Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity

Ubogu, Eroboghene E.; Sagar, Stephen M.; Lerner, Alan J.; Maddux, Brian N.; Suárez, José I.; Werz, Mary Ann

doi:10.1016/s1525-5050(02)00643-1

Cited by 96 publications

(59 citation statements)

References 13 publications

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“…The addition of ketamine infusion terminated SE within days. Ketamine is generally well tolerated, although a 44-year-old man with RSE due to neurosyphilis developed diffuse cerebellar and worsened cerebral atrophy 3 months after receiving ketamine, consistent with animal models of NMDA antagonist-mediated neurotoxicity [61].…”

Section: Miscellaneous Agents and Approachessupporting

confidence: 59%

Treatment of Refractory Status Epilepticus in Childhood

Schreiber

Gaillard

2010

Curr Neurol Neurosci Rep

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Refractory status epilepticus (RSE) is characterized by a prolonged seizure that persists despite adequate initial management. RSE accounts for almost one quarter of all status epilepticus and carries significant risk for morbidity and mortality. Treatment varies widely between institutions regarding medication choice, dose, and monitoring. Several agents including nonanesthetic antiepileptic drugs (AEDs), anesthetic AEDs, enteral AEDs, and other therapies have been used in RSE. We review the current treatment strategies for RSE, focusing on patient selection, monitoring, optimal dosing and administration of medications, efficacy, adverse effects, and treatment duration.

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Section: Miscellaneous Agents and Approachessupporting

confidence: 59%

Treatment of Refractory Status Epilepticus in Childhood

Schreiber

Gaillard

2010

Curr Neurol Neurosci Rep

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“…Recently a commonly used anesthetic ketamine, which blocks NMDA receptors, was demonstrated to control prolonged SE in the CHS model of SE (Borris et al, 2000). There are some recent case reports of treatment of human SE with ketamine (Mewasingh et al, 2003;Ubogu et al, 2003). However, a prospective, randomized, blinded and controlled clinical trial is necessary determine the efficacy of ketamine in the treatment of refractory SE.…”

Section: Discussionmentioning

confidence: 99%

A comparison of three NMDA receptor antagonists in the treatment of prolonged status epilepticus

2004

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Three different classes of NMDA receptor antagonists were compared for their effectiveness in terminating prolonged status epilepticus (SE), induced by continuous hippocampal stimulation. Animals were treated after 150 min of SE by intraperitoneal administration of increasing doses of 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), MK-801 (dizocilpine), ifenprodil, or saline. EEG recordings were used to determine seizure termination. The first experiment (n = 57 animals) determined the most effective anticonvulsant dose of each agent by determining its ability to terminate SE within the next 300 min. Five control rats treated with normal saline after 150 min of SE continued to exhibit continuous seizures for the next 300 min. All drugs were administered after 150 min of SE. CPP terminated seizures with an ED 50 of 6.4 mg/kg; the maximal effective dose was 15 mg/kg. MK-801 has an ED 50 of 1.4 mg/kg; the maximal effective dose was 2 mg/kg. Ifenprodil was maximally effective at 30 mg/kg. However, an ED 50 could not be calculated. In a subsequent experiment, the NMDA antagonists were compared for their ability to terminate prolonged SE within 60 min of their administration at the most effective dose. MK-801 (2.0 mg/kg) terminated SE in 6 of 10 animals within 60 min, CPP (15 mg/kg) terminated it in 1 of 9 animals; ifenprodil (30 mg/kg) did not terminate it in any of 9 animals treated. In the 300 min following administration, CPP (6/9) and MK-801 (6/10) were equally efficacious in terminating SE but ifenprodil (2/7) was less effective (P = 0.065, chi-square test). The results indicate that the non-competitive NMDA receptor antagonist MK-801 was superior to the competitive antagonist CPP and the pH-sensitive site antagonist ifenprodil, in terminating prolonged experimental SE.

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“…Prolonged intravenous ketamine administration in patients with refractory status epilepticus produced acute and profound cerebellar deficits and worsened cerebral function [26], raising the possibility of ketamine-induced neurotoxicity. A previous study of 20 participants revealed that ketamine abusers exhibit a persistent deficit in source memory, suggesting that repeated ketamine use chronically impairs episodic memory [27].…”

Section: Neurotoxic Effects Of Ketaminementioning

confidence: 99%

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive Nmethyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fastacting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related sideeffects. Future treatment strategies should consider using Rketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

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Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity

Cited by 96 publications

References 13 publications

Treatment of Refractory Status Epilepticus in Childhood

Treatment of Refractory Status Epilepticus in Childhood

A comparison of three NMDA receptor antagonists in the treatment of prolonged status epilepticus

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

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