South Asian Clinical Toxicology Research Collaboration Gastrointestinal Decontamination: Risk/Benefit + Evidence =Practice Andrew Dawson South Asian Clinical Toxicology Research Collaboration Sri Lanka Andrew Dawson South Asian Clinical Toxicology Research Collaboration Sri Lanka

South Asian Clinical Toxicology Research Collaboration The Challenge

South Asian Clinical Toxicology Research Collaboration Gastrointestinal Decontamination: What are our options?  Nothing  Emesis  Gastric Lavage  Activated Charcoal  cathartic  Whole bowel irrigation Our Decision should depend on a risk/benefit analysis

South Asian Clinical Toxicology Research Collaboration Risk from ingestion What is there that is not poison? All things are poison and nothing without poison. Solely the dose determines that a thing is not a poison. Paracelsus ( ) Consider Dose Dose Our knowledge about the toxicity Our knowledge about the toxicity Pharmacokinetics & Pharmacodynamics Pharmacokinetics & Pharmacodynamics Survivor Cohort Survivor CohortConsider Dose Dose Our knowledge about the toxicity Our knowledge about the toxicity Pharmacokinetics & Pharmacodynamics Pharmacokinetics & Pharmacodynamics Survivor Cohort Survivor Cohort

South Asian Clinical Toxicology Research Collaboration Risk of Intervention  Aspiration –Impaired GCS + Unprotected Airway l Emesis, Lavage, Charcoal (worse with cathartics)  Trauma –Oesphageal Injury l Emesis, Lavage, Charcoal  Electrolyte Abnormalities l Forced Emesis, Cathartics  Cardiac Arrest –Toxin induced bradycardia + Vagal Tone l Induced emesis, Lavage  Cost

South Asian Clinical Toxicology Research Collaboration Evidence  Mostly controlled experimental models rather than clinical –Intermediate Outcomes –Idealised settings  Summary –Little benefit after 1 hour –Charcoal is generally better than emesis or lavage l American Academy of Clinical Toxicology and European Association of Poison Centres and Clinical Toxicologists. Position statement: single-dose activated charcoal. J Toxicol Clin Toxicol 1997;35: l American Academy of Clinical Toxicology and European Association of Poison Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999;37:

South Asian Clinical Toxicology Research Collaboration Limitations of Experimental Evidence  Intermediate Outcomes (rather than “a cure”) –Reduction drug absorption –Enhancing drug clearance –GIT transit times  Inappropriate models  Poor correlation with drug concentration and effect  Diversity in clinical practice

South Asian Clinical Toxicology Research Collaboration Limitations of Clinical Evidence  What endpoints drive decontamination –Patient outcomes: Survival or Bed-stay –Resource Utilization  Problems –Very low mortality in most studies –The other determinates of bed stay l e.g local practice, convenience  No clear change in any of these parameters published Generalisabilty?

South Asian Clinical Toxicology Research Collaboration Evidence on gastrointestinal decontamination Evidence on gastrointestinal decontamination  Two ‘randomised’ clinical trials (Gastric emptying v none)  pseudo-randomisation (ascertainment bias)  performance bias Kulig K et al Management of acutely poisoned patients without gastric emptying. Ann Emerg Med 1985;14: Pond SM et al. Gastric emptying in acute overdose: a prospective randomised controlled trial. Med J Aust 1995;163:  No clinical benefit from gastric emptying in unselected patients with poisoning.

South Asian Clinical Toxicology Research Collaboration Gastric emptying in acute overdose: a prospective randomised controlled trial. Pond et al, Med J Aust 1995; 163:  876 randomised –Emptying (Ipecac or lavage) + Charcoal: –Not-emptied + Charcoal  Outcome –% of patients whose severity changed –Complications –LOS  Gastric emptying can be omitted

South Asian Clinical Toxicology Research Collaboration Buckley NA. et al Activated charcoal reduces the need for N-acetylcysteine treatment after paracetamol overdose. J Tox - Clin Tox. 37(6):753-7, 1999 Need for NAC Charcoal: Odds Ratio 0.36 (95% CI , p<0.0001) Lavage + Charcoal: Odds Ratio 1.12 (95% CI , p=0.86)

