Continuous intravenous pentobarbital infusion is recommended and widely used for the management of refractory status epilepticus [
The patient is a 28-year-old woman with intractable epilepsy and no preexisting cardiac disease who presented with convulsive status epilepticus in the setting of gastroenteritis and medication intolerance. She continued to have seizures despite first-line treatment with benzodiazepines and conventional antiepileptic medications including phenytoin and levetiracetam. She was subsequently intubated and received continuous infusion midazolam and propofol drips. Neuroimaging and cerebrospinal fluid studies were unremarkable. Continuous video electroencephalography monitoring was initiated.
One day following admission to the hospital and despite high doses of continuous infusion of midazolam and propofol, electroencephalography showed sharply contoured bursts originating from right, central, and temporal leads. These bursts evolved into lateralized periodic discharges and then subsequent electrographic seizures. Lacosamide and lamotrogine failed to resolve these electrographic patterns and pentobarbital was initiated and titrated to burst suppression, which was achieved at a dose of 3 mg/kg/hour. Burst suppression was maintained for 24–48 hours after which the pentobarbital infusion rate was gradually decreased.
On day 11 of admission, she developed sudden onset of severe circulatory shock and hypoxia requiring four vasopressors at near maximum doses. The patient was afebrile and no infections were identified. Lactic acid level was slightly elevated at 2.5 mmol/L. By this time, the pentobarbital infusion had been tapered to 2 mg/kg/hour and the electroencephalogram (EEG) was significant for a persistent burst suppression pattern. An emergent echocardiogram was obtained and showed diminished ejection fraction of 20% (Figure
Transesophageal echocardiogram while on pentobarbital infusion, left ventricle ejection fraction of 20%: (a) end diastole; (b) end systole.
Transesophageal echocardiogram while off pentobarbital infusion, left ventricle ejection fraction of 50%: (a) end diastole; (b) end systole.
The patient continued to have both electrographic and clinical seizures. Ketamine infusion was initiated in addition to the midazolam infusion to suppress seizures and additional conventional antiepileptic medications were progressively introduced. These included topiramate, lamotrigine, phenobarbital, perampanel, phenytoin, lacosamide, clobazam, diazepam, and pyridoxine. Further workup including magnetic resonance imaging of the brain, repeat cerebrospinal fluid analysis, and serological and urinary studies was undertaken to exclude a broad spectrum of diagnostic possibilities including porphyria, paraneoplastic encephalitides, and autoimmune encephalitides. Nevertheless, she received an empiric course of intravenous immunoglobulins and corticosteroids.
The patient underwent tracheostomy and percutaneous endoscopic gastrostomy placement on day 24. Nerve conduction study and EMG were consistent with critical illness neuromyopathy. On day 57, the patient started to keep track with her eyes, follow commands, and mouth words and began to communicate verbally. As part of the Neuroscience Intensive Care Unit initiative to improve patient and family engagement, a home visit by a neurointensivist was arranged to facilitate a video call between the patient and her mother who was bedbound at home.
To our knowledge, this case represents the first report of pentobarbital-induced myocardial stunning and cardiopulmonary failure. Postulated biological mechanisms for cardiovascular compromise are largely derived from animal models. In addition to enhanced gamma-aminobutyric acid receptor-coupled responses and direct depression of neuronal excitability, pentobarbital’s mechanism of effect in status epilepticus occurs via antagonism of brain sodium channels with inhibition of neuronal action potential propagation [
Neurogenic myocardial stunning is a well-known reversible cause of hemodynamic instability that occurs commonly in brain-injured patients due to autonomic dysregulation and catecholamine mediated myocardial injury [
Septic cardiomyopathy was considered a potential cause of cardiopulmonary deterioration due to a higher risk of infection with pentobarbital; however no active infections were diagnosed. Although status epilepticus itself may cause neurogenic myocardial stunning, continuous EEG immediately prior to and during the episode of cardiopulmonary deterioration revealed no evidence of cortical epileptic discharges.
This case report suggests that pentobarbital infusion may cause severe myocardial suppression and cardiopulmonary failure. A review of the literature suggests that the mechanism is complex and involves drug-inhibitory effects on the autonomic nervous system as well as direct myocardial suppression. Aggressive cardiopulmonary support is justified to optimize the likelihood of a favorable outcome.
Informed consent has been obtained from the family.
The authors declare that they have no competing interests or disclosures.
Tapan Kavi contributed to the design of the paper. Tapan Kavi and Donna Molaie contributed to acquisition of data. Shouri Lahiri contributed to conceptualization of study. All authors contributed to drafting and revising the paper and read and approved the final paper.