Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage
NCT ID: NCT03987139
Last Updated: 2021-10-29
Study Results
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Basic Information
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UNKNOWN
NA
45 participants
INTERVENTIONAL
2019-06-15
2022-03-01
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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NA
SEQUENTIAL
1. Induced hypertension; as well
2. (Only in mechanically ventilated patients) either
1. Mild hyper- and hypocapnia or
2. Mild hyper- and hypoxia.
In session 2 (hyper- / hypoxia or hyper- / hypocapnia), patients are randomized to order the interventions.
BASIC_SCIENCE
NONE
Study Groups
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All patients
Patients included in the study.
Hypertension
Hypertension is induced by an infusion of noradrenaline within acceptable limits Baseline recording (10 minutes) is performed. MAP gradually increases in steps of 5-10 mmHg during ongoing TCD. When the desired maximum MAP is reached, measurement is made at steady state (10 minutes).
Noradrenaline infusion is stopped. When MAP is stabilized, new baseline is measured for 10 minutes.
Hyper- and hypoxia
The mechanical ventilator is adjusted to mild hypoxia, normoxia and mild hyperoxia. Measurements are made for 10 minutes at normoxia and after steady state is reached, respectively. hyperoxia and hypoxia. Oxygenation is controlled by arterial blood gas before and during steady state.
Hyper- and hypocapnia
The mechanical ventilator is adjusted to a delta PaCO2 on the ventilator for both hypocapnia and hypercapnia. Measurements are made for 10 minutes at normocapnia and after steady state is reached, respectively. hyper- and hypocapnia.
Interventions
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Hypertension
Hypertension is induced by an infusion of noradrenaline within acceptable limits Baseline recording (10 minutes) is performed. MAP gradually increases in steps of 5-10 mmHg during ongoing TCD. When the desired maximum MAP is reached, measurement is made at steady state (10 minutes).
Noradrenaline infusion is stopped. When MAP is stabilized, new baseline is measured for 10 minutes.
Hyper- and hypoxia
The mechanical ventilator is adjusted to mild hypoxia, normoxia and mild hyperoxia. Measurements are made for 10 minutes at normoxia and after steady state is reached, respectively. hyperoxia and hypoxia. Oxygenation is controlled by arterial blood gas before and during steady state.
Hyper- and hypocapnia
The mechanical ventilator is adjusted to a delta PaCO2 on the ventilator for both hypocapnia and hypercapnia. Measurements are made for 10 minutes at normocapnia and after steady state is reached, respectively. hyper- and hypocapnia.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* 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.
18 Years
ALL
Yes
Sponsors
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Rigshospitalet, Denmark
OTHER
Responsible Party
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Markus Harboe Olsen
Research Fellow
Locations
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Department of Neuroanaesthesiology
Copenhagen, Capital Region, Denmark
Countries
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References
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Olsen MH, Orre M, Leisner ACW, Rasmussen R, Bache S, Welling KL, Eskesen V, Moller K. Delayed cerebral ischaemia in patients with aneurysmal subarachnoid haemorrhage: Functional outcome and long-term mortality. Acta Anaesthesiol Scand. 2019 Oct;63(9):1191-1199. doi: 10.1111/aas.13412. Epub 2019 Jun 7.
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Dankbaar JW, Slooter AJ, Rinkel GJ, Schaaf IC. Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review. Crit Care. 2010;14(1):R23. doi: 10.1186/cc8886. Epub 2010 Feb 22.
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Budohoski KP, Czosnyka M, Kirkpatrick PJ, Reinhard M, Varsos GV, Kasprowicz M, Zabek M, Pickard JD, Smielewski P. Bilateral failure of cerebral autoregulation is related to unfavorable outcome after subarachnoid hemorrhage. Neurocrit Care. 2015 Feb;22(1):65-73. doi: 10.1007/s12028-014-0032-6.
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Ramakrishna R, Stiefel M, Udoetuk J, Spiotta A, Levine JM, Kofke WA, Zager E, Yang W, Leroux P. Brain oxygen tension and outcome in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2008 Dec;109(6):1075-82. doi: 10.3171/JNS.2008.109.12.1075.
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Olsen MH, Capion T, Riberholt CG, Bache S, Ebdrup SR, Rasmussen R, Mathiesen T, Berg RMG, Moller K. Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage. Acta Anaesthesiol Scand. 2023 Sep;67(8):1054-1060. doi: 10.1111/aas.14277. Epub 2023 May 16.
Other Identifiers
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H-19017185
Identifier Type: -
Identifier Source: org_study_id