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Pediatrics. 2008 May;121(5):e1363-71. doi: 10.1542/peds.2007-1468. Epub 2008 Apr 14.

Effect of low-dose naloxone infusion on fentanyl requirements in critically ill children.

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  • 1Department of Pediatrics, University of Texas Southwestern, Dallas, Texas, USA. cindy.darnell@childrens.com

Abstract

OBJECTIVE:

Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance. Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation. The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children.

METHODS:

We conducted a double-blinded, randomized, placebo-control trial from December 2002 through July 2004 in a university PICU. We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for >4 days were eligible for enrollment. Those receiving additional oral analgesia or sedation, having a history of drug dependence or withdrawal, or having significant neurologic, renal, or hepatic disease were excluded. In addition to fentanyl infusions, patients received low-dose naloxone or placebo infusions. Medications were adjusted using the Modified Motor Activity Assessment Scale. Withdrawal was monitored using the Modified Narcotic Withdrawal Scale. Intervention was a low-dose naloxone infusion (0.25 microg/kg per hour) and the main outcome variable was the maximum cumulative daily fentanyl dose (micrograms per kilogram per day).

RESULTS:

There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone (N = 37) or those receiving placebo (N = 35). Adjustment for the starting fentanyl dose also failed to reveal group differences. Total fentanyl dose received throughout the study in the naloxone group (360 microg/kg) versus placebo (223 microg/kg) was not statistically different. Placebo patients trended toward fewer rescue midazolam boluses (10.7 vs 17.8), lower total midazolam dose (11.6 mg/kg vs 23.9 mg/kg), and fewer rescue fentanyl boluses (18.5 vs 23.9).

CONCLUSIONS:

We conclude that administration of low-dose naloxone (0.25 microg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

PMID:
18411237
[PubMed - indexed for MEDLINE]
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