1. Clinical Indicators for Extracorporeal Removal

Extracorporeal removal is a critical intervention reserved for life-threatening poisonings that manifest as severe metabolic, cardiac, hemodynamic, or neurologic compromise unresponsive to standard supportive care and antidotal therapy.

A. High Anion-Gap Metabolic Acidosis (HAGMA)

Pathogenesis: The accumulation of unmeasured anions, such as formate in methanol toxicity, glycolate in ethylene glycol poisoning, or organic acids in salicylate overdose, leads to a significant increase in the anion gap (AG).

• Diagnostic Thresholds: An anion gap >20 mEq/L or an arterial pH <7.25 despite aggressive sodium bicarbonate therapy are strong indicators.
• Clinical Reasoning: A persistently elevated AG accompanied by ongoing acidemia signifies that endogenous clearance mechanisms are overwhelmed, necessitating extracorporeal removal to correct the metabolic derangement and eliminate the parent toxin and its toxic metabolites.

B. Refractory Ventricular Arrhythmias and Cardiotoxicity

• Indications: QRS duration >100 ms, sustained ventricular tachycardia, or severe bradyarrhythmias that are unresponsive to standard antidotes (e.g., sodium bicarbonate, glucagon, high-dose insulin).
• Common Toxins: Tricyclic antidepressants, digoxin, and severe beta-blocker or calcium-channel blocker overdoses are classic culprits.
• Rationale: Extracorporeal therapies can rapidly accelerate the removal of the free, unbound toxin from circulation, helping to stabilize myocardial conduction, restore electrical stability, and improve overall hemodynamics.

C. Hemodynamic Instability and Neurologic Deterioration

• Hemodynamic: Persistent hypotension despite adequate fluid resuscitation and high-dose vasopressor support suggests severe toxin-induced vasodilation or myocardial depression. Continuous renal replacement therapy (CRRT) is often preferred in these hemodynamically unstable patients.
• Neurologic: Coma, refractory seizures, or profound sedation seen in baclofen or barbiturate poisoning may warrant extracorporeal removal. Early intervention can reverse CNS depression and prevent complications of prolonged immobility and mechanical ventilation.

2. Laboratory Evaluation and Toxin-Specific Assays

Quantitative toxin levels, in conjunction with routine chemistries, are essential for guiding the selection of modality, timing of initiation, and duration of extracorporeal therapy.

A. Quantitative Toxin Levels

Rebound Monitoring: It is crucial to repeat toxin levels 2–4 hours after completing a dialysis session to detect rebound phenomena, where the toxin redistributes from the intracellular to the extracellular compartment.

B. Routine Chemistries

• Electrolytes: Hypokalemia and hypomagnesemia can exacerbate cardiotoxicity and arrhythmias from various poisonings. These should be corrected promptly.
• Renal Function: An elevated serum creatinine indicates impaired endogenous clearance, prolonging the elimination of hydrophilic toxins and influencing their volume of distribution.
• Acid-Base Status: Serial measurements of bicarbonate and lactate are vital to assess the efficacy of toxin removal and guide the continuation or cessation of therapy.

C. Trends and Dynamic Monitoring

• Frequency: Repeat toxin assays and key chemistries every 2–4 hours during acute extracorporeal therapy to guide management.
• Trend Analysis: The closure of the anion gap often correlates well with the clearance of toxins like methanol, ethylene glycol, and salicylates. It can serve as a valuable surrogate marker for determining the duration of therapy.

3. Severity Classification Tools

Standardized scoring systems augment clinical judgment by objectively quantifying the severity of toxicity, which helps in predicting outcomes and justifying the use of invasive therapies.

A. Poisoning Severity Score (PSS)

The PSS is a simple, rapid tool used for triage and resource allocation. A score of 3 or higher indicates a life-threatening poisoning that likely requires urgent extracorporeal support.

B. APACHE II Score

The APACHE II score integrates 12 physiologic variables, age, and chronic health status to generate a predicted mortality risk. While not specific to toxicology, it is a robust measure of illness severity.

• Adaptation: An APACHE II score greater than 20 in the context of an acute poisoning correlates with an increased need for intensive interventions, including extracorporeal removal.

C. Combined Application in Triage

• Triggers for Consultation: A PSS ≥3 or an APACHE II score >20 should prompt an immediate nephrology and/or toxicology consultation to discuss the role of extracorporeal therapy.
• Institutional Protocols: Embedding clear, score-based thresholds into institutional poisoning protocols can help standardize care and minimize delays in initiating life-saving therapies.

4. Modality Selection Algorithm

The optimal extracorporeal modality and timing are determined by integrating clinical indicators, laboratory data, severity scores, and specific toxin characteristics.

A. Integration of Data

• Hemodynamic Stability: If the patient is stable, intermittent hemodialysis (IHD) is preferred for its efficiency and rapid clearance. If the patient is unstable and requires vasopressors, CRRT or sustained low-efficiency dialysis (SLED) provides gentler solute and fluid removal, improving hemodynamic tolerance.
• Toxin Characteristics:
  • Toxins with a molecular weight <500 Da, low protein binding (<30%), and a small volume of distribution (<1 L/kg) are readily removed by dialysis.
  • Toxins with high protein binding or a large volume of distribution may be poorly dialyzable and require alternative therapies like hemoperfusion or specialized adsorptive membranes.

B. Timing of Initiation

• Early Initiation: Therapy should be started before peak organ damage occurs. This decision is guided by a combination of rising toxin levels, worsening acid-base status (pH <7.3, AG >20), and high severity scores (PSS ≥3).
• Rescue Therapy: When initiated after end-organ compromise is already established, extracorporeal removal is considered a rescue therapy and often demands higher intensity and a longer duration of clearance.