Originalarticle
INTRODUCTION
Acutepoisoningwithagriculturepesticideisworldwidehealthproblem.EthyleneDi-bromide (EDB)iswidelyavailableinIndianmarketas5mlampoulehasbeenusedasabulkgrain fumiganttoprotectagainstinsect,pestsandnematodes.Itis acolorlessliquidatambient temperature, which decomposes inthepresenceofheatandlighttoethyleneandbromine ions.(1,2)
Oningestionitssystemiceffectsareseenimmediatelyasabdominalpain,nausea,vomiting
diarrhea.Itcausesnecrosisof hepatocytetubularepitheliumofproximalconvoluted tubuleinkidneyresultinginmetabolicacidosis.(1) Themortalityinfirst48hrisduetocirculatory failurewhilelateronduetohepatic/orrenalfailure(2)
As there is no antidote available and because of latent period in the developmentof symptoms ensuing hepatic or renal failure, use of therapeutic detoxification by plasmapheresismaybeconsidered.Mortalityrateashighas30%to60%arereportedin
variousIndianstudies.(3-4)wetriedtofindouttheclinicaloutcomeinPlasmapheresistreated group,asthereisnostudyinIndianliteraturesuggestingitsusesandeffectiveness.
MATERIALANDMETHODS
AtotaloffortycasesofEthyleneDi-bromidepoisoning,admittedoverJan 2006 –Dec
2012inourinstitution, wereincludedinthisretrospective descriptivestudyafterobtaining approvalfrominstitutionalresearchcommittee. Patientswhowereadmittedwithahistory of ingestionofethylenedibromide,butdischargedagainstmedicaladvicewereexcluded fromthis study.
All patientsreceivedgastricdecontaminationfollowedbycharcoal,to furtherinhibitthe absorptionofpoisonfromgut.Theirbiochemicalparameterswererecordedsequentially for initial2-3days.Symptomaticand supportivecarein theform,antibiotics,dialysisforthose withrenalshutdownandtransfusion offreshfrozenplasmaweregiventothosewithbleeding manifestations.Patientswithderangedliverfunctiontest(liverenzymes>2timesorPTwith INR >1.5 times) or renal functions were subjected to plasmapheresisafter taking written consents.Duringthe procedureof therapeuticplasmapheresis2-2.5 liters of plasma were removedineachsettingofplasmapheresisusing a Fresiniusmedicalcare 4008smachine bycentrifugationtechnologyviaanintravenous subclavianorfemoralveincatheter access and isreplacedbyeitherintravenous fluidslikeringerlactate,humanalbumin/orfreshfrozen plasma.
DATAANALYSIS
Dataofallpatientswerereviewedforthefollowing-
1. Demographicprofile.
2. Clinicalprofile.
3Toxicologicalprofile.
4. Outcomeinconservativeandplasmapheresisgroup.
Observations
Majorityofpatientswerelessthan30years31/40(77.5%)withfemalepredominance. The medianagewas25years(range17-50)(Table1)
Fourteenpatientsdidnotshowanyfeaturesoftoxicity orderangedbiochemicalparameter. Remaining26patients(65%)developedvariouskindsoforgantoxicities(Table4.)Acutetoxic hepatitiswithvariousdegreeofseverity wereobservedin26/40patients(65%)(Table-5).These wasintheformofjaundice,elevatedliverenzymes,increasedprothrombin timeandbleeding time.Outof26 patientswhohadderangedbiochemical parameters13patientsweretreated conservativelyandremaining13patientsweresubjectedtotherapeuticplasmapheresis.
Thoughbothgroupsdiffersas shownby the mean liver enzymeslevel, whichwere
937.6 I.U./ml(range 96-3717) in conservative group, and 2587.6 I.U./ml(126-11700) in plasmapheresisgroup.Nephrotoxicityandcardiotoxicitywere seenin4/40patients(10%)
,19/40(47.5%)patientsrespectively.(Table4)WeobservedAnoverallmortalityof10%,13%,
50%and100%withingestionof1,2,3,and>4ampoule(1ampoule=5ml) (Table3)Overall mortalitywas5/13(38.46%) inconservativegroupwhereas3/13(23%)inplasmapheresisgroup Timefromingestiontodeathwasanywherebetweenlessthantwentyhourstofourdaysinour study.
All the patients underwentatleast two session of plasmapheresis,and one patient was subjectedtohaemodialysis.Adversereactionrelatedtoplasmapheresis wasobservedintwo patients who received FFP during the procedure But those reactions did not results in cancellationofprocedure.Theaveragenumberof plasmapheresissessionwas1.84perpatient.
DISCUSSION
EthyleneDi-bromidereadilypenetratesskinclothingandotherprotectivematerial.Itsrouteof absorptioncanbeeitherbyinhalation,ingestionanddermal(1).Ourstudyshowedsuicidalintent amongtheyoungeragegroup<30years(77.5%)withmajoritybeingfemale17/31(54.83%). Thesystemicfeaturesoftoxicityweremainlygastrointestinallikenausea,vomiting(86.4%), and abdominalpain(81%)tobeginwith,followedbyprogressive dysfunctionofotherorgan systemlikeliverandkidneyaswasseeninother Indianstudies(3-5).
