Underutilization of ECT in Acute Intoxication

Extracorporeal therapy (ECT) is a set of modalities that can be used in a variety of settings to tackle issues involving volume, blood pressure, electrolyte imbalance, or any combination of these. In specific instances, the use of ECT, such as hemodialysis, can also be used for its ability to clear poisons. Since the development of the first hollow fiber dialyzer in the 1960s, advances in filter and membrane technology have increased the efficiency and capability of removing endogenous toxins and by extension, exogenous toxins (1). Modern hemodialyzers (Figure), created with synthetic polymers and manufactured with the use of nanotechnology, have increased membrane permeability and allowed for more combined diffusion and convective clearance strategies (2). Despite the infrequency of poisoning and the smaller subset of patients who meet indications for ECT, the role for use remains vital. Data published within the Annual Report of the National Poison Data System demonstrate that ECT constitutes a small fraction of the therapy provided to acute toxin exposures (3, 4). Recognition of clinical scenarios in which use of ECT may be beneficial will increase its utility as a supportive measure for acute poisoning.

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Inside of a hemodialysis dialyzer

Citation: Kidney News 16, 10/11

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When prescribing ECT for acute poisoning, several factors must be considered. First, the poisoning must be associated with serious morbidity or mortality. Although various antidotes exist for different toxins, ECT should be considered if these antidotes are unlikely to prevent further deterioration. Additionally, ECT is warranted if the poison continues to cause significant toxicity despite active treatment aimed at minimizing absorption or maximizing elimination (5). Properties of individual toxins also weigh into the clinical decision to pursue ECT. Volume of distribution, molecular weight, and protein binding make certain toxins more amenable to treatment with ECT. If a toxin is more hydrophobic or lipophilic, it will have a larger volume of distribution and be less readily cleared through ECT filtering of plasma volume. Similarly, toxins with larger molecular weight will be physically unable to clear the dialyzer due to size restriction of the membrane. From this perspective, extensive protein binding of toxins will have larger molecular weights when factoring in the molecular weight of blood proteins like albumin; thus, protein-bound toxins are less dialyzable (1, 6).

Lithium is an excellent example that highlights some of the challenges involved in prescribing ECT for poisoning. The EXTRIP (Extracorporeal Treatments in Poisoning) workgroup guidelines recommend initiation of ECT when comorbidities (e.g., arrhythmia, seizure, or coma) are present, and serum levels are elevated (7). Lithium is water-soluble, is not highly protein-bound, and has a low volume of distribution, making it easy to dialyze. However, the volume of distribution does not account for the use of sodium transport channels that slow distribution and contribute to rebound serum levels following cessation of ECT. Furthermore, the toxicity of lithium is not inherently correlated with serum level, which makes clinical practice regarding when to prescribe or stop ECT more difficult (1, 7).

ECT provides a method to rapidly reduce serum concentration and clear toxic levels of many common poisons (6). Use of modalities like hemodialysis or continuous renal replacement therapy (CRRT) has added advantages in restoring physiologic balance and correcting metabolic derangements that frequently occur concomitantly with poisonings. Maximizing the use of extracorporeal filtration and removal involves consideration of time to initiation and the method of ECT used. Hemodialysis is the preferred ECT method in most cases of acute poisoning, having higher efficiency and clearing toxins more rapidly. This efficiency relates to the ability to filter larger volumes of plasma over shorter periods of time as compared with CRRT (1). Its relatively quick set-up time and ready availability in many centers further contribute to its usefulness over other ECT methods such as hemoperfusion and hemofiltration, both which involve the use of solvents.

Despite lower efficiency with CRRT, modalities such as continuous veno-venous hemofiltration and continuous veno-venous hemodialysis have seen increased use over time (1, 5, 6). Easy application within the setting of shock and less hemodynamic effects make CRRT ideal in critical care settings. Additionally, toxins that have large volumes of distribution and are slow to equilibrate between intravascular and extracellular compartments may benefit from more continuous removal. Therapeutic plasmapheresis, another form of ECT, is yet another modality that can be used to tackle toxins that are highly protein-bound (1). Ultimately, as with the decision to pursue ECT, the decision about which modality to use is also dependent on the properties of the toxin (Table).

Table

Toxin properties and amenability of ECT modalities

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As technology continues to advance, and the availability of ECT continues to increase, it may be the case that ECT becomes a more feasible first-line alternative to supportive care. Since the inception of modern dialysis, improvements in dialyzer and membrane technology have increased the efficiency of chronic dialysis and consequently efficacy in the context of acute poisoning. As manufacturing techniques become even more refined with the integration of advanced polymers, there exists the potential to dialyze larger molecules or more protein-bound toxins. Increased use will also add to anecdotal experience and expertise in different use cases, generating more evidence for use in various clinical contexts.