prehospital use of antidotes in acute poisoning vincent danel samu - centre 15 and toxicovigilance...
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Prehospital use of antidotes in acute poisoning
Vincent DanelSAMU - Centre 15 and Toxicovigilance Centre,
University Hospital, Grenoble, France
Philippe LheureuxDepartment of Emergency Medicine
Erasme University Hospital, Brussels, Belgium
EAPCCT XXVIII international congress 6-9 May 2008, Seville, Spain
Background
‘Fewer than 1% of people who present with self poisoning develop severe clinical effects.One of the main challenges in managing poisoned patients is to identify this group as early as possible so that appropriate supportive, and if necessary, specific management steps can be instituted to prevent serious complications.’
A L Jones, P I Dargan. Advances, challenges, and controversies in poisoning. Emerg Med J 2002;19:190–191
Acute poisoning,a dynamic process
possible sequelae
possible death
Timet 0
recoveryfree interval
24 to 72 h24 to 72 h
exposureexposure
Worsening
Prehospital emergency care
Decreasing the ‘free medical interval’
Diagnosis or approximation of diagnosis
Evaluation of severity, recognition of risk factors
Supportive treatment
Specific treatment? antidotes?
Prevention of early complications
Orientation (Hospital, ICU)
As early as possible
When to senda Medical Emergency Care Unit ?Severity assessmentToxicant(s), associations Ingested dose / toxic doseFormulation (slow release or not)Patient (age, co morbidity)Time from exposure, initial management?Early complications
The French ETC score:
•Epidemiological
•Toxicological
•Clinical features
The French ETC score:
•Epidemiological
•Toxicological
•Clinical features
Prehospital use of antidotes?
Guidelines for hospital/ED antidotes availability
International Program on Chemical Safety (OMS – 1997)
US experts panel (2000)
UK experts panel (2006)
French and Belgian experts (2006, 2007)
No specific guidelines for prehospital use of antidotesapart from some French guidelines (1997, 2000)
and studies (1993 – 2006)
likely to be a subset of antidotes needed in the ED
Availability? IPCS (OMS) 1997
1. effectiveness well documented
2. widely used, but …
3. questionable usefulness
1. effectiveness well documented
2. widely used, but …
3. questionable usefulness
Availability of antidotes:
A. within 30 minutes
B. within 2 hours
C. within 6 hours
Availability of antidotes:
A. within 30 minutes
B. within 2 hours
C. within 6 hours
Availability? IPCS (OMS) 1997
Methylene blueNaloxone
OxygenPhentolamine
PhysostigminePrenalterol
Protamin sulphateSodium nitrite
Sodium nitroprussideSodium thiosulfate
Methylene blueNaloxone
OxygenPhentolamine
PhysostigminePrenalterol
Protamin sulphateSodium nitrite
Sodium nitroprussideSodium thiosulfate
AtropineBeta-blockersCalcium gluconateDicobalt edetateDigoxin antibodiesEthanolGlucagonGlucoseHydroxocobalaminIsoprenaline4-methylpyrazole
AtropineBeta-blockersCalcium gluconateDicobalt edetateDigoxin antibodiesEthanolGlucagonGlucoseHydroxocobalaminIsoprenaline4-methylpyrazole
Availability < 30 min
Well documented effectiveness
Availability < 30 min
Well documented effectiveness
21 ‘antidotes’21 ‘antidotes’
Availability? USA, 2000
Evaluation of 20 antidotesEvaluation of 20 antidotes
1. Is the antidote effective?2. Is the antidote needed within one hour?3. How many patients should a facility prepare for …?4. What amount of the antidote is needed to treat a 70-Kg
patient?
1. Is the antidote effective?2. Is the antidote needed within one hour?3. How many patients should a facility prepare for …?4. What amount of the antidote is needed to treat a 70-Kg
patient?
Availability? USA, 2000
16 recommended ‘antidotes’:AcetylcysteineAtropineCrotalid snake anvenimCalcium saltsCyanide antidote kitDeferoxamineDigoxin antibodiesDimercaprolEthanolFomepizoleGlucagonMethylene blueNaloxonePralidoximePyridoxineSodium bicarbonate
16 recommended ‘antidotes’:AcetylcysteineAtropineCrotalid snake anvenimCalcium saltsCyanide antidote kitDeferoxamineDigoxin antibodiesDimercaprolEthanolFomepizoleGlucagonMethylene blueNaloxonePralidoximePyridoxineSodium bicarbonate
2 not recommended:. Black widow antivenin. CaNa2 EDTA
2 not recommended:. Black widow antivenin. CaNa2 EDTA
No consensus:. Flumazenil. Physostigmine
No consensus:. Flumazenil. Physostigmine
Availability? UK, 2006
•Those that should be immediately available within A&E•Those that should be available for use within one hour or four hours•Those that are either not critically time dependent or are used rarelyand could be held supra-regionally
•Those that should be immediately available within A&E•Those that should be available for use within one hour or four hours•Those that are either not critically time dependent or are used rarelyand could be held supra-regionally
Availability? UK, 2006
AcetylcysteineActivated charcoalAtropineBenzatropineCalcium saltsHydroxocobalaminDiazepamDicobalt edetateEthanol
AcetylcysteineActivated charcoalAtropineBenzatropineCalcium saltsHydroxocobalaminDiazepamDicobalt edetateEthanol
FlumazenilGlucagonGlyceryl trinitrateMethylene blueNaloxoneProcyclidine injectionSodium bicarbonateSodium nitriteSodium thiosulfate
FlumazenilGlucagonGlyceryl trinitrateMethylene blueNaloxoneProcyclidine injectionSodium bicarbonateSodium nitriteSodium thiosulfate
Those that should be immediately available within A&E:18 ‘antidotes’
Those that should be immediately available within A&E:18 ‘antidotes’
Belgian and French authors
Antidotes. EMC (Elsevier Masson SAS, Paris), Médecine d’urgence, 25-030-A-30, 2007.
