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PEDIATRIC ANESTHESIOLOGY

A Comparison of Dexmedetomidine-Midazolam with Propofol for Maintenance of Anesthesia in Children Undergoing Magnetic Resonance Imaging

Christopher Heard, MBChB, FRCA^*, Frederick Burrows, MD, Kristin Johnson, PharmD, Prashant Joshi, MD, James Houck, MD^||, and Jerrold Lerman, MD, FRCPC, FANZCA^¶#

From the *Department of Anesthesiology and Division of Pediatric Critical Care, State University of New York at Buffalo, Women and Children’s Hospital of Buffalo, Buffalo, New York; Department of Anesthesiology, State University of New York at Buffalo, Women and Children’s Hospital of Buffalo, Buffalo, New York; Department of Pharmacy, Women and Children’s Hospital of Buffalo, Buffalo, New York; Division of Pediatric Critical Care, State University of New York at Buffalo, Women and Children’s Hospital of Buffalo, Buffalo, New York; ||Department of Anesthesiology, Women and Children’s Hospital of Buffalo, Buffalo, New York; ¶State University of New York at Buffalo and University of Rochester, Rochester, New York; and #Department of Anesthesiology, Women and Children’s Hospital of Buffalo, Buffalo and Strong Memorial Hospital, Rochester, New York.

Address correspondence to Dr. Christopher Heard, Department of Anesthesiology, Women and Children’s Hospital of Buffalo, 219 Bryant St., Buffalo, NY 14222. Address e-mail to heardop1{at}verizon.net.

Abstract

BACKGROUND: Dexmedetomidine is an ₂ agonist that is currently being investigated for its suitability to provide anesthesia for children. We compared the pharmacodynamic responses to dexmedetomidine-midazolam and propofol in children anesthetized with sevoflurane undergoing magnetic resonance imaging (MRI).

METHODS: Forty ASA 1 or 2 children, 1–10 yr of age, were randomized to receive either dexmedetomidine-midazolam or propofol for maintenance of anesthesia for MRI after a sevoflurane induction. Dexmedetomidine was administered as an initial loading dose (1 µg/kg) followed by a continuous infusion (0.5 µg · kg^–1 · h^–1). Midazolam (0.1 mg/kg) was administered IV when the infusion commenced. Propofol was administered as a continuous infusion (250–300 µg · kg^–1 · min^–1). Recovery times and hemodynamic responses were recorded by one nurse who was blinded to the treatments.

RESULTS: We found that the times to fully recover and to discharge from the ambulatory unit after dexmedetomidine administration were significantly greater (by 15 min) than those after propofol. Analysis of variance demonstrated that heart rate was slower and systolic blood pressure was greater with dexmedetomidine than propofol. Respiratory indices for the two treatments were similar. During recovery, hemodynamic responses were similar. Cardiorespiratory indices during anesthesia and recovery remained within normal limits for the children’s ages. No adverse events were recorded.

CONCLUSION: Dexmedetomidine-midazolam provides adequate anesthesia for MRI although recovery is prolonged when compared with propofol. Heart rate was slower and systolic blood pressure was greater with dexmedetomidine when compared with propofol. Respiratory indices were similar for the two treatments.

General anesthesia or sedation is usually required for children who require radiological studies such as magnetic resonance imaging (MRI). Although many healthy young children have been managed by radiologists and nursing with oral or IV sedation, the efficiency of this technique is poor and the failure rate, particularly in children who are cognitively challenged, is substantial.1,2 Those who are most in need of general anesthesia include children who are young (<6 yr of age), those who are unable or unwilling to remain still during the scan and those who are developmentally or cognitively challenged. The most widely used general anesthetics for MRI are propofol and sevoflurane, although more recently there has been growing interest in dexmedetomidine for this purpose.

Dexmedetomidine has been investigated as an anesthetic for ambulatory radiological procedures in children, including MRI.3–8 Most of these reports have been case series with wide variations in the dosing regimens and success rates. Dexmedetomidine was compared with midazolam and propofol for MRI in children in randomized, controlled trials.5,7 In the comparison with propofol, the failure rates (as evidenced by movement during the scan) with dexmedetomidine and propofol were 16% and 10%, respectively, the scan times were uncharacteristically brief (25 min) and hemoglobin desaturation occurred in the perioperative period.7 As a result of the scan failures with dexmedetomidine, the scans had to be rescheduled.3,5,7 The results of these studies suggested that when dexmedetomidine was administered in accordance with these study protocols, it did not provide adequate anesthesia for MRI in children.

