[Withdrawal syndrome during epidural administration of morphine after stopping treatment with clonidine]

A 70 year old hypertensive patient who had undergone a gastrectomy experienced withdrawal symptoms 10 h after a second epidural injection of morphine (150 micrograms X kg-1) for postoperative analgesia. A clonidine treatment had been stopped 129 h earlier. These symptoms disappeared shortly after a third epidural injection of morphine. Clonidine was then reintroduced. The later progressive interruption of epidural morphine analgesia did not introduce any further symptoms of withdrawal. Since physical dependence on a drug is related to repeated and prolonged administration of that drug, opiate withdrawal symptoms were highly unlikely after epidural morphine used to relieve immediate postoperative pain. Abrupt discontinuation of a long-term treatment by clonidine may produce a withdrawal syndrome, but clinical and biological signs usually occur earlier than noted in this case. Recent experimental and clinical data has provided support for the existence of a complex presynaptic regulation of noradrenergic transmission in the central nervous system, both alpha 2 and opiate receptors being implicated. The activation of such presynaptic receptors inhibits further transmitter release. Suddenly stopping the chronic administration of alpha 2 or opiate agonists was responsible for a rebound excitation of these noradrenergic neurons, inducing a withdrawal syndrome. The related withdrawal symptoms may have resulted from an interaction between the discontinuation of clonidine and the decrease in morphine activity. Practitioners should be warned of this possible side-effects.