Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation

Highlights

• Treatment of refractory convulsive status epilepticus in children

• Efficacy and safety of intravenous ketamine

• Ketamine as a practical alternative to conventional anesthetics

• Ketamine use avoids the pitfalls and dangers of endotracheal intubation.

Abstract

Objective

The purpose of this study was to report on the efficacy and safety of intravenous ketamine (KE) in refractory convulsive status epilepticus (RCSE) in children and highlight its advantages with particular reference to avoiding endotracheal intubation.

Methods

Since November 2009, we have used a protocol to treat RCSE including intravenous KE in all patients referred to the Neurology Unit of the Meyer Children's Hospital.

Results

From November 2009 to February 2015, 13 children (7 females; age: 2 months–11 years and 5 months) received KE. Eight patients were treated once, two were treated twice, and the remaining three were treated 3 times during different RCSE episodes, for a total of 19 treatments. Most of the RCSE episodes were generalized (14/19). A malformation of cortical development was the most frequent etiology (4/13 children). Ketamine was administered from a minimum of 22 h to a maximum of 17 days, at doses ranging from 7 to 60 mcg/kg/min, obtaining a resolution of the RCSE in 14/19 episodes. Five patients received KE in lieu of conventional anesthetics, thus, avoiding endotracheal intubation. Ketamine was effective in 4 of them. Suppression-burst pattern was observed after the initial bolus of 3 mg/kg in the majority of the responder RCSE episodes (10/14).

Conclusions

Ketamine is effective in treating RCSE and represents a practical alternative to conventional anesthetics for the treatment of RCSE. Its use avoids the pitfalls and dangers of endotracheal intubation, which is known to worsen RCSE prognosis.

This article is part of a Special Issue entitled “Status Epilepticus”.

Introduction

Status epilepticus (SE) is a life-threatening emergency traditionally defined as ‘an acute epileptic condition characterized by continuous seizures for at least 30 min, or by 30 min of intermittent seizures without full recovery of consciousness between seizures’ [1]. Convulsive SE is the most common and harmful form. Based on improved understanding of pathophysiology, there is now consensus that any seizure lasting longer than 5 min should be treated as SE [2].

Status epilepticus lasting longer than 120 min and not responding to first-line (benzodiazepines) and second-line (midazolam at a high dose, phenytoin, and phenobarbital) antiepileptic drugs (AEDs) is defined as “refractory” and requires Intensive Care Unit (ICU) treatment [3]. The term “super-refractory” defines SE that continues, or recurs, for 24 h or longer or recurs after withdrawal of anestheticpropofol infusion syndrome therapy [3]. Even with current best practice, neurological sequelae occur in > 50% of children with refractory convulsive status epilepticus (RCSE) [4], [5]. The mortality rate of RCSE ranges between 2.7 and 5.2% and increases up to 5–8% when only data from ICU are taken into account [4], [5]. Refractory convulsive status epilepticus is generally treated with coma induction with high-dose midazolam or thiopental or propofol [6], [7], [8]. However, the high risk of “propofol infusion syndrome” often limits its use in children [9].

Increasing evidence indicates that ketamine (KE), a potent N-methyl-d-aspartate antagonist, may be effective in treating RCSE [10]. Compared to conventional anesthetics, KE has neither cardiac nor respiratory depressant properties. Its administration, therefore, does not imply emergent endotracheal intubation, a prognostic factor of increased morbidity and mortality risk in critically ill adults and children [11], [12], [13].

Here, we report our experience using KE in a treatment protocol for children with RCSE, extending our initial series of patients [14] and including those children in whom KE was administered prior to conventional anesthetics.