Nell GillettTreatment of Cyanide Poisoning

ACMER – Cyanide Management in the Gold Industry – May 2009

Dr Nell Gillett – Medical Treatment1

Emergency Management:Emergency Management:g y gg y gTreatment of Cyanide Treatment of Cyanide

PoisoningPoisoning

Wesfarmers CSBP KwinanaWesfarmers CSBP KwinanaDr Nell Gillett Dr Nell Gillett MBBS, GradDip (OHS), CIMEMBBS, GradDip (OHS), CIME

Onsite Medical OfficerOnsite Medical Officer

IntroductionIntroduction

Cyanide is extremely toxic and Cyanide is extremely toxic and b f t lb f t lexposure may be fatalexposure may be fatal

Cyanide poisoning requires Cyanide poisoning requires immediate treatment,immediate treatment,Emergency diagnosis is difficult Emergency diagnosis is difficult

no pathognomonic signsno pathognomonic signsno pathognomonic signs no pathognomonic signs laboratory confirmation is delayed by laboratory confirmation is delayed by hours/dayshours/days



IntroductionIntroduction

Lack of International consensus on “Best Lack of International consensus on “Best P ti ” G id li f t t tP ti ” G id li f t t tPractice” Guidelines for treatmentPractice” Guidelines for treatmentIs it cyanide poisoning?Is it cyanide poisoning?

May mimic other medical conditions which May mimic other medical conditions which require prompt medical attentionrequire prompt medical attention

Review of current available literatureReview of current available literatureReview of current available literatureReview of current available literature

Routes of absorptionRoutes of absorption

InhalationInhalationIngestionIngestionThrough the eyes and skinThrough the eyes and skinDegree of symptoms depend on degree of Degree of symptoms depend on degree of exposureexposureSolid, liquid or gaseous phasesSolid, liquid or gaseous phases



Cyanide PoisoningCyanide Poisoning

Cyanide causes cellular hypoxia by Cyanide causes cellular hypoxia by enzyme inactivationenzyme inactivationenzyme inactivationenzyme inactivation“inability of cells to use oxygen”“inability of cells to use oxygen”Impaired function of vital organ systemsImpaired function of vital organ systems

Nervous SystemNervous SystemCardiovascularCardiovascularRespiratoryRespiratory

Lactic Acidosis (Metabolic)Lactic Acidosis (Metabolic)

Acute poisoningAcute poisoning

Clinical effects determined byClinical effects determined byForm of cyanide (gas produces the most rapid Form of cyanide (gas produces the most rapid onset of symptoms)onset of symptoms)Mode of entry into bodyMode of entry into bodyThe doseThe dose

Rapidly acting ie rapid onset of symptomsRapidly acting ie rapid onset of symptomsRapidly acting ie rapid onset of symptoms Rapidly acting ie rapid onset of symptoms after exposureafter exposure



Signs of mild poisoningSigns of mild poisoningHeadacheHeadacheNausea and vomitingNausea and vomitingNausea and vomitingNausea and vomitingMetallic tasteMetallic tasteDrowsinessDrowsinessDizziness Dizziness AnxietyAnxietyIrritation of mucous membranesIrritation of mucous membranesShortness of breathShortness of breath

Progression of poisoningProgression of poisoning

Increasing shortness of breathIncreasing shortness of breathCyanosis Cyanosis Falling/ low blood pressure (hypotension)Falling/ low blood pressure (hypotension)Cardiac arrhythmiasCardiac arrhythmiasImpaired conscious stateImpaired conscious state



Severe cyanide poisoningSevere cyanide poisoning

Progressive comaProgressive comaS iS iSeizuresSeizuresCardiac arrestCardiac arrest

Survivors of severe poisoning may suffer Survivors of severe poisoning may suffer permanent brain injury through permanent brain injury through direct toxic effects of cyanidedirect toxic effects of cyanidecerebral anoxiacerebral anoxia

Medical TreatmentMedical Treatment

Rescue and first aidRescue and first aidOxygenOxygenDecontaminationDecontaminationAntidotesAntidotesTransfer to Medical careTransfer to Medical care



Rescue and First AidRescue and First AidDR ABCDR ABCPrompt responsePrompt responsePrompt responsePrompt responseRaise alarmRaise alarmHazard assessment for rescuerHazard assessment for rescuer

