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.     

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

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 x 100 gr(-1) x 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.     

Regional cerebral blood flow and oxygen metabolism in normal pressure hydrocephalus after subarachnoid hemorrhage

To clarify the pathophysiology of normal pressure hydrocephalus (NPH) after subarachnoid hemorrhage, the authors measured cerebral blood flow (CBF), cerebral oxygen metabolic rates (CMRO2), the cerebral oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in eight normal volunteers, six SAH patients with NPH, and seven patients without NPH by 15O-labeled gas and positron emission tomography (PET). In the NPH group, PET revealed a decrease in CBF in the lower regions of the cerebral cortex and a diffuse decrease in CMRO2. The decrease in CBF in the lower frontal, temporal, and occipital cortices was significantly greater in the NPH than in the non-NPH group. Reduction of CMRO2 was also more extensive in the NPH group, and both CBF and CMRO2 were more markedly decreased in the lower frontal region. OEF was increased in all areas in both of the patient groups, but the increase was not significant in most areas. CBF, CMRO2 and OEF did not significantly differ between the non-NPH group and the normal volunteers. There was no significant difference in CBV among the three groups. These results indicate that NPH involves impairment of cerebral oxygen metabolism in the lower regions of the cerebral cortex, particularly in the lower frontal region.     

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.     

Cerebral blood flow decreases with time whereas cerebral oxygen consumption remains stable during hypothermic cardiopulmonary bypass in humans

Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRO2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A-VDcereO2) and CMRO2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the PaCO2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15-25 min, we hypothesized that a time-dependent decline in CBF would accentuate the CBF reduction caused by a decrease in PaCO2, but would blunt the CBF increase associated with a rise in PaCO2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32-48 mm Hg) or higher (50-71 mm Hg) range of PaCO2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower PaCO2 and the other at a higher PaCO2 within the respective ranges. Cerebrovascular responsiveness to changes in PaCO2 was calculated as specific reactivity (SR), the change in CBF divided by the change in PaCO2, expressed in mL.100 g-1.min-1.mm Hg-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of morphine on cerebral blood flow autoregulation CO2-reactivity in experimental subarachnoid hemorrhage.

Previous reports show that naloxone improves ischemic deficits and clinical conditions in patients after subarachnoid hemorrhage (SAH). These observations have raised concern about the routine use of morphine in the treatment of severe headache after SAH. The present study was carried out to investigate the effects of morphine on cerebral vasoreactivity after experimental SAH. Cerebral blood flow (CBF) autoregulation was studied in two groups of eight rats each with experimental SAH. A bolus intravenous injection of morphine, 1 mg/kg, was administered in one group and the other was used as a control group. During eucapnia, CBF was measured by the intracarotid 133Xenon method during decreasing mean arterial blood pressure (MABP). CO2-reactivity was investigated in two corresponding groups where CBF was measured at decreasing PaCO2 levels during constant MABP. Morphine decreased mean baseline CBF by 34% and 26% in the study of autoregulation and CO2-reactivity, respectively. Cerebral blood flow autoregulation was found impaired in both controls and the morphine group. However, the mean slope of the linear regression lines of CBF/MABP was 0.49 +/- 0.32 ml/100g/min/mm Hg in the morphine group, which was significantly lower than 1.24 +/- 0.59 ml/100g/min/mm Hg in the controls (p < 0.05). Also the mean CO2-reactivity was significantly lower, 0.64 +/- 0.53 %/0.1kPa, in the morphine group, compared to 2.36 +/- 0.87 %/0.1kPa in the controls (p < 0.001). The results show that in rats with SAH, morphine partially restores CBF autoregulation but attenuates CO2-reactivity.     

