Experiments in salicylic-acid-poisoned mice demonstrated that the mice had hypoglycorrhachia with relatively normal blood glucose.¹⁴ Case reports in salicylate poisoned children undergoing lumbar puncture due to clinical features resembling sepsis further illustrate hypoglycorrhachia.^15,16 While children will often have hypoglycemia with severe salicylate poisoning, adults may maintain normal blood glucose due to glycogenolysis. Additional animal experiments showed rats given supplemental dextrose consistently survived an LD50 dose of salicylate.¹⁷

Glucose supplementation may quickly improve delirium and confusion in salicylate poisoned patients.¹⁸

Critical action: Give supplemental dextrose to any salicylate poisoned patient with altered mental status even if the blood glucose concentration is normal.

Hemodialysis

Salicylate has the four properties of highly dialyzable substances (low molecular weight, water soluble, small volume of distribution, and low protein binding in overdose).¹⁹ The Extracorporeal Treatments In Poisoning group recommends hemodialysis for patients with salicylate ≥100 mg/dL or ≥90 mg/dL in the presence of impaired kidney function (defined as Stage 3b or higher chronic kidney disease, serum creatinine ≥ 2 mg/dL (176 μmol/L) in most adults, or serum creatinine ≥1.5 mg/dL (132 μmol/L) in elderly patients).¹⁹ These thresholds, however, may be too high. Warrick et al. reviewed 29 years of salicylate deaths reported to America’s Poison Centers and found that half of the fatal cases had ante-mortem concentrations below 100 mg/dL.⁷ A better threshold for considering dialysis would be salicylate more than 60 mg/dL.

Critical action: Consult your Nephrology colleagues early when the salicylate level approaches 60 mg/dL, or rises despite optimal treatment, or if the patient’s condition worsens regardless of salicylate concentration.

Potassium

Salicylate poisoned patients typically have hypokalemia on initial presentation.^20–22 Sodium bicarbonate infusion and IV fluid resuscitation, needed to alkalinize the blood and urine, tend to exacerbate the already low serum potassium concentration. Supplemental potassium is necessary to replenish lost potassium and to alkalinize the urine successfully.

Critical action 1: Replete potassium generously with IV and oral potassium salts.

Critical action 2: Measure the urine pH periodically to confirm urinary alkalinization.

Critical action 3: Monitor salicylate concentration, basic metabolic panel, and venous blood gases as frequently as every 2 hours until the patient clearly improves.

Acetazolamide

Acidosis favors salicylate protonation to un-ionized salicylic acid, which more easily crosses the blood brain barrier than salicylate. Early work in children in the 1950s indicated that acetazolamide alkalinized the urine, increased urinary excretion of salicylate, and increased salicylate clearance from blood.^23,24 In a report of three cases, one child died and had cerebral edema at autopsy.²³ Children in a larger cohort generally survived but had a mean serum salicylate of 38.7 mg/dL. Experimental animal evidence confirmed the increased urinary excretion of salicylate but also found that acetazolamide increased salicylate concentrations in both CSF and brain tissue and increased mortality in rats.^25,26 In effect, blood salicylate concentration falls in part due to increased delivery of salicylate to the brain—the target organ of salicylate toxicity.