Treatment of Poisoning with Extracorporeal Methods

Background

The range of drugs, chemicals, and natural toxins that can induce poisoning is vast, as are their manifestations. Acute poisoning may follow intentional self-poisoning or a single prescribing or dosing error; chronic poisoning most commonly follows a prescribing or dosing error leading to a drug–drug interaction or a drug–disease interaction due to intercurrent conditions, such as impaired kidney function.

Initial Treatment

The initial steps to the management of all poisoned patients are resuscitation, risk assessment, close observation, and supportive care. Careful attention to these basic critical care skills is central to management of any poisoned patient, in view of the potential for multisystem manifestations, especially when the incriminating poison and/or exposure are unknown. When the poison exposure is confirmed, toxicity should be anticipated so that necessary interventions can be instituted. Patients who are clinically unstable, or may become so, should be managed in a critical care environment. Early intubation is commonly required for airway protection and is often performed preemptively in exposures that can develop severe toxicity. Hypotension may be cardiogenic, hypovolemic, or distributive in nature, depending on the poison, and resuscitation, inotrope, or vasopressor support is guided by the specific etiology. Supportive care may also include correction of poison-induced dysrhythmias, hypothermia or hyperthermia, and seizures according to current recommendations (reviewed elsewhere).

Risk Assessment

After resuscitation, a careful risk assessment is required to guide further treatment. The risk assessment is a detailed cognitive process that incorporates consideration of the exposure (type and amount), time since the exposure, likely clinical manifestations, resources required such as critical care support, antidotes, and access to ECTRs in a clinically reasonable time frame. This may be supported by blood tests, such as the anion gap, an osmol gap, or a poison concentration. The risk assessment guides the duration of observation, place for admission, and treatments required. For example, it may prompt transfer to another institution for the purpose of treatment with ECTR. Prompt communication with a regional poison center will assist with the risk assessment and offer valuable expertise on management issues.

Decontamination

Decontamination is defined as the prevention of absorption of a poison. This may be dermal (e.g., chemical spills), ocular, or gastrointestinal. Various therapeutic options are available for gastrointestinal decontamination. Activated charcoal 1 to 2 g/kg enterally is usually the preferred agent for most poisons, but its effect is limited to use with organic nonpolar poisons such as metals and alcohols. Its main beneficial effect is within 1 hour of ingestion, although delayed administration may have a role with massive exposures, sustained-release preparations, or poisonings associated with delayed gut transit (e.g., opioid agonists or anticholinergic drugs).

Whole-bowel irrigation using polyethylene glycol 1 to 2 L/h enterally is sometimes used in the treatment of poisonings with sustained-release medications, massive exposures, or those that are not adsorbed to charcoal, such as metals including lithium, iron, and lead. Gastric lavage, forced emesis, and other cathartics have a minimal role in the majority of poisonings.

Antidotes

Antidotes are drugs that can reverse or reduce toxicity, such as naloxone for opioid poisoning, ethanol or fomepizole for toxic alcohols, oxygen for carbon monoxide, chelators for certain metals, sodium bicarbonate for sodium channel blocking agents, methylene blue for methemoglobinemia, and others.

In the event that an ECTR is also required for the treatment of such a poisoning, it is necessary to ascertain whether the ECTR will remove the antidote. If the antidote dosage is not increased accordingly, this may result in subtherapeutic concentrations; this has been demonstrated for N -acetylcysteine, ethanol, and fomepizole.

Enhanced Elimination

A final but important consideration in the medical treatment of poisoning is the potential benefit of enhanced elimination. Here, treatments increase the total clearance of the poison, with the aim of shortening poisoning duration and severity.

Multiple doses of activated charcoal (MDACs) are recommended to enhance the elimination of a number of poisons, including carbamazepine, dapsone, quinine, phenobarbital, and theophylline. MDAC may also facilitate elimination of cardiac glycosides, phenytoin, aspirin, colchicine, and amatoxin. The mechanism of action is not completely understood for each indication but may relate to interruption of enterohepatic circulation, enteral dialysis, or interfering with a prolonged absorption phase.

Urinary alkalinization with sodium bicarbonate can enhance the elimination or reduce nephrotoxicity of some poisons. Increasing urine pH either promotes solubility of the poison or, in the case of weak acids (i.e., with a dissociation constant, pKa, lower than the urinary physiologic pH), increases the proportion of poison that is ionized, which enhances urinary elimination. Clinical applications of urine alkalinization include salicylate, chlorophenoxy herbicides (e.g., 2-methyl-4-chlorophenoxyacetic acid [MCPA], 2,4-dichlorophenoxyacetic acid [2,4-D]), and to a lesser extent for methotrexate, myoglobin, and fluoride. It has also been used in phenobarbital poisoning, but the effect is less than that of MDAC, so here it is only used if MDAC cannot be given (e.g., because of ileus). Potential complications associated with urine alkalinization are alkalemia, hypokalemia, hypocalcemia, hypernatremia, and volume overload. In fact, alkaline urine is achieved only in the presence of normokalemia.

ECTRs can significantly enhance the elimination of a range of poisons (as well as their metabolites).