The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: Guideline methodology

Abstract

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

Extracorporeal Therapy for Dabigatran Removal in the Treatment of Acute Bleeding

“…Dialysate was not collected. As such, we are unable to perform standard pharmacokinetic calculations used to determine extracorporeal clearance: namely, the recovery method and the arterial-venous (A-V) pair method (27). However, some degree of extracorporeal clearance can be inferred by changes in half-life during extracorporeal therapy (28,29).…”

“…The half-life increased to 26.6 hours off dialysis. Using recently published guidelines to determine the dialyzability of toxins, if the half-life observed during extracorporeal therapy is ,25% of the half-life observed off therapy, then the drug may be dialyzable, and extracorporeal therapy may be an effective strategy for removal (27). Therefore, conservatively estimating a dabigatran half-life of 2 hours during high-flux hemodialysis versus 13 hours in normal kidney function or more than 28 hours in patients with CrCl,30 ml/min (22) suggests that IHD may be an effective means of dabigatran removal, particularly in the setting of impaired kidney function.…”

Pharmacokinetic Assessment in Patients Receiving Continuous RRT

“…The A-V pair and the recovery methods are potential approaches to determine CL EC (30). Serial plasma samples for drug and metabolite (if applicable) concentrations should be collected over at least a standard dosing interval after dosing.…”

Extracorporeal Treatment for Thallium Poisoning

“…It was assembled to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning (www.extrip-workgroup.org). Rationale, background, objectives, and complete methods of this endeavor, supported by the Acute Dialysis Quality Initiative, were reported previously (1,2).…”