Nitric Oxide Consumption as a Predictor of Vasospasm in Subarachnoid Hemorrhage

Nitric Oxide Consumption as a Predictor of Vasospasm in Subarachnoid Hemorrhage (SAH): a Prospective Observational Study

The goal of this observational study is to understand if angiographic cerebral vasospasm (CV) can be predicted by levels of nitric oxide (NO) consumption in patients with aneurysmal subarachnoid hemorrhage (SAH). To reach this goal, the investigators will compare NO consumption levels in SAH and non-SAH patients. NO consumption levels will be analyzed from samples of participants' cerebral spinal fluid (CSF).

Study Overview

• Status: Recruiting
• Conditions: Aneurysmal Subarachnoid Hemorrhage; Cerebral Vasospasm

Detailed Description

After enrollment, the investigators will collect patients' demographics and most relevant clinical characteristics of the patients.

For patients with SAH, the investigators will collect an-1 ml aliquot of CSF from the drainage circuit daily, (using a sterile procedure that involves a valve of the closed system circuit located distally to the patient, before the collection container), for a period of 15 days following SAH. The samples will be stored at -80 degrees.

The investigators will perform daily Transcranial Doppler (TCD) monitoring to assess whether the patients have cerebral vasospasm. In case of suspected vasospasm, and in all comatose patients after 4 days from the bleeding, a CT angiography will be performed to define the angiographic CV.

For the control group, discarded 1 ml-aliquot of CSF will be collected at the time of needle insertion for spinal anesthesia.

At the end of the protocol, the study population will be divided in 3 groups:

• patients with SAH and vasospasm
• patients with SAH and no vasospasm
• control group

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Lorenzo Berra, MD; Phone Number: 617-726-3030; Email: lberra@mgh.harvard.edu

Study Locations

• Italy
  • Rome, Italy, 00136
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli
    • Contact: Valentina Giammatteo, MD
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Lorenzo Berra, MD; Phone Number: 617-726-3030; Email: lberra@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The cohort of patients with SAH will be selected from patients in the Intensive Care Unit at Gemelli Hospital in Rome, Italy, within 24 hours after the onset of the hemorrhage and with an external ventricular drain. The control group will be patients at Massachusetts General Hospital who are undergoing spinal anesthesia in the operating room, or those with a spinal drain for major vascular surgery.

Description

Inclusion Criteria:

• Adult
• patient with SAH and with an external ventricular drainage (EVD) placed within 24 hours after the onset of the hemorrhage

Exclusion Criteria:

• pregnancy
• pre-existing neurological comorbidities
• coagulation disorders
• anemia
• absence of a good cranial window to perform Transcranial Doppler (TDC)
• presence of >50% stenosis of carotid arteries confirmed by doppler ultrasound
• Technical problems on EVD that prevent CSF withdrawals

For the control group, we will invite to participate patients without neurological comorbidities undergoing spinal anesthesia in the operating room or with a spinal drain for major vascular surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Aneurysmal subarachnoid hemorrhage; Patients admitted to the Intensive Care Unit following spontaneous aneurysmal subarachnoid hemorrhage
Control; Patients without neurological comorbidities undergoing spinal anesthesia in the operating room

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitric oxide consumption	Measurement taken from cerebrospinal fluid using nitric oxide consumption analyzer	Daily for 15 days following aneurysmal subarachnoid hemorrhage; for controls, once at initiation of spinal anesthesia
Occurrence of cerebral vasospasm in patients with subarachnoid hemorrhage	Transcranial Doppler monitoring will provide peak systolic velocities (PSVs) at the middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries. Suspected vasospasm will be defined as a mean flow velocity >120 cm/s and a Lindegaard ratio (LR) ≥3. The LR will be obtained by dividing the mean flow velocities of the MCA by those of ipsilateral extracranial internal carotid artery. In case of suspected vasospasm, and in all comatose patients after 4 days from the bleeding, a CT angiography will be performed to define the angiographic CV.	Daily for 15 days following aneurysmal subarachnoid hemorrhage

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitric oxide metabolite levels	Measurement taken from cerebrospinal fluid	Daily for 15 days following aneurysmal subarachnoid hemorrhage; for controls, once at initiation of spinal anesthesia
Free hemoglobin	Measurement taken from cerebrospinal fluid	Daily for 15 days following aneurysmal subarachnoid hemorrhage; for controls, once at initiation of spinal anesthesia

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Lorenzo Berra, MD, Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 22, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nitric Oxide Consumption
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Subarachnoid Hemorrhage; Vasospasm, Intracranial
• Other Study ID Numbers: 2023P003051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No