Pediatric Premedication: A Double-blind Randomized Trial of Dexmedetomidine or Ketamine Alone Versus a Combination of Dexmedetomidine and Ketamine

Hui Qiao; Zhi Xie; Jie Jia


BMC Anesthesiol. 2017;17(158) 

In This Article


Our study showed that a combination of intranasal dexmedetomidine 2 μg/kg and oral ketamine 3 mg/kg resulted in more successful venous cannulations and fewer perioperative adverse events compared with premedication using dexmedetomidine or ketamine alone. Dexmedetomidine produced satisfactory sedative effects, which were complemented by ketamine's analgesic effects. Thus, 90% of children exhibited satisfactory sedation 30 min after premedication, and the rate of successful venous cannulation with the premedication combination was as high as 80%.

The aims of premedication for pediatric patients are to reduce preoperative separation anxiety and postoperative psychological trauma, to help the patient undergo smooth induction of anesthesia, and to ensure perioperative safety. Although intranasal dexmedetomidine was reported to produce acceptable sedative effects and improve the emotional state of children when separating from their parents,[4,7,8,9] dexmedetomidine as a sole agent has not been uniformly successful for invasive procedures.[10] To overcome some of the pitfalls of dexmedetomidine alone, recent literature has shown beneficial effects of combining dexmedetomidine and ketamine for procedural sedation in pediatric patients.

The superiority of combining dexmedetomidine and ketamine was fully demonstrated for awake fiberoptic nasotracheal intubation of adults[11] and for cardiac catheterization of children, when intravenous medication maintained the required depth of sedation.[12,13] Intranasal instillation and oral administration are easy to perform, which may alleviate the fear of needles precipitated by intramuscular or intravenous injections and thereby reduce the occurrence of spasmodic sobbing, breath-holding, swallowing, abdominal distension, or other adverse events related to crying. Thus, administration of intranasal dexmedetomidine and oral ketamine was previously reported to be an optimal combination, allowing children to separate easily from their parents and accept intravenous cannulation, while maintaining hemodynamic stability and not causing excessive side effects or postoperative complications.[14] Likewise, a nebulized combination of low dose ketamine and dexmedetomidine was reported to produce more satisfactory sedation and a smoother induction of general anesthesia than nebulized ketamine or dexmedetomidine alone, with more rapid recovery and no significant side effects.[15] The current study also found that the combination of ketamine or dexmedetomidine significantly increased the success rate of venous cannulation, along with producing a smooth induction and stable recovery, without affecting the time of LMA removal. Although the time required for resumption of mental orientation was longer in patients receiving the combination, the children had stable vital signs and no adverse respiratory or cardiovascular events during the time before orientation returned.

Theoretically, a combination of dexmedetomidine and ketamine, which have complementary pharmacological characteristics, produce acceptable sedative and analgesic effects and can significantly accelerate the onset of sedation. The absolute bioavailability of dexmedetomidine has been reported to be approximately 82% following intranasal administration. The time of sedation onset for intranasal 1–4 μg/kg dexmedetomidine was approximately 15–45 min in healthy volunteers and children, with significant sedation observed for 1–2 h and an elimination half-life of 2.1–3.1 h.[16] Oral bioavailability of ketamine is poor (only 8–24%), and previous research indicates that children tend to be sedated within 20 min after oral ketamine. Pharmacodynamic analysis has shown that concentrations associated with arousal in children are analogous to those in adults, and the elimination half-life of oral ketamine is approximately 2–4 h.[5]

Furthermore, the undesirable increase in airway secretions with ketamine administration is attenuated by the xerostomia induced by dexmedetomidine, while concurrent ketamine injection prevents bradycardia and hypotension reported with dexmedetomidine.[6] Side effects of delirium, nausea, and vomiting were observed after oral administration of 4–8 mg/kg ketamine for sedation.[17] Our study also showed that five children receiving ketamine alone had evidence of upper airway irritation and irregular breathing when inhalational mask induction was performed. Emergent intubation was required in some of these patients, and a higher incidence of postoperative nausea, vomiting, hypoxia, and other respiratory-related complications was noted with ketamine alone, which are clear drawbacks to the use of ketamine alone as premedication.

This study has some limitations. First, further stratification by age was not implemented, which possibly influenced our results, as Yuen et al. reported that higher doses of dexmedetomidine were required in younger children.[7] Secondly, children with an ESS-4 score ≥ 3 points or for whom venous cannulation was not possible on the first attempt underwent inhalational induction, which may have produced respiratory effects during the induction period that potentially affected the rate of respiratory-related adverse events after surgery.