Anesthetic drugs for status epilepticus linked with death, infection risk

WASHINGTON – The use of anesthetic drugs for the treatment of refractory status epilepticus was associated with a high risk of infection and death among patients treated over a 6-year period at a tertiary academic medical center.

Although prospective, randomized controlled trials are needed to confirm the findings of this retrospective cohort study, the data should heighten awareness of the potential adverse effects of anesthetic drugs, Dr. Peter W. Kaplan said at the annual meeting of the American Epilepsy Society.

Of 171 adults who presented to University Hospital Basel, Switzerland, with status epilepticus between January 2005 and January 2011, 63 (37%) were treated with intravenous anesthetic drugs (IVADs), including thiopental, midazolam, propofol, and/or high-dose phenobarbital, and 18% of the patients died. After adjustment for status epilepticus duration and severity (based on status epilepticus severity score) and for critical medical conditions, those treated with IVADs had a significantly increased risk of death, compared with those who did not receive IVADs (relative risk = 3.16), said Dr. Kaplan of Johns Hopkins University, Baltimore.

Those who received IVADs also had a significantly higher rate of infectious complications (43% vs. 11%). The infections were diagnosed during the course of treatment, and 25 of 27 infections were respiratory infections. The remaining two cases were urinary tract infections.

No significant difference was seen between the groups with respect to seizure control, but ICU stay, a secondary outcome of the study, was significantly longer in those who received IVADs (13.5 days vs. 4.5 days), he said.

Severe hypotension also occurred more often in the patients who received IVADs.

Patients included in the study were adults with a mean age of 64 years. Those who received continuously administered IVADs were refractory to first- and second-line antiepileptic drugs and were treated according to a standard protocol; 29 received midazolam only, 22 received midazolam followed by propofol, and 12 received barbiturates after midazolam. The use of nonanesthetic antiepileptic drugs was similar in the two groups.

The findings, published online Dec. 6 in Neurology ahead of their presentation at the AES meeting, are important because data regarding the risks and benefits of anesthetic drugs for status epilepticus are lacking (Neurology 2013 Dec. 6 [doi:10.1212/WNL.0000000000000009]).

In the Neurology report, principal investigator Dr. Raoul Sutter of University Hospital Basel and his colleagues – including Dr. Kaplan – noted that "most opinion leaders recommend IVADs ... for refractory status epilepticus to induce total seizure suppression, an EEG burst-suppression pattern, or an isoelectric EEG," but explained that "the Neurocritical Care Society outlines the role of IVADs, but notes the lack of supporting data, while the European Federation of Neurological Societies points to the need for further study.

"In our cohort, the relation between the use of IVADs and death was not modified by different grades of status epilepticus severity, suggesting that the association of IVADs with an increased risk of death did not depend on to whom or when, but on the fact that IVADs were used," they wrote.

However, while the findings provide "class 3 evidence that patients with status epilepticus receiving IVADs have a higher proportion of infections and an increased risk of death, compared with those who did not receive IVADs," the findings should be considered preliminary until the association between IVADs and these outcomes are confirmed in prospective randomized trials, Dr. Kaplan said.

Dr. Kaplan reported having no disclosures. Dr. Sutter is supported by the Research Fund of University Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. He has held stock from Novartis and Roche since 2005.

WASHINGTON – The use of anesthetic drugs for the treatment of refractory status epilepticus was associated with a high risk of infection and death among patients treated over a 6-year period at a tertiary academic medical center.

Although prospective, randomized controlled trials are needed to confirm the findings of this retrospective cohort study, the data should heighten awareness of the potential adverse effects of anesthetic drugs, Dr. Peter W. Kaplan said at the annual meeting of the American Epilepsy Society.

Of 171 adults who presented to University Hospital Basel, Switzerland, with status epilepticus between January 2005 and January 2011, 63 (37%) were treated with intravenous anesthetic drugs (IVADs), including thiopental, midazolam, propofol, and/or high-dose phenobarbital, and 18% of the patients died. After adjustment for status epilepticus duration and severity (based on status epilepticus severity score) and for critical medical conditions, those treated with IVADs had a significantly increased risk of death, compared with those who did not receive IVADs (relative risk = 3.16), said Dr. Kaplan of Johns Hopkins University, Baltimore.

Those who received IVADs also had a significantly higher rate of infectious complications (43% vs. 11%). The infections were diagnosed during the course of treatment, and 25 of 27 infections were respiratory infections. The remaining two cases were urinary tract infections.

No significant difference was seen between the groups with respect to seizure control, but ICU stay, a secondary outcome of the study, was significantly longer in those who received IVADs (13.5 days vs. 4.5 days), he said.

Severe hypotension also occurred more often in the patients who received IVADs.

