Ketamine may help refractory status epilepticus

MONTREAL – Intravenous ketamine resolved refractory convulsive status epilepticus in 14 of 17 cases in a small, uncontrolled prospective study.

In addition to its efficacy, ketamine has a unique safety advantage over more commonly used anesthetics. "It does not cause respiratory depression, so it allows us to avoid intubation and ventilatory support in these children," said Dr. Anna Rosati of the University of Florence (Italy). "Because intubation can worsen the prognosis, we believe ketamine should be considered before conventional anesthetics in children with status epilepticus."

The study examined 17 incidents of convulsive status epilepticus that occurred in 13 children. In 13 cases, first-line treatment with midazolam, propofol, or thiopental had failed. Ketamine was the first-line agent in the other four cases, she reported at the 30th International Epilepsy Congress.

The children ranged in age from 2 months to 10 years. The mean duration of status epilepticus before ketamine administration was 16 days, with a range of 5 hours to 86 days. Seizure etiology included focal cortical dysplasia (2), other cortical malformations (3), hydrocephalus (1), febrile infection–related epilepsy syndrome (2), and Rett syndrome (1). One patient had MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). The etiology was unknown in three.

The ketamine protocol began with two intravenous boluses of 2-3 mg/kg given 5 minutes apart. This was immediately followed by a continuous ketamine infusion, starting at 10 mcg/kg per minute and increasing by 10-mcg increments up to 60 mcg/kg per minute. The mean dosage was 32.5 mcg/kg per minute. Patients also received midazolam as an add-on to prevent emergence reactions. Ketamine was continued for a median of 5 days, with a range of 6 hours to 17 days.

Status epilepticus resolved in 10 of the 13 cases in which ketamine was administered after the first-line drugs had failed and in all 4 cases in which ketamine was the first-line agent. In those four cases, "we were able to avoid intubation," Dr. Rosati said.

The only adverse events noted were hypersalivation, which occurred in all cases, and mild, transient increases in liver enzymes in four cases.

Electroencephalographic changes mirrored clinical improvement, Dr. Rosati said. In the 14 resolved cases, 12 showed a burst suppression pattern and two showed diffuse theta-delta activity. No EEG changes occurred in the three cases without resolution.

Two of the three children who didn’t respond to ketamine had focal cortical dysplasia. Their status resolved after a surgical excision. The third patient had an unknown etiology; status resolved only with a very high thiopental dosage. However, Dr. Rosati noted, a second status episode in that child did resolve with ketamine as a first-line drug.

In light of the small study’s positive results, Dr. Rosati said she is planning to conduct a randomized controlled study of ketamine in status epilepticus.

She said she had no relevant financial disclosures.

[email protected]

MONTREAL – Intravenous ketamine resolved refractory convulsive status epilepticus in 14 of 17 cases in a small, uncontrolled prospective study.

In addition to its efficacy, ketamine has a unique safety advantage over more commonly used anesthetics. "It does not cause respiratory depression, so it allows us to avoid intubation and ventilatory support in these children," said Dr. Anna Rosati of the University of Florence (Italy). "Because intubation can worsen the prognosis, we believe ketamine should be considered before conventional anesthetics in children with status epilepticus."

The study examined 17 incidents of convulsive status epilepticus that occurred in 13 children. In 13 cases, first-line treatment with midazolam, propofol, or thiopental had failed. Ketamine was the first-line agent in the other four cases, she reported at the 30th International Epilepsy Congress.

The children ranged in age from 2 months to 10 years. The mean duration of status epilepticus before ketamine administration was 16 days, with a range of 5 hours to 86 days. Seizure etiology included focal cortical dysplasia (2), other cortical malformations (3), hydrocephalus (1), febrile infection–related epilepsy syndrome (2), and Rett syndrome (1). One patient had MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). The etiology was unknown in three.

