Salicylate Poisoning

Salicylate toxicity, most commonly from aspirin overdose, results from direct stimulation of the respiratory center (causing an early respiratory alkalosis), uncoupling of oxidative phosphorylation (causing a later metabolic acidosis and increased heat production), and interference with several metabolic pathways, producing a complex and evolving mixed acid base picture.

Chronic salicylate toxicity (from accumulated therapeutic dosing, particularly in the elderly) can present more insidiously and is often more difficult to recognize than acute overdose, given its less dramatic onset and greater potential for symptoms to be misattributed to another cause.

• Tinnitus and hearing disturbance are classic early features, often present even at modest toxic levels.
• Nausea, vomiting, and abdominal pain from direct gastric irritation.
• Tachypnea and hyperventilation from direct respiratory center stimulation, producing an early respiratory alkalosis; this hyperventilation is often disproportionately marked relative to other findings and is a useful clinical clue.
• Sweating, fever, and flushing from uncoupled oxidative phosphorylation and increased metabolic rate.
• As toxicity progresses, a metabolic acidosis develops (from accumulation of organic acids and interference with the Krebs cycle), producing the characteristic mixed respiratory alkalosis and metabolic acidosis picture on blood gas, a pattern that is itself a strong diagnostic clue when recognized.
• Severe toxicity causes confusion, seizures, cerebral edema, non-cardiogenic pulmonary edema, and, cardiovascular collapse; deteriorating consciousness in salicylate poisoning is a particularly ominous sign, since it often heralds falling pH and worsening CNS salicylate penetration.

• Serum salicylate level, ideally repeated serially given ongoing absorption, particularly with enteric coated preparations or large ingestions forming a gastric bezoar, which can cause a delayed and prolonged absorption phase.
• Venous or arterial blood gas is essential, both to characterize the classic mixed picture and to track trajectory over time, since a falling pH despite treatment indicates worsening toxicity and increasing salicylate penetration into the central nervous system.
• U&E, glucose (hypoglycemia, including cerebral hypoglycemia despite a normal serum glucose, is a recognized complication), and coagulation profile support overall assessment.
• ECG assesses for any associated electrolyte disturbance.

Differentials include other causes of a mixed acid base disorder, other toxic ingestions causing an anion gap metabolic acidosis, and sepsis (which can also cause hyperventilation and altered mental status).

• Activated charcoal is considered if presentation is within 1 to 2 hours of ingestion, or later with large or enteric coated ingestions given delayed and prolonged absorption.
• Urinary alkalinization with intravenous sodium bicarbonate is a key specific treatment, working by ion trapping, ionized salicylate in an alkaline urine is less readily reabsorbed by renal tubules and is therefore more effectively excreted; this also helps correct the systemic acidosis, which is important since falling pH increases the proportion of non-ionized salicylate able to cross into the central nervous system, worsening neurotoxicity.
• Potassium replacement is essential alongside bicarbonate, since effective urinary alkalinization requires adequate potassium, and hypokalemia will otherwise impair the kidney's ability to excrete alkaline urine.
• Careful fluid management addresses dehydration from vomiting, sweating, and insensible losses, while avoiding fluid overload given the risk of non-cardiogenic pulmonary edema.
• Hemodialysis is indicated for severe toxicity: very high salicylate levels, significant CNS effects (confusion, seizures, coma), severe or refractory acidosis, renal failure, or pulmonary edema, since dialysis both removes salicylate directly and corrects the associated acid base and electrolyte disturbance more effectively than medical management alone in severe cases.
• Glucose should be given if there is any suggestion of neuroglycopenia, even with a normal peripheral blood glucose reading, given the recognized phenomenon of cerebral hypoglycemia in salicylate toxicity.

Referral: poison control or toxicology service for all significant ingestions; nephrology and ICU urgently where hemodialysis is being considered.