HYDROCYANIC ACID TOXICITY IN RUMINANTS BY DR N B SHRIDHAR

HCN poisoning in cattle

1. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
Karnataka Veterinary Animal and Fisheries Sciences University, Bidar
Dr N B Shridhar
Professor and Head
Department of Veterinary Pharmacology and Toxicology
Veterinary College, Shivamogga-577204
[email protected] 9448059777
CYANIDE POISONING IN RUMINANTS
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INTRODUCTION
❑Theterm“cyanides”isusedtodescribecompoundswhichcontainintheir
structurethe–C≡Ngroup.
❑DifferentformsofCyanide
Hydrocyanicacid,Hydrogencyanide(HCN)andPrussicacid
▪HCNwasisolatedfrombluedye(Prussianblue)forthefirsttimeandbecause
ofitsacidicnatureit’salsoknownas“prussicacid”
❑Othersforms:-gaseousHCN,watersolublepotassiumcyanideandsodium
cyanide,poorlywatersolublemercury,copper,goldandsilvercyanidesalts.

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➢Cyanideisarapidlyactingsubstancethatistraditionallyknownasa
poison.
➢HydrogencyanidewasfirstisolatedfromPrussianbluedyein1786
andcyanidefirstextractedfromalmondsaround1800.
➢Cyanidecanexistasagas,hydrogencyanide,asalt,potassium
cyanide.
➢Naturalsubstancesinsomefoodssuchaslimabeans,almondscan
releasecyanide.
➢Cyanideisalsofoundinmanufacturingandindustrialsourcessuchas
insecticides,photographicsolutions,plasticsmanufacturing,and
jewelrycleaner.
➢Ithasbeenusedasapoisoninmasshomicidesandsuicides.

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➢Cyanidepoisoningmayresultfromavarietyofexposures,including
structuralfires,industrialexposures,medicalexposuressuchassodium
nitroprusside,andcertainfoods.
➢Indomesticcountries,themostcommoncauseofcyanidepoisoningis
domesticfires.
➢Cyanidealsoisusedinanumberofindustrialapplicationssuchas
electroplatinginjuryproduction,photography,plasticsandrubber
manufacturing,andpesticides.
➢Sodiumnitroprusside,amedicationusedtotreatahypertensive
emergency,containsfivecyanidegroupspermolecule.
➢Toxiclevelsofcyanidemaybepresentinpatientswhoreceive
prolongedinfusionsofsodiumnitroprusside

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➢AccordingtotheToxicExposureSurveillanceSystem,therewere
3165humanexposurestocyanidefrom1993to2002.
➢Ofthatnumber,only2.5%werefatal.
➢Fireisthemostcommonsourceofcyanideexposureinindustrialized
countriessuchastheUnitedStates.
➢Approximately35%ofallfirevictimswillhavetoxiclevelsof
cyanideintheirbloodonpresentationformedicaltreatment.
➢AccordingtotheNationalPoisonDataSystemofaPoisonControl
Centersannualreport,therewere247reportedcasesofchemical
exposurestocyanideintheUnitedStatesin2007,fiveofwhichwere
fatal

6. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
Chemistryandsource
❑Hydrogencyanide(HCN)isacolorlessorpaleblueliquidorgaswithafaintbitter
almond-likeodor
❑Sodiumcyanide(NaCN)andpotassiumcyanide(KCN)arewhitecrystalline
powders
❑Cyanideoriginatesprimarilyfromanthropogenicsourcesintheenvironment,but
cyanideisalsoreleasedfrombiomassburning,volcanoes,andnaturalbiogenic
processesfromhigherplants,bacteria,andfungi
❑Amongdifferentinorganicpoisoning,cyanideisoneofthemostpotentinorganic
poisonofmammals

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➢Acutehydrogencyanidepoisoningcanresultfrominhalation
offumesfromburningpolymerproductsthatusenitrilesin
theirproduction,suchaspolyurethane,orvinyl.
➢Itcanalsobecausedbybreakdownofnitroprussideintonitric
oxideandcyanide.

8. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
Plantsource
❑Themostimportantsource
❑Hydrocyanicacid(HCN)eitherfreeorintheformof
cyanogenicglycosidesarecalledcyanogeneticplants.
❑Theyarereleasehydrogencyanideuponbreakdown.
❑ThemostcommonsourceofcyanogenicplantpoisoninginIndiaisfeedingof
immaturesorghumi.e.youngshootsofSorghumvulgareandSorghumsudanenseto
livestockoraccidentalingestionofpodsofAcacialeucocephalabysheepandgoats.

