Carbonic Anhydrase Antagonism in Subarachnoid Hemorrhage

Subarachnoid Hemorrhage (SAH) can occur commonly in the setting of trauma or brain aneurysm. SAH accounts for 10% of all the strokes. Aneurysmal SAH accounts for 80 % of cases of non-traumatic cases of SAH, 6-8% of all strokes and 22-25% of all cerebrovascular deaths. Mortality can be 50% in the first few years of aneurysmal SAH rupture, 15% are severely disabled post SAH and only 20-35% having a moderate to good recovery it has gained lot of attention and pre-clinical and clinical trials of various agents have been tried to prevent poor outcome. The United States epidemiology data reveals the fact that 1% to 5% of adults have unruptured brain aneurysm and 30,000 people suffer from aneurysm rupture annually translating to brain aneurysm rupture every 18 minutes.

Vasospasm is the most common SAH complication post 24 hours. It is the segmental or diffuse narrowing of the vessels especially the large vessels. Fifty percent of those patients who develop clinical vasospasm, progress to infarction and 15-20% will advance to disabling stroke or die of cerebral ischemia. The present treatment modalities are insufficient to prevent vasospasm. So, we need new treatment modalities to decrease the mortality and morbidity in SAH patients.

The investigators hypothesize that Acetazolamide administration can prevent development of vasospasm after aneurysmal SAH.

If the subject decides to take part in this study, they will receive acetazolamide with standard of care or standard of care only for four days. This means:

The subject will be given acetazolamide tablet orally with standard care for subarachnoid hemorrhage or standard of care only, for a maximum of 4 days. If the subject cannot take medication orally then the investigators will put a tube through the nose to stomach or small intestine. Being part of the study does not exclude the subject from receiving the standard therapy. The subject will be given the current standard of care therapy irrespective of being in the study or not. The investigators will review the subject's medical records and collect information from standard of care procedures that would have been done even if the subject were not enrolled in this study. This information will include, but will not be limited to, the subject's imaging data, sub arachnoid hemorrhage assessments and medical history. The subject's Hunt and Hess scale score and (World federation of neurologic surgeons) WFNS scale score will also be collected. Hunt and Hess and WFNS scale are used to assess the level of damage to neurologic functions of a person caused by sub arachnoid hemorrhage.

The subject will be asked to come for the follow-up at 3 months after the discharge from the hospital. The following data will be obtained from each subject at 3-month follow-up.

1. Modified Rankin Scale (m-RS) scores
2. Glasgow Outcome Scale (GOS) scores

Eligibility Criteria:
Inclusion Criteria:

1. All aneurysmal SAH patients with clinical and or radiological diagnosis.
2. Subjects with age ≥18 years and ≤80 years at the time of screening.
3. The subject or his/ her legal representative is willing to undergo informed consent process prior to enrollment into this study.
4. World Federation of Neurosurgeons scale score ≤ 2
5. Hunt and Hess Stroke scale score ≤ 2
6. Mean velocities of \< 200 cm/s in at least 1 vascular axis of the circle of Willis
7. Patients admitted within 4 days of symptom onset.

Exclusion Criteria:

1. Subject with age \< 18 years and \>80 years at the time of screening.
2. Time of symptom onset cannot be determined.
3. Subject who is pregnant or lactating.
4. Subjects who have hypersensitivity to acetazolamide, sulfa drugs, or any component of the formulation.
5. Mean velocities of ≥ 200 cm/s in at least 1 vascular axis of the circle of Willis
6. Brain CT or MRI show acute infarction
7. Any acute focal neurological deficit (including any one of these) speech problems, loss of vision, facial or extremity weakness.
8. Hunt and Hess Stroke scale scores \> 2
9. World Federation of Neurosurgeons scale scores \> 2
10. Subjects with hepatic disease or insufficiency or cirrhosis.
11. Subjects with severe renal disease or dysfunction.
12. Subjects who have decreased sodium and/or potassium levels; hyperchloremic acidosis.
13. Subjects who have adrenocortical insufficiency.
14. The subject or legal representative is unable to provide informed consent.
15. The subject is medically unstable to participate in the trial as determined by the principal investigator.
16. The subject has any end stage medical condition as determined by the principal investigator.