Hypocapnia prevents the decrease in regional cerebral metabolism during isoflurane-induced hypotension

In neurologic surgery, induced hypotension is often used while the patient is hypocapnic. We investigated, by tissue biopsy methods and scintillation counting, the regional cerebral glucose utilization (rCMRglc) and blood flow (rCBF) in rats subjected to hypocapnia alone and in combination with hypotension. Anesthesia was maintained with 1.0% isoflurane in nitrous oxide/oxygen. Seven rats were maintained at PaCO2 of 40 mm Hg, six rats were ventilated to PaCO2 of 20 mm Hg, and six animals to PaCO2 of 20 mm Hg in combination with arterial hypotension of 50 mm Hg induced by isoflurane 2.5-3.5%. During hypocapnia, rCMRglc tended to increase in all regions, but the increase was statistically insignificant; rCBF was reduced uniformly by 40%. During combined hypocapnia/hypotension, rCMRglc was unaltered when compared to hypocapnia; compared to normocapnia, increases were seen in hippocampus and cerebellum. During hypocapnia/hypotension, rCBF was unaltered in cortical areas, while increases were seen in all subcortical areas compared to hypocapnia. Regional values of the ratio of rCBF/rCMRglc indicated that during hypocapnia and hypotension induced by isoflurane in nitrous oxide/oxygen, the individual brain areas were perfused according to their metabolic needs. It is suggested that hypocapnia may prevent the decrease in rCMRglc, which is usually observed during deep isoflurane anesthesia.     

Effect of hypocapnia on arterial oxygenation during induced hypotension]

We evaluated the effects of hypocapnia on arterial oxygenation during induced hypotension with nitroglycerin (TNG) or prostaglandin E1 (PGE1) in patients undergoing mastectomy. Of the 20 patients studied, 10 belonged to TNG group and 10 belonged to PGE1 group. Mean arterial pressure during induced hypotension was maintained at 70% of the values observed before hypotension. A significant decrease in PaO2 was observed during hypotension under normocapnia (PaCO2 35-40 mmHg) in both groups. In addition, small but significant reduction in PaO2 from 128.5 +/- 23.7 mmHg to 122.5 +/- 25.5 mmHg in TNG group and from 129.9 +/- 11.9 mmHG to 116.7 +/- 15.6 mmHg in PGE1 group were induced by hypocapnia (PaCO2 27-30 mmHg) during hypotension. These findings suggest that usual dose of TNG and PGE1 might not or might partially inhibit hypoxic pulmonary vasoconstriction.     

Effect of hypocapnia on local cerebral glucose utilization in rats

The effect of hypocapnia on regional cerebral glucose utilization (L-CMRg) was studied in 14 Sprague Dawley rats. After cannulation of femoral vessels, halothane was discontinued and anesthesia was maintained with 70% N2O in oxygen. The animals' lungs were mechanically ventilated to achieve normocapnia (PaCO2 = 40 +/- 2 mmHg) in group A or hypocapnia (PaCO2 = 25 +/- 2 mmHg) in group B. L-CMRg was measured by the 14C-2-deoxyglucose autoradiographic method. Twenty-six anatomically discrete structures representing cortical, subcortical, limbic, and brainstem areas were studied. In hypocapnic animals, mean values for L-CMRg were higher in 25 out of 26 structures studied. The increase in L-CMRg was heterogenous. The structures that had higher L-CMRg during normocapnia showed the greatest increase in L-CMRg. When the two groups were compared using a profile analysis, in six regions (lateral and ventral thalamus, inferior colliculus, lateral habenulla, medial geniculate body, and auditory cortex), a value of P less than 0.05 was obtained.     

