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Pressure autoregulation of cerebral blood flow in traumatic brain injury and aneurysmal subarachnoid hemorrhage
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The ability of the brain to keep a stable and adequate cerebral blood flow (CBF) independently of fluctuations in systemic blood pressure is referred to as cerebral pressure autoregulation (CPA). When the brain is injured by trauma or hemorrhage, this ability may be impaired, leaving the brain vulnerable to events of high or low blood pressure. The aims of this thesis were to study CPA in patients with severe traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH), the relation between CPA and other physiological parameters, and the influence of CPA on outcome. Four retrospective studies are included in the thesis. All patients were treated at the neurointensive care unit, Uppsala University hospital.

In paper I, 58 TBI patients were studied. In patients with impaired CPA, cerebral perfusion pressure between 50-60 mm Hg was associated with favorable outcome while CPP > 70 and >80 mm Hg was associated with unfavorable outcome. In patients with intact CPA there was no association between CPP and outcome.

In paper II, 107 TBI patients were studied. High CPP was associated with unfavorable outcome in patients with focal injuries. In patients with diffuse injury and impaired CPA, CPP > 70 mm Hg was associated with favorable outcome.

In paper III, 47 SAH patients were studied. CBF was measured bedside with Xenon-enhance CT (Xe-CT). Patients with impaired CPA had lower CBF, both in the early (day 0-3) and late (day 4-14) acute phase of the disease.

In paper IV, 64 SAH patients were studied. Optimal CPP (CPPopt) was calculated automatically as the level of CPP where CPA works best for the patient, i.e., where PRx is lowest. Patients with actual CPP below their calculated optimum had higher amounts of low-flow regions (CBF < 10 ml/100g/min).

The findings in this thesis emphasize the importance of taking CPA into account in the management of TBI and SAH patients, and suggest that treatment should be individualized depending on status of autoregulation. PRx and CPPopt may be used bedside to guide management according to status of autoregulation. In the future CPA-guided management should be tested in prospective studies

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1257
Keyword [en]
cerebral blood flow, autoregulation, traumatic brain injury, subarachnoid hemorrhage
National Category
Neurosciences
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:uu:diva-294190ISBN: 978-91-554-9703-3OAI: oai:DiVA.org:uu-294190DiVA: diva2:974538
Public defence
2016-11-17, Enghoffsalen, Ing 50 bv, Akademiska sjukhuset, 75185, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-10-27 Created: 2016-05-18 Last updated: 2016-11-02
List of papers
1. Favorable Outcome in Traumatic Brain Injury Patients With Impaired Cerebral Pressure Autoregulation When Treated at Low Cerebral Perfusion Pressure Levels
Open this publication in new window or tab >>Favorable Outcome in Traumatic Brain Injury Patients With Impaired Cerebral Pressure Autoregulation When Treated at Low Cerebral Perfusion Pressure Levels
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2011 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, no 3, 714-721 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Cerebral pressure autoregulation (CPA) is defined as the ability of the brain vasculature to maintain a constant blood flow over a range of different systemic blood pressures by means of contraction and dilatation. OBJECTIVE: To study CPA in relation to physiological parameters, treatment, and outcome in a series of traumatic brain injury patients. METHODS: In this prospective observational study, 44 male and 14 female patients (age, 15-72 years; mean, 38.7 years; Glasgow Coma Scale score, 4-13; median, 7) were analyzed. Patients were divided into groups on the basis of status of CPA (more pressure active vs more pressure passive) and level of cerebral perfusion pressure (CPP; low vs high CPP). The proportions of favorable outcome in the groups were assessed. Differences in physiological variables in the different groups were analyzed. RESULTS: Patients with more impaired CPA treated at CPP levels below median had a significantly higher proportion of favorable outcome compared with patients with more impaired CPA treated at CPP levels above median. No significant difference in outcome was seen between patients with more intact CPA when divided by level of CPP. In patients with more impaired CPA, CPP < 50 mm Hg and CPP < 60 mm Hg were associated with favorable outcome, whereas CPP > 70 mm Hg and CPP > 80 mm Hg were associated with unfavorable outcome. In patients with more intact CPA, no difference in physiological variables was seen between patients with favorable and unfavorable outcomes. CONCLUSION: Our results support that in traumatic brain injury patients with impaired CPA, CPP should not be elevated.

Keyword
Cerebral perfusion pressure, Cerebrovascular pressure autoregulation, Head injury, Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-148495 (URN)10.1227/NEU.0b013e3182077313 (DOI)000287242300043 ()21311298 (PubMedID)
Available from: 2011-03-07 Created: 2011-03-07 Last updated: 2016-09-26Bibliographically approved
2. Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?
Open this publication in new window or tab >>Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?
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2014 (English)In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 2, 259-265 p.Article in journal (Refereed) Published
Abstract [en]

The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes. 107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to "diffuse" (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or "focal" (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 x 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP. Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx > 0.1), CPP > 70 mmHg was associated with better outcome (p = 0.03). TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.

Keyword
Cerebral perfusion pressure, Cerebrovascular pressure autoregulation, Head injury, Outcome
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-236562 (URN)10.1007/s12028-014-9954-2 (DOI)000343132900013 ()24515639 (PubMedID)
Available from: 2014-11-20 Created: 2014-11-19 Last updated: 2016-09-26Bibliographically approved
3. Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx)
Open this publication in new window or tab >>Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx)
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2016 (English)In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 25, no 1, 47-55 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH.

OBJECTIVE: To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI.

METHODS: Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically.

RESULTS: 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not.

CONCLUSION: In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

National Category
Anesthesiology and Intensive Care Neurology Surgery
Identifiers
urn:nbn:se:uu:diva-276116 (URN)10.1007/s12028-016-0240-3 (DOI)000380150700007 ()26842717 (PubMedID)
Available from: 2016-02-29 Created: 2016-02-09 Last updated: 2016-11-24Bibliographically approved
4. Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP
Open this publication in new window or tab >>Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP
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(English)In: Journal of Neurosurgical Anesthesiology, ISSN 0898-4921, E-ISSN 1537-1921Article in journal (Other academic) Submitted
Abstract [en]

Background: The ability to keep an even cerebral blood flow (CBF) during variations in systemic arterial blood pressure (MAP) is termed cerebral pressure autoregulation (CPA). Pressure reactivity index (PRx) is an established measure of CPA. Using PRx optimal CPP (CPPopt) can be calculated, i.e. the level of CPP where autoregulation functions best. CPPopt has not been extensively studied in patients with subarachnoid haemorrhage, and the relation between cerebral blood flow (CBF) and CPPopt has not been examined. The objective was to assess to which extent CPPopt can be calculated in SAH patients and to investigate CPPopt in relation to CBF.

Methods: Retrospective study of prospectively collected data. CBF was measured bedside with Xenon-enhanced CT (Xe-CT). The difference between actual CPP and CPPopt was calculated (CPP∆). Correlations between CPP∆ and CBF parameters were calculated with Spearman's rank order correlation. Separate calculations were done using all patients (day 0-14 after onset) as well as in two subgroups (day 0-3 and day 4-14).

Results: 64 patients were studied. CPPopt could be calculated in adjunct to 60 % of the Xe-CT scans (78% of the patients). Actual CPP < CPPopt was associated with higher amounts of low-flow regions (CBF < 10 ml / 100g ml) both in the early phase (day 0-3, p= 0.02) and the late acute phase (day 4-14, p = 0.02)

Conclusions: Calculation of CPPopt is possible in a majority of SAH patients. Actual CPP below CPPopt is associated with low CBF.

Keyword
cerebral blood flow, autoregulation, CPP, subarachnoid haemorrhage
National Category
Clinical Medicine
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-294191 (URN)
Available from: 2016-09-21 Created: 2016-05-18 Last updated: 2016-09-26

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