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Pupillary Diameter and Ventilatory CO₂ Sensitivity after Epidural Morphine and Buprenorphine in Volunteers

Received from the Department of Anesthesia and Intensive Care, Herlev Hospital, University of Copenhagen, Denmark.

Abstract

The aim of this study was to correlate pupillary diameter with respiratory depression for 20 hr after epidural administration of morphine or buprenorphine. Pupillary diameter and the ventilatory sensitivity to CO₂ were measured in six healthy volunteers at various times (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 20 hr) in two sessions, separated by at least 1 week, at which either epidural morphine, 4 mg, or epidural buprenorphine, 0.15 mg, was administered randomly in a double-blind manner. Three of the six volunteers received 0.3 mg buprenorphine epidurally in a third session. Pupillary diameter was measured with a modified Essilor pupillometer. The ventilatory CO₂ sensitivity was measured by a modified Read rebreathing technique. The ventilatory parameters measured were mouth occlusion pressure during the first 0.1 sec of inspiration (P_0.1), end-tidal CO₂ (PET_CO²), tidal volume (VT) and respiratory rate (RR). Slopes of the linear regression lines (P_0.1/CO₂, VT/CO₂, VE/CO₂, and RR/CO₂) and the intercept values of the regression lines and PET_CO² = 7.2 kPa (P_0.1: 7.2, VT.7.2, VE: 7.2, and RR: 7.2) were calculated. Pupillary diameter after epidural morphine was smallest at the second hour and had returned to normal after eight hours. After epidural buprenorphine there were two periods of miosis, one at 1–3 hr, the other at 10 hr. With epidural morphine, a statistically significant correlation (P < 0.05) was found between pupillary diameter and VE/CO₂, VE: 7.2, P_0.1: 7.2, and VT: 7.2. With epidural buprenorphine 0.15 mg a significant correlation was found between pupillary diameter and VE: 7.2 and P_0.1: 7.2. With epidural buprenorphine 0.3 mg the correlations between pupillary diameter and VE:CO₂, VE: 7.2, and P_0.1: 7.2 were significant. The results indicate that the neural control of respiration and of pupillary diameter is influenced synchronously by epidural opioids and that the pupillary response may serve as an indicator of respiratory depression.

Key Words: ANALGESICS—morphine, buprenorphine • ANESTHETIC TECHNIQUES, epidural-narcotics • EYE—pupil

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999