Cerebral metabolism and EEG during combination of hypocapnia and isoflurane-induced hypotension in dogs

Isoflurane (ISF)-induced hypotension causes equal reductions of cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) so that no disturbance of cerebral energy stores or metabolites occurs. While hypocapnia during ISF-induced hypotension causes a further reduction of CBF, the effects on cerebral energy stores and metabolites produced by combining hypocapnia with ISF-induced hypotension are not known. This study examined the effect of hypocapnia (PaCO2 = 20 mmHg) on CMRO2, the electroencephalogram (EEG), and levels of adenine nucleotides, phosphocreatine, lactate, pyruvate, and glucose in brain tissue in 12 dogs during ISF-induced hypotension. All dogs were examined at: normocapnia with normotension; hypocapnia with normotension; hypocapnia combined with ISF-induced hypotension to cerebral perfusion pressures of 60, 50, and 40 mmHg; and restoration of normocapnia with normotension. In six dogs CMRO2 was determined, and the EEG was evaluated using compressed spectral analysis. In the other six dogs brain tissue metabolites were determined. Hypocapnia combined with ISF-induced hypotension (all levels) caused a decrease of the power of the beta-2 spectra, an increase of the power of the alpha and beta-1 spectra, but no change in total power of the EEG. There was no change in cerebral energy stores or brain tissue metabolites. CMRO2 was reduced by approximately 27%. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites remained unchanged and CMRO2, and the power of the alpha, beta-1, and beta-2 spectra of the EEG returned to control values. These results suggest no adverse effect on cerebral metabolism or function during hypocapnia combined with ISF-induced hypotension.     

Phenylephrine increases regional cerebral blood flow following hemorrhage during isoflurane-oxygen anesthesia

Using the radioactive microsphere technique regional cerebral blood flow (rCBF) and total CBF (tCBF) were examined in rats at three time periods: baseline (CBF1) during 1.5 MAC inspired isoflurane-oxygen anesthesia, CBF2; during 1.5 MAC inspired isoflurane anesthesia combined with hypotension induced by hemorrhage and CBF3; during isoflurane and hemorrhage plus phenylephrine infused to restore mean arterial pressure (MAP) to baseline. For CBF1 MAP was 89 +/- 3 mmHg (mean +/- SEM, n = 9) with PaCO2 44 +/- 1 mmHg. For CBF2 following graded hemorrhage MAP was 48 +/- 2 mmHg and PaCO2 43 +/- 1 mmHg. For CBF3 MAP was 93 +/- 2 and PaCO2 45 +/- 1 mmHg, following infusion of phenylephrine (PE) at 13.9 +/- 4.0 micrograms.kg-1.min-1. Total CBF1 was 1.84 +/- 0.18 ml.g-1.min-1, tCBF2 1.32 +/- 0.09 ml.g-1.min-1 (P less than 0.05 vs. tCBF1) and tCBF3 2.60 +/- 0.18 (P less than 0.05 vs. tCBF1 and 2). For tCBF3 hemoglobin concentration had decreased 23% from 14.2 +/- 0.2 g.100 ml-1 to 11.0 +/- 0.5 g.100 ml-1 (P less than 0.05). Regional CBF decreased significantly in seven of 12 regions examined from CBF1 to CBF2 and was significantly higher in all regions for CBF3. For CBF1-3 infratentorial blood flows (cerebellar and brain stem) were significantly higher than flows to the supratentorial structures (cerebral cortical and basal ganglia). During isoflurane anesthesia, phenylephrine infused to support MAP following hemorrhagic hypotension effectively maintains rCBF and tCBF. There is no indication that phenylephrine infused to increase MAP following hemorrhage results in cerebral vasoconstriction in rats anesthetized with isoflurane.     

Cerebral effects of hypocapnia plus nitroglycerin-induced hypotension in dogs

This study examined the effect of hypocapnia (PaCO2 20 mm Hg) on cerebral metabolism and the electroencephalogram (EEG) findings in 12 dogs during nitroglycerin (NTG)-induced hypotension. Previous studies suggest that NTG is a more potent cerebral vasodilator than sodium nitroprusside or trimethaphan. It was speculated that combining hypocapnia with NTG-induced hypotension would cause less disturbance of cerebral metabolism and the EEG than the disturbances previously reported when hypocapnia was combined with hypotension induced by sodium nitroprusside or trimethaphan. All 12 dogs were examined at 1) normocapnia with normotension; 2) hypocapnia with normotension; and 3) hypocapnia combined with NTG-induced hypotension to mean arterial blood pressure (MABP) levels of 60, 50, and 40 mm Hg. In six dogs the cerebral metabolic rate of oxygen was determined, and the EEG was evaluated using compressed spectral analysis. Brain tissue metabolites were calculated in the other six dogs. During normotension, hypocapnia caused no deterioration of cerebral metabolism or of the EEG. Hypocapnia combined with NTG-induced hypotension caused a decrease of the power of the alpha and beta 2 spectra of the EEG at MABP's of 60 mm Hg or less. At an MABP of 40 mm Hg, brain tissue phosphocreatine and the cerebral energy charge decreased, while the brain tissue lactate:pyruvate ratio increased. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites returned to initial values, but the power of the EEG alpha and beta 2 spectra was decreased compared to baseline values. The cerebral metabolic disturbances and EEG alterations seen here with hypocapnia plus NTG-induced hypotension were similar to those previously reported with hypocapnia plus sodium nitroprusside-induced hypotension, and less than those previously reported with hypocapnia plus trimethaphan-induced hypotension. For hyperventilated patients, administration of NTG may be a better hypotensive treatment than trimethaphan, but similar in effect to sodium nitroprusside.     

