BACKGROUND:The regional cerebral blood flow (CBF) response to propofol and indomethacin may be abnormal in patients with brain tumors. First, the authors tested the hypothesis that during propofol anesthesia alone and combined with indomethacin, changes in CBF, cerebral blood volume (CBV), and plasma mean transit time (MTT) differ in the peritumoral tissue compared with the contralateral normal brain region. Second, the authors tested the hypothesis that CBF and CBV are reduced and MTT is prolonged, in both regions during propofol anesthesia and indomethacin administration compared with propofol alone.METHODS:The authors studied eight patients subjected to craniotomy under propofol-fentanyl anesthesia for supratentorial brain tumors. Magnetic resonance imaging, including perfusion- and diffusion-weighted and structural sequences, was performed (1) on the day before surgery, (2) before and (3) after administration of indomethacin in the propofol-fentanyl anesthetized patient, and (4) 2 days after surgery. Maps of CBF, CBV, and MTT were calculated. The regions of interest were peritumoral gray matter and opposite contralateral gray matter. Analysis of variance was used to analyze flow data.RESULTS:Propofol anesthesia was associated with a median 32% (range, 3-61%) and 47% (range, 17-67%) reduction in CBF in the peritumoral and contralateral regions, respectively.The interaction between intervention with propofol and indomethacin and region of interest was not significant for any flow modalities. Neither intervention nor region was significant for MTT, CBF, and CBV (P > 0.05).CONCLUSION:The CBF, CBV, and MTT responses to propofol and indomethacin are not different in the peritumoral region compared with contralateral brain tissue. Indomethacin did not further influence regional CBF, CBV, and MTT during propofol anesthesia.

Anaesthesia for craniotomy has to be carried out with emphasis on haemodynamic stability, a sufficient cerebral perfusion pressure and avoidance of agents or procedures that increase ICP. The patients presented to a current neuroanaesthesiological practice come with a multitude of intracranial pathologies, ranging from discrete unruptured aneurisms to significantly sized tumours that create a midline shift. It is important to relate the ICP measured in patients with space-occupying lesions to the ICP in patients without lesions. Studies of ICP during craniotomy in patients without space-occupying intracerebral lesions, however, are few. In this chapter data on two populations, one with supratentorial glioblastomas and the other without space-occupying lesions, are presented. Differences between the groups, in ICP and other relevant data obtained, are discussed and the relationship between neuroradiological data and measured ICP correlated.

Patients with intracerebral cysts are frequently presented to the neurosurgical team. Cerebral cysts can either be part of a tumour process or a parasitic disease, such as neurocysticercosis, or present as an arachnoid cyst. The presence of a cerebral cyst can give rise to classic symptoms of increased ICP, and during intracranial surgery a cyst can jeopardize surgical access to deep brain structures and increase the risk of cerebral ischaemia with possible worsening of the outcome. When fluid is removed from a cystic process in the cranial vault the pressure in the cyst will decrease. We have not found any literature addressing this subject. In this chapter unpublished data concerning subdural ICP monitoring in patients with intercerebral cysts and the pressure/volume relationship during emptying are discussed.

Since 1994 we have performed perioperative measurement of subdural ICP combined with arterial and jugular blood pressure and gas analysis in primarily elective patients subjected to craniotomy. ICP was measured with a 22G needle connected to a pressure transducer via a polyethylene catheter. Until now (2006), 1,833 patients have been included in our database. In this chapter the extensive material of the database is disclosed. Patients were entered consecutively over the years, some included as part of controlled trials and some as part of the normal daily routine. The demographics of the patient population are described, likewise the diagnosis, including tumour (if any) localization. The anaesthetics used and ICP-reducing procedures are summarized and the method for ICP monitoring discussed.

Supratentorial cerebral tumours represent the bulk of intracranial pathological processes presented in most clinics. Some patients have small tumours in important deep areas and others have large tumours creating midline shift but situated close to the surface of the brain. Regardless of pathology the team treating the patient must work to create the best possible environment in the surgical field, thus giving the patient optimal chances for curative surgery. The choice of anaesthetic agent is known to influence both cerebral blood volume and other cerebral haemodynamic parameters. In this chapter three studies of patients with supratentorial tumours are presented. Two of the studies investigate the anaesthetic techniques and the influence on cerebral haemodynamics, and the third includes the histopathological diagnosis of the tumour and relates this to the measured parameters.

1. Indomethacin has been used to manage raised intracranial pressure (ICP) in humans during neuroanaesthesia and neurosurgery. Indomethacin causes cerebral vasoconstriction and reduces cerebral blood flow (CBF) and, therefore, ICP. 2. The systemic kinetics, cerebral kinetics and cerebral dynamics of indomethacin (0.2 mg/kg) were measured and modelled using a population approach. Data were collected using an instrumented sheep preparation with raised ICP and under either isoflurane or propofol anaesthesia to parallel the clinical use of indomethacin in neurosurgery. 3. The systemic kinetics of indomethacin could be described by a two-compartment model, with small distribution volumes and a clearance of 0.68 L/min. The cerebral kinetics of indomethacin could be described using a model with a cerebral distribution volume between 5 and 8 mL and a loss term of 3.3 mL/min, the latter probably representing slow diffusion across the blood-brain barrier. 4. The changes in CBF lagged behind the blood concentrations of indomethacin. Indirect response models with turnover times of 1.70-4.08 min were generally better able to describe the effect of indomethacin on CBF than effect compartment models. 5. There was a non-linear concentration-effect relationship, with the maximum possible reduction in CBF being to 73-74% of baseline. 6. The data and model support the concept of indomethacin having limited uptake into the brain, with its effect on CBF being the result of its action on the endothelium, where it indirectly modifies the turnover of a compound regulating vascular tone.