Appropriate PPE and or respirator to prevent Appropriate PPE and or respirator to prevent contamination to rescuer/s is of prime importancecontamination to rescuer/s is of prime importance

Remove casualty from further exposure ie freshRemove casualty from further exposure ie freshRemove casualty from further exposure ie fresh Remove casualty from further exposure ie fresh airair

Rescue and First AidRescue and First Aid

DR ABCDR ABCAirwayAirway-- ensure clear, coma position if ensure clear, coma position if breathing spontaneously, insert airway if breathing spontaneously, insert airway if unconsciousunconsciousBreathingBreathing-- NO EAR, use bag and mask NO EAR, use bag and mask withwith 100% oxygen100% oxygenwith with 100% oxygen100% oxygenCirculationCirculation-- check for pulse, if absent check for pulse, if absent commence CPRcommence CPR



OxygenOxygen100% O2 is 100% O2 is considered the mostconsidered the mostconsidered the most considered the most useful treatment for useful treatment for early cyanide early cyanide poisoningpoisoningAdministered to Administered to anyone with anyone with suspected cyanidesuspected cyanidesuspected cyanide suspected cyanide exposure, regardless exposure, regardless of clinical conditionof clinical condition

DecontaminationDecontamination

Liquid or solid cyanide exposureLiquid or solid cyanide exposureShower and wash area with soap and Shower and wash area with soap and copious amounts of water ensuring water copious amounts of water ensuring water drains from casualtydrains from casualtyEye contaminationEye contamination-- irrigate with copious irrigate with copious water for 10 minswater for 10 minswater for 10 minswater for 10 mins



DecontaminationDecontamination

IngestionIngestion-- limited evidence to support limited evidence to support i / ti t d h li / ti t d h lemesis/activated charcoal emesis/activated charcoal

especially for exposures greater than 2 hours especially for exposures greater than 2 hours previously previously

Specialist medical decisionSpecialist medical decisionBag and seal clothing to prevent furtherBag and seal clothing to prevent furtherBag and seal clothing to prevent further Bag and seal clothing to prevent further exposure to victim or rescuer/sexposure to victim or rescuer/s

AntidotesAntidotes

Not as immediately critical as the Not as immediately critical as the d i i t ti f ff ti /fi t idd i i t ti f ff ti /fi t idadministration of effective rescue/first aid administration of effective rescue/first aid

and oxygenand oxygenInternational difference of opinion as to International difference of opinion as to most effective agentmost effective agentOut of Hospital empirical treatment VSOut of Hospital empirical treatment VSOut of Hospital empirical treatment VS Out of Hospital empirical treatment VS Specialist Medical CareSpecialist Medical Care



AntidotesAntidotes

Based on 3 main modes of actionBased on 3 main modes of actionMethemoglobin generatorsMethemoglobin generatorsDirect binding agentsDirect binding agentsSulphur donorsSulphur donors

Convert to nonConvert to non--toxic metabolitestoxic metabolites

Human Metabolism of CyanideHuman Metabolism of Cyanide



Methaemoglobin generatorsMethaemoglobin generatorsOxidising agent change Oxidising agent change ferrous (2+) to ferric (3+) ferrous (2+) to ferric (3+) i i h l bii i h l biion in haemoglobin ion in haemoglobin resulting in resulting in methaemoglobin (MetHb)methaemoglobin (MetHb)MetHb unable to MetHb unable to transport oxygentransport oxygenMetHb strongly binds to MetHb strongly binds to cyanide cyanide

Amyl nitriteAmyl nitrite (inhaled), (inhaled), sodium nitritesodium nitrite (IV), (IV), DMAPDMAP

