Intossicazione acuta mista CO‐CN 

da esposizione a fumi di incendio

Carlo Locatelli, Davide LonatiServizio di TossicologiaServizio di Tossicologia

Centro Antiveleni ‐ Centro Nazionale di Informazione Tossicologica

IRCCS Fondazione Maugeri e Università degli Studi, Pavia

Euroborg soccer stadium, Groningen

Euroborg soccer stadium, Groningen13 Aprile 2008

http://www.calcioblog.it/galleria/le-foto-dellincendio-di-groningen/49

Van Belle et al., 2010

CN levels (air) effects

18-30 ppm mild/moderate symptoms hrs after exposure

45-54 ppm 30 – 60 minutes without acute effects

110-135 ppm lethal in 30 – 60 minutes

135 ppm lethal in 30 minutes

181 ppm lethal in 10 minutes

270 ppm lethal in less than 60 seconds

Van Belle et al., 2010

270 ppm lethal in less than 60 seconds

CO

CN

Alarie, 2002

L th l 67/229 (29%)

t i th t h 95 5%

Lethal cases 67/229 (29%)

• soot in the trachea  95.5% 

• % surface area burned  75% (range of 0–100%) 

• COHb  37.5%(range of 11–68)

COHb 16 40% 56 7%• COHb 16–40%  56.7%

• COHb> 40%  36.7% 

• causes of death from forensic report were:

• asphyxia  88.1%

• burn  10.4% 

• fire  7.5% 

• complication from fire  3%Jongcherdchootrakul et al., 2011

• died on the scene  86.6% 

Hypoxia and asphyxia are the main causes of death in many fires. However, in a closedHypoxia and asphyxia are the main causes of death in many fires. However, in a closedspace fire, cyanide poisoning should be considered as cause of death. Fires often producetoxic gases when furniture made of paper, cotton, wool, plastics or ther polymers areburned. Hydrogen cyanide is one of several toxic gases produced under these conditions.y g y f g p

Cyanide poisoning is difficult to diagnose because the symptoms were not specific andsamples must be collected quickly after exposure because of its short half‐life in the body.

Most victims of a close space fire have soot in the mouth and nose, loose consciousness,become hypotensive and develop headache, dizziness, arrhythmia and apnea. These arealso typical symptoms of cyanide poisoning.

Carbon monoxide and cyanide have a synergic effect for respiratory failure, coma anddeath.

Jongcherdchootrakul et al., 2011

Depth mucosal damage ad admission (fibre-optic bronchoscopy) according to Chou’s Classification

Soot in the mouth and nose after smokefinhalation, particularly if altered mentalstatus or hypotension is present, suggeststhe possibility of cyanide poisoning

Cyanide is generally considered to be a rare source of poisoning. However, cyanideexposure occurs relatively frequently after smoke inhalation during residential orindustrial fires. Death occurs within seconds or minutes following inhalation because ofcardiac arrhythmias or blockades, myocardial ischaemia or asystolia.

Jirrazabal et al., 2008

Ick Cha et al., 2007

The cornerstone of the diagnosis of smoke inhalation in fire victims is: 

• Soot deposit in the:Soot deposit in the:• Nose• Mouth• Sputum• Sputum

Baud FJ, VIII Jornada de Toxicologia Clinica, Palma de Mallorca 2004

Smoke induced asphyxiationSmoke – induced asphyxiation

• Cellular hypoxia results in 

– Neurological 

– Metabolic Disturbances

– Cardiovascular

Disturbances

Non specific ?Cardiovascular  Non specific ?Other substances ?Alchool ?

Cyanide toxicity and cellular respiration

==

Nelson, 1996Shepherd, 2008

plasma lactate blood cyanide

systolic bloodsystolic blood pressure

arterial pH

anion gap

Baud FJ, 2002

Correlation between Plasma Lactate and Blood Cyanide concentrationCorrelation between Plasma Lactate and Blood Cyanide concentration

Baud FJ, 1991 Baud FJ, 2002

6 h

256

63 ys, man

Blood CN half-life1.14 h

(95% IC 0 84 1 80)

256

(95% IC 0.84-1.80)

40.4

Plasma lactate half-life3 94 h

53

3.94 h (2.98 – 5.78)10

Baud FJ, 1996

6 h

256

63 ys, man

Blood CN half-life1.14 h

(95% IC 0 84 1 80)

256

(95% IC 0.84-1.80)

40.4

Plasma lactate half-life3 94 h

53

3.94 h (2.98 – 5.78)10

reduced arterovenous oxigen saturation

difference < 10 mmHg

Baud FJ, 1996

Estimated half‐life of blood cyanide concentrations (n=6 fire victims before antidote or HBO)

Baud FJ, 1991

CN toxidrome• Time onset

– seconds gaseous HCN inhalationminutes CN salts i v– minutes CN salts i.v.

