Selecting Patients and Toxins

ECTR is worth its risks only when it removes a clinically meaningful amount of toxin faster than the body can, and when that removal is expected to change outcome. Three conditions must hold together. [1,24–26]

1. The toxin is removable. For hemodialysis this means low molecular weight (below roughly 10,000 Da for high-flux membranes), low protein binding (or binding that saturates in overdose, as with salicylate and valproate), water solubility, and a small volume of distribution (generally below about 1 L/kg).

2. Endogenous clearance is low. ECTR adds most when the patient's own clearance is small, for example from kidney impairment, saturated metabolism, or a long half-life. A toxin cleared rapidly by healthy kidneys or liver gains little from dialysis.

3. The poisoning is severe or predicted to be. Severity is judged by the poison-specific clinical and concentration thresholds in the next section, not by general markers such as a low GCS or aspiration.

ECTR also corrects acidemia, hyperkalemia, fluid overload and uremia. These are independent indications in any patient, but they are not by themselves a reason to dialyze for toxin removal.

Absence of an EXTRIP recommendation is not a recommendation against ECTR. For a toxin not covered here, do not infer that ECTR is either indicated or contraindicated; assess toxin-specific kinetics and evidence and consult medical toxicology and nephrology. Organophosphates, metal phosphides and paraquat are examples where no credible evidence shows that extracorporeal removal improves outcome.

Poisons With an EXTRIP Indication for ECTR

ECTR is recommended or suggested when the corresponding criterion is met, according to the recommendation strength shown in each column, and always alongside standard care and antidotes. Apply weak (suggested) criteria in the clinical context of the individual patient rather than as triggers. Concentrations are serum values.

Toxic Alcohols

Methanol recommendations: [2]. Ethylene glycol recommendations: [3].

The two anion gap formulas differ. Check which one you are using. Methanol thresholds use Na − Cl − HCO₃, without potassium. Ethylene glycol thresholds, both for starting and for stopping, use Na + K − Cl − HCO₃, with potassium. Many US laboratories report the gap without potassium. An anion gap calculated that way is lower by approximately the serum potassium concentration, commonly about 4 mmol/L, so a value taken straight off the chemistry panel will understate the gap against the EXTRIP ethylene glycol cut-offs.

The ethylene glycol osmol gap is measured minus calculated osmolality in SI units, adjusted for ethanol. [3]

EXTRIP specifies no osmol gap threshold for methanol, unlike ethylene glycol. The osmol gap may still inform the decision when a methanol concentration is unavailable (1D), but no cut-off is given. [2]

Acid–Base and Metabolic Poisons

Salicylate recommendations: [5]. Metformin recommendations: [6].

Metformin — conditions that lower the threshold for starting ECTR: shock or impaired kidney function (1D); liver failure or decreased level of consciousness (2D). These are not independent indications; their presence lowers the clinical threshold for initiating ECTR. EXTRIP does not define a separate numeric lactate or pH threshold for patients who have them. [6]

Anticonvulsants and Sedatives

Valproic acid: [7]. Carbamazepine: [9]. Long-acting barbiturates: [10]. Phenytoin: [13].

Other Poisons

Lithium: [4]. Theophylline: [8]. Acetaminophen: [11,23]. Thallium: [12].

ECTR Indications Limited to Patients With Kidney Impairment

These agents are dialyzable regardless of kidney function. What changes is the indication: EXTRIP confines it to severe poisoning with kidney impairment, and suggests against ECTR, or makes no recommendation, when kidney function is normal.

Beta-blockers: [14]. Gabapentin/pregabalin: [15]. Baclofen: [16].

Reviews from 2021 onward (ethylene glycol, beta-blockers, gabapentinoids, baclofen) use GRADE wording, strong or weak with quality of evidence, instead of the 1D/2D format. Every ethylene glycol recommendation rests on very low-quality evidence, so strong and weak there correspond to 1D and 2D.

If ECTR is used for gabapentinoids or baclofen, monitor for withdrawal afterward. [15,16]

Where the original EXTRIP criteria and the 2023 US/Canada consensus differ on acetaminophen, this guideline follows the more inclusive 2023 consensus criterion for US clinical practice. A patient meeting the consensus criterion should be dialyzed even if only one of the three EXTRIP features is present. [11,23]

Phenytoin has only weak or neutral indications, so it is labeled “ECTR optional” rather than grouped with methanol or lithium. [13]

Poisons Where EXTRIP Recommends Against ECTR

For these agents, EXTRIP recommends or suggests against routine ECTR, because the available evidence, usually of very low quality, does not show benefit sufficient to justify it in the setting specified. Exceptions are given in the right-hand column. Use supportive care and toxin-specific therapy as indicated.

