GABA receptor agonists/hydroxyzine/tramadol overdose
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Refractory shock, asystole and other toxicities: case report A 33-year-old man, who had a history of depression, developed refractory shock, asystole and other toxicities following an intentional overdose of tramadol, hydroxyzine, gabapentin and clonazepam [time to reaction onset not stated]. The man, who was found unconscious at home, had consumed an estimated maximum dose of tramadol 10g, hydroxyzine 6g, gabapentin 1g and clonazepam 80mg. He was experiencing seizures, and was hypoglycaemic (50 mg/dL) and hypotensive. He was intubated and mechanically ventilated, and was admitted to hospital with a Glasgow Coma Scale score of 3, seizures, mydriasis and no pupillary reflexes. His temperature was 35.9°C, his BP was 63/38mm Hg, and his HR was 85 beats/min. An ECG showed sinus rhythm with a complete right bundle-branch block and a QTc interval of 480 msec. The left ventricular ejection fraction was estimated to be 56%. An EEG revealed continuous generalised epileptiform discharge. Blood tests showed a serum glucose level of 162 mg/dL, an arterial pH of 7.4, an HCO3 level of 18 mmol/L, a PaO2/FiO2 ratio of 350, a creatinine level of 22 mg/dL, a creatine kinase level of 332 U/L, a lactate level of 2.2 mmol/L, an albumin level of 27 g/L and a myoglobin level of 1281 µg/L. Subsequent tests revealed a tramadol concentration of 23.9 mg/L (therapeutic range 0.1–0.8 mg/L)* and small quantities of hydroxyzine, gabapentin and clonazepam were found in his urine. The man’s condition dramatically deteriorated despite assisted ventilation, thiopental sodium administration, glycaemic control, fluid loading and treatment with vasopressors. Twelve hours after admission, he developed a sudden ventricular tachycardia requiring defibrillation. A few minutes later, he experienced brief period of asystole. Restoration of spontaneous circulation was achieved with epinephrine [adrenaline]. There was no obvious explanation for the sudden cardiac arrest. The left ventricular ejection fraction was estimated to be 25%. An ECLS device was implanted, he continued to receive vasopressors and he received treatment for his acute renal failure. His overall status gradually improved and repeat echocardiography showed improvement in his cardiac function. He was discharged from hospital on day 12 with moderate cerebral disability. Author comment: "Although [hydroxyzine, gabapentin and clonazepam] probably contributed to the patient’s CNS depression and hypotension, it is unlikely that these drugs were involved in the cardiac arrest. . .This case illustrates the fact that tramadol overdose may cause a refractory shock and asystole when taken in combination with CNS depressants." * The tramadol concentration persisted above therapeutic concentrations for 3 days. The peak desmethyltramadol concentration was 12 hours after admission, corresponding with the man’s cardiac arrest. Daubin C, et al. Refractory shock and asystole related to tramadol overdose. 801100578 Clinical Toxicology 45: 961-964, No. 8, Dec 2007 - France
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