Cerebrovascular effects of hypocapnia during adenosine-induced arterial hypotension

Profound arterial hypotension is a commonly used adjunct in surgery for aneurysms and arteriovenous malformations. Hyperventilation with hypocapnia is also used in these patients to increase brain slackness. Both measures reduce cerebral blood flow (CBF). Of concern is whether CBF is reduced below ischemic thresholds when both techniques are employed together. To determine this, 12 mongrel dogs were anesthetized with morphine, nitrous oxide, and oxygen, and then paralyzed with pancuronium and hyperventilated. Arterial pCO2 was controlled by adding CO2 to the inspired gas mixture. Cerebral blood flow was measured at arterial pCO2 levels of 40 and 20 mm Hg both before and after mean arterial pressure was lowered to 40 mm Hg with adenosine enhanced by dipyridamole. In animals where PaCO2 was reduced to 20 mm Hg and mean arterial pressure was reduced to 40 mm Hg, cardiac index decreased 42% from control and total brain blood flow decreased 45% from control while the cerebral metabolic rate of oxygen was unchanged. Hypocapnia with hypotension resulted in small but statistically significant reductions in all regional blood flows, most notably in the brain stem. The reported effects of hypocapnia on CBF during arterial hypotension vary depending on the hypotensive agents used. Profound hypotension induced with adenosine does not eliminate CO2 reactivity, nor does it lower blood flow to ischemic levels in this model, even in the presence of severe hypocapnia.     

Partial preservation of cerebral vascular responsiveness to hypocapnia during isoflurane-induced hypotension in dogs

This study was undertaken to determine whether the cerebral vascular response to hypocapnia is preserved during isoflurane-induced hypotension. In six dogs (group 1) cerebral vascular resistance and cerebral blood flow were determined at normocapnia (PaCO2 40 mm Hg) and at hypocapnia (PaCO2 20 mm Hg) while mean arterial pressure was normal, and then again during isoflurane-induced hypotension to a mean arterial pressure of 50 mm Hg. Hypocapnia increased cerebral vascular resistance and decreased cerebral blood flow during both normotension and isoflurane-induced hypotension. However, the magnitude of these responses was greater when mean arterial pressure was normal. In another six dogs (group 2), CO2 responsiveness was examined during isoflurane-induced hypotension without prior determination of CO2 responsiveness at normal mean arterial pressure and during sodium nitroprusside-induced hypotension to a mean arterial pressure of 50 mm Hg. As in group 1, partial preservation of CO2 responsiveness was observed during isoflurane-induced hypotension; the magnitude of the response in group 2 during isoflurane-induced hypotension was similar to that in group 1. In contrast, in group 2 during sodium nitroprusside-induced hypotension, hypocapnia caused no significant change of cerebral vascular resistance or cerebral blood flow. It is concluded that cerebral vessels respond to changes in PaCO2 differently during isoflurane-induced hypotension than during hypotension with other commonly used hypotensive treatments. Hypocapnia decreases cerebral blood flow during isoflurane-induced hypotension and, therefore, may also decrease cerebral blood volume, brain bulk, and intracranial pressure.     