– hours cyanogenic compounds ingestion– days nitroprusside i.v. infusion

• Acute clinical picture

MILD EXPOSURE– anxiety, headache, nausea, vomiting, syncope, confusion, hyperventilation, vertigo

MODERATE TO SEVERE– vomiting– hyperpnoea‐tachypnoea without cyanosis ( bradypnoea)– hyperpnoea‐tachypnoea without cyanosis ( bradypnoea)– headache, dizziness– hypotension– tachycardia ( bradycardia)– seizures– agitation  CNS depression to coma– metabolic acidosis + high lactates + high anion gap– cardiac arrestcardiac arrest– (fire smoke inhalation) pulmonary oedema and ALI (Acute Lung Injury)

European Survey: Risk of Cyanide Poisoning in Smoke Inhalation (RISK)

Study Type:  Observational Study S udy ype Obse a o a S udy

Design:  Observational

Model: Cohort

Time Perspective: Prospective

Main objective: prevalence of cyanide poisoning in smokeMain objective: prevalence of cyanide poisoning in smoke inhalation victims

Primary Outcome Measures: Survival 

Time Frame: participants will be followed for the duration of hospital stay, an expected average of 30 daysg y

Estimated Enrollment:  100‐200 Study 

Start Date:  April 2009 

Estimated Study Completion Date:  Jun 2012 

Toxic Blood Cyanide levelsToxic Blood Cyanide levels

Blood cyanide > 1 mg/l (40 µmol/l)  = potentially toxic

Blood cyanide > 2.7 mg/l (100 µmol/l = potentially lethal

Cyanide dosageCyanide dosage

h dFor the study

INSTITUT MEDICO LEGAL STRASBOURGINSTITUT MEDICO LEGAL STRASBOURG

‐ lithium heparin

For clinical reason:For clinical reason: 

Laboratory of Analytical Toxicology, IRCCS Policlinico San Matteo Foundation, Pavia

‐ Sodium citrate

Department Hospital City Prov. Investigator

Centers and Local investigators partecipating to the RISK Study ‐ Italy

Dipartimento Emergenza ed Accettazione Ospedale Generale Regionale AOSTA AOMassimo Pesenti Campagnoni, Vincenzo Marconi

Dipartimento Emergenza ed AccettazioneAzienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo

ALESSANDRIA ALIvo Casagranda, 

Lauritano

Dipartimento Emergenza ed Accettazione Azienda Ospedaliera S. Croce e Carle CUNEO CNBruno Tartaglino

Salvatore FrancoDipartimento Emergenza ed Accettazione Ospedale Generale Regionale BOLZANO BZ Franco De Giorgi

Dipartimento Emergenza ed AccettazioneOspedale Civile Maggiore, Azienda Ospedaliera di Verona

VERONA VR Giorgio Riccidi Verona

Dipartimento Emergenza e Accettazione Ospedale S. Anna COMO COMario Landriscina Simone Zerbi

Dipartimento Emergenza ed Accettazione STABILIMENTO OSPEDALIERO DI IMPERIA IMPERIA IM Fabio De Iaco

SSUEM 118 FONDAZIONE POLICLINICO SAN MATTEO IRCCS PAVIA PVMaurizio Raimondi,

Greta PamplonaDipartimento Emergenza ed Accettazione Ospedale San Paolo SAVONA SV Roberto Lerza

Servizio di Anestesia e RianimazioneAzienda Ospedaliero‐Universitaria di Ferrara, Arcispedale S.Anna

FERRARA FERoberto Zoppellari, 

Daria Osti

i i di i i i i d l l llPiero Vecchiarelli, Fernando

Servizio di Anestesia e Rianimazione Ospedale Belcolle VITERBO VTPiero Vecchiarelli, Fernando Ricci

Dipartimento Emergenza e Accettazione Ospedale  Civile FIDENZA PRGianni Rastelli, Giuliano Vezzani

Gianfranco CervellinPronto Soccorso Medicina d’Urgenza Policlinico S Orsola Malpighi Bologna BO Mario CavazzaPronto Soccorso – Medicina d’Urgenza Policlinico S.Orsola‐Malpighi Bologna BO Mario Cavazza

Pronto Soccorso – Medicina d’UrgenzaOspedale Civile di San Donà` di Piave, ASSL 10 Veneto Orientale

San Donà di Piave VE Carolina Prevaldi

Pronto Soccorso – Medicina d’UrgenzaAzienda Ospedaliero‐Universitaria di Modena, Policlinico

Modena MO Maura Bucciarelli

Nuovo Ospedale Civile S Agostino EstensePronto Soccorso – Medicina d’Urgenza

Nuovo Ospedale Civile S.Agostino‐Estense‐Baggiovara‐Modena

Modena MO Marco Barozzi

Dipartimento di Emergenza e Accettazione Azienda Ospedaliera Spedali Civili di Brescia Brescia BSPaolo Marzollo, Carlo Concoreggi

CAV – CNIT Pavia – Centro Coordinatore Italiano IRCCS Fondazione Salvatore Maugeri Pavia PV Carlo Locatelli

Patients included in the RISK Study y(update Nov 3, 2011) 

Date Centre Investigator Patient CN (µmol/L) pH/lact CoHb % AntDate Centre Investigator Patient CN (µmol/L) pH/lact CoHb % Ant

10.10.10 Pavia Locatelli m, 37 y 2.5 7.41/2.4 19.3 yes

07.01.11 Modena Barozzi m, 34 y 1.8 7.39/4 37.9 noy

22.01.11 Modena Barozzi m, 41 y 1.8 7.32/2.7 14.2 no

31.03.11 Como Zerbi m, 36 y 1.6 7.43/1.5 3.5 no

17.10.11 Aosta Panzarasa f,  39 y < 1.2 7.41/1.2 1.2 no

17.10.11 Como Zerbi m, 44 y 53.9 7.10/9.1 23.6 yes

21.09.11 Lampedusa  ‐‐‐ m, 28 y 9.6(4‐5 h)

‐‐‐ ‐‐‐ HBO yes

Blood cyanide > 40 µmol/L (1 mg/L )  =  potentially toxic

Fire in close space +psoot deposits + 

neurological disturbancesd

Pavia Poison Centre

and 

Blood sampleBlood sampleLithium heparin / Sodium citrate

Time elapsed from end exposure< 2 h

Emergency I t i CEmergencyDepartments

Intensive CarePre‐hospital