Cerebrovascular metabolic autoregulation is impaired during liver transplantation

BACKGROUND: We determined whether the coupling between cerebral blood flow (CBF) and oxygen metabolism (CMRO2) is preserved during liver transplantation. Because of cerebrovascular dilatation, we hypothesized that cerebral metabolic autoregulation is impaired, because CBF becomes uncoupled from CMRO2 during the reperfusion phase of the operation. MATERIALS AND METHODS: In a prospective study, 13 patients (8 women, median age 46, range 21-6) with liver failure (10 with end-stage chronic liver disease and 3 with acute liver failure) were enrolled. Catheters were placed in a femoral artery and in the internal jugular vein for calculation of the cerebral arteriovenous oxygen content difference (AVDO2). CBF was recorded by the 133Xenon injection technique, and by transcranial Doppler sonography determined mean flow velocity (Vmean) in the middle cerebral artery. The CMRO2 was calculated as the AVDO2 times CBF and the cerebrovascular resistance (CVR) as the mean arterial pressure to CBF ratio. An index of large cerebral artery diameter was expressed by the CBF to Vmean ratio. RESULTS: From induction of anesthesia to the anhepatic period, CBF decreased from a median of 47 (interquartiles 31-55) to 41 (37-48) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged (1.3 [0.9-2.5] vs. 1.7 [0.9-2.3] ml 100 g(-1) min(-1)). In the reperfusion phase, the CBF increased to 51 (45-54) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged at 1.1 (1.0-2.5) ml 100 g(-1) min(-1). The CVR decreased from 2.0 mm Hg (1.4-2.1) to 1.4 (1.1-1.8) mm Hg(-1) min 100 g ml. In the anhepatic phase, mean arterial pressure decreased from 92 mm Hg (84-98) to 85 (80-92) mm Hg and at reperfusion it was 80 (71-105) mm Hg. From the anhepatic to the reperfusion phase, the CBF increased 7% (0 to 26) for each mm Hg concomitant increase in PaCO2. The CBF to Vmean ratio remained stable (1.0 [0.8-1.2] vs. 0.9 [0.7-1.1] ml 100 g(-1) min(-1) cm(-1) sec). CONCLUSION: During the reperfusion phase of liver transplantations, cerebrovascular dilatation uncouples cerebral oxidative metabolism from blood flow. The increase in CBF is beyond what can be explained by changes in arterial carbon dioxide tension and arterial pressure.     

Cerebral blood flow and oxygen consumption during isoflurane and halothane anesthesia in man

In 13 patients, the effects on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of isoflurane and halothane administered in a clinically relevant situation were studied. Measurements were performed during fentanyl/nitrous oxide (65%) anesthesia together with moderate hyperventilation (PaCO2 approx 4.5 kPa), and repeated after addition of 0.65 MAC of isoflurane (n = 6) or halothane (n = 7). CBF was measured after intravenous administration of 133xenon and CMRO2 was calculated from the arterial venous differences of oxygen content (AVDO2) determined in arterial and jugular venous bulb blood. CBF and CMRO2 (means +/- s.e. mean) determined prior to administration of volatile agents were 28 +/- 5 ml x 100(-1) x min-1 and 2.0 +/- 0.3 ml x 100 g-1 x min-1, respectively, in the isoflurane group. In the halothane group, CBF was 25 +/- 0.4 ml x 100 g-1 x min-1 and CMRO2 was 2.0 +/- 0.4 ml x 100 g-1 x ml-1. There were no significant intergroup differences. Isoflurane did not change CBF, whereas halothane produced an increase of 36% (P less than 0.05) compared to values obtained during fentanyl/N2O anesthesia. In addition, isoflurane caused a further decrease in CMRO2 of 12% (P less than 0.01) as compared to a 20% increase (P less than 0.05) with halothane. The cerebral metabolic depression caused by the short-acting anesthetic induction agents would be expected to decrease with time, and could partly explain the observed increase in CMRO2 produced by halothane. The study suggests that the cerebrovascular and metabolic properties of isoflurane differ from those of halothane, also in man.     

