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Roleofclinicalandparaclinicalmanifestationsofmethanolpoisoninginoutcomeprediction

JResMedSci.Oct201318(10):865869.

PMCID:PMC3897070

Roleofclinicalandparaclinicalmanifestationsofmethanolpoisoningin
outcomeprediction
ShahinShadnia,MojganRahimi,KambizSoltaninejad, 1andAmirNilli2
ExcellentCenterofClinicalToxicology,ToxicologicalResearchCenter,ClinicalToxicologyDepartment,SchoolofMedicine,ShahidBeheshti
UniversityofMedicalSciences,Tehran,Iran
1
LegalMedicineResearchCenter,LegalMedicineOrganization,Tehran,Iran
2
DepartmentofToxicologyandPharmacology,FacultyofPharmacy,PharmaceuticalSciencesResearchCenter,TehranUniversityofMedical
Sciences,Tehran,Iran
Addressforcorrespondence:Dr.KambizSoltaninejad,DepartmentofForensicToxicology,LegalMedicineResearchCenter,LegalMedicine
OrganizationofIran,BeheshtStreet,KhayyamAvenue,Tehran,Iran.Email:kamsoltaninejad@yahoo.com
ReceivedJanuary20,2013RevisedFebruary10,2013AcceptedApril23,2013.
Copyright:JournalofResearchinMedicalSciences
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract
Background:

Methanolpoisoningisoneofthemostimportantpoisoningduetodrinkingofillegalandnonstandard
alcoholicbeverageinsomecountries.Relativelylimitedstudieshavebeencarriedouttoidentifythe
prognosticfactorsinmethanolpoisoning.
MaterialsandMethods:

Weperformedaretrospectivestudyonacutemethanolintoxicatedpatients,whichwereadmittedonthe
LoghmanHakimHospitalPoisonCenter(Tehran,Iran)overa24monthperiod.Thedemographicdata,
clinicalmanifestationsandparaclinicalfindings,therapeuticinterventionsandoutcome(survivorswithor
withoutcomplicationsandnonsurvivors)wereextracted.
Results:

Weevaluated30patientswithmethanolpoisoningduring2years.Allofthepatientsweremalewiththe
medianageof25.5years.Visualdisturbances,respiratorymanifestations,andlossofconsciousnesswerethe
mostcommonclinicalmanifestationsonadmissiontime.Theresultsofparaclinicalmanifestationson
admissiontimewereasfollowing:Themedianofbloodmethanollevelwas20mg/dL.ThemedianofpH,
PaCO2andHCO3was7.15,22.35mmHgand7.2mEq/L,respectively.Hyperglycemiawasobservedin
70%ofthepatientsandthemedianofbloodglucosewas184.5mg/dL.Infourteenofthepatients
hemodialysiswasperformed.Mediandurationofhospitalizationwas48h.Nineofthepatientsdied.There
wasasignificantdifferencebetweensurvivorsandnonsurvivorswithregardtocoma,bloodmethanollevel,
andPaCO2andbloodglucose.Furthermore,wedidnotobserveasignificantdifferencebetweenthesetwo
groupsregardingtopH,HCO3level,andtimeintervalbetweenalcoholingestiontohospitaladmissionand
beginningofhemodialysis.
Conclusion:

