Infant populations exposed to prolonged sedation: are they at risk for long-term sequelae?
Andrews, Colleen Maura
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OBJECTIVE: Opioids are considered standard of care for pain treatment for infants undergoing painful procedures. In addition, prolonged opioid administration is used for sedation during non-surgical treatment (e.g. infants that require intubation and prolonged ventilation). Intubated infants often receive sedative drugs for a prolonged period of time, which leads to opioid dependence and tolerance. The long-term sequelae of such treatment involving the prolonged administration of opioids are unknown. There is evidence in cell cultures and animal models that prolonged opioid exposure is associated with increased neuronal apoptosis (neuronal cell death). In addition, human studies in premature children have suggested that prolonged opioid treatment is associated with decreased visual intelligence, social skills, and memory function. The goal of this study was to identify the population of the youngest patients (less than one year old) that requires prolonged administration of opioids for pain and sedation management. Our overarching hypothesis is that a select group of patients might be at risk for long-term neurologic sequelae from prolonged opioid treatment. METHODS: A retrospective chart review for admission cases over a period of one year was conducted to identify infants that received prolonged administration of opioids and/or benzodiazepines for their treatment. Infants were included if they were less than one year old, full-term (born 37-42 weeks of gestational age), and received prolonged treatment with opioids (e.g. fentanyl, morphine, hydromorphone) and/or benzodiazepines (e.g. midazolam, diazepam, lorazepam). Data on their diagnoses and sedation management at Boston Children's Hospital, including total dose of drugs received and if they developed dependence, was collected. RESULTS: Out of the 221 charts reviewed, only 46 infants were exposed to prolonged sedation and were full-term. Of these 46 infants, the largest proportion (35%; 16/46) was diagnosed with congenital anomalies. The other diagnoses included respiratory diseases (24%; 11/46), neurological diseases (13%; 6/46), and the remaining infants had a combination of two to three of these diagnoses (28%; 13/46). Infants with congenital diseases had a longer duration of sedation management (59.3 days ± 31.3 days) than infants with respiratory distress/infection (5.9 days ± 3.4 days). Those receiving the longest opioid treatments also exhibited signs of withdrawal when drugs were discontinued, which suggested the development of opioid dependence and required weaning treatment. Patients with sedation for 4 days or less did not show withdrawal symptoms, while those with sedation of 6 days or more required an opioid and benzodiazepine weaning regimen. CONCLUSION: The chart review was valuable from several perspectives. Sedation management at Boston Children's Hospital included prolonged administration not only of opioids, but also benzodiazepines. Such treatment is considered the standard of care. Even otherwise healthy, full-term children that received such sedation for the management of an acute illness (e.g. pneumonia) were at risk for opioid and benzodiazepine dependence if they required intubation and sedation for longer than 4 days. However, the majority of full-term children at risk for potential long-term sequelae of prolonged sedation presented with other confounding factors (e.g. congenital diseases, surgeries, exposure to anesthetic agents). In summary, future research on potential long-term sequelae of prolonged opioid administration should include infants with complex medical diseases as they were exposed to such treatment the longest.