Cerebral glucose and energy metabolism,cerebral oxygen consumption,and blood flow in arterial hypoxaemia

Summary The influence of moderately reduced arterial oxygen tension (aPO₂ of about 45 Torr) on the metabolism and the blood flow of the brain was tested in 20 anaesthetized, artificially ventilated normotensive, normocapnic beagle dogs. It is demonstrated that the decrease in systemic oxygen delivery to the brain is countered by an appropriate increase in flow (CBF being 60.3 ml/100 g min at normoxia and 84.5 mg/100 g min m hypoxaemia) which maintained the cerebral oxygen consumption unchanged (CMRO₂ 3.80 versus 3.32 ml/100 g min). The cortical tissue content of energy-rich phosphates such as ATP, ADP, AMP, and phosphocreatine was also found to be unaltered. Neuropathological examinations excluded any hypoxic cell damage. This reactive vasodilatory reaction of the cerebral vessels is apparently a sensitive regulatory process which protects the brain against marked oxygen lack. However, a normal carbohydrate metabolism is not restored by this cerebrovascular mechanism. For, significantly increased CMRlactate (0.32 versus 1.46 ml/100 g min) indicated raised cerebral glycolysis, and the tissue metabolites of glucose suggested an increased glycolytic flux in the brain. It is concluded that in moderate arterial hypoxaemia, which is not uncommon in clinical practice, cerebral blood flow plays an effective homeostatic role in preventing a disturbance of the energy metabolism of the brain.     

The effect of ketanserin on cerebral blood flow and oxygen metabolism in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on average global cerebral blood flow (CBF) and average global cerebral oxygen metabolism (CMRO₂) was examined in 8 healthy volunteers. CBF and CMRO₂ were measured with the Kety-Schmidt technique before ketanserin administration (baseline) and after administration of 2 different doses of ketanserin intravenously (dose I: 10 mg bolus and an infusion of 6 mg/h; dose II: 20 mg bolus and an ifusion of 20 mg/ h). Baseline CBF and CMRO₂ were 60 and 3.6 ml/100 g/min, respectively, and were not changed by administration of ketanserin dose I. During administration of dose II, however, CBF fell to 52 ml/ 100 g/min (p=0.05) and CMRO₂ was reduced to 3.2 ml/100 g/min (p < 0.05).We conclude that when administered in a high dose, ketanserin has the ability to depress cerebral oxygen metabolism, but when administered in a clinically relevant dose ketanserin does not influence average global CBF or average global CMRO₂. Ketanserin could be a safe antihypertensive drug in neuroanaesthesia or in the neuro-intesive care unit.     

Sequential changes in cerebral blood flow and metabolism in patients with subarachnoid haemorrhage

Summary Haemodynamic and metabolic sequences were investigated in nine patients having subarachnoid haemorrhage (SAH) up to 3 months following aneurysmal rupture, using positron emission tomography (PET). In the pre-spasm stage (2–4 days after SAH) cerebral blood flow (CBF, ml/100 ml/min) was 45±11, the cerebral metabolic rate of oxygen (CMRO₂, ml/100 ml/min) was 2.68±0.50, and cerebral blood volume (CBV, ml/100 ml) was 5.5±1.2. CBF within the normal range and a relatively low CMRO₂, indicated relative hyperaemia. This was possibly due to the direct toxic effect of SAH on the brain metabolism. CBV was considerably elevated. The spasm stage (6–15 days after SAH) showed CBF values of 39±7, CMRO₂ values of 2.42±0.50, and CBV values of 5.4±1.7. CBF decreased significantly (p<0.05 vs pre-spasm stage), and CMRO₂ also tended to decrease, while they were coupling. It is likely that this may have been induced by vasospasm. Thereafter, the PET parameters normalized gradually. During all the stages studied, significant laterality of the PET parameters was not observed. This may be because SAH and vasospasm provide diffuse pathophysiological conditions for the entire brain and cerebral arteries.     