South Asian Clinical Toxicology Research Collaboration Repeat dose of activated charcoal  de Silva HA et al Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo- controlled trial. Lancet 2003;361:

South Asian Clinical Toxicology Research Collaboration COMPLIANCE FOR SINGLE AND MULTIPLE DOSE REGIMENS OF ACTIVATED CHARCOAL: A PROSPECTIVE STUDY OF PATIENTS IN A CLINICAL TRIAL Fahim Mohamed, Lalith Senarathna, Michael Eddleston South Asian Clinical Toxicology Research Collaboration (SACTRC), North Central Province, Sri Lanka

South Asian Clinical Toxicology Research Collaboration Number of patients refusing each doses of activated charcoal (n=691)

South Asian Clinical Toxicology Research Collaboration Where Is the Evidence for Treatments Used in Pesticide Poisoning? Is Clinical Toxicology Fiddling While the Developing World Burns?  Buckley NA, Karalliedde L, Dawson A, Senanayake N, Eddleston M. Journal of Toxicology Clinical Toxicology 3 Vol. 42, No. 1, pp. 1–4, 2004

South Asian Clinical Toxicology Research Collaboration Burden of Disease: Deliberate Self Poisoning  Australia –5% of admissions l treatment costs of $600 million –50% of suicides  Asia and Africa –> 250,000 deaths per year deliberate pesticides ingestion –100,000 deaths per year from envenomation

South Asian Clinical Toxicology Research Collaboration  Multi-national group based in Sri Lanka  Funding –Wellcome Trust Fellowship Grant –Wellcome Trust & Australian NHMRC Capacity Grants

South Asian Clinical Toxicology Research Collaboration

“Reducing deaths from pesticide poisoning - Establishing a regional toxicology research centre”

South Asian Clinical Toxicology Research Collaboration Relative Toxicity Anti-cholinesterases

South Asian Clinical Toxicology Research Collaboration

Time to Death following Ingestion: Chlorpyrifos, Dimethoate & Fenthion

South Asian Clinical Toxicology Research Collaboration

average cases of poisoning?  An alert & cooperative 40 kg 16 year old woman presents 2 hours after ingestion of:  8 grams of paracetamol What decontamination?  Induced Emesis  Gastric Lavage  Activated Charcoal  Nothing 100 mls of fenthion What decontamination? Induced Emesis Gastric Lavage Activated Charcoal Nothing 100 mls of fenthion What decontamination? Induced Emesis Gastric Lavage Activated Charcoal Nothing

South Asian Clinical Toxicology Research Collaboration GI decontamination in pesticide poisoning Chief Investigator: Michael Eddleston

South Asian Clinical Toxicology Research Collaboration Activated charcoal RCT - Study design Patients: all patients with a history of self-poisoning (>13yrs, not pregnant, not hydrocarbon/corrosive) Outcome:vital status at discharge Power:to detect a reduction in all-cause mortality from 10% to 7%, 1400 patients must be recruited to each of the 3 arms of the study (4200 in total) Interventions:- no charcoal. - 50g superactivated charcoal on admission only. - 50g on admission, then q4h for 24hrs.

South Asian Clinical Toxicology Research Collaboration Overall results  4216 patients recruited  Overall death rate around 7%, pesticide death rate around 13% –No significant difference between groups  Primary Outcome (death rate in combined charcoal groups vs no charcoal) –Odds Ratio 0.98 (95% CI: 0.75, 1.28)

South Asian Clinical Toxicology Research Collaboration Sub-groups - Poison

South Asian Clinical Toxicology Research Collaboration Sub-groups - time

South Asian Clinical Toxicology Research Collaboration Sub-groups - Symptoms

South Asian Clinical Toxicology Research Collaboration Conclusion  Don’t just do nothing…..stand there and think  While the evidence is limited gastric decontamination should be considered in high risk poisonings when it can be done safely  Probably no role for emesis if charcoal is available

South Asian Clinical Toxicology Research Collaboration Acknowledgments  Wellcome Trust & NHMRC  Sri Lankan Ministry of Health  SACTRC North Central Province –VPs at Anuradhapura and Polonnaruwa –Lalith Senarathna, Mohammed Fahim –60 SACTRC pre-interns North Central Province  Michael Eddleston, Rezvi Sheriff, Nick Buckley  Contact: