Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography.

BACKGROUND: General anaesthetics can alter the relationship between regional cerebral glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF). With the present study, we wanted to assess quantitatively the effects of propofol on rCBF and rGMR in the same healthy volunteers measured with positron emission tomography (PET). METHODS: (15)O-labelled water and (18)F fluorodeoxyglucose were used as PET tracers to determine rCBF and rGMR, respectively, in eight healthy volunteers during the waking state (baseline) and during propofol anaesthesia. Propofol was titrated to keep a constant hypnotic depth (Bispectral Indes 35-40) throughout the anaesthesia. Changes in rGMR and rCBF were quantified using region-of-interest and voxel-based analyses. RESULTS: The measured mean propofol concentration was 4.1 ± 0.8 µg/ml during anaesthesia. Compared with the conscious state, total CBF and GMR decreased during the anaesthetic state with 47% and 54%, respectively. In the white and grey matter, rCBF and rGMR were reduced by 37% and 49%, and by 45% and 57%, respectively. Propofol decreased rCBF in all brain structures by 46-55% (P ≤ 0.01) with highest significant decreases in the thalamus and parietal lobe. Regional GMR was reduced in all brain areas to 48-66% (P ≤ 0.01) with highest significant reductions in the occipital lobe, the lingual gyrus, parietal lobe, temporal lobe and thalamus. No increases in rCBF or rGMR happened anywhere. CONCLUSIONS: General anaesthesia with propofol is associated with a global metabolic and vascular depression in the human brain, with significant shifts in regional blood flow and metabolism indicating marked metabolic and vascular responsiveness in some cortical areas and thalamus.

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET.

BACKGROUND: Arterial carbon dioxide tension (PaCO(2)) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). METHODS: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H(2)(15)O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. RESULTS: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO(2) was decreased from 5.5 + or - 0.7 to 3.8 + or - 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. CONCLUSIONS: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.

Regional cerebral glucose metabolism during sevoflurane anaesthesia in healthy subjects studied with positron emission tomography.

BACKGROUND: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. METHODS: Eight volunteers underwent two dynamic 18F-fluorodeoxyglucose positron emission tomography (PET) scans. One scan assessed conscious-baseline metabolism and the other scan assessed metabolism during 1 minimum alveolar concentration (MAC) sevoflurane anaesthesia. Cardiovascular and respiratory parameters were monitored and bispectral index responses were registered. Statistical parametric maps and conventional regions of interest analysis were used to determine rGMR differences. RESULTS: All subjects were unconsciousness at 1.0 MAC sevoflurane. Cardiovascular and respiratory parameters were constant over time. In the awake state, rGMR ranged from 0.24 to 0.35 mumol/g/min in the selected regions. Compared with the conscious state, total GMR decreased 56% in sevoflurane anaesthesia. In white and grey matter, GMR was averaged 42% and 58% of normal, respectively. Sevoflurane reduced the absolute rGMR in all selected areas by 48-71% of the baseline (P< or = 0.01), with the most significant reductions in the lingual gyrus (71%), occipital lobe in general (68%) and thalamus (63%). No increases in rGMR were observed. CONCLUSIONS: Sevoflurane caused a global whole-brain metabolic reduction of GMR in all regions of the human brain, with the most marked metabolic suppression in the lingual gyrus, thalamus and occipital lobe.

The relationship between intracranial pressure and the degree of brain swelling in patients subjected to infratentorial surgery.

BACKGROUND: In patients with supratentorial tumours, intracranial pressure is a strong predictor of intra-operative brain swelling and thresholds for ICP associated with brain swelling have been defined. Whether these ICP thresholds can be applied during infratentorial surgery is uncertain. We studied the relationship between subdural ICP and the degree of brain swelling after opening of the dura mater in patients subjected to infratentorial surgery. Thresholds for ICP associated with brain swelling were defined. METHODS: One hundred and nine adult patients subjected to infratentorial surgery were studied. Subdural ICP was measured immediately before opening of the dura and the degree of brain swelling was estimated by the neurosurgeon according to a four-point scale. FINDINGS: At ICP less than 7 mmHg brain swelling did not occur. In the range from 7 to 13 mmHg 21 of 39 patients (54%) had moderate swelling, but not pronounced swelling. At ICP greater than 13 mmHg some degree of swelling occurred in all patients, and at ICP exceeding 24 mmHg pronounced cerebral swelling was found in all patients. Using logistic regression analysis specific thresholds for ICP associated with brain swelling were defined as follows: at an ICP equal to or greater than 13 mmHg, brain swelling occurred with 95% probability; and at an ICP less than 6 mmHg brain swelling occurred with 5% probability. CONCLUSIONS: Subdural ICP measured before opening of the dura mater can predict the risk of brain swelling during infratentorial surgery. Thresholds for ICP associated with brain swelling are close to thresholds defined in patients undergoing supratentorial surgery.