Cerebral blood flow and oxygen metabolism measured with the Kety–Schmidt method using nitrous oxide

Background: The Kety–Schmidt method is the reference method for measuring global cerebral blood flow (CBF), cerebral metabolic rates (CMR) and flux, especially where scanners are unavailable or impractical. Our primary objective was to assess the repeatability of the Kety–Schmidt method in a variety of different approaches using inhaled nitrous oxide (N₂O) as the tracer, combined with photoacoustic spectrometry. A secondary objective was to assess the impact of this tracer on the systemic vascular concentration of nitrite (NO₂^?). Methods: Twenty‐nine healthy male volunteers underwent 61 CBF measurements by breathing a normoxic gas mixture containing 5% N₂O until tension equilibrium. Paired blood samples were collected from an arterial and a jugular bulb catheter in the saturation or desaturation phase, by continuous or the discontinuous sampling. N₂O concentration was measured with photoacoustic spectrometry after equilibration of blood samples with air. CBF was calculated by the Kety–Schmidt equation. CMR of oxygen (CMRO₂) was determined by the Fick principle. NO₂^? in plasma and red blood cells (RBC) was measured by ozone‐based chemiluminescence. Results: The most robust approach for CBF measurement was achieved by discontinuous sampling in the desaturation phase [CBF, 64 (95% confidence interval, 59–71 ml)] 100 g/min; CMRO₂ 1.8 (1.7–2.0) μmol/g/min). The tracer did not influence plasma or RBC NO₂^? (P>0.05 vs. baseline). Conclusion: These findings confirm the reliability and robustness of the Kety–Schmidt method using inhaled N₂O for the measurement of global CBF and CMR. At the low tracer concentration used, altered NO metabolism is unlikely to have affected cerebral haemodynamic function.     

The acute effect of nimodipine on cerebral blood flow,its CO2 reactivity,and cerebral oxygen metabolism in human volunteers

Summary The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO₂ reactivity, and CMRO₂. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO₂ reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/ 100 g/min (48–53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92–99). MABP was slightly reduced, by 8 mmHg (7–9), and 9 mmHg (4–11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO₂, revealed a slight increase after 4 hours (p=0.08). CMRO2 was 3.5 ml/100 g/min (3.2–3.5) and was not changed by the infusion of NIM. At arterial CO₂ tensions ranging from 4.0 to 6.5 Kpa the CO₂ reactivity was 3.0% CBF/ 0.1 kPa (2.6–3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8–3.2) after the infusion of NIM for 3 hours (p=0.02). The median slope of the LnCBFsat/PaCO₂ relationship was 1.5 at baseline compared to 1.3 after NIM (p<0.01). No side effects were observed.The present study shows a decreased CO₂ of the cerebral vessels and a maintained coupling of CBF and CMRO₂ during the infusion of nimodipine.     

Zum Einfluß der präischämischen Blutzuckerkonzentration auf Hämodynamik und regionale Organdurchblutung während und nach kardiopulmonaler Reanimation (CPR) beim Schwein

Blood glucose alterations prior to cerebral ischaemia are associated with poor neurologic outcome, possibly due to extensive lactic acidosis or energy failure. Cerebral effects of hyper- or hypoglycaemia during cardiopulmonary resuscitation (CPR) are less well known. In addition, little information is available concerning cardiac effects of blood glucose alterations. The aim of this study was to evaluate the effects of pre-cardiac-arrest hypo- or hyperglycaemia compared to normoglycaemia upon haemodynamics, cerebral blood flow (CBF) and metabolism (CMRO₂), and regional cardiac blood flow during CPR subsequent to 3?min of cardiac and respiratory arrest and after restoration of spontaneous circulation. Methods. After approval by the State Animal Investigation Committee, 29 mechanically ventilated, anaesthetised pigs were instrumented for haemodynamic monitoring and blood flow determination by the radiolabeled microsphere technique. The animals were randomly assigned to one of three groups: in group I (n=9) blood glucose was not manipulated; in group II (n=10) blood glucose was increased by slow infusion of 40% glucose to 319±13 mg/dl; in group III (n=10) blood glucose was lowered by careful titration with insulin to 34±2 mg/dl. After 3 min of untreated ventricular fibrillation and respiratory arrest, CPR (chest compressor/ventilator (Thumper^®) and epinephrine infusion) was commenced and continued for 8?min. Thereafter, defibrillation was attempted, and if successful, the animals were observed for another 240?min. Cerebral perfusion pressure (CPP), CBF, CMRO₂, coronary perfusion pressure (CorPP), and regional cardiac blood flow were determined at control, after 3?min of CPR, and at 10, 30, and 240?min post-CPR. Results. In group I, 4/9 animals (44%) could be successfully resuscitated; in group II 4/10 (40%); and in group III 0/10 (0%). Prior to cardiac arrest, mean arterial pressure, CPP, and CorPP in group III were significantly lower compared to groups I and II. In group I, CPP during CPR was 26±6?mmHg; CBF 31±9?ml/min/100?g CMRO₂ 3.8±1.2 ml/min/100?g; CorPP 18±5 mmHg; and left ventricular (LV) flow 35±15 ml/min/100 g. In group II: CPP=21±5; CBF 21±7; CMRO₂ 1.8±0.8; CorPP 16±6; and LV flow 22±9; and in group III: CPP 15±3; CBF 11±8; CMRO₂ 1.5±1.1; CorPP 4±2; and LV flow 19±10. During the 240-min post-resuscitation period, there were no differences in CBF, CMRO₂, or LV flow between groups I and II. Conclusion. Hypoglycaemia prior to cardiac arrest appears to be predictive for a poor cardiac outcome, whereas hyperglycaemia does not impair resuscitability compared to normoglycaemia. In addition, hyperglycaemia did not affect LV flow, CBF, or CMRO₂. However, it has to be kept in mind that haemodynamics and organ blood flow do not permit conclusions with respect to functional neurologic recovery or histopathologic damage to the brain, which is very likely to be associated with hyperglycaemia.     

