Hagen N, Swanson R. Strychnine-like multifocal myoclonus and seizures in extremely high-dose opioid administration: treatment strategies. J Pain Symptom Manage 1997;14:51–58.
Shohami E, Evron S, Weinstock M, et al. A new animal model for action myoclonus. Adv Neurol 1986;43:545–552.
Kona-Boun JJ, Pibarot P, Quesnel A. Myoclonus and urinary retention following subarachnoid morphine injection in a dog. Vet Anaesth Analg 2003;30:257–264.
Cannesson M, Nargues N, Bryssine B, et al. Intrathecal morphine overdose during combined spinal-epidural block for caesarean delivery. Br J Anaesth 2002;89:925–927.
Andersen G, Christrup L, Sjogren P. Relationships among morphine metabolism, pain and side effects during long-term treatment: an update. J Pain Symptom Manage 2003;25:74–91.
De Conno F, Caraceni A, Martini C, et al. Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine. Pain 1991;47:337–339.
Werz MA, MacDonald RL. Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action. Brain Res 1982;236:107–119.
Yilmaz A, Sogut A, Kilinc M, et al. Successful treatment of intrathecal morphine overdose. Neurol India 2003;51:410–411.
Okura T, Saito M, Nakanishi M, et al. Different distribution of morphine and morphine-6 B-glucuronide after intracerebroventricular injection in rats. Br J Pharmacol 2003;140:211–217.
Sandouk P, Serrie A, Scherrmann JM, et al. Presence of morphine metabolites in human cerebrospinal fluid after intracerebroventricular administration of morphine. Eur J Drug Metab Pharmacokinet 1991;Spec No 3:166–171.
Hemstapat K, Smith SA, Monteith GR, et al. The neuroexcitatory morphine metabolite, morphine-3-glucuronide (M3G), is not neurotoxic in primary cultures of either hippocampal or cerebellar granule neurones. Pharmacol Toxicol 2003;93:197–200.
Pelligrino DA, Riegler FX, Albrecht RF. Ventilatory effects of fourth cerebroventricular infusions of morphine-6- or morphine-3-glucuronide in the awake dog. Anesthesiology 1989;71:936–940.
Sjogren P, Thunedborg LP, Christrup L, et al. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration? Six case histories. Acta Anaesthesiol Scand 1998;42:1070–1075.
Adler MW, Geller EB, Rosow CE, et al. The opioid system and temperature regulation. Ann Rev Pharmacol Toxicol 1988;28:429–449.
Stoelting R. Opioid agonists and antagonists. In:Stoelting R, ed.Pharmacology and physiology in anesthetic practice. 3rd ed.Baltimore: Lippincott Williams & Wilkins, 1999;1999
Hennis PJ, Fahey MR, Canfell PC, et al. Pharmacology of laudanosine in dogs. Anesthesiology 1986;65:56–60.
Groudine SB, Cresanti-Daknis C, Lumb PD. Successful treatment of a massive intrathecal morphine overdose. Anesthesiology 1995;82:292–295.
Sauter K, Kaufman HH, Bloomfield SM, et al. Treatment of high-dose intrathecal morphine overdose. J Neurosurg 1994;81:143–146.
Advertisement
Case Description—A healthy 6-year-old 28.5-kg (62.7-lb) spayed female Boxer undergoing surgical repair of a ruptured cranial cruciate ligament was inadvertently administered an overdose of morphine (1.3 mg/kg [0.59 mg/lb]) via subarachnoid injection.
Clinical Findings—50 minutes after administration of the overdose, mild multifocal myoclonic contractions became apparent at the level of the tail; the contractions migrated cranially and progressively increased in intensity and frequency during completion of the surgery.
Treatment and Outcome—The myoclonic contractions were refractory to treatment with midazolam, naloxone, phenobarbital, and pentobarbital; only atracurium (0.1 mg/kg [0.045 mg/lb], IV) was effective in controlling the movements. The dog developed hypertension, dysphoria, hyperthermia, and hypercapnia. The dog remained anesthetized and ventilated mechanically; treatments included continuous rate IV infusions of propofol (1 mg/kg/h [0.45 mg/lb/h]), diazepam (0.25 mg/kg/h [0.11 mg/lb/h]), atracurium (0.1 to 0.3 mg/kg/h [0.045 to 0.14 mg/lb/h]), and naloxone (0.02 mg/kg/h [0.009 mg/lb/h]). Twenty-two hours after the overdose, the myoclonus was no longer present, and the dog was able to ventilate without mechanical assistance. The dog remained sedated until 60 hours after the overdose, at which time its mentation improved, including recognition of caregivers and response to voice commands. No neurologic abnormalities were detectable at discharge (approx 68 hours after the overdose) or at a recheck evaluation 1 week later.
Clinical Relevance—Although intrathecal administration of an overdose of morphine can be associated with major and potentially fatal complications, it is possible that affected dogs can completely recover with immediate treatment and extensive supportive care.