Literature Review

Reviewed by Daniel J. Sedillo, MD

Comparison of Rescue Techniques for Failed Chloral Hydrate Sedation for Magnetic Resonance Imaging Scans – Additional Chloral Hydrate vs Intranasal Dexmedetomidine

Zhang W, Wang Z, Song X, et al.  Pediatric Anesthesia 2015 Dec 30 (early view)


Background: Chloral hydrate, a commonly used sedative in children during noninvasive diagnostic procedures, is associated with side effects like prolonged sedation, paradoxical excitement, delirium, and unpleasant taste.  Dexmedetomidine, a highly selective alpha-2 agonist, has better pharmacokinetic properties than chloral hydrate. This is a prospective, double-blind, randomized controlled trial to evaluate efficacy of intranasal Dexmedetomidine with that of a second oral dose of chloral hydrate for rescue sedation during magnetic resonance imaging (MRI) studies in infants.

Methods: One hundred and fifty infants (age group: 1-6 months), who were not adequately sedated after initial oral dose of 50 mg/kg chloral hydrate, were randomly divided into three groups with the following protocol for each group:  Group C:  second oral dose chloral hydrate 25 mg/kg; Group L and Group H:  intranasal dexmedetomidine in a dosage of one and two mcg/kg, respectively.  Status of sedation, induction time, time to wake up, vital signs, oxygen saturation, and recovery characteristics were recorded.

Results: Successful rescue sedation in Group C, L, and H were achieved in 40 (80%), 47 (94%), and 49 (98%) of infants respectively, on an intention to treat analysis, and the proportion of infants successfully sedated in Group H was more than that of Group L (P < 0.01).  There were no significant differences in sedation induction time.  However, the time to wake up was significantly shorter in Group L as compared to that in Group C or H (P < 0.01).  No significant adverse hemodynamic or hypoxemic effects were observed in the study.

Conclusion: Intranasal dexmedetomidine induced satisfactory rescue sedation in 1- to 6-month old infants during MRI study, and appears to cause sedation in a dose-dependent manner.

This is now one of several recent articles that pediatric sedation practitioners can review and incorporate into their sedation practices, as many pediatric sedation programs worldwide turn to other sedation alternatives to chloral hydrate, either due to its side effect profile or due to its decreasing availability in an oral formulation.  The pharmacokinetic properties of intranasal dexmedetomidine appear to make it a superior substitute for chloral hydrate.

This research group in 2014 previously reported on their experience of utilizing intranasal dexmedetomidine in a rescue fashion, following failed chloral hydrate sedation in children (ages 1 month to 13 years) undergoing non-invasive diagnostic procedures to include CT scan, auditory brainstem response, or visual evoked potentials.1  Their protocol included an initial chloral hydrate dose of 50 mg/kg with a reported failure rate of 23.1%.  Patients who failed were randomized to receive 1, 1.5, or 2 mcg/kg of intranasal dexmedetomidine.  Successful rescue sedation was 83.6%, 89.2%, and 96.2%, respectively, with the intranasal dexmedetomidine rescue regimens. 

More specifically, this study included infants between the ages of 1 and 6 months, who were undergoing non-contrast MRI scans of less than 30 minutes duration.  These infants initially received 50 mg/kg of chloral hydrate orally, as in the previous study.  Failure of that first dose was assessed at 30 minutes post-dose administration.  The patients were then randomized to receive either additional chloral hydrate or intranasal dexmedetomidine.   The rescue success rate was slightly better in this cohort of patients as compared to the 2014 study.

The infant population is an interesting group who may have altered pharmacokinetic and pharmacodynamics properties than the older children.  Additionally, disruption of their usual sleep and feeding cycle may increase their pre-procedure level of anxiety and agitation, which may impact the sedation regimen success. 

Furthermore, the cognitive and developmental effects of sedative and anesthetic agents is still under question, especially in this age group. Dexmedetomidine is an agent that may not have these toxic concerns, but more importantly, may be neuroprotective.2  Ongoing studies may help guide clinicians and families who must often make the decision on whether to subject a young child to a sedation or anesthetic agent. 

A program that utilizes intranasal sedation as a mainstay of their pediatric sedation service, has to factor in the lag time between dosing and onset of sedation.  This lag time may be offset by the time required to prepare and place a peripheral intravenous catheter, along with the avoidance of this often painful and distressful procedure to both the patient and their family.  Families are often very relieved and appreciative if their child does not require placement of a peripheral intravenous catheter which is a “routine” and often relatively easy procedure in the pediatric medical environment, but at times can be very challenging and have unrecognized long-lasting emotional trauma to the child and their families. 

The future success of non-invasive pediatric sedation services will depend upon the utilization of multiple modalities, to include topical anesthetics, distraction and visual imagery techniques. In addition, a re-engineering of their patient flow, to account for the delay in sedation onset, and to have a sedation rescue, or rather, a pro-active, secondary sedation plan in the event of sedation failure from the initial dosing.  This may include re-dosing of intranasal sedative agents, the use of inhaled nitrous oxide, or  intravenous sedative agents. 

Similar to the delivery of beta-2 agonist agents to the asthmatic patient, the mode and methodology of intranasal sedative agent delivery may impact the pharmacologic properties of these agents, and therefore, patient sedation success.  The usage of commercially available, standardized delivery devices may address some of these concerns.

Furthermore, this type of sedation service can be safely administered by non-anesthesiologists, to include experienced pediatric hospitalists and registered nurses.  This could potentially expand the availability of sedated non-invasive diagnostic testing and services for children. 

Irrespective of this and other studies, which demonstrate the safety and efficacy of intranasal sedation in children, the sedation practitioner must not take use of these agents lightly.  Practitioners who administer these agents must still possess a thorough understanding of sedation pharmacology and their cardiopulmonary effects, and possess the skills to recognize and promptly intervene for any cardiopulmonary compromise that these agents may potentially cause.3,4


  1. Li BL, Yuen VM, Song XR, et al.  Intranasal dexmedetomidine following failed chloral hydrate sedation in children.  Anaesthesia 2014;69:240-44
  2. Degos V, Le Charpentier T, Chhor V, et al.  Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression.  Anesthesiology 2013;118:1123-32
  3. American Society of Anesthesiologists Task force on Sedation and Analgesia by Non-Anesthesiologists.  Practice guidelines for sedation and analgesia by non-anesthesiologists.  Anesthesiology 2002;96:1004-17
  4. Cote CJ, Wilson S.  Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: An update.  Pediatrics 2006;118:2587-2602

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