To address the substantial failure rates during MRI scans, larger doses of dexmedetomidine have been studied for MRI in children.9 However, many clinicians have been hesitant to administer large doses of dexmedetomidine for these outpatient surgeries as the elimination half-life of dexmedetomidine in children is prolonged, approximately 2 h,10 and there is concern of hypotension and bradycardia. Nonetheless, large initial loading doses of dexmedetomidine (2–3 µg/kg) combined with increased infusion rates (up to 2 µg · kg^–1 · h^–1) were recently reported in children for MRI and found to be effective in reducing the scan failure rates.9

In a pilot study, we investigated several strategies to optimize the anesthetic, i.e., prevent movement, using standard doses of dexmedetomidine. Our preliminary data indicated that, after a brief inhaled induction, a single IV dose of midazolam combined with dexmedetomidine provided not only effective and reliable anesthesia for MRI without movement, but provided rapid recovery and stable cardiorespiratory responses that appeared to be comparable with our experience with propofol.8 Accordingly, we designed this study to compare the recovery characteristics and pharmacodynamics (cardiorespiratory responses) of dexmedetomidine (combined with midazolam) with those of propofol during and after anesthesia for ambulatory MRI in children.

METHODS

With local IRB approval and informed written consent from the Children and Youth Institutional Review Board, Woman and Children’s Hospital of Buffalo, 40 children, ages 1–10 yr, scheduled for elective MRI under anesthesia were recruited. Exclusion criteria were: age <1 yr, the presence of congenital heart disease, a recent upper respiratory infection, pneumonia or episode of acute asthma in the preceding 2 wk, behavioral problems (i.e., attention deficit hyperactivity disorder), gastroesophageal reflux disease requiring treatment, recent use of digoxin, β blockers, ₂ agonists, anticonvulsants or psychotropic medications, allergies to ₂ agonists or propofol, sleep apnea, difficult airway or one that required tracheal intubation or laryngeal mask airway, body mass index (BMI) <5% or >95% or a scan expected to last more than 90 min.

After application of electrocardiogram, noninvasive arterial blood pressure and pulse oximeter, anesthesia was induced with 8% inspired sevoflurane, 60% nitrous oxide in oxygen by facemask in the MRI scan room. With loss of consciousness, IV access was established and a balanced salt solution was administered according to standard fluid guidelines. The facemask was then replaced with baffled nasal prongs through which supplemental oxygen was delivered at 2 L/m via one prong, and the carbon dioxide (CO₂) tension was monitored via the second prong (Pediatric ETCO₂ Divided Sampling Cannula, Salter Labs®, Arvin, CA). The child was positioned with a soft roll under the shoulder and the neck extended. A stable capnogram was established before proceeding. If evidence of airway obstruction was present, supplemental airway maneuvering and interventions were instituted. Electrocardiogram, pulse oximetry, and CO₂ were monitored continuously throughout the anesthetic. Noninvasive arterial blood pressure was monitored at 5 min intervals throughout the anesthetic.

After induction of anesthesia, the children were randomly assigned to receive either a dexmedetomidine or propofol by infusion. Randomization was determined in advance of the study using random number tables to assign the numbers between 1 and 40 to the 2 groups. The randomization assignment was concealed until the parents consented to the study.

For those who were assigned to receive dexmedetomidine, an initial loading dose of dexmedetomidine, 1 µg/kg, was infused IV over 10 min followed by a continuous infusion at 0.5 µg · kg^–1 · h^–1. For those who were scheduled to receive propofol, propofol was infused IV at 300 µg · kg^–1 · min^–1 for the first 10 min and then at 250 µg · kg^–1 · min^–1 for the remainder of the MRI. At the 10 min mark, 0.1 mg/kg midazolam was given IV to children in the dexmedetomidine group and a similar volume of saline was given IV to those in the propofol group. All infusions were attached to the clave in the IV tubing set closest to the child. Once the infusion of dexmedetomidine (initial loading dose) or propofol was established, the child entered the MRI scanner.

