salicylate s
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SalicylateSalicylatePoisoningPoisoning
Blaine (Jess) Benson,Blaine (Jess) Benson, PharmPharm.D..D.
Director, NMPDCDirector, NMPDC
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Case ReportCase Report
An 18 yearAn 18 year--old female is brought to theold female is brought to the
ED by ambulance after her familyED by ambulance after her family
witnessed a generalized seizure lastingwitnessed a generalized seizure lasting
two minutes. The patient confessed totwo minutes. The patient confessed toingesting two hundred 325 mg aspirin,ingesting two hundred 325 mg aspirin,
eight hours prior to the seizure. Theeight hours prior to the seizure. The
patient arrived unresponsive to verbalpatient arrived unresponsive to verbal
stimuli or pain.stimuli or pain.
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Case Report ContinuedCase Report Continued Vital signs:Vital signs:
BP 120/50, HR 119, RR 40, T 103 FBP 120/50, HR 119, RR 40, T 103 F
CXR shows pulmonary edemaCXR shows pulmonary edema
ASA level is 140 mg%ASA level is 140 mg% 3 hours post admission3 hours post admission
ABGsABGs: pH7.45, CO: pH7.45, CO22 19, O19, O22 112,112, BicarbBicarb 1313
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Therapeutic Uses OfTherapeutic Uses OfSalicylatesSalicylates
AnalgesicAnalgesic
AntiAnti--inflammatoryinflammatory
AntipyreticAntipyretic
KeratolyticKeratolytic
RubifacientRubifacient
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Trends InTrends In SalicylateSalicylatePoisoningPoisoning
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ChronicChronic vsvsAcuteAcute SalicylateSalicylate
PoisoningPoisoning
Acute Chronic
Victim Young Adult Elderly
Circumstances Intentional AccidentalTime To Diagnosis Short LongMortality 2% 25%
Morbidity 16% 30%
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SalicylateSalicylateProduct StrengthsProduct Strengths
Adult AspirinAdult Aspirin
5 grain (325 mg)5 grain (325 mg)
Baby AspirinBaby Aspirin
1.25 grain (81 mg)1.25 grain (81 mg)
MethylsalicylateMethylsalicylate
1 teaspoonful (100% MS) = 21 adult1 teaspoonful (100% MS) = 21 adultstrength aspirinstrength aspirin
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Inherent ToxicityInherent Toxicity
AspirinAspirin
Toxic dose = 1 grain/lbs or 150 mg/kgToxic dose = 1 grain/lbs or 150 mg/kg
Minimal lethal dose = 3Minimal lethal dose = 3--4 grains/lbs or4 grains/lbs or
450450mg/kgmg/kg
MethylsalicylateMethylsalicylate
Lethal dose in children = 4 cc of 100% MSLethal dose in children = 4 cc of 100% MS Lethal dose in adults = 6 cc of 100% MSLethal dose in adults = 6 cc of 100% MS
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Factors InfluencingFactors InfluencingSalicylateSalicylate
ToxicityToxicity
DoseDose
Age Of VictimAge Of Victim
Renal FunctionRenal Function
DehydrationDehydration
FeverFever
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PharmacokineticPharmacokineticParametersParameters
Therapeutic Overdose
Peak Blood Level 2 hours >6 hours
Protein Binding 70%-90% 70%-90%*Vd 0.15-0.2 L/kg 0.35 L/kg
Half-life 2-4 hours 18-20 hours*Increased unbound drug
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Aspirin AbsorptionAspirin AbsorptionSolid Dosage FormSolid Dosage Form
DisintegrationDisintegration
Solid ParticlesSolid Particles
Dissolution*Dissolution*
Drug In SolutionDrug In Solution
AbsorptionAbsorption
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Aspirin MetabolismAspirin Metabolism
Salicyl acyl glucuronide
(5%)
Salicyl phenolic glucuronide
(10%)
Salicyluric acid
(75%)
Gentisic acid
(
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OxidativeOxidativePhosphorylationPhosphorylation
