Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning

Accelerated HEmodiafiltration in Severe Acute Diquat (AHEAD) Poisoning: a Single-center, Single-arm, Open-label, Clinical Trial

Diquat (1,1'-ethylene-2,2'-bipyridinium) is a bipyridine herbicide that shares a similar physicochemical structure and redox cycling mechanism with paraquat. Upon ingestion, it is rapidly absorbed and distributes widely, including gastrointestinal tract, kidneys, liver, skeletal muscle, lungs, myocardium, and central nervous system. Severe diquat poisoning commonly causes toxic encephalopathy, circulatory collapse, and multiorgan dysfunction. Extracorporeal treatments, including hemoperfusion, hemodialysis, and continuous kidney replacement therapy, are frequently used in management. Continuous veno-venous hemodiafiltration (CVVHDF), the most frequently used continuous kidney replacement therapy modality, is primarily indicated for acute kidney injury. Acute kidney injury occurs in up to 73.3% of patients with acute diquat poisoning, and nearly all patients with severe acute diquat poisoning are at risk of developing acute kidney injury. In clinical practice, patients with severe acute diquat poisoning are typically defined as those with a plasma diquat concentration of ≥1000 ng/mL measured at the time of presentation to the emergency department. However, the Extracorporeal Treatments in Poisoning (EXTRIP) workgroup has not issued any definitive recommendations on initiating extracorporeal treatments for diquat poisoning, and the optimal timing for starting CVVHDF has not been evaluated in clinical trials. Current practice typically delays CVVHDF until acute kidney injury occurs. A preliminary retrospective cohort study suggested that, among severe acute diquat poisoning patients treated with combined hemoperfusion and CVVHDF, an interval of <30 minutes between hemoperfusion and CVVHDF was associated with a significantly lower risk of death compared with longer intervals (≥30 minutes). Accordingly, this study proposes a single-arm trial (SAT) to determine whether accelerated initiation of CVVHDF immediately following hemoperfusion improves outcomes in patients with severe acute diquat poisoning.

Inclusion criteria:

1. Age ≥ 18 years; and
2. A history of oral exposure to diquat solution, reported by patient(s) or their legal proxies; and
3. An exposure time (time form exposure to presentation at ED) ≤ 48 hours, reported by patient(s) or their legal proxies; and
4. Plasma diquat concentration measured upon ED presentation ≥ 1,000 ng/mL.

Exclusion criteria:

1. Evidence of co-ingestion of other toxic substances alongside diquat; and/or
2. Withholding of CVVHDF due to limitations on the escalation of life-sustaining therapies; and/or
3. Any CKRT within the previous 2 months; and/or
4. Kidney transplant within the past 365 days; and/or
5. Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate calculated using serum creatine (eGFRer) of less than 30 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, if pre-hospitalization serum creatine is available; and/or (6) Treating clinician(s) believe(s) that either immediate or deferral of CVVHDF initiation is mandated; and/or (7) Pregnant or breast feeding.