South Asian Clinical Toxicology Research Collaboration
Gastrointestinal Gastrointestinal Decontamination:Decontamination:
Risk/Benefit + Evidence =Risk/Benefit + Evidence =PracticePractice
Gastrointestinal Gastrointestinal Decontamination:Decontamination:
Risk/Benefit + Evidence =Risk/Benefit + Evidence =PracticePractice
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
Gastrointestinal Decontamination: Gastrointestinal Decontamination: What are our options?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 ingestionRisk 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)
ConsiderConsider• DoseDose• Our knowledge about the toxicityOur knowledge about the toxicity• Pharmacokinetics & PharmacodynamicsPharmacokinetics & Pharmacodynamics
• Survivor CohortSurvivor Cohort
ConsiderConsider• DoseDose• Our knowledge about the toxicityOur knowledge about the toxicity• Pharmacokinetics & PharmacodynamicsPharmacokinetics & Pharmacodynamics
• Survivor CohortSurvivor Cohort
South Asian Clinical Toxicology Research Collaboration
Risk of InterventionRisk 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
South Asian Clinical Toxicology Research Collaboration
EvidenceEvidence 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.
South Asian Clinical Toxicology Research Collaboration
Limitations of Experimental Limitations of Experimental EvidenceEvidence
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 EvidenceLimitations 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?Generalisabilty?
South Asian Clinical Toxicology Research Collaboration
Evidence on gastrointestinal Evidence on gastrointestinal decontaminationdecontamination
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.
South Asian Clinical Toxicology Research Collaboration
Gastric emptying in acute overdose: a Gastric emptying in acute overdose: a prospective randomised controlled trialprospective randomised controlled trial. . Pond et al, Med J Aust 1995; 163: 345-349Pond 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
South Asian Clinical Toxicology Research Collaboration
Buckley NA. et al Activated charcoal reduces the Buckley NA. et al Activated charcoal reduces the need for N-acetylcysteine treatment after paracetamol need for N-acetylcysteine treatment after paracetamol overdose. J Tox - Clin Tox. 37(6):753-7, 1999overdose. J Tox - Clin Tox. 37(6):753-7, 1999
No GI decontamination
(n=167)
Charcoal alone
(n=163)
Lavage & Charcoal
(n=120)
p value (combined charcoal
vs none)
Median Amount (G)
15 (10-75)
12.5 (10-77)
15 (10-70)
0.65
Median Time to Presentation (min)
385 (10-13380)
135 (5-885)
120 (14-840)
0.0001
Probable or high risk concentration
50 (29.9%) 21 (12.9%) 17 (14.2%) <0.0001
LOS (hours)
22.3 (1-170) 19.2 (2-285) 18.8 (2.7-154) 0.04
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)
South Asian Clinical Toxicology Research Collaboration
Repeat dose of activated Repeat dose of activated charcoalcharcoal
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.
South Asian Clinical Toxicology Research Collaboration
COMPLIANCE FOR SINGLE AND COMPLIANCE FOR SINGLE AND MULTIPLE DOSE REGIMENS OF MULTIPLE DOSE REGIMENS OF
ACTIVATED CHARCOAL: A ACTIVATED CHARCOAL: A PROSPECTIVE STUDY OF PATIENTS PROSPECTIVE STUDY OF PATIENTS
IN A CLINICAL TRIALIN 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 Number of patients refusing each doses of activated charcoal doses of activated charcoal
(n=691)(n=691)
02468
10121416
SDM
D1M
D2M
D3M
D4M
D5M
D6
charcoal regimen
% p
atie
nt
% absoluterefusals
South Asian Clinical Toxicology Research Collaboration
Where Is the Evidence for Treatments Where Is the Evidence for Treatments Used in Pesticide Poisoning? Used in Pesticide Poisoning? Is Clinical Toxicology Fiddling While the Is Clinical Toxicology Fiddling While the Developing World Burns?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 Burden of Disease: Deliberate Self PoisoningSelf 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
South Asian Clinical Toxicology Research Collaboration
South Asian Clinical Toxicology South Asian Clinical Toxicology Research CollaborationResearch 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
South Asian Clinical Toxicology South Asian Clinical Toxicology Research CollaborationResearch Collaboration
“Reducing deaths from pesticide poisoning - Establishing a regional toxicology research centre”
South Asian Clinical Toxicology Research Collaboration
Relative Toxicity Relative Toxicity Anti-cholinesterasesAnti-cholinesterases
0 10 20 30 40
carbofuranfenobucarbcarbosulfan
malathion
phenthoatediazinon
chlorpyrifosfenthion
profenofosquinalphosdimethoate
Case fatality ratio (95% CI)
South Asian Clinical Toxicology Research Collaboration
Time to Death following Ingestion:Time to Death following Ingestion:
Chlorpyrifos, Dimethoate & FenthionChlorpyrifos, Dimethoate & Fenthion
South Asian Clinical Toxicology Research Collaboration
average cases of poisoning?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 GI decontamination in pesticide poisoningin pesticide poisoning
Chief Investigator: Michael Eddleston
South Asian Clinical Toxicology Research Collaboration
Activated charcoal RCT - Study designActivated 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 resultsOverall 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 - PoisonSub-groups - Poison
0.1 1 10
Overall
Medication/other
Other-unknown pesticde
Oleander
OP/Carbamate
Odds ratio
South Asian Clinical Toxicology Research Collaboration
Sub-groups - timeSub-groups - time
0.1 1 10
Overall
Missing
> 8 hours
4-8 hours
2-4 hours
< 2 hours
Odds ratio
South Asian Clinical Toxicology Research Collaboration
Sub-groups - SymptomsSub-groups - Symptoms
0.1 1 10
Overall
Symptomatic GCS< 14
Symptomatic GCS 14-15
Asymptomatic
Odds ratio
South Asian Clinical Toxicology Research Collaboration
ConclusionConclusion 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
AcknowledgmentsAcknowledgments 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: – [email protected]
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