salicylate s

7/29/2019 Salicylate s

1/33

SalicylateSalicylatePoisoningPoisoning

Blaine (Jess) Benson,Blaine (Jess) Benson, PharmPharm.D..D.

Director, NMPDCDirector, NMPDC


2/33

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.


3/33

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


4/33

Therapeutic Uses OfTherapeutic Uses OfSalicylatesSalicylates

AnalgesicAnalgesic

AntiAnti--inflammatoryinflammatory

AntipyreticAntipyretic

KeratolyticKeratolytic

RubifacientRubifacient


5/33

Trends InTrends In SalicylateSalicylatePoisoningPoisoning


6/33

ChronicChronic vsvsAcuteAcute SalicylateSalicylate

PoisoningPoisoning

Acute Chronic

Victim Young Adult Elderly

Circumstances Intentional AccidentalTime To Diagnosis Short LongMortality 2% 25%

Morbidity 16% 30%


7/33

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


8/33

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


9/33

Factors InfluencingFactors InfluencingSalicylateSalicylate

ToxicityToxicity

DoseDose

Age Of VictimAge Of Victim

Renal FunctionRenal Function

DehydrationDehydration

FeverFever


10/33

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


11/33

Aspirin AbsorptionAspirin AbsorptionSolid Dosage FormSolid Dosage Form

DisintegrationDisintegration

Solid ParticlesSolid Particles

Dissolution*Dissolution*

Drug In SolutionDrug In Solution

AbsorptionAbsorption


12/33

Aspirin MetabolismAspirin Metabolism

Salicyl acyl glucuronide

(5%)

Salicyl phenolic glucuronide

(10%)

Salicyluric acid

(75%)

Gentisic acid

(


13/33

OxidativeOxidativePhosphorylationPhosphorylation


14/33

Cytochrome Oxidase System


15/33

Krebs Citric Acid Cycle


16/33

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


17/33

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


18/33

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


19/33

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


20/33

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


21/33

Complications OfComplications OfSalicylateSalicylate

PoisoningPoisoning Pulmonary edemaPulmonary edema

Renal damageRenal damage

HemorrhageHemorrhage

AssessingAssessing SalicylateSalicylate PoisoningPoisoning


22/33

AssessingAssessingSalicylateSalicylatePoisoningPoisoning--

DoseDose

150 mg/kg No toxicity expected

150-300 mg/kg Mild to moderate

toxicity expected300-500 mg/kg Life-threatening toxicity

expected



23/33


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



24/33


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


25/33

Done Nomogram


26/33

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


27/33

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



28/33


PoisoningPoisoning Preventing absorptionPreventing absorption

IpecacIpecac

LavageLavage

Charcoal and catharticCharcoal and cathartic



29/33


PoisoningPoisoning Enhancing EliminationEnhancing Elimination

Forced alkalineForced alkaline diuresisdiuresis

HemodialysisHemodialysis

HemoperfusionHemoperfusion


30/33

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)


31/33

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


32/33

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


33/33

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

salicylate s

Documents