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Cytochrome Oxidase System
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Krebs Citric Acid Cycle
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PharmacologyPharmacology
Uncouples oxidativeUncouples oxidative--phosphorylationphosphorylation
Inhibits keyInhibits keydehydrogenasedehydrogenase enzymesenzymes
Interferes with carbohydrate metabolismInterferes with carbohydrate metabolism
Interferes with protein metabolismInterferes with protein metabolism
Interferes with lipid metabolismInterferes with lipid metabolism
S li l tS li l t Eff t O Eff t O
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SalicylateSalicylates Effects Ons Effects On
Carbohydrate MetabolismCarbohydrate Metabolism HyperglycemiaHyperglycemia
Stimulation of adrenal medullaStimulation of adrenal medulla
Stimulation of adrenal cortexStimulation of adrenal cortex
Increased glucoseIncreased glucose--66--phosphatasephosphatase activityactivity HypoglycemiaHypoglycemia
IncreasedIncreasedglycolysisglycolysis
ImpairedImpairedgluconeogenesisgluconeogenesis from nonfrom non--carbohydrate precursorscarbohydrate precursors
S li l tS li l t Eff t O P t i Eff t O P t i
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SalicylateSalicylates Effects On Proteins Effects On Protein
MetabolismMetabolism Inhibits protein synthesisInhibits protein synthesis
Accelerates protein breakdownAccelerates protein breakdown
Inhibits tubularInhibits tubularreabsorptionreabsorption of aminoof amino
acidsacids
S li l tSalicylate Eff t O Li ids Effects On Lipid
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SalicylateSalicylates Effects On Lipids Effects On Lipid
MetabolismMetabolism DecreaseDecrease lipogenesislipogenesis
IncreasedIncreasedlipolysislipolysis
Displaces fatty acids from plasmaDisplaces fatty acids from plasma
proteinprotein
Manifestations OfManifestations Of SalicylateSalicylate
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Manifestations OfManifestations OfSalicylateSalicylate
PoisoningPoisoning VomitingVomiting
Hyperventilation (30 minutes)Hyperventilation (30 minutes)
Metabolic acidosis (12Metabolic acidosis (12--24 hours)24 hours)
Electrolytes imbalance & dehydrationElectrolytes imbalance & dehydration
HyperthermiaHyperthermia
ConvulsionsConvulsions
DeathDeath
Complications OfComplications Of SalicylateSalicylate
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Complications OfComplications OfSalicylateSalicylate
PoisoningPoisoning Pulmonary edemaPulmonary edema
Renal damageRenal damage
HemorrhageHemorrhage
AssessingAssessing SalicylateSalicylate PoisoningPoisoning
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AssessingAssessingSalicylateSalicylatePoisoningPoisoning--
DoseDose
150 mg/kg No toxicity expected
150-300 mg/kg Mild to moderate
toxicity expected300-500 mg/kg Life-threatening toxicity
expected
AssessingAssessing SalicylateSalicylate PoisoningPoisoning
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AssessingAssessingSalicylateSalicylatePoisoningPoisoning--
Clinical EvaluationClinical EvaluationMild (150
mg/kg)
Moderate (150-
300 mg/kg)
Severe (300-
500 mg/kg)Nausea Nausea Delerium
Vomiting Vomiting Hallucinations
Dizziness Tinnitus ConvulsionsHeadache Coma
Confusion Respiratory arrest
HyperventilationTachycardia
Fever
AssessingAssessing SalicylateSalicylate PoisoningPoisoning
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AssessingAssessingSalicylateSalicylatePoisoningPoisoning--
Laboratory EvaluationLaboratory Evaluation Patient StatusPatient Status
Arterial blood gasesArterial blood gases
Blood glucoseBlood glucose
CoagulationCoagulation -- INRINR
ElectrolytesElectrolytes
Severe exposuresSevere exposures
BUN, S. Cr.BUN, S. Cr.
