Cerebral O2 Extraction Research Articles

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Cerebral oxygen sensing and the integrated regulation of hypoxic vasodilatation.

Efficacy of volume therapy guided by stroke volume variability in patients undergoing surgery for severe traumatic brain injury

Objective To evaluate the efficacy of volume therapy guided by stroke volume variability (SVV) in the patients undergoing surgery for severe traumatic brain injury. Methods Thirty patients of both sexes with severe traumatic brain injury, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅲ, who were admitted to the hospital within 24 h after injury, with Glasgow Coma Scale (GCS) score≤8, were divided into control group (C group, n=15) and SVV group (n=15) using a random number table method.In group C, conventional fluid administration was performed to maintain mean arterial pressure at 65-110 mmHg, central venous pressure at 5-12 cmH2O and urine volume>1 ml·kg-1·h-1.Fluid was given according to SVV, maintaining SVV≤13% and mean arterial pressure at 65-110 mmHg in group SVV.Immediately after skin incision (T0), immediately after opening cerebral dura mater (T1), at 1 h after opening cerebral dura mater (T2), immediately after suturing cerebral dura mater (T3) and at the end of operation (T4), blood samples were collected from the radial artery and internal jugular venous bulb for blood gas analysis, the jugular venous oxygen partial pressure, jugular venous bulb oxygen saturation, blood lactate, arterial oxygen partial pressure, arterial oxygen saturation and Hb were recorded, and the cerebral artery and arteriovenous blood O2 content difference and cerebral O2 extraction rate were calculated.Blood samples were collected from the internal jugular venous bulb at T0-2, T4 and 24 h after operation (T5) for determination of S100β protein concentrations by enzyme-linked immunosorbent assay.The intraoperative volume of fluid intake and output and consumption of vasoactive drugs were recorded.GCS scores were recorded immediately after admission to the operating room, and at 1, 3, 7 and 14 days after operation.The development of postoperative length of hospitalization and complications (pulmonary infection and brain edema) was recorded.Glasgow Outcome Scale Score was used to assess the early postoperative quality of life. Results Compared with group C, the urine volume was significantly increased, the consumption of vasoactive drugs was reduced, jugular venous bulb oxygen saturation was increased at T2, 3, the cerebral O2 extraction rate was decreased at T2-4, the serum S100β protein concentration was decreased at T2, and the GCS score was increased at day 3 after operation (P 0.05). Conclusion SVV-guided volume therapy can improve cerebral oxygen metabolism, ensure adequate tissue perfusion and reduce craniocerebral injury in the patients undergoing surgery for severe traumatic brain injury. Key words: Stroke volume; Fluid therapy; Craniocerebral trauma

Cerebral Oxygenation of Premature Lambs Supported by an Artificial Placenta.

An artificial placenta (AP) using venovenous extracorporeal life support (VV-ECLS) could represent a paradigm shift in the treatment of extremely premature infants. However, AP support could potentially alter cerebral oxygen delivery. We assessed cerebral perfusion in fetal lambs on AP support using near-infrared spectroscopy (NIRS) and carotid arterial flow (CAF). Fourteen premature lambs at estimated gestational age (EGA) 130 days (term = 145) underwent cannulation of the right jugular vein and umbilical vein with initiation of VV-ECLS. An ultrasonic flow probe was placed around the right carotid artery (CA), and a NIRS sensor was placed on the scalp. Lambs were not ventilated. CAF, percentage of regional oxygen saturation (rSO2) as measured by NIRS, hemodynamic data, and blood gases were collected at baseline (native placental support) and regularly during AP support. Fetal lambs were maintained on AP support for a mean of 55 ± 27 hours. Baseline rSO2 on native placental support was 40% ± 3%, compared with a mean rSO2 during AP support of 50% ± 11% (p = 0.027). Baseline CAF was 27.4 ± 5.4 ml/kg/min compared with an average CAF of 23.7 ± 7.7 ml/kg/min during AP support. Cerebral fractional tissue oxygen extraction (FTOE) correlated negatively with CAF (r = -0.382; p < 0.001) and mean arterial pressure (r = -0.425; p < 0.001). FTOE weakly correlated with systemic O2 saturation (r = 0.091; p = 0.017). Cerebral oxygenation and blood flow in premature lambs are maintained during support with an AP. Cerebral O2 extraction is inversely related to carotid flow and is weakly correlated with systemic O2 saturation.

Cerebral Oxygen Saturation in Children With Congenital Heart Disease and Chronic Hypoxemia.

