Biphasic Depression of Ventilatory Responses to CO2 Following Epidural Morphine

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Abstract
The duration of effects of lumbar epidural morphine (0.1 mg/kg) on control of ventilation (CO2 response), pain relief, segmental analgesia (loss of pain in response to a painful stimulus) and loss of temperature discrimination, and plasma morphine concentrations in 7 patients with chronic low back pain at 1, 2, 4, 8, 12 and 24 h postinjection were studied. Maximal depression of the slope of the minute ventilation response to CO2 occurred at 1-2 h postinjection and expressed as percent reduction from control (measured day before epidural morphine injection) (.+-. SEM [standard error of the mean]) was -35 .+-. 7 (P < 0.01); the tidal volume and average inspiratory flow responses were displaced to the right, -29 .+-. 3 (P < 0.01) and -37 .+-. 4% (P < 0.001), respectively. At 8 h postinjection, the minute ventilation and average inspiratory flow were displaced to the right, and as % reduction from control were -52 .+-. 19 (P < 0.05) and -36 .+-. 13 (P < 0.05), respectively. At 4, 12 and 24 h postinjection, the CO2 responses were not significantly different from control. The segmental level of analgesia and loss of temperature discrimination, which was highest at 8 h postinjection, rose in different patients to high thoracic, cervical or trigeminal nerve segments. Plasma concentrations of unconjugated morphine were highest at 0.25 h postinjection and declined polyexponentially. Apparently, epidural morphine causes biphasic depression of control of ventilation by 2 mechanisms: an early depression resulting from absorption into the epidural veins and circulatory redistribution to the brain, and a late phase associated with a rise in the segmental level of analgesia which is the result of cephalad movement of morphine in the CSF. The rise in segmental analgesia and loss of temperature discrimination therefore may be an essential clinical sign of impending late depression of control of ventilation.