Severe head injuries: effects of pre-hospital mechanical ventilation on capnia]

OBJECTIVE: To assess the effect on PaCO2 of mechanical ventilation during prehospital management of severely head-injured patients. STUDY DESIGN: Retrospective observational study. PATIENTS: Severely head-injured patients with Glasgow coma score < or = 8. All patients were sedated, with the trachea intubated and the lungs mechanically ventilated. METHODS: According to the capnia measured at the admission in the neurosurgical intensive therapy unit they were allocated into one of the following three groups: hypocapnia group (PaCO2 < 30 mmHg), recommended capnia group (PaCO2 = 30-38 mmHg) and hypercapnia group (PaCO2 > 38 mmHg). RESULTS: Out of the 42 patients with similarly severe head injuries, 19% were included in the recommended capnia group (PaCO2: 34 +/- 2 mmHg), 38% in the hypocapnia group (PaCO2: 23 +/- 3 mmHg) and 43% in the hypercapnia group (PaCO2: 47 +/- 7 mmHg). In all except three, PaO2 was above 95 mmHg. The settings of ventilatory parameters on the ventilators were similar. CONCLUSION: In 81% of patients, mechanical ventilation was inadequate as far as PaCO2 levels are concerned. Major hypocapnia and hypercapnia carry a potential risk for cerebral ischaemic. Therefore it is recommended to monitor PETCO2 during prehospital transport in medical ambulances and to determine arterial blood gases at arrival of severely head-injured patients in the admission unit for emergencies.     

Cerebral vascular responses to hypocapnia during nitroglycerin-induced hypotension

For many neurosurgical procedures, elective hypotension is used to reduce the risk of cerebral vessel rupture and hypocapnia is used to constrict cerebral vessels, thereby reducing cerebral blood volume. Although nitroglycerin (NTG) often is used to produce hypotension during neurological surgery, it is not known whether NTG-induced cerebral vasodilation interferes with the cerebral vasoconstrictor response to hypocapnia. This study examined cerebral vascular responses to hypocapnia during NTG-induced hypotension in eight dogs that were lightly anesthetized with halothane and had an open cranium. Cerebral vascular resistance (CVR) and cerebral blood flow (CBF) at PaCO2 = 40 mm Hg and at PaCO2 = 20 mm Hg were examined first at normal mean arterial pressure (MAP) and then at MAP = 50 mm Hg. CO2 responsiveness, as indicated by increased CVR and decreased CBF, was intact at normal MAP but absent during hypotension. These results suggest that the cerebral vasodilation that accompanies NTG-induced hypotension exerts a greater influence on cerebral vessels than the cerebral vasoconstricting influence of hypocapnia. It is concluded that, during NTG-induced hypotension and craniotomy, hypocapnia will not reduce cerebral blood volume or further decrease CBF to cause ischemia.     

Cerebral and systemic effects of hypotension induced by adenosine or ATP in dogs

The authors evaluated the systemic and cerebral hemodynamic and metabolic effects of 1 h of hypotension to a mean arterial pressure of either 50 mmHg or 40 mmHg induced by intravenous adenosine or ATP in dogs maintained on 70% nitrous oxide and 0.1% halothane. Following the hypotensive period, brain biopsy specimens were taken for the determination of cerebral metabolites and calculation of the energy charge. Hypotension induced by either adenosine or ATP produced a marked 40-62% decrease in systemic vascular resistance with little change in cardiac index or oxygen consumption but resulted in a mild metabolic acidosis. Because of a profound decrease in cerebral perfusion pressure with hypotension (to 31-33 mmHg at an MAP of 50 mmHg and 22-24 mmHg at an MAP of 40 mmHg) CBF decreased 54-65% and was inadequate to meet the unchanged cerebral oxygen demands, resulting in some anaerobic metabolism with an accumulation of lactate. While the ease with which one can induce and maintain hypotension with these agents may be advantageous in clinical practice, the effects of adenosine and ATP on cerebral hemodynamics and metabolism may offer no advantage over other hypotensive agents.     

