Guidelines for the management of paracetamol overdose For Poisons Information Call Australia 131 126 New Zealand 0800 764 766 Paracetamol Treatment Nomogram8 TreatALLpatientswithserumparacetamollevelsabovethenomogramtreatmentline. 1. Paracetamoloverdoseisasignificantcauseofhospitaladmission,butsevereliverinjury israreandevenwhenitdoesoccurtheprognosisisusuallygood.1 Asinglenomogramtreatmentlineisrecommended.Thislinehasbeenloweredby25%fromstandardlinestotakeintoaccount: Deathfromparacetamolpoisoningisrareanddoesnotoccurinpatientstreatedwith N-acetylcysteine(NAC)within8hoursofacuteingestion.2,3 1. Potentialforminorerrorestimatingtheoftimeofingestion 2. Increasedsafetyforallpatientswithpotentialriskfactors Ensurethatcorrectunitsareused(ieµmol/Lormg/L) 2. Signsconsistentwithparacetamolpoisoningincluderepeatedvomiting,abdominal tendernessintherightupperquadrantormentalstatuschanges.4 160 Hypoglycaemiaonpresentationisveryrare,butisimportanttoconsiderinlate presentationsifliverfailurehasoccurred. 1000 3. Anypatientshouldbeconsideredtobeatriskofsevereliverinjuryiftheyhaveingested paracetamolabovethethresholdsbelow(SeeTable1).4 900 Adultandpaediatricpatientswithoutdeliberateself-poisoningwhoarenot consideredatriskaccordingtothethresholdsinTable1belowdonotrequireserum paracetamollevels,LFTsorfollow-up. 800 TABLE 1. Thresholds: Potentially Hepatotoxic Paracetamol Overdoses Adults and children over 6 years of age Children (aged 0-6 years) Acute Single Ingestion Atleast10gor200mg/kg(whichever 200mg/kgormoreoveraperiod islower)overaperiodoflessthan 8hours. Repeated Supratherapeutic Ingestion (RSTI) oflessthan8hours. Deathhasnotbeenreportedin thissetting Atleast10gor200mg/kg(whichever 200mg/kgormoreover islower)overasingle24-hour asingle24-hourperiod. period. 150mg/kgormoreper24-hour Atleast6gor150mg/kg(whichever periodforthepreceding48hours. islower)per24-hourperiodforthe 100mg/kgormoreper24-hour preceding48hours. periodforthepreceding72hours. Morethan4g/dayor100mg/kg (whicheverisless)inpatientswith pre-disposingriskfactors(seebelow). Cmppe!qbsbdfubnpm!dpodfousbujpo!)¶npm0M* Regardlessofthepotentialingesteddose,allpatientswithdeliberate-selfpoisoning shouldhaveaserumparacetamollevelmeasuredtofurtherrefinetheriskofhepatic injuryandthustheneedforNAC. 150 140 130 120 110 700 100 600 90 80 500 70 400 60 50 300 40 200 4. Followingacuteoverdose,the most important factor that determines prognosis is the delay beyond 8 hours before the initiation of NAC.2,4 30 20 100 5. Theoreticalpatientfactorsthatmightincreasetheriskofliverinjuryinclude:5 Chronicalcoholabuse 10 0 Patientstakingmicrosomal-inducingdrugssuchasbarbiturates,carbamazepine, rifampicinandisoniazid(notphenytoin) 0 0 1 2 3 4 5 6 7 8 9 10 11 Patientslikelytohaveglutathionedepletion(egrecentprolongedfasting,acuteillness withprolongedvomitingordehydration,anorexianervosa,bulimia,malnutritionfor otherreasonssuchasmalignancy,HIV-AIDS) 12 13 14 15 16 17 18 NACisusuallywelltolerated.Severereactionsareuncommonandmaybedue toaccidentaloverdoseorpredisposingfactorssuchasasthma.Anaphylactoid reactionsoccurduringtheinitialinfusionsin4-23%,manifestedbyrash, bronchospasm,andrarely,hypotension.3,6Ifthereisareaction,theinfusionshould bestoppeduntilthereactionhasresolved,thenreinstitutedatareducedrateand slowlytitratedbackup. Bebqufe!gspn!Svnbdl!boe!Nbuifx )Tnjmltufjo!fu!bm/!Boo!Fnfsh!Nfe!2::2<!31;!2169.74* Management of Acute Single Ingestions What To Do When The Nomogram Does Not Apply Decontamination Unknown Time Of Paracetamol Ingestion Nodecontaminationofanykindisindicatedinpaediatricpatients. DecontaminationusingactivatedcharcoalisindicatedinadultpatientsifALLof thefollowingcriteriaaremet: Administration of NAC Third Infusion:Thethirddose(100mg/kg)isdilutedin1000mLof5%glucoseis infusedoverthenext16hours. PrescriptionerrorscanoccurwhencalculatingthedoseofNACusingthe