First aid interventions by laypeople for acute oral poisoning

Bert Avau; Vere Borra; Anne‐Catherine Vanhove; Philippe Vandekerckhove; Peter De Paepe; Emmy De Buck

doi:10.1002/14651858.CD013230

. 2018 Dec 19;2018(12):CD013230. doi: 10.1002/14651858.CD013230

First aid interventions by laypeople for acute oral poisoning

Bert Avau ^1,^2,^✉, Vere Borra ¹, Anne‐Catherine Vanhove ^1,², Philippe Vandekerckhove ^3,⁴, Peter De Paepe ⁵, Emmy De Buck ^1,⁴

Editor: Cochrane Injuries Group

PMCID: PMC6438817 PMID: 30565220

Abstract

Background

Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives.

Objectives

To assess the effects of pre‐hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help.

Search methods

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 4 December 2018, and we also carried out reference checking and citation searching.

Selection criteria

We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre‐hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning.

Data collection and analysis

Two review authors independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission.

Main results

We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.

All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre‐hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Twenty‐one trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.

First aid interventions that limit or delay the absorption of the poison in the body

We are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.

Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low‐certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) −0.15, 95% CI −0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.

This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.

First aid interventions that evacuate the poison from the gastrointestinal tract

We found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre‐hospital setting. Low‐certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).

In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.

No studies used cathartics as an individual intervention.

First aid interventions that neutralize or dilute the poison

No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.

Authors' conclusions

The studies included in this review provided mostly low‐ or very low‐certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre‐hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.

Plain language summary

First aid treatments for oral poisoning

Review question

We reviewed the evidence on the effects of first aid treatments for poisoning that could be feasibly given by people who are not health professionals.

Background

Many first aid treatments are recommended for treating people who have ingested poisonous substances. Some treatments, such as activated charcoal (AC), bind to the poison, limiting the body's absorption of it. Others may induce vomiting (such as syrup of ipecac) or dilute or neutralize the poison (such as drinking water, milk or juices). Adjusting the person's body position may also have an effect.

Study characteristics

In December 2018 we searched for high‐quality studies (randomly dividing participants into different treatment groups) investigating treatments for poisoning that laypeople can perform. We found 24 studies with 7099 participants. All but one study took place in hospitals; the remaining one was in a home setting.

Fourteen studies either did not specify the type of poison or studied different kinds. The others investigated overdoses of specific medicines (paracetamol, carbamazepine, antidepressant, benzodiazepine) or poisonous plants (yellow oleander or poisonous berries).

Twenty‐one trials studied different treatments with activated charcoal: as a single dose or multiple doses, with or without other first aid treatments (a substance to speed up bowel transit), and with or without hospital treatments. Six studies compared syrup of ipecac, with or without other first aid treatments (single‐dose activated charcoal plus bowel transit enhancing substance) versus no treatment. We found no studies that investigated the neutralization or dilution of the poison or the use of certain body positions.

Key results

Two studies compared a single dose of activated charcoal to no treatment following poisoning with paracetamol or different kinds of poisoning. We are uncertain about the treatment's side effects, admission to intensive care or worsening of the patient, and there was no information about effects on death, symptom duration, poison uptake or hospitalization.

One study compared a single dose of activated charcoal to ipecac in mixed types of poisoning. We are uncertain about the effect of activated charcoal compared to ipecac, on the patient's level of coma or the number of unwanted effects. There was no information about effects on death, symptom duration, poison uptake, hospitalization or intensive care admission.

One study compared ipecac to no treatment in children who ate poisonous berries at home. There may be an increase in the number of unwanted effects for ipecac. There was no information about effects on death, poisoning symptoms, symptoms duration, poison uptake, hospitalization or intensive care admission.

We also investigated the use of single‐dose or multi‐dose activated charcoal, with or without hospital treatment, compared to each other or no treatment. Furthermore, we investigated the added value of ipecac to single‐dose activated charcoal and the added value of adding bowel transit enhancing substances to AC.

Certainty of the evidence

All but one study took place in a hospital setting, which means that the results cannot be directly applied to the lay setting. Because studies did not always report the methods they used, we are uncertain about the quality of the research conduct for many. Outcomes important to patients and pre‐specified by us as important outcomes for this review were often absent or incompletely reported. Our certainty about the results of this review is mostly low to very low. Therefore future research is highly likely to change the findings.

Conclusion

Based on the identified evidence, we cannot draw any conclusions about the effects of any of the investigated first aid treatments in a lay setting.

Summary of findings

Background

Description of the condition

Poisoning can be defined as exposure of the body to exogenous substances, in sufficiently large amounts to cause harm to the individual. This can happen through chronic exposure to low doses of a substance, or more acutely through sudden exposure to a harmful dose. Acute poisoning can happen either accidentally or voluntarily, as a way to end one's own or another's life or as a 'cry for help'.

Poisoning inflicts a major burden of morbidity and mortality worldwide. The World Health Organization (WHO) estimates that 108,000 deaths a year are caused by unintentional poisoning (WHO 2016), accompanied by the loss of a staggering 6,558,000 disability adjusted life years (DALYs) (WHO 2016). In addition to this, auto‐intoxication is one of the most common methods to attempt suicide. Yearly, around 800,000 people worldwide commit suicide, and around 30% of their attempts occur through the intake of pesticides, a phenomenon typically occurring in rural areas in lower‐ and middle‐income countries (WHO 2018). As most attempted suicides are unsuccessful, the actual burden will be much higher (Albert 2015). Poisoning can happen via different routes of exposure, such as through inhalation, injection or dermal absorption, but by far the most common is through deliberate or accidental ingestion of a toxic substance (Mowry 2016), which is the focus of this review. An important patient group to suffer from unintentional poisoning are young children. Roughly 20% of all accidental poisonings are thought to occur in children aged under 5 years (WHO 2016). In high‐income countries, this proportion is even larger: up to 47% of the incoming calls to the American Poison Control Centers concern exposures in this age group (Mowry 2016). This is most likely because young children are curious to explore their environment and do not realize the dangers of putting unknown and potentially harmful things in their mouth. Indeed, large numbers of exposures are to cosmetics and household products (25% of all reported exposures in children aged 5 years or younger; Mowry 2016).

Hospital treatment of acute oral poisoning focuses initially on supportive therapy: hypertonic glucose infusion, maintaining the victim's vital parameters and keeping poison‐induced symptoms under control (Isbister 2016; Nelson 2011). If practitioners can identify a toxin syndrome, they can administer a poison‐specific antidote, for example N‐acetylcysteine for a paracetamol overdose or naloxone for an opioid overdose (Chiew 2018; Wilkerson 2016). Third‐line treatment options include gastrointestinal decontamination procedures: activated charcoal can adsorb the poisonous substance (Corcoran 2016), while gastric lavage or whole bowel irrigation are procedures that attempt to eliminate the poison out of the gastrointestinal tract before absorption into the blood (Donkor 2016; Thanacoody 2015). A final treatment strategy is to eliminate toxins that have already been absorbed through multiple doses of activated charcoal, haemodialysis or blood/urinary alkalinization (Decker 2015; Gaudreault 2005; Proudfoot 2003; Roberts 2005).

In cases of acute oral poisoning, a swift reaction is crucial. For activated charcoal (AC), experimental studies have shown that its efficacy in limiting drug absorption decreases dramatically over time (Chyka 2005). Therefore, treatment guidelines recommend using AC within an hour after ingestion of the poison, although AC may still produce effects after that time, especially in drugs administered in a delayed release formula (Chyka 2005; Juurlink 2015). However, it is difficult to adhere to these guidelines in emergency services, mainly due to the delay between ingestion and presentation at the emergency department (Karim 2001; LoVecchio 2007; Tuuri 2009). Thus, any effective first aid measure that would neutralize, limit or delay uptake, or promote evacuation from the gastrointestinal tract in case of acute oral poisoning, could save precious time for professionals, potentially making the difference between life and death, or serious morbidity, for the poisoned patient.

First aid, as defined by the International Liaison Committee On Resuscitation (ILCOR), is the immediate help provided to a sick and injured person until professional help arrives. First aid interventions seek to preserve life, alleviate suffering, prevent further illness or injury and promote recovery (Zideman 2015). This definition implies that a first aid intervention must be both available to and feasible for a layperson in a pre‐hospital setting. Of the previously mentioned hospital interventions, only activated charcoal, which is relatively easy to administer orally and available without prescription, is feasible. In addition to these, other suggested first aid techniques include administering emetics, such as syrup of ipecac (or ipecacuanha) (Quang 2000); using cathartics, such as sorbitol (Keller 1990), drinking water, milk, vinegar or citrus juice to dilute and/or neutralize the poison (Rumack 1977); or adjusting the poisoned victim's body position to slow down the uptake of the poison (Vance 1992).