Electrical correlates of brain injury resulting from severe hypotension and hemodilution in monkeys

The effects of hypotension, hemodilution, and their combination on the relationship between concurrent brain electrical activity and resulting brain injury were studied in anesthetized monkeys. The authors compared changes in the electroencephalogram and somatosensory and auditory evoked potentials with eventual neuropathologic outcome. Our goals were: 1) to define the margin of safety for the monkey brain during hemodilution and hypotension under several simulated clinical conditions; and 2) to determine whether noninvasive measurements of brain electrical activity can predict ischemic brain cell damage. Forty-one monkeys were anesthetized with halothane (0.8 vol % inspired) and ventilated mechanically. Arterial hypotension was induced with trimethaphan (25 +/- 8 mmHg mean arterial blood pressure [MABP] for 30 min). Hemodilution was induced by replacing blood with lactated Ringer's solution (14 +/- 2% hematocrit for 1 h). Combined hemodilution and hypotension consisted of 30 min of hemodilution alone followed by superimposing hypotension for 30 min (16 +/- 3% hematocrit and 29 +/- 5 mmHg MABP). Ten monkeys died following severe hypotension alone or combined hemodilution and hypertension as a consequence of cardiac arrest or undetermined (possibly neurologic) causes. No histologic evidence of ischemic brain cell injury was found in surviving monkeys subjected to hemodilution or hypotension alone. Neuropathologic alterations in the cerebral cortex, cerebellum, hippocampus and globus pallidus as well as neurologic and behavioral deficits were found in seven of 16 surviving monkeys subjected to both hemodilution and hypotension. These findings resulted from combinations of hematocrit less than 20% and MABP below 40 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypercapnia increases cerebral tissue oxygen tension in anesthetized rats

PURPOSE: To test the hypotheses that deliberate elevation of PaCO(2) increases cerebral tissue oxygen tension (PBrO(2)) by augmenting PaO(2) and regional cerebral blood flow (rCBF). METHODS: Anesthetized rats were exposed to increasing levels of inspired oxygen (O(2)) or carbon dioxide (CO(2); 5%, 10% and 15%, n = 6). Mean arterial blood pressure (MAP), PBrO(2) and rCBF were measured continuously. Blood gas analysis and hemoglobin concentrations were determined for each change in inspired gas concentration. Data are presented as mean +/- standard deviation with P < 0.05 taken to be significant. RESULTS: The PBrO(2) increased in proportion to arterial oxygenation (PaO(2)) when the percentage of inspired O(2) was increased. Proportional increases in PaCO(2) (48.7 +/- 4.9, 72.3 +/- 6.0 and 95.3 +/- 15.4 mmHg), PaO(2) (172.2 +/- 33.1, 191.7 +/- 42.5 and 216.0 +/- 41.8 mmHg), and PBrO(2) (29.1 +/- 9.2, 49.4 +/- 19.5 and 60.5 +/- 23.0 mmHg) were observed when inspired CO(2) concentrations were increased from 0% to 5%, 10% and 15%, respectively, while arterial pH decreased (P < 0.05 for each). Exposure to CO(2) increased rCBF from 1.04 +/- 0.67 to a peak value of 1.49 +/- 0.45 (P < 0.05). Following removal of exogenous CO(2), arterial blood gas values returned to baseline while rCBF and PBrO(2) remained elevated for over 30 min. The hypercapnia induced increase in PBrO(2) was threefold higher than that resulting from a comparable increase in PaO(2) achieved by increasing the inspired O(2) concentration (34.9 +/- 14.5 vs 11.4 +/- 5.0 mmHg, P < 0.05). CONCLUSION: These data support the hypothesis that the combined effect of increased CBF, PaO(2) and reduced pH collectively contribute to augmenting cerebral PBrO(2) during hypercapnia.     

Cerebral metabolism and the electroencephalogram during hypocapnia plus hypotension induced by sodium nitroprusside or trimethaphan in dogs

