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 distributed to the gastrointestinal tract, kidneys, liver, skeletal muscle, lungs, myocardium, and central nervous system. Patients with severe diquat poisoning often develop toxic encephalopathy, circulatory collapse, and multi-organ dysfunction. Extracorporeal treatments, including hemoperfusion, hemodialysis, and continuous kidney replacement therapy (CKRT), are widely employed to manage diquat poisoning. Continuous veno-venous hemodiafiltration (CVVHDF), the most frequently used CKRT modality, is primarily indicated for acute kidney injury (AKI). AKI 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 AKI. 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 (ED). 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 yet to be evaluated in clinical trials. Currently, the standard practice delays initiation of CVVHDF until AKI has developed. Accordingly, this study proposes a pragmatic cluster-randomized controlled trial (RCT) to determine whether, in severe acute diquat poisoning patients, accelerated initiation of CVVHDF following hemoperfusion is preferred compared to a standard approach in which CVVHDF is initiated only in the presence of AKI or at the discretion of the treating clinician.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
267
CVVHDF will be delivered following hemoperfusion with a dialysate-to-replacement fluid ratio maintained at 1:1, a blood flow rate of 150-200 mL/min, and a target dialysis dose of 30 mL/kg/h (excluding additional fluid removal). Regional anticoagulation (e.g., heparin or other agent per device requirements) will be used to prevent clotting within the circuit. Once CVVHDF is initiated in either arm, it will not be discontinued until one of the following encountered: (i) death; or (ii) a change in goals of care with withdrawal of life-sustaining interventions; or (3) recovery of kidney function, as determined by treating clinician(s), such that CVVHDF will be no longer required. However, CVVHDF will be reinitiated at the discretion of treating clinician(s), if kidney function comes suboptimal after a period of discontinuation.
All-cause mortality rate
Time frame: 90 days within the index date of randomization
Time from exposure to death
The primary outcome measure included time from exposure to death.
Time frame: 90 days within the index date of randomization
ICU-free days
Time frame: 90 days within the index date of randomization
Ventilator-free days
Time frame: 90 days within the index date of randomization
Vasoactive-free days
Time frame: 90 days within the index date of randomization
CVVHDF dependence rate
Time frame: 90 days within the index date of randomization
Hospitalization-free days
Time frame: 90 days within the index date of randomization
Major adverse kidney events rate
The secondary outcome measure included major adverse kidney events at 90 days after randomization, defined as the composite of death, CVVHDF dependence, or sustained reduction of kidney function (defined as eGFR \<75% of the lowest eGFR measured during hospitalization).
Time frame: 90 days within the index date of randomization
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