Summary of findings 3. MDAC + hospital intervention versus SDAC + hospital intervention for first aid in patients with acute oral poisoning.

MDAC + hospital intervention versus SDAC + hospital intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (carbamazepine, yellow oleander, or combinations of different drugs) Setting: hospital setting Intervention: multiple dose of activated charcoal (MDAC) + hospital intervention Comparison: single‐dose activated charcoal (SDAC) + hospital intervention
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with SDAC + hospital intervention	Risk with MDAC + hospital intervention
Incidence of mortality	Study population		RR 0.59 (0.21 to 1.63)	3476 (2 RCTs)	⊕⊝⊝⊝ Very lowa,b,c	Combining the studies resulted in statistically significant heterogeneity, for which explanations remain speculative. We are uncertain about the effects of MDAC in addition to hospital treatment, compared to SDAC, in addition to hospital treatment.
	72 per 1000	42 per 1000 (15 to 117)
Incidence of adverse events	Study population		Peto OR 3.55 (1.85 to 6.79)	3476 (2 RCTs)	⊕⊕⊝⊝ Lowb,c	There was statistically significant heterogeneity, which may be attributable to different adverse events measured in individual studies. MDAC in addition to hospital treatment may increase abdominal discomfort/diarrhoea and absent bowel sounds, compared to SDAC in addition to hospital treatment.
	4 per 1000	14 per 1000 (7 to 27)
Incidence and severity of symptoms of poisoning: incidence of need for intubation	Study population		RR 1.01 (0.75 to 1.38)	3097 (2 RCTs)	⊕⊕⊝⊝ Lowb,c	MDAC in addition to hospital treatment may make little or no difference in the incidence of need for intubation, compared to SDAC in addition to hospital treatment.
	49 per 1000	49 per 1000 (37 to 67)
Duration of toxic symptoms: duration of intubation (h)	Brahmi 2006: intervention group: 24.1 (SD 4.2 h and control group 36.4 (SD 3.6 h (MD: 12.30 h lower, 95% CI −18.56 to −6.04, 6 participants). Eddleston 2008: intervention group median (IQR): 83.8 (35.0 to 173.0) h and control group median (IQR): 112.0 (36.6 to 234.9) h (median difference: 28.2 h), unclear number of participants		—	(2 RCTs)	⊕⊝⊝⊝ Very lowb,d,e	Data were reported as means with SD in one study or medians with IQR in another study, without information on participant numbers or statement of significance. We are uncertain about the effects of MDAC in addition to hospital treatment on duration of intubation, compared to SDAC in addition to hospital treatment.
Drug absorption: cardenolide: AUC (µg × L/h) Follow‐up: 1 days	The median (IQR) in intervention group was 17.3 (12.8 to 21.7) (µg/L) × h and in the control group 17.7 (11.1 to 21.8) (µg/L) × h (median difference −0.4, P > 0.05).		—	64 (1 RCT)	⊕⊝⊝⊝ Very lowb,e,f	We are uncertain about the effects of MDAC in addition to hospital treatment on cardenolide drug absorption, compared to SDAC in addition to hospital treatment.
Incidence of hospitalization	No studies collected or reported this outcome
Incidence of ICU admission	Study population		RR 0.31 (0.12 to 0.83)	401 (1 RCT)	⊕⊕⊝⊝ Lowb,g	MDAC in addition to hospital treatment may result in a decreased incidence of ICU admission, compared to SDAC in addition to hospital treatment.
	80 per 1000	25 per 1000 (10 to 66)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). AUC: area under the receiver operating curve; CI: confidence interval; ICU: intensive care unit; IQR: interquartile range; MDAC: multi‐dose activated charcoal; RCT: randomized controlled trial; RR: risk ratio; SD: standard deviation; SDAC: single‐dose activated charcoal; OR: odds ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded one level for serious inconsistency: combining results resulted in a considerable and statistically significant degree of heterogeneity (I² > 60%, P < 0.10).
 ^bDowngraded one level for serious indirectness: study conducted in a hospital setting.
 ^cDowngraded one level for serious imprecision: low number of events and wide confidence intervals.
 ^dDowngraded one level for other limitations: inconsistent conclusions made by the studies.
 ^eDowngraded one level for serious imprecision: low sample size and lack of data.
 ^fDowngraded one level for serious study limitations: high risk of other bias: it is not entirely clear what is measured with the assay used. The fact that both active cardenolides and (inactive) metabolites might be detected by the assay compromise the results of these analyses, as they might explain the wide variability observed.
 ^gDowngraded one level for serious imprecision: low number of events.