recommendedmg/kgdose.Usingthe“NACintravenousinfusionguide”allowsthedose inmLtobecalculatedandchartedinonestep,reducingthepotentialforcalculation andtranscriptionerrors.7 NAC Intravenous Infusion Dosage Guide Specific Paediatric Considerations Decontaminationisnotindicated. Accidentalexposuresinchildren6yearsorlessarebasedontheparacetamol doseingested: Sustained-Release Paracetamol Preparations If theestimateddoseingestedislessthan200mg/kgreferraltohospital, decontamination,serumparacetamollevelandfollow-uparenotrequired. Ifmorethan10gor200mg/kg(whicheverisless)hasbeeningested commenceNAC. If thedoseingestedisestimatedtobemorethan200mg/kg,manageasperthe Acute Ingestion Management Flow-Chart Measureserumparacetamollevelat4ormorehourspost-ingestion,thenagain 4hourslaterifthefirstlevelisbelowthenomogramline. IfbothlevelsarebelowthenomogramlineNACmaybediscontinued. Management Flow-Chart ApreviousadversereactiontoNACpromptscautionduringtheinitialinfusion,butisnot acontraindicationtoitsuse. 1!ipvs Activated Charcoal* TABLE 2. NAC Intravenous Infusion Dosage Guide. THIRDVolume (mL)ofNAC tobeaddedto 1000mLof5% glucose 1.8!ipvst Measure serum paracetamol level within 4-8 hours of ingestion 50 37.5 12.5 25 75 60 45.0 15.0 30 90 70 52.5 17.5 35 105 80 60.0 20.0 40 120 90 67.5 22.5 45 135 X 0.75X 0.25X 0.50X 1.5X Epft!uif!qbujfou!nffu!uif! dsjufsjb!gps!sfqfbufe! tvqsbuifsbqfvujd!johftujpo@ Commence NAC infusion UNDER nomogram treatment line Plot serum paracetamol level on nomogram Plot serum paracetamol level on nomogram Medical treatment not required OVER nomogram treatment line OVER nomogram treatment line Children<20kgbodyweight: 150mg/kgin3mL/kgof5%dextroseover15minutes followedby50mg/kgin7mL/kgof5%dextroseover4hours followedby50mg/kgin7mL/kgof5%dextroseover8hours followedby50mg/kgin7mL/kgof5%dextroseover8hours Children>20kgbodyweight: 150mg/kgin100mLof5%dextroseover15minutes followedby50mg/kgin250mLof5%dextroseover4hours followedby50mg/kgin250mLof5%dextroseover8hours followedby50mg/kgin250mLof5%dextroseover8hours Reference List 1. 2. 3. 4. 5. 6. 7. 8. Sheen CL, et al. QJM 2002; 95(9):609-619. Smilkstein MJ, et al. N Engl J Med 1988;319:1557-1562. Buckley NA, et al. J Toxicol Clin Toxicol 1999;37:759-767. Dart RC, et al. Clin Toxicol 2006; 44(1):1-18. Reid D & Hazell W. Emerg Med 2003;15:486-496. Buckley N & Eddleston M. Clin Evid 2005;1738-1744. Little M, et al. Med J Aust 2005;183(10):535-536. Smilkstein MJ, et al. Ann Emerg Med 1991;20:1058-1063. No UNDER treatment line or >24hrs post OD ALT normal s !T LEAST G OR MGKG WHICHEVER IS LOWER OVER A SINGLE HOUR PERIOD s !T LEAST G OR MGKG WHICHEVER IS LOWER PER HOUR PERIOD FOR THE PRECEDING HOURS s -ORE THAN GDAY OR MGKG WHICHEVER IS LESS IN PATIENTS WITH PREDISPOSING RISK FACTORS Dijmesfo s MGKG OR MORE OVER A SINGLE HOUR PERIOD s MGKG OR MORE PER HOUR PERIOD FOR THE PRECEDING HOURS s MGKG OR MORE PER HOUR PERIOD FOR THE PRECEDING HOURS .O FURTHER MANAGEMENT REQUIRED Yes -EASURE SERUM PARACETAMOL LEVEL !,4 Bevmut!'!Dijmesfo!7,!zfbst !,4 NORMAL SERUM PARACETAMOL LEVEL µMOL, MG, !.9 /4(%2 2%35,4 #OMMENCE .!# INFUSION .O FURTHER TREATMENT REQUIRED 2EPEAT SERUM PARACETAMOL LEVEL !,4 AT HOURS Commence NAC infusion Continue NAC infusion NO No further investigations required Measure ALT at b end of NAC infusion STOP NAC ALT normal No further treatment required No Continue NAC and monitor #ONTINUE .!