Cerebral blood flow and metabolism during adenosine–induced hypotension in patients undergoing cerebral aneurysm surgery

The effects of adenosine-induced hypotension on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral lactate production, together with systemic haemodynamics, were studied in 10 patients undergoing cerebral aneurysm surgery in neurolept anaesthesia with controlled hyperventilation. CBF changes were determined in six of the patients with a retrograde thermodilution technique in the jugular vein. Hypotension was induced with a continuous infusion of adenosine in the superior vena cava. The dose range was 0.06-0.35 mg/kg/min, and this caused a 42% reduction in mean arterial blood pressure (MABP) from 79 +/- 4 to 46 +/- 1 mmHg (10.5 +/- 0.5 to 6.1 +/- 0.1 kPa) through a profound reduction in systemic vascular resistance (SVR), which amounted to 61%. No significant change occurred in CBF. Whole body AV-difference of oxygen was decreased by 37%, and cerebral AV-difference by 28%, corresponding to reductions in whole body oxygen uptake and CMRO2 of 16 and 17%, respectively. Cerebral AV-difference of lactate did not change. In the posthypotensive period MABP was increased by 10%, together with a minor increase in CBF (15%). It is concluded, that adenosine-induced hypotension at MABP levels between 40-50 mmHg (5.3-6.7 kPa) does not affect cerebral oxygenation unfavourably, and may even offer a protective effect by reducing cerebral oxygen demand. The slight CBF increase in the posthypotensive period was probably secondary to an increase in MABP together with a blunted autoregulation, but in no case was this effect considered to be harmful for the patient.     

Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions

Mean hemispheric cerebral blood flow (CBF) and intracranial pressure (ICP) were measured in 19 severely head-injured patients treated with barbiturate coma. The CBF was calculated from the clearance of tracer substance monitored by extracranial scintillation detectors after intravenous administration of xenon-133. In 11 of the patients cerebral arteriovenous oxygen differences were measured simultaneously. In all patients the effects of pronounced hyperventilation were recorded prior to initiation of barbiturate treatment. A normal CBF response to hyperventilation (delta CBF/delta PaCO2 greater than or equal to 1) was obtained in eight patients. In these patients induction of barbiturate coma was accompanied by physiological decreases in CBF and in the calculated cerebral metabolic rate of oxygen (CMRO2); they also exhibited a rapid and lasting decrease in ICP. A decreased or an abolished CO2 reactivity was recorded (delta CBF/delta PaCO2 less than 1) in 11 patients. In 10 of these 11 patients the physiological decreases in CBF and CMRO2 were not obtained during barbiturate treatment and the decrease in ICP was transitory. This study demonstrates a correlation between cerebral vasoreactivity, physiological effects of barbiturate therapy, and clinical outcome.     

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2

Measurement of 133Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.     

Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failure

BACKGROUND: Our previous study reported that cerebral oxygen extraction fraction (OEF) increased in hemodialysis patients with anemia. The increased OEF suggests that the cerebral vasodilatory capacity might be impaired in these patients. To clarify this issue, we measured the CO2 response in patients with anemia secondary to chronic renal failure (CRF) using positron emission tomography (PET). METHODS: Ten anemic patients with CRF (6 females and 4 males) and 6 age-matched normal controls were studied. The underlying diseases of CRF were glomerulonephritis in 8 patients, systemic lupus erythematosus (SLE) in one patient, and hypertension in one patient; in this cohort, 5 patients were on hemodialysis treatment and the remaining 5 patients were in a pre-hemodialysis state. The cerebral blood flow (CBF) was measured by the O-15 H2O bolus injection method with each patient in a resting state and during 5% CO2 inhalation. The CO2 response was estimated as the percentage change of CBF per 1 mm Hg change of PaCO2. RESULTS: The CO2 response was significantly attenuated in anemic patients with CRF in comparison to the normal controls, and it inversely correlated with the severity of anemia. There was no significant difference in the CO2 response between the hemodialysis and pre-hemodialysis patients. The CO2 response significantly correlated with CBF and the cerebral metabolic rate for oxygen (CMRO2) at rest, however, it did not correlate with OEF and cerebral blood volume (CBV). CONCLUSIONS: The present study revealed the existence of a reduced cerebral vasodilatory capacity in anemic patients with CRF, suggesting that chronic hypoxic brain damage might play a role in the impaired cerebrovascular response to CO2.     

