Toxicology Primer 
Acetaminophen (APAP) Poisoning
General Recommendation
General Recommendation
ECTR is suggested in severe APAP poisoning (2D)
Indications
Indications
Indications
ECTR is recommended
- If the [APAP] more than 1000 mg/L (6620 μmol/L) and NAC is NOT administered (1D)
- If the patient presents with altered mental status, metabolic acidosis, with an elevated lactate, and an [APAP] is more than 700 mg/L (4630 μmol/L) and NAC is NOT administered (1D)
- If the patient presents with an altered mental status, metabolic acidosis, an elevated lactate, and an [APAP] is more than 900 mg/L (5960 μmol/L) even if NAC is administered (1D)
ECTR is not recommended
- On the basis of the reported ingested dose if NAC is administered (1D)
ECTR is not suggested
- On the basis of reported ingested dose alone even if NAC is NOT administered (2D)
- Solely on the basis of the [APAP] if NAC is administered (2D).
Cessation of ECTR
Cessation of ECTR
- ECTR is recommended until sustained clinical improvement is apparent (1D)
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is the preferred ECTR in patients with APAP poisoning (1D)
The following are acceptable alternatives if HD is not available:
- Intermittent HP (1D)
- CRRT (3D)
- Exchange transfusion in neonates (2D)
Miscellaneous
Miscellaneous
- NAC therapy should be continued during ECTR at an increased rate (1D)
Barbiturates Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe long-acting barbiturate poisoning (1D)
Indications
Indications
ECTR is recommended
- If prolonged coma is present or expected (1D)
- If shock is present after fluid resuscitation (1D)
- If, despite MDAC treatment, toxicity persists (1D)
ECTR is suggested
- If, despite MDAC treatment, serum barbiturate concentration rises or remains elevated (2D)
- If respiratory depression necessitating mechanical ventilation is present (2D)
Choice of ECTR
Choice of ECTR
- Intermittent HD is the preferred mode of ECTR of severe barbiturate poisoning (1D)
- HP (1D) or CRRT (3D) are acceptable alternative modalities in adults if HD is not available
Cessation of ECTR
Cessation of ECTR
- Cessation of ECTR is indicated when clinical improvement is apparent (1D)
Carbamazepine Poisoning
General Recommendation
General Recommendation
- ECTR is suggested in severe carbamazepine poisoning (2D)
Indications
Indications
ECTR is recommended if ANY of the following conditions are present:
- If multiple seizures refractory to treatment occur (1D)
- If life-threatening dysrhythmias occur (1D)
ECTR is suggested if ANY of the following conditions are present:
- If prolonged coma and/or respiratory depression requiring mechanical ventilation is present or expected (2D)
- If significant toxicity persists, especially if carbamazepine concentrations rise or remain elevated, despite MDAC and support measures (2D)
Cessation of ECTR
Cessation of ECTR
- Clinical improvement is apparent (1D)
- Carbamazepine concentration is below 10 mg/L (42 µmol/L) (2D)
Choice of ECTR
Choice of ECTR
- Intermittent HD is the preferred ECTR in carbamazepine poisoning (1D)
The following are alternatives if hemodialysis is not available:
- Intermittent hemoperfusion (1D)
- Continuous renal replacement therapy (3D)
Miscellaneous
Miscellaneous
- MDAC should be continued during ECTR (1D)
Methanol Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe methanol poisoning (1D)
Indications
Indications
ECTR is recommended if ANY of the following conditions are present:
- Coma (Grade 1D)
- Seizures (Grade 1D)
- New vision deficits (Grade 1D)
- Blood pH ≤7.15 (Grade 1D)
- Persistent metabolic acidosis despite adequate supportive measures and antidotes (Grade 1D)
- Serum anion gap higher than 24 mmol/L (Grade 1D); calculated by serum [Na+] – [Cl-] – [HCO3-].