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Johnsongrass (Sorghum halepense). Chokecherry (Prunus virginiana).

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❑Cassava is one of livestock feed and regularly
fed to sheep and goats on small-scale subsistence farms.
Cassava tuber contains cyanogenic glycosides,
known as Linamarinand Lotaustralin
❑Rapidintakeofplantequivalentto
about4mgHCN/kgofb.wislethal.
Plant source cont…………..

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❑Theamountinplantsvarieswithplantspeciesandenvironmentaleffects
❑Environmentalconditions
•Damagerelevantplantspecies
•Reduceproteinsynthesis
•Enhancetheconversionofnitrate
toaminoacids
•Inhibitβ-cyanoalaninesynthase
Synthesis of cyanogenicglycosides in plants

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Etiology
❑Theprimarycauseofcyanidepoisoninginruminantsistheingestionofplants
containingcyanide-producingcompoundscalledcyanogenicglycosides
❑Atleast55cyanogenicglycosidesareknowntooccurinplants,manybeing
synthesizedfromaminoacidsaspartofnormalplantmetabolism.
❑Amygdalin,Prunacin,Linamaryn,Lotaustralyn,Dhurryn,Taxiphylyn,
Vicianyn,ProteacynveandGynocardynhavebeendetectedasmostcommon
glycosidesincyanogenicplants.

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Manihotesculenta Viciasativa
Triraphismollis Leptopusdecaisnei
Lotus spp., e.g. L. australis, Zeamays
Macadamia spp., e.g. M.
integrifolia,
Malusspp., e.g. M. sylvestris
Juncusspp., e.g. J. effusus
Sorghum spp.
e.g. S. halepense
Droseraspp.
Phaseoluscuneatus
Suckleyasuckleyana Stillingiatreculeana
Xylomelumspp Ximeniaamericana
Some of plants with enough cyanogenic potential

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Manihot esculenta

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Suckleya suckleyana

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Vicia sativa

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Stillingia treculeana

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❑Thecontentofcyanogeneticglucosidesintheplantsvarieswidelybetween
seasonsandbetweendifferentpartsoftheplant,withyoung,growingleafusually
havingthegreatestconcentration
❑Crushingormasticationofpotentiallycyanogenicplantsisimportantin
developmentoftheacutetoxidrome,becausethisreleasescyanogenicglycosides
fromplantcellvacuolesandexposesthemtocatabolismbyβglucosidaseand
hydroxynitrilelyasepresentintheplantcellcytosol.
❑Generally,plantcyanogenesisinresponsetoenvironmentalstressorsisan
importantpartoftheetiologyandriskofacutecyanogenicglycosidepoisoning
Release of cyanide in plants

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CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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DHURRIN

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Release of cyanide in plants

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Epidemiology
Occurrence
❑Cyanideispresentinmanyindustrialandmunicipalwastewaters,amongthese
mines,metallurgicalplantsandexhaustgasfromvehicles.
❑Cyanideionsgetintotheenvironmentmainlyfromwastewater.
❑Thesecompoundscanalsoentertheenvironmentasaresultoffiresatindustrial
workshopsandhousesaswellasfromtobaccosmoke.
❑Cyanideionsaregeneratednaturallyduringbiogenicprocessesofhigherplant,
bacteriaandfungi

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Sources of
cyanide
emission
Artificial
Industry
Reactive salt
species
Insoluble salt
species
Sewage
HCN,CN
M(CN)
Fire
HCN
Tobacco
smoke
HCN
Natural
Plants
Cyanogenic
glycosides
Cyanide forms and species

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Plantandenvironmentalfactors:-
❑Itisreportedthat,poisoningismostlikelytooccurwhenthecyanidecontentof
thematerialishighanditiseatenquickly.
❑Plantswithacyanidepotentialofmorethan200mgHCN/kgplantdrymatter
arepotentiallytoxic.
❑Highsoilcontentofnitrogenandlowphosphorusisfavorableforhighcyanide
contentinplantgrownthere
Risk Factors

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❑Theriskofpoisoningtoruminantsdecreasesasforagesmature
❑Moreover,leafbladesarehigherriskthanleafsheathsorstems,upperleavesare
higherriskthanolderleaves,andseedheadsareconsideredlowrisk
❑However,dryingplantsdecreasesthecyanogenicpotentialovertimesohayis
rarelyhazardousifadequatelycured
❑Ensilingplantswillsignificantlyreducethecyanogenicglycosidecontent
Plantfactorscont…………………..

