(P70) A Strange Case of Refractory Shock: Valproic Acid Toxicity

Chief Complaint : A 64-year-old man is brought in by EMS from a group home after being found unresponsive, hypotensive throughout the prehospital course.

History of Present Illness : A 64-year-old man with past medical history of COPD, chronic knee pain is brought in by EMS from a group facility after being found unresponsive. EMS pre-notification to the ED notable for minimal collateral information available on scene, with field intubation due to severe respiratory depression. He was noted to be hypotensive and bradycardic prior to hospital arrival. Per EMS, he was found in his room in the group home by another occupant who could not identify the patient. He remained obtunded and was ultimately intubated by EMS, and was unable to provide further history.

Pertinent Physical Exam: Upon arrival to the ED, the patient’s vital signs were notable for a persistent hypotension of 70/37 after receiving fluids by EMS, alongside a bradycardia with a heart rate of 54. Rectal temperature was 91.7 F. He was intubated, on a mechanical ventilator, and fully obtunded with no response to painful stimuli. There were no visible signs of trauma, nor any visible wounds or obvious sources of infection. He remained profoundly hypotensive and bradycardic despite 3 liters of fluids, broad-spectrum antibiotic coverage, external warming, and the initiation of norepinephrine, vasopressin, and hydrocortisone.

Pertinent Laboratory Data: Laboratory results revealed a BUN of 30.4 and creatinine of 2.8, a lactic acidosis of 5.4, and an anion gap metabolic acidosis (pH 7.176, pCO2 33.5, HCO3 12.1, anion gap 18). Ammonia level was found to be elevated at 162.40. Urinalysis and urine drug screen were both negative. A COVID-19 swab was negative, and chest x-ray did not show signs of infectious process. CT head, cervical spine, chest, abdomen, and pelvis were negative. Ultimately, a valproic acid level was found to be elevated beyond the upper measurable threshold of 300, and serum acetaminophen level was elevated as well.

Case Discussion: This case represents an uncommon toxic overdose leading to refractory shock. With minimal collateral information, much of his initial management was focused on a presumed septic shock. Ultimately, the patient was found to have overdosed on valproic acid (VPA) as well as acetaminophen leading to his rapid deterioration. His ICU course was notable for the development of a nephrogenic diabetes insipidus, thought to have been a complication of his overdose, which eventually responded to thiazide and indomethacin treatment. He remained in the ICU for 40 days, before ultimately making a full neurologic recovery. Upon awakening, he confirmed the intentional overdose of prescribed medications in an attempt to end his life. After a prolonged admission and psychiatric evaluation, he was eventually discharged home with no lasting deficits.

VPA is an anti-epileptic drug used to treat seizures, acute mania, bipolar disorder, and migraine headaches. As VPA has fallen out of favor, VPA toxicity is an uncommon toxidrome which is difficult to distinguish from other pathologies. The present case demonstrated severe features of VPA and acetaminophen overdose - metabolic acidosis, coma, hypotension, respiratory depression, pancytopenia, and hyperammonemia. While hyperthermia is commonly seen in VPA toxicity, our patient was hypothermic to 91.7F. His presentation was also complicated by the co-ingestion of acetaminophen, which can both cause hepatic injury, hepatic encephalopathy, cerebral edema, and hypotension.

While uncommon, the emergency physician must maintain a broad differential when faced with complex presentations with minimal collateral information. Ultimately, VPA toxicity was considered several hours into his ED course, when a medication reconciliation revealed the recently prescribed medication. This case highlights the importance of parsing through all available information even when history is limited, and considering rare causes of refractory shock.

References and Acknowledgements (Optional): N/A