Safety and efficacy of flumazenil for reversal of iatrogenic benzodiazepine-associated delirium toxicity during treatment of alcohol withdrawal, a retrospective review at one center.

Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10-530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1-11 days) after abstinence, and average dose was 0.5 mg (0.2-1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety in two patients: 1 patient who received 0.5 mg on abstinence day 2 and another patient who received 0.2 mg flumazenil on abstinence day 11. This is the largest series diagnosing benzodiazepine delirium after AWS in patients receiving flumazenil. During the treatment of AWS, if delirium is present on day 5, a test dose of flumazenil may be considered to establish benzodiazepine delirium. With the limited data set often accompanying patients with AWS, flumazenil diagnosed benzodiazepine delirium during the treatment of AWS and improved impairments in cognition and behavior without serious or life-threatening adverse events in our patients.

Serotonin syndrome precipitated by fentanyl during procedural sedation.

Fentanyl is frequently used for analgesia during emergency procedures. We present the cases of 2 patients who developed agitation and delirium after intravenous fentanyl administration. These patients were chronically taking selective serotonin reuptake inhibitors (SSRIs). Both developed neuromuscular examinations consistent with serotonin syndrome, a diagnosis that must be established on the basis of clinical criteria. Although they required aggressive supportive care, including mechanical ventilation, both patients made a full recovery. Use of fentanyl for procedural sedation may precipitate serotonin syndrome in patients taking SSRIs or other serotonergic drugs.

Tricyclic antidepressant toxicity treated with massive sodium bicarbonate.

Tricyclic antidepressant (TCA) morbitity is primarily due to cardiac arrhythmias and hypotension, which become more refractory to treatment as acidosis progresses (Ann Emerg Med. 1985;14:1-9; Clin Toxicol. 2007;45:203-233; Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank's toxicologic emergencies. 8th ed. McGraw-Hill Companies, Inc, 2006). Early recognition and aggressive treatment are necessary for patient survival.

Management of isolated yew berry toxicity with sodium bicarbonate: a case report in treatment efficacy.

INTRODUCTION: Taxus species are known to be toxic and may result in significant dysrhythmias. Treatment of taxus induced cardiac dysrhythmias is based largely on case reports. We describe a case of a 24-year-old male with Taxus cuspidate (yew berry) toxicity initially treated with amiodarone bolus and infusion and subsequently managed with sodium bicarbonate boluses and continuous infusion. CASE REPORT: The patient was found at home by his parents with witnessed "seizure-like"activity 2 hours after reportedly chewing and swallowing 168 yew seeds. The initial prehospital rhythm strip demonstrated ventricular tachycardia (VT); the patient was hypotensive with fluctuating levels of alertness. Prehospital cardioversion was attempted without success. Staff at the local presenting emergency department (ED) consulted toxicology for management of the presumed yew berry ingestion, complicated by cardiac dysrhythmias and mental status change with seizure. Amiodarone 300-mg IV and diazepam 5-mg IV were given. Cardioversion was attempted 4 times without change in the wide complex tachycardia, presumed to be VT, at a rate of 166. An amiodarone drip at 1 mg/min was initiated. The patient was transferred to an intensive care unit (ICU) at a regional toxicology center. On arrival to the toxicology center the patient was alert and verbally appropriate without complaints. Initial heart rate was 76 and regular with premature ventricular contractions (PVCs). A wide complex tachycardia associated with hypotension recurred; however, normal mental status was maintained. A bolus of 100 mEq of sodium bicarbonate (NaHCO3) was given intravenously followed by sodium bicarbonate infusion at 37.5 mEq/hr. The amiodarone drip was discontinued. Subsequent electrocardiograms (EKG's) revealed a prolonged, but steadily narrowing QRS complex. Ultimately, the QRS complex closed to 92 ms, with a rate of 94, PR 154 and a QT/QTc of 390/487. CONCLUSION: This case describes successful treatment of an isolated Taxus cuspidate (yew berry) ingestion with significant toxicity initially with amiodarone bolus and infusion. Due to lack of significant change in telemetry recordings with amiodarone, treatment with sodium bicarbonate bolus and infusion was initiated. While the QRS narrowed significantly temporally related to the bicarbonate, it is difficult to determine if correction of the cardiac dysrhythmias was solely due to the sodium bicarbonate, or the synergism of sodium bicarbonate and amiodarone, or possibly spontaneous improvement due to taxine clearance. One should use caution while drawing conclusions from a single case; however, based on the clinical improvement of this patient, both with EKG recordings and vital signs, this report would suggest that isolated Taxus cuspidate ingestion from yew berry plants can be treated with sodium bicarbonate.

A preliminary study of tricyclic antidepressant (TCA) ovine FAB for TCA toxicity.

BACKGROUND: Animal studies suggest that tricyclic antidepressant antibody fragments (TCA Fab) may be a useful therapy for tricyclic antidepressant poisoning. The objective of this study is to determine if TCA Fab increases total serum TCA levels without raising free serum TCA levels in human overdose patients, indicating that TCA Fab effectively binds TCA. METHODS: This was a prospective, dose escalation study of patients with mild to moderate TCA poisoning. Patients were treated with an escalating intravenous infusion totaling 7 or 14 gm of TCA Fab. The outcomes of interest were serum TCA levels (total and free), worsening of TCA toxicity, and adverse effects. RESULTS: Seven patients were treated with Fab. Infusion of TCA Fab was associated with a dramatic increase in total serum TCA levels, while free TCA levels fell in both dosing groups. There were no significant changes in QRS duration, heart rate or mean arterial pressure associated with the Fab Infusion. Worsening of TCA toxicity did not occur despite marked elevation of total serum TCA concentrations. The two patients with the greatest prolongation of QRS showed a prompt shortening in their QRS duration temporally associated with the Fab infusion. Mild wheezing was observed in one asthmatic patient. CONCLUSIONS: 1) TCA Fab raises total serum TCA levels while lowering free levels in TCA poisoned patients; 2) no toxic effects were associated with the increase in TCA levels and no severe adverse effects were observed during the hospital course following Fab infusion.

Disaster management during a nuclear accident

This paper offers some guidelines on the basic components of a plan for effective handling of a nuclear accident. Special referencÐ 9q made to emergency medical services, regional planning, evacuation, communication, decontamination and triage priorities