Gerard F. A. Jansen

Cerebral Autoregulation in Subjects Adapted and Not Adapted to High Altitude

Background and Purpose Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude. Methods We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP. Results In the sea-level group, at a relative MABP increase of 23±4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2±7%, P =0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29±7%, there was a uniform and significant increase of Vmca of 24±9% (P <0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21±6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%. Conclusions All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.

Jugular bulb oxygen saturation during propofol and isoflurane/nitrous oxide anesthesia in patients undergoing brain tumor surgery.

UNLABELLED We investigated, in brain tumor patients, the jugular bulb venous oxygen partial pressure (PjO2) and hemoglobin saturation (SjO2), the arterial to jugular bulb venous oxygen content difference (AJDO2), and middle cerebral artery blood flow velocity (Vmca) during anesthesia, and the effect of hyperventilation on these variables. Twenty patients were randomized to receive either isoflurane/ nitrous oxide/fentanyl (Group 1) or propofol/fentanyl (Group 2). At normoventilation (PacO2 35 +/- 2 mm Hg in Group 1 and 33 +/- 3 mm Hg in Group 2), SjO2 and PjO2 were significantly higher in Group 1 than in Group 2 (SjO2 60% +/- 6% and 49% +/- 13%, respectively; P = 0.019) (PjO2 32 +/- 3 and 27 +/- 5 mm Hg, respectively; P = 0.027). In Group 2, 5 of 10 patients had SjO2 < 50%, and 3 of these patients had SjO2 < 40% and AJDO2 > 9 mL/dL. All patients in Group 1 had SjO2 > 50%. During hyperventilation, there were no differences in SjO2, PjO2, or AJDO2 between the two groups. On hyperventilation, there was no correlation between the relative decreases of Vmca and 1/AJDO2 (r = 0.21, P = 0.41). The results indicate during propofol anesthesia, half of the brain tumor patients showed signs of cerebral hypoperfusion, but not during isoflurane/nitrous oxide anesthesia. Furthermore, during PacO2 manipulations, shifts in Vmca are inadequate to evaluate brian oxygen delivery in these patients. IMPLICATIONS During propofol anesthesia at normoventilation, 50% of brain tumor patients showed signs suggesting cerebral hypoperfusion, but this could not be demonstrated during isoflurane/nitrous oxide anesthesia. During PacO2 manipulations, consecutive measurements of the cerebral blood flow velocity may be inadequate to assess cerebral oxygenation.

Basilar artery blood flow velocity and the ventilatory response to acute hypoxia in mountaineers

Hypoxic ventilatory response is higher in successful extreme-altitude climbers than in controls. We hypothesized that these climbers have lower brainstem blood flow secondary to hypoxia which may possibly cause retention of medullary CO(2) and greater ventilatory drive. Using transcranial Doppler, basilar artery blood flow velocity (Vba) was measured at sea level in 7 extreme-altitude climbers and 10 controls in response to 10 min sequential exposures to inspired oxygen fractions (FI(O(2))) of 0.21 (baseline), 0.13, 0.11, 0.10, 0.09, 0.08 and 0.07. Sa(O(2)) was higher in climbers at FI(O(2)) of 0.11 (P<0.05), 0.08 and 0.07 (both P<0.0001). Expired ventilation (VE) increased more (n.s.), and PET(CO(2)) decreased more (n.s.) in the climbers than in controls. Vba did not significantly change in both groups at FI(O(2)) of 0.13-0.09. At FI(O(2)) of 0.08 and 0.07, Vba decreased 21% (P<0.03) and 27% (P<0.01), respectively, in climbers, and increased 29% (P<0.01) and 27% (P<0.01), respectively, in controls. The conflicting effects of hypoxia and hypocapnia on both medullary blood flow and ventilatory drive thus balance out, giving climbers a greater drive and higher Sa(O(2)), despite lower PET(CO(2)) and lower brain stem blood flow.

Brain Blood Flow in Andean and Himalayan High-Altitude Populations: Evidence of Different Traits for the Same Environmental Constraint

Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330 m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans. The CBF in Himalayans was slightly elevated compared with sea-level subjects, and was 24% higher compared with Andeans. After correction for hematorit and arterial oxygen saturation, CBF was ~20% higher in Himalayans compared with Andeans. Altered brain metabolism in Andeans, and/or increased nitric oxide availability in Himalayans may have a role to explain this difference in brain blood flow.

Intraoperative monitoring of brain tissue oxygen and carbon dioxide pressures reveals low oxygenation in peritumoral brain edema.

Brain edema and swelling often complicate surgery for brain tumors. Its pathophysiology is unclear, as is the relationship with brain tissue oxygenation. Our hypothesis was that brain edema around tumor is cytotoxic type caused by impaired local tissue oxygenation due to increased local tissue pressure. Therefore, we monitored brain tissue oxygen pressure (ptiO2) and carbon dioxide pressure (ptiCO2) in 19 patients undergoing craniotomy for removal of a brain tumor and specifically studied the effect of decompression by dura opening and by tumor removal with respect to the presence of brain swelling. Before craniotomy, multiparameter sensors were inserted into the peritumoral brain tissue guided by MRI-based stereotaxy. In eight patients who had severe brain swelling upon opening of the dura mater, ptiO2 immediately rose from 7 ± 8 mm Hg to 24 ± 15 mm Hg (P < 0.05), whereas in patients who did not have swelling, ptiO2 went from 16 ± 9 to 18 ± 10 mm Hg after opening of the dura. The mean ptiO2 of all patients at the start of resection of the tumor was 18 ± 11 mm Hg, and increased to 30 ± 15 mm Hg after resection was completed (P < 0.05). The effect on ptiO2 of raising the FiO2 to 1.0 was limited in this group of patients, as an increase greater than 50% was found in only six of twelve patients. Notably, in six patients, sensor malfunctions or associated hardware problems occurred, prohibiting useful data acquisition. We conclude that brain tissue oxygenation is reduced in the peritumoral area and improves after local tissue pressure relief, especially in patients with brain swelling. Thus, ischemic processes may contribute to brain edema around tumors. Intraoperative ptiO2 monitoring may enhance the safety of neuroanesthesia, but the high incidence of failures with this type of sensor remains a matter of concern.

Intraoperative Monitoring of Brain Tissue Oxygen and Carbon Dioxide Pressure in Peritumoural Oedema by Stereotactic Placement of Multiparameter Microsensors

Ischaemia may play an important role in peritumoural brain oedema and swelling, but little data exist so far on brain tissue oxygenation adjacent to a tumour mass. We have monitored brain tissue oxygen tension (ptiO2) and brain tissue CO2 tension (ptiCO2) in 19 patients undergoing craniotomy for resection of a brain tumour using a multiparameter sensor placed in the brain parenchyma. Accurate placement of this probe in the peritumoural area was accomplished with the aid of a 3-D neuronavigation system. Due to various problems we obtained useful data in only 13/19 patients. The presence of brain swelling was associated with a significant rise in ptiO2 upon opening of the dura from 7.1 +/- 7.8 to 23.6 +/- 14.7 mm Hg. The average ptiO2 before tumour resection was 18.1 +/- 10.8 mm Hg. A significant improvement in ptiO2 occurred after tumour resection to an average ptiO2 of 29.7 +/- 15.2 mm Hg. From these preliminary data, we conclude that ptiO2 is depressed in the peritumoural area, and improves following tumour resection. Stereotactic placement of sensors for intraoperative ptiO2 monitoring is feasible and may enhance data quality. Nevertheless, the high incidence of failures with this type of sensor remains a matter of concern.