Regardingtheresultsofthisstudy,itcanbesuggestedthatcoma,PaCO2andhyperglycemiaonadmission
timecouldbeusedasstrongpredictorsofpooroutcome.
Keywords:Hyperglycemia,methanol,outcome,partialpressureofcarbondioxide,poisoning,prognostic
factors
INTRODUCTION
Methanolisatoxicalcohol,whichiswidelyusedasasolventandtodenatureethanol.[1]Almostallcasesof
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acutemethanoltoxicityresultfromingestion.Rarely,poisoningfollowsinhalationordermalabsorption.
Ingestionofaslittleas30mLofpuremethanolhascausedpermanentblindnessand30240mLis
potentiallyfatal,thoughindividualsusceptibilityvarieswidely.[2]
Methanolitselfhasarelativelylowtoxicity,butproducestoxicmetabolitesasformaldehydeandformicacid.
Thereisadirectcorrelationbetweenformicacidconcentrationandmorbidityandmortality.[3]Theacidosis
appearstobecausedbyformicacidproductionandformicacid/formateistheprincipalcauseofocular
toxicity.[2]
Asmethanolischeapandeasilyaccessible,ithasbeenusedintheproductionofimitatedspiritsandwine,so
causethemortalityandormorbidityinmanypeople.[4]
InIran,accordingtolegalandreligiousbaninproductionofalcoholicbeverages,theuseofillegalandnon
standardalcoholicbeveragesiscommonanditmaybeamajorroleforanincreaseintheprevalenceof
methanolintoxicationamongthealcoholabusersinthecountry.[5,6]
Therearerelativelylimitedstudiesthatreportedtheparameterssuchasrespiratoryarrest,coma,serum
formateconcentration,severemetabolicacidosis,bloodmethanollevelasacriterionforthediagnosisand
prognosisofacutemethanolpoisoning.[6,7,8]Theaimofthisstudywastoassesstheclinicalmanifestations
andparaclinicalfindingsinmethanolintoxicationandtheirroleinthepredictionofoutcome.
METHODS
Thiswasaretrospectivestudyonacutemethanolintoxicatedpatients,whichwereadmittedontheLoghman
HakimHospitalPoisonCenter(LHHPC)overa24monthperiod.Thediagnosisinallcaseswasbasedon
thehistoryofexposure,clinicalmanifestationsandpositivebloodmethanollevel.Acutemethanol
intoxicatedpatientswithnohistoryofdiabetes,cardiovascular,respiratory,renalandhepaticfailure,andno
advancedmedicalmanagementsuchashemodialysisandantidotetherapyformethanolpoisoninginany
medicalcenterbeforeadmissioninLHHPC,wereincludedinthestudy.Furthermore,weexcludethecases
withcoingestionofotherdrugsandchemicalsexceptethanolbasedonthehistoryand/ortoxicologicaldata.
Thequalifyingcaserecordswereextractedfromthepatients,medicalfiles.Wecollectedandabstracted
patients,informationregardinggender,age,historyofchronicabuseofalcohol,typeofalcoholicbeverage,
timebetweenintakeofalcoholtoadmissiononhospital,signsandsymptomsofintoxicationonadmission
time,laboratoryfindings,therapeuticinterventions,durationofhospitalizationandoutcome.Datawerekept
confidentialinallstagesofthestudy.
Comagradewascalculatedonadmissiontimeintheemergencydepartment.[9]Allpatientswerefollowed
untildischargefromthehospitalordeath.Accordingtotheoutcome,thepatientsweredividedintosurvivors
(withorwithoutcomplications)andnonsurvivors.
AlldatawereanalyzedwithSPSSsoftware(version12)andSTATAsoftware(version11).Thedatawere
expressedasmedianormeanSDfornumericvariablesandasfrequencyandpercentageforcategorical
variables.Chisquaretestwasusedforstatisticalcomparisonofqualitativevariables.Thefisherexacttest
wasusedifthenumberofcaseswaslessthan5.
ThenormaldistributionofquantitativevariableswastestedbyKolmogorovSmirnovtest.Thestatistical
comparisonwascarriedoutwithMannWhitneyUtestfornonparametricvariablesandindependentstudent
ttestwasusedforparametricvariables.WeusedthePearsontestfortheanalysisofcorrelationinthe
continuousvariablesandoddsratioswascalculatedforthebinaryvariables.Pvaluesof0.05orlesswere
consideredtobestatisticallysignificant.
RESULTS
Atotalof30patientswithacutemethanolpoisoningwereincludedinthestudy.Allofthepatientswere
malewiththemedianageof25.5years(range1552years)[Table1].
Inallofthepatients,therouteofexposurewasoralingestion.Only9(30%)ofthepatientshadthehistoryof
