Infant pupillary response to methadone administration during treatment for neonatal abstinence syndrome: A feasibility study

Abstract Background Pupil diameter is a frequently assessed objective index of the pharmacodynamic effects of opioids in adults, but to our knowledge has never been examined in infants. Such a measure could improve assessment and treatment of neonates exposed to opioids in utero. The present study examined changes in pupil diameter after opioid administration in opioid-exposed infants who required pharmacological treatment for neonatal abstinence syndrome (NAS) to test the feasibility of using pupil diameter as a measure of opioid effects in these infants. Methods Ten infants (2–7 days old) receiving methadone (0.4–0.5 mg every 12 h) for the treatment of NAS participated. A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0–1, 2–4, 5–7, and 8–10 h after dosing. The diameters of the pupil and iris were measured and relative pupil diameter (pupil diameter expressed as a percentage of iris diameter) was analyzed. Results Mean (±SE) relative pupil diameter decreased significantly after dosing from 41 ± 2% to 29 ± 2%. After dosing, a significant increasing linear trend was observed over time, with values of 29 ± 2%, 33 ± 3%, 38 ± 3%, and 41 ± 3% at 0–1, 2–4, 5–7, and 8–10 h after dosing. Conclusions Infant pupils respond to opioid administration in the same sensitive, orderly manner as is commonly observed in adults. Pupil diameter appears to be an objective, sensitive measure of neonatal response to opioids that may be a useful complement to, or perhaps at times a replacement for, observer-rated scale scores.