Ingestionof smallamountof EDBcouldbe nonfatal,(6) butexposuretomorethan5mlis
usuallyfatal(7).Weobservedanoverallmortalityof10%,13%,50%and100%withingestion of1,2,3,and>4ampoulerespectively(1ampoule=5ml)(Table3)
Plasmapheresis ortherapeuticplasmaexchangeisanextracorporealtechniquedesignedfor removaloflargemolecularweightsubstanceshighlyboundtoplasmaprotein.Besidestreating forremovalofautoantibody (primarybiliarycirrhosis,acutehumoralrejectionposthepatic transplant) its role is rapidly increasing in treatment of poisoning with drugs ( like Phenytoin,Theophylline,Tri-andTetra-cyclicantidepressant,L-thyroxin,Verapamil,Diltiazem, Carbamezapineetc,),heavymetalintoxication(MercuryandVandate),snakebiteandPhalloid
mushroom intoxication,for which there is no antidote.(8-15)According to the volume of distribution,proteinbindingandsolubilityinwater,differentmethodsarechosen.Haemodialysis
isbestforwatersolubleanddialyzable substances(ethyleneglycol,methanol), Haemoperfusion
(Charcoal)isusedforPhenobarbital.Plasmapheresisisthebestoptionforsubstancethatisnot
removedeffectivelybyeitherhaemodialysisorhaemoperfusion(8).Documentationofremovalof toxicsubstances frombloodremainsthemajorobjective fortheeffectivenessofPlasmapheresis
inanyintoxication.EDBiscovalentlyboundtoalbumin(16)andinplasmapheresis;toxicmetabolite
2bromoacetaldehydeboundtoplasmaproteinisremoved,beforeit causesorgandamagelike nephrotoxicityandhepatotoxicity.InEDB,serumbromidelevelcanbeusedtodocumentthat exposuredidoccurbutbromidelevelsdonotaccurately predicttheclinicalcourse(3)
Plasmapheresishas beenobservedin reducingthemortalityfromas highas 35-50%with conventionaltherapy to20%-10%inphalloidmushroomintoxicationandthe besttherapeutic
results canbeexpectedwhen thedetoxificationtechniqueareappliedwithinfirst36-48hours.(8-10)
In our study we observed a reduction inmortality ratefrom 38.46%to23% inEDB intoxication.Thoughbothgroupswerenoncomparable,asseverehepatotoxicity (liver enzymes>25 times)wereobservedin38.4%(5/13)ofpatientsinplasmapheresis groupwith mortalityrateof60%,whileinconservativegroupitwas23%(3/13)with100%mortalityrate. Thusthereisareduction in mortality rate of 40% in plasmapheresis groupwithsevere hepatotxicity. The mean liver enzyme level were 937.6 I.U. / ml(range 96-3717) in conservativelytreatedpatients,whilein plasmapheresisgroupthemeanliverenzymewere
2587.6I.U./ml(126-11700).Thereisnocontrolledstudy ontheusefulnessofPlasmapheresisin any particular intoxication because of lack of large reported series .Case reports are published instead, and dependingon the severityof the reported intoxicationand on the Plasmapheresis protocol used; either dramatic improvement or no effect is reported. Documentation ofremovalofthetoxicsubstancefromthebloodthereforeremainsthemajor objectivejudgmentoftheeffectivenessofPlasmapheresisinanyparticulartypeofintoxication
CONCLUSION
Ethylenedibromide ishighly toxicsubstance;uptooneampoule maybelethalifnottreated immediately.Withmortalityrateashighasupto60%,therapeuticplasmapheresis can beconsideredasatreatment option.Weobservedasignificantreductioninmortalityin plasmapheresisgroupespeciallythosewithseverehepatotoxicity.
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TABLE1:DEMOGRAPHICPROFILE
AGE(YEARS) / MALE / FEMALE / TOTAL11-20 / 5 / 6 / 11
21-30 / 9 / 11 / 20
31-40 / 6 / 2 / 8
41-50 / 0 / 1 / 1
TOTAL / 20 / 20 / 40
TABLE2: ClinicalCharacteristicsof EthyleneDibromidePoisoning
SYMPTOM / NUMBEROFPATIENTS / PERCENTAGEAbdominalpain / 33 / 82.5%
Nauseavomiting / 35 / 87.5%
Drowsiness / 10 / 25%
Oliguria / 4 / 10%
Haematmesis / 3 / 7.5%
TABLE:3Numberofampoulesconsumedandmortalitypattern
AMPOULES / PLASMAPHERESIS / CONSERVATIVE / TOTALSURVIVED / EXPIRED / SURVIVED / EXPIRED
1 / 4 / 1 / 12 / 1 / 19
2 / 4 / 0 / 9 / 2 / 15
3 / 2 / 1 / 0 / 0 / 3
4 / 0 / 1 / 0 / 1 / 2
5 / 0 / 0 / 0 / 1 / 1
10 / 3 / 225 / 40
TABLE4:TOXICITYPROFILEinEthyleneDibromidePoisoning
CONSERVATIVE / PLASMAPHERESIS / TOTALHEPATIC / 15 / 11 / 26
RENAL / 4 / 6 / 10
CARDIAC / 7 / 12 / 19
HEMATOLOGICAL / 1 / 2 / 2
C.N.S / 2 / 2 / 2
NOBIOCHEMICAL
ABNORMALITY / 14 / 0 / 14
TABLE:5HEPATOTOXICITYPROFILEinEthyleneDibromidePoisoning(n=26)
PEAKLIVER ENZYMES LEVELS(IU/ml) / PLASMAPHERESIS / CONSERVATIVESURVIVED / EXPIRED / SURVIVED / EXPIRED
Upto3
times(<,120) / 4 / 0 / 3 / 0
Upto10
times(<400) / 4 / 1 / 5 / 0
Upto25
times(<1000) / 0 / 1 / 0 / 0
>25times / 0 / 3 / 2 / 3
Total / 8 / 5 / 10 / 3