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Opioid Analgesia in Mechanically Ventilated Children: Results From the Multicenter Measuring Opioid Tolerance Induced by Fentanyl Study*

Anand, Kanwaljeet J. S. MBBS, DPhil1; Clark, Amy E. MS2; Willson, Douglas F. MD3; Berger, John MD4; Meert, Kathleen L. MD5; Zimmerman, Jerry J. MD, PhD6; Harrison, Rick MD7; Carcillo, Joseph A. MD8; Newth, Christopher J. L. MD, FRCPC9; Bisping, Stephanie BSN, RN, CCRP2; Holubkov, Richard PhD2; Dean, J. Michael MD, MBA2; Nicholson, Carol E. MD, MS10

Pediatric Critical Care Medicine: January 2013 - Volume 14 - Issue 1 - p 27–36
doi: 10.1097/PCC.0b013e318253c80e
Feature Articles

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.

Supplemental Digital Content is available in the text.

1 Departments of Pediatrics, Anesthesiology, and Neurobiology, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN.

2 Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT.

3 Department of Pediatrics, University of Virginia Children’s Hospital, Charlottesville, VA.

4 Department of Pediatrics, Children’s National Medical Center, Washington DC.

5 Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI.

6 Department of Pediatrics, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, WA.

7 Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA.

8 Department of Critical Care Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA.

9 Department of Anesthesiology and Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles, CA.

10 Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda, MD.

*See also p. 101.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

This work was supported, in part, by cooperative agreements (U10HD500009, U10HD050096, U10HD049981, U10HD049945, U10HD049983, U10HD050012, and U01HD049934) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Health and Human Services.

The authors have not disclosed any potential conflicts of interest.

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©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies