Abstract Introduction Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness caused by antibodies against mostly the acetylcholine receptor. Diagnosis is confirmed by antibody assays or, in seronegative MG, single-fiber electromyography. Management is achieved through acetylcholinesterase inhibitors, while long-term remission requires immunosuppression with corticosteroids or biological agents. For myasthenic crisis, therapeutic plasma exchange (TPE) is a mainstay of therapy. However, repeated TPE using 4 % albumin, which contains a high chloride concentration (∼145 mmol/L), may cause hyperchloremic non-anion-gap metabolic acidosis (NAGMA). In MG, even mild acidosis increases central chemoreceptor drive, leading to hyperventilation and respiratory muscle fatigue. We report a case of chronic, compensated NAGMA induced by albumin-based plasma exchange in a woman with refractory seronegative MG. Case Report A 45-year-old woman with refractory seronegative MG, diagnosed in 2020, developed progressive ventilatory weakness requiring chronic plasma exchange (PLEX) since 2021. She had previously failed guideline directed therapy. Maintenance therapy included pyridostigmine, tacrolimus, and nighttime non-invasive ventilation (NIV). From 2021 onward, she demonstrated persistently low serum CO2 (18-21 mmol/L) with normal pH and hyperchloremia, consistent with chronic, compensated NAGMA. This was accompanied by air hunger even with NIV use. Between December 2024 and January 2025, while undergoing PLEX every 2-3 weeks, the patient experienced post-exchange dyspnea, orthopnea, and fatigue, coinciding with bicarbonate nadirs (∼19 mmol/L). On January 20, 2025, her FVC was 2.61 L (88 % predicted) and FEV1 2.43 L (98 %), but subsequent decline in FVC to 1.58 L (53 %) by March 2025 reflected diaphragmatic fatigue. Oral sodium bicarbonate was initiated in February 2025 (650 mg daily, increased to 1,300 mg pre-PLEX). At her most recent follow-up, she continues PLEX every 3 weeks with 1,300 mg NaHCO3 pre-session and use of non-invasive ventilation during each session with improvement in her ventilatory mechanics. Discussion/conclusion Each session of plasma exchange replaces plasma with a chloride-rich solution, reducing plasma bicarbonate concentration. Large or repeated exchanges can therefore cause dilutional hyperchloremic metabolic acidosis. In this case, the consistent timing of low CO2 following PLEX and presumed absence of renal tubular dysfunction points towards an iatrogenic source of the acidosis.MG patients frequently exhibit impaired FVC and inspiratory pressures, reflecting reduced diaphragmatic endurance. Even mild metabolic acidosis heightens ventilatory drive through central chemoreceptor stimulation, increasing minute ventilation and respiratory muscle workload resulting in tachypnea, orthopnea, and apparent “myasthenic flares.” Recognizing this reversible metabolic factor can avert misinterpretation and optimize management. This abstract is funded by: none
Khan et al. (Fri,) studied this question.