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Intrinsic and extrinsic protection of the brain
Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The brain is a complex organ and critically dependent on its oxygen metabolism and blood supply. The purpose of the present study was twofold: firstly to design, evaluate, and adopt a physiologically stable experimental model for repeated measurements of cerebral cortical microvascular perfusion by a new laser Doppler technique (experimental part (I) - intrinsic model). Secondly, to examine the complication rates of a brief period of hypothermia for protection of the brain in patients who  were operated on for subarachnoid aneurysms (clinical part (II) - extrinsic model).

Method. Part I. In contrast to conventional laser Doppler flowmetry, the laser Doppler perfusion imager (LDPI) creates a two-dimensional map of the tissue perfusion in an area of up to 120 x 120 mm, comprising 4096 measurement points. Measurements were made in a closed cranial window in ventilated anaesthetised pigs (n=25). Provocations that altered cerebral blood flow (CBF) were those that can occur during anaesthesia and critical care, including varying arterial concentration of carbon dioxide and mean arterial blood pressure (MABP), and those caused by different types (isoflurane and sevoflurane) and concentrations (minimum alveolar concentration, MAC, 0.3-1.2) of volatile anaesthetics.

Part II. The feasibility and complication rates of rapidly-induced moderate hypothermia in 359 operations were examined prospectively. The complications that we sought were: altered haemostasis, infections, haemodynamic instability, and increased need for postoperative ventilatory support. Hypothermia was produced by cold (4°C) intravenous infusions and convective cooling. This lowered the body temperature at a mean (SD) 4 (0.4)oC h1 to 32.5 (0.4)oC. The body temperature returned to normal in all patients by 5 (2) hours postoperatively.

Results. Part I. Cortical CBF was distributed highly heterogeneously and it was strongly dependent on MABP, as well as concentrations of CO2 During decreasing MABP the lower limit of autoregulation varied locally in the cortex and the 'classic' autoregulatory pressure-flow relation was present in only a few areas. Alterations in PaC02 concentration did not affect the pressure-flow relation at low perfusion pressures, whereas at normal or above normal values, hypercapnia increased CBF considerably (p < 0.001). CBF was not affected by the anaesthetic (isoflurane or sevoflurane) or dose (MAC 0.3-1.2) used.

Part II. Perioperative and postoperative complications itcluded: circulatory instability (10%), arrhythmias (5%), abnormalities of coagulation, need for blood transfusions (47%), infections (8%), and puhnonary complications including infiltrates or oedema while on ventilatory support (27%). There was no correlation between the extent of hypothermia and any of the complications. However, there was a strong correlation (p < 0.001) between the incidence of complications and the severity of the underlying neurological disease as assessed by the Hunt and Hess score.

Conclusion Part I. The LDPI method was useful and relevant for measurement of cortical CBF in this experimental model. 'Classic' autoregulatory patterns were found only when all values sampled wereclustered together, whereas the autoregulatory capacity is often lacking at the local level in the cortex. Volatile anaesthestics (isoflurane and sevoflurane) in the doses 0.3 - 1.2 (MAC) did not affect the regulation of CBF in this model. Part II. Moderate hypothermia can be achieved within 1 hour of induction of anaesthesia and seems to be safe as far as the risks of perioperative and postoperative complications are concerned.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2005. , 76 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 897
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-31533Local ID: 17332ISBN: 91-85299-07-3 (print)OAI: oai:DiVA.org:liu-31533DiVA: diva2:252356
Public defence
2005-05-21, Berzeliussalen, Hälsouniversitetets bibliotek, Campus US, Linköpings Universitet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-28Bibliographically approved
List of papers
1. Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging
Open this publication in new window or tab >>Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging
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1997 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 159, no 1, 15-22 p.Article in journal (Refereed) Published
Abstract [en]

A novel application of laser Doppler flowmetry (LDF), laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two-dimensional maps of the tissue perfusion in a well defined area of up to 120×120 mm comprising 4096 measurement points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine-mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia-caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex, also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-82034 (URN)10.1046/j.1365-201X.1997.560333000.x (DOI)
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2017-12-07Bibliographically approved
2. Cortical blood flow autoregulation revisited using laser Doppler perfusion imaging
Open this publication in new window or tab >>Cortical blood flow autoregulation revisited using laser Doppler perfusion imaging
2002 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 176, no 4, 255-262 p.Article in journal (Refereed) Published
Abstract [en]

