Xenon CT cerebral blood flow in patients with head injury: influence of pulmonary trauma on the input function.

The noninvasive xenon-enhanced CT (Xe CT) cerebral blood flow (CBF) method has been used in patients with severe traumatic brain injury (TBI) to identify the blood-flow thresholds for the development of irreversible ischaemia or infarction following severe TBI. Quantitative regional CBF (rCBF) estimates are based on the assumption of identity between the end-tidal xenon concentration curve, used as the input function, and the arterial xenon concentration curve, being the true input function to the brain. Accordingly, rCBF data addressing the issue of ischaemia should be viewed in relation to possible deviations between the end-tidal and arterial xenon concentration curves. To evaluate this possible source of error, we studied five patients with severe TBI (Glasgow coma score < or =7) who also had pulmonary trauma. CBF was studied with the Xe CT CBF method and flow rates were determined by fitting the Kety equation to each CT voxel using either the end-tidal or the arterial xenon curve as input function. In all patients rCBF estimates were lower using the end-tidal xenon curve than with the arterial xenon curve; the mean underestimation was 20.3% in gray metter and 17.3 % in white matter. The deviation between the end-tidal and arterial xenon concentration curves should be considered as a source of error when defining critical flow values according to the flow thresholds of tissue viability.

The influence of the input function on quantitative rCBF by the Xe/CT method.

Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-tidal xenon curve which is applied as input function, and the arterial xenon curve being the true input function to the brain. In this study corresponding end-tidal and arterial xenon curves were measured in an experimental animal model (part 1) and in 5 patients with traumatic brain injury (part 2) and used for rCBF calculation. In both studies rCBF was underestimated by using the end-tidal xenon concentration curve as brain input function. In part 1 rCBF underestimation was depended on pulmonary gas exchange; high or low levels of rCBF; tissue type; and xenon inhalation protocols. In part 2 the mean rCBF underestimation was 18.8 +/- 8.3%. In conclusion, non-invasive estimate of the input function should be considered as a source of error when defining quantitative blood flow values e.g. the flow thresholds of ischaemic infarction.

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.

Pulmonary function affects the quantification of rCBF by non-invasive xenon methods.

Estimates of regional cerebral blood flow (rCBF) by non-invasive xenon methods (133-xenon inhalation, xenon-enhanced computed tomography (Xe/CT) and 133-xenon iv injection) are frequently applied in the diagnosis and evaluation of patients suffering from diseases which cause disturbances in the cerebrovascular circulation. These methods all depend on an estimate of the arterial xenon concentration curve derived non-invasively from measurements of the end-tidal xenon concentration curve and used as brain input function in the Kety equation. We have studied the influence of impaired pulmonary gas exchange on the end-tidal and arterial xenon concentration curves in nine anaesthetized pigs by simultaneously measurements of both the end-tidal xenon and arterial xenon concentration curves. Computer simulations were performed to determine the deviations in the calculated rCBF values when using the end-tidal as compared to the arterial xenon concentration curve as brain input function. The results indicated that impairment of the pulmonary gas exchange caused a significant further 'delay' in the arterial xenon concentration curve in comparison to the end-tidal xenon concentration curve. The time constants of arterial curve delay were 11.9 s in the normal pulmonary group, 21 s in the right lung atelectasis group, and 19.7 s in the left pulmonary artery occlusion group. Accordingly, computer simulations indicated a statistically significant 'underestimation' of rCBF due to: (1) pulmonary gas exchange; (2) high or low levels of rCBF; (3) partition coefficient (lambda) of gray and white matter; and (4) xenon inhalation protocols. Our results indicate that quantitative measurements of rCBF by non-invasive xenon methods are markedly affected by deviations between the end-tidal and arterial xenon concentration curve, so that estimates of flow thresholds for infarction are problematic under conditions of impaired pulmonary gas exchange.

[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.

[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.

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.

CO(2) and indomethacin vasoreactivity in patients with head injury.

The purpose of this study was to compare the effect of hyperventilation and indomethacin on cerebral circulation, metabolism and pressures in patients with acute severe head injury in order to see if indomethacin may act supplementary to hyperventilation. Fourteen severely head injured patients entered the study. Intracranial pressure (ICP), mean arterial blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored continuously. Within the first four days after the trauma the CO(2) and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous (133)Xe technique) and arterio-venous difference of oxygen (AVdO(2)). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO(2)), lactate and lactate/oxygen index (LOI). Data are presented as medians and ranges, results are significant unless otherwise indicated. Before intervention ICP was well controlled ,(14.8 (9-24) mmHg) and basic CBF level was 39.1 (21.6-75.0) ml/100 g/min). The arterio-venous oxygen differences were generally decreased (AVdO(2) = 4.3 (1.8-8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO(2) were decreased (1.54 (0.7-3.2) ml/100 g/min) as well. During hyperventilation (delta PaCO(2)=0.88 (0.62-1.55) kPa) CBF decreased with 11.8 (-33.4-29.7) %/kPa and ICP decreased with 3.8 (0-10) mmHg. AVdO(2) increased 34.0 (4.0-139.2) %/kPa, MABP was unchanged, CMRO(2) and CPP increased (delta CPP = 3.9 (-10-20) mmHg). AVD (lactate) and LOI were unchanged. No correlations between CBF responses to hypocapnia and outcomes were observed. An i.v. bolus dose of indomethacin (30 mg) decreased CBF 14.7 (-16.7-57.4)% and ICP decreased 4.3 (-1-17) mmHg. AVdO(2) increased 27.8 (-40.0-66.7)%, MABP (delta MABP = 4.9 (-2-21) mmHg) and CPP (delta CPP = 8.7 (3-29) mmHg) increased while CMRO2 was unchanged. No changes in AVd (lactate) and LOI indicating cerebral ischaemia were found. Compared to hyperventilation (changes per 1 kPa, at PaCO(2) level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO(2), ICP, SvjO(2) and LOI were of the same order of magnitude. No correlation between relative reactivities to indomethacin and CO(2), evaluated from changes in CBF and AVdO(2), or between the decrease in ICP after the two procedures were found. Thus, some patients reacted to indomethacin but not to hyperventilation, and vice versa. These results suggest that indomethacin and hyperventilation might act independently, or in a complementary fashion in the treatment of patients with severe head injury.