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/kg Methyl 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 parameters
Therapeutic Over dose

Peak blood level

Protein binding Vd Half life

2 hrs
90% 0.15-0.22 L/kg 2-4 hrs

>6 hrs
70-90% 0.35 L/kg 18-20 hrs

methylsalicylate
Free tissue SA increases
Hydrolysis in GI tract, liver, RBCs

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

2.5% excreted unchanged in urine (pH independent)

zero order kinetics once saturated

zero order kinetics once saturated

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 enzymes Rate of metabolism 02 consumption ,glucose utilization ,C02 & heat production Interferes with carbohydrate, protein& lipid metabolism Inhibit hepatic synthesis of clotting factors

Acute Salicylate Poisoning

Toxicity 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 contd
Acid-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 contd
Metabolic Hyperthermia Hypoglycemia Hyperglycemia Ketonuria Pulmonary Tachypnea Non Cardiogenic Pulmonary oedema Renal Sodium& water retention Proteinuria

Phase
EARLY

Toxicity
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 Dehydration Age Circumstances ACUTE Overdose moderate Young adult Intentional CHRONIC Therapeutic misuse severe Elderly Accidental Lung 25%

Time to diagnosis Short Mortality 2%

Morbidity

16%

30%

Diagnosis
History 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/kg 1st 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, comma ingestion >300mg/kg Elderly at high risk