In case of ingestion of toxic alcohols (e.g. methanol, ethylene glycol), ethanol could be considered a potential home remedy due to its wide availability. However, the use of large volumes of ethanol is dangerous and needs to be monitored carefully (Rietjens 2014). Therefore, it is not recommended for use in a lay setting without professional guidance. Current recommendations for laypeople are limited to placing the victim in the lateral decubitus position and seeking professional help (e.g. contacting poison control centres if available) and following their advice (IFRC 2016).

Description of the intervention

The focus of this Cochrane Review is any intervention that is readily available to and administrable by laypeople before professional help arrives, targeted at neutralizing, limiting or delaying the absorption, or promoting the evacuation of a poison.

Limiting the absorption of a poison can be achieved by administering an adsorbent, such as activated charcoal. This black powder is produced through pyrolysis of carbon‐rich materials and activation by steam to remove already adsorbed substances (Olson 2010). This process results in a material with a very large surface area and hence adsorbing capacity. It needs to be mixed with water to form a slurry that can be ingested.

Placing the poisoning victim on their left side might be another method to decrease absorption of the poison (Vance 1992).

Substances that can promote the evacuation of a poison from the gastrointestinal tract firstly include emetics. The best known and most recommended is syrup of ipecacuanha, or ipecac. This syrup is derived from the roots and rhizome of Cephaelis ipecacuanha (Lee 2008). Other suggested emetics are apomorphine and copper sulphate. Apomorphine is believed to induce vomiting faster than ipecac (MacLean 1973), but it is not feasible to administer in a home setting and can cause central nervous depression, so it is not recommended, especially in children (MacLean 1973). Copper sulphate has also been used to induce vomiting in people with oral poisoning due to its action as a local irritant in the stomach (Karlsson 1965). However, it is a common source of intoxication itself, hence its use is also discouraged (Nastoulis 2017).

A second class of substances that can theoretically speed up the evacuation of an ingested poison from the gastrointestinal tract are cathartics. Patients who have ingested slow‐absorbing materials might benefit most from these treatments, although current guidelines suggest not using cathartics without activated charcoal (American Academy of Clinical Toxicology 2004). Examples of suggested cathartics include sugars, such as mannitol, lactulose and sorbitol, or salts, including magnesium sulphate, magnesium citrate and sodium sulphate.

In addition, diluting and neutralizing poisons, especially caustic substances such as lye, could occur through the intake of water, milk, vinegar or citrus juice (Rumack 1977). Milk might also have some adsorbing capacity (Chin 1969).

How the intervention might work

First aid interventions to treat poisoning can be categorized in four groups:

those that either limit or delay absorption of the poison in the body, such as activated charcoal or certain body positions;
interventions that evacuate the poison from the gastrointestinal tract, either by vomiting or by defecation;
combinations of first aid interventions that limit uptake and promote evacuation of the poison, e.g. sorbitol and activated charcoal;
first aid interventions that neutralize or dilute the poison, such as drinking water, milk, vinegar or citrus juice.

Furthermore, other combinations of first aid interventions may also be used.

A. First aid interventions that limit or delay the absorption of the poison in the body

One way to limit the absorption of a poison is to administer a substance that binds to the poison, thus preventing it from being absorbed by the body. Activated charcoal (AC) is one such adsorbent. Its enormous surface area can adsorb large quantities of drugs through the generation of Van der Waals forces between the charcoal and the adsorbed molecule (Olson 2010). Not all substances are equally effectively bound by AC. For example, lithium, iron, cyanide or alcohols bind to AC only to a minor extent, which means its appropriateness needs to be carefully considered in these cases (Bateman 1999; Juurlink 2015; Olson 2010). The optimal dose regimen for activated charcoal administration is not entirely clear, but 25 g to 100 g is considered to be a standard dose for adults (Chyka 2005). In practice, ingesting more than 50 g seems to be difficult to achieve for patients.

A certain body position might also slow down the uptake of the poison. The primary site of absorption for most pharmacologic substances is the small intestine, because of its large surface area and thin epithelium. Therefore, any factor that would delay gastric emptying into the small intestine should decrease the rate of absorption and limit the potential toxic effects of the ingested drug. Studies indicate that laying on the right side accelerates gastric emptying (Loots 2013; Valeur 2015; Van Wijk 2007). In contrast, placing the patient in the left lateral decubitus position might slow the rate of absorption of the ingested poison, because the anatomy of the stomach, combined with gravity, would allow the gastric content to stay in the greater curvature of the stomach (Vance 1992).

B. First aid interventions that evacuate the poison from the gastrointestinal tract

Evacuation of the poison from the gastrointestinal tract as quickly as possible can be achieved by inducing vomiting or accelerating defecation. Two types of drugs can be considered: emetics induce vomiting, while cathartics accelerate defecation.

As mentioned before, syrup of ipecac is the best known type of emetic. The main active substances of the ipecacuanha plant are emetine and cephaeline, which induce emesis and diarrhoea by acting both as a local irritant in the upper gastrointestinal tract and by targeting the chemoreceptor trigger zone in the medulla oblongata of the brain, the body's vomiting centre (Lee 2008). A potential risk associated with the use of emetics is lung injury through vomit aspiration (Höjer 2013).

Cathartics draw water into the large intestine, thereby stimulating bowel movements and thus accelerating defecation (American Academy of Clinical Toxicology 2004).

C. First aid interventions that limit uptake and promote evacuation of the poison from the gastrointestinal tract

Cathartics can be used with activated charcoal. This combination is thought to reduce drug uptake by accelerating evacuation out of the small bowel (Moon 2015). Furthermore, cathartics counteract the constipating effects of AC (James 1995). On the other hand, in vitro studies have suggested that cathartics might influence the adsorbing capacity of AC (Orisakwe 2001).

D. First aid interventions that neutralize or dilute the poison

A commonly used home remedy for poisoning by caustic substances is drinking large amounts of fluids, such as water, milk, vinegar or citrus juice (Rumack 1977). The rationale behind this is not only to dilute the poison, but also to change the pH in the stomach, thereby neutralizing the caustic effects of the ingested poison. Considerations that need to be made when using this approach are the chemical properties of the ingested substance (acidic or basic), the heat production that might occur during neutralization and sufficient availability of the neutralizing substance. In addition to its potential neutralizing effect, in vitro data suggest that milk has some adsorbing capacity (Chin 1969). However, increasing the volume of fluids in the stomach might also increase the rate of emptying into the small bowel, where the absorption of the poison takes place (Blain 2011). Furthermore, drinking large amounts of water might cause water intoxication (Lai 2016). A final consideration is that drinking large volumes of fluids might increase the risk of vomiting, which could be problematic in cases of caustic poisoning, as the caustic substance would contact the oesophagus for a second time.

Why it is important to do this review

There are several Cochrane Reviews concerning the treatment and prevention of poisoning. Kendrick 2012 provided evidence on interventions to prevent injuries at home, including cases of oral poisoning, while Hawton 2015 investigated potential interventions to decrease self‐harm in children, adolescents and adults. A review by Nussbaumer‐Streit 2016 documented potential household interventions to prevent domestic lead exposure in children. In addition, numerous Cochrane Reviews have investigated the use of hospital interventions to treat a range of specific intoxications, such as for example paracetamol or lithium poisoning (Chiew 2018; Lavonas 2015).

This Cochrane Review fills the gap between prevention and hospital treatment of poisoning, by investigating which pre‐hospital interventions, available and feasible for a lay person in a non‐healthcare setting, are effective in cases of acute oral poisoning. Identified interventions can be used in first aid guidelines targeted at lay people in settings such as nightclubs, childcare centres or the workplace, to be applied before arrival of professional help. As time is a crucial factor in acute oral poisoning, effective interventions conducted by laypeople would save valuable time and could therefore be crucial to survival (Chyka 2005; Juurlink 2015).

Objectives

To assess the effects of pre‐hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help.

Methods

Criteria for considering studies for this review

Types of studies

We considered randomized controlled trials (RCTs) in actual poisoning patients. We excluded studies involving healthy volunteers and preclinical studies (animal studies, in vitro research).

