Delayed Cerebral Ischaemia and Coagulation Alterations After Aneurysmal Subarachnoid Haemorrhage

Study Overview
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Brief Summary
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Despite the advances in neurosurgical and -radiological techniques and intensive care, the mortality and morbidity rates in SAH have not changed in recent years. There is still only a limited understanding of the mechanisms of secondary insults causing brain injury after SAH, also called delayed cerebral ischemia (DCI). In this study, the investigators are exploring the use of quantifiable biomarkers from blood and continuous EEG monitoring as tools for the diagnostics of DCI. Additionally, the investigators are looking into other clinical variables (eg. pain, heart function) as factors of DCI.

Detailed Description
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Subarachnoidal hemorrhage (SAH) is a cause of long-term disability and death. Annually about 1000 people in Finland suffer from SAH, their average age being under 50 years. SAH has a mortality rate of 12 % acutely and 40 % of patients die within a month from admission to hospital. In addition, 30 % of the surviving patients remain with neurological deficits. Most survivors of the primary insult suffer from a secondary injury during the first 2-3 weeks from the insult. Despite the advances in neurosurgical and -radiological techniques and intensive care, the mortality and morbidity rates in SAH have not changed in recent years. There is still only a limited understanding of the mechanisms of secondary insults causing brain injury after SAH, also called delayed cerebral ischemia (DCI). In this study, the investigators are exploring the use of quantifiable biomarkers from blood and continuous EEG monitoring as tools for the diagnostics of DCI. Additionally, the investigators are looking into other clinical variables (eg. pain, heart function) as factors of DCI.

Official Title
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Delayed Cerebral Ischaemia and Coagulation Alterations After Aneurysmal Subarachnoid Haemorrhage: a Clinical Observational Trial

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Device: ROTEM
* Procedure: EEG
* Procedure: bilateral compression ultrasound of the lower extremity veins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Admitted to the Tampere University Hospital ICU due to aneurysmal SAH Acute subarachnoid haemorrhage (confirmed by computed tomography, CT, AND confirmed origin either with computed angiography (CTA) or digital subtraction angiography (DSA) Definite or approximated time for the onset of symptoms and delay to ICU admission no more than 24 hours Expected treatment time at least 120 hours in the Tampere University Hospital Exclusion Criteria: Known pregnancy Any long-term anticoagulant or antithrombotic medication, except for low-dose aspirin (under 150 mg/day) Known active cancer or cirrhotic liver disease or end-stage renal disease requiring renal replacement therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aneurysmal SAH patients<br>Patients suffering from aneurysmal subarachnoid haemorrhage | Device: ROTEM<br>* ROTEM measurements 24,48, 72, 120, 192 and 288 hours from aneurysmal SAH<br>Procedure: EEG<br>* Continuous EEG-monitoring after aneurysm treatment until patient transferred to ward or up to 14 days after aneurysmal SAH<br>Procedure: bilateral compression ultrasound of the lower extremity veins<br>* to exclude asymptomatic deep venous thrombosis once over days 3 to 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of delayed cerebral ischemia | Incidence of DCI (delayed cerebral ischemia) | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal clot firmness of FIBTEM (FIBTEM-MCF) analysis | Maximal clot firmness of FIBTEM analysis (FIBTEM-MCF) using rotational thromboelastometry (ROTEM) assay | at 72 hours | 
| Incidence of deep venous thrombosis | Incidence of deep venous thrombosis | Within 3-7 days | 
| Other rotational thromboelastometry analysis | Maximal clot firmness of extrinsic (EXTEM) analysis (EXTEM-MCF) using rotational thromboelastometry | from 24 to 288 hours | 
| Assessment of neurological outcome | Description of the neurological outcome by using extended Glasgow Outcome Score Death Vegetative sate Lower severe disability Upper severe disability Lower moderate disability Upper moderate disability Lower good recovery Upper good recovery | 90 days | 
| Assessment of pain | Critical Care Pain Observation Tool values, from 0: no pain to 8: maximum pain | Up to 14 days | 
| Assessment of cardiopulmonary function by transthoracic echocardiography | Function of the left and right ventricle using scale 1. hyperkinetic,2. normal, 3. moderately impaired, 4. severely impaired | At admission and at at 24±4 hours | 
| Continuous electroencephalography | Continuous electroencephalography will be evaluated for signs that are potential surrogates of developing delayed cerebral ischemia (such as alpha-delta-ratio, focal slowing, epileptiform abnormalities, relative alpha variability) | From 48 hours to 14 days | 
| Neuroglial brain injury biomarkers | Peripheral blood biomarkers potentially reflecting neuroglial injury will be analysed with enzyme-linked immunosorbent assays | From 24 to 288 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia, Intensive Care Unit, Neurosurgery