(127) Amphetamine salts in hepatic impairment: a case of spontaneous subdural hemorrhage

Abstract:

Background:

Valproic acid (VPA), which is hepatically metabolized, is contraindicated in patients with cirrhotic disease and is associated with hyperammonemia and delirium (Lewis 2017). Mixed amphetamine salts (MAS), also hepatically metabolized, has been linked to risk of stroke, both ischemic and hemorrhagic (Darke 2019).

Case:

A 53 year old woman with a history of alcoholic cirrhosis, ADHD, and bipolar I disorder presented to the ED for nausea, vomiting, and right upper quadrant pain. Imaging showed unchanged cirrhosis with no acute pathology. Her ammonia (reference range 20-70) and INR (reference range 0.9-1.1) were 51 and 1.5, respectively. She was admitted for liver failure and restarted on a previous psychiatric regimen: VPA 500mg QDAY and MAS 30mg TID. She had not taken these medications in at least six months.

On day four the patient became restless and labile. She was given lorazepam and psychiatry was consulted for delirium management. She was sedated on evaluation. Recommendations included discontinuing psychotropics and ordering a VPA level. Overnight she became anisocoric and unresponsive to sternal rub. Imaging showed a right subdural bleed with midline shift. No trauma was documented. She was intubated, underwent right craniotomy, and transferred to the ICU. Ammonia resulted at 144. An EEG showed epileptiform activity and she was transitioned to intravenous VPA. MAS was stopped. On day seven VPA was stopped. She remained unresponsive, her mentation did not improve, ammonia remained elevated (98-124), and she was discharged to LTACH.

Discussion:

There are limited reports of subdural bleeds associated with amphetamines. One additional report recognizes atraumatic subdural hemorrhage after initiating amphetamines (Nagele 2017). Suggested pathophysiology includes changes in catecholamine release affecting vascular integrity (Nagele 2017). Increased serum metabolites in hepatic impairment theoretically increase the risk of vasculitis (Schlatter 2009).

Conclusion:

In the case we present a patient with cirrhosis, delirium due to hyperammonemia, and development of spontaneous subdural hematoma after initiation of MAS, which contributes to limited literature on subdural hemorrhages in amphetamine-use.

References:

Darke S, Duflou J, Kaye S, Farrell M, Lappin J. Psychostimulant Use and Fatal Stroke in Young Adults. J Forensic Sci. 2019;64(5):1421-1426. doi:10.1111/1556-4029.14056

Lewis C, Tesar GE, Dale R. Valproate-Induced Hyperammonemic Encephalopathy in General Hospital Patients With One or More Psychiatric Disorders. Psychosomatics. 2017;58(4):415-420. doi:10.1016/j.psym.2017.02.003

Nagele EP, Ross A, Then RK, Kavi T. Interhemispheric subdural and subarachnoid haemorrhage in a patient with amphetamine-induced vasculitis. BMJ Case Reports. Published online December 7, 2017:bcr-2017-222918. doi:10.1136/bcr-2017-222918

Schlatter C, Egger SS, Tchambaz L, Krähenbühl S. Pharmacokinetic Changes of Psychotropic Drugs in Patients with Liver Disease. Drug Safety. 2009;32(7):561-578. doi:10.2165/00002018-200932070-00003

Presenting Author(s)

Zachary Bean, MD (he/him/his)

Resident Physician
University of Chicago Medical Center
Chicago, IL, United States

Co-Author(s)
DC

David B. Cao, n/a

Medical Student
University of Chicago
Chicago, Illinois, United States

Shivani Kumar, MD

Assistant Professor of Psychiatry
University of Chicago Medicine
Chicago, IL, United States

MT

Marie Tobin, MD, FACLP

Professor
Professor of Psychiatry, University of Chicago
Chicago, Illinois, United States