Methaemoglobin GeneratorsMethaemoglobin Generators

Not recommended for empirical treatment Not recommended for empirical treatment of cyanide poisoningof cyanide poisoningof cyanide poisoningof cyanide poisoningRelative contraRelative contra--indication when carbon indication when carbon monoxide poisoning also suspected ie fire monoxide poisoning also suspected ie fire (carboxyheamaglobin)(carboxyheamaglobin)Amyl nitrite removed as treatment from Amyl nitrite removed as treatment from WA R S f t M di l B ll ti iWA R S f t M di l B ll ti iWA Resources Safety Medical Bulletin in WA Resources Safety Medical Bulletin in April 2008 revisionApril 2008 revision

http://www.dmp.wa.gov.au/PDF/Bulletins/MS_GMP_OH_MB5_CyanidePoisoning.pdf



Amyl Amyl NitriteNitriteAmyl Amyl Nitrite Nitrite should only should only be used if he patient is be used if he patient is ppclearly deteriorating, clearly deteriorating, despite oxygen and there despite oxygen and there is a reasonable is a reasonable confidence that cyanide is confidence that cyanide is the cause of their the cause of their symptomssymptomsMay be used by trainedMay be used by trainedMay be used by trained May be used by trained personnel until IV access personnel until IV access is obtainedis obtained

Cummings TF. The treatment of cyanide poisoning. Occupational Med 2004; 54: 82-85.

Direct binding AgentsDirect binding Agents

Based on cobalt chemistry and directly Based on cobalt chemistry and directly chelate cyanide to a nonchelate cyanide to a non toxic metabolitetoxic metabolitechelate cyanide to a nonchelate cyanide to a non--toxic metabolitetoxic metaboliteHydroxocobalaminHydroxocobalamin (Cyanokit),(Cyanokit),dicobolt edetatedicobolt edetate (Kelocyanor)(Kelocyanor)

Dicobolt edetate has a significant toxicityDicobolt edetate has a significant toxicityDicobolt edetate has a significant toxicity Dicobolt edetate has a significant toxicity profile and is not recommended for profile and is not recommended for empirical useempirical use



Hydroxocobalamin CYANOKITHydroxocobalamin CYANOKIT

Precursor Vitamin B12 that directly binds cyanide to form Precursor Vitamin B12 that directly binds cyanide to form Vitamin B12Vitamin B12First demonstrated as effective antidote in 1952First demonstrated as effective antidote in 1952Administer 5Administer 5--15 g IV over 30 mins15 g IV over 30 mins

Hydroxocobalamin to Vit B12Hydroxocobalamin to Vit B12



Hydroxocobalamin CYANOKITHydroxocobalamin CYANOKIT

Human and Animal studies Human and Animal studies Prospecti e retrospecti e trials case seriesProspecti e retrospecti e trials case seriesProspective, retrospective trials, case seriesProspective, retrospective trials, case series

69 enclosed space fire victims in Paris 69 enclosed space fire victims in Paris 19891989--19941994

37 comatosed, 14 cardiopulmonary arrest37 comatosed, 14 cardiopulmonary arrestSurvival rate 72% (50/69)Survival rate 72% (50/69)No neurological sequelae 82% (41/50)No neurological sequelae 82% (41/50)

Borron S, Magarbane B. Hydroxocobalamin for empiric treatment of smoke inhalation-associated cyanide poisoning:results of a prospective study in the prehospital setting. Ann Emerg Med. 2005;46:S77

HydroxocobalaminHydroxocobalamin

Side effectsSide effectsTransient reddishTransient reddish--brown discolouration of brown discolouration of skin, mucous membranes and urineskin, mucous membranes and urineTransient hypertension and reflex bradycardia Transient hypertension and reflex bradycardia without ECG changeswithout ECG changesHeadache, rash, erythema at infusion siteHeadache, rash, erythema at infusion site

Uhl W, Nolting A et al. Safety of hydroxocobalamin in healthy volunteers in a radomised, placebo-controlled study. Clin Toxicol. 2006; 44:17-28



Sulphur donorsSulphur donorsMajor route of Major route of detoxification is detoxification is

i f id ti f id tconversion of cyanide to conversion of cyanide to thiocyanatethiocyanatedetoxification in the liver detoxification in the liver (by the mitochondrial (by the mitochondrial enzyme rhodanese) enzyme rhodanese) catalyses the transfer of catalyses the transfer of sulphur to the cyanide ion sulphur to the cyanide ion to form thiocyanateto form thiocyanateto form thiocyanateto form thiocyanateSodium thiosulphateSodium thiosulphate

Sodium ThiosulphateSodium ThiosulphateNo clinical trials to No clinical trials to evaluate efficacy asevaluate efficacy asevaluate efficacy as evaluate efficacy as stand alone antidotestand alone antidoteData based on human Data based on human case studies or case studies or animal modelsanimal modelsSlower mode of Slower mode of

ti f CYANOKITti f CYANOKITaction cf CYANOKITaction cf CYANOKIT



Sodium ThiosulphateSodium Thiosulphate

No longer preferred first line empirical No longer preferred first line empirical tid ttid tantidoteantidote

