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.