Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study

Abstract

Objective: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit.

Design: Prospective, observational study with 100% accrual of eligible patients.

Setting: Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network.

Patients: Four hundred nineteen children treated with morphine or fentanyl infusions.

Interventions: None.

Measurements and main results: Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03).

Conclusions: Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

Figure 1

CONSORT (Consolidated Standards of Reporting Trials) Diagram showing subjects screened, enrolled, and included in this analysis.

Figure 2

Number of patients who required doubling of their opioid doses after initiation of opioid therapy.

Figure 3

Kaplan-Meier “freedom from event” curve for patients meeting the criterion for the primary outcome (time to doubling of the initial opioid dose). Patients not achieving this outcome were censored at the time of study exit.

Figure 4

Patterns of opioid dosing at the participating sites. Each line represents a single clinical site, showing the median daily opioid dose used at that site each day during the study. Morphine doses were converted to fentanyl equivalents using well-defined opioid potency ratios (1:80).