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Environmental factors
❑Crushing,wilting,freezing,
❑Highenvironmentaltemperatures
❑Herbicidetreatment
❑Waterstress
❑Coolmoistgrowingconditions
❑Nitratefertilization

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Environmental factors cont………………
❑Lowsoilsulfur(decreasesdetoxificationofcyanogenicglycosidestothiocyanates
withinplants)
❑Insectattackandvariousplantdiseases.
❑Anyphysicaldamagetoplanttissuesuchasfreezing(frost),macerating
(rumination),cuttinganddrying,allowsplantenzymestocomeinclosecontact
withandresultinginmorehydrolysistoreleasemorefreeHCN

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Animalfactors:
❑TherateofconversionoftheglycosidetoHCNintherumenalsoaffectsthe
toxicityofthefeed.
❑Cattleorsheepmaybreakoutofdry,summerpasturesintofieldsofyoung,lush,
immaturesorghumorSudangrassandgorgeonit.
❑Asruminantsconsumeplantmaterialscontainingcyanogenicglycosides,
hydrogencyanideisliberatedintherumen,rapidlyabsorbedintothebloodstream
andpreventshemoglobinfromreleasingitsoxygentothetissues.

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❑HigherpHincreasestherateofconversionofcyanogenicglycosidetoHCNand
therebygreatentherisk
❑Thisnon-enzymaticpathwayispH-dependent.Waterdrunkafteranimalshave
eatencyanogenicplantsenhancesthehydrolysisoftheglycosides
❑Ruminantsthatareonhighenergygrainrationswheretherumenismoreacidic
(pH4-6)haveaslowerreleaseofHCNthaniftheywerefedagrass,hay,oralfalfa
diet
Animalfactorscont……………………

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❑HighruminalandabomasalpHincreasetheseverityoftoxicity.However,ifthe
pHislowerthan5.0,theenzymesthatseparatetheglycosidesfromthecyano
becomedenaturedandtoxicitydoesnotoccur.
❑Ruminantsaremoresusceptibletopoisoningbycyanogenicplants,whichrelease
hydrogencyanidethanhorsesandpigsduetomoreefficienthydrolysisofthe
cyanogenicglycosides.
❑MonogastricanimalswithlowstomachpHarealsosomewhatlesssusceptibleto
cyanogenicglycosidepoisoning.
Animalfactorscont……………………

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Lethal dose:
➢ThelethaldosageofHCNinmostanimalspeciesisinrangeof2-2.5
mg/kg.
➢TheminimumlethaldoseofHCNisabout2mg/kgBWforcattleand
sheep,withinamongruminants,goatsappeartobethemostsusceptibleto
cyanide.
➢Basedontheavailabledatathefollowingintakemg(HCN)/kgb.w.perday
seemstobetolerated:
Pigs:- 2.9mg/kgperday
Poultry:- 2.8mg/kgperday
Ruminants:-onthebasisofgoatsstudies-0.25mg/kgperday
Horses:-0.4mg/kgperday

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Sr. NoHCN/kg
feed(ppm)
Effects of HCN on animals
1 0-500 Generally safe
2 600-1000 Potentially toxic
3 >1000 Dangerous to cattle and usually
cause death
Level of HCN in forages (dry matter basis) and potential effect on animals

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Pathogenesis
❑Ingestionofplantsthateitherconstitutivelycontainscyanogenicglycosidesoris
inducedtoproducecyanogenicglycosidesandcyanolipids
❑Innormalcasestheglycosidesoccurinvacuolesinplantstissue,whereasthe
enzymesarefoundinthecytosol.
❑Whentheediblepartsoftheplantsaremacerated,thecatabolicintracellular
enzymeß-glucosidasecanbereleased,comingintocontactwiththeglycosides.
❑Thisenzymehydrolyzesthecyanogenicglycosidestoproducehydrogencyanide
andglucoseandketonesorbenzaldehyde.Thehydrogencyanideisthemajor
toxiccompoundcausingthetoxiceffects.

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AcuteIntoxication
❑Ruminantsaremoresusceptiblebecauserumenmicroorganismsreadilyrelease
cyanidefromtheglycoside.
❑Cyanideishighlylethalbecauseitdiffusesintotissuesandbindstotargetsites
withinseconds.
❑Toxicokineticsofcyanideshowsintravenousandinhaledexposuresproduce
morerapidonsetofsignsandsymptoms.

