Delayed Cerebral Ischemia, Delayed Ischemic Neurological Deficit, Subarachnoid Hemorrhage, Aneurysmal, Vasospasm
Conditions
Keywords
Cerebrospinal Fluid, Hemoglobins
Brief summary
The primary objective of this study is to evaluate the association between hemoglobin levels in the cerebrospinal fluid (CSF-Hb) and the occurrence of secondary brain injury in patients after aneurysmal subarachnoid hemorrhage (SAH-SBI) during the first 14 days after bleeding.
Detailed description
This is an international multicentre observational study to validate cerebrospinal fluid hemoglobin (CSF-Hb) as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI). It is hypothesized that there is an association between the concentration of CSF-Hb and the occurrence of SAH-SBI during the first 14 days after the bleeding (post-SAH). The primary objective of this study is to evaluate the association between ventricular CSF-Hb and SAH-SBI during the first 14 days post-SAH. The secondary objectives are to investigate: * the association between ventricular CSF-Hb and angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI) and delayed ischemic neurological deficits (DIND) during the first 14 days post-SAH, * the accuracy of ventricular CSF-Hb to monitor for aVSP, DCI and DIND during the first 14 days post-SAH, * the association between lumbar CSF-Hb and SAH-SBI, aVSP, DCI and DIND during the first 14 days post-SAH, * the accuracy of lumbar CSF-Hb to monitor for aVSP, DCI and DIND during the first 14 days post-SAH, * the association between baseline measures and CSF-Hb (ventricular and lumbar during the first 14 days post-SAH), * the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and co-interventions/complications, * the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and chronic hydrocephalus at 12 weeks follow-up, * the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and functional outcome at 12 weeks follow-up, * exploratory CSF proteome/metabolome analyses to assess Hb toxicity, inflammation, neuronal, or vascular damage.
Interventions
None listed
Sponsors
University of Zurich
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age ≥ 18 years * hospital admission due to an aneurysmal subarachnoid hemorrhage (diagnosis radiologically confirmed)
Exclusion criteria
* non-aneurysmal subarachnoid hemorrhage (eg. trauma, perimesencephalic subarachnoid hemorrhage). * participation in another study with CSF sampling or an interventional medical product within the 30 days preceding and during the present study. * previous enrolment into the current study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI) | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | Composite outcome consisting of angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI), or delayed ischemic neurological deficits (DIND). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Angiographic vasospasms (aVSP) | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 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. |
| Delayed cerebral ischemia (DCI) | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 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. |
| Delayed ischemic neurologic deficits (DIND) | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 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). |
| Co-intervention 1: Nimodipine treatment | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | Whether the patient received preventive nimodipine treatment within the past 24 hours. |
| Co-intervention 2: Spasmolysis | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | Whether a rescue therapy with pharmacological spasmolysis or balloon angioplasty was performed within the past 24 hours. |
| Co-intervention 3: Intraventricular administration of rtPA (ICV-rtPA) | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | Whether rtPA was administered via the EVD to induce blood clot lysis within the past 24 hours. |
| Co-intervention 5: Decompression | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | A surgical decompression (e.g. decompressive hemicraniectomy) was performed within the past 24 hours. |
| Complication 1: CSF infection | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 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). |
| Complication 2: Surgical site infection | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | Evidence for a surgical site infection at the EVD/LD skin entrance site. |
| Chronic hydrocephalus | 12 weeks follow-up visit | — |
| Functional status 1: Glasgow Outcome Scale Extended [1-8] | 12 weeks follow-up visit | 1. Death 2. Vegetative state (unresponsive and speechless) 3. Lower severe disability (requires frequent help of someone to be around at home most of the time every day) 4. Upper severe diasbility (can be left alone \> 8h during the day, but unable to travel and/or go shopping without assistance) 5. Lower moderate disability (unable to work or only in sheltered workshop) 6. Upper moderate disability (reduced work capacity; resumes \<50% of the pre-injury level of social and leisure activities) 7. Lower good recovery (minor problems that affect daily life; resumes \>50% of the pre-injury level of social and leisure activities) 8. Upper good recovery (no current problems related to the brain injury that affect daily life) |
| Functional status 2: modified Rankin Scale [0-6] | 12 weeks follow-up visit | 0 No symptoms 1. No significant disability. Able to carry out all usual activities, despite some symptoms. 2. Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. Moderate disability. Requires some helpt, but able to walk unassisted. 4. Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. Dead |
| Co-intervention 4: Triple-H-therapy | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | A triple-H-therapy or elements of it (hypertension, hypervolemia or hemodilution) was induced within the past 24 hours. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cerebrospinal fluid hemoglobin | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 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. |
Countries
Austria, Germany, Switzerland
Outcome results
None listed