The effects on cerebral metabolism and the electroencephalogram (EEG) of combining hypocapnia with hypotension have been only incompletely examined. The present study examined the possibility that hypocapnia may worsen the cerebral metabolic and EEG disturbances caused by hypotension. Cerebral metabolism and the EEG were studied at three levels of hypotension during hypocapnia (PaCO2 = 20 mm Hg) in dogs under light halothane anesthesia. A sequential decrease of the mean arterial pressure (MAP) to 60, 50, and 40 mm Hg (30 minutes at each level) was achieved with sodium nitroprusside (SNP) (n = 12) or trimethaphan (TMP) (n = 12). With SNP-induced hypotension plus hypocapnia, the power of the alpha and beta 2 spectra of the EEG decreased at MAP less than or equal to 60 mm Hg. Cerebral metabolic values were unchanged at a MAP of 60 or 50 mm Hg. Brain tissue phosphocreatine and the cerebral energy charge decreased, and the lactate/pyruvate ratio increased at a MAP of 40 mm Hg. With TMP-induced hypotension plus hypocapnia, power decreased in the alpha and beta 2 spectra of the EEG at MAP less than or equal to 60 mm Hg. Cerebral metabolic values were unchanged at a MAP of 60 mm Hg. At MAP less than or equal to 50 mm Hg, power in the beta 1 spectrum, brain tissue phosphocreatine, and the cerebral energy charge all decreased. At a MAP of 40 mm Hg, the cerebral glucose value decreased and the lactate/pyruvate ratio increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow and cerebral oxygen consumption during nitroprusside-induced hypotension to less than 50 mmHg

The authors determined the effect of profound induced hypotension (i.e., mean arterial blood pressure less than 50 mmHg) during craniotomy for cerebral aneurysm on cerebral blood flow and cerebral metabolic rate for oxygen before, during, and after (20 min and 40 min after) the hypotensive period. The study was performed on nine adults (mean age, 29.2 yr) who were awake and conscious without peripheral neurologic deficits at the time of surgery. The study was conducted with the dura open with the use of a radial artery cannula, a 7-Fr thermodilution flow-directed pulmonary artery catheter, and an internal jugular vein catheter. The 133xenon intraarterial injection technique was used to determine regional cerebral blood flow (rCBF) in the nonoperated hemisphere. rCBF remained unchanged (from 22.8 +/- 4.1 ml.100 g-1.min-1 to 23.8 +/- 4.6 ml.100 g-1.min-1) during the hypotensive period (MAP from 87.8 +/- 10.4 mmHg to 40.0 +/- 4.4 mmHg; P less than 0.001) despite an increase in cardiac index since cerebral perfusion pressure and cerebrovascular resistance decreased to a similar degree. No gross cerebral metabolic disturbances were observed. A period of decreased cerebrovascular resistance and increased rCBF followed induced hypotension. rCBF increased from 23.8 +/- 4.6 ml.100 g-1.min-1 to 30.0 +/- 5.8 ml.100 g-1.min-1 (P less than 0.001) 20 min after sodium nitroprusside (SNP) was stopped without rebound hypertension. These modifications disappeared 20 min later. Reduction of mean arterial blood pressure to 40 mmHg by SNP was apparently safe for the brain, although the possibility of low perfused regions and local brain and cerebrospinal fluid lactoacidosis, particularly in the retracted hemisphere, cannot be excluded.     

The responsiveness of cerebral blood flow to changes in arterial carbon dioxide is maintained during propofol-nitrous oxide anesthesia in humans.

Because it is common to manipulate PaCO2 during neurosurgery, it is essential to characterize the relationship between cerebral blood flow (CBF) and changes in PaCO2. The purpose of this study was to investigate the effects of propofol-N2O anesthesia on the CBF response to changes in PaCO2 in healthy subjects. In seven patients, anesthesia was induced with propofol 2.0-2.5 mg/kg and then maintained with a propofol infusion of 12 mg.kg-1.h-1 for 10 min and then 9 mg.kg-1.h-1 for 10 min and then was reduced to 3-6 mg.kg-1.h-1 for the remainder of the study. The subjects' lungs were ventilated with N2O in O2 (FIO2 0.3) to the end-tidal CO2 present before anesthesia, and then CBF was measured using intravenous 133Xe and ten scintillation counters, five over each cerebral hemisphere. ETCO2 then was increased to 50 mmHg and CBF measurement repeated; ETCO2 then was reduced to 30 mmHg and CBF measurement repeated. Concurrent with each CBF measurement, arterial blood was sampled for PaCO2 and hemoglobin measurement. CBF at normocapnia (PaCO2 42 +/- 2 mmHg) was 33 +/- 7 ml.100 g-1.min-1, which increased to 58 +/- 10 ml.100 g-1.min-1 and decreased to 19 +/- 4 ml.100 g-1.min-1 on increasing PaCO2 (53 +/- 4 mmHg) and decreasing PaCO2 (31 +/- 2 mmHg), respectively. Both the PaCO2 and CBF values were statistically different from those measured at any other time (CBF P less than 0.002, PaCO2 P less than 0.001). The slope of CBF versus PaCO2 was 1.56 ml.100 g-1.min-1.mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nicardipine-, nitroglycerin-, and prostaglandin E1-induced hypotension on human cerebrovascular carbon dioxide reactivity during propofol-fentanyl anesthesia

