257 - Cumulative Exposure to Opioids and Benzodiazepines in Extremely Preterm Neonates

Poster Number: 257
Publication Number: 257.1973

Background: Sedation and/or analgesia are frequently used in the most preterm neonates to treat pain and agitation. However, there are concerns that opioid exposure may lead to lower cortical and cerebellar volumes and benzodiazepines may cause neuronal apoptosis.

Objective: To quantify exposure of opioids and benzodiazepines in preterm neonates and identify how these exposures differ by gestational age, facility, and comorbid conditions/treatments.

Design/Methods: Cross-sectional study of neonates born at 23 0/7 to 28 6/7 weeks gestation between 2011 and 2021. Neonates were treated at 7 Level III NICUs. Neonates who died within the first 7 days after birth or were transferred out of the health system were excluded. Medication exposure was obtained from the electronic administration record. For opioids, cumulative morphine milligram equivalent (MME) per kg were calculated using standard conversion factors for all opioid infusion and discrete dosages. Similarly, cumulative lorazepam equivalents per kg were calculated for all benzodiazepines. Clinical information was obtained from pre-existing research databases. Logistic regression was used to evaluate the association between neonatal comorbidities/treatments and ≥10 MME/kg opioid exposure, adjusting for antenatal steroids, sex, and gestational age.

Results: In a population of 1,501 neonates, 30% were exposed to both opioids and benzodiazepines, 24% to opioids alone, and 1.5% to benzodiazepines alone. The distribution of the cumulative exposure was highly right skewed for both drugs (Figure 1); however, 17% of infants received ≥10 MME/kg and 9% received ≥2 lorazepam equivalent mg/kg. Opioid exposure was inversely related to gestational age, with substantially higher median cumulative exposure in the most preterm neonates (Figure 2). A similar pattern was seen for benzodiazepines. Considerable variation in the percentage of neonates exposed as well as cumulative exposure was observed among facilities (Figure 3). Mechanical ventilation aOR 3.7 (95%CI 2.5-5.4), vasopressor use aOR 4.6 (95%CI 3.4-6.4), supplemental oxygen at 36 weeks corrected post menstrual age aOR 1.7 (95%CI 1.3-2.4), and severe intraventricular hemorrhage aOR 2.5 (95%CI 1.5-4.1) were associated with cumulative opioid exposure ≥10 MME/kg.

Conclusion(s): Significant exposure to opioids and benzodiazepines occurs in extremely preterm neonates, but there is significant variation in practice. More research is needed to evaluate if opioid exposure is merely a marker of severity of illness or contributes to the need for interventions and risk of adverse outcomes.