In order to be eligible for inclusion in the review, all RCTs taking place after 2010 must have been prospectively registered (Roberts 2015). All RCTs conducted prior to 2010 were eligible for inclusion.

Types of participants

We included participants poisoned via oral ingestion, both deliberately and accidentally. In addition to studies in a community setting, we considered studies conducted in a healthcare setting, including a hospital setting or ambulatory care, as most studies identified would likely have been performed in a controlled setting. Although this may be a source of indirectness, we feel that excluding these studies would result in selection bias.

Types of interventions

All identified first aid interventions, alone or in combination and feasible for a layperson in a pre‐hospital setting, were eligible. These included, among others, activated charcoal and other adsorbents (single‐ or multi‐dose); syrup of ipecac and other emetics (single or multi‐dose); cathartics (single or multi‐dose); body positioning; and water, milk, vinegar or citrus juice.

We compared the interventions to each other or to no intervention. We did not compare them to typical hospital interventions such as gastric lavage, whole bowel irrigation or the use of antidotes. However, if pre‐hospital treatments were used in adjuvant to an established hospital treatment, we included these studies. The reason for not considering established hospital treatments as comparisons is that we are interested in the most efficacious treatments in a non‐healthcare setting. It is likely that these would be less efficient than a hospital treatment, but they might still be useful as a first aid measure, which typically takes place before presentation to a healthcare facility.

Co‐interventions were allowed if all groups received them in equal doses. We separately explored interventions aiming to limit or delay absorption of poison, evacuate poison, limit uptake and evacuate poison, and neutralize or dilute poison.

Types of outcome measures

Timings of outcomes are defined as early (within 24 h after poisoning), intermediate (24 h to one week after poisoning) and late (more than one week and less than one year after poisoning).

Primary outcomes

Incidence of mortality
Incidence of adverse events due to the intervention
Incidence and severity of symptoms of poisoning, reported for example with the Poisoning Severity Score (PSS) (Persson 1998)

Secondary outcomes

Duration of toxic symptoms
Drug absorption: measured as maximal concentration of drug in the blood (C_max), time to C_max (T_max) or area under the curve (AUC) of drug concentration versus time
Incidence of hospitalization
Incidence of intensive care unit (ICU) admission

Search methods for identification of studies

Electronic searches

We searched the following databases on 4 December 2018, without any language restrictions or date limits.

The Cochrane Library (2018, Issue 11, searched 4 December 2018; www.cochranelibrary.com), including the following databases.
- The Cochrane Database of Systematic Reviews.
- The Cochrane Central Register of Controlled Trials (CENTRAL), for reports of RCTs from MEDLINE, Embase and records submitted from Cochrane Specialized Registers, including the Cochrane Injuries Group.
- DARE (Database of Abstracts of Reviews of Effect).
MEDLINE, using the PubMed interface (1966 to 4 December 2018).
Embase, using the Embase.com interface (1947 to 4 December 2018).
CINAHL, using the EBSCO host interface (1982 to 4 December 2018).
ISI Web of Science: Science Citation Index Expanded (SCI‐EXPANDED) and Conference Proceedings Citation Index‐Science (CPCI‐S) (1900 to 4 December 2018).
International Pharmaceutical Abstracts, using the Ovid interface (1970 to 4 December 2018).
Clinicaltrials.gov (clinicaltrials.gov).
EU Clinical Trials Register (www.clinicaltrialsregister.eu).
WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/en/).

For each of the articles included, we did a search in MEDLINE (via the PubMed interface) and screened the first 20 similar articles for additional relevant publications. Search strategies can be found in Appendix 1. Furthermore, we searched previously published systematic reviews and evidence‐based guidelines that were identified during the database searches (Table 7).

1. Sources of individual studies.

Author and year of publication	Title
Abrass 2012	The evidence for activated charcoal in resource poor settings: a systematic review
American Academy of Clinical Toxicology 1999	Position statement and practice guidelines on the use of multi‐dose activated charcoal in the treatment of acute poisoning
American Academy of Clinical Toxicology 2004	Position paper: cathartics
Chiew 2018	Interventions for paracetamol (acetaminophen) overdoses
Chyka 2005	Position paper: single‐dose activated charcoal
Eddleston 2003	Does gastric lavage really push poisons beyond the pylorus? A systematic review of the evidence
Blain 2011	Organophosphorus poisoning (acute)
Höjer 2013	Position paper update: ipecac syrup for gastrointestinal decontamination.
Jones 2002	Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Activated charcoal and gastric absorption of iron compounds
Manoguerra 2005	Guideline on the use of ipecac syrup in the out‐of‐hospital management of ingested poisons
Qureshi 2011	Adverse effects of activated charcoal used for the treatment of poisoning
Roberts 2011	Enhanced elimination in acute barbiturate poisoning ‐ a systematic review

Comparison	Type of poisoning	Study
A. First aid interventions that limit or delay the absorption of the poison in the body
SDAC  vs no intervention	Not specified	Merigian 1990
SDAC  vs no intervention	Paracetamol	Underhill 1990
SDAC + hospital intervention vs  hospital intervention	Not specified	Comstock 1982
	Benzodiazepines + paracetamol or other drug combinations	Cooper 2005
	Tricyclic antidepressants	Crome 1983
	Yellow oleander, organophosphorus/carbamate pesticide, organochlorine, other/unknown pesticide or paraquat, medicine or unknown	Eddleston 2008
	Amitriptyline, clomipramine, mianserin, imipramine, dothiepin, doxepin, nortriptyline, mixed overdoses with most commonly benzodiazepines or alcohol	Hultén 1988
	Not specified	Merigian 2002
	Yellow oleander	Roberts 2006
MDAC + hospital intervention  vs SDAC + hospital intervention	Carbamazepine	Behnoush 2009
	Carbamazepine	Brahmi 2006
	Yellow oleander	De Silva 2003
	Yellow oleander, organophosphorus/carbamate pesticide, organochlorine, other/unknown pesticide or paraquat, medicine or unknown	Eddleston 2008
	Yellow oleander	Roberts 2006
SDAC  vs syrup of ipecac	Anti‐inflammatory drugs, analgesics or psychotropic drugs	Amigó Tadín 2002
MDAC + hospital intervention  vs hospital intervention	Benzodiazepine	Bouget 1989
	Yellow oleander, organophosphorus/carbamate pesticide, organochlorine, other/unknown pesticide or paraquat, medicine or unknown	Eddleston 2008
	Yellow oleander	Roberts 2006
B. First aid interventions that evacuate the poison from the gastrointestinal tract
Emetics
Syrup of ipecac vs no intervention	Toxic berries	Wax 1999
Syrup of ipecac + SDAC + cathartic  vs SDAC + cathartic	Not specified	Albertson 1989
	Wide variety, most commonly paracetamol	Kornberg 1991
	Not specified	Kulig 1985
	Paracetamol, salicylate, phenothiazines or ethanol, or other drugs	Pond 1995
Syrup of ipecac 15 mL vs syrup of ipecac 30 mL (dose)	Benzodiazepine tranquillizers or hypnotics, other tranquillizers, other hypnotics, antidepressants, analgesics, antihistamines, miscellaneous drugs and chemicals	Ilett 1977
Cathartics
SDAC + cathartic  vs SDAC	Not specified	Sue 1994
SDAC + cathartic  vs  SDAC	Analgesics, anticonvulsants, antihistamines and decongestants, asthma therapies, automotive products, cardiovascular drugs, gastrointestinal preparations, insecticides, mushrooms, psychotropic drugs, rodenticides, topicals, miscellaneous drugs	James 1995
SDAC + cathartic  vs SDAC + cathartic (dose)	Not specified	Sue 1994
SDAC + cathartic  vs  SDAC + cathartic (type)	Analgesics, anticonvulsants, antihistamines and decongestants, asthma therapies, automotive products, cardiovascular drugs, gastrointestinal preparations, insecticides, mushrooms, psychotropic drugs, rodenticides, topicals, miscellaneous drugs	James 1995
C. Combined first aid interventions that limit uptake and promote evacuation of the poison from the gastrointestinal tract
SDAC + cathartic + hospital intervention  vs hospital intervention	Benzodiazepines, barbiturates or imipramine	Passeron 1989
MDAC + cathartic + hospital intervention  vs hospital intervention	Paracetamol	Montoya‐Cabrera 1999
D. First aid interventions that neutralize or dilute the poison
No studies were identified

SDAC versus no intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (paracetamol or not specified)  Setting: hospital setting  Intervention: single‐dose activated charcoal (SDAC)  Comparison: no intervention
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with no intervention	Risk with SDAC
Incidence of mortality	No studies collected or reported this outcome
Incidence of adverse events	Control group: 0/236; intervention group: 4/240 (Peto OR 4.17, 95% CI 0.30 to 57.26)		—	476  (2 RCTs)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain of the effect of SDAC on the incidence of adverse events.
Incidence and severity of symptoms of poisoning: incidence of clinical deterioration during stay in the hospital	—		—	451  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d	The relative effect was not estimable due to the absence of events in the intervention (0/220) and the control group (0/231). We are uncertain of the effect of SDAC on incidence and severity on poisoning.
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption	No studies collected or reported this outcome
Incidence of hospitalization	No studies collected or reported this outcome
Incidence of ICU admission	Control group: 0/231; intervention group: 1/220 (Peto OR 7.77, 95% CI 0.15 to 391.93)		—	451  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain of the effect of SDAC on the incidence of ICU admission.
*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).  CI: confidence interval; ICU: intensive care unit; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio; 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.