The infusions were discontinued when the scan was completed. The child was then transferred to the postanesthesia care unit (PACU) while breathing supplemental oxygen administered by a facemask and monitored by pulse oximetry. After recovery from anesthesia in the PACU, the children were transferred to the ambulatory unit until discharge.

A single observer, who was blinded to the treatment assignment, was present throughout the MRI and recovery periods. Blinding was assured by concealing the infusion pump and tubing using green towels and by standardizing the two infusion protocols such that each required only one adjustment, at 10 min after they were started. At the completion of the anesthetic, the IV tubing was flushed with saline to eliminate any residual propofol to maintain observer blinding.

The observer recorded the heart rate, systolic and diastolic blood pressures, respiratory rate, hemoglobin oxygen saturation, and CO₂ tension (via the nasal cannula) every 5 min during the anesthetic and heart rate, systolic and diastolic blood pressures, respiratory rate, and hemoglobin oxygen saturation every 5 min in the PACU. The observer also recorded all complications and side effects during or after the anesthetic. The times from the application of the facemask until start of the infusion (a measure of the sevoflurane exposure), from the beginning to the end of the treatment infusion and the total time in the MRI scan suite were recorded. The time intervals from the termination of the anesthetic until spontaneous eye opening, recovery of full responsiveness (based on a modified Aldrete score of 10/10) and discharge from PACU were recorded. The time intervals from PACU discharge until hospital discharge and from end of the scan until hospital discharge were also determined. Discharge criteria from the ambulatory unit were based on standard discharge criteria used at our institution regardless of the anesthetic administered. A follow-up phone call was completed within 72 h of completion of anesthesia to determine if there were any adverse events or sequelae noted by the parents after discharge.

Sample size was estimated based on pilot and published data of the recovery times after dexmedetomidine and propofol in children undergoing MRI.7,8 With a difference between the mean recovery times of 25 min and a standard deviation of 13 min, two tailed 0.05 and power of 0.8, only 6 children were required in each group. For MRI scanning at our institution, we use large doses of propofol to reduce the risk of movement (i.e., failed scans), a practice that could increase the recovery time after propofol administration. To account for an anticipated smaller difference in the recovery times between the dexmedetomidine and propofol, 20 children were enrolled in each treatment arm.

The primary outcome variable was the time interval from discontinuation of the infusion until full recovery of responsiveness after anesthesia as defined by the modified Aldrete score (Appendix). Secondary outcome variables included the times in the PACU to eye opening, and to discharge from the PACU and the ambulatory unit, as well as heart rates, systolic and diastolic blood pressure responses, respiratory rates, end-tidal CO₂ tensions, and the incidence of complications.

Demographic data (age, weight), anesthesia and MRI scan times and recovery times were compared between treatments using the Student’s t-test. Continuous measurements (heart rate, systolic and diastolic blood pressures, respiratory rate, and ETCO₂ tension) during anesthesia and in the PACU were analyzed using a two-factor (treatment and time) repeated-measures analysis of variance model with the Student-Newman-Keuls test for post hoc multiple comparisons. All data were evaluated using Bartlett’s test for homogeneity of variances and Kolmogorov-Smirnov test for normalcy of data distribution. Effects of treatment, time and the interaction, treatment x time are reported as F values for each analysis of variance and P values for each post hoc comparison. P < 0.05 was accepted.

RESULTS

Forty children completed this study, 20 in each group. Demographic data for the two groups were similar (Table 1). The number of children who were taking medications before the study (three children required asthma medications, three required seizure medications, two required laxatives) was similar in the two groups. The reasons for the MRI scans were developmental delay (n = 11), tethered cord (n = 8), seizures (n = 5), cerebral palsy (n = 3), tumor (n = 2), headache (n = 3), syrinx (n = 2), and others (n = 6). All children completed their scans using the anesthetic regimen to which they had been randomized. The average overall doses of dexmedetomidine and propofol infused were 1.7 µg/kg ± 0.25 and 9.3 mg/kg ± 3.1, respectively.

