Clinical, Pharmacological and Molecular Effects of IV and Oral Acetaminophen in Adults With aSAH

In individuals diagnosed with subarachnoid hemorrhage (SAH), fevers have been shown to have
detrimental micro and macroscopic effects on the brain that can ultimately cause secondary
brain injury. The anti-pyretic effects of oral acetaminophen have been studied in critically
ill patients but no study has been able to compare these effects to the IV form of
acetaminophen also known as OFIRMEV. The investigators wish to explore the notion that IV
acetaminophen will be more effective than enteral acetaminophen in reducing the incidence of
non-infectious fevers in critically ill patients. In addition, the investigators propose to
study the levels of inflammatory cytokines after administration of IV or enteral
acetaminophen, as well as, determine the incidence of vasospasm in SAH patients treated with
IV acetaminophen. Currently, external ventricular drain (EVD) placement is the "standard of
care" in patients who present with SAH and altered mental status/coma. The presence of an EVD
allows for continuous sampling and removal of cerebral spinal fluid (CSF) as necessary to
alleviate dangerous elevations in intracranial pressure. This clinical scenario allows for a
unique, continuous outlet to access the CSF, without placing patients at risk, and without
further invasive procedures (i.e. repeated spinal taps). These samples of CSF can be assayed
for levels of acetaminophen, as well as inflammatory markers of fever which include
interleukin-1 (IL-1), interleukin-6 (IL-6), and thromboxane-2 (TXA-2), in patients selected
to be given enteral or IV acetaminophen.

Inclusion Criteria:

- Diagnosis of subarachnoid hemorrhage (must be confirmed by CT, CTA, lumbar puncture,
or MRI).

- Fisher Grade between 1-3 (subarachnoid blood without signs of intraventricular
hemorrhage or parenchymal extension).

- Placement of an external ventricular drain.

- Adults aged 18-100 years.

Exclusion Criteria:

- Anyone under the age of 18 or over the age of 100.

- Adult patients with subarachnoid hemorrhage with interventricular hemorrhage or
parenchymal extension (Fisher Grade 4).

- Contraindication to acetaminophen such as a known hypersensitivity, severe hepatic
impairment, or severe active liver disease.

- Severe renal impairment (creatinine clearance ≤ 30 mL/min).