The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: Guideline methodology

Figures & data

Table 1. Represented societies.

American Academy of Clinical Toxicology*	European Renal Best Practice*
American College of Medical Toxicology*	European Society of Emergency Medicine*
American Society of Nephrology	European Society of Intensive Care Medicine*
American Society of Pediatric Nephrology	French Language Society of Resuscitation*
Asia Pacific Association of Medical Toxicology*	German Society of Nephrology*
Australian and New Zealand Intensive Care Society*	International Pediatric Nephrology Association
Australian and New Zealand Society of Nephrology*	International Society of Nephrology*
Brazilian Association of Information Centres and Toxicologic Assistance*	Latin American Society of Nephrology and Hypertension*
Brazilian Society of Nephrology*	National Kidney Foundation*
Brazilian Society of Toxicology*	Pediatric Continuous Renal Replacement Therapy*
Canadian Association of Poison Control Centres*	Pediatric Critical Care Medicine
Canadian Association of Emergency Physicians*	Quebec Association of Emergency Physicians*
Canadian Society of Nephrology*	Quebec Association of Specialists in Emergency Medicine*
Chinese College of Emergency Physicians*	Quebec Society of Nephrology*
	Renal Association*
Chinese Medical Doctor Association*	Society of Critical Care Medicine*
European Association of Poison Centres and Clinical Toxicologists	Spanish Clinical Toxicology Foundation*

*Designates official support or endorsement.

Table 2. Poison selection.

Methanol	Paraquat/Diquat	Amanita	Fluoride
Ethylene glycol	Carbamazepine	Phenytoin	Baclofen
Lithium	Quinine/Chloroquine	Diethylene glycol	Isoniazid
Salicylates	Theophylline/methylxanthines	Organophosphates	Methotrexate
Valproic acid	Tricyclic antidepressants	Digoxin/Digitalis	Thallium
Acetaminophen	Phenobarbital/Barbiturates	Isopropanol	Metformin

Fig. 1. Result of preliminary search (conducted October 22nd 2011).

Table 3. Scoring the quality of evidence for kinetic outcomes (individual studies*.

Quality of evidence score	Interpretation and application to individual studies
High	Sufficient PK data present; % removed is reported or can be calculated; reported calculations are appropriate.
Moderate	Sufficient PK data present, but % removed is NOT reported or CANNOT be calculated; reported calculations (e.g., CLEC/CLTOT) are appropriate.
Low	Sufficient PK parameters may be reported, but supporting data absent or suspect, reported calculations inappropriate, or other serious limitations exist.
Very Low	Sufficient PK parameters and supporting data not adequately reported, questionable or no calculations reported. However, based on theoretical knowledge of VD, protein binding, CLSYS, molecular weight, etc., some assumptions can be made about dialyzability.
Reject	Questionable parameters reported with no supporting data, fatal flaw in study design.

*Modified from the GRADE system.

Table 4. Summary of the effect and the quality of evidence per type of outcome.

	Summary of effect	Summary of quality of evidence
Clinical outcomes
Case reports and case series only	Qualitative estimate	Estimate using GRADE system (Table 5) (assume very low quality of evidence for case reports and low or very low for consecutive case series)
At least one observational study	Quantitative estimate (size and/or range of the effect)	Estimate using GRADE system (Table 5) with confirmation with epidemiologist
Kinetic outcomes
All study designs	Quantitative estimate of dialyzability (Table 7)	Merge quality of evidence score (Tables 3 and 6) with confirmation by designated kineticist

Table 5. Summary of quality of evidence for clinical outcomes: GRADE system.⁶

Initial grade based on studies design	Reduce grade	Raise grade*	Final grade	Reporting
Randomized trial = high	Study quality	Strength of association	High	A
	• Serious (− 1) or very serious (− 2) limitation to study quality	• Strong evidence of association (RR > 2) based on consistent evidence from 2 or more observational studies, with no plausible confounders (+ 1) equivalent to magnitude of effect. Or very strong evidence of association (RR > 5) based on direct evidence with no major threats to validity (+ 2)	Moderate	B
Observational study = low	Consistency		Low	C
	• Important inconsistency (− 1)		Very Low	D
	Directness
Any other evidence = very low	• Some (− 1) or major (− 2) uncertainty about directness		Very Low	D
	• Imprecise or sparse data (− 1)	• Evidence of a dose response gradient (+ 1)
	• High probability of reporting bias (− 1)	• All plausible confounders would have reduced the effect (+ 1)

*Examples of situations with potential upgrade in the level of the quality of evidence: 1) Magnitude of effect, e.g., 80% less mortality in the ECTR group compared to the control group. 2) Antagonistic bias, e.g., Survival in ECTR group equal to control group (but ECTR likely sicker). 3) Dose-response gradient, e.g., the longer ECTR is performed, the lower mortality rate.

Table 6. Summary of quality of evidence for kinetic outcomes: Quality of evidence score.

Quality of evidence score	Reporting	Interpretation
High	A	We are confident that the true effect lies close to our estimate of the effect.
Moderate	B	The true effect is likely to be close to our estimate of the effect, but there is a possibility that it is substantially different.
Low*	C	The true effect may be substantially different from our estimate of the effect.
Very Low*	D	Our estimate of the effect is just a guess, and it is very likely that the true effect is substantially different from our estimate of the effect.

*If the quality of the evidence is low or very low, literature from non-poisoning contexts may be used, such as CKD pharmacokinetics, animal, and in-vitro studies.

Table 7. Summary of the effect for dialyzability.

Dialyzability^&	Primary criteria % Removed*	Alternative criteria 1 CLEC/CLTOT (%)^#	Alternative criteria 2 T1/2 EC/T1/2 (%)	Alternative criteria 3 ReEC/ReTOT (%)^#
D, Dialyzable	>30	>75	< 25	>75
M, Moderately dialyzable	>10 – 30	>50 – 75	> 25 –50	>50 – 75
S, Slightly dialyzable	≥3 – 10	≥25 – 50	≥ 50 – 75	≥25 – 50
N, Not dialyzable	<3	<25	< 75	<25

These criteria should only be applied if measured or calculated (not reported) endogenous half-life is > 4hours (otherwise, ECTR is considered not clinically relevant). Furthermore, the primary criteria is preferred for poisons having a large Vd (> 5L/Kg).

^&Applicable to all modalities of ECTR, including hemodialysis, hemoperfusion, hemofiltration.

*Corresponds to % removal of ingested dose or total body burden in a 6-hour ECTR period.

^#Measured during the same period of time.

Fig. 2. Voting process for recommendations.

Table 8. Strength of recommendation: Interpretation.

Grading			Interpretation
Strong recommendation	‘We recommend (should)…’	Level 1	The course of action is considered appropriate by the large majority of experts with no major dissension. The panel is confident that the desirable effects of adherence to the recommendation outweigh the undesirable effects.
Weak recommendation	‘We suggest (might)…’	Level 2	The course of action is considered appropriate by the majority of experts but some degree of dissension exists among the panel. The desirable effects of adherence to the recommendation probably outweigh the undesirable effects.
Neutral position	‘It would be reasonable to…’	Level 3	The course of action could be considered appropriate in the right context.
No recommendation	‘No agreement reached…’		No agreement was reached by the group of experts.

Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, . Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490. Epub 2004/06/19.

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