STUDY OBJECTIVE: To investigate the effects of nicardipine-, nitroglycerin-, and prostaglandine E1-induced hypotension on cerebrovascular carbon dioxide (CO2) reactivity over a wide range of arterial CO2 tension (PaCO2) (PaCO2; range 25 to 50 mmHg). DESIGN: Prospective, randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 36 ASA physical status I and II patients without cerebrovascular disease, hypertension, or diabetes mellitus, undergoing an elective abdominal surgery. INTERVENTIONS: Patients were randomly allocated to one of three groups (nicardipine-, nitroglycerin-, or prostaglandin E1-induced hypotension group; 12 in each group). Anesthesia was induced and maintained with a bolus dose, followed by a continuous infusion of propofol (6.7 +/- 1.5 mg/kg/hr) and fentanyl (1.68 +/- 0.4 micrograms/kg/hr). Deliberate hypotension of mean arterial pressure 55 to 60 mmHg was induced and maintained with a bolus dose, followed by a continuous infusion of nicardipine (6.80 +/- 0.75 micrograms/kg/min), nitroglycerin (3.20 +/- 1.10 micrograms/kg/min), or prostaglandin E1 (0.103 +/- 0.052 microgram/kg/min). MEASUREMENTS AND MAIN RESULTS: Time-averaged mean red blood cell velocity in the right middle cerebral artery (Vmca) at PaCO2 ranging from 25 to 50 mmHg was measured with transcranial Doppler ultrasonography. A minimum of six simultaneous measurements of Vmca and PaCO2 were obtained during baseline and deliberate hypotension in each patient. Absolute slope between Vmca and PaCO2 during baseline and deliberate hypotension was determined individually by linear regression analysis. Absolute slope was treated as the variable, because it yielded a significant close correlation coefficient (r > 0.95; p < 0.05). Comparisons between baseline and deliberate hypotension were made by analysis of variance for repeated measures. Mean absolute slope was significantly reduced from 1.88 +/- 0.57 cm/sec/mmHg (mean +/- SD) to 1.21 +/- 0.46 in the nicardipine group (p < 0.05), from 1.75 +/- 0.69 to 1.35 +/- 0.47 in the nitroglycerin group (p < 0.05), and from 1.95 +/- 0.89 to 1.33 +/- 0.70 (p < 0.05) in the prostaglandin E1 group, respectively. CONCLUSION: Nicardipine-, nitroglycerin-, and prostaglandin E1-induced hypotension attenuate the human cerebrovascular CO2 reactivity during propofol-fentanyl anesthesia.     

The cerebral and systemic hemodynamic and metabolic effects of desflurane-induced hypotension in dogs

The cerebral and systemic hemodynamic and metabolic effects of hypotension induced with desflurane were examined in 11 dogs. During a steady-state baseline period under 1 MAC desflurane (7.2%), the following were measured or derived: arterial, pulmonary artery, and pulmonary artery occlusion pressures; arterial, mixed venous, and sagittal sinus blood gases; cardiac index and cerebral blood flow (CBF); whole-body and cerebral O2 consumption; systemic and cerebral vascular resistance; intracranial pressure; and blood glucose and lactate concentrations. After the baseline period, hypotension to a mean arterial pressure (MAP) of 50 mmHg was produced by 15.5% (2.2 MAC), and hypotension to an MAP of 40 mmHg was produced by 17.1% (2.4 MAC) for 1 h. During this hypotensive period all measurements were taken at 5- or 15-min intervals. At the end of the hypotensive period, brain biopsy specimens were taken for measurement of cerebral concentrations of ATP, phosphocreatine, and lactate to determine whether there was any metabolic evidence of cerebral ischemia. Desflurane-induced hypotension produced a significant, 40-50% decrease in cardiac index with a significant change in systemic vascular resistance at the lower blood pressure, but produced little change in heart rate. Even though whole-body O2 consumption did not decrease, adequate peripheral perfusion was maintained with the lower cardiac output, as evidenced by lack of accumulation of blood lactate. Induced hypotension caused a significant, 50 (at MAP = 50 mmHg) to 64% (at MAP = 40 mmHg) decrease in cerebral perfusion pressure, accompanied by a significant, 36 (at MAP = 50 mmHg) to 60% (at MAP = 40 mmHg) decrease in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral blood flow and response to carbon dioxide during controlled hypotension with isoflurane anesthesia in the rat

