Abstract: TH-PO0420
Lactic Acidosis from Antipsychotic Toxicity: A Rare Cause of Mitochondrial Dysfunction
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Moore, Kareen, Yale University, New Haven, Connecticut, United States
- Albert, David A., Berkshire Medical Center, Pittsfield, Massachusetts, United States
- Alsmaan, Hafez, Berkshire Medical Center, Pittsfield, Massachusetts, United States
Introduction
Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients and a marker of illness severity. While commonly associated with hypoperfusion and impaired tissue oxygenation, mitochondrial dysfunction caused by certain medications has emerged as a potential mechanism of lactate overproduction.
Case Description
A 46-year-old male with schizophrenia presented after being found unresponsive at home, surrounded by empty Clozapine and Risperidone bottles. On arrival, he was comatose, hypotensive and hypoxic. Laboratory workup revealed leukocytosis, metabolic acidosis, and markedly elevated lactate of 10.4 mmol/L. Other labs, including electrolytes, creatinine, serum osmolality, liver enzymes, troponin, and β-hydroxybutyrate, were within normal limits. Toxicology screening, including toxic alcohols, was negative. Serum Clozapine and Norclozapine levels were elevated at >4000 ng/mL and 1249 ng/mL, respectively. Neuroimaging and chest CT angiogram were unremarkable. Echocardiogram showed no abnormalities. The patient was intubated, sedated with Fentanyl and Midazolam, and started on Norepinephrine and Vasopressin for hemodynamic support. Broad-spectrum antibiotics were initiated empirically. Within 24 hours, vasopressors were discontinued, the infectious workup returned negative, antibiotics were stopped, and lactate level normalized. He subsequently developed oliguric acute kidney injury due to acute tubular injury, with creatinine rising to 2.6 mg/dL, hyperkalemia, and recurrent anion gap metabolic acidosis with lactic acid reaching 15.2 mmol/L. Acidosis persisted despite sodium bicarbonate infusion and intravenous thiamine, necessitating hemodialysis. Following multiple sessions, lactate level normalized and the acidosis resolved. He was extubated within several days and transitioned to psychiatric care.
Discussion
Mitochondrial dysfunction from antipsychotics use was demonstrated in limited number of studies. Antipsychotics may impair oxidative phosphorylation by downregulating electron transport chain components, leading to increased lactate generation. Additionally, genetic predisposition including polymorphisms in mitochondrial function observed in schizophrenic patients may exacerbate this effect. Awareness of this potential mechanism is essential, as early recognition and treatment can significantly influence clinical outcomes.