# AND CHECK !,4 AT HOURLY INTERVALS YES Inchildrenthevolumeof5%glucoseintowhichNACisdilutedshouldbeanappropriate volumeforthepatient’sweight.Forexample: Repeated Supratherapeutic Ingestion in Adults and Children Repeated Supratherapeutic Ingestion Management Flow-Chart 8!ipvst Measure serum paracetamol level & ALT TotalVolume (mL)ofNAC givenover20 hours IfeitherlevelisabovethenomogramlineNACshouldbecontinuedandmanagement followedaccordingtotheAcute Ingestion management Flow Chart. Ifthepatienthasingestedsufficientdosestosuggestriskofdevelopinghepaticinjury (seeTable1),manageaspertheRepeated Supratherapeutic Ingestion Management Flow-Chart,below. Acute Ingestion Management Flow-Chart w Inchildren,oradultsmorethan90kg,thevolumeofNACrequirediscalculatedusing theformulainthebottomrowofTable2.Foradults>110kg,calculatevolumebased on110kg. IfindoubtcontactPIC. w Table2allowseasycalculationofthevolume(andthuscorrectdose)of200mg/mLNAC requiredforeachinfusion.Patientleanbodyweightisestimatedtothenearest10kg. PATIENT’SLEAN BODYWEIGHT(kg) IfithasbeenMOREthan8hourssincethefirstdose,treatthepatientasperthe >8hoursscenariointheAcute Ingestion Management Flow-Chart. Deliberateselfpoisoningshouldbeconsideredinpatientsolderthan6years. Treatmentrecommendationsarebasedonthetimeelapsedfromtheparacetamol ingestion.RefertotheAcute Ingestion Management Flow-Chart. NACissuppliedin10mLampoules. SECONDVolume (mL)ofNAC tobeaddedto 500mLof5% glucose Ifthepatienthastakenanoverdoseofparacetamolattwotimeintervalswithin thelast8hours,interpretthelevelasifallparacetamolwastakenattheearliest overdoseandtreatthepatientasperthe1-8hoursscenariointheAcute Ingestion Management Flow-Chart. Sorbitolisnotindicated. Second Infusion:Theseconddose(50mg/kg)isdilutedin500mLof5%glucose andinfusedoverthenext4hours. INITIALVolume (mL)ofNAC tobeaddedto 200mLof5% glucose Astaggeredoverdosecomprisesseveralingestionsoveraperiodoflessthan24hours. 3. Ingestionofgreaterthan10gor200mg/kg(whicheverisless) Whenrequired,NACisinfusedina3stageintravenousinfusiongivingatotaldoseof 300mg/kgofover20hours.7 Ifthereisadetectableparacetamollevelwithanunknowntimeofingestion,commence NACandtreatthepatientaspertheendofthe>8hoursscenario(i.e.at†onthe Acute Ingestion Management Flow-Chart). Staggered Overdose 1. Presentationwithin1hour 2. Cooperativepatient First Infusion:Theinitialdose(150mg/kg)isdilutedin200mLof5%glucoseand infusedover15to60minutesunderclosemedicalsupervisionduetotheincidence ofanaphylactoidreactions. 19 20 21 22 23 24 Ujnf!)ipvst* Patientswithotherfactorscausingliverinjury(egviralhepatitis,alcoholichepatitis) 6. NACisaneffectiveantidotethatpreventsmortalityifadministeredwithin8hoursofan acuteoverdose.Ithasalsobeenshowntoimproveprognosisifadministeredatany time(beyond8hours)followingoverdose. Cmppe!qbsbdfubnpm!dpodfousbujpo!)nh0M* General Information YES NO Yes /THER PARAMETERS ARE MEASURED AS INDICATED * Cooperative adult patients who have potentially ingested greater than 10g or 200mg/kg, whichever is less b Please refer to the section “What to do when the nomogram does not apply; unknown time of paracetamol ingestion.” These guidelines are not meant to be prescriptive. Each case should be considered individually. Health care professionals should use their clinical judgement to determine the most appropriate course of action. If in any doubt the Poisons Information Centre should be contacted. Prepared in consultation with Frank FS Daly‡, John S Fountain§, Lindsay Murray**, Andis Graudins†† and Nicholas A Buckley‡‡. ‡ § ** †† Frank FS Daly, Clinical Toxicologist and Emergency Physician Royal Perth Hospital, Perth WA 6009 John S Fountain, National Poisons Centre University of Otago, Dunedin, New Zealand Lindsay Murray, Clinical Toxicologist and Emergency Physician Sir Charles Gairdner Hospital, Perth WA 6009 Andis Graudins, Medical Director, NSW Poison Information Centre The Childrens Hospital at Westmead, Westmead, 2145. Clinical Toxicologist and Emergency Physician,Prince of Wales Hospital,Randwick, NSW, 2031 ‡ ‡ Nicholas A Buckley, A/Prof in Clinical Pharmacology & Toxicology The Australian National University Medical School, Canberra ACT 0200 !,4 NORMAL OR STATIC Revised and updated in September 2007 (version 4) GlaxoSmithKline Consumer Healthcare 82 Hughes Avenue, Ermington NSW 2115 Tel: (02) 9684 0888 Fax: (02) 9684 4312 GS12833135