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic spect device

SummaryObjective To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using¹³³Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis.Design Prospective studySetting General intensive care unit in a universitary teaching hospitalSubjects 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours.Measurements and main results CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622; r_s = 0.251, p = 0.246). CMRO₂ was depressed in relation to the severity of injury, specifically ranging from 0.9±0.5 ml/ 100 g/min in patients with GCS 3 to 1.7 ±0.8 ml/100 g/min in patients with GCS 6–7. In no patient with a CMRO₂ less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (r_s = 0.699, p = 0.0002), between CMRO₂ and GOS (F = 4.303, p = 0.031; r_s = 0.525, p = 0.013) and between AJDO₂ and GOS (F = 3.602, p = 0.046; r_s = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (²=18.658, p = 0.001) but did not correlate either with prognosis (² = 1.626, p = 0.443) or with severity (² = 1.913, p = 0.384).Conclusions CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO₂ are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming post-traumatic hypofrontalism but does not correlate with severity and prognosis.     

Cerebral blood flow rate during cardiopulmonary bypass and optimal cerebral perfusion flow rate during separated brain perfusion--a clinical study

There is no established theory to determine the cerebral blood flow rate (CBF) during not only the standard cardiopulmonary bypass but during the cardiopulmonary bypass with separated brain perfusion. This study was carried out to answer the following questions. (1) what is the relationship during the cardiopulmonary bypass between CBF and systemic flow rate or blood pressure?. (2) what is the optimal flow rate to the innominate artery during the separated brain perfusion? Twenty-one patients were selected for this study, who were operated under the cardiopulmonary bypass with a standard roller pump and a membrane oxygenator under moderate hypothermia (nasopharyngeal temperature of 26-28 degrees C). Systemic flow rate was maintained between 40 and 70 ml/kg/min. CBF before the cardiopulmonary bypass was 30.6 +/- 5.5 ml/100 g brain/min, and increased to 33.8 +/- 8.9 ml/100 g brain/min during the cardiopulmonary bypass. CBF was proportional to systemic flow rate (r = 0.62, p less than 0.01) and showed poor association with blood pressure ranged from 35 to 94 mmHg. As for the relationship between innominate arterial and cerebral blood flow rate, CBF linearly followed the decrease of innominate arterial flow rate to below about 9 ml/kg/min, but showed almost no changes when innominate arterial flow rate was over 9 ml/kg/min. It was observed that cerebral oxygen consumption did not decrease significantly under moderate hypothermia (26-28 degrees C), as far as CBF of 25 ml/100 g brain/min was maintained. Based on the relationship between innominate arterial and cerebral blood flow rate, it was shown that the innominate arterial flow rate to provide CBF of 25 ml/100 g brain/min was 5.5 ml/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

Summary Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO₂), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO₂ from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO₂, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr⁻¹·min⁻¹ were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO₂, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