chronicmisuseofalcohol.In24(80%)ofthepatients,thetypeofalcoholwasillegalhandmadealcoholic
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beverages.Only3(10%)ofthepatientshadahistoryofconsumptionofindustrialalcohol(akindof
alcoholicproductthatusedonlyasahouseholdcleanerandnotforadrink),andin3(10%)ofthepatients
thetypeofalcoholsourcewasunknown.Themediantimebetweenintakeofalcoholtoadmissionona
hospitalwas24h(range496h)[Table1].
Visualdisturbances,respiratorymanifestations,andlossofconsciousnesswerethemostcommonclinical
manifestations64%(95%confidenceinterval[CI]:0.440.80),47%(95%CI:0.280.66)and47%(95%CI:
0.280.66)respectivelyonadmissiontime.13patients(43%)hadmydriasis.In5(17%)ofthepatients,the
pupilswereunresponsivetolight[Table2].
Themedianofbloodmethanollevelwas20mg/dL(range775mg/dL)[Table1].Atotalof11patients
(37%)hadmethanollevel20mg/dLto<50mg/dLandsevenpatients(23%)hadmethanollevelmorethan
50mg/dL,oneofthemsurvivedandtheothersixonesdied.Onlythreepatients(10%)hadmethanollevel
5mg/dLto<10mg/dLandinothers,methanollevelwas10mg/dLto<20mg/dL.
AnalyzeofvenousbloodgasonadmissionshowedthatthemedianofpHwas7.15witharangeof6.73
7.32[Table1].Mostofthepatients(60%)hadpH7<to7.20,12ofthemsurvivedandsixothersdied.
FurthermorefromsevenpatientswhohadpH7.20<to7.30,sixpatientssurvivedandonlyonepatient
died.AllofthethreepatientswhohadthepHabove7.30,survivedandtwopatientswhohadthepHless
than7died.
ThemedianofPaCO2was22.35mmHg(rangeof2.7046.60mmHg)[Table1].Inmostofthepatients
(80%),PaCO2waslessthan35mmHg.Onlytwopatients(7%)hadPaCO235mmHgto<45mmHg,one
ofthemsurvivedandtheotherdied[Figure1].Figure2showstherelationshipbetweenpHandPaCO2in
survivorsandnonsurvivors.
ThemedianofHCO3was7.2mEq/Lwitharangeof120mEq/L[Table1].Inmostofthepatients(47%),
HCO3levelwas5<mEq/Lto10mEq/L.NoneofthemhadHCO3levelmorethan20mEq/L,andonly
fivepatients(17%)hadHCO3level15<mEq/Lto20mEq/L,threeofthemsurvivedandtwoothersdied.
Mostofthepatients(60%)hadleukocytosis,andinothersthenumbersofwhitebloodcells(WBC)were
withinnormalrange.ThemediannumberofWBCwas13400/Lwiththerangeof600026400/L.40%of
thepatientsshowedhyperkalemiaandinothersthelevelofpotassiumwasinthenormalrange.
Hyperglycemiawasalsoobservedin21(70%)ofthepatientsandinothers,thebloodglucoselevelwasin
thenormalrange.Themedianofbloodsugarwas184.5mg/dLwiththerangeof70540mg/dL[Table1].
Allpatientsweregivensodiumbicarbonateandfolicacid.Themedianoftotaldoseofsodiumbicarbonate,
whichwasadministeredinpatients,was425mEq/Lwitharangeof752100mEq/L.Exceptfortwo
patientsallofthemweretreatedwithoralethanolsolution10%asanantidote.Themediandurationof
ethanoltherapywas1daywiththerangeof04days.In14(46%)ofthepatientshemodialysiswas
performed.4from16patientswhoreceivednohemodialysisdied.Themediantimeintervalbetween
hospitaladmissionandbeginningofhemodialysiswas4hwiththerangeof017h[Table1].
Atotalof8(27%)ofthepatientswereadmittedinintensivecareunit.Themediandurationofhospitalization
was48h(range3240h)[Table1].Total9(30%)ofthepatientsdiedwhiletwooftheremainingsurvivors
becameblind.
Mortalityrateincomatoseandnoncomatosecaseswas50%versus12.5%,respectivelywithoddsratio7
(1.1442.97,95%CI).Themortalityrateinpatientswithrespiratorydepressionwas80%incompareto20%
inpatientswithoutdepressionofrespiration,withoddsratio16(1.45176.45,95%CI).Therewasa
correlationbetweenmethanollevel(r=0.44,P=0.01),PaCO2(r=0.43,P=0.02),leukocytosis(r=0.41,
P=0.03),bloodsugar(r=0.60,P=0.000)anddeath.
DISCUSSION
Thepresentstudyshowsthattheoralingestionofillegalhandmadespiritsisamostcommoncauseofacute
methanolpoisoninginTehran.Thisresultissimilartoourpreviousfindingandotherresearchers.[6,7,10]In
Iran,accordingtonationalregulations,selling,buying,andconsumptionofalcoholicdrinksisapunishable
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crime.Therefore,theuseofhomemade,illegalandnonstandardalcoholicbeveragescancauseacute
methanolintoxication.
Thepresentresultsshowthattheyoungmenarethemajorpatientssufferfrommethanolpoisoning.Thisis
