Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP
Anselm Wong1,2,3, Robert S Hoffman4, Steven J Walsh5
1Austin Toxicology Unit and Emergency Department, Victorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australia.
Insights
Extracorporeal treatments (ECTRs) are not recommended for severe calcium channel blocker (CCB) poisoning. Clinical data and drug dialyzability do not support their use for amlodipine, diltiazem, or verapamil poisoning.
Area of Science:
- Toxicology
- Pharmacology
- Nephrology
Background:
- Calcium channel blockers (CCBs) are widely prescribed for hypertension and arrhythmias.
- CCB overdose can cause severe toxicity and mortality.
- The role of extracorporeal treatments (ECTRs) in managing CCB poisoning requires evaluation.
Purpose of the Study:
- To assess the efficacy and utility of extracorporeal treatments (ECTRs) in managing severe calcium channel blocker (CCB) poisoning.
- To provide evidence-based recommendations for the use of ECTRs in CCB overdose.
Main Methods:
- Systematic literature review using EXTRIP methodology.
- Screening and data extraction from 83 relevant publications.
- Analysis of toxicokinetic, pharmacokinetic, and clinical data from poisoned patients.
Main Results:
- Most CCBs, including amlodipine, diltiazem, and verapamil, demonstrated low dialyzability.
- Clinical data from 78 poisoned patients did not show improved outcomes with ECTR.
- Strong recommendations against ECTR for amlodipine, diltiazem, and verapamil poisoning were formulated due to very low-quality evidence.
Conclusions:
- Dialyzability and clinical evidence do not support the use of ECTRs for CCB poisoning.
- Extracorporeal methods are not recommended for enhancing elimination in severe amlodipine, diltiazem, or verapamil poisoning.
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.
Related Concept Videos
01:25Extracorporeal Removal of Drugs: Hemoperfusion and Hemofiltration
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
01:26Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:26Anticholinesterase Agents: Poisoning and Treatment
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
01:28Acute Coronary Syndrome IV: Interprofessional Care