see: [ABG Aspirin overdose example](x-devonthink-item://645DC5F2-F669-4F46-AF3E-9E5F4A066001?page=75), [RCH -Salicylates ](https://www.rch.org.au/clinicalguide/guideline_index/Salicylates_Posioning/), [Austin - Urinary Alkalinisation Guideline Feb 2023](x-devonthink-item://6BD67CD2-6A19-45A3-9F83-B9DCE65B19F7) > [!key points] > **Classic symptoms:** > - vomiting > - tinnitus > - hyperventilation > - resp alkalosis + metabolic acidosis > > severe features: ALOC, seizures > > **Risk dose:** ==>300mg/kg severe== > Antidote:: [[HCO3 therapy]], urinary alkalinisation, MDAC, haemodialysis if severe, IV dextrose if ALOC even if glucose normal - *Methyl salicylate* (oil of [[Essential oils|wintergreen]]; 5mL = 6g of salicylate (elsewhere says 1mL = 1400 mg in Austin tox) # risk assessment - <150mg/kg -- minimal sx - ==150-300mg/kg== - mild-mod intoxication, tinnitus, vomiting, tachyponea - \>400mg/kg -- severe intoxication, met acidosis, ALOC, seizures - \>500mg/kg potentially lethal # Clinical features > toxicity is mostly manifested by GIT and CNS symptoms and is enhanced by acidosis > - metabolic acidosis is a late sign - progressive over hours; severe tox takes 6-12 hours to develop, then rapid deterioration - resp alkalosis followed by metabolic acidosis - tinnitus - vomiting - pulm oedema - [[Seizures]] - hypotension - [[Hot and bothered|hyperthermia]] - sign of *severe tox*, see below - [[hypoglycaemia]] - Depressed or altered mental status should be empirically treated with dextrose, as salicylism has been demonstrated to cause “==neuroglycopenia==” (central hypoglycemia) even despite a normal serum glucose concentration. - May present with hyperglycaemia - nausea - dehydration - pyrexia - confusion - nephrotoxicity - Non-cardiogenic pulmonary oedema - Cerebral oedema - The typical course of acute ingestions begin with non-specific GI symptoms due to local gastric irritation (nausea/vomiting) and tinnitus (cochlear COX inhibition). - Early tachypnea and hyperpnea occur as a result of direct stimulation of medullary respiratory neurons and may lead to a respiratory alkalosis. - The development of an anion gap metabolic acidosis soon follows. - ==Hyperthermia== can occur secondary to uncoupling of oxidative phosphorylation, and is often considered ==a pre-terminal sign==. - As the acidosis worsens, grave clinical consequences ensue: cerebral edema, coagulopathy, and ARDS. # mechanism - uncoupling oxidative physphorylation (similar to [[Cyanide]] tox); aspirin just makes it really difficult - increased fatty acid metabolism (*ketones* and *hypoglycaemia*) - ineffective use of energy → ↑ heat production (hyperthermia) - **zero order kinetics** (fixed amount of drug excreted per unit time) kills you via **neuroglycopenia** (hypoglycaemia in brain) - goal is to STOP aspirin from crossing blood brain barrier by keeping in ionised form - keep serum alkali - keep pH 7.5 - keep potassium normal >4.5 (K/H exchange) # Investigations - salicylate level - levels correlate poorly with severity of toxicity - likely because pharmacobazar in large doses → pyloric spasming from concentrations → absorption in batches - needs falling levels 2 hours apart x 3 - this is why we focus on toxic dosing per kg rather than peak levels in salicylate tox - [[hypokalemia]] (from hyperventilation) [Blood gas](x-devonthink-item://645DC5F2-F669-4F46-AF3E-9E5F4A066001?page=75): classic triple disturbance (only one that does this generally) - metabolic acidosis ([[Lactic acidosis|lactate]], ketones, bicarb loss) - metabolic alkalosis (vomiting) ; +ve BE - resp alkalosis (hyperventilating) # Treatment - **any altered GCS** → Give IV dextrose 50mL 50% dextrose *even if normal