Guidelines for the management of paracetamol overdose 131 126 0800 764 766

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).
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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.
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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
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[email protected]
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.
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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)
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