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury

OBJECT: Hyperventilation therapy, blood pressure augmentation, and metabolic suppression therapy are often used to reduce intracranial pressure (ICP) and improve cerebral perfusion pressure (CPP) in intubated head-injured patients. In this study, as part of routine vasoreactivity testing, these three therapies were assessed in their effectiveness in reducing ICP. METHODS: Thirty-three patients with a mean age of 33 +/- 13 years and a median Glasgow Coma Scale (GCS) score of 7 underwent a total of 70 vasoreactivity testing sessions from postinjury Days 0 to 13. After an initial 133Xe cerebral blood flow (CBF) assessment, transcranial Doppler ultrasonography recordings of the middle cerebral arteries were obtained to assess blood flow velocity changes resulting from transient hyperventilation (57 studies in 27 patients), phenylephrine-induced hypertension (55 studies in 26 patients), and propofol-induced metabolic suppression (43 studies in 21 patients). Changes in ICP, mean arterial blood pressure (MABP), CPP, PaCO2, and jugular venous oxygen saturation (SjvO2) were recorded. With hyperventilation therapy, patients experienced a mean decrease in PaCO2 from 35 +/- 5 to 27 +/- 5 mm Hg and in ICP from 20 +/- 11 to 13 +/- 8 mm Hg (p < 0.001). In no patient who underwent hyperventilation therapy did SjvO2 fall below 55%. With induced hypertension, MABP in patients increased by 14 +/- 5 mm Hg and ICP increased from 16 +/- 9 to 19 +/- 9 mm Hg (p = 0.001). With the aid of metabolic suppression, MABP remained stable and ICP decreased from 20 +/- 10 to 16 +/- 11 mm Hg (p < 0.001). A decrease in ICP of more than 20% below the baseline value was observed in 77.2, 5.5, and 48.8% of hyperventilation, induced-hypertension, and metabolic suppression tests, respectively (p < 0.001 for all comparisons). Predictors of an effective reduction in ICP included a high PaCO2 for hyperventilation, a high study GCS score for induced hypertension, and a high PaCO2 and a high CBF for metabolic suppression. CONCLUSIONS: Of the three modalities tested to reduce ICP, hyperventilation therapy was the most consistently effective, metabolic suppression therapy was variably effective, and induced hypertension was generally ineffective and in some instances significantly raised ICP. The results of this study suggest that hyperventilation may be used more aggressively to control ICP in head-injured patients, provided it is performed in conjunction with monitoring of SjvO2.     

Arterial CO2 tension and cerebral vascular reactivity during the induction of acute hypertension and hypotension in the awake human

The CO2 reactivity was calculated at mean arterial blood pressure (MABP) values ranging from 40 to 140 mm Hg in 15 normotensive volunteers and in 7 patients with chronic arterial hypertension. The cerebral vascular reactivity (CVR) was estimated from indirect measurements of cerebral blood flow (CBF) by the arteriovenous oxygen saturation method. In all subjects but one of the hypertensive patients, there was a significant linear correlation of CVR with PaCO2 over the total range of MABP. The median CO2 reactivity in the volunteers and in the hypertensive patients was 2.7 and 2.8% CBF/0.1 kPa, respectively (NS). At MABP values corresponding to the plateau of CBF autoregulation (baseline MABP +/- 20%), the median CO2 reactivity was 3.0% CBF/0.1 kPa in both groups. During a cross-sectional correlation analysis of the pooled data from all volunteers, the CO2 reactivity increased with increasing MABP in the range of 50-110 mm Hg. Outside this range there was no correlation of CVR with PaCO2. In conclusion, our results confirmed that during acute hypo- and hypertension, the influence of PaCO2 on the CVR is reduced. The full CO2 reactivity of the cerebral vessel exists only at the plateau of CBF autoregulation.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

Hemodynamic and metabolic effects of cerebral revascularization

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.     