Methods of laser Doppler perfusion monitoring (LDPM) and imaging (LDPI) have been validated and found useful for measurements of brain blood flow in several studies. The present work was undertaken to examine the cortical blood flow autoregulatory phenomenon as it has lately been questioned and claimed to be method-dependent and related to sample volume. Spatial variations in cerebral cortical blood flow (CBFcortex) in the pressure range 20–140 mmHg (static cerebral autoregulation; caval block/angiotensin infusion) were studied in six mechanically ventilated (hypocapnic, normocapnic and hypercapnic) pigs anaesthetized with propofol and fentanyl. Although the cortical blood flow values sampled were highly heterogeneously distributed, they were strongly pressure-dependent as well as CO2-dependent (P < 0.001). A cumulative cerebral blood flow (CBF)–pressure (MAP) plot comprising all values obtained indicated a pressure range between 70 and 120 mmHg where CBF remained almost constant. However, at the local level in the cortex (mm2) the same type of ‘classic’ autoregulatory flow : pressure graphs (FPG) were found in only a few of the cases of the cortical areas examined (n = 96). Alterations in blood PaCO2 saturation did not affect the pressure : flow relationship at low perfusion pressures, whereas at normal or above normal values, and as anticipated, hypercapnia considerably increased CBF (P < 0.001). ‘Classic’ autoregulatory FPGs were found only when all values sampled were clustered together, whereas, as a new finding, data are presented indicating that autoregulatory capacity is lacking at the local level at some cortical surface areas.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25358 (URN)10.1046/j.1365-201X.2002.01034.x (DOI)9800 (Local ID)9800 (Archive number)9800 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
3. Dose effect of sevoflurane and isoflurane anesthetics on cortical blood flow during controlled hypotension in the pig
Open this publication in new window or tab >>Dose effect of sevoflurane and isoflurane anesthetics on cortical blood flow during controlled hypotension in the pig
2007 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 5, 607-613 p.Article in journal (Refereed) Published
Abstract [en]

Background:  The ability of the brain to preserve adequate cerebral blood flow (CBF) during alterations in systemic perfusion pressure is of fundamental importance. At increasing concentrations, isoflurane and sevoflurane have been known to alter CBF, which may be disadvantageous for patients with increased intracranial pressure. The aim was to examine the effects of isoflurane and sevoflurane at increasing minimum alveolar concentrations (MAC) on CBF, during controlled hypotension.

Methods:  We studied eight pigs during variations in perfusion pressure induced by caval block (100, 60, 50, and 40 mmHg) under normocapnia. CBF was measured locally in a defined area (4 × 5 measurement points covering 1 cm2) of the motor cortex using laser Doppler perfusion imaging. Physiological variables, assessed by analysis of arterial O2 and CO2, hemoglobin and hematocrit, were controlled. CBF was measured during propofol (10 mg × kg−1× h−1) and fentanyl (0.002 mg × kg−1× h−1) anesthesia, and then during anesthesia with either isoflurane or sevoflurane (given in random order) at increasing MAC (0.3–1.2). After a washout period, the measurements were repeated with the other gas.

Results:  CBF was significantly higher in the cortex during normotensive (control) settings, MAP ∼100 mmHg, compared with during hypotension (MAP 40–60 mmHg). Neither different anesthetic nor MAC or local measurement sites were found to influence CBF at any perfusion pressure.

Conclusion:  In this experimental model, the effect of hypotension on CBF was not altered by the anesthetics used [isoflurane, sevoflurane (MAC 0.3–1.2) or propofol (10 mg × kg−1× h−1)]. In this aspect (cortical tissue perspective), these volatile agents appear as suitable as propofol for neurosurgical anesthesia for patients at risk.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39479 (URN)10.1111/j.1399-6576.2007.01281.x (DOI)48851 (Local ID)48851 (Archive number)48851 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
4. Moderate hypothermia for 359 operations to clip cerebral aneurysms
Open this publication in new window or tab >>Moderate hypothermia for 359 operations to clip cerebral aneurysms
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2004 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 93, no 3, 343-347 p.Article in journal (Refereed) Published
Abstract [en]

Background. Experimental data have suggested that hypothermia (32–34°C) may improve outcome after cerebral ischaemia, but its efficacy has not yet been established conclusively in humans. In this study we examined the feasibility and safety of deliberate moderate perioperative hypothermia during operations for subarachnoid aneurysms.

Methods. A total of 359 operations for intracranial cerebral aneurysms were included in this prospective study. By using cold intravenous infusions (4°C) and convective cooling our aim was to reduce the patient's core temperature to more than 34°C within 1 h before operation. The protocol assessed postoperative complications such as infections, prolonged mechanical ventilation, pulmonary complications and coagulopathies.

Results. During surgery, the body temperature was reduced to a mean of 32.5 (sd 0.4) °C. Cooling was accomplished at a rate of 4.0 (sd 0.4) °C h−1. All patients were normothermic at 5 (sd 2) h postoperatively. Peri/postoperative complications included circulatory instability (n=36, 10%), arrhythmias (n=17, 5%) coagulation abnormalities and blood transfusion (n=169, 47%), infections (n=29, 8%) and pulmonary complications (infiltrate or oedema while on ventilatory support) (n=97, 27%). Eighteen patients died within 30 days (5%). There was no significant correlation between the extent of hypothermia and any of the complications. However, there was a strong correlation between the occurrence of complications and the severity of the underlying neurological disease as assessed by the Hunt and Hess score.

Conclusion. Moderate hypothermia accomplished within 1 h of induction of anaesthesia and maintained during surgery for subarachnoid aneurysms appears to be a safe method as far as the risks of peri/postoperative complications such as circulatory instability, coagulation abnormalities and infections are concerned.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24033 (URN)10.1093/bja/aeh206 (DOI)3589 (Local ID)3589 (Archive number)3589 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved

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