The time interval from application of the facemask until start of the infusions, the duration of the infusions and the time in the MRI suite were similar for the two treatments (Table 2). Although the times to eye opening after the two treatments were similar, the primary outcome variable, the time to recovery of full responsiveness, was significantly greater after dexmedetomidine administration than it was after propofol by 50% or 15 min (P < 0.05). The time to PACU discharge after dexmedetomidine exceeded that after propofol by almost 50%, or 15 min (P < 0.05). The times in the ambulatory unit (post-PACU discharge) was similar for the two treatments. The total time interval between completion of the scan and hospital discharge after dexmedetomidine was significantly greater than that after propofol, with virtually all of the excess time occurring in the PACU (Table 2).

Heart rates for both treatments at baseline were similar (Fig. 1). During the MRI, heart rate differed significantly between the two treatments. Heart rate changes during the MRI were dependent on both the treatment (F_{0.05 (1) 1,38} = 4.2, P < 0.048) and the interaction, treatment x time, (F_{0.05 (1) 5,190} = 5.7, P < 0.00006); time did not affect heart rate. Heart rate at all times in the dexmedetomidine group was significantly less than baseline (P < 0.00004), whereas heart rate in the propofol group did not differ significantly from baseline at any time. Heart rate in the dexmedetomidine group at 5 and 10 min was significantly less than that in the propofol group (P < 0.00007). At no time was the heart rate <60 bpm in either group. The slowest heart rate in the dexmedetomidine group was 64 bpm (n = 3) and that in the propofol group was 66 bpm (n = 1).

View larger version (16K): [in this window] [in a new window]   Figure 1. Heart rate during magnetic resonance imaging (MRI). Heart rate responses to dexmedetomidine-midazolam (Dex) and propofol during MRI scans. Treatment (P < 0.048) and the interaction, treatment x time, (P < 0.00006) yielded significant effects on heart rate. Heart rate in the dexmedetomidine group was significantly less than the baseline value at all times (P < 0.00004) whereas heart rate in the propofol group did not differ significantly from the baseline value at any time. Data are means ± sd. *P < 0.00007 compared with dexmedetomidine. P < 0.00004 compared with baseline value.

Systolic blood pressures in the two treatments were similar at baseline (Fig. 2). Treatment (F_{0.05 (1) 1,38} = 15.5, P < 0.0003) and the interaction, treatment x time, (F_{0.05, (1) 5,190} = 7.1, P < 0.000004) yielded significant effects on systolic blood pressure, whereas time did not. Systolic blood pressure in the dexmedetomidine group at 20 min was significantly greater than baseline (P < 0.02), whereas those in the propofol group at 20 and 25 min were less than baseline (P < 0.02). Systolic blood pressures in the dexmedetomidine group were greater than those in the propofol group at 10 min (P < 0.0003) and at 15, 20, and 25 min (P < 0.00003). The minimum systolic blood pressure recorded in the dexmedetomidine group was 70 mm Hg (n = 2) and in the propofol group, 64 mm Hg (n = 2). Diastolic blood pressures in the two treatments were similar at baseline (Fig. 2). Treatment (F_{0.05 (1) 1,38} = 29.1, P < 0.000004) and the interaction, treatment x time (F_{0.05 (1) 1,38} = 9.2, P < 0.0000001) yielded significant effects on diastolic blood pressure. Diastolic blood pressures at 15, 20 and 25 min in both groups were significantly different from baseline. Diastolic blood pressures in the propofol group were significantly less than those in the dexmedetomidine group at 5 min (P < 0.006) and at 10, 15, 20, and 25 min (P < 0.00003).

View larger version (16K): [in this window] [in a new window]   Figure 2. Blood pressure during magnetic resonance imaging (MRI). Systolic and diastolic blood pressure responses to dexmedetomidine-midazolam (Dex) and propofol during MRI scans. Treatment and the interaction, treatment x time, yielded significant differences for both systolic and diastolic blood pressures (see Results for significance levels). Data are means ± sd. *P < 0.0003; **P < 0.00003 between dexmedetomidine and propofol. P < 0.02; P < 0.0035; P < 0.048 compared with baseline.