CO2 and indomethacin vasoreactivity in patients with head injury

Summary The purpose of this study was to compare the effect of hyper-ventilation 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 CO₂ and indomethacin vasoreactivities were studied by measurements of cerebral blood flow (CBF) (Cerebrograph 10a, intravenous¹³³Xe technique) and arterio-venous difference of oxygen (AVdO₂). Ischaemia was evaluated from changes in CBF, saturation of oxygen in the jugular bulb (SvjO₂), 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 (AVdO₂ = 4.3 (1.8–8.1) ml/100 ml) indicating moderate luxury perfusion. Levels of CMRO₂ were decreased (1.54 (0.7–3.2) ml/100 g/min) as well.Duringhyperventilation (APaCO₂ = 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. AVdO₂ increased 34.0 (4.0–139.2) %/kPa, MABP was unchanged, CMRO₂ and CPP increased (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 ofindomethacin (30 mg) decreased CBF 14.7 (–16.7–57.4) % and ICP decreased 4.3 (–1–17) mmHg. AVdO₂ increased 27.8 (–40.0–66.7)%, MABP (MABP = 4.9 (–2–21) mmHg) and CPP (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 PaCO₂ level = 4.05 kPa) the changes in MABP, CPP and CBF were significantly greater after indomethacin, while the changes in AVdO₂, ICP, SvjO₂, and LOI were of the same order of magnitude.Nocorrelation between relative reactivities to indomethacin and CO₂, evaluated from changes in CBF and AVdO₂, 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.     

Cerebral oxygen metabolism during total body flow and antegrade cerebral perfusion at deep and moderate hypothermia

The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200 mL/kg/min. After cooling to 18°C (n = 6) or 25°C (n = 7), flow was reduced to 100 mL/kg/min (half‐flow, HF) for 15 min and ACP was initiated at 40 mL/kg/min for 45 min. Following rewarming, animals were weaned from bypass and survived for 4 h. At baseline, HF, ACP, and 4 h post‐CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO₂) and cerebral metabolic rate of oxygen (CMRO₂) were monitored. Regional cranial oxygen saturation (rSO₂) was continuously recorded throughout the procedure using near‐infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO₂ trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO₂ at ACP matched that at HF. Cranial rSO₂ was significantly greater at HF and ACP (P < 0.001, P < 0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO₂ was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO₂ at ACP was greater than that at HF (P = 0.001). Cranial rSO₂ was significantly greater at HF (P = 0.01), equal at ACP, and lower after CPB (P = 0.03). Lactate was significantly higher at all time points (P = 0.036, P < 0.001, and P < 0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100 mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.     

Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.

OBJECT: Recently, concern has been raised that hyperventilation following severe traumatic brain injury (TBI) could lead to cerebral ischemia. In acute ischemic stroke, in which the baseline metabolic rate is normal, reduction in cerebral blood flow (CBF) below a threshold of 18 to 20 ml/100 g/min is associated with energy failure. In severe TBI, however, the metabolic rate of cerebral oxygen (CMRO2) is low. The authors previously reported that moderate hyperventilation lowered global hemispheric CBF to 25 ml/100 g/min but did not alter CMRO2. In the present study they sought to determine if hyperventilation lowers CBF below the ischemic threshold of 18 to 20 ml/100 g/ min in any brain region and if those reductions cause energy failure (defined as a fall in CMRO2). METHODS: Two groups of patients were studied. The moderate hyperventilation group (nine patients) underwent hyperventilation to PaCO2 of 30 +/- 2 mm Hg early after TBI, regardless of intracranial pressure (ICP). The severe hyperventilation group (four patients) underwent hyperventilation to PaCO2 of 25 +/- 2 mm Hg 1 to 5 days postinjury while ICP was elevated (20-30 mm Hg). The ICP, mean arterial blood pressure, and jugular venous O2 content were monitored, and cerebral perfusion pressure was maintained at 70 mm Hg or higher by using vasopressors when needed. All data are given as the mean +/- standard deviation unless specified otherwise. The moderate hyperventilation group was studied 11.2 +/- 1.6 hours (range 8-14 hours) postinjury, the admission Glasgow Coma Scale (GCS) score was 5.6 +/- 1.8, the mean age was 27 +/- 9 years, and eight of the nine patients were men. In the severe hyperventilation group, the admission GCS score was 4.3 +/- 1.5, the mean age was 31 +/- 6 years, and all patients were men. Positron emission tomography measurements of regional CBF, cerebral blood volume, CMRO2, and oxygen extraction fraction (OEF) were obtained before and during hyperventilation. In all 13 patients an automated search routine was used to identify 2.1-cm spherical nonoverlapping regions with CBF values below thresholds of 20, 15, and 10 ml/ 100 g/min during hyperventilation, and the change in CMRO2 in those regions was determined. In the regions in which CBF was less than 20 ml/100 g/min during hyperventilation, it fell from 26 +/- 6.2 to 13.7 +/- 1 ml/ 100 g/min (p < 0.0001), OEF rose from 0.31 to 0.59 (p < 0.0001), and CMRO2 was unchanged (1.12 +/- 0.29 compared with 1.14 +/- 0.03 ml/100 g/min; p = 0.8). In the regions in which CBF was less than 15 ml/100 g/min during hyperventilation, it fell from 23.3 +/- 6.6 to 11.1 +/- 1.2 ml/100 g/min (p < 0.0001), OEF rose from 0.31 to 0.63 (p < 0.0001), and CMRO2 was unchanged (0.98 +/- 0.19 compared with 0.97 +/- 0.23 ml/100 g/min; p = 0.92). In the regions in which CBF was less than 10 ml/100 g/min during hyperventilation, it fell from 18.2 +/- 4.5 to 8.1 +/- 0 ml/100 g/min (p < 0.0001), OEF rose from 0.3 to 0.71 (p < 0.0001), and CMRO2 was unchanged (0.78 +/- 0.26 compared with 0.84 +/- 0.32 ml/100 g/min; p = 0.64). CONCLUSIONS: After severe TBI, brief hyperventilation produced large reductions in CBF but not energy failure, even in regions in which CBF fell below the threshold for energy failure defined in acute ischemia. Oxygen metabolism was preserved due to the low baseline metabolic rate and compensatory increases in OEF; thus, these reductions in CBF are unlikely to cause further brain injury.     

