SALICYLATE POISONING

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SALICYLATE POISONING
www.anaesthesia.co.in anaesthesia.co.in_at_gmail.c
om
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• Aspirin
• Therapeutic dose 325-650mg 4 hrly
• adults (gt50kg) 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

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• Factors influencing salicylates toxicity
• Dose
• age of victim
• renal function
• dehydration
• fever

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Pharmacokinetic parameters
Therapeutic Over dose
Peak blood level 2 hrs gt6 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
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methylsalicylate
Free tissue SA increases
Hydrolysis in GI tract, liver, RBCs
of free SA bound to albumin decreases as the
serum increases 75 bound _at_ 40mgdL 50 bound _at_
75mg/dL
2.5 excreted unchanged in urine (pH independent)
First order kinetics
zero order kinetics once saturated
zero order kinetics once saturated
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• Metabolism in overdose
• Overdose?hepatic 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
• Acidosis?more unionised (Diffusable) SA ?greater
  tissue penetration

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• 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

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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

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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

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C/F contd

• G I System
• NV
• Haemorrhagic gastritis
• ?G I motility
• Hepatic
• ?Liver enz
• Altered glucose metabolism

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C/F contd

• Metabolic
• Hyperthermia
• Hypoglycemia
• Hyperglycemia
• Ketonuria
• Pulmonary
• Tachypnea
• Non Cardiogenic Pulmonary oedema
• Renal
• Sodium water retention
• Proteinuria

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Phase Toxicity
EARLY No objective findings,subjective complaints
Tachypnea
Resp. alkalosis
Tinnitus
Nausea
Vomiting
Irritability
LATE Hyperpnea
Hyperthermia
Met. Acidosis
Neurologic (convulsion)
GI coagulation abnormalities
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Chronic ingestion

• Dose - may occur when gt100mg/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

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Chronic vs acute salicylatepoisoning
Etiology ACUTE Overdose CHRONIC Therapeutic misuse
Dehydration moderate severe
Age Young adult Elderly
Circumstances Intentional Accidental
Time to diagnosis Short Lung
Mortality 2 25
Morbidity 16 30
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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)

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• Lab Findings
• Met.acidosis ?anion gap
• ?PT
• ? SGOT,SGPT
• ?Hct WBC
• Hypernatremia
• Hypo or Hyperglycemia
• Hypokalemia

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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

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Forced alkaline diuresis

• Indications
• Salicylates level gt50mg accompanied by symptoms
  biochemical abnormalities
• Rehydrate with 0/9 saline _at_ 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
  _at_2-6cc/kg/hr
• Goal urine flow _at_ 2-3ml/kg/hr
• Monitoring
• Acid Base status
• Na, K, Ca2
• Volume status
• Urine pH 7.5-8

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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

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Hemodialysis

• Indications
• Absolute
• Renal failure, cardiac failure
• Hepatic compromise, pulmonary oedema
• Relative
• ASA level gt120mg
• Unresponsive acidosis
• Persistent severe CNS manifestations
• Progressive deterioration despite supportive care

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• 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

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• 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

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Mgmt contd.

• Pts with minor symptoms (N V, Tinnitus)
• ingestion lt150mg/kg
• 1st blood lt 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 gt300mg/kg
• Elderly at high risk