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

Abstract

N-H, HOLK IK. Pupillary diameter and ventilatory C 0 2 sensitivity after epidural morphine and buprenorphine in volunteers. Anesth Analg 1987;66:847-51.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 CO, 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 CO, 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 (Po,l), end-tidal CO, PET^^^), tidal volume (VT) and respiratory rate (RR). Slopes of the h e a r regression lines (P,,/CO,, vT/coz, VEICO,, and RRICO,) and the intercept values of the regression lines and PET^^^ = 7.2 kPa (Po 1:7.2, V~: 7 . 2 , V~: 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 VEICO~, V~: 7 . 2 , P,,:7.2, and V~: 7 . 2 . With epidural buprenorphine 0.15 mg a significant correlation was found between pupillary diameter and V~: 7 . 2 and Po ,:7.2. With epidural buprenorphine 0.3 mg the correlations between pupillary diameter and VE:Co,, k 7 . 2 , and P0.,: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.The dose-dependent pupillary constriction produced in humans by opioids is easily observed and quantified. The possibility of correlation between miosis and respiratory depression during analgesic therapy with opioids has not been evaluated. With the introduction of epidural opioid administration, the necessity to monitor respiration has been accentuated because of late respiratory depression. Several reports on life-threatening late respiratory depression (1,2) have restricted the use of epidural opioid administration in pain treatment.The aim of this study was to measure changes in pupillary diameter after epidural administration of

Epidural analgesia after scoliosis surgery: electrophysiologic and clinical assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine 0.2% plus morphine

“…Sucato et al [6] nevertheless reported a frequency of 7% respiratory depression after epidural administration of hydromorphone + bupivacaine 0.1%. Other authors found respiratory depression even with lower doses of morphine, based on depressed CO 2 sensitivity [27,28].…”

Dose-related Effects of Controlled Release Dihydrocodeine on Oro-Cecal Transit and Pupillary Light Reflex

“…Taking the pupillary light reflex as an index of central receptor occupancy and affinity, it was demonstrated that pupillary constriction was reduced 6.5 and 7.2 fold after 60 and 120 mg of DHC, respectively, when compared to placebo. Pupillary constriction is selective for opioid receptor binding as it had been described for morphine, buprenorphine [8] and tilidine/naloxone [51]. When compared to morphine, analgesic potency of DHC is 0.2−0.35 fold and that of tilidine is 0.05−0.07 fold [2].…”

“…Also, but to a much lesser degree, additionally peripheral receptor sites in the iris seem to be involved in the opioid-induced miotic reaction [32,33]. Since the degree of miosis is directly related to the degree of affinity and the degree of conformational change of the receptor [8] by the ligand, it was of interest to demonstrate whether the opioid, when given in two incremental amounts, induced dose-related effects on the sphincter pupillae. In order to measure the reaction profile of the pupil, an electronical pupillometer (Pupilscan  , Fairville Medical Optics, Amersham, England) was used.…”

“…We therefore set out to study the effect of this opioid in clinically relevant doses in human volunteers with respect to its constipating effect where no other drug was taken which otherwise might have masked the net effect of the analgesic on intestinal motility. But aside from quantifying the constipating effect of DHC, its miotic effect which is mediated centrally [7,8] was also evaluated. By using concentrations which are within the usual therapeutic range, and comparing the effects to placebo, a clinical situation was mimicked and the results could be taken as relevant.…”

Morphine‐Fluoxetine Interactions in Healthy Volunteers: Analgesia and Side Effects

“…The effect of drug administration on pupil size was measured using a modified Essilor pupilometer as previously described. 24…”