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* From the Department of Anesthesiology, Chang Gung Memorial Hospital, Tao Yuan, Taiwan; and
the Department of Anesthesiology and Perioperative Medicine and OUTCOMES RESEARCHTM Institute, University of Louisville, Kentucky, USA.
Address correspondence to: Dr. Chun-Ming Lin, Department of Anesthesiology, Chang Gung Memorial Hospital, 5, Fu-Hsing St., Tao Yuan, Taiwan. E-mail: sam2498{at}adm.cgmh.org.tw. Reprints will not be available by the authors.
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Clinical features: Seizure activities as a complication of opioid administration have been reported in laboratory animals and humans. We report the case of a 30-yr-old primiparous woman with a history of epilepsy under carbamazepine treatment, who had epidural anesthesia for elective Cesarean section at 38 weeks gestation. Postoperatively, 1.5 mg of morphine were administered epidurally for pain control. Three hours later the patient suffered from clonic movements of the right arm without loss of consciousness. One day later, she again received 1 mg of epidural morphine twice at a 12-hr interval and similar seizure episodes recurred eight hours after each dose. A relation between the administration of morphine and seizure activity was suspected and the use of opioids for pain control was stopped. The patient was discharged on the fifth postoperative day and, more than one year after the last episode, she remains free of any seizure activity.
Conclusion: Our report indicates that even a remote history of epilepsy carries a pro-convulsant potential in the peripartum period, even following the administration of small doses of epidural morphine.
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Epidural anesthesia was accomplished with an 18-G Tuohy needle via the L4–5 intervertebral space, using a midline, loss-of-resistance approach with 2 mL air. A 3-mL test dose of lidocaine was given before the lidocaine bolus and a total bolus of 20 mL 2% lidocaine with 1:200,000 epinephrine and 50 µg fentanyl was administered through the needle and an epidural catheter was placed atraumatically. The dermatomal level achieved was T6 20 min after induction of epidural anesthesia. The operation was completed without any complications and the newborn was extracted in good health. The patient was comfortable upon arrival in the postanesthesia care unit and 1.5 mg of morphine sulfate diluted in 10 mL normal saline were administered epidurally for pain control.
After resolution of the sensory block to L1 level, the patient was discharged to the ward. Two hours later and three hours after the morphine administration, she suffered from involuntary movements of the right arm without loss of consciousness. At the beginning, we did not know the reason why she had such abnormal movements. We immediately checked electrolytes, blood glucose, magnesium, and calcium levels which were all within their normal ranges. The patient described her symptoms as being similar to those she had experienced during the seizure attacks at the age of 17. Since she had used carbamazepine to achieve succesful control her epilepsy, we gave her 200 mg of carbamazepine po. The seizure activity lasted for approximately one hour with several brief seizure-free intervals, and it gradually resolved after the 200 mg dose of carbamazepine. One day later, she again received epidurally 1 mg of morphine (2nd and 3rd doses) within a 12-hr interval, and a similar seizure episode occurred eight hours after each dose. Because the seizures occurred at the same relative time after morphine injection, a relation between the administration of morphine and the seizure activity was suspected and the use of opioids for pain control was stopped. No more seizure activity occurred after disconnection of the intermittent administration of epidural morphine. The normal carbamazepine regimen of 200 mg po bid was continued throughout the perioperative period. The patient was discharged on the fifth postoperative day. After discharge, an EEG evaluation showed no change from the previous examination. The patient was followed by the neurology services and she remained free of any seizure over a one-year follow-up period.
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Animal models8,9 show that opioid-induced seizures may involve multiple opioid receptor-mediated mechanisms, while a stereospecific kappa-receptor mechanism is directly implicated.8 Nonetheless, evidence that naloxone was unable to completely reverse opioid-induced myoclonous2 disputes opioid receptors as mediators of neuroexcitation. Indirect opioid-induced effects on different excitatory and inhibitory systems at various central nervous system levels may explain this discrepancy.2,10 Thus, N-methyl-D-aspartate mediated excitation,11 as well as gamma-aminobutyric acid (GABA)-mediated inhibition12 have been also a factor in opioid-induced neuroexcitation, while morphine-induced glycine and GABA antagonism were associated with paroxysmal depolarizations of spinal cord neurons in vitro.10
Active metabolites,13 as well as preservatives3 of different opioid agents have been implicated in causing generalized seizures in humans after systemic administration of high dose opioids, although the parent compounds have their own neuroexcitatory potential.
