Prolonged Respiratory Alkalosis Induced by Caffeine at Subtoxic Serum Concentrations

Respiratory alkalosis due to hyperventilation is a common acid-base disturbance in emergency care settings. While often linked to anxiety or panic attacks, drug-induced causes must also be considered. Caffeine, a widely consumed methylxanthine, is known to induce respiratory alkalosis due to tachypnea in severe overdoses. However, the effects of caffeine at subtoxic serum concentrations are not well characterized, and the possibility of caffeine-induced respiratory alkalosis in the absence of tachypnea is not usually recognized. A 47-year-old underweight female patient with a history of depression presented with general weakness. Her vital signs were stable, and her respiratory rate was 15 breaths per minute. Physical examination revealed carpopedal spasms and extremity weakness. Laboratory tests showed hypokalemia and a venous blood gas with a pH of 7.57 and partial pressure of carbon dioxide (pCO₂) of 27.4 mmHg, consistent with respiratory alkalosis. Despite intravenous electrolyte replacement, respiratory alkalosis persisted for over 20 hours without evidence of tachypnea. Serum caffeine concentration measured by liquid chromatography-mass spectrometry was 13.6 µg/mL at admission and 6.6 µg/mL at 36 hours post-presentation. No other toxic agents were detected. She recovered with supportive care 36 hours after admission. The final diagnosis was caffeine-induced respiratory alkalosis, occurring in the absence of tachypnea and at subtoxic serum caffeine concentrations. This case illustrates that caffeine can provoke respiratory alkalosis through increased tidal volume, even at subtoxic serum concentrations and in the absence of tachypnea. Clinicians should consider caffeine toxicity in the differential diagnosis of unexplained respiratory alkalosis and obtain a detailed history, including dietary and supplement use.