SDAC + hospital intervention versus hospital intervention alone for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (not specified, tricyclic antidepressants, combinations of different drugs or yellow oleander)  Setting: hospital setting  Intervention: single‐dose activated charcoal (SDAC) + hospital intervention  Comparison: hospital intervention
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with hospital intervention	Risk with SDAC + hospital intervention
Incidence of mortality	Study population		Peto OR 1.04  (0.79 to 1.37)	3425  (2 RCTs)	⊕⊕⊝⊝  Low^a,b	SDAC in addition to hospital treatments may make little or no difference on incidence of mortality.
	62 per 1000	64 per 1000  (49 to 85)
Incidence of adverse events	Incidence of vomiting: intervention group: 118/570 and control group: 163/1236 (RR 1.44, 95% CI 0.88 to 2.37; 1806 participants; 2 studies). Incidence of absent bowel sounds: intervention group: 7/1544 and control group: 17/1554 (RR 0.41, 95% CI 0.17 to 1.00, 1 study, 3098 participants).		—	4904  (3 RCTs)	⊕⊝⊝⊝  Very low^a,c,d	Statistically significant heterogeneity was found, which may be explained partially by subgroup analyses per type of adverse event.  We are uncertain about the effect of SDAC in addition to hospital treatments on incidence of adverse events.
Incidence and severity of symptoms of poisoning: incidence of need for intubation	Patients that received gastric lavage prior to SDAC: intervention group: 80/1578 and control group: 87/1597 (RR 0.95, 95% CI 0.70 to 1.27, 2 studies, 3175 participants). Patients that did not receive gastric lavage prior to SDAC: intervention group: 24/194 and control group: 10/193 (RR 2.61, 95% CI 1.38 to 4.93, 1 study, 387 participants).		—	3562  (4 RCTs)	⊕⊝⊝⊝  Very low^a,b,c	Statistically significant heterogeneity was found, which may be explained by subgroup analyses in patients receiving or not receiving gastric lavage.  We are uncertain about the effect of SDAC on incidence of need for intubation.
Duration of toxic symptoms: duration of intubation (h)	Eddleston 2008: intervention group median (IQR): 112.0 (36.6 to 234.9) h and control group median (IQR): 88.5 (38.5 to 203.1) h (median difference: 23.5 h, P > 0.05). Merigian 2002: intervention group mean: 54.6 h and control group mean: 39.9 h (MD: 14.7 h, P = 0.70).		—	(2 RCTs)	⊕⊕⊝⊝  Low^a,e	Data were reported as median with IQR in one or means without measure of spread in another study, without information on participant numbers. SDAC in addition to hospital treatments may make little or no difference on the duration of intubation.
Drug absorption: cardenolide: AUC (µg/L) × h  Follow‐up: 1 days	The median (IQR) in intervention group was 17.7 (11.1 to 21.8) (µg/L) × h and in the control group 19.0 (13.7 to 24.3) (µg/L) × h (median difference: −1.3 h, P > 0.05)		—	68  (1 RCT)	⊕⊝⊝⊝  Very low^a,f,g	We are uncertain about the effect of SDAC in addition to hospital treatments on cardenolide absorption.
Incidence of hospitalization	125 per 1000	196 per 1000 (152 to 252)	RR 1.57 (1.22 to 2.02)	1479  (1 RCT)	⊕⊝⊝⊝  Very low^a,g,h	We are uncertain about the effect of SDAC in addition to hospital treatments on incidence of hospitalization.
Incidence of ICU admission	30 per 1000	69 per 1000 (42 to 114)	RR 2.33 (1.42 to 3.82)	1479  (1 RCT)	⊕⊝⊝⊝  Very low^a,g,h	We are uncertain about the effect of SDAC in addition to hospital treatments on incidence of ICU admission.
*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).  CI: confidence interval; ICU: intensive care unit; IQR: interquartile range; RCT: randomized controlled trial; RR: risk ratio; 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.

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 low^a,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)	⊕⊕⊝⊝  Low^b,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)	⊕⊕⊝⊝  Low^b,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 low^b,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 low^b,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)	⊕⊕⊝⊝  Low^b,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.

SDAC versus syrup of ipecac for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (anti‐inflammatory drugs, analgesics or psychotropic drugs)  Setting: hospital setting  Intervention: single‐dose activated charcoal (SDAC)  Comparison: syrup of ipecac
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with syrup of ipecac	Risk with SDAC
Incidence of mortality	No studies collected this outcome
Incidence of adverse events	Study population		RR 1.24  (0.26 to 5.83)	34  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain about the effect of SDAC, compared to syrup of ipecac on incidence of adverse events.
	154 per 1000	191 per 1000  (40 to 897)
Incidence and severity of symptoms of poisoning: level of coma assessed with Glasgow Coma Scale  Scale from: 3 to 15  Follow‐up: 1 h	The mean incidence and severity of symptoms of poisoning: level of coma was 14.91	MD 0.15 lower  (0.43 lower to 0.13 higher)	—	34  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d	We are uncertain about the effect of SDAC, compared to syrup of ipecac on the level of coma.
Duration of toxic symptoms	No studies collected this outcome
Drug absorption	No studies collected this outcome
Incidence of hospitalization	No studies collected this outcome
Incidence of ICU admission	No studies collected this outcome
*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).  CI: confidence interval; ICU: intensive care unit; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio; SDAC: single‐dose activated charcoal.
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.

MDAC + hospital intervention versus hospital intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (benzodiazepines, yellow oleander or combinations of different drugs)  Setting: hospital setting  Intervention: multi‐dose activated charcoal (MDAC) + hospital intervention  Comparison: hospital intervention
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with hospital intervention	Risk with MDAC + hospital intervention
Incidence of mortality	Study population		RR 0.94  (0.72 to 1.22)	3085  (1 RCT)	⊕⊕⊝⊝  Low^a,b	MDAC in addition to hospital treatment may make little or no difference in incidence of mortality.
	68 per 1000	64 per 1000  (49 to 82)
Incidence of adverse events	Study population		RR 1.02  (0.52 to 1.98)	3085  (1 RCT)	⊕⊕⊝⊝  Low^a,b	MDAC in addition to hospital treatment may make little or no difference in incidence of adverse events.
	11 per 1000	11 per 1000  (6 to 22)
Incidence and severity of symptoms of poisoning: incidence of need for intubation	Study population		RR 0.97  (0.71 to 1.33)	3085  (1 RCT)	⊕⊕⊝⊝  Low^a,b	MDAC in addition to hospital treatment may make little or no difference in incidence of need for intubation.
	49 per 1000	47 per 1000  (35 to 65)
Duration of toxic symptoms: length of intubation (h)	The median (IQR) length of intubation in the intervention group was 83.8 (35.0 to 173.0) h and 88.5 (38.5 to 203.1) h in the control group and was reported not to differ significantly (P > 0.05); unclear number of participants		—	(1 RCT)	⊕⊕⊝⊝  Low^a,c	The number of participants analysed was not reported. MDAC in addition to hospital treatment may make little or no difference in length of intubation
Drug absorption: cardenolide: AUC (µg/L × h)  Follow‐up: 1 day	The median (IQR) cardenolide AUC in the intervention group was 17.3 (12.8 to 21.7) (µg/L) × h and 19.0 (13.7 to 24.3) (µg/L) × h in the control group.		—	76  (1 RCT)	⊕⊝⊝⊝  Very low^a,c,d	We are uncertain about the effects of MDAC in addition to hospital treatment on cardenolide drug absorption.
Incidence of hospitalization	No studies collected or reported this outcome
Incidence of ICU admission	No studies collected or reported this outcome
*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.
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.

