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

Cindy Maria Darnell, Jennifer Thompson, Daniel Stromberg, Lonnie Roy, Paul Sheeran

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 maximumcumulative 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 fent-anyl 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 μg/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 μg/kg) versus placebo (223 μug/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 μg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

Original languageEnglish (US)
JournalPediatrics
Volume121
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Fentanyl
Naloxone
Critical Illness
Placebos
Opioid Analgesics
Midazolam
Narcotics
Artificial Respiration
Adenylyl Cyclases
Cyclic AMP
Analgesia
Nervous System
Substance-Related Disorders
Motor Activity
Kidney
Liver

Keywords

  • Controlled trial
  • Critically ill children
  • Opiate dependent neonate
  • Pain management
  • Randomized
  • Sedation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Effect of low-dose naloxone infusion on fentanyl requirements in critically ill children. / Darnell, Cindy Maria; Thompson, Jennifer; Stromberg, Daniel; Roy, Lonnie; Sheeran, Paul.

In: Pediatrics, Vol. 121, No. 5, 05.2008.

Research output: Contribution to journalArticle

Darnell, Cindy Maria ; Thompson, Jennifer ; Stromberg, Daniel ; Roy, Lonnie ; Sheeran, Paul. / Effect of low-dose naloxone infusion on fentanyl requirements in critically ill children. In: Pediatrics. 2008 ; Vol. 121, No. 5.
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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 maximumcumulative 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 fent-anyl 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 μg/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 μg/kg) versus placebo (223 μug/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 μg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.",
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N2 - 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 maximumcumulative 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 fent-anyl 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 μg/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 μg/kg) versus placebo (223 μug/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 μg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

AB - 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 maximumcumulative 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 fent-anyl 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 μg/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 μg/kg) versus placebo (223 μug/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 μg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

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