].sub.2]-adrenergic agonist dexmedetomidine in the locus

coeruleus of the rat. Anesthesiologv 1994;81:1527-1534.

10. Sculptoreanu A, Scheuer T, Catterall WA. Voltage-dependent

potentiation of L-type [Ca.sup.2+] channels due to phosphorylation by

cAMP-dependent protein kinase. Nature 1993;364:240-243 (letter).

11. Correa-Sales C, Rabin BC, Maze M. A hypnotic response to

dexmedetomidine, an [[alpha].sub.2] agonist, is mediated in the locus

coeruleus in rats. Anesthesiology 1992;76:948-952.

12. Doze VA, Chen BX, Maze M. Dexmedetomidine produces a

hypnoticanesthetic action in rats via activation of central

[[alpha].sub.2] adrenoceptors. Anesthesiology 1989;71:75-79.

13. Nelson LE, Lu J, Guo T, et al. The [[alpha].sub.2]-adrenoceptor

agonist dexmedetomidine converges on an endogenous sleep-promoting

pathway to exert its sedative effects. Anesthesiology 2003;98:428-436.

14. Talke P, Chen R, Thomas B, et al. The hemodynamic and

adrenergic effects of perioperative dexmedetomidine infusion after

vascular surgery. Anesth Analg 2000;90:834-839.

15. Peden CJ, Cloote AH, Stratford N, et al. The effect of

intravenous dexmedetomidine premedication on the dose requirement of

propofol to induce loss of consciousness in patients receiving

alfentanil. Anaesthesia 2001;56:408-413.

16. Bloor BC, Ward DS, Belleville JP, et al. Effects of intravenous

dexmedetomidine in humans: Part II--Hemodynamic changes. Anesthesiology

1992;77:1134-1142.

17. Belleville JP, Ward DS, Bloor BC, et al. Effects of intravenous

dexmedetomidine in humans: Part I--Sedation, ventilation, and metabolic

rate. Anesthesiology 1992;77:1125-1133.

18. Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and

analgesic properties of small-dose dexmedetomidine infusions. Anesth

Analg 2000;90:699-705.

RELATED ARTICLE: Key Points

* Dexmedetomidine is a centrally acting, [[alpha].sub.2] agonist

which is currently FDA approved for short-term use ([less than or equal

to] 24 hours) to provide sedation in adults.

* When administered at a dose of 0.25 [micro]g/kg/h,

dexmedetomidine provided a level of sedation equivalent to midazolam of

0.22 mg/kg/h.
* Dexmedetomidine at 0.5 [micro]g/kg/h provided superior sedation

to midazolam as evidenced by a decrease in the 24 hour requirement for

supplemental morphine and a decrease in the number of Ramsay scores of 1

(inadequate sedation).

* Dexmedetomidine was less effective in patients less than 12

months of age, as 5 of the 6 patients who received a Ramsay score of 1

during the infusion of either dexmedetomidine dose (0.25 or 0.5

[micro]g/kg/h) were less than 12 months of age.

Joseph D. Tobias, MD, and John W. Berkenbosch, MD

From the Division of Pediatric Critical Care/Pediatric

Anesthesiology, Departments of Child Health and Anesthesiology,

University of Missouri, Columbia, MO.

Abbott Pharmaceuticals provided dexmedetomidine free of charge for

the purpose of this study. This study was performed at the University of

Missouri, Columbia, MO.

Reprint requests to Joseph D. Tobias, MD, Department of

Anesthesiology, University of Missouri, 3W40H, One Hospital Drive,

Columbia, MO 65212. Email: tobiasj@health.missouri.edu