May still be a useful adjunct to May still be a useful adjunct to hydroxocobalaminhydroxocobalaminAdministered through separate IV line Administered through separate IV line

12 5 g over 1012 5 g over 10 20 mins20 mins12.5 g over 1012.5 g over 10--20 mins20 mins

International PerspectiveInternational Perspective

USUS--sodium nitritesodium nitriteUKUK di b lt d t tdi b lt d t tUKUK-- dicobolt edetatedicobolt edetateFranceFrance--CYANOKITCYANOKITGermanyGermany-- DMAPDMAPAustraliaAustralia--CYANOKIT/ sodium thiosulphateCYANOKIT/ sodium thiosulphate

Hydrogen Cyanide Symposium Florida Hydrogen Cyanide Symposium Florida 20032003-- CYANOKITCYANOKIT



Prior to approaching casualty wear appropriate PPE and assess personal danger

Check casualty, remove from source of contamination if possible and where required. Contact Control Room by radio and advise of situation and any special services / assistance required

CN LIQUID/SOLID - Remove all clothing and

shower (20 minutes)* - Administer 02 100% as

required

HCN/GAS - Remove to fresh air - Administer 02 100%

If symptoms resolve

Transfer to medical centre for assessment.

After hours contact Shift Supervisor and On-call Doctor

Urine specimen at time and 24 hours later or at commencement

of next shift and refrigerate

SiteSafe

If symptoms deteriorate - DRABC - Request Control Room

Operator to ensure medical assistance is alerted

- Continue with 02 100%

St John’s Ambulance (Code Red), Occupational Health

Nurse and Doctor is required

If cyanide poisoning is strongly suspected as cause,

Administer Amyl Nitrite

* Bag and seal clothing including boots and socks to avoid further

contamination

On arrival medical team will administer IV antidote

Transfer to hospital for observation/evaluation

Cyanide Kit to go with patient in ambulance to hospital and

retrieved at a later time

If not breathing, do not attempt mouth to mouth/nose

resuscitation. Maintain breathing with bag/mask,

Oxyport or Oxy-Viva

Commence CPR and continue until ER or medical assistance

arrives

contamination.

Note: All SCP Core Operators and Shift Coordinators to be Senior First Aid, Oxy-Viva

and Amyl Nitrite Administration trained.

Cyanide KitCyanide KitThe cyanide antidote kit should contain:The cyanide antidote kit should contain:Copy of current MSDSCopy of current MSDSCopy of current MSDSCopy of current MSDSCopy of WA Resources Safety Medical Bulletin Copy of WA Resources Safety Medical Bulletin No 5No 5Copy of CSBP cyanide exposure protocolCopy of CSBP cyanide exposure protocolAmyl NitrateAmyl NitrateHydroxocobalaminHydroxocobalamin CyanokitCyanokitHydroxocobalamin Hydroxocobalamin –– CyanokitCyanokitSodium ThiosulphateSodium ThiosulphateIV giving sets, cannulas and fluidsIV giving sets, cannulas and fluids



Arrival of AmbulanceArrival of Ambulance

All patients with suspected or proven All patients with suspected or proven id i i h ld b t k tid i i h ld b t k tcyanide poisoning should be taken to cyanide poisoning should be taken to

hospital for evaluation and observationhospital for evaluation and observation

Cyanide kit must go to the hospital in the Cyanide kit must go to the hospital in the Ambulance as it has clear instructions forAmbulance as it has clear instructions forAmbulance as it has clear instructions for Ambulance as it has clear instructions for medical personnelmedical personnel

Take Home MessagesTake Home Messages

Primum non NocePrimum non NoceTo rescuersTo rescuers? Is it cyanide poisoning? Is it cyanide poisoning

Oxygen and supportive first aidOxygen and supportive first aidLack of International consensusLack of International consensus

N d f lit d tN d f lit d tNeed for more quality dataNeed for more quality dataHydroxocobalamin (CYANOKIT)Hydroxocobalamin (CYANOKIT)



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Nell GillettTreatment of Cyanide Poisoning

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