Increased hemoglobin (Hb) concentration accompanying hypoxemia is a compensatory response to maintain tissue oxygen delivery. Near infrared spectroscopy (NIRS) is used clinically to detect abnormalities in the balance of cerebral tissue oxygen delivery and consumption, including in children with congenital heart disease (CHD). Although NIRS-measured cerebral tissue O2 saturation (ScO2) correlates with arterial oxygen saturation (SaO2), jugular bulb O2 saturation (SjbO2), and Hb, little data exist on the interplay between these factors and cerebral O2 extraction (COE). This study investigated the associations of ScO2 and ΔSaO2-ScO2 with SaO2 and Hb and verified the normal range of ScO2 in children with CHD. Children undergoing cardiac catheterization for CHD were enrolled in a calibration and validation study of the FORE-SIGHT NIRS monitor. Two pairs of simultaneous arterial and jugular bulb samples were drawn for co-oximetry, calculation of a reference ScO2 (REF CX), and estimation of COE. Pearson correlation and linear regression were used to determine relationships between O2 saturation parameters and Hb. Data were also analyzed according to diagnostic group defined as acyanotic (SaO2 ≥ 90%) and cyanotic (SaO2 < 90%). Of 65 children studied, acceptable jugular bulb samples (SjbO2 absolute difference between samples ≤10%) were obtained in 57 (88%). The ΔSaO2-SjbO2, ΔSaO2-ScO2, and ΔSaO2-REF CX were positively correlated with SaO2 and negatively correlated with Hb (all P < .001). Although by diagnostic group ScO2 differed statistically (P = .002), values in the cyanotic patients were within the range considered normal (69% ± 6%). COE estimated by the difference between arterial and jugular bulb O2 content (ΔCaO2-CjbO2, mL O2/100 mL) was not different for cyanotic and acyanotic patients (P = .10), but estimates using ΔSaO2-SjbO2, ΔSaO2-ScO2, or ΔSaO2-ScO2/SaO2 were significantly different between the cyanotic and acyanotic children (P < .001). Children with adequately compensated chronic hypoxemia appear to have ScO2 values within the normal range. The ΔSaO2-ScO2 is inversely related to Hb, with the implication that in the presence of reduced Hb, particularly if coupled with a decreased cardiac output, the ScO2 can fall to values associated with brain injury in laboratory studies.

Effect of therapeutic hypercapnia on cerebral oxygen metabolism in patients undergoing thoracoscopic surgery in beach chair position

Objective To evaluate the effect of therapeutic hypercapnia on cerebral oxygen metabolism in the patients undergoing thoracoscopic surgery in beach chair position (BCP). Methods Sixty patients of both sexes, aged 18-32 yr, with body mass index of 19-24 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective bilateral thoracic sympathectomy performed via a thoracoscope, were divided into control group (group C) and hypercapnia group (group H), with 30 patients in each group using a random number table.After induction of anesthesia, all the patients in both groups were tracheally intubated and mechanically ventilated using the ventilation regimen low tidal volume intermittent positive pressure ventilation combined with low level of positive end-expiratory pressure (5 cmH2O), maintaining arterial carbon dioxide partial pressure (PaCO2) at 35-45 mmHg.PaCO2 was maintained at 45-55 mmHg by adjusting the respiratory rate after the patients were placed in BCP in group H. Anesthesia was maintained with target-controlled infusion of propofol and intermittent intravenous boluses of rocuronium and sufentanil.Bispectral index value was maintained at 45-55.Before anesthesia induction (baseline), at 5 min after intubation, and at 5, 10, 15 and 20 min after the patients were placed in BCP, blood samples were taken from the radial artery and jugular bulb for blood gas analysis, jugular venous bulb oxygen saturation was measured, and arteriovenous blood O2 content difference, cerebral O2 extraction rate, and venous to arterial blood lactate concentration difference were calculated. Results Compared with group C, PaCO2 and jugular venous bulb oxygen saturation were significantly increased, and arteriovenous blood O2 content difference and cerebral O2 extraction rate were significantly decreased at at 5, 10, 15 and 20 min after the patients were placed in BCP in group H (P 0.05). Conclusion Therapeutic hypercapnia can improve the cerebral oxygen metabolism in the patients undergoing thoracoscopic surgery in BCP. Key words: Hypercapnia; Posture; Oxygen consumption; Brain

Effects of sedation induced with dexmedetomidine versus propofol on intracranial pressure and cerebral oxygen metabolism in patients with permissive hypercapnia

