National Intravenous Acetaminophen Use in Pediatric Inpatients From 2011-2016.

OBJECTIVE: To 1) determine current intravenous (IV) acetaminophen use in pediatric inpatients; and 2) determine the association between opioid medication duration when used with or without IV acetaminophen. METHODS: A retrospective analysis of pediatric inpatients exposed to IV acetaminophen from January 2011 to June 2016, using the national database Health Facts. RESULTS: Eighteen thousand one hundred ninety-seven (2.0%) of 893,293 pediatric inpatients received IV acetaminophen for a median of 14 doses per patient (IQR, 8-56). A greater proportion of IV acetaminophen patients were admitted to the intensive care unit (ICU) (14.8% vs 5.1%, p < 0.0001), received positive pressure ventilation (2.0% vs 1.5%, p < 0.0001), had a higher hospital mortality rate (0.9% vs 0.3%, p < 0.0001), and were operative (35.5% vs 12.8%, p < 0.001) than those not receiving IV acetaminophen. The most common operations associated with IV acetaminophen use were musculoskeletal and digestive system operations. Prescription of IV acetaminophen increased over time, both in prescription rates and number of per patient doses. Of the 18,197 patients prescribed IV acetaminophen, 16,241 (89.2%) also were prescribed opioids during their hospitalization. A multivariate analysis revealed patients prescribed both IV acetaminophen and opioids had a 54.8% increase in opioid duration as compared with patients who received opioids alone. CONCLUSIONS: This is the first study to assess IV acetaminophen prescription practices for pediatric inpatients. Intravenous acetaminophen prescription was greater in the non-operative pediatric inpatient population than operative patients. Intravenous acetaminophen prescription was associated with an increase in opioid duration as compared with patients who received opioids alone, suggesting that it is commonly used to supplement opioids for pain relief.

Association of Intravenous Acetaminophen Administration With the Duration of Intravenous Opioid Use Among Hospitalized Pediatric Patients.

Importance: Adoption of multimodal pain regimens that incorporate nonopioid analgesic medications to reduce inpatient opioid administration can prevent serious opioid-related adverse effects in children, including tolerance, withdrawal, delirium, and respiratory depression. Intravenous (IV) acetaminophen is in widespread pediatric use; however, its effectiveness as an opioid-sparing agent has not been evaluated in general pediatric inpatients. Objective: To determine if IV acetaminophen administered prior to IV opioids is associated with a reduction in the total duration of IV opioids administered compared with IV opioids administered without IV acetaminophen in general pediatric inpatients. Design, Setting, and Participants: This comparative effectiveness research study included data on pediatric inpatients from 274 US hospitals between January 2011 and June 2016 collected from a national database. Outcomes were compared with a propensity score-matched analysis of pediatric inpatients administered IV opioids without IV acetaminophen (control) and those administered IV acetaminophen prior to IV opioids (intervention). Data were analyzed from January 2020 through October 2021. Exposures: Patients in the intervention group received IV acetaminophen prior to IV opioids. Patients in the control group received IV opioids without IV acetaminophen. Main Outcomes and Measures: Total duration of all IV opioids administered during a patient's hospitalization. Results: Of 893 293 pediatric inpatients, a total of 104 579 were included in analysis (median [IQR] age, 1.3 [0-14.7] years; 59 806 [57.2%] female; 21 485 [21.5%] African American, 56 309 [53.8%] White), of whom 18 197 (2.0%) received IV acetaminophen, and 287 504 (34.0%) received IV opioids. After applying exclusion criteria, among patients who received IV acetaminophen, 1739 (10.8%) received IV acetaminophen prior to IV opioids within a median (IQR) treatment time of 1.5 (0.02-7.3) hours. After propensity score matching produced comparable groups in the control and intervention groups (with 839 patients in each group), the multivariable model estimated a 15.5% shorter duration of IV opioid use in the intervention group, with an absolute IV opioid reduction of 7.5 hours (95% CI, 0.7-15.8 hours). Conclusions and Relevance: In this comparative effectiveness study, IV acetaminophen administered prior to IV opioids was associated with a reduction in IV opioid duration by 15.5%. Multimodal pain regimens that use IV acetaminophen prior to IV opioids could reduce IV opioid duration.

Medications for Children Receiving Intensive Care: A National Sample.

OBJECTIVE: To examine medication administration records through electronic health record data to provide a broad description of the pharmaceutical exposure of critically ill children. DESIGN: Retrospective cohort study using the Cerner Health Facts database. SETTING: United States. PATIENTS: A total of 43,374 children 7 days old to less than 22 years old receiving intensive care with available pharmacy data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 907,440 courses of 1,080 unique medications were prescribed with a median of nine medications (range, 1-99; 25-75th percentile, 5-16) per patient. The most common medications were acetaminophen, ondansetron, and morphine. Only 45 medications (4.2%) were prescribed to more than 5% of patients, and these accounted for 442,067 (48.7%) of the total courses of medications. Each additional medication was associated with increased univariate risk of mortality (odds ratio, 1.05; 95% CI, 1.05-1.06; p < 0.001). CONCLUSIONS: Children receiving intensive care receive a median of nine medications per patient and one quarter are prescribed at least than 16 medications. Only 45 medications were prescribed to more than 5% of patients, but these accounted for almost half of all medication courses.

Sedation, Analgesia, and Neuromuscular Blockade: An Assessment of Practices From 2009 to 2016 in a National Sample of 66,443 Pediatric Patients Cared for in the ICU.

OBJECTIVES: To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs. DESIGN: A retrospective analysis using data extracted from the national database Health Facts. SETTING: One hundred sixty-one ICUs in the United States with pediatric admissions. PATIENTS: Children in ICUs receiving medications from 2009 to 2016. EXPOSURE/INTERVENTION: Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications. MEASUREMENTS AND MAIN RESULTS: Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes. CONCLUSIONS: Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.