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❑Ifthecyanideistakentothebody,it’srapidlyabsorbedandcirculated,thenit’s
mergedwithmethemoglobinandformscyanomethemoglobin.
❑Itisreportedthattheprimarymechanismofcyanideexcretionisformationof
thiocyanatewithintheliver.
❑Rhodanesecatalyzestheconversionofcyanidetothiocyanateintheliver,and
thiocyanateisthenexcretedviathekidneys
Metabolism of cyanide

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METABOLISM OF CYANIDE

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❑Cyanideionhasahighaffinityforferric(trivalent)ironinthecytochromeoxidase
systemandcombineswithit.
❑Cytochromecoxidase(CcOorcomplexIV)isthelastenzyme(terminaloxidase)
intherespiratoryelectrontransportchainlocatedinthemitochondrial
membrane.
❑Thiscausesblockingofelectrontransportandmolecularoxygentransferfrom
oxyhemoglobintotissues,resultingintoreversiblecellularhypoxiaorhistotoxic
anoxia
Mechanism of cyanide toxicity

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Effect of cyanide on cellular respiration

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➢Cyanidereversiblybindstotheferricionincytochromeoxidasea3withinthe
mitochondria,effectivelyhaltingcellularrespirationbyblockingthereductionof
oxygentowater.
➢Inbovines,thislargetransmembraneproteincomplexcontainstwohemes(iron
sites)i.e.cytochromea(haemea)andcytochromea3(haemea3),andtwocopper
centers,theCuAandCuBcenters
➢Cytochromea3isthesiteforoxygen(O2)bindingwhenitisinthereducedstate
andactsastheO2reductionsiteinconjunctionwithCuBwhichislocatednearby
➢FullyreducedCcOhasunusuallyhighaffinitytoCN-andnotHCN.
Cellular mechanism of cyanide toxicity

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➢Cyanide(CN-)boundformundergoesafairlylargeconformationalchangein
theO2reductionsite.
➢Itblockselectrontransportresultingindecreasedoxidativemetabolismand
oxygenutilizationeveninthepresenceofadequateoxygenstores
➢ThedecreasedO2causesoxygentensionstoriseinperipheraltissuesresulting
indecreasedunloadinggradientforoxyhemoglobinandthus,oxyhemoglobin
arecarriedinthevenousblood.
➢Thepatientcannotusecaloricoxygenandcellularrespirationstops
immediately.
➢Asaresultofthisprocess,deathoccursduetohistotoxicanoxia,thisprocessis
reversible.

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Chronic poisoning of cyanide
➢Chronic,low-levelcyanide/cyanogenicglycosideexposureisassociatedwith
neuropathysyndromesinhorsesandruminants.
➢Incaseofgoatsreceivinglowdoseofcyanideshowedlowerbodyweightgainsand
adecreaseinplasmaT3concentrations.
➢Behavioralchangeshavealsobeenreportedingoatsfollowingsub-lethalcyanide
intoxicationwithdelayedsignsoftoxicity.

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➢Cyanidesingestedinsmallamounts,however,areknowntobegoitrogenicthrough
theeffectsofthiocyanate,
e.g.pregnantewesgrazingonstargrass(Cynodonnlemfuensis)developgoiterdue
partlytoalowiodineintakeandpartlytothecyanideintake.
➢Theirlambsmayalsobegoitrousandhaveskeletaldeformities.Leucomyelomalacia
(cystitisataxiasyndrome)inruminants.
➢Generally,developmentaldefectswereobservedincowsassociatedwithchronic
cyanidetoxicity
Chronic poisoning cont……….

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➢Theproblemiscausedbythelossofthemyelinsheathsurroundingthe
peripheralnerves,resultinginlossofnervefunction.
➢Thisdemyelinationofthenervesisthoughttoresultfromtheconversionofthe
cyanogenicglycosidetoT-glutamylB-cyanoalanine,aknownlathyrogenthat
interfereswithneurotransmitteractivity.
➢Affectedanimalsdevelopposteriorataxia,urinaryincontinence,andcystitis
resultingfromlowerspinalcorddegeneration.
➢Kidneyinfectionisacomplicatingfactorinthiscystitis.