Objective To compare the effects of sedation induced with dexmedetomidine and propofol on intracranial pressure and cerebral oxygen metabolism in patients with permissive hypercapnia. Methods Twentyfour patients with acute respiratory distress syndrome (ARDS) were randomly divided into 2 groups ( n = 12 each) :dexmedetomidine group (group D) and propofol group (group P) . Their APACHE Ⅱ scores were 11-18. The patients were mechanically ventilated (VT 5-7 ml/kg, RR 12-17 bpm, PEEP 6-10 cm H2O, FiO2 40-60%). PaCO2 was maintained at 50-65 mm Hg. Radial artery was cannulated for direct BP monitoring and blood sampling. Right internal jugular vein was cannulated and the catheter was advanced cephalad until jugular bulb. Continuous infusion of dexmedetomidine was started at 0.5 μg· kg-1· h-1 and TCI of propofol was started at target plasma concentration (Cp) of 0.4 μg/ml. The infusion of both drugs was gradually increased until Ramsay score (1= fully awake, 6 =asleep, unresponsive to loud verbal stimulus) reached 3,4,5. Transcranial Doppler monitoring was used to determine cerebral blood flow velocity (CBFV), pulsatility index (PI) and resistance index (RI) before administration of dexmedetomidine and propofol (T0 ) and at 30 min after the 3 levels of sedation were reached (T1-3) . Meanwhile blood samples were taken from radial artery and jugular bulb for blood gas analyses. Cerebral O2 metabolic rate (CMRO2), cerebral A-V O2 content differences (Da-jvO2) and cerebral O2 extraction rate (CERO2) were calculated .ResultsCBFV, PI, RI and CMRO2 were significantly decreased at T1-3 as compared with the baseline values at T0 in both groups. CBFV was positively correlated with CMRO2 in both group D (r = 0.80) and group P ( r = 0.76) . CBFV, PI and RI were significantly lower at T1-3 in group D than in group P. There was no significant change in Da-jvO2 and CERO2 at T1-3 as compared with the baseline values at T0 in both groups. Conclusion At different sedation levels, dexmedetomidine results in lower intracranial pressure than propofol and maintains the balance between cerebral O2 supply and demand in patients with permissive hypercapnia. Key words: Dexmedetomidine; Propofol; Intracranial pressure; Brain; Oxygen consumption; Hypercapnia

Acute intermittent hypoxia exposures enhance arterial oxygen delivery

Physiological adaptations to intermittent hypoxia (IH) conditioning are based on the cumulative effect of repeated IH exposures. The present study sought to test the hypothesis that acute IH exposures would promote arterial O(2) delivery and regional tissue oxygenation. Changes in arterial O(2) saturation (SaO(2), oximeter), forearm muscle and cerebral tissue oxygenations (SmO(2) and ScO(2), near-infrared spectroscopy) were compared during five repeated hypoxia exposures (10 +/- 0.2% O(2) for 5-min each) interposed with four-minute inhalation of room air in 11 healthy subjects (24 +/- 0.9 y). Baseline, prehypoxia partial pressure of end-tidal O(2) (P(ET)O(2), mass spectrometer) and SaO(2) (107 +/- 2 mmHg and 97.3 +/- 0.3%) were decreased (P < 0.05) after the first bout as compared with those during normoxia prior to the second (94 +/- 2 mmHg and 96.2 +/- 0.4%) and the fifth (92 +/- 3 mmHg and 95.7 +/- 0.7%) episodes of IH exposures, whereas partial pressure of end-tidal CO(2), tidal volume and breathing frequency were similar. Arterial O(2) dissociation in terms of per unit decrease in P(ET)O(2) during hypoxia, i.e. the slope of SaO(2)/P(ET)O(2), was augmented (P = 0.0025) from 0.71 +/- 0.09%/mmHg during the first hypoxia bout to 1.39 +/- 0.15%/mmHg and 1.47 +/- 0.16%/mmHg during the second and the fifth bouts, respectively. Fractional muscle tissue O(2) extraction rate (SmO(2)D, i.e. normalized difference between SaO(2) and SmO(2)) progressively decreased (P < 0.01) during IH; however, fractional cerebral tissue O(2) extraction rate (ScO(2)D, i.e. normalized difference between SaO(2) and ScO(2)) did not decrease during hypoxia (P = 0.94). ScO(2)D during normoxia tended to increase (P = 0.089) following repeated IH exposures. We conclude that enhanced arterial O(2) delivery with repeated IH exposures serves as a compensatory mechanism to potentiate O(2) availability during hypoxia.

Comparison of the effects of etomidate versus propofol on cerebral oxygen metabolism in patients undergoing abdominal surgery

