Cerebrospinal Fluid Hemoglobin to Monitor for Aneurysmal Subarachnoid Hemorrhage Related Secondary Brain Injury

Composite outcome consisting of angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI), or delayed ischemic neurological deficits (DIND).

The definition of aVSP comprises a narrowing of cerebral arteries based on a digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA). In the absence of an appropriate imaging procedure on the respective day, this will be noted as no imaging performed.

DCI is defined as new ischemia or new infarction on CT/perfusion CT or MRI. In the absence of an appropriate imaging procedure on the respective day, this will be noted as no imaging performed.

DIND is defined as a new focal neurological deficit or a decrease in Glasgow Coma Scale (GCS) of at least 2 points for at least 2 hours. In case the patient cannot be clinically assessed (e.g., sedation), this will be noted as non-assessable).

Whether the patient received preventive nimodipine treatment within the past 24 hours.

Whether a rescue therapy with pharmacological spasmolysis or balloon angioplasty was performed within the past 24 hours.

Whether rtPA was administered via the EVD to induce blood clot lysis within the past 24 hours.

A triple-H-therapy or elements of it (hypertension, hypervolemia or hemodilution) was induced within the past 24 hours.

A surgical decompression (e.g. decompressive hemicraniectomy) was performed within the past 24 hours.

Differentiated between infection (Clinical symptoms and signs of CSF infection and positive CSF culture), colonization (2 positive CSF cultures without clinical symptoms and signs) and contamination (1 positive CSF culture with consecutive culture being negative).

Evidence for a surgical site infection at the EVD/LD skin entrance site.

• Death
• Vegetative state (unresponsive and speechless)
• Lower severe disability (requires frequent help of someone to be around at home most of the time every day)
• Upper severe diasbility (can be left alone > 8h during the day, but unable to travel and/or go shopping without assistance)
• Lower moderate disability (unable to work or only in sheltered workshop)
• Upper moderate disability (reduced work capacity; resumes <50% of the pre-injury level of social and leisure activities)
• Lower good recovery (minor problems that affect daily life; resumes >50% of the pre-injury level of social and leisure activities)
• Upper good recovery (no current problems related to the brain injury that affect daily life)

0 No symptoms

• No significant disability. Able to carry out all usual activities, despite some symptoms.
• Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
• Moderate disability. Requires some helpt, but able to walk unassisted.
• Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
• Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
• Dead

CSF sampling: CSF sampling will be performed via EVD or LD, depending on the patient's access to the CSF space. The decision regarding the insertion of an EVD or LD is made independently of this study and according to the clinical standard of care. 2ml of CSF will be sampled on a daily basis at approximately the same time in the morning.

CSF centrifugation and storage: Immediately after sample collection, the CSF will be centrifuged at 1500 G for 15 minutes. The cell-free CSF supernatant will be stored at -80°C until analysis.

Spectrophotometric cerebrospinal fluid hemoglobin (CSF-Hb) measurements: Absorption spectra in the visual range between 350 and 650 nm of all CSF samples will be measured. Quantification of oxyhemoglobin in CSF (CSF-Hb) will be performed using spectral deconvolution.