The effects of 10 degrees reverse Trendelenburg position on subdural intracranial pressure and cerebral perfusion pressure in patients subjected to craniotomy for cerebral aneurysm.

The aim of the current study was to examine the effects of 10 degrees reverse Trendelenburg position (rTp) on subdural intracranial pressure (ICP), cerebral perfusion pressure (CPP), and dural tension. Additionally, the relationship between preoperative Hunt and Hess (H and H) grade and the subdural ICP in patients scheduled for cerebral aneurysm surgery was investigated. Twenty-eight consecutive patients with a cerebral aneurysm were subjected to craniotomy in propofol/fentanyl or propofol/remifentanil anesthesia. Subdural ICP was measured after opening of the bone flap and exposure of dura. After reference measurements of subdural ICP and mean arterial blood pressure (MABP), the measurements were repeated during 10 degrees rTp. No significant differences between the anesthetic groups were disclosed. During 10 degrees rTp, a significant decrease in MABP, ICP, and jugular bulb pressure was observed whereas CPP remained unchanged. In H and H 0 patients (unruptured aneurysm), the ICP decreased from 2.9 +/- 2.6 mmHg to 0.4 +/- 2.2 mmHg at 10 degrees rTp. In H and H I to II patients, the ICP decreased from 9.3 +/- 3.8 mmHg to 4.6 +/- 3.3 mmHg at 10 degrees rTp. A significant difference in the mean baseline subdural ICP and DeltaICP (change in ICP) was found between patients with unruptured aneurysm and patients with subarachnoid hemorrhage (H&H I and II). Furthermore, the relationship between the subdural ICP at neutral position and DeltaICP was significant. In patients without intracranial hypertension, 10 degrees rTp decreases subdural ICP and dural tension in patients with ruptured as well as patients with unruptured cerebral aneurysm; CPP is unchanged.

Subdural intracranial pressure, cerebral perfusion pressure, and degree of cerebral swelling in supra- and infratentorial space-occupying lesions in children.

UNLABELLED: To our knowledge comparative studies of intracranial pressure (ICP) and degree of cerebral swelling during craniotomy for supratentorial or infratentorial space occupying lesion in children are not available. In this prospective study subdural ICP, cerebral perfusion pressure (CPP), dural tension, and the degree of cerebral swelling were analysed in supine and prone positioned children subjected to craniotomy for space occupying lesions. MATERIAL AND METHOD: 48 children with space occupying tumours were subjected to either isoflurane/nitrous oxide 50%/fentanyl (n = 22) or propofol/fentanyl/air/oxygen (n = 26). 25 children were operated supratentorially in supine position, while 23 patients were operated infratentorially in the prone position. Subdural ICP, mean arterial blood pressure (MABP), and CPP were measured just before opening of the dura. Dural tension was estimated before opening of dura, and the degree of cerebral swelling was estimated after opening of dura. RESULTS: The age and weight of children anaesthetised with isoflurane in the prone position were significantly lower than the propofol anaesthetised groups. No significant inter-group differences as regards tumour size, midline shift, rectal temperature, MABP or PaCO2 were found. ICP in prone positioned children averaged 16.9 mm Hg against 9.0 mm Hg in supine positioned children (p < 0.001). In prone positioned children the dura was significantly tenser, and the degree of brain swelling after opening of dura was significantly more pronounced. No significant difference as regard ICP was disclosed when isoflurane/nitrous oxide/fentanyl and propofol/ fentanyl anaesthetized children were compared, but MABP and CPP were significantly lower in isoflurane anaesthetised children. CONCLUSION: In children with cerebral tumours ICP is higher, and the degree of cerebral swelling more pronounced in the prone-compared with supine positioned children. Choice of anaesthesia did not influence ICP, but CPP was significantly lower during isoflurane anaesthesia.