Regional (frontal, parietal, occipital, cortical, and basal ganglia) cerebral blood flow (rCBF) was examined at 1.5 and 3.5 MAC inspired isoflurane/O2 anesthesia in the rat using the radioactive microsphere technique to determine the effects of controlled hypotension with deep isoflurane anesthesia on rCBF and the response of rCBF to changes in PaCO2 when mean blood pressure (BP) was decreased to levels below the lower limit of the autoregulatory threshold. Four groups of six rats were studied with rCBF 1 determined at 1.5 MAC (mean BP 80-90 mm Hg) followed by two rCBF determinations at 3.5 MAC (mean BP 46-48 mm Hg). For CBF 1 the regional CO2 response was a 3.1-3.9% increase in rCBF/mm Hg increase in CO2. Regional cerebral blood flow (ml/g/min) ranged from 0.64 +/- 0.05-0.83 +/- 0.15 at PaCO2 of 19 mm Hg to 1.34 +/- 0.11-1.80 +/- 0.33 at PaCO2 of 41 mm Hg to 2.61 +/- 0.26-3.72 +/- 0.37 at PaCO2 of 59 mm Hg (mean +/- SEM). With controlled hypotension (CBF 2) rCBF was unchanged during normocarbia, increased 100% during hypocarbia, P less than 0.01 vs CBF 1 and decreased 30% during hypercarbia, P less than 0.01 vs CBF 1. For rCBF 3 measurements, the BP and inspired concentration of isoflurane were kept constant, while PaCO2 was increased in two and decreased in two of the four groups. Within-group comparisons between rCBF 2 and rCBF 3 results demonstrated loss of CO2 responsiveness of the rat cerebrovasculature in every region during controlled hypotension to below the autoregulatory threshold at 3.5 MAC isoflurane/O2 anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of arterial carbon dioxide tension on regional myocardial tissue oxygen tension in the dog]

We investigated the effects of arterial carbon dioxide tension on the myocardial tissue oxygen tensions of subepicardium and subendocardium in the anesthetized dogs. The study was done in fourteen open-chest mongrel dogs, weighing 13 +/- 1 kg, anesthetized with sodium pentobarbital (30 mg.kg-1 iv), and mechanically ventilated with 100% oxygen to maintain normocapnia. End tidal CO2 fraction (FECO2) was monitored continuously by capnograph. Regional myocardial tissue PO2 was measured using a monopolar polarographic needle electrode. Two pairs of combined needle sensors were carefully inserted, one in the epicardial and the other in the endocardial layer of the beating heart. Electromagnetic blood flow probe was applied on the left anterior descending artery (LAD). After a stable normocapnic ventilation, hypocapnia was induced by increasing the respiratory rate, and this mechanical hyperventilation was kept fixed throughout the experiments. To induce hypercapnia, exogenous carbon dioxide was added to the inspired gas step-wise until FECO2 reached 10%. Hypocapnic hyperventilation (PaCO2: 22 mmHg) invariably resulted in a significant reduction of coronary blood flow (LADBF) and left ventricular myocardial tissue PO2 in both epicardial and endocardial layers, while addition of carbon dioxide to the inspired gas (hypercapnic hyperventilation) reversed the change by increased LADBF and arterial PaCO2 in a dose-dependent manner. These results indicate that injudicious and severe hypocapnic hyperventilation may induce impaired myocardial tissue perfusion and oxygenation although normal cardiac output and arterial blood oxygenation are maintained.