Objeoctive To compare the effects of etomidate and propofol on cerebral oxygen metabolism in patients undergoing abdominal surgery.Methods Thirty-six ASA Ⅰ or Ⅱ patients aged 30-64 yr weighing 42-73 kg undergoing abdominal surgery under general anesthesia were randomly divided into 2 groups (n=18 each):group E etomidate and group P propofol.Left radial artery was cannulated for continuous direct BP monitoring.A catheter was inserted into right internal jugular vein(LJV) and advanced cephalad until jngatar bulb for blood sampling.Both groups received midazolam 0.08 ms/ks,fentanyl 3μg/kg and vecurunium 0.1 mg/kg and in addition group P received propofol 1.5 mg/ks and group E etomidate 0.3 mg/kg respectively for induction of anesthesia.Anesthesia was maintained with propofol infusion at 4-6 mg·kg-1·h-1 in group P and etomidate infusion at 0.4-0.7 mg·kg-1·h-1 in group E and intermittent iv boluses of fentanyl and vecuronium.ECG,MAP,HR,SpO2 and PET CO2 were continuously monitored.Blood samples were taken from radial artery and IJV for blood gas analysis and lactic acid measurement before induction of anesthesia(T1),immediately after intubation (T2),30 min after skin incision (T3) and at the end of operation(T4).The rate of cerebral O2 extraction (CERO2) was calculated.Results The hemodynamic variables were within the normal range throughout the anesthesia and operation.The oxygen saturation and oxygen partial pressure of both arterial and venous blood(SaO2,SjvO2,PaO2,PjvO2) rose significantly after induction of anesthesia in both groups.There was no significant difference in arterial and venous blood lactic acid level and SaO2,SjvO2,CaO2,CjvO2,Da-jvO2 or CERO2 at all time points between the two groups.Conclusion Both etomidate and propofol combined with midazolam and fentanyl can decrease cerebral O2 metabolic rate and there is no significant difference between the two groups. Key words: Etomidate; Propofol; Brain; Oxygen consumption

Effects of remifentanil-induced controlled hypotension on cerebral oxygen metabolism in patients undergoing radical operation for gastric cancer

Objective To investigate the effects of remifentanil-indueed controlled hypoteusion (CH) on the cerebral oxygen metabolism in patients undergoing radical operation for gastric cancer. Methods Forty-two ASA Ⅰ or Ⅱ patients (26 male, 16 female) aged 30-64 yr with body nuts index < 30 kg/m2 undergoing elective radical operation for gastric cancer were randomly divided into 3 groups (n = 14 each): group R remifentanil-induced controlled hypotension; group N sodium nitroprusside-induced CH and group C normal BP. Radial artery was cannulated for continuous BP monitoring and blood sampling. A catheter was inserted into right internal jugular vein and advanced cephalad until jugular bulb for blood sampling. MAP, HR, ECG and SpO2were continuously monitored. Anesthesia was induced with midazolam 0.1 mg/kg, fentanyl 5 μg/kg, propofol 2 mg/kg and vecuronium 0.08 mg/kg and maintained with isoflurane (end-tidal concentration 1. 1% ), iv infusion of propofol (50-100 μg·kg-1·min-1 ) and remifentanil (0.1 μg·kg-1·min-1) and intermittent iv boluses of vecuronium. The patients were mechanically ventilated (VT 8-10 ml/kg, RR 12 bpm, I: E 1:1.5) after tracheal intubation. End-tidal CO2was maintained at 30-35 mm Hg. CH was started after abdomen was opened. In group R the remifentanil infusion rate was increased from 0.1 μg·kg-1·min-1 in 0.05 μg·kg-1·min-1 increment every minute until the1 μg·kg-1min-1 in 0.5 μg·kg-1·min-1 increment every minute until the desired BP was achieved. MAP was reduced to 70% of the baseline value but never below 50 mm Hg. CH induction time and BP recovery time were recorded. Arterial and jugular bulb venous blood samples were obtained before induction of anesthesia (T0), immediately before induction of CH (T1), at 10 and 30 min of CH (T2,3) and 20 min after termination of CH (T4). The arterial and jugular bulb venous O2content difference (Da-jvO2) and cerebral O2extraction rate ( CERO2) were calculated. The difference between arterial and jugular bulb venous blood lactic acid concentration (Da-jvL) was also calculated. Results The CH induction time and BP recovery time were significantly longer in group R than in group N, but BP was stabler during CH in group R than in group N. Compared with group C, Da-jvO2, CERO2and Da-jvL were significantly decreased in group R, while CERO2and Da-jvL were significantly increased in group N. Conclusion Remifentanil can effectively induce CH and reduce cerebral O2consumption in patients undergoing radical operation for gastric cancer. Key words: Piperidines; Hypotehsion,controlled; Brain; Oxygen consumption

Increased cerebral oxygen consumption in Eker rats and effects of N‐methyl‐D‐aspartate blockade: Implications for autism

Because there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that these animals would have an altered regional cerebral O2 consumption that might be associated with autism. We also examined whether the altered cerebral O2 consumption was related to changes in the importance of N-methyl-D-aspartate (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg, competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O2 consumption in the cortex (6.2 +/- 0.6 ml O2/min/100 g Eker vs. 4.7 +/- 0.4 Long Evans), hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated in Eker rats at baseline, but cerebral O2 extraction was similar. CGS-19755 significantly lowered O2 consumption in the cortex (2.8 +/- 0.3), hippocampus, and pons of the Long Evans rats but had no effect on cortex (5.8 +/- 0.8) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. NMDA receptor protein levels (NR1 subunit) were similar between groups. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not related to NMDA receptor activation. In fact, the importance of NMDA receptors in the control of basal cerebral O2 consumption was reduced. This might have important implications in the treatment of autism.

