Negative Anion Gap in Critically Ill Patients: A Case Study of Metabolic Alkalosis and Clinical Strategies

BACKGROUND The anion gap is a critical parameter in the clinical assessment of acid-base disorders. While metabolic acidosis with an elevated anion gap is commonly encountered, cases involving a negative anion gap are rare and have been reported in the context of hypoalbuminemia, severe hyperkalemia, bromide intoxication, and laboratory error. Notably, metabolic alkalosis as a cause of negative anion gap has been rarely described in the literature. CASE REPORT A 73-year-old woman with a 4-year history of interstitial pulmonary fibrosis and a 1-year history of coronary artery disease had been taking oral spironolactone for the past year. Six months before admission, torasemide was added to her regimen in combination with spironolactone. Five days prior to admission, she developed progressive dyspnea and respiratory failure. Initial investigations revealed hypokalemia, hyponatremia, metabolic alkalosis (HCO₃⁻=61.6 mmol/L), and a negative anion gap (-9.00 mmol/L), which remained negative after albumin correction (-6.35 mmol/L). Further evaluation identified loop diuretic overuse as the primary cause of severe metabolic alkalosis and negative anion gap. The application of targeted next-generation sequencing (t-NGS) successfully identified the infectious pathogen responsible for the patient's clinical deterioration, thereby guiding appropriate antimicrobial therapy. CONCLUSIONS This case illustrates the diagnostic and educational value of recognizing a negative anion gap as a rare but physiologically predictable artifact of severe chloride-depletion alkalosis, underscoring the importance of mechanism-based interpretation in complex acid-base disorders.