Salicylate (Aspirin) Overdose — SAQ

Stem

A 23-year-old female university student is brought to the emergency department by her flatmate, who found her distressed in her room alongside two empty blister packs of aspirin (300 mg tablets, 40 tablets, 12 g total) and a half-empty bottle of wine. The flatmate states the patient had been arguing with her boyfriend earlier that day. The patient reports ingesting the aspirin "all at once, about 4 hours ago" with a glass of wine. She weighs 60 kg. She has no significant past medical history, takes the combined oral contraceptive pill, and drinks alcohol most weekends.^[3]

On examination she is agitated, sweating, and flushing, and is breathing deeply and rapidly (28 per minute). She complains of ringing in her ears. Pulse 112/min, BP 104/68 mmHg, RR 28/min, SpO2 99 percent on room air, temperature 37.9 degrees C, capillary glucose 5.4 mmol/L. GCS 15. Auscultation of the chest is clear. Abdomen is soft with no organomegaly. No stigmata of chronic liver disease. The 4-hour serum salicylate level is 580 mg/L. Sodium 142, potassium 3.1, chloride 102, bicarbonate 17 mmol/L, creatinine 78 micromol/L, INR 1.1, paracetamol undetectable. Arterial blood gas: pH 7.46, PaCO2 24 mmHg, PaO2 96 mmHg, bicarbonate 17 mmol/L, base excess -5, lactate 4.2 mmol/L.^[3]

Questions

a) What is the diagnosis, what is the acid-base disorder, and what is the underlying toxic mechanism? Give the full reasoning. (3 marks)^[2][3]

The diagnosis is acute salicylate (aspirin) overdose (12 g = 200 mg/kg, well above the 150 mg/kg toxic threshold) at 4 hours post-ingestion, with moderate toxicity (salicylate level 580 mg/L, in the 450 to 700 mg/L moderate band). The acid-base disorder is a MIXED respiratory alkalosis PLUS high anion-gap metabolic acidosis — the classic adult salicylate blood gas. The primary respiratory alkalosis is shown by the low PaCO2 of 24 mmHg with a pH on the alkalotic side of normal (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 (4.2 mmol/L). Crucially, a bicarbonate of 17 mmol/L in a patient with a primary respiratory alkalosis is already abnormal — in pure respiratory alkalosis the bicarbonate should not fall this far — so a "normal" or near-normal bicarbonate in a tachypnoeic salicylate patient masks a metabolic acidosis. The underlying toxic mechanism is three-fold: (1) direct stimulation of the medullary respiratory centre producing hyperventilation and respiratory alkalosis; (2) uncoupling of oxidative phosphorylation (salicylate is a protonophore, dissipating the proton-motive force across the inner mitochondrial membrane, accelerating oxygen consumption and lactate production); and (3) disturbance of the Krebs cycle (inhibition of dehydrogenases, generating ketoacids and organic acids). The tinnitus (beginning around 200 to 300 mg/L) is a useful bedside severity marker.^[3]

b) Outline the immediate resuscitation AND the definitive enhanced-elimination treatment, with doses. (3 marks)^[2][3]

Resuscitation:^[2]

1. ABCDE, IV access, continuous cardiac monitoring, capillary glucose (5.4, normal but the brain may still be starved).
2. Intravenous fluids WITH DEXTROSE — she is volume-depleted from vomiting, hyperventilation, fever, and obligate diuresis. Use a balanced crystalloid (Hartmann's or 0.9 percent saline) with 5 percent dextrose to maintain normoglycaemia AND prevent cerebral hypoglycaemia (salicylate inhibits cerebral glucose utilisation; give glucose even when plasma glucose is normal or high).
3. Activated charcoal 50 g orally within 1 to 2 hours of ingestion (she is at 4 hours, so charcoal is of limited benefit but may be considered with large ingestions; multiple-dose charcoal 50 g every 4 hours enhances elimination by gut dialysis).
4. Correct the hypokalaemia — potassium 3.1 mmol/L MUST be corrected to over 4.0 mmol/L with intravenous potassium chloride (20 to 40 mmol per litre of fluid) BEFORE urinary alkalinisation will work.