The ketamine protocol began with two intravenous boluses of 2-3 mg/kg given 5 minutes apart. This was immediately followed by a continuous ketamine infusion, starting at 10 mcg/kg per minute and increasing by 10-mcg increments up to 60 mcg/kg per minute. The mean dosage was 32.5 mcg/kg per minute. Patients also received midazolam as an add-on to prevent emergence reactions. Ketamine was continued for a median of 5 days, with a range of 6 hours to 17 days.

Status epilepticus resolved in 10 of the 13 cases in which ketamine was administered after the first-line drugs had failed and in all 4 cases in which ketamine was the first-line agent. In those four cases, "we were able to avoid intubation," Dr. Rosati said.

The only adverse events noted were hypersalivation, which occurred in all cases, and mild, transient increases in liver enzymes in four cases.

Electroencephalographic changes mirrored clinical improvement, Dr. Rosati said. In the 14 resolved cases, 12 showed a burst suppression pattern and two showed diffuse theta-delta activity. No EEG changes occurred in the three cases without resolution.

Two of the three children who didn’t respond to ketamine had focal cortical dysplasia. Their status resolved after a surgical excision. The third patient had an unknown etiology; status resolved only with a very high thiopental dosage. However, Dr. Rosati noted, a second status episode in that child did resolve with ketamine as a first-line drug.

In light of the small study’s positive results, Dr. Rosati said she is planning to conduct a randomized controlled study of ketamine in status epilepticus.

She said she had no relevant financial disclosures.

[email protected]

MONTREAL – Intravenous ketamine resolved refractory convulsive status epilepticus in 14 of 17 cases in a small, uncontrolled prospective study.

In addition to its efficacy, ketamine has a unique safety advantage over more commonly used anesthetics. "It does not cause respiratory depression, so it allows us to avoid intubation and ventilatory support in these children," said Dr. Anna Rosati of the University of Florence (Italy). "Because intubation can worsen the prognosis, we believe ketamine should be considered before conventional anesthetics in children with status epilepticus."

The study examined 17 incidents of convulsive status epilepticus that occurred in 13 children. In 13 cases, first-line treatment with midazolam, propofol, or thiopental had failed. Ketamine was the first-line agent in the other four cases, she reported at the 30th International Epilepsy Congress.

The children ranged in age from 2 months to 10 years. The mean duration of status epilepticus before ketamine administration was 16 days, with a range of 5 hours to 86 days. Seizure etiology included focal cortical dysplasia (2), other cortical malformations (3), hydrocephalus (1), febrile infection–related epilepsy syndrome (2), and Rett syndrome (1). One patient had MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). The etiology was unknown in three.

The ketamine protocol began with two intravenous boluses of 2-3 mg/kg given 5 minutes apart. This was immediately followed by a continuous ketamine infusion, starting at 10 mcg/kg per minute and increasing by 10-mcg increments up to 60 mcg/kg per minute. The mean dosage was 32.5 mcg/kg per minute. Patients also received midazolam as an add-on to prevent emergence reactions. Ketamine was continued for a median of 5 days, with a range of 6 hours to 17 days.

Status epilepticus resolved in 10 of the 13 cases in which ketamine was administered after the first-line drugs had failed and in all 4 cases in which ketamine was the first-line agent. In those four cases, "we were able to avoid intubation," Dr. Rosati said.

The only adverse events noted were hypersalivation, which occurred in all cases, and mild, transient increases in liver enzymes in four cases.

Electroencephalographic changes mirrored clinical improvement, Dr. Rosati said. In the 14 resolved cases, 12 showed a burst suppression pattern and two showed diffuse theta-delta activity. No EEG changes occurred in the three cases without resolution.

Two of the three children who didn’t respond to ketamine had focal cortical dysplasia. Their status resolved after a surgical excision. The third patient had an unknown etiology; status resolved only with a very high thiopental dosage. However, Dr. Rosati noted, a second status episode in that child did resolve with ketamine as a first-line drug.

In light of the small study’s positive results, Dr. Rosati said she is planning to conduct a randomized controlled study of ketamine in status epilepticus.

She said she had no relevant financial disclosures.

[email protected]