south asian clinical toxicology research collaboration gastrointestinal decontamination:...

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


Sri Lanka

Andrew Dawson


Sri Lanka


The ChallengeThe Challenge


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


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


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


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.


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


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?


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.


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


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)


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.


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


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


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


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 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 South Asian Clinical Toxicology Research CollaborationResearch Collaboration

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


Relative Toxicity Relative Toxicity Anti-cholinesterasesAnti-cholinesterases

0 10 20 30 40

carbofuranfenobucarbcarbosulfan

malathion

phenthoatediazinon

chlorpyrifosfenthion

profenofosquinalphosdimethoate

Case fatality ratio (95% CI)


Time to Death following Ingestion:Time to Death following Ingestion:

Chlorpyrifos, Dimethoate & FenthionChlorpyrifos, Dimethoate & Fenthion


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


•Induced Emesis•Gastric Lavage•Activated Charcoal•Nothing

•100 mls of fenthion


•Induced Emesis•Gastric Lavage•Activated Charcoal•Nothing


GI decontamination GI decontamination in pesticide poisoningin pesticide poisoning

Chief Investigator: Michael Eddleston


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.


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)


Sub-groups - PoisonSub-groups - Poison

0.1 1 10

Overall

Medication/other

Other-unknown pesticde

Oleander

OP/Carbamate

Odds ratio


Sub-groups - timeSub-groups - time

0.1 1 10

Overall

Missing

> 8 hours

4-8 hours

2-4 hours

< 2 hours

Odds ratio


Sub-groups - SymptomsSub-groups - Symptoms

0.1 1 10

Overall

Symptomatic GCS< 14

Symptomatic GCS 14-15

Asymptomatic

Odds ratio


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


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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