References: TCA [17]; digoxin [18]; calcium channel blockers [19]; propranolol [14]; quinine/chloroquine [20]; methotrexate [21]; isoniazid [22]; baclofen [16]; gabapentinoids [15].

Within the beta-blocker class, propranolol, carvedilol, labetalol and timolol are not dialyzable, while atenolol, nadolol, practolol and sotalol are. For sotalol, EXTRIP also suggests against ECTR based on the QT interval alone. [14]

EXTRIP has not yet issued recommendations for amatoxins; that review is listed as pending.

Choosing the Modality

Use intermittent hemodialysis whenever it is available. It gives the highest clearance per hour and is the EXTRIP-preferred modality for every poison in the indications table. [1,24–26]

1. Intermittent hemodialysis (IHD). First line, including in hypotensive patients, who can usually be dialyzed with vasopressor support.

2. Intermittent hemoperfusion (HP). An acceptable alternative when IHD is unavailable for several poisons (for example carbamazepine, theophylline, valproate). Cartridges are now scarce in many US centers, and HP carries more thrombocytopenia and hypocalcemia.

3. Continuous renal replacement therapy (CRRT). An acceptable alternative only when IHD is unavailable or the patient truly cannot tolerate it. Clearance per hour is several times lower, so it may fail to lower concentrations in time. After an initial IHD session, CRRT and IHD are equally acceptable for lithium (1D) and for repeat metformin sessions (1D).

High protein binding does not by itself rule out hemodialysis. Binding often saturates in overdose, and modern high-efficiency HD still achieves useful clearance; EXTRIP prefers IHD over HP even for valproate and carbamazepine. Reserve HP for situations where IHD is unavailable.

Always continue multiple-dose activated charcoal (MDAC) and antidotes where the table lists them, since these work in parallel with ECTR.

Dialysis Prescription and Monitoring

The goal is maximal clearance, unlike maintenance dialysis. Prescribe for toxin removal, then adjust for the patient's electrolytes and hemodynamics. The operational parameters below follow Bouchard et al., Semin Dial 2014. [26]

Monitor during the run: vital signs continuously; poison concentration, blood gas, potassium, phosphate, ionized calcium, magnesium and glucose every 2–4 h; and mental status.

If the concentration is not falling as expected, check access recirculation, Qb and dialyzer clotting before extending the run.

Antidotes and Co-Therapy During ECTR

Hemodialysis removes several antidotes as efficiently as it removes the poison. Adjust them for the duration of the run.

Poison-specific support: methanol [2], ethylene glycol [3], salicylates [5], valproate [7], theophylline [8], carbamazepine [9], barbiturates [10], acetaminophen [11,23], and thallium [12].

Stopping ECTR and Post-ECTR Care

Stop when the poison-specific criterion in the indications table is met. Do not stop on a time limit alone while the patient remains toxic.

• Check for rebound. For lithium, obtain serial lithium concentrations over 12 h after stopping to decide on further sessions (EXTRIP 1D). For metformin, monitor lactate and acid–base status closely after the run. Recheck levels after valproate, theophylline and carbamazepine, which can redistribute from tissue. Restart ECTR if an indication recurs. [4,6–9]

• Continue antidotes until their own end point, which may come after ECTR stops (for example fomepizole until methanol or ethylene glycol is below the treatment threshold with a normal pH).

• Correct electrolytes after the run, particularly potassium, phosphate and magnesium.

• Reassess for a second session when the patient has impaired kidney function, a sustained-release ingestion, or a concentration still above threshold.

• Watch for withdrawal after ECTR for gabapentinoid or baclofen toxicity, especially in long-term users. [15,16]

Contraindications and Cautions

There are few absolute contraindications once an EXTRIP indication is met. The main risks are from vascular access and the run itself.

• Hypotension is not a contraindication. Dialyze with vasopressor support; consider CRRT only if IHD truly cannot be tolerated.

• Bleeding risk or coagulopathy. Run heparin-free and place the catheter under ultrasound at a compressible site.

• No vascular access possible, or patient or surrogate refusal, are the practical absolute contraindications.

• Goals of care that exclude invasive therapy.

• Do not delay ECTR waiting for a confirmatory level when clinical criteria are already met.

• Children. Indications generally follow the same toxin-specific principles, with age-specific exceptions (for example the theophylline threshold under 6 months, and exchange transfusion as an alternative in neonates for salicylates, theophylline and acetaminophen). Access, circuit priming volume and blood flow need pediatric nephrology input.