Salicylate (Aspirin) Overdose — Viva

Q1: Recognition and mechanism (3 min)

Examiner: A 23-year-old woman is brought to casualty 4 hours after ingesting 12 g of aspirin in a suicide attempt. She is agitated, sweating, hyperventilating at 28 per minute, and complaining of ringing in her ears. Pulse 112, BP 104/68, temperature 37.9 degrees C. Arterial blood gas: pH 7.46, PaCO2 24, bicarbonate 17, lactate 4.2. Sodium 142, chloride 102. Salicylate level 580 mg/L. What is your diagnosis, what is the acid-base disorder, and what is the molecular mechanism?^[2][3]

Candidate: The diagnosis is acute salicylate (aspirin) overdose with moderate toxicity (salicylate 580 mg/L). The acid-base disorder is the classic adult MIXED respiratory alkalosis PLUS high anion-gap metabolic acidosis. The primary respiratory alkalosis is shown by the low PaCO2 of 24 with a pH of 7.46; the concurrent high anion-gap metabolic acidosis is shown by the raised anion gap (142 minus (102 plus 17) equals 23, normal 8 to 12) and the raised lactate. A bicarbonate of 17 in a tachypnoeic salicylate patient is ALREADY abnormal — in pure respiratory alkalosis the kidney conserves more bicarbonate. The molecular mechanism is three-fold: (1) direct stimulation of the medullary respiratory centre (hyperpnoea, respiratory alkalosis); (2) uncoupling of oxidative phosphorylation — salicylate is a protonophore that carries protons across the inner mitochondrial membrane, dissipating the proton-motive force, driving up oxygen consumption and heat (hyperthermia) and switching cells to anaerobic glycolysis (lactate); (3) disturbance of the Krebs cycle — inhibition of dehydrogenases (isocitrate and alpha-ketoglutarate dehydrogenase) and amino-acid transamination, generating ketoacids and organic acids. Together these give the high anion-gap metabolic acidosis. The tinnitus is a useful bedside marker and begins around 200 to 300 mg/L.^[2][3]

Q2: The kidney, potassium, and urinary alkalinisation (3 min)

Examiner: Tell me the rationale for urinary alkalinisation, the target, and why you must correct the potassium first.^[2][3]

Candidate: Rationale: salicylic acid is a weak acid with a pKa of about 3.0, so it is mostly ionised at physiological pH and crosses biological membranes as the unionised HA. In an alkaline tubular urine (pH 7.5 to 8.0), HA diffusing into the tubule is deprotonated to the salicylate anion A-, which is charged and cannot back-diffuse — it is ion-trapped for urinary excretion. Renal clearance rises roughly 5-fold at urine pH 8 versus pH 5. The evidence base is the Prescott 1982 BMJ study, which showed that ALKALINISATION of urine (not large fluid volumes) is the active component of enhanced elimination; this is why we now favour urinary alkalinisation over forced alkaline diuresis. Regimen: IV sodium bicarbonate 1 to 2 mmol/kg bolus (8.4 percent), then an infusion of 100 to 150 mmol NaHCO3 in 1 L of 5 percent dextrose over 2 to 4 h, titrated to a urine pH of 7.5 to 8.0, checked every 1 to 2 h. Potassium MUST be corrected to over 4.0 mmol/L first — hypokalaemia causes the distal tubule to reabsorb potassium in exchange for secreting hydrogen ions (the distal H+/K+ exchange), which ACIDIFIES the urine and prevents it reaching pH 7.5 to 8.0. Give IV potassium chloride 20 to 40 mmol per litre of fluid.^[2][3]

Q3: Resuscitation and the glucose point (2 min)

Examiner: She is on fluids. Her plasma glucose is 7.4 — why have you put dextrose in the fluids?^[2][3]

Candidate: Because salicylate inhibits CEREBRAL glucose utilisation, producing central (CNS) hypoglycaemia — a LOW CSF glucose with a normal or even high PLASMA glucose. The brain is starved of glucose even when the bedside capillary glucose is normal. This contributes to CNS toxicity (confusion, seizures, coma) and is especially dangerous in children. So glucose-containing fluid (5 percent dextrose or dextrose-saline) MUST be given even when the plasma glucose is normal or high. The patient is also volume-depleted from vomiting, hyperventilation, fever, and an obligate solute diuresis, so IV fluids are mandatory regardless; including dextrose protects the brain.^[2][3]

Q4: Haemodialysis — indications (EXTRIP 2015) (3 min)

Examiner: A different patient — 19-year-old man, 2 hours after 25 g of aspirin. Level 780 mg/L, arterial pH 7.18, GCS 14, clear chest. What definitive treatment?^[2][3]