Syrup of ipecac versus no intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (toxic berries)  Setting: pre‐hospital setting  Intervention: syrup of ipecac  Comparison: no intervention
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with no intervention	Risk with Syrup of ipecac
Incidence of mortality	No studies collected this outcome
Incidence of adverse events: diarrhoea  Follow‐up: 1 day	Study population		RR 4.08  (1.66 to 10.04)	103  (1 RCT)	⊕⊕⊝⊝  Low^a,b	Syrup of ipecac may result in an increased incidence of diarrhoea.
	96 per 1000	392 per 1000  (160 to 965)
Incidence and severity of symptoms of poisoning	No studies collected this outcome
Duration of toxic symptoms	No studies collected this outcome
Drug absorption	No studies collected this outcome
Hospitalization: incidence of hospitalization  Follow‐up: 1 days	—		—	103  (1 RCT)	⊕⊕⊝⊝  Low^a,b	The effect was not estimable due to the absence of events in the intervention (0/52) and the control group (0/51).
ICU admission	No studies collected this outcome
*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).  CI: confidence interval; ICU: intensive care unit; RCT: randomized controlled trial; RR: risk 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.

A. First aid interventions that limit or delay the absorption of the poison in the body
SDAC vs no intervention
Incidence of clinical deterioration
	SDAC		No intervention
Study	Events	Total	Events	Total	Peto OR (95% CI)
Merigian 1990	0	220	0	231	Not estimable
Incidence of ICU admission
	SDAC		No intervention
Study	Events	Total	Events	Total	Peto OR (95% CI)
Merigian 1990	0	220	0	231	7.77 (0.15 to 391.93)
SDAC + hospitalintervention vs hospitalintervention
Incidence of clinical deterioration
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	Peto OR (95% CI)
Merigian 2002	0	455	0	1075	Not estimable
Grade of coma (4 h after admission)
	SDAC + hospital treatment (N = 9)		Hospital treatment (N = 7)
Study	Median	IQR	Median	IQR	Median difference (P value)
Crome 1983	2	(1 to 3)	2	(1 to 2.5)	0 (P = 0.55)
Grade of coma (8 h after admission)
	SDAC + hospital treatment (N = 9)		Hospital treatment (N = 7)
Study	Median	IQR	Median	IQR	Median difference (P value)
Crome 1983	2	(1 to 3)	1	(0.5 to 2)	1 (P = 0.38)
Grade of coma (24 h after admission)
	SDAC + hospital treatment (N = 9)		Hospital treatment (N = 7)
Study	Median	IQR	Median	IQR	Median difference (P value)
Crome 1983	1	(0 to 2)	0	(0 to 0.5)	1 (P = 0.27)
Incidence of coma grade III (4 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	7	34	6	43	1.48 (0.55 to 3.98)
Incidence of coma grade IV (4 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	1	34	7	43	0.18 (0.02 to 1.40)
Incidence of coma grade III (8 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	2	34	2	43	1.26 (0.19 to 8.52)
Incidence of coma grade IV (8 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	0	34	2	43	0.16 (0.01 to 2.70)
Incidence of coma grade III (24 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	Peto OR (95% CI)
Hultén 1988	0	34	0	43	Not estimable
Incidence of coma grade IV (24 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	Peto OR (95% CI)
Hultén 1988	0	34	0	43	Not estimable
Incidence of need for cardiac pacing/antitoxin
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Eddleston 2008	101	549	101	555	1.01 (0.79 to 1.30)
Incidence of need for respirator
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	2	34	9	43	0.28 (0.06 to 1.22)
Incidence of systolic blood pressure < 100 mmHg (4 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	4	34	8	43	0.63 (0.21 to 1.92)
Incidence of systolic blood pressure < 100 mmHg (8 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	1	34	5	43	0.25 (0.03 to 2.06)
Incidence of systolic blood pressure < 100 mmHg (24 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	0	34	2	43	0.16 (0.01 to 2.70)
Incidence of heart rate > 100 bpm (4 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	10	34	15	43	0.84 (0.44 to 1.63)
Incidence of heart rate > 100 bpm (8 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	8	34	10	43	1.01 (0.45 to 2.28)
Incidence of heart rate > 100 bpm (24 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	10	34	10	43	1.26 (0.60 to 2.68)
Incidence of cardiac arrhythmias (4 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	1	34	4	43	0.32 (0.04 to 2.70)
Incidence of cardiac arrhythmias (8 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	1	34	3	43	0.42 (0.05 to 3.87)
Incidence of cardiac arrhythmias (24 h after admission)
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	1	34	2	43	0.63 (0.06 to 6.68)
Incidence of intubation > 8 h
	SDAC + hospital treatment		Hospital treatment
Study	Events	Total	Events	Total	RR (95% CI)
Hultén 1988	4	34	9	43	0.56 (0.19 to 1.67)
B. First aid interventions that evacuate the poison from the gastrointestinal tract
Syrup of ipecac vs no intervention
Incidence of referrals to the emergency department
	Syrup of ipecac		No intervention
Study	Events	Total	Events	Total	Peto OR (95% CI)
Wax 1999	1	51	0	52	7.54 (0.15 to 378.83)
Incidence of hospitalizations
	Syrup of ipecac		No intervention
Study	Events	Total	Events	Total	Peto OR (95% CI)
Wax 1999	0	51	0	52	Not estimable
SDAC + cathartic vs SDAC (higher dose)
Incidence of adverse events (6 mL vs 4 mL)
	SDAC + 6 mL cathartic		SDAC + 4 mL cathartic
Study	Events	Total	Events	Total	Peto OR (95% CI)
Sue 1994	0	16	0	16	Not estimable
Incidence of adverse events (8 mL vs 4 mL)
	SDAC + 8 mL cathartic		SDAC + 4 mL cathartic
Study	Events	Total	Events	Total	Peto OR (95% CI)
Sue 1994	0	18	0	16	Not estimable
Incidence of adverse events (8 mL vs 6 mL)
	SDAC + 8 mL cathartic		SDAC + 6 mL cathartic
Study	Events	Total	Events	Total	Peto OR (95% CI)
Sue 1994	0	18	0	16	Not estimable
Incidence of hospitalization (6 mL vs 4 mL)
	SDAC + 6 mL cathartic		SDAC + 4 mL cathartic
Study	Events	Total	Events	Total	Peto OR (95% CI)
Sue 1994	1	16	0	16	7.39 (0.15 to 372.38)
Incidence of hospitalization (8 mL vs 4 mL)
	SDAC + 8 mL cathartic		SDAC + 4 mL cathartic
Study	Events	Total	Events	Total	Peto OR (95% CI)
Sue 1994	2	18	0	16	7.01 (0.42 to 117.63)
C. Combined first aid interventions that limit uptake and promote removal of the poison
MDAC + cathartic + hospitalintervention vs hospitalintervention
Incidence of adverse events
	MDAC + cathartic + hospital intervention		Hospital intervention
Study	Events	Total	Events	Total	Peto OR (95% CI)
Montoya‐Cabrera 1999	0	7	0	7	Not estimable
T_1/2 (h)
	MDAC + cathartic + hospital intervention (N = 7)		Hospital intervention (N = 7)
Study	Mean	SD	Mean	SD	MD (95% CI)
Montoya‐Cabrera 1999	10	N/A	17	N/A	−7 (not estimable)

Duration of intubation (h)
Study	SDAC	No SDAC	Summary estimate (P value)	# participants
Eddleston 2008	median (IQR): 112.0 (36.6–234.9)	median (IQR): 88.5 (38.5–203.1)	median difference: 23.5 (P > 0.05)	No information
Merigian 2002	mean: 54.6	mean: 39.9	mean difference: 14.7 (P = 0.70)	No information

AUC ((µg/L) × h)
Study	SDAC (median (IQR))	no SDAC (median (IQR))	Summary estimate (P value)	# participants
Roberts 2006	17.7 (11.1;21.8)	19.0 (13.7;24.3)	‐1.3 (P > 0.05)	28 vs 40

Number of atropine boluses administered
Study	MDAC (median (range))	SDAC (median (range))	Median difference [95% CI]	P value	# participants
De Silva 2003	1 (1‐6)	2 (1‐12)	0.0 (0.0‐1.0)	P < 0.0001	201 vs 200

