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 8-10h 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 8-10h 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.

Conflict of interest statement

Conflict of Interest

The authors have no conflict of interest to declare.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Mean (± SE) relative pupil diameter for 10 neonates exposed to opioids in utero who required pharmacological treatment for NAS postnatally. Neonates were stabilized on methadone (0.4–0.5 mg every 12 hours) and relative pupil diameter measurements were calculated from pictures taken just prior to dosing (Pre) and 0–1, 2–4, 5–7, and 8–10 hours after dosing. * Indicates the 0–1 time point is significantly different from the Pre time point (p <.001). ** Indicates a significant linear time trend across the 4 post-dosing time points (p <.001).