17Beta-estradiol suppresses AMPA-induced increases in regional cerebral O2 consumption

We tested the hypothesis that 17beta-estradiol would reduce the cerebral O2 consumption response resulting from glutamate receptor stimulation by alpha amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA). Fourteen ovariectomized rats were separated into 17beta-estradiol (0.5 mg 21 day release pellet) and control (placebo pellet) groups to determine cerebral blood flow (14C-iodoantipyrine) and O2 consumption (microspectrophotometry). After topical cortical stimulation with 10-3 M and 10-4 M AMPA, cerebral blood flow increased significantly in both groups in a concentration-dependent manner. Cerebral O2 extraction was not significantly different in any region of the 17beta-estradiol treated group. In the placebo treated group, the O2 extraction in the saline treated cortex and in the 10-3 M AMPA treated cortex was significanly higher when compared to the 10-4 M AMPA treated cortex. Cerebral O2 consumption in the control group increased by 20%, from 5.2 ± 0.6 to 6.1 ± 0.7, with 10-4 M AMPA and significantly increased by 64% to 8.5 ± 0.8 ml O2 min-1 100 g-1 with 10-3 M AMPA. The 17beta-estradiol group demonstrated no statistically significant difference in O2 consumption between the saline treated and AMPA treated cortex. Thus, 17beta-estradiol reduced the effects of AMPA in increasing cerebral O2 consumption.

Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study.

The authors investigated the effects of hyperoxia on brain tissue PO2 and on glucose metabolism in cerebral and adipose tissue after traumatic brain injury (TBI). After 3 hours of ventilation with pure O2, 18 tests were performed on different days in eight comatose patients with TBI. Lactate, pyruvate, glucose, glutamate, and brain tissue PO2 were measured in the cerebral extracellular fluid (ECF) by using microdialysis. Analytes were also measured in the ECF of abdominal adipose tissue. After 3 hours of increase in the fraction of inspired O2, brain tissue PO2 rose from the baseline value of 32.7 +/- 18 to 122.6 +/- 45.2 mm Hg (p < 0.0001), whereas brain lactate dropped from its baseline (3.21 +/- 2.77 mmol/L), reaching its lowest value (2.90 +/- 2.58 mmol/L) after 3 hours of hyperoxia (p < 0.01). Pyruvate dropped as well, from 153 +/- 56 to 141 +/- 56 micromol/L (p < 0.05), so the lactate/pyruvate ratio did not change. No significant changes were observed in glucose and glutamate. The arteriovenous difference in O2 content dropped, although not significantly, from a baseline of 4.52 +/- 1.22 to 4.15 +/- 0.76 m/100 ml. The mean concentration of lactate in adipose tissue fell significantly as well (p < 0.01), but the lactate/pyruvate ratio did not change. Hyperoxia slightly reduced lactate levels in brain tissue after TBI. The estimated redox status of the cells, however, did not change and cerebral O2 extraction seemed to be reduced. These data indicate that oxidation of glucose was not improved by hyperoxia in cerebral and adipose tissue, and might even be impaired.

Regional brain blood flow and cerebral hemispheric oxygen consumption during acute hypoxaemia in the llama fetus.

Unlike fetal animals of lowland species, the llama fetus does not increase its cerebral blood flow during an episode of acute hypoxaemia. This study tested the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral O2 extraction rather than decreasing cerebral oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically instrumented under general anaesthesia at 217 days of gestation (term ca 350 days) with vascular and amniotic catheters in order to carry out cardiorespiratory studies. Following a control period of 1 h, the llama fetuses underwent 3 x 20 min episodes of progressive hypoxaemia, induced by maternal inhalational hypoxia. During basal conditions and during each of the 20 min of hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres, cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2 consumption was determined by the modified Fick principle. During hypoxaemia, fetal arterial O2 tension and fetal pH decreased progressively from 24 +/- 1 to 20 +/- 1 Torr and from 7.36 +/- 0.01 to 7.33 +/- 0.01, respectively, during the first 20 min episode, to 16 +/- 1 Torr and 7.25 +/- 0.05 during the second 20 min episode and to 14 +/- 1 Torr and 7.21 +/- 0.04 during the final 20 min episode. Fetal arterial partial pressure of CO2 (P(a,CO2), 42 +/- 2 Torr) remained unaltered from baseline throughout the experiment. Fetal cerebral hemispheric blood flow and cerebral hemispheric oxygen extraction were unaltered from baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge. In conclusion, these data do not support the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral hemispheric O2 extraction. Rather, the data show that in the llama fetus, a reduction in cerebral hemispheric metabolism occurs during acute hypoxaemia.

Cerebral blood flow during hypoxic hypoxia with plasma-based hemoglobin at reduced hematocrit.

