Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
Fever, defined as temperature higher than 38.3C (100.9 F), is common in patients with head
 injuries and is associated with poor recovery after injury. The current standard of care is
 to use oral acetaminophen (Tylenol) followed by a body cooling device. This method can
 effectively reduce fever but results in a high rate of shivering. Shivering is stressful to
 the heart and can further worsen brain injury. Methods to combat shivering have been
 developed and are successful in limiting the stress in the majority of patients that use a
 body cooling device. However, the drugs used to control shivering are sedating and may also
 interfere with brain recovery.

 The purpose of this study is to assess whether ibuprofen given intravenously is more
 effective in combating fever than the current standard of care. Should results from this
 study demonstrate that ibuprofen infusion is effective, a larger study will be conducted to
 determine whether this aggressive fever control regimen leads to improved recovery after
 brain injury.
This is an open-label, investigator initiated single center, randomized, prospective study.
 Subjects meeting enrollment criteria will be randomly assigned 1:1 to one of two groups:

 1. Standard Care: Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed
 for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU,
 whichever comes first.

 2. Ibuprofen 400 mg/100 mL NS IV over 30 minutes, followed by a continuous infusion of 2000
 mg/500 mL NS at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from
 the Neuro ICU, whichever comes first.

 Patients/surrogates will be approached for consent and randomized upon admission. Therapy
 will only be initiated once a patient becomes febrile (>=38.3 C, 100.9 F). The use of
 temperature modulating devices will be permitted as per institutionally approved guidelines
 in those patients continuing to demonstrate a fever (T>38.3 C, 100.9 F) with either therapy.
Inclusion Criteria:

 -  18 years of age or older

 -  Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after
 admission.

 -  Intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) < 10

 -  Presence of intraventricular hemorrhage on initial brain computerized tomography (CT)
 scan

 Exclusion Criteria:

 -  Imminent death within 72 hours of admission.

 -  Plan for discharge from the Neuro intensive care unit (ICU) within 72 hours of
 admission.

 -  Diagnosis with sepsis (Systemic inflammatory response syndrome (SIRS) criteria plus
 the presence of known or suspected infection)

 -  Presence of coagulopathy (international normalized ratio (INR) > 1.7)

 -  Thrombocytopenia (platelet count < 100,000)

 -  History of gastrointestinal bleed

 -  Abnormal liver function tests (aspartate aminotransferase (AST)/alanine
 aminotransferase (ALT)/alkaline phosphatase (AP)/Gamma-glutamyl transferase (GGT) 2x
 normal)

 -  Hypersensitivity to ibuprofen

 -  Pregnancy as determined by urine beta human chorionic gonadotropin (hCG), or lactating
 postpartum women

 -  Renal impairment (Creatinine > 1.5 mg/dL)

 -  Measured body weight < 50 kg