Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup.

BACKGROUND: Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods. RESULTS: A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR. CONCLUSIONS: Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.

Intravenous rifampicin use in the management of amanita phalloides toxicity.

Context: Amanita phalloides related toxicity from amatoxins can result in acute liver and multi-organ failure and is responsible for 90% of all mushroom poisoning death. However, more evidence is needed in regards to different management strategies.Case details: We present two cases of amanita mushroom ingestion who were treated with intravenous rifampicin.Discussion: Further study is needed to establish the efficacy and role of rifampicin in amatoxin related mushroom poisoning.

Treatment for beta-blocker poisoning: a systematic review.

Introduction: Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality.Objective: To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning.Methods: Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response).Results: The risk of bias was high for all interventions.Gastric decontamination: Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival.Catecholamines, inotropes and vasopressors: The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics.Atropine: Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report.Calcium: Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies.High-dose insulin euglycaemic therapy: The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects.Glucagon: Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies.Methylthioninium chloride (methylene blue): Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine.Intravenous lipid emulsion therapy: There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports.Lignocaine: There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity.Other treatments: Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. .Veno-arterial extracorporeal membrane oxygenation: Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series.Dialysis: The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established.Pacing: One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity.Conclusions: Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.

The utility of droperidol in the treatment of cannabinoid hyperemesis syndrome.

Introduction: Cannabinoid hyperemesis syndrome (CHS) can be characterized by recurrent paroxysmal episodes of intractable nausea and vomiting, abdominal pain, and compulsive hot showers/baths with symptom relief, on the background of chronic cannabis use. We reported the use of droperidol in the management of CHS. Methods: We performed a retrospective review of electronic medical records of Emergency Department presentations to a single tertiary level metropolitan hospital between January 2006 and December 2016 using search keywords: "cannabis", "cannabinoid", "cannabis", "hyperemesis", and "droperidol". A secondary search of pharmacy droperidol dispensing records was cross matched with electronic medical record data. We reviewed each record to determine if the presentation met previously published diagnostic criteria for CHS. Data were dichotomised into presentations with droperidol administered or not administered. The primary outcome was defined as the total length of hospital stay. Secondary outcomes measures included time until discharge following last drug administration, and the total number of antiemetic dosages administered. Results: Six-hundred and eighty-nine records were identified and 76 met CHS diagnostic criteria. Thirty-seven presentations were treated with droperidol and 39 were not. Droperidol treatment group median length of stay was significantly lower compared to the no droperidol treatment group (6.7 vs. 13.9 hours, p = .014). Median time to discharge after final drug administration in the droperidol treatment group was 137 minutes (IQR 65, 203) vs. the no droperidol treatment group of 185 minutes (IQR 149, 403). The most frequent dosage of droperidol used was 0.625mg intravenously. The frequency of ondansetron (n = 100) and metoclopramide (n = 27) in the no droperidol treatment group was double that of the droperidol group. Conclusions: Use of droperidol to treat CHS associated nausea and vomiting resulted in less overall use of antiemetics and reduced length of stay.