We determined whether cerebral blood flow (CBF) remained related to arterial O2 content (CaO2) during hypoxic hypoxia when hematocrit and hemoglobin concentration were independently varied with cell-free, tetramerically stabilized hemoglobin transfusion. Three groups of pentobarbital sodium-anesthetized cats were studied with graded reductions in arterial O2 saturation to 50%: 1) a control group with a hematocrit of 31 +/- 1% (mean +/- SE; n = 7); 2) an anemia group with a hematocrit of 21 +/- 1% that underwent an isovolumic exchange transfusion with an albumin solution (n = 8); and 3) a group transfused with an intramolecularly cross-linked hemoglobin solution to decrease hematocrit to 21 +/- 1% (n = 10). Total arterial hemoglobin concentration (g/dl) after hemoglobin transfusion (8.8 +/- 0.2) was intermediate between that of the control (10.3 +/- 0.3) and albumin (7.2 +/- 0.4) groups. Forebrain CBF increased after albumin and hemoglobin transfusion at normoxic O2 tensions to levels attained at equivalent reductions in CaO2 in the control group during graded hypoxia. Over a wide range of arterial O2 saturation and sagittal sinus PO2, CBF remained greater in the albumin group. When CBF was plotted against CaO2 for all three groups, a single relationship was formed. Cerebral O2 transport, O2 consumption, and fractional O2 extraction were constant during hypoxia and equivalent among groups. We conclude that CBF remains related to CaO2 during hypoxemia when hematocrit is reduced with and without proportional reductions in O2-carrying capacity. Thus O2 transport to the brain is well regulated at a constant level independently of alterations in hematocrit, hemoglobin concentration, and O2 saturation.

Effects of ethanol in an experimental model of combined traumatic brain injury and hemorrhagic shock.

Given that clinical and laboratory studies suggest that ethanol and hemorrhagic shock (HS) potentiate traumatic brain injury (TBI), the authors studied the effects of ethanol in a model of combined TBI and HS. A controlled porcine model of combined TBI and HS was evaluated for the effect of ethanol on survival time, hemodynamic function, and cerebral tissue perfusion. Anesthetized swine (17-24 kg) were instrumented, splenectomized, and subjected to fluid percussion TBI with concurrent 25-mL/kg graded hemorrhage over 30 minutes. Two groups were studied: control (n = 11) and ethanol (n = 11). Ethanol, 3.5 g/kg intragastric, was given 100 minutes prior to TBI/HS. Systemic and cerebral physiologic and metabolic parameters were monitored for 2 hours without resuscitation. Regional cerebral blood flow (rCBF) and renal blood flow were measured with dye-labeled microspheres. Data were analyzed with 2-sample t-test and repeated-measures ANOVA. Ethanol levels at the time of injury were 162 +/- 68 mg/dL. Average TBI was 2.65 +/- 0.35 atm. Survival time was significantly shorter in the ethanol group (60 +/- 27 min vs 94 +/- 28 min, p = 0.011). The ethanol group had significantly lower mean arterial pressure, cerebral perfusion pressure, and cerebral venous O2 saturation in the postinjury period. Cerebral O2 extraction ratios and cerebral venous lactate levels were significantly higher in the ethanol group. A trend toward lower postinjury rCBF in all brain regions was observed in the ethanol group. In this TBI/HS model, ethanol administration decreased survival time, impaired the hemodynamic response, and worsened measures of cerebral tissue perfusion.

Effects of excitatory amino acids on cerebral oxygen consumption and blood flow in rat.

This investigation tested the importance of excitatory amino acids' effects on regional cerebral O2 consumption and the concomitant changes in cerebral blood flow (rCBF) in isoflurane anesthetized rats. In the glutamate or N-methyl-D-aspartate (NMDA) groups, 10(-2) M glutamate or NMDA was topically applied to the right cortex and the left cortex was used as a control. One mg/kg dizocilpine maleate (MK-801), a non-competitive NMDA receptor antagonist, was administered (iv) to the MK-801 group and saline was given to the control group. Cortical rCBF was determined using 14C-iodoantipyrine and regional O2 extraction was measured microspectrophotometrically. Cerebral O2 consumption increased 77% after glutamate (contralateral cortex: 9.0 +/- 1.1 ml O2/min/100 g, glutamate treated cortex: 15.9 +/- 3.9), while a 46% increase was observed with the same concentration of NMDA (contralateral cortex: 9.8 +/- 2.0, NMDA treated cortex: 14.3 +/- 5.5). After MK-801, the O2 consumption decreased to 37% of the control value (control cortex: 7.0 +/- 1.3, MK-801 treated cortex: 2.6 +/- 3.9). MK-801 significantly decreased cerebral O2 extraction from 7.1 +/- 1.3 ml O2/100 ml (control cortex) to 5.3 +/- 0.6 (MK-801 treated cortex). However, there was no significant difference in cerebral O2 extraction between treated and contralateral cortex in either the glutamate or NMDA groups. The increase in O2 consumption caused by glutamate or NMDA was coupled with increased rCBF. Glutamate increased rCBF from 95 +/- 5 ml/min/100 g (contralateral cortex) to 165 +/- 31 (treated cortex), while NMDA increased rCBF from 114 +/- 12 (contralateral cortex) to 178 +/- 60 (treated cortex). MK-801 decreased O2 consumption with a lesser decrease of rCBF. The rCBF was 48 +/- 9 in the MK-801 treated cortex and 99 +/- 22 in the control cortex. Some substances produced by the activation of NMDA receptors may be related to the coupling of cerebral metabolism and blood flow, since after blockade of NMDA receptors with MK-801, this relationship is uncoupled. These findings suggest that glutamatergic processes have a major effect on cerebral O2 consumption and that this is at least partly due to NMDA receptors.