Neuroexcitation usually occurs after large doses of intrathecal,6 epidural14 or iv4 opioids. None of the patients described in the literature had a history of seizure disorder and myoclonic activity was never observed with an epidural dose of morphine lower than 12 mg·hr–1.4 Nonetheless, tonic-clonic activity has been reported in an epileptic woman who had elective Cesarean section, six hours after the epidural administration of 3 mg of morphine.7
Human studies have shown that central effects of epidurally administered morphine, like delayed ventilatory depression14 and nausea,15 are mostly due to rostral spread of the drug through the cerebrospinal fluid and have an onset time between four and nine hours. In our case, myoclonic activity occurred three and eight hours after epidural administration of 1.5 and 1 mg of morphine, respectively. Thus, the time course of the seizure effect supports a central mechanism of action through the cephalad spread of morphine.
Despite the fact that systemic administration of low doses of morphine has a rather anticonvulsant effect, neuroexcitation can also occur in a pro-convulsant environment.16,17 The endogenous opioid system has been implicated in exerting a continuous anti-convulsant action.16,18 A step rise in plasma endogenous opioids during late pregnancy and parturition19 might be responsible for decreased seizure susceptibility.16 However, the acute resolution of this situation in the post-partum period could also have a pro-convulsant "opioid withdrawal" effect,20 especially on the grounds of seizure disorder.
Our patient, and that described by Borgeat et al.,7 share a history of epilepsy and recent pregnancy. An epileptic pathology, even with the form of a dormant focus, might have interacted with the condition of pregnancy to produce a pro-convulsant environment for the seizure-inducing effect of small doses of morphine. The time course and the pattern of convulsive activity, as well as the fact that it promptly resolved with carbamazepine support the case of seizure recurrence due to epidural morphine administration.
Our report indicates that a remote history of epilepsy carries a pro-convulsant potential in the peri-partum period, even following the administration of small doses of epidural morphine.
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2 Shohami E, Evron S. Intrathecal morphine induces myoclonic seizures in the rat. Acta Pharmacol Toxicol (Copenh) 1985; 56: 50–4.[Medline]
3 Gregory RE, Grossman S, Sheidler VR. Grand mal seizures associated with high-dose intravenous morphine infusions: incidence and possible etiology. Pain 1992; 51: 255–8.[Medline]
4 Rozan JP, Kahn CH, Warfield CA. Epidural and intravenous opioid-induced neuroexcitation. Anesthesiology 1995; 83: 860–3.[Medline]
5 Young GB, da Silva OP. Effects of morphine on the electroencephalograms of neonates: a prospective, observational study. Clin Neurophysiol 2000; 111: 1955–60.[Medline]
6 De Conno F, Caraceni A, Martini C, Spoldi E, Salvetti M, Ventafridda V. Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine. Pain 1991; 47: 337–9.[Medline]
7 Borgeat A, Biollaz J, Depierraz B, Neff R. Grand mal seizure after extradural morphine analgesia. Br J Anaesth 1988; 60: 733–5.
8 Bansinath M, Ramabadran K, Turndorf H, Shukla VK. Intracerebroventricular administration of kappa-agonists induces convulsions in mice. Brain Res Bull 1991; 27: 75–9.[Medline]
9 Crain SM, Shen KF. Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons. Trends Pharmacol Sci 1990; 11: 77–81.[Medline]
10 Werz MA, Macdonald RL. Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action. Brain Res 1982; 236: 107–19.[Medline]
11 Chen L, Huang LY. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid. Neuron 1991; 7: 319–26.[Medline]
12 Foote F, Gale K. Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat. Eur J Pharmacol 1983; 95: 259–64.[Medline]
13 Yaksh TL, Harty GJ. Pharmacology of the allodynia in rats evoked by high dose intrathecal morphine. J Pharmacol Exp Ther 1988; 244: 501–7.
14 Knill RL, Clement JL, Thompson WR. Epidural morphine causes delayed and prolonged ventilatory depression. Can Anaesth Soc J 1981; 28: 537–43.[Medline]
15 Bromage PR, Camporesi EM, Durant PA, Nielsen CH. Nonrespiratory side effects of epidural morphine. Anesth Analg 1982; 61: 490–5.
16 Frenk H. Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems. Brain Res 1983; 287: 197–210.[Medline]
17 Bertran F, Denise P, Letellier P. Nonconvulsive status epilepticus: the role of morphine and its antagonist. Neurophysiol Clin 2000; 30: 109–12.[Medline]
18 Frost JJ, Mayberg HS, Fisher RS, et al. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988; 23: 231–7.[Medline]
19 Abboud TK. Maternal and fetal beta endorphin: effects of pregnancy and labour. Arch Dis Child 1988; 63: 707–9.[Medline]
20 Smolen A, Smolen TN, van de Kamp JL. The effect of naloxone administration on pregnancy-associated seizures. Life Sci 1986; 38: 1899–905.[Medline]
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