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Clinical Signs
➢Affectedanimalsrarelysurvivemorethan1-2hoursafterconsuminglethal
quantitiesofcyanogenicplantsandusuallydiewithin5-15minutesofdeveloping
clinicalsignsofpoisoning.
➢Generally,hyperventilation,decreasedbloodpressure,hypoxemia-induced
convulsions,coma,shock,respiratoryfailureanddeath.
➢Theprogressionaftertheonsetofconvulsionisrapidandanimalhas
characteristicbrightcheeryredcoloredmucousmembrane.

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➢Inthemorecommon,acute,casestheanimalsshowdepression,
staggering,grossmuscletremoranddyspnea.
➢Theremaybehyperesthesiaandlacrimation.
➢Thepulseissmall,weakandrapid,andmaybeirregular.
➢Thereisdilatationofthepupils,nystagmus,withcongestionand
cyanosis.
➢Thebloodofbotharterialandvenousbecomescherryredfrom
accumulatedoxyhemoglobin.
Clinical signs cont…………..

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➢Theskinmayalsobeabrightpinkcolorfromthehighconcentrationof
oxyhemoglobininthevenousreturn.
➢Whentheintracellularcyanideconcentration
islessthan0.2µg/ml,symptomsofpoisoning
donotoccur.
Clinical signs cont…………..

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Sub-lethalcyanideintoxicationingoatsresultedintransientclinical
signs:-
▪Depressionandlethargy
▪Mildhyperpnoeaandhyperthermia
▪Arrhythmias,abundantsalivation,
▪Vocalizations,expiratorydyspnoea
▪Jerkymovementsandheadpressingandconvulsion
Ifcyanidelevelis,0.5-1μg/ml:hyperemiaoftheskin,tachycardia
1-2.5µg/ml:unconsciousnessandexcitement.
>1-2.5µg/ml:patientswilleasilyentercomaanddie.
Asymptomofpoisoningoccursduetohypoxia.

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Clinical signs in chronic poisoning :-
➢Decrease of productivity, difficulty on conception and abortion can be also seen
in such patients .
➢In sheep, the syndrome includes weakness, ataxia, head shaking, fetlock
knuckling, recumbency, and opisthotonos.
➢As result of fetal central nervous damage by cyanide, cows grazing sorghum may
rarely produce offspring with arthrogryposisprobably as result of fetal central
nervous system damage by cyanide .

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➢Hypotension and bradycardia are pathognomonic for cyanide
poisoning
➢Seizures are also common in cyanide poisoning. They are relatively
rare in carbon monoxide poisoning. Suspect cyanide poisoning in
patients who have soot or carbonaceous material in the nose or
around the mouth or in the oropharynx. Take note of the pupils as
well.
➢Cyanide poisoning causes pupillary dilation

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Necropsy Findings
➢Venousbloodisclassicallydescribedasbeing"brightcherryred".
➢Mucousmembranesmayalsobepinkinitially,andthenbecomecyanoticafter
respirationceases.
➢Therumenmaybedistendedwithgas;insomecases,theodorof“bitter
almonds”maybedetectedafteropening.
➢Subendocardialandsubepicardialpetecchialandecchymotichemorrhages
typicalofanagonaldeathmaybepresent.
➢A“bitteralmond”or“cherrycoke”odourfromstomachcontentsmaybe
detectable.
➢Cyanoticmucosa,darkmuscles,lungedemaandhemorrhageswereobserved
atpostmortemofdiedcattle

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Diagnosis
➢Cyanideisrapidlylostfromanimaltissuesunlesscollectedwithinafew
hoursofdeathandpromptlyfrozen.
➢Collectionandtransmit,samplesmustbeplacedinacontainerthatcanbe
tightlysealed,samplesmustbefrozen,andtheymustbetransportedincold
chain.
➢Cyanideanalysismustbeperformedonsuspectedfeedsandplantsorcattle’s
rumencontentforthediagnosis.
➢Suitablespecimensformoresophisticatedtestingincludethesuspectedfood
source,rumen/stomachcontents,andsamplesoftherumengascap,
heparinizedwholeblood,liver,andmuscle

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➢Toidentifyplantsintheareaaccessibletotheanimalsanddetermineiftheyare
likelytocontaincyanogenicglycosides.
➢liversamplesmustbetakenwithin4hoursofdeathandmuscletissuewithin20
hours.
➢Themethodsofcyanideiondeterminationarespectrophotometrictechniques
aswellasgasandliquidchromatography.
➢AlevelofHCNof0.63J.lg/mLinmusclejustifiesadiagnosisofpoisoning.
➢SerumandrumenfluidofpoisonedcattlehavebeenassayedusingGC-MS(Gas
ChromatographyMassSpectrometry.
Diagnosiscont………..

