Opioid Analgesia in Mechanically Ventilated Children
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.
Children requiring mechanical ventilation and invasive monitoring routinely receive opioids for analgesia/sedation in the pediatric intensive care unit (PICU). Use of opioid analgesics and other sedatives helps to reduce pain, anxiety, or agitation, facilitate mechanical ventilation, prevent physiological stress responses, and avoid secondary complications. Opioid therapy may lead to opioid-induced hyperalgesia or opioid tolerance, dependence, and withdrawal. These effects occur more commonly in children than in adults because of developmental changes in metabolism, excretion, drug efficacy, receptor subtypes, signal transduction, receptor induction, or cellular regulatory pathways.
Surveys of analgesia/sedation practices in PICUs demonstrated wide variability in clinical practices. The use of several drug classes, multiple agents, large variations in the doses, frequency, and routes of administration, off-label use of analgesic drugs, or untested drug combinations occurs routinely, often driven by individual preferences or local culture. Consensus guidelines for sedation, analgesia, or neuromuscular blockade in PICU patients have highlighted the paucity of high-quality evidence and called for more randomized trials in this area.
Given this variability, it is difficult to define best practices, develop guidelines, or launch scientific efforts to investigate the key hypotheses in this area. Randomized trials in this population await descriptive observational studies to determine associations between clinical practices and patient outcomes, needed for generating hypotheses that can be tested formally. The Collaborative Pediatric Critical Care Research Network designed this prospective, observational study to characterize the exposure to opioid analgesia among mechanically ventilated children in the PICU, in order to prepare for a randomized trial comparing alternative analgesic strategies.
Abstract and Introduction
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.
Introduction
Children requiring mechanical ventilation and invasive monitoring routinely receive opioids for analgesia/sedation in the pediatric intensive care unit (PICU). Use of opioid analgesics and other sedatives helps to reduce pain, anxiety, or agitation, facilitate mechanical ventilation, prevent physiological stress responses, and avoid secondary complications. Opioid therapy may lead to opioid-induced hyperalgesia or opioid tolerance, dependence, and withdrawal. These effects occur more commonly in children than in adults because of developmental changes in metabolism, excretion, drug efficacy, receptor subtypes, signal transduction, receptor induction, or cellular regulatory pathways.
Surveys of analgesia/sedation practices in PICUs demonstrated wide variability in clinical practices. The use of several drug classes, multiple agents, large variations in the doses, frequency, and routes of administration, off-label use of analgesic drugs, or untested drug combinations occurs routinely, often driven by individual preferences or local culture. Consensus guidelines for sedation, analgesia, or neuromuscular blockade in PICU patients have highlighted the paucity of high-quality evidence and called for more randomized trials in this area.
Given this variability, it is difficult to define best practices, develop guidelines, or launch scientific efforts to investigate the key hypotheses in this area. Randomized trials in this population await descriptive observational studies to determine associations between clinical practices and patient outcomes, needed for generating hypotheses that can be tested formally. The Collaborative Pediatric Critical Care Research Network designed this prospective, observational study to characterize the exposure to opioid analgesia among mechanically ventilated children in the PICU, in order to prepare for a randomized trial comparing alternative analgesic strategies.