Refractory delirium tremens treated with ketamine.

Abstract

Dear Editor, Delirium tremens (DT) is a severe form of alcohol withdrawal syndrome (AWS). DT presents commonly on the third to fifth day after alcohol abstinence and lasts about 24 h to 6 days. DT requires high level of monitoring and intensive care unit (ICU) treatment. From a pathophysiological point of view, alcohol’s inhibitory effects in the brain are primarily achieved through the γ-aminobutyric acid (GABA) neurotransmitter, resulting in a global slowing of neurotransmission with consequent anxiolysis, sedation, and anticonvulsant activity (Schmidt et al., 2016). In addition, alcohol also produces physiological changes in excitatory neurotransmission. Alcohol competitively inhibits the binding of glycine to the N-methyl-d-aspartate (NMDA) receptors in the brain, consequently preventing the action of the major excitatory neurotransmitter glutamate on the NMDA receptors. The human brain undergoes functional adaptations that eventually result in tolerance in the presence of chronic alcohol ingestion. There is a progressively higher expression of excitatory NMDA receptors and a compensatory downregulation of GABAA receptors (Schmidt et al., 2016). DT needs to be managed as medical emergency. The goal of treatment of alcohol withdrawal is to ameliorate agitation and other symptoms of delirium, recognition and treatment of underlying medical co-morbidities, and of course prompt, adequate, and protocol-driven treatment of alcohol withdrawal. Standard management for any patient with suspected alcohol withdrawal is initial resuscitation and rehydration. Benzodiazepines remain the cornerstone of therapy in the treatment of alcohol withdrawal. Benzodiazepines act on the same GABAA receptors as alcohol, thereby mimicking the inhibitory effects. However, the superiority of one benzodiazepine over another remains unclear in the literature (Schmidt et al., 2016). Benzodiazepine refractory delirium is defined as, “frank delirium or inability to control symptoms despite medication” and/or “requirement of 200 mg in the initial 3 h or 400 mg of diazepam in the first 8 h or 30 mg in the initial 3 h or 60 mg of lorazepam in the initial 8 h.” Several other drugs can be used for the treatment of refractory DT. Propofol potentiates GABA receptor activity and can also inhibit NMDA receptors, thus acting at several receptors to decrease withdrawal effects (Schmidt et al., 2016). Case series and trials have supported the use of propofol in refractory DT and withdrawal. However, patients on propofol frequently experienced more days of mechanical ventilation and length of stay, which may be due to more refractory cases of alcohol withdrawal (Brotherton et al., 2016). A great deal of controversy surrounds the use of dexmedetomidine in alcohol withdrawal and DT. Ketamine is an enantiomeric, lipid-soluble phencyclidine derivative and, like ethanol, ketamine is a nonselective NMDA receptor antagonist. Unfortunately, ketamine has largely remained unstudied for the treatment of severe alcohol withdrawal (Schmidt et al., 2016). In this letter to the editor, we present a case of a 64-year-oldwoman affected by refractory DT treated with ketamine. The patients had a history of alcohol abuse, hypertension, and chronic anxiety. She had recently been hospitalized for alcohol withdrawal syndrome with seizures and pneumonia and was discharged after a few days of hospitalization. She was admitted to our hospital after her husband found her soporous and diaphoretic; her husband stated that she hadn’t taken alcohol for 2 days. For the suspicious of overdose in patients in therapy with long-acting benzodiazepine, the Emergency medical services (EMS) personnel administered benzodiazepine antagonist. Tonic-clonic seizures were observed and, consequently, she was sedated with midazolam and transported to our hospital. On arrival to the emergency department, she was sedated, tachycardic, hyperthermic (38.3°C), and with severe metabolic lactic acidosis. Brain computed tomography (CT) scan was performed; there was no injury to justify that initial state of unconsciousness. After neurological counseling, anti-epileptic therapy was started. In addition, thoraco-abdominal CT scan showed acute pyelonephritis for which empiric antibiotic therapy was performed. ICU stay was characterized by multiple episodes of psychomotor agitation with diffuse tremor every time that sedation was reduced. Even more she was tachycardic, tachypneic with thoracoabdominal asynchrony with high blood pressure and sialorrhea. Therefore, it was crucial to find the right sedative balance with the drugs available in continuous infusion: initially propofol and sufentanil were used; we quickly observed the resolution of all symptoms, but we were forced to use high dosages to control symptoms with consequent hemodynamic depression and no Refractory delirium tremens treated with ketamine