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➢Severemetabolicacidosis(elevatedbloodlactateorreducedbloodpH)together
withanincreasedanionicgapareindicative.
➢Whole,heparinizedbloodsamplescollectedinairtightcontainerswithnoairspace
(submittedimmediatelyorfrozen)canalsobeanalyzedforcyanohaemoglobinor
cyanide.
➢Alkalinepicratetreatedfilterpaperstripscanbeusedfortestingplantmaterials
andfreshrumencontentsbymodifiedGuignardtest.Thisisasensitiveand
qualitativetestpopularlyknownasPicratePapertest.
Diagnosiscont………..

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Differential Diagnosis
Thechallengesinrecognizingacutecyanidepoisoningcanbeoriginatedfrom
nonspecificearlysymptomsoftoxicitysuchasdizziness,weakness,diaphoresis,
hyperpneaandlaboredbreathingandtheyare
•Nitrate-nitritepoisoning
•Organophosphoruspoisoning
•Sulphurpoisoning
•Urea–ammoniapoisonig
•IpomeanolandBluegreenalgaepoisoning
•Electricalshockorlightningstrike
•Acutepulmonaryoedema
•Anaphylaxis

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Differential Diagnosis ..contd (Humans)
•Smoke inhalation injury
•Carbon monoxide poisoning
•Hypoxia
•Inhaled chlorine, chloramine, hydrogen chloride, ammonia, riot
control agents
•Hydrogen sulfide
•Phosphine
•Methyl halides
•Arsine

61. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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•Sarin gas
•Salicylate toxicity
•Tricyclic overdose
•Strychnine
•Organic phosphates
•Methemoglobinemia

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Treatment
Principlesoftherapy
•Preventionofaccessofcyanide(CN)intothetissues
•Allowingforrhodanaseaction
•Ameanstosupplysulfurforthiocyanateformation.
•Promotetheproductionofbloodmethemaglobin(Hb-Fe3+).
•TheantidotaleffectisbasedonthereadinesswithwhichfreeCNcombineswith
theHb-Fe3+toformcyanomethemoglobin(Hb-Fe3+-CN).
Inhumanonly2cyanideantidotes,hydroxocobalaminandacomponentofthe
cyanideantidotekitsodiumthiosulfate,havebeenproposedforempirictherapyin
cyanidepoisoning.

63. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
63
➢Hydroxycobalaministheantidoteofchoiceforacutecyanide
poisoning,especiallyifthepatienthascoexistingcarbon
monoxidepoisoning.
➢Otherantidotes,whichwillbediscussedlater,impairoxygen-
carryingcapacityandworsencellularhypoxiaandacidosis.
➢Thestandarddoseis5gramsgivenintravenously(Over15
minutes
➢Beawarethatthisantidoteturnsurinedarkred;thisisnotdue
tomyoglobinuria.
➢Acyanideantidotekitmaybeusedinplaceofhydroxocobalaminifit
isnotavailable.

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CYANIDEANTIDOTEKIT
➢Thekitthatiscurrentlyavailablecontainssodiumnitriteandsodium
thiosulfate.
➢Sodiumnitrite300mgampuleor10mg/kggivenIVfor3to5
minutesinadults.
➢Thepediatricdoseis0.2mL/kg,nottoexceed10mLinpediatric
patients.
➢Thedoseofsodiumthiosulfateisoneampuleor12.5gramsin50
mL,givenintravenouslyfor30minutesinadults.
➢Thedoseforpediatricpatientsis7g/m2andnottoexceed12.5
grams.

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(Hamel,2011)

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➢Emergencybasistreatment.
➢Oraldosingwithsodiumthiosulfateintotherumenand/orstomachhas
beensuggestedwellbecausethereactionbetweenthiosulfateandcyanide
canalsooccurnonenzymatically,andthismayreduceanyongoing
productionofcyanideintherumen/stomachenvironments.
➢Theantidoteofchoiceinmostofanimals
iscombinationofsodiumnitriteand
sodiumthiosulfate.
Treatment cont………..

74. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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➢Thesodiumnitriteactasmethemoglobinformingagentandisadministeredto
formmethemoglobinandbindcyanide.
➢Amylnitriteisanothermethemoglobinformingagentusedaloneorwith
sodiumnitrite.
➢Sodiumthiosulfateisadministeredincombinationwiththenitritestoclear
cyanidebyactingasasulfhydryldonor.
➢Theunbound,extracellularcyanidebindswithsulfurofthiosulfatetoformthe
renallyexcretedthiocyanate.
Treatment cont………..

75. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
75
➢Hydroxocobalamin(alsoan
antidote)combineswithcyanide
toform cyanocobalamin
(vitaminB-12),whichisrenally
cleared.
➢Alternatively,cyanocobalamin
maydissociatefromcyanideata
slowenoughratetoallowfor
cyanidedetoxificationbythe
mitochondrial enzyme
rhodanese.

76. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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Biochemical mechanism of reversal of cyanide poisoning

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The standard primary treatment is the IV injection of a mixture of sodium nitrite
and sodium thiosulfate
Cattle:-5 g sodium nitrite, 15 g sodium thiosulfatein 200 ml water
Sheep :-1 g sodium nitrite, 3 g sodium thiosulfatein 50 ml water
Nonspecific supportive treatment, including respiratory stimulants and artificial
respiration are unlikely to have any effect on the course of the disease.
Treatment cont………..

78. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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Sodiumthiosulfate:-
➢Ruminantscanbetreatedwiththiosulfatealoneusinga30–40%solution
intravenousatadoseof25–50g/100kgbodyweight
➢Thisisduetointhepresenceofasulfurdonor(e.g.thiosulfate)andasulfur
transferaseenzyme(e.g.rhodanese);80%ofadoseofCNismetabolizedtoSCN−
➢Fortreatmentofcyanideintoxicationofruminants,dosesofsodiumnitrite
shouldbesmallerthanthoserecommendedforotheranimalsbecauseruminants
aremoresusceptibletothetoxiceffectsofsodiumnitrite.
➢Treatmentwithanychoiceofregimenshouldberepeatedbecauseoffurther
liberationofHCN.

79. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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Hydroxycobalamin(vitaminB12a)
➢Hydroxycobalamindetoxifiescyanidebybindingtoitandforming
cyanocobalamin,whichisthenexcretedinurine.
➢Ithastheadvantagesthatitisrelativelywell
tolerated,doesnotcompromiseblood
oxygen-carryingcapacityanddoesnot
producehypotension.
➢Thesuggesteddosageis70mg/kg,infused
IVover15min,repeatedasnecessary.

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➢IMtreatmentwith10%novelaqueousformulationofdimethyl
trisulfide(DMTS)improvessurvivalandclinicaloutcomesin
non-anesthetizedrodentmodelsofacuteCNtoxicity.
➢Additionally,theuseofanSCKCNdelayed-treatmentmodel
inratsisadvisedtoassesstheperformanceofacandidateCN
countermeasureinamorerealisticexposure/treatmentscenario
(Lippneretal.,2022).

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Glyoxylatecan also me used in cyanide poisoning treatment but still in
experimental phase.
Lactate dehydrogenase is required for this effect which distinguishes the
mechanism of glyoxylate rescue as distinct from countermeasures based solely on
chemical cyanide scavenging.
Glyoxylate confers survival at least in part by reversing the cyanide-induced
redox imbalances in the cytosol and mitochondria.
Hence, glyoxylatemay be a potential cyanide countermeasure operating through
a novel mechanism of metabolic modulation (Nielson et al., 2022).
81

82. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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Hyperbaric oxygen therapy:-
➢100%oxygenbreathedintermittently
atapressure>1atmosphereabsolute)
causesanabove-normalpartial
Pressureofoxygen(PO2)inarterial
bloodandmarkedlyincreasesthe
amountofoxygendissolvedinplasma.

83. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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Miscellaneous
➢Oral therapy with glucose, molasses, or glyceraldehydemay provide a benefit.
These products act as slow antagonists by tying up free HCN into cyanohydrin
Slow detoxification, not be used as a primary treatment
❑Sulfenegenwhichrecentlydevelopedantidotethathasbeenproved100per
centeffectiveinreducingbloodcyanidelevel.
❑Rumenotomycanbeconductedtotransfernormalrumencontent.Patient’s
rumencontentshouldberemovedandreplacedwithcontentsfromahealthy
animal.

