SALICYLATE POISONING

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Aspirin Therapeutic dose 325-650mg 4 hrly adults (>50kg) max 390mg/day child max 15mg/kg 4hrly Toxic dose – 150mg/kg Minimal lethal dose – 450mg/kgMethyl salicylate(Oil of Wintergreen) contains 7gm/tsf lethal dose children 4cc of 100% MS Adults 6cc of 100% MS

Factors influencing salicylates toxicity

• Dose

• age of victim

• renal function

• dehydration

• fever

Pharmacokinetic parametersTherapeutic Over dose

Peak blood level 2 hrs >6 hrs

Protein binding 90% 70-90%

Vd 0.15-0.22 L/kg 0.35 L/kg

Half life 2-4 hrs 18-20 hrs

methylsalicylate

Hydrolysis in GI tract, liver, RBC’s

2.5% excreted unchanged in urine (pH independent)

zero order kinetics once saturated

zero order kinetics once saturated

% of free SA bound to albumin decreases as the [serum] increases: 75% bound @ 40mgdL 50% bound @ 75mg/dL

Free tissue SA increases

First order kinetics

Metabolism in overdose

Overdosehepatic enz saturated drug half life to 18-36 hrs

albumin binding at toxic levels more free drugs

SA = Weak Acid

At physiological pH most SA is ionized not penetrate tissue well

Acidosismore unionised (Diffusable) SA greater tissue penetration

• Stimulates Resp centre (medulla) Hyperventilation

• Uncouples oxidative phosphorylation

• Inhibit key dehydrogenase enzymesRate of metabolism 02

consumption ,glucose utilization ,C02 & heat production

• Interferes with carbohydrate, protein& lipid metabolism

• Inhibit hepatic synthesis of clotting factors

Acute Salicylate PoisoningToxicity dose Mild( 150 mg/kg) Mod(150-300mg/kg) Severe(300-500mg/kg)

CLINICAL FEATURES

CNS Tinnitus,Auditory acuity, Deafness,Vertigo Agitation,Hyperactivity Delerium,Coma,Convulsion Cerebral oedema

C/F contdAcid-Base & Electrolyte disturbances

Resp Alkalosis

Metabolic Acidosis

Anion gap

Hyper or Hyponatremia

Hypokalemia

Coagulation Abnormalities

Hypoprothrombinemia

Inhibition of Factors V, VII, X

Platelet dysfunction

C/F contd

G I System

N&V

Haemorrhagic gastritis

G I motility

Hepatic

Liver enz

Altered glucose metabolism

C/F contdMetabolic

Hyperthermia

Hypoglycemia

Hyperglycemia

Ketonuria

Pulmonary

Tachypnea

Non Cardiogenic Pulmonary oedema

Renal

Sodium& water retention

Proteinuria

Phase ToxicityEARLY No objective findings,subjective

complaints

Tachypnea

Resp. alkalosis

Tinnitus

Nausea

Vomiting

Irritability

LATE Hyperpnea

Hyperthermia

Met. Acidosis

Neurologic (convulsion)

GI & coagulation abnormalities

Chronic ingestion

• Dose - may occur when >100mg/kg/day ingested for 2 or more days

usu in older pts with chr.med illness

• Clinical abnormalities – Severe CNS symptoms, dehydration,

hyperventilation

• Salicylates levels of no prognostic valve

• Toxicity – at lower blood level

Chronic vs acute salicylatepoisoning

Etiology

ACUTEOverdose

CHRONICTherapeutic misuse

Dehydration moderate severe

Age Young adult Elderly

Circumstances Intentional Accidental

Time to diagnosis Short Lung

Mortality 2% 25%

Morbidity 16% 30%

DiagnosisHistory

C/F

ABG- resp alkalosis + met.acidosis in absence of diabetic or renal failure

Fecl3 test - Urine purple

Phenistix Urine/Serum brown

Quanitative Serum Salicylate level ( 6 hrs post ingestion)

Lab Findings

Met.acidosis & anion gap

PT

SGOT,SGPT

Hct & WBC

Hypernatremia

Hypo or Hyperglycemia

Hypokalemia

Management

• Preventing absorption

gastric lavage with in 2-4 hrs multi dose activated charcoal (1gm/kg)

cathartic(sorbitol)

• Enhancing elimination – Forced alkaline diuresis– Hemodialysis– Hemoperfusion

Forced alkaline diuresis• Indications

– Salicylates level >50mg% accompanied by symptoms & biochemical abnormalities

– Rehydrate with 0/9% saline @ 10-20ml/hr over 1-2 – till urine 3-6ml/kg/hr

– Diuresis / alkalization with 1 L5% D +88-132mgq/L Sodabicarb + 20-40meq KCl @2-6cc/kg/hr

• Goal urine – flow @ 2-3ml/kg/hr

Monitoring

Acid Base status

Na, K, Ca2

Volume status

Urine – pH 7.5-8

Forced alkaline diuresis Contd

• Decrease fluid load - elderly ,Pts with renal ds , cardiac ds

• Utility– No studies demonstrating a decrease morbidity

or mortality with this treatment

• Dangers – Alkalosis, hypernatremia, fluid overload – Decrease ionized Ca++ and tetany

Hemodialysis

• Indications • Absolute

– Renal failure, cardiac failure– Hepatic compromise, pulmonary oedema

• Relative – ASA level >120mg%– Unresponsive acidosis – Persistent severe CNS manifestations– Progressive deterioration despite supportive care

• Exchange transfusions– 49% SA eliminated per exchange complications

include sensitization and decrease Ca++

• Hemoperfusion – Clearance of upto 116ml/min does not correct

fluid or electrolyte imbalances

Supplemental glucose & 02

Hyperthermia Sponge bath, fans, cold water

Submersion

Acidaemia NaHCO3 to correct pH

pulmonary oedema – IPPV + high FiO2 +PEEP

Cerebral oedema – hyperventilation, mannitol, phenobarbitone

Coagulopathy – Vit K

Seizures – Bzd

Mgmt contd….• Pts with minor symptoms (N + V, Tinnitus)

ingestion <150mg/kg1st blood < 65mg/dl

Can be treated in emergency• Repeat blood level 2hrly• Admit moderately symptomatic pts – atleast 24hr• Severe overdose – admit in ICU

tachypnea, dehydration, pulm oedema, altered mentation, seizures, commaingestion >300mg/kg

• Elderly – at high risk