Article Text

Download PDFPDF

Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus
  1. S Knake,
  2. J Gruener,
  3. K Hattemer,
  4. K M Klein,
  5. S Bauer,
  6. W H Oertel,
  7. H M Hamer,
  8. F Rosenow
  1. Department of Neurology, Philipps-University, Marburg, Germany
  1. PD Dr S Knake, Epilepsy Centre Marburg, Department of Neurology, Philipps-University Marburg, Rudolf-Bultmann-Str 8, 35033 Marburg, Germany; knake{at}staff.uni-marburg.de

Abstract

In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.

Statistics from Altmetric.com

Status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality.13 Early and effective treatment is important to reduce complications. Usually, benzodiazepines and phenytoin are used as firstline treatment and are effective in about 60% of cases with generalised tonic–clonic SE.4 However, a sizeable portion of patients remain refractory to this initial treatment.

In May 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. To date, there are few reports on the oral use of LEV in refractory, non-convulsive SE and only a single case on administration of ivLEV in one patient with non-convulsive SE.58 We report our experience with the use of ivLEV in 16 patients with 18 episodes of focal convulsive and non-convulsive SE.

PATIENTS AND METHODS

We retrospectively identified patients with SE who were treated with ivLEV in our department from May 2006 to February 2007. SE was defined as at least 30 min of continuous seizure activity or a series of seizures without return to full consciousness between seizures lasting for ⩾30 min. Inhouse records and a hospital diagnosis database were used for identification. All patients treated with ivLEV were analysed regarding epilepsy syndrome, aetiology, treatment success and side effects.

RESULTS

Sixteen patients with 18 episodes of SE were treated with ivLEV. All patients were diagnosed with focal SE, either from complex partial SE associated with motor symptoms (12 episodes), complex partial SE without motor symptoms (“non-convulsive”) (two episodes) or from secondary generalised SE (four episodes) (table 1).

Table 1 Overview of all patients with status epilepticus treated with intravenous levetiracetam

SE was controlled in all patients by administration of a combination of different antiepileptic drugs. One patient died within 30 days after SE as a consequence of the underlying aetiology (intracerebral haemorrhage, patient No 12). All patients were treated in the intensive care unit to monitor cardiorespiratory function. During 17/18 (94%) episodes, an ictal EEG was recorded. One patient needed intubation and sedation (patient No 1). Seven patients had already been previously diagnosed with focal epilepsy, three of them were treated with oral LEV prior to admission. The combination of medication in the order given to the patient is noted in table 1. All patients received at least a benzodiazepine (lorazepam in 94%) before ivLEV was given. In 16 episodes, ivLEV was the last drug administered. In two patients (patient Nos 1 and 2), further treatment with other anticonvulsive drugs was necessary. The mean loading dose, usually given within 30 min, was 944 (SD 396) mg ivLEV, the mean maintenance dose over 24 h was 2166 (SD 1280) mg. IvLEV was always given through a peripheral line, using normal saline (14×) or glucose solution (4×) as solvent. All patients tolerated the levetiracetam injection without any severe adverse events: no respiratory failure, arrhythmia, seizure worsening or changes in blood count, liver enzymes or serum creatinine or skin reaction were noted. Two patients reported sedation after treatment. All patients were discharged on oral LEV with a mean oral dose of 2058 (SD 532) mg/day.

The main rationale for choosing ivLEV for treatment was failure of previously given benzodiazepine, liver failure, to avoid interaction with other medications such as cumarine, antibiotics or chemotherapy, or to avoid aggravation of cardiac arrhythmia under phenytoin treatment.

DISCUSSION

IvLEV appeared to be effective and was well tolerated. SE ceased after administration of a combination of anticonvulsive drugs in all patients and only two patients needed additional intravenous antiepileptic drugs after ivLEV was given.

Previous studies on the tolerability and safety of ivLEV have shown that ivLEV was well tolerated in healthy subjects, even when administered rapidly in high doses of up to 4000 mg/15 min and that it is bioequivalent to the oral formulation.9 However, ivLEV is not specifically approved for the therapy of SE. We used it in patients that could not receive oral medication and that had already received a benzodiazepine (lorazepam in 94%) as a standard therapy.4 A central venous line and intubation were avoided in 17/18 episodes (94%). IvLEV was selected as a treatment option in this highly selected group of patients with liver failure, raised liver enzymes, cardiac arrhythmia or multiple comedication because of its pharmacological profile, including lack of: (a) hepatic metabolism, (b) interaction with other medication and (c) relative paucity of cardiac side and peripheral venous effects compared with phenytoin.

Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.

REFERENCES

Footnotes

  • Competing interests: SK, HMH and FR have received speakers honoraria from UCB, the company that produces intravenous levetiracetam. FR, HMH, SK and WHO received research grants from UCB.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles