Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage

Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage

The purpose is, in patients with aneurysmal subarachnoid haemorrhage in the early phase after ictus, to examine the following:

1. The effect of spontaneous and induced changes on the brain's static and dynamic autoregulation calculated by transcranial Doppler (TCD), ICP and MAP (primary purposes) and ICP and PbtO2;
2. The effect of mild hyper- and hypocapnia as well as of mild hyper- and hypoxia on the brain's static and dynamic autoregulation, ICP and PbtO2;
3. The relationship between brain autoregulation, mild hyper- and hypocapnia, as well as of mild hyper- and hypoxia and metabolism in microdialysate on the one hand and the occurrence of DCI during hospitalization and poor neurological outcome one year after ictus on the other.

Spontaneous aneurysm subarachnoid hemorrhage (SAH) occurs annually in approximately 400 people in Denmark. SAH is most commonly seen in younger (median age 56 years) and women (71%), have a high mortality (21-44%) and result in a poor neurological outcome in about 50% of patients. Due to the relatively young patient population and high mortality and morbidity, SAH in the population causes the same number of lost working years as blood clots in the brain.

The occurrence of complications like hydrocephalus and re-bleeding can be minimized by rapid external ventricular drainage and aneurysm closure, and so-called delayed cerebral ischaemia (DCI) is currently considered to be the most frequent serious complication of SAH. DCI occurs in 20-30% of patients, most often within the first 14 days, is characterized by a reduction in consciousness or focal neurological deficit lasting at least one hour without any other underlying cause and is associated with a significantly increased risk of a poor outcome. The cause and treatment of DCI is controversial, and the previous hypothesis of vasospasm as the sole contributor is currently supplemented by a broader focus on several other mechanisms, including the brain's blood supply and its regulation.

The brain's blood supply (CBF) is kept relatively constant in healthy by changing cardiac diameter and thus the cerebrovascular resistance (CVR) during changes in brain perfusion pressure (CPP, measured as mean arterial pressure (MAP) minus intracranial pressure (ICP)) within certain limits. This mechanism is known as cerebral autoregulation. Outside these limits, respectively. decreases and increases CBF, with the consequent risk of hypoperfusion/ischemia and hyperperfusion/vasogenic edema with prolonged changes.

Weakened autoregulation, i.e. that CBF varies passively with CPP also within the normal autoregulation limits, is described in e.g. traumatic brain injury (TBI), ischemic stroke, acute liver failure and meningitis, with complete or partial restoration of autoregulation by hyperventilation (mild hypocapnia). SAH also describes impaired autoregulation with varying association with disease severity, DCI and outcome. It is not known whether mild hypocapnia restores autoregulation in patients with SAH, whereas animal experimental studies suggest this.

Reduced intracerebral oxygenation (PbtO2) is associated with a worse outcome after SAH. Cerebral microdialysis measures the concentration of certain metabolites in the brain and can provide an insight into whether metabolic activity is affected by oxygen deficiency, and so-called anaerobic combustion occurs. Microdialysis measurements with elevated lactate concentration, which is a metabolic product, among other things. Anaerobic combustion appears to occur prior to clinical signs of DCI, as well as during the DCI episodes, decreasing PbtO2. It is possible that these findings could be due to a condition of impaired autoregulation and too low perfusion pressure to meet brain metabolic needs, but this has not previously been elucidated. It is also unknown if it is possible to improve brain metabolism by increasing the brain's perfusion pressure.

The purpose of this study is therefore to investigate brain autoregulation in patients with SAH.

Inclusion Criteria, patients:

• Admittance to neurointensive care unit, Rigshospitalet
• Age ≥ 18 years old
• Aneurysmal subarachnoid haemorrhage
• Clinical indication for placement of an external ventricular drain
• Measurements can be done within 3 days of ictus
• Closest relatives understand written and spoken danish

Exclusion Criteria, patients:

• No aneurysm identified
• Conservative og failed treatment of aneurysm
• Pupils dilated and do not react to light
• Incarceration before inclusion
• Expected death within 48 hours
• Acute or chronic diseases associated with impaired autoregulation
• Severe chronic lung failure with a PaCO2 > 6.5 kPa or PaO2 < 8 kPa.

Inclusion Criteria, healthy subjects:

• Age ≥ 18 years old;
• Understands written and spoken danish
• Oral and written consent
• No medication expect hay fever medications
• Alcohol consumption within the limits from the danish health care board
• Healthy without previous or current cerebrovascular diseases
• Insonation is possible from the middle cerebral artery