Cerebral blood flow measurements by magnetic resonance imaging bolus tracking: comparison with [(15)O]H2O positron emission tomography in humans.

In six young, healthy volunteers, a novel method to determine cerebral blood flow (CBF) using magnetic resonance (MR) bolus tracking was compared with [(15)O]H2O positron emission tomography (PET). The method yielded parametric CBF images with tissue contrast in good agreement with parametric PET CBF images. Introducing a common conversion factor, MR CBF values could be converted into absolute flow rates, allowing comparison of CBF values among normal subjects.

Cerebral blood flow in volunteers measured by PET and Xe CT/CBF. A comparison.

Aim of this study was to compare two quantitative CBF methods. Seven young, healthy volunteers were studied with PET (15-0 labelled water) and afterwards with Xe CT/CBF (30% xenon in oxygen, 3 minutes wash-in, 5 minutes washout protocol). Xe CT/CBF showed greater differences between high and low flow areas than PET CBF. Correlation was found within subjects between ROI's, but no agreement or correlation between the methods could be demonstrated. The disagreement in this study could be due to changes in PCO2.

Effects of perioperative indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients subjected to craniotomy for cerebral tumors.

This study was carried out to evaluate the effects of perioperative indomethacin on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolism. Twenty patients subjected to craniotomy for supratentorial cerebral tumors were anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa (median) was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. ICP was measured continuously subdurally with a 22-gauge canula connected to a transducer. CBF and the arteriovenous difference of oxygen (AVDO2) were measured twice, before and after indomethacin/placebo administration. A significant decrease in ICP from 6.5 to 1.5 mm Hg (median) was found after indomethacin administration. This decrease was caused by a significant decrease in CBF associated with a significant increase in AVDO2. Indomethacin did not affect the cerebral metabolic rate of oxygen, the arteriovenous difference of lactate, or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients and dura was opened without the occurrence of cerebral swelling. In one patient, mannitol treatment was necessary to prevent dural tightness. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anesthesia for craniotomy.

Effects of dihydroergotamine on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients undergoing craniotomy for brain tumors.

In a search for a nonsurgical intervention to control intracranial hypertension during craniotomy, the authors studied the effects of dihydroergotamine on mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and cerebral metabolism in patients who underwent craniotomy for supratentorial brain tumors. Twenty patients were randomized to receive either dihydroergotamine 0.25 mg intravenously or placebo as a bolus dose during craniotomy. Anesthesia was induced with thiopental/fentanyl/atracurium, and maintained with isoflurane/N2O/fentanyl at normocapnia. After removal of the bone flap and exposure of intact dura, ICP was measured subdurally and dihydroergotamine/placebo was administered. Intracranial pressure and MABP were measured continuously. Cerebral blood flow (after intravenous administration of 133Xe) and arteriojugular venous difference of oxygen (AVDO2) were measured before, and 30 minutes after, dihydroergotamine/placebo administration. Cerebral metabolic rate of oxygen (CMRO2) was calculated. After administration of dihydroergotamine, a significant increase in MABP from 74 to 87 mm Hg (median) and CPP from 65 to 72 mm Hg (median) were found. Simultaneously to the increase in MABP, a significant increase in ICP from 9.5 to 11.5 mm Hg (median) was disclosed, whereas no significant differences in CBF, AVDO2, or CMRO2 were found. Intracranial pressure was significantly higher after dihydroergotamine than after placebo. In conclusion, no ICP decreasing effect of a bolus dose of dihydroergotamine was found when administered to patients with brain tumors during isoflurane/N2O anesthesia. Corresponding increases in MABP and ICP suggest that abolished cerebral autoregulation might explain why dihydroergotamine was associated with an ICP increase.

Subdural monitoring of ICP during craniotomy: thresholds of cerebral swelling/herniation.