Cerebral Blood Flow and Oxygen Uptake in Endotoxic Shock. An Experimental Study in Dogs

Cerebral blood flow (CBF), cerebral oxygen uptake (CMRo₂) and central haemodynamics in anaesthetized dogs with controlled ventilation were studied at intervals for 2 h following an intravenous injection of E. coli endotoxin, 1.0–1.5 mg/kg. CBF showed a 30% decrease within 15 min after the endotoxin administration, while the arterial blood pressure was still not markedly depressed. Autoregulation to arterial blood pressure changes was maintained during endotoxinaemia and the cerebrovascular reaction to changes in arterial carbon dioxide tension (Paco₂) depressed. Normocapnic animals (PacO₂ ≥ 4.0 kPa) showed an increase in CMRO₂ of over 40%, that was obvious 1 h after the administration of endotoxin. The intracranial pressure was decreased within 5 min of the administration of endotoxin irrespective of the prevailing arterial blood pressure. Thereafter, it was raised above the control level. Two hours after endotoxin increased protein concentrations in cerebrospinal fluid were seen, results compatible with blood-brain barrier damage and penetration of other substances; e.g. monoamines released during endotoxinaemia could thus be expected to have a direct influence on both cerebral blood flow and metabolism.     

EFFECTS OF ALTHESIN ON CEREBRAL BLOOD FLOW AND OXYGEN CONSUMPTION IN MAN

Cerebral circulation and metabolism during Althesin anaesthesiawere studied in seven healthy patients. Althesin was given ina single dose of 0.1 ml/kg and thereafter infused at a constantrate of 0.3 ml/kg/h. During Althesin infusion, the cerebralblood flow (CBF), the cerebral metabolic rate for oxygen (CMRo₂)were 29 ±10 ml/100 g/min and 1.7 ± 0.4 ml/100g/min, respectively. These values were significantly differentfrom those obtained in awake subjects in our laboratory (CBF:46±7 ml/100 g/min; CMRo₂: 3.1 ±0.6 ml/100 g/min).During CBF measurement, the mean cerebral perfusion pressure,cerebral vascular resistance (CVR) and arterial carbon dioxidetension (Pa_CO2) were 89±16mmHg,3.4±1.3 mm Hg/ml/100g/min, and 36±9mmHg, respectively. The relationship betweenCBF and .Pa_CO2 was studied and it was found that during Althesinanaesthesia reactivity of cerebral vessels to the alterationof Pa_CO2 was maintained. It is concluded that Althesin causedcerebral metabolic depression which was accompanied by a decreasein CBF and an increase in CVR.     