- Serum methanol concentration greater than 700 mg/L or 21.8 mmol/L in the context of fomepizole therapy (Grade 1D)
- Serum methanol concentration greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment (Grade 1D)
- Serum methanol concentration greater than 500 mg/L or 15.6 mmol/L in the absence of an ADH blocker (Grade 1D)
- In the absence of a methanol concentration, the osmolal/osmolar gap may be informative (Grade 1D)
- In context of impaired kidney function (Grade 1D)
Cessation of ECTR
Cessation of ECTR
- ECTR can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed (Grade 1D)
- Prediction of time on HD: 3.39 x (ln(MCi/4))
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is the modality of choice in methanol poisoning (Grade 1D)
- Continuous modalities are acceptable alternatives if intermittent hemodialysis is not available (Grade 1D)
Miscellaneous
Miscellaneous
- ADH inhibitors are to be continued during ECTR for methanol poisoning (Grade 1D); as well as folic acid
Lithium Poisoning
General Recommendations
General Recommendation
- ECTR is recommended in patients with severe Li poisoning (1D)
Indications
Indications
ECTR is recommended:
- If kidney function is impaired and the [Li+]>4.0 mEq/L (1D)
- In the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of [Li+] (1D)
- if the [Li+]>5.0 mEq/L (2D)
- If confusion is present (2D)
- If the expected time to obtain a [Li+]<1.0 mEq/L with optimal management is >36 h (2D)
Cessation of ECTR
Cessation of ECTR
- When the [Li+] <1.0 mEq/L or clinical improvement is apparent (1D)
- After a minimum of 6 h of ECTR if the [Li+] is not readily available (1D)
- After interruption of ECTR, serial [Li+] measurements should be obtained over 12 h to determine use of subsequent ECTR sessions (1D)
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is the preferred ECTR (1D)
- Continuous RRT is an acceptable alternative if intermittent hemodialysis is not available (1D)
- After initial treatment, both continuous RRT and intermittent hemodialysis are equally acceptable (1D)
Metformin Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe metformin poisoning (1D)
Indications
Indications
ECTR is indicated if ANY of the following conditions are present:
- Lactate concentration greater than 20 mmol/L (1D)
- pH less than or equal to 7.0 (1D)
- Shock (1D)
- Failure of standard supportive measures (1D)
- Decreased level of consciousness (2D)
Cessation of ECTR
Cessation of ECTR
- Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D)
AND
pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal treatment.
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is preferred initially (1D)
- Continuous renal replacement therapies may be considered if hemodialysis is unavailable (2D)
- Repeat extracorporeal treatment sessions may use hemodialysis (1D) or continuous renal replacement therapy (1D)
Salicylates Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe salicylate poisoning (1D)
Indications
Indications
ECTR is recommended if ANY of the following are met:
- If [salicylate] > 7.2 mmol/L (100 mg/dL) (1D)
- If [salicylate] > 6.5 mmol/L (90 mg/dL) in the presence of impaired kidney function (1D)
- In the presence of altered mental status (1D)
- In the presence of new hypoxemia requiring supplemental oxygen (1D)
If standard therapy (supportive measures, bicarbonate, etc.) fails (1D), ECTR is suggested if any of the following are met:
- If [salicylate] > 6.5 mmol/L (90 mg/dL) (2D)
- If [salicylate] > 5.8 mmol/L (80 mg/dL) in the presence of impaired kidney function (2D)
- If the systemic pH is ≤ 7.20 (2D)
=Cessation of ECTR
Cessation of ECTR
Is indicated if:
- Clinical improvement is apparent (1D) AND
- [salicylate] < 1.4 mmol/L (19 mg/dL (1D) or ECTR has been performed for a period of at least 4-6 h when salicylate concentrations are not readily available (2D)
Choice of ECTR
Choice of ECTR
- Intermittent HD is the preferred modality in patients with salicylate poisoning (1D)
The following are acceptable alternative if HD is not available:
- Intermittent HP (1D)
- CRRT (3D)
- Exchange transfusion in neonates (1D)
Miscellaneous
Miscellaneous
- It is recommended to continue intravenous bicarbonate therapy between ECTR sessions (1D).
