Epinephrine Reduces Systemic Absorption of Extradural Diacetylmorphine

The effect of epinephrine on the vascular absorption of morphine from the extradural space is uncertain; this study examined the effect of epinephrine on the related but more lipophilic opiate diacetylmorphine (diamorphine, heroin) because any effects of vasoconstriction on diacetylmorphine absorption should be maximally apparent. With this experiment, we hoped to resolve whether epinephrine does or does not alter vascular absorption of extradurally injected opiates. Thirty patients undergoing lumbar laminectomy were given either extradural diacetylmorphine, 5 mg, extradural diacetylmorphine, 5 mg with 1:200,000 epinephrine, or 1:200,000 epinephrine followed 5 min later by 5 mg extradural diacetylmorphine. Plasma morphine concentrations were measured by radioimmunoassay because of the rapid conversion of diacetylmorphine to morphine in plasma; repeated blood samples were obtained the first 30 min after injection into the epidural space. Significantly lower plasma morphine levels occurred between 3 and 20 min when epinephrine was added to diacetylmorphine. Peak plasma morphine levels (mean ± SEM) were 179 ± 37 nmol/L with diacetylmorphine alone, 87 ± 16 nmol/L with diacetylmorphine and epinephrine given together and 44 ± 11 nmoll L with epinephrine pretreatment, all significantly different from one another. The mean peak plasma morphine concentration was 8.7 ± 1.1 min for diacetylmorphine alone, but addition of epinephrine (together or sequentially) meant that 15 of 20 patients had no peak level before 120 min. Epinephrine reduced absorption of diacetylmorphine from the extradural site by at least 55% over the first 30 min. The incidence of patients with more than 9 hr analgesic duration was significantly (P = 0.033) greater in patients who had diacetylmorphine and epinephrine. The use of diacetylmorphine as a model for lipophilic opiates showed that addition of epinephrine not only reduced systemic absorption but also increased analgesic duration. The addition of epinephrine to similarly lipophilic opiates should have the same clinically desirable consequence.