The effect of ketanserin on cerebral blood flow and cerebrovascular CO2 reactivity in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on the cerebral blood flow (CBF) and the cerebrovascular CO₂ reactivity was examined in 10 healthy volunteers. Ketanserin was administered as an intravenous bolus of 10 mg followed by an infusion of 6mg/h. Before administration CBF was measured by single photon emission computerized tomography (SPECT) of inhaled¹³³ Xenon. Then arterial CO₂ tension was subsequently decreased by voluntary hyperventilation and increased by breathing an air/CO₂ mixture. The relative changes in CBF induced by the changes in arterial CO₂ tension were estimated by the cerebral arterio-venous oxygen content difference method. One hour following the start of ketanserin infusion the SPECT measurement and CO₂ manipulations were repeated.The CO₂ reactivity (expressed as the slope of the regression line of the linear relation between CBF and PaCO₂), was unchanged, i.e. 3.2%/0.1 kPa before ketanserin and 4. 1%/0.1 kPa during ketanserin, respectively. Using regression lines from a semi-logarithmic plot the CO₂ reactivity was also unchanged 3.4%/0.1 kPa and 3.5%/0.1 kPa, respectively. Ketanserin did not change CBF. The cerebral oxygen metabolism (CMRO₂) was decreased 19% one hour after the start of infusion of ketanserin.In conclusion administration of ketanserin in a clinically relevant dose to healthy volunteers does not change the regional CBF not the cerebrovascular CO₂ reactivity, but a decrease in CMRO₂ was observed. However further studies are needed to clarify whether ketanserin in fact has a depressing effect on CMRO₂ or whether the different results are caused by methodological errors or stocastic variation.     

pH-Stat Management Reduces the Cerebral Metabolic Rate for Oxygen during Profound Hypothermia (17 degrees Celsius): A Study during Cardiopulmonary Bypass in Rabbits

Background: Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management.

Methods: New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees Celsius with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees Celsius. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation.

Results: In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 plus/minus 17 vs. 21 plus/minus 4 ml *symbol* 100 g sup -1 *symbol* min sup -1 [median plus/minus quartile deviation]; P = 0.017); and CMRO2 (0.54 plus/minus 0.13 vs. 0.32 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 plus/minus 2 vs. 78 plus/minus 2 mm Hg) nor hemispheric CBF (40 plus/minus 10 vs. 48 plus/minus 6 ml *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 plus/minus 0.10 vs. 0.45 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.002).     

Measurement of cerebral blood flow by single photon emission computed tomography in cases of internal carotid artery occlusion

Cerebral blood flow (CBF) was measured with 133xenon inhalation and single photon emission computed tomography in 33 cases of internal carotid artery occlusion, in the resting state and 25 minutes after acetazolamide (Diamox) administration. The patient population consisted of 24 males and nine females with a mean age of 57 years, who presented with transient ischemic attacks or stroke. Acetazolamide inhibits carbonic anhydrase, and CBF increases as a result of dilatation of cerebral arteries due to CO2 accumulation. The mean CBF was 46 ml/100/g/min on the affected hemisphere and 56 ml/100/g/min on the unaffected hemisphere. The mean CBF value obtained by the same method in 10 normal volunteers was 55 ml/100/g/min. Thus, in the patients, CBF decreased on the affected side. The average increase in CBF after acetazolamide administration was 9% on the affected side and 17% on the unaffected side. The average increase in 10 normal volunteers was 32%. The reduced cerebral arterial reactivity to acetazolamide administration was bilateral in the patient group, which suggests that the cerebral arteries were dilated in order to maintain normal CBF. Extra-intracranial (EC-IC) bypass surgery was performed in nine patients. Preoperatively, the mean CBF was 48 ml/100 g/min on the affected side and 57 ml/100 g/min on the unaffected side; the postoperative CBF was 48 ml/100 g/min on the affected side and 56 ml/100 g/min on the unaffected side. Thus, there was no notable change in CBF on either side after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pression tissulaire cérébrale en oxygène : pour quoi faire et pour qui ?