Thallium Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe Tl poisoning (1D)
Indications
ECTR is indicated if ANY of the following conditions are present:
- If Tl exposure is highly suspected on the basis of history or clinical features (2D)
- Assuming Tl concentrations are readily available, if Tl concentration is >1.0 mg/L (2D)
- Assuming Tl concentrations are readily available, if Tl concentration is between 0.4 and 1.0 mg/L (3D)
Timing of ECTR
- ECTR should be initiated as soon as possible, ideally within 24–48 hr of Tl exposure (1D)
Cessation of ECTR
Cessation of ECTR
- Is suggested until Tl serum concentration is 0.1 mg/L for a minimal duration of 72 hr (2D)
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is the preferred initial ECTR, especially after an acute Tl ingestion (1D) Intermittent hemoperfusion or continuous renal replacement modalities are valid alternatives if intermittent hemodialysis is not available (1D)
Tricyclic Antidepressants Poisoning
General Recommendations
General Recommendation
- We recommend NOT to perform ECTR in patients with TCA poisoning. (1D)
Valproic Acid Poisoning
General Recommendation
General Recommendation
- ECTR is recommended in severe VPA poisoning (1D)
Indications
Indications
ECTR is recommended if any of the following is present:
- If the [VPA] is > 1300 mg/L (9000 μ mol/L) (1D)
- If shock is present (1D)
- If cerebral edema is present (1D)
ECTR is suggested
If any of the following is present:
- If the [VPA] is > 900 mg/L (6250 μ mol/L) (2D)
- If coma or respiratory depression requiring mechanical ventilation is present (2D)
- If acute hyperammonemia is present (2D)
- If pH is < 7.10 (2D)
Cessation of ECTR
Cessation of ECTR
Is indicated if any of the following is present:
- Clinical improvement is apparent (1D)
- [VPA] is between 50 and 100 mg/L (350 – 700 μ mol/L) (2D)
Choice of ECTR
Choice of ECTR
- Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D)
- If hemodialysis is not available, both intermittent hemoperfusion (1D) and CRRT (2D) are acceptable alternatives
NB: ECTR = extracorporeal treatment
Click here for levels of evidence
Level | Therapy / Prevention, Aetiology / Harm | Prognosis | Diagnosis | Differential diagnosis / symptom prevalence study | Economic and decision analyses |
---|---|---|---|---|---|
1a | SR (with homogeneity*) of RCTs | SR (with homogeneity*) of inception cohort studies; CDR” validated in different populations | SR (with homogeneity*) of Level 1 diagnostic studies; CDR” with 1b studies from different clinical centres | SR (with homogeneity*) of prospective cohort studies | SR (with homogeneity*) of Level 1 economic studies |
1b | Individual RCT (with narrow Confidence Interval”¡) | Individual inception cohort study with > 80% follow-up; CDR” validated in a single population | Validating** cohort study with good” ” ” reference standards; or CDR” tested within one clinical centre | Prospective cohort study with good follow-up**** | Analysis based on clinically sensible costs or alternatives; systematic review(s) of the evidence; and including multi-way sensitivity analyses |
1c | All or none§ | All or none case-series | Absolute SpPins and SnNouts” “ | All or none case-series | Absolute better-value or worse-value analyses ” ” ” “ |
2a | SR (with homogeneity*) of cohort studies | SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs | SR (with homogeneity*) of Level >2 diagnostic studies | SR (with homogeneity*) of 2b and better studies | SR (with homogeneity*) of Level >2 economic studies |
2b | Individual cohort study (including low quality RCT; e.g., <80% follow-up) | Retrospective cohort study or follow-up of untreated control patients in an RCT; Derivation of CDR” or validated on split-sample§§§ only | Exploratory** cohort study with good” ” ” reference standards; CDR” after derivation, or validated only on split-sample§§§ or databases | Retrospective cohort study, or poor follow-up | Analysis based on clinically sensible costs or alternatives; limited review(s) of the evidence, or single studies; and including multi-way sensitivity analyses |
2c | “Outcomes” Research; Ecological studies | “Outcomes” Research | Ecological studies | Audit or outcomes research | |
3a | SR (with homogeneity*) of case-control studies | SR (with homogeneity*) of 3b and better studies | SR (with homogeneity*) of 3b and better studies | SR (with homogeneity*) of 3b and better studies | |
3b | Individual Case-Control Study | Non-consecutive study; or without consistently applied reference standards | Non-consecutive cohort study, or very limited population | Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensible variations. | |
4 | Case-series (and poor quality cohort and case-control studies§§) | Case-series (and poor quality prognostic cohort studies***) | Case-control study, poor or non-independent reference standard | Case-series or superseded reference standards | Analysis with no sensitivity analysis |
5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” | Expert opinion without explicit critical appraisal, or based on economic theory or “first principles” |