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Intranasal fentanyl and high-concentration inhaled nitrous oxide for procedural sedation: A prospective observational pilot study of adverse events and depth of sedation

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Literature Review

Is the Addition of Dexmedetomidine to a Ketamine-Propofol Combination in Pediatric Cardiac Catheterization Useful?

Ulgey A, Aksu R, Bicer C, et al.  Pediatric Cardiol 2012;33(5):770-774.

Reviewed by Daniel Tsze, MD and Joseph Cravero, MD

Dexmedetomidine (DEX) is an alpha two agonist with sedative and analgesic properties that preserves spontaneous ventilation, features that make it an increasingly popular choice for sedations.  This paper is interesting as it one of the first to describe the addition of DEX infusion to a ketamine-propofol combination (ketofol) and document the effect of this novel combination on children undergoing cardiac catheterizations.

The study was carried out in a randomized, placebo-controlled, double-blinded fashion and enrolled 60 children undergoing cardiac catheterization for evaluation or intervention for congenital heart disease (CHD).  Children were randomly assigned to receive either ketamine and propofol (KP), 1 mg/kg of each, and a normal saline (NS) infusion, or the same dose of ketamine and propofol plus a DEX infusion (KPD), 1 µ/kg for induction, then 0.5 µ/kg/h infusion.  Both groups received propofol 0.2 mg/kg as needed to maintain adequate sedation.

The main differences were a greater number of patients in the KP group required a chin-lift maneuver in response to airway obstruction and experienced arterial desaturation (SpO2 < 90%).  Patients in the KP group also demonstrated more movement during the local anesthesia infiltration and the catheterization, and had a longer mean recovery time (5.86 min vs. 3.13 min).  These findings were all in the context of a significantly greater amount of propofol required in the KP group.  These observations indicate that a significantly deeper level of sedation/anesthesia was achieved in the group that received the added DEX infusion.  Sedative medications were administered by anesthesiologists in this study, but it is evident that sedation using a combination of ketamine and propofol or ketamine/propofol/DEX in these doses clearly requires providers that can rescue a patient from a state of general anesthesia.

The benefit of adding DEX appears to be the propofol-sparing effect.  The higher mean dose of propofol used in the KP compared to the KPD group (9.86 ± 3.13 mg/kg vs. 2.53 ± 1.71 mg/kg, respectively) is likely responsible for the observed differences in airway and oxygenation.  In addition, the use of a continuous DEX infusion also appeared to produce conditions more amenable to catheterization compared to repeated boluses of propofol.

Although there may have been concerns that adding a sedative with a longer duration of action may have prolonged recovery time, that did not appear to be the case in this study.  On the other hand, one may question whether the benefits observed were solely due to the propofol-sparing effect of a DEX infusion, or due to the fact that a continous sedative infusion was better than providing sedation than relying on repeated PRN boluses.  Previous studies using DEX as a sole sedative at relatively high doses have documented a low but not insignificant rate of bradycardia (without severe hemodynamic deterioration).1  On the other hand, this study documented a lower heart rate in the group that received a DEX infusion but without any significant bradycardia.

This study would be improved if similar outcomes were compared between the KPD and KP group if the latter was supplemented by a propofol infusion.  One might speculate that the presence of a low-dose propofol infusion may not have caused as many complications as observed with the described (intermittent dosing) regimen and could have achieved similar procedural compliance. 

This study demonstrates that the addition of a DEX infusion to ketamine and propofol (intermittent bolus) sedation has benefits which appear to be related to its propofol-sparing effects. It may represent a viable strategy for reducing airway and oxygenation issues during sedations using ketamine and propofol.


  1. Wong J, Steil GM, Curtis M, Papas A, Zurakowski D, Mason KP.  Cardiovascular effects of dexmedetomidine sedation in children. Anesth Analg. 2012 Jan;114(1):193-9.


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