Correspondence

Seizure associated with low-dose naloxone

There has been much debate regarding the potential influence of stress on epilepsy. Many studies have reported that stress can affect seizure susceptibility through eliciting either proconvulsant or anticonvulsant effects within the nervous system. In this study, we investigated the potential anticonvulsant effect of a 10-min swim stress on convulsions induced by a single systemic injection of lithium chloride followed 4 h later with pilocarpine. Rats pretreated with lithium chloride and exposed to a 10-min swim stressor prior to pilocarpine injection displayed a significant delay to seizure onset compared to unstressed rats or rats exposed to swim stress 10 min after lithium chloride, 2 h after lithium chloride, or immediately after pilocarpine injection. We then determined whether administration of a glucocorticoid antagonist (mifepristone; 10 or 50 mg/kg), an α₂-adrenergic antagonist (yohimbine; 2 or 5 mg/kg), or a nonspecific opioid blocker (naloxone; 0.2 or 1 mg/kg) could prevent the anticonvulsant effect of swim stress. Only the high dose of yohimbine was capable of inhibiting the anticonvulsant effect of swim stress on lithium–pilocarpine seizures. Our findings highlight the importance of an endogenous noradrenergic-dependent anticonvulsant system in mediating the effects of swim stress on seizures. Further studies exploring the benefits of treatments with noradrenergic acting drugs in epilepsy is well warranted.

Intensivists are confronted with poisoned patients on a routine basis, with clinical scenarios ranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, or accidental exposure. In addition, drug toxicity can also manifest in hospitalized patients from inappropriate dosing and drug interactions. In this review article, we describe the epidemiology of poisoning in the United States, review physical examination findings and laboratory data that may aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) or specific poisoning, and describe a rational and systematic approach to the poisoned patient. It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. However, the most current recommendations by the American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists will be reviewed. Specific poisonings will be reviewed in the second section of these review articles.

A77-year-old woman with no history of epilepsy presented a probable nonconvulsive status epilepticus while receiving continuous intravenous morphine for back pain relating to vertebral metastasis of a malignant lymphoma. A generalized tonic-clonic seizure occurred a few minutes after injection of the morphine antagonist naloxone. No cerebral lesion was detected. This observation supports the notion of a possible pro-epileptogenic effect of opioid substances in association with metabolic and other toxic factors. Various hypotheses as to the complex actions of morphine and its antagonist in epileptogenesis are discussed.

État de mal épileptique non convulsif : rôle de la morphine et de son antagoniste.

Une patiente de 77 ans sans antécédents épileptiques ni lésion intracérébrale présenta un probable état de mal épileptique non convulsif au cours d'un traitement par perfusion continue de morphine, administré pour des douleurs vertébrales métastatiques d'un lymphome malin. Quelques minutes après l'injection de l'antagoniste de la morphine (la naloxone) survint une crise généralisée tonicoclonique. Cette observation fait discuter les effets complexes de la morphine et de son antagoniste sur l'épileptogenèse et le caractère potentiellement épileptogène des substances opioïdes en association avec des anomalies métaboliques ou d'autres facteurs toxiques.

Studies were made on the role of μ₁-receptors on electrically induced convulsions in mice. A relatively selective μ₁-agonist, DAGO ([$\text{d}\text{-Ala}{}^2\text{-N-}\text{methyl-Phe}{}^4\text{-}\text{Gly-ol]-enkephalin}$) decreased the durations of tonic and clonic convulsions in C57BL/6 mice, but not in opioid μ-deficient CXBK mice, indicating that the activation of μ₁-rreceptors had an anticonvulsive effect on these convulsions in mice. The selective μ₁-antagonists naloxonazine and naltrexonazine promoted the clonic phase of electrically induced convulsion in C57BL/6 mice. Moreover, the duration of the clonic phase was longer in μ-deficient CXBK mice than in C57BL/6 mice. These data for CXBK mice confirmed, at least some proconvulsant effects of μ₁-antagonists in C57BL/6 mice. Thus, blockade of μ₁-receptors has a proconvulsant effect, and μ₁-receptors have at least some protective role against electrically induced convulsions.