inconcordancewithourpreviousstudiesaboutgeneralpatternofacutechemicalandpharmaceutical
poisoninginTehran.[5]Inthisstudy,themediantimeintervalbetweenmethanolintakestoadmissionona
hospitalwas24h.Itcanbeduetothisfactthatmethanolisnottoxicbyitselfanditmustbemetabolizedto
toxicmetaboliteslikeasformate.Methanolisoxidizedbyalcoholdehydrogenasetoformaldehyde,whichis
oxidizedtoformicacidbyformaldehydedehydrogenase.Then,formicacidisconvertedtocarbondioxide
andwater.Thisprocessistimeconsumingandfromthisview,theclinicalpresentationsinmethanol
poisoningappearafteralatentperiod.[11]
Themortalityinourstudywas30%.Itissimilartoourpreviousfindingaboutmortalityinacutemethanol
poisoningandotherresearchers.[6,7,12]
Theophthalmic,respiratory,andcentralnervoussysteminvolvementswerethemostcommonclinical
manifestations.Theseresultssupportedbypreviousstudies.[6,8,13]
Although,inthepresentstudy,themeanbloodmethanollevelinourpatientsislowerthanotherstudies,[8]
butitissimilartoourpreviousresult.[6]Thismayberelatedtothedelayofadmissionofthepatientsinthe
hospital.[6]
Thetreatment,includingdurationofethanoltherapy,totaldoseofbicarbonateandtimeintervalbetween
hospitaladmissionandbeginningofhemodialysiswassimilarinbothsurvivorandnonsurvivorgroupsso
thedifferenceintheoutcomeofthepatientscouldberelatedtotheirclinicalandparaclinicalstatuson
admissiontime.Inthepresentstudy,wefoundasignificantdifferencebetweensurvivorsandnonsurvivors
withregardtocomagrade,depressionofrespiration,PaCO2,bloodmethanollevel,leukocytosis,andblood
sugar.Furthermore,therewasacorrelationbetweencomagrade,depressionofrespiration,PaCO2,blood
methanollevel,leukocytosis,bloodsugaranddeath,whichisthesameaspreviouspublisheddata.
[6,7,8,11,12]
RespiratoryarrestandincreasedPaCO2intheseverelyacidoticmethanolintoxicatedcaseshavebeen
suggestedasanewmarker.[7,8]Thecurrentstudyconfirmsearlierstudiesshowingmortalitycorrelating
withthelackofcompensatoryhyperventilationinspiteofandonlywhenthereisaprofoundmetabolic
acidosis.
Hyperglycemiaisrecentlyshownasaprognosticmarker[12]andthesamefindinginthisstudyisthusvery
interesting.Theexactmechanismofhyperglycemiaisnotclearbutithasbeensupposedthatmethanol
poisoningcanbeassociatedwithacutepancreatitisandthiscanbesuggestiveincreatinghyperglycemia.[14]
Furthermoreincreasedcounterregulatoryhormonesfromtheacutestressofmethanolpoisoningcouldbe
anothersuggestivemechanism.[15]
Inspiteoftheresultsofpreviousstudies,whichshowedacorrelationbetweenbloodpHandpoorprognosis,
[6,7,8,11]wedidnotfindanysignificantdifferenceinbloodpHbetweensurvivorandnonsurvivorgroups.
OneoftheexplanationsisthatthebloodH+concentrationisregulatedbyPCO2andlevelofbloodHCO3,
soitwillnotnecessarilybefoundinallpatientpopulationsdependingonthetheircompensatorysituations.
Theotherreasonscouldbethefactthatthisstudyisretrospectiveandthenumberofpatientsisrelatively
small,whichcouldbeconsideredasalimitationofthisstudy.
CONCLUSION
Accordingtotheresultsofthisstudy,itcouldbeconcludedthatcoma,respiratorydepression,PaCO2and
hyperglycemiaarestrongpredictorsofpooroutcome.
Furthermore,hyperglycemiamightbeanewprognosticfactorinmethanolpoisoning,butfurtherstudiesare
neededtodeterminewhethercontrollinghyperglycemiahastherapeuticconsequences.
Footnotes
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SourceofSupport:Nil
ConflictofInterest:Nonedeclared.

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FiguresandTables
Table1

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Comparisonofdemographic,clinicalandparaclinicalmanifestationsinsurvivalandnonsurvivalgroups
Table2

Distributionofpatientsaccordingtoclinicalmanifestationsonadmissiontime
Figure1

DistributionofpatientsregardingtotheirPaCO2andoutcome
Figure2

RelationshipofpHwithPaCO2insurvivorsandnonsurvivors
ArticlesfromJournalofResearchinMedicalSciences:TheOfficialJournalofIsfahanUniversityofMedical
SciencesareprovidedherecourtesyofMedknowPublications

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