Definitive enhanced elimination — urinary alkalinisation:^[2][3]

• Intravenous sodium bicarbonate: 1 to 2 mmol/kg bolus (8.4 percent), followed by an infusion of 100 to 150 mmol NaHCO3 in 1 L of 5 percent dextrose over 2 to 4 hours.^[2][3]
• Target urine pH 7.5 to 8.0 — check urinary pH every 1 to 2 hours. The mechanism is ion-trapping: unionised salicylic acid (HA) diffuses into the alkaline tubular urine and is deprotonated to the impermeant salicylate anion (A-), which is trapped for excretion. Renal clearance rises roughly 5-fold at urine pH 8 versus pH 5.^[2][3]
• Serial salicylate levels every 2 to 4 hours until clearly falling.^[2][3]

c) This patient does NOT currently meet criteria for haemodialysis. State the EXTRIP 2015 indications for urgent haemodialysis in salicylate poisoning. (2 marks)^[2][3]

The EXTRIP 2015 recommendations (class 1, grade 1D) give the following indications for urgent intermittent haemodialysis — ANY ONE met:^[1]

1. High concentration regardless of signs and symptoms: over 7.2 mmol/L (100 mg/dL, 1000 mg/L) carries a 1D recommendation, over 6.5 mmol/L (90 mg/dL, 900 mg/L) a 2D, with LOWER thresholds when kidney function is impaired (over 6.5 mmol/L — 1D; over 5.8 mmol/L, 80 mg/dL — 2D).^[1][2]
2. Severe metabolic acidosis — arterial pH under 7.20 to 7.25 unresponsive to bicarbonate.
3. CNS toxicity — confusion, delirium, seizures, coma.
4. Non-cardiogenic pulmonary oedema or ARDS.
5. Acute renal failure or inability to alkalinise the urine.
6. Severe refractory hypokalaemia.
7. Clinical deterioration despite standard therapy (fluids, alkalinisation).

She does NOT meet any — her level (580 mg/L) is below the 6.5 mmol/L (900 mg/L) 2D threshold, her pH (7.46) is not acidotic, she has no CNS toxicity beyond agitation, no pulmonary oedema, normal renal function, and only mild hypokalaemia (correctable).^[1][2]

d) Forty-eight hours later she is asymptomatic, the level is falling, and you plan to stop the bicarbonate infusion and discharge her. What is the critical safety step before discharge, and why? (1 mark)^[2][3]

The critical safety step is to continue urinary alkalinisation and recheck the salicylate level every 2 to 4 hours for at least unless symptoms recrudesce (routine repeat concentrations after stopping are unnecessary per the 377-case rebound study — 2.1 per cent rebound, mostly asymptomatic)ours after stopping, because of REBOUND (O'Keefe 2023, Clinical Toxicology). Salicylate distributes widely into tissues; after stopping alkalinisation, tissue salicylate redistributes into the blood, sometimes to toxic levels, causing a recurrence of symptoms (hyperventilation, agitation, tinnitus) and a rising salicylate level. Discharge is appropriate only when the patient is asymptomatic (no tinnitus, hyperpnoea, agitation, CNS signs), the level is clearly falling, the acid-base is normal, no pulmonary or CNS signs, AND a documented psychiatric assessment (mandatory in deliberate self-harm; medico-legal requirement under the Mental Healthcare Act 2017 in India) with a safety plan and crisis numbers.^[1][2]

e) Name two further mandatory steps before this patient is discharged. (1 mark)^[2][3]

1. Mandatory psychiatric assessment before discharge in all deliberate self-harm overdoses (medico-legal requirement in many jurisdictions, including India under the Mental Healthcare Act 2017) — assess suicide risk, underlying mental health, and arrange follow-up. She must not be left unattended in the interim.
2. Counsel the patient on the dangers of further salicylate use, with a documented safety plan and crisis contact numbers; advise that salicylate products (including over-the-counter analgesics, combination products, and topical liniments) should be avoided. Document the history and preserve the containers.

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