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of adverse events	2	476	Peto Odds Ratio (Peto, Fixed, 95% CI)	4.17 [0.30, 57.26]
1.1 Incidence of adverse events	1	451	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Incidence of vomiting	1	25	Peto Odds Ratio (Peto, Fixed, 95% CI)	4.17 [0.30, 57.26]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of mortality	2	3425	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.04 [0.79, 1.37]
2 Incidence of adverse events	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 Incidence of vomiting	2	1806	Risk Ratio (M‐H, Random, 95% CI)	1.44 [0.88, 2.37]
2.2 Incidence of absent bowel sounds	1	3098	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.17, 1.00]
3 Incidence of need for intubation	4	3562	Risk Ratio (M‐H, Random, 95% CI)	1.37 [0.76, 2.47]
3.1 Gastric lavage prior to SDAC	2	3175	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.70, 1.27]
3.2 No gastric lavage prior to SDAC	2	387	Risk Ratio (M‐H, Random, 95% CI)	2.61 [1.38, 4.93]
4 Incidence of convulsions	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
5 Duration of intubation (h)			Other data	No numeric data
6 AUC ((µg/L) × h)			Other data	No numeric data
7 C_max (µg/L)			Other data	No numeric data
8 T_max (h)			Other data	No numeric data
9 Incidence of hospitalization	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10 Incidence of ICU admission	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Incidence of adverse events	1	Risk Difference (M‐H, Random, 95% CI)	Totals not selected
2 Glasgow Coma Scale score	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Mean arterial blood pressure (mmHg)	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
4 Heart rate (bpm)	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
5 Respiratory rate (breaths/min)	1	Mean Difference (IV, Random, 95% CI)	Totals not selected

Duration of intubation (h)
Study	MDAC	SDAC	Summary estimate	P value	# participants
Brahmi 2006	mean±SD: 24.1±4.2	mean±SD: 36.4±3.6	MD: ‐12.30, 95%CI [‐18.56;‐6.04]	P = 0.0001	3 vs 3
Eddleston 2008	median [IQR]: 83.8 (35.0–173.0)	median [IQR]: 112.0 (36.6–234.9)	median difference: ‐28.2	No information	No information

Length of intubation (h)
Study	MDAC (median IQR)	no intervention (median IQR)	Summary estimate	P value	# participants
Eddleston 2008	83.8 (35.0–173.0)	88.5 (38.5–203.1)	median difference: ‐4.7	P > 0.05	No information

Syrup of ipecac + SDAC + cathartic versus SDAC + cathartic for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (combination of different drugs or not specified)  Setting: hospital setting  Intervention: syrup of ipecac + single‐dose activated charcoal (SDAC) + Cathartic  Comparison: SDAC + Cathartic
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with SDAC + cathartic	Risk with syrup of ipecac + SDAC + cathartic
Incidence of mortality	—		—	573  (2 RCTs)	⊕⊝⊝⊝  Very low^a,b,c	The effect was not estimable due to zero events in intervention group (0/300) and control group (0/273). We are uncertain about the effect of syrup of ipecac in addition to SDAC + cathartic on incidence of mortality.
Incidence of adverse events	Study population		RR 2.59  (1.37 to 4.91)	764  (3 RCTs)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain about the effect of syrup of ipecac in addition to SDAC + cathartic on incidence of adverse events.
	41 per 1000	105 per 1000  (56 to 199)
Incidence and severity of symptoms of poisoning: incidence of clinical improvement	Study population		RR 1.00  (0.83 to 1.21)	989  (3 RCTs)	⊕⊕⊝⊝  Low^a,b	Syrup of ipecac in addition to SDAC + cathartic may make little or no difference in incidence of clinical improvement.
	548 per 1000	548 per 1000  (455 to 663)
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption	No studies collected or reported this outcome
Incidence of hospitalization	76 per 1000	89 per 1000 (53 to 151)	Peto OR 1.17 (0.69 to 1.98)	746  (3 RCTs)	⊕⊝⊝⊝  Very low^a,b,d	We are uncertain about the effect of Syrup of ipecac in addition to SDAC + cathartic on incidence of hospitalization
Incidence of ICU admission	47 per 1000	64 per 1000 (21 to 205)	RR 1.38 (0.44 to 4.38)	200  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d	We are uncertain about the effect of Syrup of ipecac in addition to SDAC + cathartic on incidence of ICU admission
*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).  CI: confidence interval; ICU: intensive care unit; RCT: randomized controlled trial; RR: risk ratio; OR: odds ratio; SDAC: single‐dose activated charcoal.
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.

SDAC + cathartic versus SDAC for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (not specified or a combination of different drugs)  Setting: hospital setting  Intervention: single‐dose activated charcoal (SDAC) + cathartic  Comparison: SDAC
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with SDAC	Risk with SDAC + cathartic
Incidence of mortality	No studies collected or reported this outcome
Incidence of adverse events	Study population		RR 1.46  (0.61 to 3.49)	180  (2 RCTs)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain about the effect of SDAC + cathartic, compared to SDAC alone on the incidence of adverse events.
	119 per 1000	174 per 1000  (73 to 415)
Incidence and severity of symptoms of poisoning ‐ not reported	No studies looked at this outcome
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption	No studies collected or reported this outcome
Incidence of hospitalization	Study population		RR 0.84  (0.09 to 7.46)	64  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c	We are uncertain about the effect of SDAC + cathartic, compared to SDAC alone on the incidence of ICU admission.
	71 per 1000	60 per 1000  (6 to 533)
Incidence of ICU admission	No studies collected or reported this outcome
*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).  CI: confidence interval; ICU: intensive care unit; RCT: randomized controlled trial; RR: risk ratio; SDAC: single‐dose activated charcoal.
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.

SDAC + cathartic compared to SDAC + cathartic (higher dose) for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (not specified)  Setting: hospital setting  Intervention: single‐dose activated charcoal (SDAC) + Cathartic  Comparison: SDAC + Cathartic (higher dose)
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with SDAC + cathartic (higher dose)	Risk with SDAC + cathartic
Incidence of mortality	No studies collected or reported this outcome
Incidence of adverse events: 8 mL vs 4 mL magnesium citrate	—		—	34  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c	The effect was not estimable due to zero events in intervention group (0/18) and control group (0/16). We are uncertain about the effects of SDAC + cathartic (higher dose) on the incidence of adverse events.
Occurrence and severity of symptoms of poisoning	No studies collected or reported this outcome
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption	No studies collected or reported this outcome
Incidence of hospitalization (8 mL vs 4 mL magnesium citrate)	control:0/16 and intervention 2/18 (Peto OR 7.01, 95% CI 0.42 to 117.63).		—	34  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d	We are uncertain about the effects of SDAC + cathartic (higher dose) on the incidence of hospitalization.
Incidence of ICU admission	No studies collected or reported this outcome
*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).  CI: confidence interval; RCT: randomized controlled trial; OR: odds ratio; SDAC: single‐dose activated charcoal;
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.

SDAC + cathartic + hospital intervention versus hospital intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning  Setting: hospital setting  Intervention: SDAC + cathartic + hospital intervention  Comparison: hospital intervention
Outcomes	Impact	№ of participants  (studies)	Certainty of the evidence  (GRADE)
Incidence of mortality	No studies collected or reported this outcome
Incidence of adverse events	Control group: 0/16 and intervention group: 5/16 (Peto OR 9.94, 95% CI 1.52 to 65.02). We are uncertain of the effect of SDAC + cathartic on the incidence of adverse events.	32  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c
Incidence and severity of symptoms of poisoning: level of coma  assessed with: Glasgow Coma Scale  Follow‐up: 2 days	No numeric data were provided about Glasgow Coma Scale scores, but the course of the scores was reported not to differ significantly between treatments (P = 0.49). We are uncertain of the effect of SDAC + cathartic on the level of coma.	32  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption	No studies collected or reported this outcome
Hospitalization	No studies collected or reported this outcome
ICU admission	No studies collected or reported this outcome
*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).  CI: confidence interval; ICU: intensive care unit; OR: odds ratio; RCT: randomized controlled trial; SDAC: single‐dose activated charcoal.
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.

