Download Gastrointestinal Decontamination Jaffna 2

Gastrointestinal
Decontamination:
Risk/Benefit + Evidence =Practice
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 (1493-1541)
Consider
• Dose
• Our knowledge about the toxicity
• Pharmacokinetics & Pharmacodynamics
• Survivor Cohort
South Asian Clinical Toxicology Research Collaboration
Risk of Intervention

Aspiration
– Impaired GCS + Unprotected Airway


Emesis, Lavage, Charcoal (worse with cathartics)
Trauma
– Oesphageal Injury


Electrolyte Abnormalities


Emesis, Lavage, Charcoal
Forced Emesis, Cathartics
Cardiac Arrest
– Toxin induced bradycardia + Vagal Tone


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


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
Evidence

Intermediate Outcomes (rather than “a cure”)
– Reduction drug absorption
– Enhancing drug clearance
– GIT transit times


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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

Generalisabilty?
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
South Asian Clinical Toxicology Research Collaboration
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.
South Asian Clinical Toxicology Research Collaboration
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
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
(n=163)
Lavage
& Charcoal
(n=120)
p value
(combined charcoal
vs none)
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
Median
Amount
(G)
No GI
decontamination
(n=167)
Charcoal alone
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
charcoal

de Silva HA et al Multiple-dose activated
charcoal for treatment of yellow oleander
poisoning: a single-blind, randomised, placebocontrolled trial. Lancet 2003;361:1935-8.
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
16
14
12
10
8
6
4
2
0
% absolute
refusals
SD
M
D
1
M
D
2
M
D
3
M
D
4
M
D
5
M
D
6
% patient
Number of patients refusing each
doses of activated charcoal
(n=691)
charcoal regimen
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

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
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
South Asian Clinical Toxicology Research Collaboration
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
dimethoate
quinalphos
profenofos
fenthion
chlorpyrifos
diazinon
phenthoate
malathion
carbosulfan
fenobucarb
carbofuran
0
10
20
30
40
Case fatality ratio (95% CI)
South Asian Clinical Toxicology Research Collaboration
South Asian Clinical Toxicology Research Collaboration
Time to Death following Ingestion:
Chlorpyrifos, Dimethoate & Fenthion
South Asian Clinical Toxicology Research Collaboration
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?


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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
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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
OP/Carbamate
Oleander
Other-unknown pesticde
Medication/other
Overall
0.1
1
10
Odds ratio
South Asian Clinical Toxicology Research Collaboration
Sub-groups - time
< 2 hours
2-4 hours
4-8 hours
> 8 hours
Missing
Overall
0.1
1
10
Odds ratio
South Asian Clinical Toxicology Research Collaboration
Sub-groups - Symptoms
Asymptomatic
Symptomatic GCS 14-15
Symptomatic GCS< 14
Overall
0.1
1
10
Odds ratio
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
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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]
South Asian Clinical Toxicology Research Collaboration