AcetylcysteineAtropineCalcium saltsDiazepamFlumazenilHydroxocobalaminNaloxonePhytomenadionePralidoximeSodium bicarbonateTropatepine
AcetylcysteineAtropineCalcium saltsDiazepamFlumazenilHydroxocobalaminNaloxonePhytomenadionePralidoximeSodium bicarbonateTropatepine
Prehospital availability?French data
Activated charcoalAdrenalineAtropineCalcium saltsDobutamineFlumazenilHydroxocobalaminHypertonic glucoseIsoprenalineNaloxonePropranololThiosulfate
Activated charcoalAdrenalineAtropineCalcium saltsDobutamineFlumazenilHydroxocobalaminHypertonic glucoseIsoprenalineNaloxonePropranololThiosulfate
‘Antidotes’ needed
in a Medical Emergency Care Unit
(France, 1997)
Prehospital availability?
Which antidotes are actually used?
French data:Acute poisoning = 3 10 % MECU interventions Dherbecourt V. Indication d’administration des antidotes sur
les lieux d’intervention ou pendant les transferts par le SAMU. Thèse Université de Lille, 1993
Lardeur et al. Régulation et prise en charge des intoxications volontaires par un SAMU.Presse Medicale 2001; 30: 626-630.
Labourel et al. Analyse épidemiologique des intoxications médicamenteuses volontaires aiguës: prise en charge par un SMUR. Rev Med Liège 2006:61: 3: 185-189.
Which antidotes?
Most used: Flumazenil Hydroxocobalamin Hypertonic glucose Naloxone Sodium bicarbonate/lactate
Rarely used: acetylcysteine, adrenaline, atropine,
diazepam,digoxin antibodies, ethanol, fomepizole, glucagon
Prehospital use of antidotes
Quality of the first call medical assessment
Early lifesaving value, with little or no alternative measure
Distance and time interval to the hospital
Clinical situation: great value of toxidromes!
Probability of use,
depending on local epidemiology and industrial activities
Particular risk of mass casualties (strategic storage)
(hydroxocobalamin, atropine, pralidoxime, …)
Prehospital use of antidotes
Ease and safety of use, possible adverse effects
Storage conditions, shelf life (glucagon, fomepizole,
hydroxocobalamine, …)
Cost, including waste of unused or outdated products
(hydroxocobalamin, digoxin antibodies, viper antivenom, ..)
Qualification and skill level of the prehospital emergency
team (good knowledge of toxidromes)
Naloxone and opiate toxidrome
Narcotic ‘simple’ overdose: miosis, bradypnea, bradycardia, CNS depression, needle tracks…
Goal of prehospital naloxone therapy is to simply reverse respiratory depression
No indication in the severe complicated overdose
Should only be administered in small, diluted and titrated doses
Short duration of a ‘toxicodynamic’ action:we ‘treat’ the patient not the ‘overdose’
Flumazenil and BZD toxidrome
CNS depression, hypotonia, no focal sign,Normal ECG and blood pressure, no cyanosis
Many people are benzodiazepine-dependentbenzodiazepine withdrawal tremors, high
levels of anxiety, muscle jerks, seizures
Many people co-ingest other drugs convulsions, arrythmias,…
Should only be administered in small, diluted and titrated doses
Short duration of a ‘toxicodynamic’ action:we ‘treat’ the patient not the ‘overdose’
Na salts (bicarbonate / lactate)
Na channel blockade:‘membrane stabilizing effect’
Indications:widening of QRS complexarrhythmiashypotension
Small volumes(heavy load of alcaline and sodium salts)
With added K+
Cyanide antidotes
Hydroxocobalamine +/- thiosulfate Expensive
Very safe
First choice if uncertain CN poisoningor smoke exposure: any sign of tissue hypoxia
Dicobalt Edetate (Kelocyanor®) Relatively cheap
Cardiovascular side-effects
Mass CN poisoning (industrial, terrorism) ?
Conclusion
In most acute poisoning conditions, primary care of the patient is mainly supportive
Early medical intervention (MECU) gives the opportunity to start specific treatments
Antidotes used in the prehospital settings are a subset of those used in ED
Main conditions are:good phone call assessment of the situationwell trained medical teamsa clear history and a well defined toxidrome
Risk of mass casualties must be anticipated
The French ETC score
Leveau P. Normand R.- Les appels pour tentative de suicide par intoxication médicamenteuse aiguë. Revue des SAMU 1992; 20:159-66.