Cerebral lactate production in relation to intracranial pressure, cranial computed tomography findings, and outcome in patients with severe head injury

Severe head injury is frequently associated with focal or global disturbances of cerebral blood flow and metabolism. Routine monitoring of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these patients does not provide information about critically reduced local or global cerebral blood flow. Measurements of cerebral lactate difference, Lactate-Oxygen-Index (LOI) and cerebral oxygen extraction were evaluated for advanced monitoring by comparing these parameters with ICP, cranial computed tomography (CCT) findings, and outcome in a group of severely head-injured patients. In 21 patients with severe brain trauma (GCS < or = 8), arterial as well as jugular venous lactate levels and oxygen saturation were measured in vitro every 6 h after admission of patients to the intensive care unit (ICU) throughout the acute course of treatment. Arterial blood pressure, blood gases, and ICP were assessed by standard monitoring measurements. CCT was performed initially after admission of the patients to the hospital, during the acute period in the ICU, if indicated, and 10 to 14 days after trauma. Outcome was classified according to the Glasgow outcome scale (GOS) at six months after injury. Data were averaged in each patient for every day after trauma and over the entire monitoring period. Resulting values were tested for correlation by regression analysis. Additionally, the data of the group of patients with normal to minimally elevated mean ICP (ICP < 20 mmHg, n = 12) were compared to those of the patients with increased mean ICP (ICP > 20 mmHg, n = 9). The cerebral lactate difference in all patients on the day of trauma was significantly increased as compared to the later period (0.20 vs. 0.11-0.07 mmol/l, p < 0.05), but was not different with high or normal to minimally elevated ICP. In patients with intracranial hypertension, the cerebral lactate difference remained significantly increased from the first to the fifth day after injury, whereas it normalized in this period in the group with normal to minimally elevated ICP. Averaged over the acute course, patients with increased ICP had significantly higher mean lactate differences (0.18 +/- 0.16 vs. 0.067 +/- 0.025 mmol/l, p = 0.001) and higher mean LOIs (0.072 +/- 0.071 vs. 0.028 +/- 0.013, p = 0.011). There was a significant correlation of increased mean cerebral lactate difference to poor outcome (r = 0.46, p = 0.035). Cerebral oxygen extraction in all patients tended to increase on the day of trauma (36.7% vs. 29.2% to 31.5% during the subsequent course), but this difference was not significant. The initial degree of brain swelling, classified by CCT according to Marshall et al. (1991), showed no correlation with cerebral lactate differences, ICP, O2-extraction, or outcome. Neither was there a correlation of cerebral oxygen extraction to ICP nor to outcome. In conclusion, the severity of brain trauma and outcome of patients was reflected by increased cerebral lactate production. Unchanged values of global cerebral oxygen extraction suggest that the regulatory mechanisms of brain oxygen supply were not impaired by trauma. Measurements of cerebral lactate differences and brain oxygen extraction may contribute to advanced monitoring in severe head injury.

Continuous fiberoptic monitoring of oxygen saturation in cerebral veins in severe craniocerebral trauma--experiences and results

