Salicylates

Question 1

Discuss risk assessment in salicylates

Answer 1

The severity of a salicylate overdose is dose dependent as follows

<150mg/kg - minimal sympomts
150-300 mg/kg - mild to moderate intoxication, salicylism with hypernoea, tinnitus and vomiting
>300mg/kg - severe intoxication - metabolic acidosis, altered mental state, seizures
>500 mg/kg –> potentially lethal

Chronic poisoning is assoacited with an increase risk of adverse affects, morbidity and mortality

Children rarely ingest enough aspirin to be toxic howevere other salicylate containing products (oil of wintergreen) may cause severe toxicitiy

Question 2

Discuss the toxic mechanism of salicylates

Answer 2

• Cause irreversible inhibtion of COX resulting in decrease in PG synthesis.
• Stimulation of the resp centre causes hyperventilation and respiratory allkalosis.
• Uncoupling of oxidative phosphorylation results in accumulation of lactic acid contibuting to a metabolic acidosis.
• Promotion of fatty acid metbaolism and generation of ketones also contribute to metabolic acidosis
• Death is associated with very high levels of salicylate in the CNS

Question 3

Describe toxicokinetics of salicylate intoxication

Answer 3

Rapidly absorbed following oral administration and highly protein bound
Small VD of 0.1-0.3L/KG

Absorption may be delayed with enteric coated forms or if large tablet masses form in the stomach (bezoar)

IN overdose protein binding is saturated and free salicylates are increased, In acidaemia more salicylate is un ionised favoring movement into extravascular spaces including the CNS>

Hepatic metabolism and kinetics change from first order to zero order in overdose. Changing normal elimiantion half life of 2-4 hours to up to 24 hours

Urinary PH effects renal elimination, hihg Ph promotes urinary salicylate excretion as a greater proportion of the salicylate is ionised and unable to be reabsorbed

Question 4

Described clinical features of acute salicylate intoxication

Answer 4

Progressive over hours and severe toxicity may not be evident until 6-12 hours post infection. Deterioation can be rapid

GIT
-nausea and vomting

CNS

• Tinnitus, decreased hearing and vertigo
• CNS stimulation, agitation, seizures
• May progress to cerebral oedema and death

Acid- base

• resp alkalosis
• HAGMA
• Actual acidaemia occurs alte and indicates imminent demies wihtout intervention

Other
-Hyperthermia
-Hyper/hypoglycaemia
Hypokalaemia

Question 5

Discuss Clinical features of chronic salicylate intoxication

Answer 5

DIfficult to diagnose clinically

Most common in elderly

Often present with non specific symptoms such as
confusion, delirium, dehydration, fever and unexplained metabolis acidosis

-Cerebral and pulmonary oedema are more common than in acute poisoning

Question 6

What Investigations to perfomr in salicylate

Answer 6

ECG, BSL, paracetamol
Salicylate level – correates poorly wiht severity of toxicity
ABG
UEC

Question 7

Discuss management of salicylate poisoning

Answer 7

Resus, supportive care and monitoring

• If I&V is needed ensure maintenance of hyperventilation to maintain respiratory alkalosis
• Control seizures with benzos

Decontimation

• Activated charcoal up to 8 hours post ingestion of a dose of >150mg/kg
• Following infestion fo >300mg/kg administer activated charcoal 50g via a NG tube and again 4 hours later if levels continue to rise

Enhanced elimination
-Urinary alkalinisation
-HD is effective but rarely required if early decontamination and urinary alkalinisation is implemented
-COnsider HD if
—Urinary alkalinisation not feasible
Serum salicylate levels rising despite decontamination and alkalinisation
—Severe toxicity as evidenced by altered mental status, acidaemia or renal failrue – anyone who needs a tube
—Very high salicylate levels (Acute >7.2mmol/L, Chronic >4.4 mmol/L) Lower threshold in the elderly greater than 4.4 for anyone

Question 8

Discuss disposition

Answer 8

All children suspected of ingesting methyl salicylate produts should be observed in the hospital for signs of salicylate toxciity for at least 6 hours

All symptomatic patient require admission for careful monitoring and enahnced elimianation techniques. Therapy is ceased when salicylate level falls to within normal rnage.