August2008
The MeltingPot - A Case Study in
ForensicToxicology CherylL. Golson,BS,CLS,M. DouglasBearden, Md CLS(NCA),MT (ASCP)andGeorgeB. Kudolo,PhD, FAIC,FACB Departmentof ClinicalLaboratorySciences UT HealthScience CentetSanAntonio Corespondingauthor: GeorgeB. Kudolo,PhD Department of CLS-MSC62'16,UT HealthScience Center. 7703FloydCurlDrire. SanAnlonio,TX 78229-3900
Casesummary:A 33-1earold blackman.lastseenalivearound midnight,wasfoundunresponsive by his brotherat 6:20am. He hadbloodshoteyeswith obviousscleralhemorrhages and a brownishpurgewasprotrudingfrom his noseandmouth. Paramedics pronounced him deadat the scene.Drug paraphernalia wasfoundrvhichincludeda baggiewith brownish granularsubstance, a sy-ringe. and a spoonwith possibledrug resrdue.However,lV drug usecould not be confirmeddueto the inabilit_v to breakrigor mortisin thearms. Whattvasthecause andmannerof death? Results& Discussion:Thepostmortem toxicologyreportfrom themedicalexaminer'soffrce(Tablel) showedthatthedecedent hadingestedalcohol,severalprescriptionmedications, andtwo drugsof abuse.First ofall, ethanolw"s detected andconfirmed in boththe femoralbloodandvitreoushumorspecimens. The |itreoushumoris protectedfrom the systemiccirculationand thereforedruglevelsfoundin this chamber,especially ethanol, accurately reflectsantemortem levelsin forensictoxicologr.t Thereis a verycloserelationshipbet$.een the vitreoushumor andthebloodalcohollevelsasseenin the decedent. The results clearlyshowthatthedecedent waslegallydrunk(legallimit is 0.08g/dl (or %o).At 0.168g/dl,thiswouldbeconsisrent wirh selerecentralnenousslstem(CNS)depression, impairedmotor functionanddecreased bloodflow to thebrain.r Benzoylecgonine, detectedin boththe bloodandurine specimens. is a metaboliteof cocaine.Cocainehasa very short halfJife (l-2 hours)and.unlessit wasrecentlyingested,maynot be detectable. However,b€nzoylecgonine hasa relativelylonger half-life(6-8hours)andis a reliableindicatorofcocaineuse. Cocaineis a potentCNSstimulator,horve!er approximately rr!*o hoursafterusea periodofdebilitatingexhaustionmayoccul3 The decedent's bloodwaspositivefor the opiatesdrug screen (ELISAmethod).In forensictoxicolots)it is importantto determinewhetherthepresence ofopiateswasfrom licit or illicit sources.Confirmationby GC,MSshowedthepresence of (6-MAM). Promethazine, codeineandmonoacetllmorphine an antiemetic(Phenergan) mayalsobe availableover-the-counter as a coughs1rupin combinationrvithcodeineandalcohol.Illicit heroin(diacet-vlmorphine) is an opiatewith a \,eryshorthalf-life (9-20minutes)andfor that reasonmaynot be detected but is metabolized to 6-MAM. morphine(half life, 2-3hours)and codeine.However-the insestionofcodeine-aswith
promethazine. mayproducemorphinebut net€r6-MAM (Table l). Therefore.thepresence of 6-MAM confirmsheroinusein the decedent.r Diazepam(Valium)is a benzodiazepine (activemetabolite. nordiazepam) prescribed for amiety or musclespasms.5 (metabolite, Carisoprodol meprobamate) is a musclerelaxantthat maybeavailablein combinationrith aspirin(Equagesic@) or codeinefor painmanagement.6 Co-ingestion ofalcoholandother CNS depressants rvith carisoprodolis stronglydiscouraged b1 the manufacturer Promethazineis a highly addictivedrug that is glorified in "rap music" $ith lyricsthatreferto "sippingon syrup.sizzurup andpurpledrank"3andhasbeenimplicatedin severalcelebrir_l* deaths."ro Takentogether,the presentcaseillustratesthe gro\ring incidenceof multipledrugingestions(pollpharmacy)resultingin fatal outcomes. First ofall. the co-ingestion ofcocaineand alcoholyieldscocaethylene in the bodyrvhichhaspro\€n to be morepotentthaneitheralcoholor cocainealone.rrPeak promethazine plasmale\€lsfor therapeutic purfnsesare0.01I .023mg/L andlevelsabove0. l0 mg/L arefatal.sSincewhole bloodis usedfor drug analysesin the forensictoxicolog.v laboratoryit is importantto determinewhattheplasmalevelsfor
F i g .1 . Heroin& CodeineMetabolism HEROIN (Dacety'morphine)
Norcoderne Nj.mst'taro
CODEINE -
o{6m.trta!o1
*,*"1
MORPHINE -
6-Monoacetylmorphne (6-MAM)
MajorMetabolite Moryhin+3-Glucurcnide
promethazine wouldhavebeen.Assuminga hematocritof4550olo, thedecedent's bloodvalue(0.05mg/L) wouldgivea plasma levelofapproxirnately 0.10mg/L,$hich is at thelethallevel.Also. promethazine exhibitsanticholinergic properties by blocking acetylcholineaction3muchlike thebonrlinumtoxin, inlfbiting acelylcholine actionresultingin paralysis,uhich in the pulmonarybed,mayprovefatal.rrrs Conclusion:The causeofdeathwaspromethazine overdose exacerbated by multi-drugtoxici6, andthemannerofdeathwas accidental. This caseillustratesthat a meltingpot ofbenign medicinessuchasa coughmixture,anda hostofproper$ prescribed drugsandalcoholis a recipefor a fataloutcome. References l. Ellion S.P(2007).Guideto ObtainingSp€cimens arposrmortemfor Anal!1icalToxicology.RegionalLaboratory contnued on pqge I l
August2008
11
Case Study
from page 9
Tabte1 Alcohols(Ethanol) Femoralblood Vitreous humor
0.149g/dl 0.168g/dl
Specimen: Femoralblood A c i d / n e u t r adl r u g s
Nonedetected
A l k a l i n ed r u g s Meprobamate Carisoprodol Codeine Promethazine Diazepam Nordiazepam Benzoylecgonine Opiates Morphine Codeine Monoacetylmorphine Soecimen: Urine Codeine Monoacetylmorphine Benzoylecgonine
+
J.os mgl0.32mg/L 0.38mg/L +
0.14mg/L +
+ + + +
(+) denotes thepresence ofthe drugbutwasnot quantitated because levelswerelessthanthelimit of quantitation (LOQ).Druglevelswereconfirmedand quantitated usinggaschromatography/mass spâ‚Źctrometry (GC.MC). Thescreen testfor opiates wasperformed using theELISAmethod.
for Toxicologt, http;//\r $ \r loxlabco. uk/postmort.httrL Accessed on May 26, 2008. Centersfor DiseaseControlandPrevention.Alcohol. http://rlr"$'.cdc.go\.y'alcohol/faqs.htm#2. Accessed on May29,2008. Claustre A.. Bresch-Rieu I., FouilheN. ( 1993).Cocaine (PIM 139).IPCSINCHElrl, http://rru:inchem.org documentypims/pharrn/piml39e.htm. Accessed on May 26.2@8. McMillin G andUrryR (2007).DrugTestingGuidefor ChronicPainManagement Services.ARUPClinicql DrugAbuseTesting,l-7. Long-PW MD. (2008).Diazepam.IntemetMentql Health, http:II vwv;.mentalhealth.corn/dng/p30rOl.html.Accessed onMay28,2008. ForresterM.B.(2006).Carisoprodol Abusein Texas, 1998-2203. Journalof .trledical Toxico log), 2(l), 8-13. 7. SOMA(carisoprodol). MedPointePharmaceuticals. Somerset. NJ. 2005.
Woods,D.J.(1990).Promethazine (PIM 439).IPCS I NCHEltI, http://*rv.inchem.org/documents/pims/ phamt prometha. htm#SectionTide:4.2olo2oTherapeun {/o20dosage. Accessed on May 28, 2008. 9. BreakingNews:PimpC's DeathCausedBy Cough Syrup Overdose.ltlemphisRap.com.httpl / / wrvu.memphisrap. com./cgi-bin/content pub9990263694 I 55.cgr?itemid=gg90279 122986&& actionliewad&page=I &placeonpage=6&totaldispla!ed :10&categoryid=9980263694460. Accessed May26. 2m8. Coroner:Chris Penndied accidentally. USATotlay, http://w'w-r'. usatoday.com/life/people/2006-02I 3-pennaccidentx.htm. Accessed May 29,2008. l l . HearnWL.. RoseS.,WagnerJ. . CiarleglioA.. andMash D.C. (1991).Cocaethylene is morepotentthancocaine in mediatinglethaliq;.PharmacologtBiochemistry& Behwior 39.531-533. RubinM. (2008).DisordersofNeuromuscular Transmission.Theltfercklttanuals,hltpJ/ rrrrl. merck.com/mmpe/sec I 6/cM23lch223b. htnl. Accessed on Ma! 29, 2008. 13. BumsJ.J.(2008).Toxici0,Anticholinergic.eltfedicine SpeciaIti es, http://$"$.rv.emedicine.con/emerg/ topic36.htm.Accessed on Mav 29. 2008.
Patient Salety
Jiom page 3
management administrators, nursingpractitioners, clinicians. infonnation sen-icespersonnel,public health departments.and thebeneficiaryof clinicallaboratorytestingsenices-the patient. ProductDevelopmentwill createpatient safetyliteraturefor the publicand providers:standardized protocolsto achieve standardizedmeasuresboth measuringand reporting laboratory paiient safety:and a registry and repository-a placeto report bestpraclicesin clinical laboratoryscienceand colleclsuccess stories,andto collectandreportdataregardingthe levelof safetyof clinicallaboratories. Research is mandatoryto developa standarddefinitionofan enor in clinicallaboratorytestingservices. It is imperatilâ‚Źto identiry the ttpe of errors that occur,how and $here they occur in theTotalTestingProcess. their impactandifthere are situationsor health careseftingsthat are moreprone to eror. Oncethereis a broadunderstanding oferrorsin the clinical laboratorytestingprocess,methodsand protocolsto improve thequality-i.e. amelioratethe errorproneprocesses-need to be dweloped,examinedand reportedto clinical laboratory practitioners, cliniciansandpatients.Understanding. through research,is imperativefor developingthe productsnecessaryto improveclinical laboratorypatient safety. ASASCLSmovesfonvardin its implementation of the PatientSafetyStrategicPlanwe needyour commentsandyour participation.Ifyou havean interestin helping,pleasecontact ASCLSPresidentScottAikey at saikey@comcast.net or Cathy Otto at ottoc@ohsu.edu.