BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial with a sequential parallel comparison design (SPCD) of bilateral pterygopalatine fossa (PPF) injections with 20mg ropivacaine + 4mg dexamethasone (active, PPF-block) compared to saline (placebo) for headache in survivors of aneurysmal subarachnoid hemorrhage (SAH), while monitoring intracranial arterial mean flow velocities with transcranial Doppler (TCD) peri-intervention (intervention = PPF-injections: active or placebo)

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Provision of signed and dated ICF by participant or a legally authorized representative (LAR)

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged ≥18 and ≤ 85 years

4. Admitted with a primary diagnosis of spontaneous, non-traumatic, SAH within 72 hours of ictus hemorrhage

5. Disease-specific inclusion criteria:

   1. Spontaneous, non-traumatic SAH
   2. Subarachnoid pattern of hemorrhage warranting diagnostic DSA due to involvement of at least one of the following regions: quadrigeminal plate, prepontine cistern, perimesencephalic cistern, Sylvian fissure, or surrounding Circle of Willis
   3. Modified Fisher grade 1-4 (on presentation imaging)
   4. Hunt and Hess 1-3 or World Federation of Neurosurgeons grade 1-4 (on screening, included only if also fulfilling Glasgow Coma Scale verbal subscore ≥4)
   5. Minimum Glasgow Coma Scale verbal subscore of 4 (on screening)

6. Able to verbalize pain scale scores according to 11-point numeric pain scale

   In order to be enrolled and undergo randomization in this study, an individual must meet all of the additional criteria:

7. Stabilization period criteria:

   1. A minimum of 4 hours from DSA with clipping or coiling procedure (whenever applicable)
   2. Successful treatment of culprit vascular lesion (i.e., ≥90% obliteration of aneurysm), when applicable

8. Requiring a minimum of 15mg OME prn for headache analgesia during any 24-hour period during eligibility period

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Premorbid conditions:

   1. Pre-existing neurologic, psychiatric, or other condition that would confound neurologic assessment or would make difficult/impossible to accurately assess neurologic and/or functional outcome
   2. Pre-existing diffuse flow-limiting narrowing of arteries in the Circle of Willis, regardless of etiology (e.g., atherosclerosis, vasculitis, Moya-Moya syndrome)
   3. Prior use of opioid or barbiturate analgesics for at least two-thirds of the days in previous month, regardless of indication
   4. Diagnosis of substance use disorder in the previous year
   5. Infected or wounded skin, or a skin lesion at the site of puncture for PPF- injection

2. Uncorrected coagulopathy

   1. Platelet count < 50,000/μL, International Normalized Ratio (INR) > 1.7
   2. Requiring use of systemic anticoagulation and antiplatelet therapy (except for aspirin monotherapy).

3. SAH-specific:

   1. Head trauma as etiology of SAH
   2. Infection as cause for aneurysm or SAH (i.e., mycotic aneurysms)
   3. Inability to successfully treat culprit vascular lesion
   4. Diffuse vasospasm on pre-enrollment diagnostic CTA or DSA. Vasospasm is defined as moderate-to-severe arterial narrowing on DSA or CTA not attributable to atherosclerosis, catheter-induced spasm, or vessel hypoplasia, as determined by a neuroradiologist or neurointerventionalist

4. Standard pain regimen conditions

   1. Elevation of hepatic enzymes prohibiting use of scheduled APAP (i.e., AST or ALT > 3x upper limit level)
   2. Chronic liver condition with absolute contra-indication for APAP (even at lower maximum daily doses)

5. Participation in a concurrent investigational/interventional study (observational studies allowed)

6. Known to be pregnant, or with a positive pregnancy test

7. Allergy or intolerance to the medications used in the PPF-block (i.e., ropivacaine, dexamethasone) or standard pain regimen (APAP)

8. Vulnerable populations such as prisoners and inmates (abiding GCP per the study IRB)

9. Unable to receive first PPF-injection within 96 hours of ictus hemorrhage