MDAC + cathartic + hospital intervention versus hospital intervention for first aid in patients with acute oral poisoning
Patient or population: first aid in patients with acute oral poisoning (paracetamol)  Setting: hospital setting  Intervention: multiple dose of activated charcoal (MDAC) + Cathartic + Hospital intervention  Comparison: hospital intervention
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	№ of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with hospital intervention	Risk with MDAC + cathartic + hospital intervention
Incidence of mortality	No studies collected or reported this outcome
Incidence of adverse events	—		—	14  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,c	The effect was not estimable due to the absence of events in the intervention (0/7) and the control group (0/7). We are uncertain about the effect of MDAC with a cathartic on the incidence of adverse events.
Incidence and severity of symptoms of poisoning	No studies collected or reported this outcome
Duration of toxic symptoms	No studies collected or reported this outcome
Drug absorption: paracetamol: elimination half‐life T_1/2 (h)	The mean drug absorption: paracetamol: elimination half‐life T_1/2 (h) was 17 h	MD 7 h lower	—	14  (1 RCT)	⊕⊝⊝⊝  Very low^a,b,d	The study reported no standard deviations or other measures of data spread. We are uncertain about the effect of MDAC with a cathartic on paracetamol elimination half‐life.
Incidence of hospitalization	No studies collected or reported this outcome
Incidence of ICU admission	No studies collected or reported this outcome
*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).  CI: confidence interval; ICU: intensive care unit; MD: mean difference; MDAC: multi‐dose activated charcoal; RCT: randomized controlled trial.
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.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of mortality	2	3476	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.21, 1.63]
2 Incidence of adverse events	2	3476	Peto Odds Ratio (Peto, Fixed, 95% CI)	3.55 [1.85, 6.79]
3 Incidence of need for cardiac pacing/antitoxin treatment	2	1490	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.02, 4.18]
4 Incidence of life‐threatening arrhythmias	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
5 Amount of atropine administered (mg)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6 Number of atropine boluses administered			Other data	No numeric data
7 Incidence of need for intubation	2	3097	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.75, 1.38]
8 Incidence of convulsions	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
9 Duration of coma (h)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
10 Duration of intubation (h)			Other data	No numeric data
11 C_max (µg/L)			Other data	No numeric data
12 T_max (h)			Other data	No numeric data
13 T_1/2 (h)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
14 AUC ((µg/L) × h)			Other data	No numeric data
15 Incidence of ICU admission	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Incidence of diarrhoea	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2 Incidence of abdominal pain	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
3 Incidence of sedation	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
4 Incidence of agitation	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Incidence of adverse events	2	Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.1 Vomiting	1	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Lethargy during follow‐up	1	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Incidence of hospitalization	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

PERMALINK

First aid interventions by laypeople for acute oral poisoning

Bert Avau

Vere Borra

Anne‐Catherine Vanhove

Philippe Vandekerckhove

Peter De Paepe

Emmy De Buck

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

A. First aid interventions that limit or delay the absorption of the poison in the body

B. First aid interventions that evacuate the poison from the gastrointestinal tract

C. First aid interventions that limit uptake and promote evacuation of the poison from the gastrointestinal tract

D. First aid interventions that neutralize or dilute the poison

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

1. Sources of individual studies.

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' table

Results

Description of studies

Results of the search

1.

Included studies

2. Overview of comparisons.

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. SDAC versus no intervention for first aid in patients with acute oral poisoning.

Summary of findings 2. SDAC + hospital intervention versus hospital intervention alone for first aid in patients with acute oral poisoning.

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

Summary of findings 4. SDAC versus syrup of ipecac for first aid in patients with acute oral poisoning.

Summary of findings 5. MDAC + hospital intervention versus hospital intervention for first aid in patients with acute oral poisoning.

Summary of findings 6. Syrup of ipecac versus no intervention for first aid in patients with acute oral poisoning.

A. First aid interventions that limit or delay the absorption of the poison in the body

1. Single‐dose activated charcoal versus no intervention

Primary outcomes

Incidence of mortality

Adverse events

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Incidence of vomiting (sorbitol vs magnesium sulphate	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2 Incidence of vomiting (sorbitol vs magnesium citrate)	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
3 Incidence of vomiting (magnesium sulphate vs magnesium citrate)	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Methods	Study design: randomized controlled trial Study duration: 24 months ending December 1987 Setting: emergency department (ED) at UC Davis Medical Center Country: USA Number of individuals randomized: 200 Number of individuals receiving the intervention: 93 Number of individuals receiving the control: 107 Number of individuals lost to follow‐up: 0 Sample size calculated: no information
Participants	Sex: 113 women, 87 men Age: 30.1 (SEM 0.8), range 18‐77 years Country (if different from study authors'): NA Type, dose and timing of poisoning: all participants with mild or moderate oral overdose, 56% had mixed overdoses, most frequently with ethanol, timing could not be reliably obtained in most participants Inclusion criteria: awake with gag reflex, > 18 years, cooperative Exclusion criteria: rapidly deteriorating level of consciousness, previous vomiting, received ipecac syrup at home or en route, ingested substance with contraindication for ipecac syrup, ingested strong acids or bases, camphor, volatile petroleum distillates and strychnine, ingested large amounts of iron and lithium alone
Interventions	Intervention arm: Type: syrup of ipecac followed with activated charcoal‐sorbitol after vomiting subsided Timing: Syrup of ipecac: no information AC‐sorbitol: after induced vomiting Dose: 30 mL ipecac syrup + 1 g/kg AC (50 g AC‐sorbitol‐water suspension Frequency: 1× ipecac unless no response then repeated after 30 min + 1× AC Integrity: no information Control arm: Type: activated charcoal‐sorbitol Timing: no information Dose: 1 g/kg AC (50 g AC‐sorbitol‐water suspension) Frequency: 1× Integrity: no information
Outcomes	Type (unit): Mean time in the emergency department (h) (see Table 21) Proportion requiring hospitalization Number of days hospitalized (see Table 21) Proportion admitted to the intensive care unit Number of days in ICU (see Table 21) Proportion of complications Timing: during time in the hospital (early)
Funding	No information
Notes	75% had toxicology screen done but was not a criterion for inclusion or exclusion
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "were randomized by hospital unit numbers to two treatment groups" Comment: not an adequate randomisation method
Allocation concealment (selection bias)	High risk	Quote: "were randomized by hospital unit numbers to two treatment groups" Comment: allocation scheme does not allow allocation concealment
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	No information to support judgment, but lack of blinding may affect outcomes studied
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	No information to support judgment, but lack of blinding may affect outcomes studied (e.g. mean time spend in the emergency department)
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No specific information, but no failure to adhere to intervention reported
Selective reporting (reporting bias)	High risk	No assessment of symptom severity
Other bias	High risk	Quote: "Most patients (75%) had partial or complete toxicological analysis of blood and/or urine performed, although this was not a requirement of the study." Comment: for 25% of the participants, actual poisoning was not verified by means other than history.

Methods	Study design: randomized controlled study Study duration: October 1975 to June 1976 Setting: hospital (emergency department of the Ben Taub hospital, Houston, Texas) Country: USA Number of individuals randomized: 339 Number of individuals receiving the intervention: 131 Number of individuals receiving the control: 208 Number of individuals lost to follow‐up:277 at the start of follow‐up, 308 at the 3‐5 h sample Sample size calculated: no information
Participants	Sex: no information Age: no information Country (if different from study authors'): NA Type, dose and timing of poisoning: Participants presenting with illness associated with acute oral drug overdose, and at the discretion of the attending physician selected for gastric lavage. Of these, chemical evidence of intake of sedative‐hypnotics or aspiring in the blood and at least 2 blood samples (1 at lavage and 1 afterwards) were available for 62 participants (25 AC and 37 control participants) Inclusion criteria: taken a sedative‐hypnotic or aspirin Degree of functional decompensation: moderate ‐ slight impairment to unconscious, normal gag reflex and deep tendon reflexes, responsive to superficial pain; severe ‐ unconscious with depressed or absent pain response, gag reflex and deep tendon reflexes to respiratory arrest Chemical proof of intake of sedative‐hypnotics or aspirin
Interventions	Intervention arm: Type: gastric lavage + activated charcoal via nasogastric tube Timing: no information Dose: gastric lavage followed by 100 g AC Frequency: 1× Integrity: no information Control arm: Type: gastric lavage Timing: no information Dose: no information Frequency: 1× Integrity: no information
Outcomes	Type (unit): percentage of participants showing increased blood drug concentrations (%) (data not extracted) Timing: blood samples were taken at the time of lavage and at 2 h to 4 h intervals thereafter when possible (early)
Funding	Supported by grant from the National Institute of Drug Abuse: grant 1 H81 DA 0175301
Notes	Of the initially 339 selected participants, only 62 had chemical proof of sedative‐hypnotics or aspirin at at least 1 blood sample available, which constituted the study sample
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Following gastric lavage, 131 patients were randomly chosen to receive a slurry of 100 g of activated charcoal (Norit A) via the gastric tube." Comment: not enough information to make a judgment
Allocation concealment (selection bias)	Unclear risk	Quote: "Following gastric lavage, 131 patients were randomly chosen to receive a slurry of 100 g of activated charcoal (Norit A) via the gastric tube." Comment: not enough information to make a judgment
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	No information to support judgment, but lack of blinding may affect outcomes studied
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	No information to support judgment, but lack of blinding is not likely to affect measurement of the outcomes studied
Incomplete outcome data (attrition bias)   All outcomes	High risk	Quote: "Of the total population, 25 AC treated patients and 37 control patients had chemical evidence for the presence of one of the sedative‐hypnotics listed in Tables la and lb or aspirin in the blood, and at least one blood sample in addition to the sample taken at lavage. These 62 patients constituted the population under study." Comment: only data from 62 out 339 randomized patients (18%) is presented. Loss to follow‐up increases over time
Selective reporting (reporting bias)	High risk	Several clinically relevant outcomes (symptoms, adverse events) not reported
Other bias	High risk	Quote: "995 were ingestions by history and 339 or 34% were selected for gastric lavage at the discretion of the attending physician." Comment: potential bias during selection of the study population