It is possible to define thresholds for cerebral swelling or herniation during craniotomy. In 178 patients subjected to craniotomy for space occupying processes subdural ICP was measured before opening of dura. The subdural ICP was correlated to the degree of cerebral swelling or herniation after opening of dura. At subdural ICP < 7 mm Hg cerebral swelling/herniation after opening of dura rarely occurs, while at ICP > or = 10 mm Hg cerebral swelling/herniation occurs with high probability. These ICP thresholds are independent of the pathophysiology (SAH, cerebral tumor), the anaesthetic agent (isoflurane, propofol) and the PaCO2 level (< or = 4.0 kPa, > 4.0 kPa). Generally, a good correlation between the tactile estimation of dural tension and the tendency to cerebral swelling or herniation after opening of dura was found. However, in 8.5% the surgeons were unable to predict swelling/herniation.

ICP during anaesthesia with sevoflurane: a dose-response study. Effect of hypocapnia.

In patients with a supratentorial cerebral tumor, an increase in sevoflurane concentration from 1.5% (0.7 MAC) to 2.5% (1.3 MAC) did not change the intracranial pressure (ICP) significantly (12 to 14 mm Hg (medians)). However, a significant increase in cerebral blood flow (CBF) from 29 to 39 ml/100 g/min (medians) was disclosed. During administration of sevoflurane 1.5% and 2.5%, a significant decrease in ICP (3.5 and 3.0 mm Hg (median) respectively) was found when PaCO2 was decreased by 0.8 kPa.

ICP is lower during propofol anaesthesia compared to isoflurane and sevoflurane.

OBJECTIVES: Propofol is a cerebral vasoconstrictor while inhalation anaesthetics like isoflurane and sevoflurane act as cerebral vasodilators in both animal and human studies. This difference of action upon cerebral vessels might implicate a lower ICP during propofol anaesthesia. Cerebral metabolism is decreased by all three anaesthetics. In a prospective, randomised multicenter study ICP was compared during anaesthesia with propofol, isoflurane and sevoflurane. METHODS: 117 patients subjected to elective craniotomy for supratentorial tumour. Propofol: N = 41; isoflurane: N = 38; sevoflurane: N = 38. Nitrous oxide was omitted and all anaesthetics were supplemented with a continuous infusion of fentanyl. ICP was measured subdurally after removal of the bone flap. MABP, CPP, PCO2, AVDO2, rectal temperature, tumour size and midline shift were registered too. STATISTICS: Kruskal-Wallis Variance on Ranks. All values in medians with range. P < 0.05 was considered significant. RESULTS: ICP (mmHg): propofol 7 (-1-20), isoflurane 12 (1-29), sevoflurane 11 (2-32). ICP was significantly lower in the propofol group compared to the isofluane and sevoflurane groups. CPP (mmHg): propofol 80 (45-104), isoflurane 60 (32-84), sevoflurane 63 (44-77). CPP was significantly higher in the propofol group compared to the isoflurane and sevoflurane groups. AVDO2 (mmol/l): propofol 3.1 (0.9-5.1), isoflurane 2.5 (1.1-4.5), sevoflurane 2.6 (0.8-4.1). AVDO2 was significantly higher in the propofol group compared to the isoflurane and sevoflurane groups. No significant differences in PCO2, rectal temperature, tumour size and midline shift were found. CONCLUSIONS: Subdural ICP is significantly lower during propofol anaesthesia compared to isoflurane and sevoflurane anaesthesia. CPP and AVDO2 are significantly higher during propofol anaesthesia compared to isoflurane and sevoflurane anaesthesia.

[Use of controlled hyperventilation in the treatment of comatose patients with cranial injuries]. / Anvendelse af kontrolleret hyperventilation i behandlingen af komatøse patienter med kranietraume.

Controlled hyperventilation is a recognized method by which it is possible to reduce the intracerebral blood volume and thus the intracranial pressure (ICP). In the review, the physiological conditions involved in the regulation of ICP are illustrated, particularly in connection with acute cranial traumata and effect of controlled hyperventilation in these situations is discussed. Controlled hyperventilation is recommended in the hyperacute phase for all patients with cranial trauma prolonged impairment of consciousness (Glasgow Coma Scale less than 7 for more than 30 minutes) and other clinical evidence of expanding space-occupying intracranial process. Prolonged hyperventilation is recommended for younger patients as these have most frequently hyperaemia and retained CO2 reactivity and for patients with predominantly cortical lesions as assessed by CT scanning. Caution in the employment of hyperventilation is advised in elderly patients, severely traumatized patients and late in the course of cerebral trauma.