Respiratory rate decreased significantly with time (F_{0.05, (1) 5,190} = 8.7, P < 0.0000002), although treatment and the interaction, treatment x time, did not. During the MRI, respiratory rate for both treatments decreased at 10 min (P < 0.009), at 15 min (P < 0.03), at 20 min (P < 0.0003), and 25 min (P < 0.00002) (Fig. 3). The slowest respiratory rate detected was 14 breaths per minute (n = 1) in the dexmedetomidine group and 10 in the propofol group (n = 1). There were no episodes of apnea. ETCO₂ tension did not differ within or between the groups at any time (Fig. 4). The maximum ETCO₂ tension detected was 57 mm Hg in the dexmedetomidine group (n = 1) and 52 mm Hg in the propofol group (n = 1).

View larger version (10K): [in this window] [in a new window]   Figure 3. Respiratory rate during magnetic resonance imaging (MRI) scan. Respiratory rate responses to dexmedetomidine-midazolam (Dex) and propofol during MRI scans. Time exerted a significant effect on respiratory rate. In both groups, the respiratory rate at 10 min (P < 0.009), 15 min (P < 00026), 20 min (P < 0.0003) and 25 min (P < 0.00002) decreased compared with baseline. Data are means ± sd.

View larger version (11K): [in this window] [in a new window]   Figure 4. End-tidal CO2 during magnetic resonance imaging (MRI) scan. End-tidal carbon dioxide tension to dexmedetomidine-midazolam (Dex) and propofol during MRI scanning. Carbon dioxide tensions did not differ between or within the treatments at any time. Data are means ± sd.

There were no episodes of desaturation or airway obstruction in either group.

The mean heart rates after dexmedetomidine and propofol administration were similar in PACU (Fig. 5). Heart rate did not change significantly within or between the two treatments at any time. The slowest heart rates with dexmedetomidine were 66 (n = 1), 67 (n = 1), and 68 bpm (n = 1) and with propofol were 58 (n = 1) and 62 bpm (n = 1).

View larger version (14K): [in this window] [in a new window]   Figure 5. Heart rate in postanesthesia care unit (PACU). Heart rate responses to dexmedetomidine (Dex) and propofol in the PACU. The interaction, treatment x time, yielded significant differences in heart rate. All error bars for propofol are upright and for dexmedetomidine downward. Data are means ± sd. *Compared with dexmedetomidine (P < 0.013). Compared with baseline (P < 0.005).

The mean systolic and diastolic blood pressures changed significantly after dexmedetomidine and propofol administration in the PACU (Fig. 6). For systolic blood pressure, the interaction term, treatment x time, yielded significant differences (F_{0.05, (1) 5,190} = 3.54, P < 0.0044), whereas treatment and time did not. The minimum systolic blood pressure in the dexmedetomidine (n = 1) and propofol groups (n = 2) was 72 mm Hg. For diastolic blood pressure, treatment (F_{0.05, (1) 1.38} = 10.5, P < 0.0025) and the interaction, treatment x time, (F_{0.05, (1) 5,190} = 2.99, P < 0.013) yielded significant differences (Fig. 6). Diastolic blood pressures after dexmedetomidine administration were significantly greater than those after propofol at baseline and 5 min (P < 0.000048) as well as at 10 and 15 min (P < 0.0013).

View larger version (14K): [in this window] [in a new window]   Figure 6. Blood pressure in postanesthesia care unit (PACU). Systolic and diastolic blood pressures after dexmedetomidine (Dex) and propofol anesthesia in PACU. Systolic blood pressure changed significantly with the interaction, treatment x time (P < 0.0044); there was no independent effect of treatment or time. Diastolic blood pressure changed significantly with treatment (P < 0.0025) and the interaction, treatment x time (P < 0.013). Data are means ± sd. *P < 0.00005; **P < 0.0013; P < 0.02 compared with dexmedetomidine.

There were no cardiorespiratory complications during the MRI or in the PACU with either treatment. One child who received dexmedetomidine was agitated in the PACU but required no treatment. The same child was also mildly agitated in the day surgical unit but was discharged without any delay and without sequelae. No child who received propofol developed agitation. During follow-up phone calls, all of the parents expressed satisfaction with their child’s anesthetic. There were no complaints or complications reported after discharge.

