I. Epidemiology and Incidence of Poisonings Requiring Extracorporeal Removal

Although rare, poisonings that necessitate extracorporeal clearance carry a high burden of morbidity and mortality. Global incidence rates are estimated at 3–15 cases per 100,000 people annually. In the intensive care unit (ICU), a significant portion of dialysis sessions for poisonings are attributed to a few key agents: methanol, ethylene glycol, salicylates, and lithium. The prevalence of these cases often shows regional variation, reflecting local patterns of toxin exposure and the availability of specialized resources.

Key Points

• Incidence: Approximately 1–2% of ICU dialysis sessions for poisonings are for lithium toxicity, while 5–8% are for salicylates.
• Common Agents: The most frequently encountered toxins include methanol (often from illicit alcohol outbreaks), ethylene glycol, salicylates (typically in cases of self-harm), lithium (especially in elderly patients on chronic therapy), and metformin (leading to lactic acidosis in diabetic populations).
• Demographics: The primary demographic is adults aged 30–60. Pediatric cases are less common but present unique pharmacokinetic challenges.
• High-Risk Groups: Patients with chronic kidney disease (CKD), hepatic dysfunction, or hypoalbuminemia are at increased risk. Delayed presentation, common in rural or disadvantaged populations, also worsens prognosis.
• Resource Impact: In low-resource settings, limited access to high-flux membranes and specific antidotes can prolong ICU stays and lead to poorer outcomes.

II. Mechanisms of Toxin Accumulation and Rationale for Extracorporeal Removal

In an overdose scenario, the body’s standard ADME (Absorption, Distribution, Metabolism, Excretion) processes become overwhelmed. Saturation of metabolic pathways and impaired elimination mechanisms lead to a prolonged toxin half-life and escalating toxicity. Extracorporeal techniques, such as dialysis, provide a life-saving intervention by directly intercepting toxins and their harmful metabolites from the blood compartment.

Physicochemical Properties Favoring Removal

The effectiveness of extracorporeal toxin removal (ECTR) is largely determined by the toxin’s inherent properties. Ideal candidates for removal exhibit the following characteristics:

• Molecular Weight: Small molecules (<500 Daltons) pass easily through dialysis membranes.
• Protein Binding: Low protein binding (<80%) ensures a large free fraction of the toxin is available in the plasma for removal.
• Volume of Distribution: A small volume of distribution (<1 L/kg) indicates the toxin remains primarily within the bloodstream, making it accessible to the dialysis circuit.
• Hydrophilicity: Water-soluble toxins are more readily cleared by dialysis.

III. Impact of Chronic Comorbidities on Toxin Kinetics

Pre-existing renal and hepatic dysfunction dramatically reduces the body’s endogenous ability to clear toxins and their metabolites. This impairment significantly lowers the threshold at which artificial removal becomes necessary and urgent.

Key Points

• Renal Impairment: In patients with CKD stages 3–5, the elimination half-lives of renally cleared toxins are markedly prolonged (e.g., lithium half-life can increase from 24 hours to over 60 hours). This condition also impairs the ability to perform urinary alkalinization, a key treatment for salicylate poisoning.
• Hepatic Dysfunction: Reduced liver function impairs Phase I and Phase II metabolism of many drugs and toxins. It can also alter the clearance of antidotes; for example, fomepizole dosing often requires adjustment during dialysis.
• Other Factors: Comorbidities like heart failure reduce organ perfusion, further slowing toxin clearance. Hypoalbuminemia, common in critically ill or malnourished patients, increases the free fraction of highly protein-bound drugs, potentially increasing their toxicity.

IV. Social Determinants of Health and Access to Care

Patient outcomes in severe poisonings are heavily influenced by social and economic factors. Delayed presentation to medical care, limited health literacy, and geographic barriers to specialized centers can all increase the time to definitive therapy like ECTR, leading to worse outcomes.

Key Factors

• Delayed Presentation: A delay of more than 4 hours between ingestion and presentation is strongly correlated with higher mortality. This is due to deeper tissue distribution of the toxin and the onset of irreversible organ injury.
• Health Literacy: Misinterpretation of early symptoms or a lack of understanding of the danger can delay self-presentation and the implementation of crucial decontamination measures.
• Center Resources: Access to high-volume centers with 24/7 toxicology consultation, nephrology services, and advanced technologies like high-flux dialysis membranes is proven to reduce mortality and ICU length of stay.

V. Clinical Implications and Patient Selection

Effective patient selection for ECTR requires a holistic approach that integrates epidemiology, toxin properties, patient comorbidities, and social context. The decision to initiate therapy should be guided by established consensus thresholds for specific toxins and clinical scenarios.

Patient Selection Framework

1. Identify High-Risk Toxins: Recognize poisonings with agents known to be effectively removed by ECTR and check if plasma concentrations exceed critical thresholds (e.g., methanol >20 mg/dL; salicylate >100 mg/dL in acute ingestion).
2. Assess Comorbidities: Evaluate the patient for underlying conditions (renal, hepatic, cardiac failure) that impair endogenous toxin clearance.
3. Evaluate Social Factors: Consider the impact of presentation delay and transport logistics on the overall clinical picture.
4. Apply Standardized Criteria: Use evidence-based guidelines, such as those from the EXTRIP (Extracorporeal Treatments in Poisoning) workgroup, to standardize initiation thresholds.
5. Choose Modality: Select intermittent hemodialysis for rapid clearance in stable patients or CRRT for hemodynamically unstable patients requiring slower, continuous removal.
6. Set Time-to-Treatment Goals: Aim for ECTR initiation within 6 hours of a high-risk ingestion to maximize the chance of survival and good neurological outcome.