BGL* - urinary alkalinization (bicarb 2ml/kg then 25%/hour - avoid intubation unless absolutely necessary (want compensating resp) ## decontamination - ==activated charcoal up to 8 hours following od >150mg/kg== - if >300mg/kg, give via NGT in either case, give second dose [[Decontamination#Multi dose activated charcoal]] after 4 hours if rising serum levels ## urinary alkalinisation (enhanced elimination) - indicated in pts with symptomatic poisoning - Start with a 1-2 mEq/kg [[HCO3 therapy|NaHCO3]] bolus followed by an infusion at 1.5-2x maintenance (Add 150 mL of 8.4% NaHCO3 to 1000 mL 5% dextrose and commence infusion at 200 mL/hour). Or just 25 mmol/hour HCO3 - Goal urine pH should be maintained at 7.5-8.0 - Do not drive plasma pH > 7.5 - Resultant hypokalemia (due to induced alkalosis) must be corrected in order to achieve maximum alkalinization. → give 5-10 mmol KCl/hour to maintain serum K 3.5-4.5 > need to have enough potassium to prevent K/H exchange in kidney ; won't work if hypokalemic. ## haemodialysis indications - haemodialysis works well - do if urinary alkalinisation not feasible - serum salicylate levels >4.4mmol/L or 700 mg/L despite decontamination - Austin tox says Salicylate concentration >7.2 mmol/L (1000 mg/L) OR > 6.5 mmol/L (900 mg/L) with renal failure - severe toxicity (ALOC, acidaemia, renal failure) # avoid intubation See [[Peri-intubation collapse#metabolic acidosis|manage peri-intubation acidosis]] - Avoid intubation if possible as there is a high degree of morbidity and mortality with mechanical ventilation ([Stolbach 2008](https://pubmed.ncbi.nlm.nih.gov/18821862/)). Keeping in mind that acidosis worsens systemic toxicity, any degree of apnea during the peri-intubation period or hypoventilation on the ventilator will exacerbate end organ damage. - If intubation is necessary, consider awake intubation or ketamine facilitated intubation to minimize/eliminate apneic time. - Matching pre-intubation minute ventilation is critical to prevent worsening acidosis (high tidal volumes and respiratory rates). | | indication | dosing | | ---- | ---- | ---- | | decontamination<br>(activated charcoal) | >150 mg/kg<br>(NGT if >300)<br><br>give up to 8 hrs post | 50g oral charcoal<br>[[Decontamination#Multi dose activated charcoal\|MDAC]] after 4 hours if rising levels / large ingestion | | urinary alkalinsation | symptomatic poisoning | 1-2 mmol/kg bolus of [[HCO3 therapy\|NaHCO3]] then 25 mmol/hour HCO3<br>aim *urinary pH >7.5* | | haemodialysis | severe toxicity with:<br>- pre-existing renal/cardiac failure precluding urinary alkalinisation<br>- pulm oedema <br>- severe acidosis<br>- elevated salicylate level > 700 mg/LL or 4.4mmol/L | [[haemodialysis]] | *** # Ibuprofen / NSAID overdose - GIT features similar to those of aspirin toxicity - ​usually less severe - metabolic changes - ​changes clotting - ​thermal complications *ibuprofen* - lowest incidence of GIT irritation of NSAIDs. <100mg/kg usually asymptomatic. >400mg/kg can cause symptoms *piroxicam* - can cause toxicity, need [[Decontamination#Multi dose activated charcoal]] ## management - ​supportive treatment usually only required - ​antiemetic - gastric acid suppression - ​multiple dose activated charcoal indicated for significant toxicity with *piroxicam* # Related Questions ## salicylate overdose - [ ] 14Q: [Salicylate Overdose](x-devonthink-item://84CE632D-3DD4-4F41-A900-23F41BE57287?page=7) -- [Answer](x-devonthink-item://D25C2F83-6C30-4F45-8B5B-6E7E57BD24A3?page=23) - [ ] [AFEM 2023.2 Q22 - salicylate OD](x-devonthink-item://E50B2E75-61B9-43CD-9559-D5EBB0B3E220?page=37) # OSCE - [Cabrini 2019](x-devonthink-item://6F6656A7-158B-45CD-9B9D-8ABEB2D6A607)