Monitoring of jugular-venous O2-saturation (SjO2) enables the assessment of cerebral oxygen supply and the rapid detection of cerebral desaturation in patients with severe head injury. Furthermore, it may help to optimize circulation, ventilation, and intracranial hypertension therapy in these patients. This study was performed to evaluate the reliability of SjO2-monitoring as well as to measure cerebral O2-extraction and the frequency of episodes of cerebral desaturation after traumatic brain injury. In 16 patients with severe head injury (GCS 3-8), SjO2 (fibreoptic system), arterial blood pressure, and intracranial pressure were continuously recorded after admission of the patients to the intensive care unit. Fluctuations of SjO2 (> 10% within 30 min), which were not included by therapeutic measures, were classified by off-line analysis as irregular-isolated or irregular-combined, if accompanied by similar fluctuations of ICP and arterial blood pressure. Recordings which were unreliable due to technical reasons, mainly because of wall adherence of the tip of the fibreoptic catheter, were evaluated separately. Episodes of cerebral desaturations (SjO2 < 50%) were assessed with regard to their frequency, duration (5-10/> 10 min) and underlying mechanisms. Cerebral O2-extraction was calculated as the difference between arterial and cerebrovenous O2-saturation and averaged for each day after trauma. Mean time of measurement for each patient was 194 hrs, a total of 3106 hrs were recorded. The correlation coefficient between in-vivo and in-vitro measured SjO2 was r = 0.62 (n = 367, p < 0.001). Reliable and artifact-free measurements of SjO2 were obtained only during 58.3% of all hours. Irregular-isolated fluctuations of the SjO2 occurred in 22.2% of the hours, and technical problems in 14.5%. Erroneous readings due to irregular-combined fluctuations of the jugular-venous O2-saturation were detected in 5.0% of the time periods. A total number of 66 episodes of cerebral desaturation (SjO2 < 50%) were found in all 16 patients, 41 of them had a duration of more than 10 minutes. Cerebral hypoxia was attributed to low cerebral perfusion pressure in 35% and hypocapnia in 17%. Global cerebral O2-extraction was significantly elevated at the day of injury compared to days 1-5 after trauma (37.4% vs. 28.9%-31.9%, p < 0.05). Monitoring of SjO2 in severe head injury provides an estimate of cerebral oxygen supply and may improve the assessment of therapeutic measures in these patients. The high incidence of erroneous readings of the SjO2 is a major drawback of this method. Initially after trauma, a high extraction of oxygen was found, followed by a marked decrease in the subsequent days, presumably reflecting an early, decreased cerebral blood flow and a hyperaemic flow pattern thereafter. Continuous measurements of SjO2 may contribute to advanced, organ-specific cerebral monitoring in severe craniocerebral trauma. The reliability of data, however, should be considerably improved for common clinical use.

Disturbance of cerebral oxygenation and hemodynamics related to the opening of the bypass bridge during veno-arterial extracorporeal membrane oxygenation.

The objective of this study was to investigate changes of cerebral oxygenation and hemodynamics related to opening of the bypass bridge during veno-arterial extracorporeal membrane oxygenation (ECMO). Ten newborn infants and 12 piglets were studied during opening of the bridge for 10 and 1 s, respectively. Changes in cerebral concentration of oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb), (oxidized-reduced) cytochrome aa3 (cCyt.aa3), and blood volume (CBV) were continuously measured by near infrared spectrophotometry. Heart rate, arterial O2 saturation (saO2), and mean arterial blood pressure (MABP) were measured simultaneously. In the piglets, central venous pressure (CVP), intracranial pressure (ICP), and left common carotid artery blood flow (CaBF) were also measured. Opening of the bridge for 10 s in the infants resulted in a significant decrease in MABP, saO2, and cO2Hb, whereas cHHb increased. CBV did not change significantly. In piglets biphasic changes were observed for MABP, CaBF, cO2Hb, and CBV, showing an initial decrease followed by a smaller increase. cHHb and CVP showed reverse biphasic changes. ICP increased but saO2 was unchanged. In all cases heart rate and cCyt.aa3 did not change significantly. Opening of the bridge for 1 s resulted in minor changes in only a few variables. In conclusion, opening of the bridge resulted in a decrease of CBV and cerebral O2 supply due to a decrease of cerebral blood flow, followed by a compensatory increase of cerebral O2 extraction and vasodilatation. The return of oxygenated blood after reclosing resulted in an increase of CBV with overcompensation of cerebral O2 supply.

Ethanol, morphine and barbiturate alter the hemodynamic and cerebral response to cocaine in newborn pigs.

Newborns delivered to cocaine-abusing mothers are often exposed to other concurrently consumed illicit drugs, which may alter the hemodynamic and cerebral response to cocaine. This study examined the interaction of ethanol, morphine or barbiturate with cocaine on mean arterial pressure (MAP), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in newborn pigs. CBF, CMRO2 and cerebral O2 extraction (CEO2) were measured before and 4 and 10 min after cocaine (1.5 mg/kg i.v.) was administered in piglets that were awake, or pretreated with morphine, ethanol or pentobarbital. In awake piglets, cocaine increased CMRO2 and CEO2 while it had no significant effect on CBF. Conversely, in morphine- and ethanol-pretreated piglets, cocaine decreased CMRO2, decreased CBF and had not effect on CEO2. In awake piglets, cocaine increased MAP, whereas in morphine- or ethanol-pretreated piglets, cocaine decreased MAP. In the pentobarbital group, cocaine had no effect. These data demonstrate that other drugs of abuse alter the hemodynamic and cerebral effects of cocaine in the immature animal and may contribute to the central nervous system abnormalities in 'crack babies'.