LFTs
Bedside TestsBedside Tests
Ferric chloride testFerric chloride test
PhenistixPhenistix
Quantitative TestQuantitative Test SalicylateSalicylate level (6level (6hours post ingestion)hours post ingestion)
LFTs
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Done Nomogram
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Chronic IngestionChronic Ingestion DoseDose
May occur when >100 mg/kg/day ingestedMay occur when >100 mg/kg/day ingestedfor two or more daysfor two or more days
Clinical abnormalitiesClinical abnormalities Severe CNS symptoms, dehydration,Severe CNS symptoms, dehydration,hyperventilationhyperventilation
SalicylateSalicylate levelslevels Of no prognostic valueOf no prognostic value
Management ofManagement of SalicylateSalicylate
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Management ofManagement ofSalicylateSalicylate
PoisoningPoisoning Supportive CareSupportive Care
Fluid/electrolyte managementFluid/electrolyte management RehydrateRehydrate with 0.9% saline @ 10with 0.9% saline @ 10--20 cc/hr over 120 cc/hr over 1--22
hours, until urine flow is 3hours, until urine flow is 3--6 cc/kg/hr6 cc/kg/hr
DiuresisDiuresis/alkalization with D5W with 88/alkalization with D5W with 88--132132mEqmEq/L/Lbicarbbicarb, plus 20, plus 20--4040mEqmEq KClKCl@ 2@ 2--3 cc/kg/hr. Goal: urine3 cc/kg/hr. Goal: urine
flow of 2flow of 2--3 cc/kg/hr and urine pH of 7.53 cc/kg/hr and urine pH of 7.5--8.08.0
Reduce fluid load with elderly and patients with renal orReduce fluid load with elderly and patients with renal or
cardiac diseasecardiac disease
HyperthermiaHyperthermia
Sponge bath, fans, cold water submersionSponge bath, fans, cold water submersion
Management ofManagement of SalicylateSalicylate
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Management ofManagement ofSalicylateSalicylate
PoisoningPoisoning Preventing absorptionPreventing absorption
IpecacIpecac
LavageLavage
Charcoal and catharticCharcoal and cathartic
Management ofManagement of SalicylateSalicylate
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Management ofManagement ofSalicylateSalicylate
PoisoningPoisoning Enhancing EliminationEnhancing Elimination
Forced alkalineForced alkaline diuresisdiuresis
HemodialysisHemodialysis
HemoperfusionHemoperfusion
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Forced AlkalineForced AlkalineDiuresisDiuresis
HAHA
HH++ + A+ A--
HAHA
HH++ + A+ A--
HAHA
HH++ + A+ A--
pH = 6.8pH = 6.8 pH = 7.4pH = 7.4 pH = 8.0pH = 8.0
TissueTissuePlasmaPlasma Urine (Alkaline)Urine (Alkaline)
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Forced AlkalineForced AlkalineDiuresisDiuresis IndicationsIndications
SalicylateSalicylate level >50 mg% accompanied bylevel >50 mg% accompanied bysymptoms and biochemical abnormalitiessymptoms and biochemical abnormalities
UtilityUtility
No studies demonstrating a decreased morbidityNo studies demonstrating a decreased morbidity
or mortality with this treatmentor mortality with this treatment
DangersDangers Alkalosis,Alkalosis, hypernatremiahypernatremia, fluid overload,, fluid overload,
decreased ionized Cadecreased ionized Ca++++ andandtetanytetany
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HemodialysisHemodialysis ClearanceClearance
HemodialysisHemodialysis -- 80 ml/min80 ml/min
Peritoneal dialysisPeritoneal dialysis -- 1010--30 ml/min30 ml/min
IndicationsIndications
Absolute: renal failure, cardiac failure, hepaticAbsolute: renal failure, cardiac failure, hepatic
compromise, pulmonary edemacompromise, pulmonary edema
Relative: ASA level of 120 mg%, unresponsiveRelative: ASA level of 120 mg%, unresponsiveacidosis; persistent severe CNS manifestations,acidosis; persistent severe CNS manifestations,
progressive deterioration despite supportive careprogressive deterioration despite supportive care
Other Less Commonly UsedOther Less Commonly Used
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Other Less Commonly UsedOthe ess Commonly Used
Methods To Enhance EliminationMethods To Enhance Elimination Exchange transfusionsExchange transfusions
49%49% salicylatesalicylate eliminated per exchangeeliminated per exchange
Complications include sensitization andComplications include sensitization and
hypocalcemiahypocalcemia HemoperfusionHemoperfusion
Clearance of up to 116 ml/minClearance of up to 116 ml/min
Does not correct fluid and electrolyteDoes not correct fluid and electrolyte
imbalancesimbalances
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