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Gastrointestinal Decontamination: Risk/Benefit + Evidence = Practice

Gastrointestinal Decontamination: Risk/Benefit + Evidence = Practice. Andrew Dawson South Asian Clinical Toxicology Research Collaboration Sri Lanka. The Challenge. Gastrointestinal Decontamination: What are our options?. Nothing Emesis Gastric Lavage Activated Charcoal ± cathartic

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Gastrointestinal Decontamination: Risk/Benefit + Evidence = Practice

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

  2. The Challenge

  3. 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

  4. 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 (1493-1541) • Consider • Dose • Our knowledge about the toxicity • Pharmacokinetics & Pharmacodynamics • Survivor Cohort

  5. Risk of Intervention • Aspiration • Impaired GCS + Unprotected Airway • Emesis, Lavage, Charcoal (worse with cathartics) • Trauma • Oesphageal Injury • Emesis, Lavage, Charcoal • Electrolyte Abnormalities • Forced Emesis, Cathartics • Cardiac Arrest • Toxin induced bradycardia + Vagal Tone • Induced emesis, Lavage • Cost

  6. 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 • 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;35:721-41. • 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;37:731-51.

  7. 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

  8. 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 • e.g local practice, convenience • No clear change in any of these parameters published Generalisabilty?

  9. 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;14:562-567. • Pond SM et al. Gastric emptying in acute overdose: a prospective randomised controlled trial. Med J Aust 1995;163:345-349. • No clinical benefit from gastric emptying in unselected patients with poisoning.

  10. Gastric emptying in acute overdose: a prospective randomised controlled trial. Pond et al, Med J Aust 1995; 163: 345-349 • 876 randomised • Emptying (Ipecac or lavage) + Charcoal: • Not-emptied + Charcoal • Outcome • % of patients whose severity changed • Complications • LOS • Gastric emptying can be omitted

  11. 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 0.23-0.58, p<0.0001) • Lavage + Charcoal: Odds Ratio 1.12 (95% CI 0.57-2.20, p=0.86)

  12. 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;361:1935-8.

  13. 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

  14. Number of patients refusing each doses of activated charcoal (n=691)

  15. 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

  16. Burden of Disease: Deliberate Self Poisoning • Australia • 5% of admissions • treatment costs of $600 million 1995-96 • 50% of suicides • Asia and Africa • > 250,000 deaths per year deliberate pesticides ingestion • 100,000 deaths per year from envenomation

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

  18. South Asian Clinical Toxicology Research Collaboration “Reducing deaths from pesticide poisoning - Establishing a regional toxicology research centre”

  19. Relative Toxicity Anti-cholinesterases

  20. Time to Death following Ingestion: Chlorpyrifos, Dimethoate & Fenthion

  21. 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 average cases of poisoning? • 100 mls of fenthion • What decontamination? • Induced Emesis • Gastric Lavage • Activated Charcoal • Nothing

  22. GI decontamination in pesticide poisoning Chief Investigator: Michael Eddleston

  23. 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.

  24. 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)

  25. Sub-groups - Poison

  26. Sub-groups - time

  27. Sub-groups - Symptoms

  28. 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

  29. 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: • adawson@sactrc.org

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