Propofol Treatment of Refractory Status Epilepticus: A Study of 31 Episodes

Rossetti, Andrea O.; Reichhart, Marc; Schaller, Marie-Denise; Despland, P. A.; Bogousslavsky, Julien

doi:10.1111/j.0013-9580.2004.01904.x

Cited by 167 publications

(119 citation statements)

References 65 publications

(90 reference statements)

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“…Propofol at subanesthetic concentrations exhibits anticonvulsant properties in refractory status epilepticus patients (Brown and Levin, 1998;Prasad et al, 2001;Rossetti et al, 2004). However, several studies have cautioned against the use of propofol as an anticonvulsant because of serious side effects (Claassen et al, 2002;Marik, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…general anesthetic; however, at subanesthetic doses, propofol is used clinically during refractory status epilepticus, a critical medical emergency with mortality rates as high as 76% in elderly patients (Prasad et al, 2001;Claassen et al, 2002;Marik and Varon, 2004;Rossetti et al, 2004). Propofol has been shown to inhibit sodium currents in mammalian cell lines expressing rat Na v 1.2 (Rehberg and Duch, 1999), to activate GABA currents in hippocampal neurons (Orser et al, 1994), and to inhibit L-type calcium currents in cortical neurons (Martella et al, 2005).…”

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confidence: 99%

“…However, its modulation of sodium currents (Martella et al, 2005) has been suggested to be important for its AED activity in both veratridine-induced seizures (Otoom and Hasan, 2004) and amygdala-kindled rats (Borowicz and Czuczwar, 2003). Although the mechanisms of action for propofol remain unclear, it continues to be an effective alternative to barbiturates and first line AEDs when treating refractory status epilepticus (Rossetti et al, 2004).…”

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confidence: 99%

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Hydroxyamide Analogs of Propofol Exhibit State-Dependent Block of Sodium Channels in Hippocampal Neurons: Implications for Anticonvulsant Activity

Jones¹,

Wang²,

Smith³

et al. 2006

J Pharmacol Exp Ther

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Although propofol is most commonly known for its general anesthetic properties, at subanesthetic doses, propofol has been effectively used to suppress seizures during refractory status epilepticus, a mechanism, in part, attributed to the inhibition of neuronal sodium channels. In this study, we have designed and synthesized two novel analogs of propofol, HS245[2-(3-ethyl-4-hydroxy-5-isopropyl-phenyl)-3,3,3-trifluoro-2-hydroxy-propionamide] and HS357 [2-hydroxy-8-(4-hydroxy-3,5-diisopropyl-phenyl)-2-trifluoromethyl-octanoic acid amide], and determined their effects on sodium currents recorded from cultured hippocampal neurons. HS357 had greater affinity for the inactivated state of the sodium channel than propofol and HS245 (0.22 versus 0.74 and 1.2 M, respectively) and exhibited the greatest ratio of affinity for the resting over the inactivated state. HS357 also demonstrated greater use-dependent block and delayed recovery from inactivation in comparison with propofol and HS245. Under currentclamp conditions, action potentials from hippocampal CA1 neurons in slices were evoked by current injection, or following perfusion with a zero Mg 2ϩ /7 mM K ϩ artificial cerebrospinal fluid solution. Propofol and HS357 reduced the number of current-induced action potentials; however, HS357 caused a greater reduction in the number of spontaneous action potentials. Consistent with these electrophysiology studies, propofol and HS357 protected mice against acute seizures in the 6-Hz (22-mA) partial psychomotor model. Efficacious doses of propofol were associated with an impairment of motor coordination as assessed in the rotorod toxicity assay. In contrast, HS357 demonstrated a 2-fold greater protective index than propofol. Thus, propofol analogs represent an important structural class from which not only effective, but also safer, anticonvulsants may be developed.Epilepsy is a neurological disorder that affects approximately 1 to 2% of the population. Treatment of epilepsy focuses on the suppression of seizures via the use of antiepileptic drugs (AEDs) (Browne and Holmes, 2001). First generation AEDs, such as phenytoin, carbamazepine, phenobarbital, and sodium valproate, along with second generation AEDs, such as topiramate, gabapentin, lamotrigine, and zonisamide, offer a wide selection of possible therapeutic treatments for suppression of seizures. Although the number of AEDs has increased, the percentage of patients who fail to be treated successfully remains constant at an alarming 30% (Loscher and Schmidt, 2002). Substantial problems exist with toxicity, resistance, and idiosyncratic reactions in a number of the currently used AEDs (Brodie, 2001), all of which likely contribute to their failure rate. In view of this failure rate, there remains a need for a better understanding of the mechanisms involved in suppression of epileptic seizures with minimal side effects.Voltage-gated sodium channels play an important role in determining neuronal excitability and, therefore, constitute a proven target for the suppressi...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hydroxyamide Analogs of Propofol Exhibit State-Dependent Block of Sodium Channels in Hippocampal Neurons: Implications for Anticonvulsant Activity

Jones¹,

Wang²,

Smith³

et al. 2006

J Pharmacol Exp Ther

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“…1,2 Despite the claims of proconvulsant activity of propofol, there is also evidence of its anticonvulsant action. [3][4][5] Severe neuroexcitatory symptoms are rare side effect of propofol which can occur during the induction, maintenance or emergence from anesthesia. 6 We present one such case of severe neuroexcitatory symptoms after induction with propofol which was managed with injection thiopentone and midazolam.…”

Section: Introductionmentioning

confidence: 99%

Propofol induced severe neuroexcitatory symptoms during emergency laparotomy

Banga¹,

Dadu²,

Sharma³

2013

Int J Basic Clin Pharmacol

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Propofol is a widely used intravenous agent for general anesthesia and sedation. Propofol is associated with a variety of neuroexcitatory events including: opisthotonus, muscle rigidity, myoclonus, and seizures collectively termed as seizure-like phenomenon (SLP). We report a rare case of propofol induced severe neuroexcitatory symptoms at the time of induction in a young male presenting for emergency laparotomy. He developed generalized tonic- clonic seizures which resulted in dislodgement of intravenous cannula. Immediately a new intravenous cannula was inserted with difficulty during convulsions and injection thiopentone 200 mg bolus was given. Convulsions subsided within a minute. Patient remained hemodynamically stable and surgery was uneventful. He developed emergence agitation which was treated with injection midazolam. Patient recovered with no neurologic sequelae. [Int J Basic Clin Pharmacol 2013; 2(5.000): 645-646

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“…A retrospective study of 33 children with refractory status epilepticus indicated that propofol was more effective than thiopental in terminating seizures [15] and studies in adults indicated that propofol terminated seizures in 67% of patients [16]. With this information in mind, we therefore aimed at investigating the effects of propofol on epileptiform activity and hippocampal morphology in rat models of seizure induced by hyperthermia and/or pilocarpine induced Status Epilepticus (SE), alone or in combination.…”

Section: Introductionmentioning

confidence: 99%

Effects of Propofol on Epileptiform Activity and Hippocampal Morphology in Febrile Convulsions and Pilocarpine Induced Seizures

Bican¹

2012

J Clinic Experiment Pathol

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Epidemiological and recent prospective analyses of long Febrile Seizures (FS) support the idea that such seizures can provoke Temporal Lobe Epilepsy (TLE) in some children. Because of the high prevalence of these seizures, if epilepsy was to arise as their direct consequence, this would constitute a significant clinical problem. Animal studies have revealed that exposure of hippocampal neurons to FS early in life, particularly prolonged or frequently repetitive FS, or together with brain malformation, may lead to sustained dysfunction of these cells including long-term memory impairment or epileptogenesis, in spite of the absence of neuronal damage. We established a hyperthermia model of febrile convulsions in young adult rats, and studied the effects of propofol treatment general anesthetic acting via GABA-A receptor on epileptiform activity and the morphological features of medial temporal lobe.We found statistically significant neuronal losses in the CA1, CA3 and dentate gyrus regions of hyperthermiaapplied rats as compared to the control rats. We also observed that propofol administration suppressed epileptic discharges in EEG and prevented clinical seizures behaviors. It took a median of 11 (range, 6-40) minutes for propofol to stop seizures. We conclude that prevention of epilepsy-related damage can be achieved via epileptogenesis-based clinical approaches, and that propofol is an effective agent in the hyperthermia-induced status epilepticus model.

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Propofol Treatment of Refractory Status Epilepticus: A Study of 31 Episodes

Cited by 167 publications

References 65 publications

Hydroxyamide Analogs of Propofol Exhibit State-Dependent Block of Sodium Channels in Hippocampal Neurons: Implications for Anticonvulsant Activity

Hydroxyamide Analogs of Propofol Exhibit State-Dependent Block of Sodium Channels in Hippocampal Neurons: Implications for Anticonvulsant Activity

Propofol induced severe neuroexcitatory symptoms during emergency laparotomy

Effects of Propofol on Epileptiform Activity and Hippocampal Morphology in Febrile Convulsions and Pilocarpine Induced Seizures

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