Approach to a Poisoned Patient: Fundamentals Nephrologists Need to Know

The World Health Organization estimates that 3 million cases of intoxication occur globally each year due to various toxic agents, according to a recent article in the Journal of Family Medicine and Primary Care (1). Treatment of an individual who is poisoned starts with providing supportive care, evaluating organ dysfunction, and identifying potential or confirmed toxins. It is important to consider the likelihood of multiple substances being ingested, especially in cases of deliberate exposure or suicide attempts.

Most poisonings occur through ingestion, with enteric decontamination aimed at preventing toxin absorption from the gastrointestinal tract. This typically includes activated charcoal, which adsorbs various toxins if administered within 1 hour of consuming the toxin (2). Other methods like gastric lavage, cathartics, and ipecac-induced emesis are generally not recommended due to a lack of evidence for a clinical benefit and potential risks, such as aspiration and pneumonitis. Whole bowel irrigation may be beneficial in specific instances involving sustained-release or enteric-coated drugs or ingesting substances such as lithium, iron, or potassium tablets. However, it is generally not advised as a routine procedure and is contraindicated in patients with bowel complications (3).

Antidotes mitigate toxicity using mechanisms like competitive receptor antagonism, accelerating the metabolism of the toxin to less harmful substances, inhibiting the production of toxic metabolites, promoting immune clearance, and exerting various other molecular effects (4) (Table).

Table

Antidotes for drug overdoses and poisoning

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Intravenous lipid emulsion (Intralipid 20%) (5) is suggested off-label for strong poisoning from local anesthetics such as bupivacaine, which can cause cardiac arrest, and intractable cases with amitriptyline and bupropion. However, caution is advised because of possible adverse effects, including fat embolism, lung injury, and complications while performing extracorporeal membrane oxygenation.

Enhancing elimination techniques involve increasing the clearance of drugs or toxins by modulating urinary pH (6), ion trapping, diuresis, or forced diuresis (7) and using enteric decontamination and extracorporeal therapies. Drug excretion is enhanced by ion trapping by adjusting urine pH to ensure that drugs remain ionized within the urinary lumen, thus preventing reabsorption. For instance, increasing the urine pH above 7.5 can significantly enhance the elimination of salicylates, which are weak acids, by keeping them in an ionized state (6). Conversely, acidification of urine can increase the clearance of basic drugs like amphetamines by maintaining a low urine pH. These maneuvers, however, require careful monitoring of electrolytes and pH levels due to potential complications such as alkalosis and hypokalemia. Alkalinization is also used in managing moderate salicylate poisoning and as part of the strategy to prevent toxicity from high-dose methotrexate. However, acidification is generally discouraged due to risks like exacerbating myoglobinuric renal injury.

Intermittent hemodialysis, using high-efficiency and high-flux biocompatible synthetic membranes, is the most common extracorporeal modality used for poisoning treatment, with hemofiltration being used occasionally and hemoperfusion very rarely. Clinical indications for dialysis include patients with deteriorating conditions despite supportive care, acute kidney injury, electrolyte disturbance, or acid-base imbalances (Figure) (8). Hemodialysis factors influencing drug removal include molecular weight (preferably <500 Da), water solubility, the degree of protein binding, distribution volume, and the equilibration rate from tissue to plasma. Modern dialyzers enhance this process by allowing both diffusive and convective solute removal, effectively clearing substances like lithium, methanol, ethylene glycol, and salicylates (9).

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Indications for hemodialysis in poisoning

Citation: Kidney News 16, 8

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Hemofiltration targets larger molecules up to 50,000 Da, which is especially useful for drugs with large distribution volumes or slow plasma equilibration. It is often used in continuous modes like continuous venovenous hemofiltration for patients who are hemodynamically unstable. Hemoperfusion, although less frequently used due to its limitations and cost, involves drug adsorption from blood using activated charcoal or resin columns. It effectively removes a range of molecules from 100 to 40,000 Da. Despite its specific use for certain poisonings like paraquat, hemodialysis with high-flux membranes has largely supplanted hemoperfusion due to its broader applicability, lower cost, and higher solute clearance capabilities.

Peritoneal dialysis is usually used in younger children when other extracorporeal therapies are unavailable. Patients who are already on peritoneal dialysis can perform rapid exchanges for removing dialyzable drugs.

Chelation therapy uses chelators to bind and excrete toxic metals from the body. It is commonly applied to treat metal intoxications such as arsenic, lead, and mercury, which are known neurotoxins. Chelation therapy must be approached with caution due to the potential depletion of essential minerals such as copper, selenium, zinc, and magnesium, necessitating close monitoring for deficiencies.

Combining chelation with extracorporeal detoxification methods, such as dialysis or hemofiltration, enhances the removal of metal-chelator complexes. For example, deferoxamine treats iron overload when used with high-flux polysulfone membranes compared with charcoal hemoperfusion. The pairing of dimercaptosuccinic acid or dimercaptopropane sulfonate with dialysis has shown promise in managing heavy metal toxicity, particularly in kidney dysfunction.

A novel method involving displacer-augmented hemodialysis has been developed to enhance the clearance of highly protein-bound toxins. This technique uses competitive binding inhibitors like ibuprofen to displace toxins from albumin, thereby increasing their unbound fraction and removal efficiency during dialysis. This approach could revolutionize the treatment of poisoning from highly protein-bound drugs. Specifically, studies are done by using ibuprofen for carbamazepine and aspirin for phenytoin intoxication.