The main purpose of neurointensive care is to fight against cerebral ischaemia. Ischaemia is the cell energy failure following inadequacy between supply of glucose and oxygen and demand. Ischemia monitoring starts with a global approach, especially with cerebral perfusion pressure (CPP) determined by mean arterial pressure and intracranial pressure (ICP). However, global monitoring is insufficient to detect “regional” ischaemia, leading to development of local monitoring such as brain oxygen partial pressure (PtiO₂). PtiO₂ is measured on a volume of a few mm³ from a probe implanted in the cerebral tissue. The normal value is classically included between 25 and 35 mmHg and critical ischemic threshold is 10 mmHg. Understanding what exactly is PtiO₂ is still a matter of debate. PtiO₂ is more an indicator of oxygen diffusion depending of oxygen arterial pressure (PaO₂) and local cerebral blood flow (CBF). Increase PaO₂ to treat PtiO₂ would hide information about local CBF. PtiO₂ is useful for the detection of low local CBF even when ICP is low as in hypocapnia-induced vasoconstriction. PtiO₂-guided management could lead to a continuous optimization of arterial oxygen transport for an optimal cerebral tissue oxygenation. Finally, PtiO₂ has probably a global prognostic value because studies showed that hypoxic values for a long period of time lead to an unfavourable neurologic outcome. In conclusion, PtiO₂ provides additional information for regional monitoring of cerebral ischaemia and deserves more intensive use to better understand it and probably improve neurointensive care management.     

Ist die hirnvenöse Sauerstoffsättigung ein Maß für die zerebrale Durchblutung?

The arteriovenous oxygen content difference (avDO₂) of the brain is dependent on O₂ consumption (CMRO₂) and cerebral blood flow (CBF). With unchanging arterial O₂ content, avDO₂ is inversely related to cerebral venous O₂ saturation (SO₂). Measurement of SO₂ in the jugular bulb not only provides information about the O₂ balance of the brain, but may give an important estimation of CBF if a clinically useful correlation is proven. The aim of the present study was to verify this aspect. Methods. Sixty-two male patients undergoing coronary revascularisation were investigated. The study was approved by the local Ethical Committee and each patient gave written informed consent on the preoperative day. At four points during the perioperative course arterial and cerebral venous SO₂ and CBF were measured. Cerebral venous blood was sampled from a catheter in the superior bulb of the right internal jugular vein. CBF was measured using the argon wash-in technique. All sampled data were pooled and evaluated. Results. As expected from theory, cerebral venous SO₂ and avDO₂ showed a close linear relationship (r=?0.892). However, only a weak hyperbolic relationship was found between cerebral venous SO₂ and CBF. In addition, no direct correlation between CMRO₂ and SO₂ in the jugular bulb could be demonstrated. Conclusions. In this clinical study, a close relationship between cerebral venous SO₂ and CBF was not found. This was primarily due to the high variability of cerebral O₂ uptake. Changes in cerebral venous SO₂ may therefore not be used as an estimate of perioperative changes in CBF.     

Measurements of CO2 reactivity and barbiturate reactivity in patients with severe head injury

Summary In nine patients with severe head injury subjected to continuous hyperventilation and barbiturate coma treatment with pentobarbitone, the regional cerebral blood flow was measured as initial slope index (ISI) with a 32 channel Cerebrograph, and cerebral metabolic rate of oxygen (CMRO₂) was calculated as the product of mean global CBF and the arterio-venous oxygen content difference.CBF was measured at strategic intervals either to follow the treatment (hyperventilation and/or pentobarbitone), or to determine whether these principles of treatment should be intensified or reduced. During the flow measurements the CO₂ reactivity and the reactivity to a bolus injection of thiopentone 5 mg/kg were calculated globally and regionally. The global CO₂ reactivity was calculated as relative (%change CBF/PaCO₂ mmHg) and absolute (CBF/ PaCO₂ mmHg), and the reactivity to barbiturate was calculated globally as CMRO₂, and regionally as %change rCBF.The absolute and relative global CO₂ reactivities correlated positively with the mean. CBF values before hyperventilation, and the global barbiturate reactivity was dependent on the CMRO₂ value obtained before hyperventilation. However, at low levels of CMRO₂ ranging between 1.0 and 1.1 ml O₂ the barbiturate reactivity was abolished. The regional studies of CBF, CMRO₂, CO₂ reactivity and barbiturate reactivity gave important information, when decisions concerning therapeutic regimes with special reference to hyperventilation and sedation with pentobarbitone were necessary.