Retrospective Comparison of Intranasal Dexmedetomidine and Oral Chloral Hydrate for Sedated Auditory Brainstem Response Exams

Discussion

This study has shown that sedation with IN DEX at a dose of 4 μg/kg was effective for ABR examinations. However, the ability to begin the examination sooner and complete the examination with a single dose suggests IN DEX may be a superior alternative to oral chloral hydrate. An additional benefit is the lower incidence of procedural hypoxemia requiring supplemental oxygen in the IN DEX group. Although the outcomes of this study may be related to the medication itself, there are several other potential explanations.

The first is the route of administration. Oral chloral hydrate is generally administered with an oral syringe and requires a semi-cooperative child. Despite the best attempts, some children may not receive the entire dose because they “spit it out” or some of the medication is lost during attempts to get the child to swallow the medication. Conversely, intranasal administration with a mucosal atomizing device is a much more reliable way to administer medications. Thus, more reliable drug delivery could account for some of the differences in this study, especially the improved success with a single dose in the IN DEX cohort.

A second explanation involves the absorption of medications delivered intranasally. The clinical effects of medications delivered nasally are believed to be a consequence of drugs traversing the nasal mucosa and entering the bloodstream where they avoid first-pass metabolism in the liver. This mechanism is an obvious advantage of IN DEX. However, it has also been demonstrated that there is a nose–brain pathway in which drugs can enter the central nervous system directly across the nasal mucosa or via a transport mechanism across the olfactory nerves.²³ All of these mechanisms would favor IN DEX over orally administered medications and may account for the shortened onset time for satisfactory sedation to permit the start of the ABR examination.

There are few published data on the use and safety profile of high-dose IN DEX. We selected the dosing protocol for this study based on published reports regarding the bioavailability of dexmedetomidine delivered across mucosal membranes and on dose-related reports of the safety of high-dose intravenous dexmedetomidine. Given a reported bioavailability between 35% and 93%, we would expect a single IN DEX dose of 4 μg/kg to be equivalent to intravenous dosing between 1.4 and 3.73 μg/kg, with a peak effect seen at 38 minutes. This outcome would be well within the reported safe range when using intravenous dexmedetomidine as a sole agent for MRI examinations in children.¹¹ Lower doses of 2.5 and 3 μg/kg of IN DEX have been used to provide satisfactory conditions for CT scans and transthoracic echocardiograms, respectively.^18,19

An unexpected difference between the 2 cohorts was noted in the need for supplemental oxygen. In the chloral hydrate cohort, supplemental oxygen was administered to 12 (6%) of 200 patients (95% confidence interval [CI], 7.5–16.5). This finding is consistent with the reported incidence of supplemental oxygen administration from the much larger Pediatric Sedation Research Consortium.²⁴ However, none of the 100 patients (95% CI, 0–3.7) in the IN DEX group required supplemental oxygen. This finding was not significantly different from the incidence of 1.6% (95% CI, 0–3.6) noted in the study by Mekitarian et al,¹⁸ in which a lower dose of IN DEX was given for CT imaging. The results from the present study may be due to factors intrinsic to the medications, reflect a difference in care between the original cohorts of chloral hydrate–treated patients versus the subsequent IN DEX–treated patients, or just be a consequence of other differences that can affect airway patency during sedation in the 2 samples.

Obesity and obstructive sleep apnea are factors known to be associated with increased hypoxemia. Because data on the heights of all subjects were not available, we could not calculate their BMI. However, obesity is a relative contraindication for nurse-administered sedation in our institution, and this policy was not changed between the 2 epochs. It is of interest that children in the IN DEX group had significantly higher weights although the ages were similar. The incidence of hypoxemia was lower than in the chloral hydrate group, however.

Bradycardia, hypertension, and hypotension have been reported with intravenous dexmedetomidine sedation. Even though these effects are common, they generally resolve and do not require intervention.²⁵ The original studies that examined high-dose intravenous dexmedetomidine for MRI scans noted ∼16% of children with a heart rate 20% below the age-specific normal values, and a few children had heart rates <60 beats/min.^10,25 In subsequent studies of IN DEX for CT imaging, Mekitarian et al¹⁸ noted a 15% incidence of decrease in heart rate 20% below baseline. However, baseline heart rate and blood pressures in children undergoing procedures are probably higher than sleeping values as a result of anxiety. In addition, these minor alterations in heart rate and blood pressure associated with dexmedetomidine sedation are not of clinical significance, as they do not warrant interventions. We defined bradycardia as a heart rate <60 beats /min, which is in keeping with the definitions of the American Heart Association guidelines for interventions in the Pediatric Advanced Life Support Provider manual.²⁶ Consistent with the consensus-based recommendation for standardized terminology and reporting adverse events during procedural sedation and analgesia, we only considered bradycardia an adverse event if it required intervention.²¹ Our definition of hypotension was also based on the same criteria as in the Pediatric Advanced Life Support manual and the aforementioned consensus-based recommendations.

No patient in either cohort met our criteria for bradycardia or hypotension as an adverse event. This finding differs from reports of patients receiving high-dose intravenous dexmedetomidine that used decreases from baseline values as the criteria for cardiovascular changes. However, it is consistent with the report by Mekitarian et al¹⁸ that noted 1 of 63 administrations of IN DEX was associated with a 20% reduction in mean arterial blood pressure. The causes for the difference between the reported incidence of hypotension between intravenous and intranasal administration is unclear but may reflect differences in the definition of hypotension. Another likely explanation is the relatively slower absorption of intranasal medications with subsequently diminished physiologic alterations.

A major limitation of the present study was its retrospective design, which only reflects data that were documented and collected from the nursing sedation record. Thus, it is possible that the overall number of events was underreported. It is also important to note that severe cardiorespiratory adverse events that require interventions are rare in the setting of an organized sedation program. Thus, it is difficult to make any definitive conclusions regarding the overall safety of either medication based on this study alone because it was not adequately powered to detect differences in the low incidence of adverse effects. Much larger studies may be required to determine these adverse effect profiles.

A second limitation was the temporal gap between the 2 groups of patients. Small differences in efficiency or patient selection may have made considerable differences in the outcomes described in our study. However, this study does suggest IN DEX is an effective medication for sedation in ABR examinations. A randomized controlled study will be required before any definitive conclusions can be drawn regarding the superiority of this technique over the previous standard chloral hydrate regimen.

A third limitation of the study was the method of data collection. We only collected data on patients who were enrolled in the study and did not collect data on the reasons patients were excluded from receiving nurse-administered sedation. Because the same exclusion criteria were applied to both patient cohorts, the 2 patient cohorts should be similar at baseline.

It is important to note that there are many different models for sedation delivery in children. Although there are clear guidelines from professional organizations such as the American Academy of Pediatrics and the American Society of Anesthesiologists, there is often no consensus on best practice.⁷ At our institution, we have developed a tiered system for sedation delivery that utilizes nurses; specially trained, nonanesthesiologist sedation pediatricians; and fellowship-trained pediatric anesthesiologists. A potential advantage of using IN DEX for most cases and limiting propofol or general inhalation anesthesia to those who failed nurse-administered IN DEX sedation is that more procedures can be performed at a lower cost. In addition, given the concerns regarding anesthetic neurotoxicity and neuroapoptosis, dexmedetomidine sedation regimens, where appropriate, may be preferable in young children.²⁷