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Control and Prevention
Feedingmanagement:-
▪Hungrycattleandsheepshouldnotbeallowedaccesstotoxicplants,especially
cultivatedSorghumspp.whentheyarechronicallydrought-stressed,immature,
wilted,frostbitten,orgrowingrapidlyafterastageofretardedgrowth.
▪FormostSorghumcultivars,stockshouldbeallowedtograzethem,orbefed
greenchopmadefromthem,onlyaftertheplantsexceed75cminheight
▪Plantsmustnotbegrazedduringdroughtperiodswhengrowthisseverely
reducedortheplantiswiltedortwisted.
▪Animalsmusthavebeenprovidedsufficientfeed,likehay,sotheywillnotbe
hungrywhentheyenterfreshpastures.

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Preventive measures to livestock owners :
➢Ensureanimalgrazeonlyoldsorghumandavoidnewgrowth
➢Mediumstrengthnitratefertilizersshouldbeusedwithmanurewhichhas
highphosphatelevel
➢Animalsshouldberestrictedfromgrazingsorghumsduringearlyre-growth
aftertheplantshavebeencut,drought,orfrosted
➢Allowingsorghumforagestogrowatleast2feethighbeforeallowinganimals
tograzethem
➢Haymakingandensilagingreducesthecyanidecontent

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Preventive measures cont…….
➢Hybridvarieties(sudan-grass)andselectedforagesorghumsthathavebeen
specificallydevelopedforlowcyanogenicglycosidecontentshouldbeusedas
foragecrops
➢ThepHinthestomachplaysamajorroleinthehydrolysisofthecyanogenic
glycoside.LoweringthestomachpHbyfeedmanagementandsupplements
reducestherisksfromcyanogenicforage
➢Sulphursupplementsinsaltcanalsobeusedtoincreasetherateofnatural
detoxificationandresistance.

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Conclusion
➢Cyanidepoisoningisoneofthemostimportantpoisoningthatcanaffect
livestock,Itishighlylethalandrapidlyactingtoxintowhichruminantsaremore
susceptible
➢Therisksofpoisoningcanbeaffectedbylevelofcyanideinplantmaterialthat
varieswithenvironmentalstressorstoplantsaswellasstageofplantgrowth.
➢Themechanismofcyanidetoxicityisassociatedwithinhibitionofoxygen
utilizationbybindingwithferric(trivalent)ionincytochromeoxidasea3within
mitochondriaandresultingintohistotoxicanoxia.
➢Theclinicalsignsarethereflectionofintracellularhypoxia,discolorationof
mucosae,pronouncedrespiratorydistressandneurological.

88. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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➢Immediatediagnosisandtreatmentswithsodiumthiosulphateandsodium
nitritecanbedoneintogetherwithsupportivetherapyforearlynoticedcases.
➢Sinceanystressconditiontoplantsthatretardtheirgrowthresultsincreasedlevel
ofcyanideinplantswithcyanogeneticpotential
➢Avoidingofruminantsaccesstodroughtstressed,immature,wilted,frostbitten
orrapidlygrowingplants
➢Providingofgrainorhaybeforeturningtopastureissoundcontrolmethodof
hydrocyanicacid(HCN)poisoninginruminants
Conclusion cont………

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Recommendations :
➢Therapidadministrationofsodiumthiosulphatealoneorincombinationwith
sodiumnitriteintravenously(IV)toearlynoticedshouldbedonetoreduce
lossesoflivestock.
➢LoweringofrumenpHbyfeedsupplementandmanagementshouldbeapplied
topreventriskofcyanidepoisoningfrompotentiallydangerousforages.
➢Clinicallyusefuldiagnosticmethodsshouldbedevelopedtoconfirmdiagnosis
andinordertomakeresultsavailableinreasonabletime.

90. CYANIDE POISONING IN RUMINANTS BY DR N B SHRIDHAR
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➢Awarenesscreationtolivestockownersonprussicacidpoisoningandits
preventionmeasuresshouldbeconducted.
➢Agriculturalindustriesshouldcontinuetoproduceforagecropswithlow
cyanogenicpotentialisrecommended.
➢Researchshouldbeconductedonprussicacidpoisoninginruminantsto
proposeframeworkoneconomicimpact,accuratediagnostictechniquesand
onstrategicimplementationofpreventionmeasures.
Recommendations cont……………

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Signs of Cyanide Poisoning in Chicken
➢Chickensthatdiefromcyanidepoisoninghavebrightred,
oxygenatedbloodandbodilytissuesareusuallycongested
withblood.
➢ThereportedoralLD50fordomesticchickensis11.1mg/kgof
bodyweight.
➢Chickenswillusuallydiewithin15to30minutesofingestion
ofthetoxicsubstance.

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