The cost of dexmedetomidine and propofol was the number of vials (no splitting of the contents among children) required to deliver the total infusion dose plus the dose required to prime the infusion circuit. Based on these assumptions, the cost to sedate with propofol, $19.50, was $33.00 less than with dexmedetomidine, $52.40. The pharmacy acquisition cost for dexmedetomidine-midazolam per child based on the mean dose of dexmedetomidine infused, 29 µg, and midazolam, 1.9 mg, was $10.80 and $1.86, respectively or a combined cost of $12.66. The pharmacy acquisition cost for the mean dose of propofol infused, 202 mg, was $10.10, similar to that of dexmedetomidine.

DISCUSSION

The purpose of this study was to compare the recovery characteristics and pharmacodynamics of a dexmedetomidine-midazolam combination with those of propofol for maintenance of anesthesia in children undergoing elective MRI. We found that the time to recovery of full responsiveness, the primary outcome variable, after dexmedetomidine-midazolam was significantly greater than that after propofol by 50% or 15 min (P < 0.05). This accounted for the excess time in the PACU after dexmedetomidine-midazolam administration compared with propofol. Once discharged from the PACU though, the times to discharge from the hospital for both treatment groups were similar. We also noted that 100% of the children in both treatments completed their MRI scans without interruption or interventions (i.e., no failures) and without complications. Heart rate and systolic blood pressure changes were transient and statistically significant, but not of sufficient magnitude to warrant interventions. Respiratory responses to both dexmedetomidine- midazolam and propofol were similar and unchanged over time.

In previous studies of dexmedetomidine, the failure rates to complete the MRI, 16% to 20%, were attributed to movement during the scans.3,5–7 These rates are similar to those reported with other sedatives for MRI in children.1,2 However, larger doses of dexmedetomidine have recently been shown to reduce the failure rate of MRI scans.9 The combination of standard doses of dexmedetomidine and a single IV dose of 0.1 mg/kg midazolam attenuated the rate of movement and failed scans substantively, to 7% in a preliminary report,8 and to 0% in the current study. The external validity of our 0% incidence of failed scans, however, must be tempered by the small sample size in this study. With only 20 children receiving dexmedetomidine in the current study, the long-run risk of zero failed scans after dexmedetomidine-midazolam administration in the entire population of healthy children is only 85%.11 Nonetheless, these data are very encouraging and suggest that larger studies are warranted to confirm the effectiveness of a dexmedetomidine-midazolam combination for maintenance of anesthesia for children undergoing MRI.

At our institution, IV access is usually established after a sevoflurane and nitrous oxide inhaled induction. The infusions of dexmedetomidine or propofol are commenced after discontinuing the inhaled anesthetic. This practice precludes determining the precise onset time of the maintenance anesthetics, but does provide a smooth transition from inhaled induction to IV maintenance in unpremedicated children who do not have IV access established preoperatively.

To facilitate ambulatory radiological procedures in children, the anesthetic prescription should facilitate rapid recovery. Recovery after administration of propofol for MRI in children is rapid, complete and associated with few complications.12–15 However, there is growing concern regarding the use of propofol infusions in children. First, federal regulatory agencies have expressed concerns regarding the risk of developing propofol infusion syndrome in children.^* Second, preliminary evidence suggests that subclinical metabolic acidosis may occur after even a brief exposure to a propofol infusion.16,17 In an effort to present an alternative strategy to propofol, it has become important to investigate the use of alternative anesthetics, such as dexmedetomidine, for procedures in children.

Recent pharmacokinetic data for dexmedetomidine in children indicated that the elimination half-life after a single bolus, 2 h,10 although similar to that in adults, far exceeds that of propofol (approximately 25 min).18,19 Consequently, one might expect that recovery after receiving dexmedetomidine may be delayed compared with propofol. In the current study, the times to full recovery after dexmedetomidine and to discharge from the PACU were statistically significantly greater than those after propofol, although the differences (15 min) were of minor clinical import. One might be tempted to attribute the delay in recovery after dexmedetomidine in this study to the single dose of midazolam, although this is unlikely to be the case as a single dose of midazolam did not delay recovery after dexmedetomidine in a previous study.8 Both dexmedetomidine-midazolam and propofol facilitated rapid recovery and discharge after MRI.

