The Feasibility, Safety and Effectiveness of a Ketogenic Diet for Refractory Status Epilepticus in Adults in the Intensive Care Unit.

BACKGROUND: Status, refractory status and super refractory status epilepticus are common neurologic emergencies. The objective of this study is to investigate the feasibility, safety and effectiveness of a ketogenic diet (KD) for refractory status epilepticus (RSE) in adults in the intensive care unit (ICU). METHODS: We performed a retrospective, single-center study of patients between ages 18 and 80 years with RSE treated with a KD treatment algorithm from November 2016 through April 2018. The primary outcome measure was urine ketone body production as a biomarker of feasibility. Secondary measures included resolution of RSE and KD-related side effects. RESULTS: There were 11 adults who were diagnosed with RSE that were treated with the KD. The mean age was 48 years, and 45% (n = 5) of the patients were women. The patients were prescribed a median of three anti-seizure medications before initiating the KD. The median duration of RSE before initiation of the KD was 1 day. Treatment delays were the result of Propofol administration. 90.9% (n = 10) of patients achieved ketosis within a median of 1 day. RSE resolved in 72.7% (n = 8) of patients; however, 27.3% (n = 3) developed super-refractory status epilepticus. Side effects included metabolic acidosis, hypoglycemia and hyponatremia. One patient (20%) died. CONCLUSIONS: KD may be feasible, safe and effective for treatment of RSE in the ICU. A randomized controlled trial (RCT) may be indicated to further test the safety and efficacy of KD.

L-2-Hydroxyglutaric aciduria presenting as status epilepticus.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria with a slowly progressive course regarding CNS involvement. We present a 13.5-year-old female patient who presented at the Emergency Department with a generalized status epilepticus, which promptly responded to intravenous phenytoin. CT and MRI demonstrated subcortical white matter alterations. The neurological examination revealed mild mental retardation, macrocephaly and ataxic gait with cerebellar signs. Repeated urinary organic acid analysis demonstrated increased excretion of 2-hydroxyglutaric acid which was of the L-configuration. The constellation of macrocephaly in a patient with mental retardation, cerebellar tract involvement and subcortical white matter signal alterations on MRI should alert the physician to the possibility of L-2-HGA. Although rare, epileptic seizures or even status epilepticus can be among the presenting symptoms in organic acidurias with a slow course, such as L-2-HGA.

Urinary excretion of phenobarbital and its metabolite p-hydroxyphenobarbital in convulsing and non-convulsing patients.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied:(group 1) five patients (4 M + 1 F; 48 +/- 28 years old; 64 +/- 6 kg body weight; mean +/- SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 +/- 13 years old; 71 +/- 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients--higher values in the patients who had had an episode of SE, and in urine flow--slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.

Urinary free cortisol values in children under stress.

Children with adrenocortical insufficiency are commonly instructed to increase their baseline glucocorticoid replacement doses by three to five times during periods of stress such as surgery or febrille illness. We conducted this to determine whether these recommendations reflect the actual change in urinary free cortisol (UFC) output during stress. The 24-hour UFC excretion was determined in 78 children who were admitted to a general pediatric department or intensive care unit with temperature > 38.7 degrees C, after major surgery, or during status epilepticus; we reevaluated 43 of the patients 2 weeks after recovery. In addition, the 24-hour UFC levels were determined in 127 healthy children aged 1.8 to 17 years. The UFC level positively correlated with age (r = 0.254; p < 0.001). The amount of UFC per gram of creatinine was inversely correlated with age (r = 0.255; p < 0.001). The amount of UFC per surface area was independent of age. The mean change in the level of UFC per square meter surface area was highest among children who had cardiothoracic surgery and those with multiple trauma. The increase in UFC level during bacterial infection was significantly greater than that during viral infection. The current recommendation to increase the dose to three to five times the baseline glucocorticoid dose during times of stress may underestimate the changes in UFC found in some patients with major surgery, trauma, or certain serious bacterial infections. Production rate studies are needed to prove this point.