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

Abstract

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.

Keywords:

• Cardiovascular; EXTRIP; hemodialysis; hemoperfusion; calcium channel blocker; overdose

Acknowledgments

We would like to acknowledge the valuable help of our dedicated translators, librarian, data extractors, and meeting secretary. Official translators were Alexandra Angulo, Alla Abbott, Anant Vipat, Andreas Betz, Angelina Kovaleva, Denise Gemmellaro, Ewa Brodziuk, Helen Johnson, Junzheng Peng, Marcela Covic, Nathalie Eeckhout, Rosie Finnegan, Salih Topal, and Vilma Etchard. The librarian was Elena Guadagno. Data extractors for EXTRIP-2 included Maria Rif, François Filion, Karine Mardini, Maria Rif, Tudor Botnaru, Elizabeth Koo, and Gabrielle Wilson. The meeting secretary was Brenda Gallant. We also acknowledge the participation of our patient representative (name undisclosed).

Author contributions

Marc Ghannoum, Sophie Gosselin, Robert S. Hoffman, Valery Lavergne, Thomas D. Nolin, and Darren M. Roberts designed the study; Marc Ghannoum, Steven J Walsh, and Anselm Wong carried out extractions. Anselm Wong, Marc Ghannoum, Robert S. Hoffman, and Darren M. Roberts drafted the manuscript. Anselm Wong, Marc Ghannoum, and Valery Lavergne made the tables and figures; all authors drafted and revised the paper; and all authors approved the final version of the manuscript.

Disclosure statement

Thomas D. Nolin reports personal fees from MediBeacon, CytoSorbents, and McGraw-Hill Education outside the submitted work. Marc Ghannoum is a scholar of the Fonds de Recherche du Québec – Santé. Darren Roberts acknowledges support of St. Vincent’s Centre for Applied Medical Research Clinician “Buy-Out” Program. Anitha Vijayan reports consulting functions for NxStage, Astute Medical, and Boehringer-Ingelheim and speaker fees from Sanofi-Aventis. Marlies Ostermann has received speaker honoraria and research funding from Fresenius Medical and Baxter and has had consulting functions for Nxstage and Baxter. All remaining authors have nothing to disclose. No potential conflict of interest was reported by the author(s).

Additional information

Funding

EXTRIP received support consisting of an unrestricted grant of $60,633 Canadian from the Verdun Research Fund (the institution of Marc Ghannoum) solely for the reimbursement of travel expenses for the in-person guideline meeting and payment to dedicated translators for retrieval and translation of foreign language articles.