The hemodynamic responses to dexmedetomidine and propofol have been documented.4,7,10 Decreases in heart rate have been reported over time with dexmedetomidine in children.4,7,10 Our results are consistent with those data. However, there were no instances of bradycardia with either treatment in this study. Whether the absence of bradycardia is the result of a type II statistical error (adverse hemodynamic responses were not the primary outcome variable) or to the brevity of the anesthetic is unclear. A review of all prospective case reports and studies that included dexmedetomidine in infants and children yielded only one instance of bradycardia in 251 children.3–5,7,10,20–22 Because that single instance included the use of digoxin, which likely interacted with dexmedetomidine and that it occurred in a very young infant,21 we presumed that that single instance did not represent the true incidence of bradycardia that would otherwise occur in the population of healthy children without heart disease (and who were not receiving digoxin). Excusing that single report because of a drug interaction, the upper 95% confidence interval of the long-run risk of developing bradycardia in children who received dexmedetomidine, based on zero episodes in 250 children, is 1.2%.11 In contrast, the incidence of bradycardia during administration of larger doses of dexmedetomidine, in some cases combined with pentobarbital, was 16%.9 Heart rates as slow as 40 bpm were reported in that study. Bradycardia remains a potentially serious side effect associated with the use of dexmedetomidine in children, the severity of which depends on the dose of dexmedetomidine.

Respiratory rate and ETCO₂ tensions remained clinically unchanged during the two treatments. This, together with the absence of any episodes of apnea or bradypnea, suggests that neither dexmedetomidine nor propofol depresses respiration excessively in children when used in the dose range and manner used in this study. Inducing anesthesia with sevoflurane and after that with an initial loading dose and an infusion of dexmedetomidine or an infusion of propofol supports adequate respiration in spontaneously breathing children during MRI.

No side effects or complications were attributed to either anesthetic in this study. Nausea and vomiting did not occur after either treatment during the hospital stay or after discharge. The lack of nausea and vomiting after receiving propofol is consistent with its antiemetic action. Whether dexmedetomidine prevents nausea and vomiting cannot be established with any certainty given the small number of children in each group.

Among the limitations of this study, the time to onset of the anesthesia with dexmedetomidine could not be evaluated because we induced anesthesia with an inhaled induction with sevoflurane. We do not believe that sevoflurane affected the success rate of the MRI scans as the exposure to sevoflurane was brief (<5 min) and the solubility of sevoflurane is very small. The advantages of inducing anesthesia by inhalation in children include the ability to establish IV access after the child is anesthetized and that the residual sevoflurane could bridge the interval between recovery from the initial loading dose of dexmedetomidine and start of the infusion.9 In addition, residual sevoflurane may have bridged the need for an induction dose of propofol, thereby reducing the risk of apnea during transition to the propofol infusion.9 Disadvantages of this technique include the exclusion of nonanesthesiology practitioners from using it as they are not qualified to administer inhaled anesthesia. The external validity of this study is limited, in part, because of the broad exclusion criteria for patient recruitment. Children with recent upper respiratory infections, asthma and those with behavior difficulties (i.e., cognitively impaired, autism) are common co-morbidities in children who require anesthesia. Whether the responses to dexmedetomidine-midazolam and propofol in that population would mirror those obtained in this study remain to be established.

CONCLUSION

After induction of anesthesia with sevoflurane, dexmedetomidine supplemented with a single IV dose of midazolam provided adequate conditions for MRI without failures in this small study. However, when compared with propofol, recovery to full responsiveness after dexmedetomidine was statistically, although not clinically, prolonged. Heart rate and systolic blood pressure changes were transient and of limited clinical import at the doses of anesthetic treatments studied. Respiratory indices were similar with the two treatments.

Appendix 1

Footnotes

*www.fda.gov/medwatch/safety/2001/safety01.htm#dipriv (accessed on November 12, 2007).

Accepted for publication July 2, 2008.

Supported by Departmental Funds.

Presented, in part, at the Annual meeting of the American Society of Anesthesiologists, San Francisco, CA, October 15th, 2007.

Reprints will not be available from the author.

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