Study	Reason for exclusion
Afshari 2010a	Ineligible intervention: IV administration of intervention
Afshari 2010b	Ineligible intervention: IV administration of intervention
Auerbach 1986	Ineligible intervention: comparison between gastric lavage and ipecac
Belon 2007	Ineligible intervention: homeopathic remedy
Berg 1982	Ineligible study population: not oral poisoning
Berlinger 1983	Ineligible population: not oral poisoning
Bhalla 2014	Ineligible intervention: IV administration of intervention
Bosse 1995	Ineligible intervention: not possible to determine the additional effect of activated charcoal on top of hospital treatment
Boxer 1969	Ineligible comparison: hospital treatment vs ipecac
Boyd 1999	Ineligible comparison: 2 types of charcoal compared, no control group without charcoal
Campbell 1992	Ineligible intervention: repeat dose of activated charcoal, no control group without activated charcoal
Chamberlain 1993	Ineligible intervention: different groups received different doses of N‐acetylcysteine. Impossible to distinguish the effect of AC from this
Corby 1968	Ineligible intervention: control is apomorphine
Crome 1976	Ineligible intervention: methionine
Dorooshi 2016	Recent trial that was not prospectively registered in a trials register
Eddleston 2009	Ineligible intervention: pralidoxime
Ekins 1987	Ineligible study population: not poisoned patients
Escalante 2016	Recent trial that was not prospectively registered in a trials register
Espinosa 1987	Ineligible intervention: feasibility of administration
Filippone 1987	Ineligible intervention: pre‐absorbed durg‐charcoal mixture
Fischer 1999	Ineligible comparison: 2 types of charcoal compared, no control group without charcoal
Frenia 1996	Ineligible study population: not oral poisoning
Gomez 1997	Ineligible intervention: pre‐absorbed durg‐charcoal mixture
Grierson 2000	Ineligible intervention: gastric lavage
Hoegberg 2005	Ineligible intervention: yoghourt
Hoegberg 2012	Ineligible intervention: alcohol
Ilkhanipour 1992	Ineligible study population: not oral poisoning
Ilkhanipour 1993	Ineligible study population: not oral poisoning
IRCT138811142717N1 2010	Ineligible intervention: IV administration of intervention
IRCT20180118038426N2 2018	Recent trial that was not prospectively registered in a trials register. The trial was registered after recruitment had started
Isbister 2011	Ineligible study population: not oral poisoning
ISRCTN50739829 2006	Ineligible intervention: IV administration of treatment
Karim 2001	Ineligible intervention: feasibility of administration
Krenzelok 1985a	Ineligible study population: not poisoning patients
Ly 2004	Ineligible intervention: whole bowel irrigation
MacLean 1973	Ineligible intervention: apomorphine
Mahutte 1983	Ineligible study population: not oral poisoning
Merigian 1988	Ineligible intervention: gastric emptying not specified
Navabi 2017	Ineligible intervention: hospital treatments
Nogue 1987	Ineligible intervention: two formulations of ipecac compared
Olsen 1993	Ineligible intervention: whole bowel irrigation
Olsen 1995	Ineligible intervention: whole bowel irrigation
Pond 1984	Ineligible comparison: no suitable comparison
Roberts 1997	Ineligible intervention: comparison of 2 brands of activated charcoal
Schofferman 1976	Ineligible intervention: apomorphine
Skinner 2012	Ineligible population: chronic poisoning patients
Smith 1967	Ineligible intervention: montmorillonite
Tincu 2017	Recent trial that was not prospectively registered in a trials register
Varipapa 1977	Ineligible study population: not oral poisoning
Vijayakumar 2017	Ineligible intervention: IV administration of intervention
Young 1993	Inelgible comparison: hospital treatment vs ipecac

A. First aid interventions that limit or delay the absorption of the poison in the body
SDAC vs no intervention
Length of stay in the emergency department (min)
	SDAC			No intervention
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Merigian 1990	252	279	220	230	166	231	22.00 (−20.63 to 64.63)
SDAC + hospitalintervention vs hospitalintervention
Length of ICU stay (h)
	SDAC + hospital intervention			Hospital intervention
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Merigian 2002	54.4	93.15	28	45.5	36.3	32	8.90 (−27.82 to 45.62)
Incidence of ICU stay > 3 days
	SDAC + hospital intervention			Hospital intervention
Study	Events	Total		Events	Total		RR (95% CI)
Hultén 1988	0	34		5	43		0.11 (0.01 to 2.00)
Length of hospital stay (h)
	SDAC + hospital intervention			Hospital intervention
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Merigian 2002	63.8	79.8	51	91.7	103.97	102	−27.90 (−57.68 to 1.88)
Study	Median	IQR	N	Median	IQR	N	Median difference (P value)
Cooper 2005	6.8	(4.0 to 14.0)	166	5.5	(3.0 to 12.0)	161	1.3 (P = 0.11)
Incidence of hospital stay > 3 days
	SDAC + hospital intervention			Hospital intervention
Study	Events	Total		Events	Total		RR (95% CI)
Hultén 1988	1	34		4	43		0.32 (0.04 to 2.70)
Length of stay in the emergency department (h)
	SDAC + hospital intervention			Hospital intervention
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Merigian 2002	6.2	3.9	325	5.3	3.9	941	0.90 (0.41 to 1.39)
MDAC + hospitalintervention vs hospitalintervention
Length of hospital stay (h)
	MDAC + hospital intervention			Hospital intervention
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Behnoush 2009	31.0	8.9	30	55.0	8.5	30	−24.00 (−28.40 to −19.60)
Brahmi 2006	30.3	3.4	6	39.7	7.3	6	−9.40 (−15.84 to −2.96)
	Median	IQR	N	Median	IQR	N	Median difference (P value)
De Silva 2003	3	(0.25 to 24)	201	3	(0.5 to 10)	200	0 (P = 0.90)
SDAC vs syrup of ipecac
Length of stay in the emergency department (min)
	Syrup of ipecac			SDAC
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Amigó Tadín 2002	113.21	66.0	21	81.46	27.92	13	31.75 (−0.30 to 63.80)
B. First aid interventions that evacuate the poison from the gastrointestinal tract
Syrup of ipecac + SDAC + cathartic vs SDAC + cathartic
Length of hospital stay (days)
	Syrup of ipecac + SDAC + cathartic			SDAC + cathartic
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Albertson 1989	2.4	5.8	13	1.7	5.2	12	0.70 (−3.61 to 5.01)
Length of stay in the emergency department (h)
	Syrup of ipecac + SDAC + cathartic			SDAC + cathartic
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Albertson 1989	6.8	2.9	93	6.0	2.1	107	0.80 (0.09 to 1.51)
Kornberg 1991	4.1	1.1	29	3.4	1.2	38	0.70 (0.15 to 1.25)
Length of ICU stay (h)
	Syrup of ipecac + SDAC + cathartic			SDAC + cathartic
Study	Mean	SD	N	Mean	SD	N	MD (95% CI)
Albertson 1989	1.8	3.9	6	1.0	0.0	5	Not estimable