To minimize the influence of exogenous factors, 13 volunteers were anesthetized with sevoflurane 1 MAC while exposed to manual acupuncture stimulation of LI-4 (Group 1, n = 7) or a placebo point in the space between the third and fourth metacarpals (Group II, n = 6). During anesthesia (baseline) and anesthesia + acupuncture, one H2(15)O scan was performed, respectively. Group I demonstrated a significant decrease in regional cerebral blood flow in the right medial frontal gyrus (20%) and in the left putamen (17%). In Group II regional cerebral blood flow was decreased in the right medial frontal gyrus (22%); in the putamen no significant changes were observed. These data suggest that needle penetration of the skin affects the medial frontal gyrus, whereas acupuncture of LI-4 influences the putamen.

The effect of indomethacin in reducing intracranial pressure (ICP) may be dependent on the choice of anesthetic regimen. We studied the effects of indomethacin on ICP and cerebral blood flow (CBF) during isoflurane or propofol anesthesia in a sheep model of intracranial hypertension. A crossover design was applied in which six sheep were anesthetized with isoflurane and propofol in a random order. Anesthetic depth was measured with response and state entropy. Changes in CBF, ICP, mean arterial blood pressure, arterio-venous oxygen difference, and Paco(2) were measured at specific times before and after an IV indomethacin bolus (0.2 mg/kg). Response and state entropy values during anesthesia were similar in both groups. Isoflurane and propofol reduced CBF by 11% and 34%, respectively. Indomethacin caused a reduction in ICP within 15 s during both anesthetic regimens, with the decrease in ICP being significantly more pronounced during isoflurane (P = 0.009). In both anesthetic groups, indomethacin caused a simultaneous increase in mean arterial blood pressure and a further 17% versus 14% decrease in CBF from predrug values for isoflurane and propofol, respectively. The reduction in CBF was significantly more pronounced for propofol (P = 0.02). The effect on ICP, however, was most pronounced during isoflurane anesthesia. We suggest that the effect of indomethacin is partly mediated by an autoregulatory response.

Object. Plateau waves are sudden and steep increases in intracranial pressure (ICP) that can develop in patients with cerebral injuries, reduced pressure-volume compensatory reserve, and preserved autoregulation. They arecaused by cerebral vasodilation in response to a reduction in cerebral perfusion and are associated with increased cerebral blood volume and reduced cerebral blood flow. The authors evaluated the hypothesis that administration of indomethacin, a potent cerebral arteriolar vasoconstrictor, could interrupt the vicious cycle that occurs during plateau waves, extinguishing these waves and, ultimately, restoring cerebral perfusion and oxygenation. Methods. Plateau waves developed in nine patients, seven with severe traumatic brain injury and two with intraparenchymal hemorrhage. One to four episodes of plateau waves per patient were treated with indomethacin (15-20 mg), which was delivered by an intravenous bolus injection. Each patient's mean arterial blood flow (MABP), ICP, cerebral perfusion pressure (CPP), and cerebral tissue PO 2 were continuously monitored and the data obtained were stored in a personal computer. Each patient's jugular venous O 2 saturation (SjvO 2 ) and venoarterial difference in PCO 2 were evaluated by intermittent blood sampling. During five episodes of plateau waves, middle cerebral artery flow velocities were evaluated by transcranial Doppler ultrasonography. Indomethacin extinguished all plateau waves. On average, the ICP decreased from an initial value of 58.9 ′ 11.6 mm Hg to 21.2 ′ 8.6 and 25.8 ′ 13.7 mm Hg after 5 and 10 minutes, respectively (p < 0.01). The MABP did not change significantly. As a consequence the CPP increased by 98 and 81% after 5 and 10 minutes, respectively (p < 0.01). Five and 10 minutes after indomethacin was administered, SjvO 2 increased from an initial value of 50 ′ 10.5% to 62 ′ 7.6 and 59.9 ′ 9.3%, respectively (p < 0.01); the cerebral tissue PO 2 increased from an initial value of 13.4 ′ 10.6 mm Hg to 23.6 ′ 9.58 and 21.9 ′ 9.2 mm Hg, respectively (p < 0.05); and the venous-arterial PCO 2 decreased significantly. The mean and diastolic flow velocities increased significantly, whereas the pulsatility index decreased from 1.39 ′ 0.56 to 1.09 ′ 0.4 at 5 minutes and 1.06 ′ 0.36 at 10 minutes (p < 0.05). Conclusions. The findings confirm that plateau waves are caused by vasodilation and show that indomethacin, by constricting the cerebral arteries, is effective in extinguishing plateau waves, ultimately restoring cerebral perfusion and oxygenation.

The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR(O(2))) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR(O(2)) in five, young healthy volunteers before and during COX inhibition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR(O(2)) changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

Sixteen patients with supratentorial cerebral tumours were subjected to craniotomy under thiopentone, fentanyl, nitrous oxide, halothane anaesthesia during moderate hypocapnia (PaCO2 level 4.0 kPa). The arterio-venous oxygen content difference (AVDO2) was measured peroperatively, and repeatedly during the first three hours after extubation.