Candidate: He meets MULTIPLE EXTRIP 2015 class-1 indications for urgent intermittent haemodialysis: (1) high concentration — over 7.2 mmol/L (100 mg/dL, 1000 mg/L) 1D or over 6.5 mmol/L (900 mg/L) 2D regardless of signs and symptoms, lower with impaired kidney function (he has 780); (2) severe metabolic acidosis (arterial pH 7.18, under 7.20 to 7.25 unresponsive to bicarbonate). EXTRIP gives a class 1, grade 1D recommendation for INTERMITTENT HAEMODIALYSIS (not haemofiltration) in severe salicylate poisoning, clearing salicylate at roughly 80 to 100 mL/min and correcting acidosis, fluid overload, and electrolytes simultaneously. I would use a bicarbonate-based dialysate; a single 4 to 6 h run usually reduces the level substantially. After dialysis I would CONTINUE urinary alkalinisation and recheck the level because of REBOUND — tissue salicylate redistributes into the blood (O'Keefe 2023, Clinical Toxicology). The other EXTRIP indications to know are: CNS toxicity (confusion, seizures, coma), non-cardiogenic pulmonary oedema or ARDS, acute renal failure or inability to alkalinise the urine, severe refractory hypokalaemia, and clinical deterioration despite standard therapy. In chronic poisoning the level threshold is LOWER — over the clinical indicators (altered mental status, ARDS on oxygen, failing therapy) at any level — because chronic salicylism is more toxic at any given concentration, EXTRIP lowered the pure-concentration thresholds only for impaired kidney function, not for chronicity.^[2][3]

Q5: The intubation trap (2 min)

Examiner: Your 19-year-old patient with the 780 mg/L level and pulmonary oedema needs intubation. How do you do it without killing him?^[2][3]

Candidate: Intubation is a HIGH-RISK intervention in salicylate toxicity. The patient is RELYING on hyperventilation to compensate his metabolic acidosis. Sedation, paralysis, and a normally-set ventilator cause PaCO2 to RISE, pH to FALL, and salicylate (in its unionised HA form) to SHIFT into the central nervous system, causing a rapid, often fatal deterioration. My strategy: (1) pre-intubation bolus of intravenous sodium bicarbonate to optimise pH; (2) pre-oxygenate; (3) rapid-sequence intubation; (4) set the ventilator to MAINTAIN the pre-intubation hypocapnia — respiratory rate 20 to 30, minute ventilation matched to pre-intubation, EtCO2 matched; (5) have haemodialysis ready because acidosis will still worsen. The rule is: if you MUST intubate, you MUST hyperventilate to match the patient's own compensation, AND have dialysis ready.^[2][3]

Q6: Special populations — the elderly and chronic salicylism (2 min)

Examiner: An 82-year-old woman in a nursing home, 3 days of progressive confusion, slurred speech, hallucinations. Takes aspirin 75 mg daily, furosemide. RR 16, GCS 13. Sodium 144, potassium 3.4, chloride 104, bicarbonate 18, lactate 3.1. Salicylate 520 mg/L. CT brain normal. What is going on?^[2][3]

Candidate: This is chronic salicylism in the elderly — the highest-yield atypical salicylate presentation. Three teaching points: (1) chronic salicylism presents with an insidious, neuro-predominant picture (confusion, slurred speech, hallucinations, staggering) WITHOUT the classic hyperventilation and tinnitus of acute poisoning — and is frequently MISDIAGNOSED as delirium, dementia, sepsis, or stroke; (2) chronic salicylism is MORE toxic at any given serum level than acute poisoning — greater tissue distribution, reduced protein binding, more CNS effects — so a level of 520 mg/L in this woman is far more dangerous than 520 mg/L in an acute overdose; (3) the dialysis threshold is LOWER in chronic poisoning — over 6.5 mmol/L (900 mg/L, 2D) versus over 7.2 mmol/L (1000 mg/L, 1D) in acute — the kidney-function status, not the chronicity, moves the concentration thresholds. My plan: admit, IV fluids with dextrose, correct the hypokalaemia (over 4.0 mmol/L), urinary alkalinisation to urine pH 7.5 to 8.0, and a LOW threshold for haemodialysis — she is at the chronic threshold. Withhold salicylate and review her medication list. Chronic salicylism has the highest case-fatality of any salicylate presentation precisely because it is missed.^[2][3]

Q7: Rebound and discharge (1 min)

Examiner: When can you discharge a salicylate-overdose patient?^[2][3]

Candidate: Discharge only when ALL of: (1) patient asymptomatic — no tinnitus, hyperpnoea, agitation, CNS signs; (2) salicylate level clearly falling on serial measurement; (3) normal acid-base; (4) no pulmonary or CNS signs. Critically, after stopping urinary alkalinisation I continue to recheck the level every 2 to 4 hours for at least unless symptoms recrudesceours, because of REBOUND — tissue salicylate redistributes into the blood, sometimes to toxic levels, causing a recurrence. Mandatory psychiatric assessment before discharge in all deliberate self-harm cases (medico-legal requirement under the Mental Healthcare Act 2017 in India), with a safety plan and crisis numbers.^[2][3]

References4ShowHide

1. [1]Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup Ann Emerg Med, 2015.PMID 25986310
2. [2]Proudfoot AT, Krenzelok EP, Vale JA. Position Paper on urine alkalinization J Toxicol Clin Toxicol, 2004.PMID 15083932
3. [3]Temple AR. Acute and chronic effects of aspirin toxicity and their treatment Arch Intern Med, 1981.PMID 7469627
4. [4]McCabe DJ, Lupu AL, Cienki JJ. The association of hemodialysis and survival in intubated salicylate-poisoned patients Am J Emerg Med, 2017.PMID 28438446