Patients included in the study were adults with a mean age of 64 years. Those who received continuously administered IVADs were refractory to first- and second-line antiepileptic drugs and were treated according to a standard protocol; 29 received midazolam only, 22 received midazolam followed by propofol, and 12 received barbiturates after midazolam. The use of nonanesthetic antiepileptic drugs was similar in the two groups.

The findings, published online Dec. 6 in Neurology ahead of their presentation at the AES meeting, are important because data regarding the risks and benefits of anesthetic drugs for status epilepticus are lacking (Neurology 2013 Dec. 6 [doi:10.1212/WNL.0000000000000009]).

In the Neurology report, principal investigator Dr. Raoul Sutter of University Hospital Basel and his colleagues – including Dr. Kaplan – noted that "most opinion leaders recommend IVADs ... for refractory status epilepticus to induce total seizure suppression, an EEG burst-suppression pattern, or an isoelectric EEG," but explained that "the Neurocritical Care Society outlines the role of IVADs, but notes the lack of supporting data, while the European Federation of Neurological Societies points to the need for further study.

"In our cohort, the relation between the use of IVADs and death was not modified by different grades of status epilepticus severity, suggesting that the association of IVADs with an increased risk of death did not depend on to whom or when, but on the fact that IVADs were used," they wrote.

However, while the findings provide "class 3 evidence that patients with status epilepticus receiving IVADs have a higher proportion of infections and an increased risk of death, compared with those who did not receive IVADs," the findings should be considered preliminary until the association between IVADs and these outcomes are confirmed in prospective randomized trials, Dr. Kaplan said.

Dr. Kaplan reported having no disclosures. Dr. Sutter is supported by the Research Fund of University Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. He has held stock from Novartis and Roche since 2005.

WASHINGTON – The use of anesthetic drugs for the treatment of refractory status epilepticus was associated with a high risk of infection and death among patients treated over a 6-year period at a tertiary academic medical center.

Although prospective, randomized controlled trials are needed to confirm the findings of this retrospective cohort study, the data should heighten awareness of the potential adverse effects of anesthetic drugs, Dr. Peter W. Kaplan said at the annual meeting of the American Epilepsy Society.

Of 171 adults who presented to University Hospital Basel, Switzerland, with status epilepticus between January 2005 and January 2011, 63 (37%) were treated with intravenous anesthetic drugs (IVADs), including thiopental, midazolam, propofol, and/or high-dose phenobarbital, and 18% of the patients died. After adjustment for status epilepticus duration and severity (based on status epilepticus severity score) and for critical medical conditions, those treated with IVADs had a significantly increased risk of death, compared with those who did not receive IVADs (relative risk = 3.16), said Dr. Kaplan of Johns Hopkins University, Baltimore.

Those who received IVADs also had a significantly higher rate of infectious complications (43% vs. 11%). The infections were diagnosed during the course of treatment, and 25 of 27 infections were respiratory infections. The remaining two cases were urinary tract infections.

No significant difference was seen between the groups with respect to seizure control, but ICU stay, a secondary outcome of the study, was significantly longer in those who received IVADs (13.5 days vs. 4.5 days), he said.

Severe hypotension also occurred more often in the patients who received IVADs.

Patients included in the study were adults with a mean age of 64 years. Those who received continuously administered IVADs were refractory to first- and second-line antiepileptic drugs and were treated according to a standard protocol; 29 received midazolam only, 22 received midazolam followed by propofol, and 12 received barbiturates after midazolam. The use of nonanesthetic antiepileptic drugs was similar in the two groups.

The findings, published online Dec. 6 in Neurology ahead of their presentation at the AES meeting, are important because data regarding the risks and benefits of anesthetic drugs for status epilepticus are lacking (Neurology 2013 Dec. 6 [doi:10.1212/WNL.0000000000000009]).

In the Neurology report, principal investigator Dr. Raoul Sutter of University Hospital Basel and his colleagues – including Dr. Kaplan – noted that "most opinion leaders recommend IVADs ... for refractory status epilepticus to induce total seizure suppression, an EEG burst-suppression pattern, or an isoelectric EEG," but explained that "the Neurocritical Care Society outlines the role of IVADs, but notes the lack of supporting data, while the European Federation of Neurological Societies points to the need for further study.

"In our cohort, the relation between the use of IVADs and death was not modified by different grades of status epilepticus severity, suggesting that the association of IVADs with an increased risk of death did not depend on to whom or when, but on the fact that IVADs were used," they wrote.

However, while the findings provide "class 3 evidence that patients with status epilepticus receiving IVADs have a higher proportion of infections and an increased risk of death, compared with those who did not receive IVADs," the findings should be considered preliminary until the association between IVADs and these outcomes are confirmed in prospective randomized trials, Dr. Kaplan said.

Dr. Kaplan reported having no disclosures. Dr. Sutter is supported by the Research Fund of University Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. He has held stock from Novartis and Roche since 2005.