[Primary care and transportation of patients with neural trauma]. / Primaer behandling og transport af den neurotraumatiserede patient.

It is well-known that it is difficult for the inexperienced doctor to estimate the need for treatment regarding patients with acute brain trauma. Brain ischaemia developing after a brain trauma (secondary cerebral ischaemia) is known to severely worsen the prognosis of the patient. This article gives a review of the most important pathophysiological changes occurring during the acute phase of severe brain trauma. The principles of prevention and management of cerebral ischaemia after brain trauma and during transportation of the patient are discussed.

[Changes in PaO2, PaCO2 and pH during the apnea test]. / Aendringer i PaO2, PaCO2 og pH under apnøtest.

Changes in PaCO2, PaO2 and arterial pH were monitored during a 10 min apnoea test in nine clinically brain dead subjects. The patients were preoxygenated for 15 min with 100% O2. During the apnoea test they were oxygenated by tracheal cannulation with 5 l O2 per min. PaCO2 rose 1.3-2.1 kPa during the first two minutes of apnoea. Patients with PaCO2 greater than or equal to 5.5 kPa at the beginning of apnoea all had PaCO2 greater than 8 kPa after 5 min of apnoea for five minutes. With one exception, all of the patients were sufficient oxygenated during the apnoea test. If patients are ventilated to a PaCO2 greater than or equal to 5.5 kPa then 5 min of apnoea testing will increase PaCO2 above 8 kPa. As a few patients may develop hypoxemia, patients should be monitored with pulseoximetry.

[Effect of indomethacin on the intracranial pressure]. / Indomethacins virkning på det intrakranielle tryk.

Twenty patients subjected to craniotomy for supratentorial cerebral tumours were anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. A significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was found after indomethacin administration. This decrease was caused by a significant decrease in cerebral blood flow associated with a significant increase in the arterio-venous oxygen difference. Indomethacin did not affect cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischaemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients, and dura was opened without the occurrence of cerebral swelling. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anaesthesia for craniotomy.

[CO2 and indomethacin vasoreactivity in patients with cranial trauma]. / CO2-og indometacinvasoreaktivitet hos patienter med kranietraume.

The purpose of this study was to compare the effect of hyperventilation and indomethacin on cerebral circulation, metabolism and systemic and intracerebral pressures in patients with severe head injury. Fourteen moderately (PaCO2 = 4.05 kPa) hyperventilated patients with median [CP = 14.8 mmHg entered the study. Cerebral blood flow (CBF), intracranial pressure (ICP), arteriovenous difference of oxygen (AVDO2) and lactate (AVdL) and oxygen saturation in the jugular bulb (SvjO2) were measured before and after hyperventilation and after a bolus dose of indomethacin (30 mg). During hyperventilation CBF decreased by 11.8%/kPa and ICP decreased by 3.8 mmHg. AVDO2 increased by 34.0%/kPa. After indomethacin CBF decreased by 14.7% and ICP decreased by 4.3 mmHg. AVDO2 increased with 27.8%. No changes in median SvjO2 and AVdL were observed after the two treatments. The risk of cerebral ischaemia seems identical after the two treatments. No correlations between the effects of the two treatments on CBF, ICP and AVDO2 were found. These results suggest that indomethacin and hyperventilation might act independently or in a complementary fashion in the treatment of patients with severe head injury.

[Indomethacin in severe cerebral contusions with intracranial hypertension]. / L'indométacine dans les contusions cérébrales sévères avec hypertension intracrânienne.

In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control ICP by hyperventilation and barbiturate sedation, indomethacin Confortid was used as a cerebral vasoconstrictor drug. In all patients indomethacin reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in cerebral blood flow (CBF) at 2 hours. After 7 hours. ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In two patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. Outcome scaling has not yet been performed, but all patients left hospital without neurological deficits. These results suggest that indomethacin is an alternative in the treatment of intracranial hypertension in head-injured patients.