The response of the canine cerebral circulation to hyperventilation during anesthesia with desflurane

Arterial CO2 tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) and cerebral vascular resistance (CVR) in animals and humans. The normal responsiveness of the cerebral vasculature to PaCO2 is approximately 2 ml.min-1.100 g-1.mmHg-1. This study examined the effect of desflurane, a new volatile anesthetic, on the responsiveness of the cerebral vasculature to changes in PaCO2. Mean arterial pressure (MAP), CBF, CVR, intracranial pressure (ICP), and cerebral metabolic rate for O2 (CMRO2) were measured in five dogs anesthetized with desflurane (0.5-1.5 MAC) at normocapnia (PaCO2 = 40 mmHg) and at two levels of hypocapnia (PaCO2 = approximately 30 and approximately 20 mmHg). Under desflurane anesthesia, similar changes in CBF and CVR occurred with hyperventilation at all MAC levels of desflurane. At 0.5 MAC, CBF decreased significantly, from 81 +/- 6 to 40 +/- 3 ml.min-1.100 g-1 (P less than 0.05, mean +/- SE) when PaCO2 was decreased from 40 to 24 mmHg; i.e., the CBF decreased approximately 2.6 ml.min-1.100 g-1.mmHg-1. At 1.0 MAC desflurane, CBF decreased significantly, from 79 +/- 10 to 43 +/- 5 ml.min-1.100 g-1 with hyperventilation (2.0 ml.min-1.100 g-1.mmHg-1); at 1.5 MAC desflurane, CBF decreased from 65 +/- 6 to 38 +/- 2 ml.min-1.100 g-1 with hyperventilation (1.6 ml.min-1.100 g-1.mmHg-1). Despite the significant decreases in CBF with hyperventilation, there was no significant change in ICP. Dose-dependent decreases in MAP were observed with increasing concentrations of desflurane but were not significantly affected by ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of 1 MAC desflurane on cerebral metabolism, blood flow and carbon dioxide reactivity in humans

We investigated the cerebral haemodynamic effects of 1 MAC desflurane anaesthesia in nine male patients scheduled for elective coronary bypass grafting. For the measurement of cerebral blood flow (CBF) a modified Kety-Schmidt saturation technique with argon as inert tracer gas was used. Measurements of CBF were made before induction of anaesthesia and 30 min after induction under normocapnic, hypocapnic and hypercapnic conditions in sequence. Changes in mean arterial pressure after induction of anaesthesia and during the course of the study were minimized using norepinephrine infusion. In comparison with the awake state under normocapnic conditions, desflurane reduced mean cerebral metabolic rate of oxygen (CMRO2) by 51% and mean cerebral metabolic rate of glucose (CMRglc) by 35%. Concomitantly, CBF was significantly reduced by 22%; jugular venous oxygen saturation (SjvO2) increased from 58 to 74%. Hypo- and hypercapnia caused a 22% decrease and a 178% increase in CBF, respectively. These findings may be interpreted as the result of two opposing mechanisms: cerebral vasoconstriction induced by a reduction of cerebral metabolism and a direct vasodilator effect of desflurane. CBF alterations under variation of PaCO2 indicate that cerebrovascular carbon dioxide reactivity is not impaired by application of 1 MAC desflurane.      

Effects of adenosine–induced hypotension on cerebral blood flow and metabolism in the pig

The cerebral and systemic effects of hypotension induced by adenosine (0.61 +/- 0.07 mg.kg-1.min-1) were studied in eight pigs anesthetized with droperidol, phenoperidine and nitrous oxide. Mean arterial blood pressure (MABP) was reduced by 58%, from 17.2 kPa (128 mmHg) to 6.9 kPa (53 mmHg) during a 30-min period. The hypotension was caused by a decrease in systemic vascular resistance (58%) while the cardiac output was unaffected. Cerebral blood flow (CBF), as determined by microsphere distribution, and the cerebral metabolic rate for oxygen (CMRO2) remained unchanged. Cerebral vascular resistance decreased by 61%. There were no signs of cerebral lactate release. After discontinuation of adenosine infusion, the MABP returned to control levels within 5 min. Thirty minutes later the CBF was increased by approximately 60% in comparison to the control, while the CMRO2 was unchanged. It is concluded that adenosine-induced hypotension in pigs is associated with preserved CBF and CMRO2, whereas cerebral hyperperfusion is present in the early post-hypotensive period.