bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-flow Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal Insufficiency
Authors: Conzen Peter F. , Kharasch Evan D. , Czerner Stephan F. A. , Artru Alan A. , Reichle Florian M. , Michalowski Piotr , Rooke G. Alec , Weiss Branko M. , Ebert Thomas J. 
Published: November 2003

Background
Sevoflurane is degraded to compound A (CpA) by carbon dioxide absorbents containing strong base. CpA is nephrotoxic in rats. Patient exposure to CpA is increased with low fresh gas flow rates, use of Baralyme, and high sevoflurane concentrations. CpA formation during low-flow and closed circuit sevoflurane anesthesia had no significant renal effects in surgical patients with normal renal function. Preexisting renal insufficiency is a risk factor for postoperative renal dysfunction. Although preexisting renal insufficiency is not affected by high-flow sevoflurane, the effect of low-flow sevoflurane in patients with renal insufficiency is unknown.

Methods
After obtaining institutional review board approval, 116 patients with a stable preoperative serum creatinine concentration 1.5 mg/dl or greater were assessable. Patients were randomized to receive either sevoflurane (n = 59, 0.8-2.5 vol%) or isoflurane (n = 57, 0.5-1.4 vol%) at a fresh gas flow rate of 1 l/min or less. Use of opioids was restricted to a minimum, and Baralyme was used to increase CpA exposure. Inspiratory and expiratory CpA concentrations were measured during anesthesia. Renal function (serum creatinine and blood urea nitrogen, urine protein and glucose, creatinine clearance) was measured preoperatively and 24 and 72 h after induction.

Results
Demographic patient data did not differ between groups. Patients received 3.1 +/- 2.4 minimum alveolar concentration-hours sevoflurane or 3.8 +/- 2.6 minimum alveolar concentration-hours isoflurane (mean +/- SD). Durations of low flow were 201.3 +/- 98.0 and 213.6 +/- 83.4 min, respectively. Maximum inspiratory CpA with sevoflurane was 18.9 +/- 7.6 ppm (mean +/- SD), resulting in an average total CpA exposure of 44.0 +/- 30.6 ppm/h. There were no statistically significant changes from baseline to 24- and 72-h values for serum creatinine or blood urea nitrogen, creatinine clearance, urine protein, and glucose, nor were there significant differences between both anesthetics.

Conclusion
There were no statistically significant differences in measured parameters of renal function after low-flow sevoflurane anesthesia compared with isoflurane. These results suggest that low-flow sevoflurane anesthesia is as safe as low-flow isoflurane and does not alter kidney function in patients with preexisting renal disease.
Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery
Authors: Kong Robert S. , Butterworth John , Aveling Wynne , Stump David A. , Harrison Michael J. G. , Hammon John , Stygall Jan , Rorie Kashemi D. , Newman Stanton P. 
Published: November 2003

Background
The neuroprotective property of clomethiazole has been demonstrated in several animal models of global and focal brain ischemia. In this study the authors investigated the effect of clomethiazole on cerebral outcome in patients undergoing coronary artery bypass surgery.

Methods
Two hundred forty-five patients scheduled for coronary artery bypass surgery were recruited at two centers and prospectively randomized to clomethiazole edisilate (0.8%), 225 ml (1.8 mg) loading dose followed by a maintenance dose of 100 ml/h (0.8 mg/h) during surgery, or 0.9% NaCl (placebo) in a double-blind trial. Coronary artery grafting was completed during moderate hypothermic (28-32 degrees C) cardiopulmonary bypass. Plasma clomethiazole was measured at several intervals during and up to 24 h after the end of infusion. A battery of eight neuropsychological tests was administered preoperatively and repeated 4-7 weeks after surgery. Analysis of the change in neuropsychological test scores from baseline was used to determine the effect of treatment.

Results
Neuropsychological assessments were completed in 219 patients (110 clomethiazole; 109 placebo). The mean plasma concentration of clomethiazole during surgery was 66.2 microm. There was no difference between the clomethiazole and placebo group in the postoperative change in neuropsychological test scores.

Conclusion
Clomethiazole did not improve cerebral outcome following coronary artery bypass surgery.
Effect of Low Isoflurane Concentrations on the Ventilation–Perfusion Distribution in Injured Canine Lungs
Authors: Putensen Christian , Räsänen Jukka , Putensen-Himmer Gabriele , Downs John B. 
Published: November 2003

Background
Rapid recovery and weaning from ventilatory support and cardiovascular stability are suggested advantages of isoflurane inhalation, in concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical ventilated patients. This study was designed to determine whether isoflurane in low concentrations impairs pulmonary gas exchange by increasing ventilation and perfusion (V(A)/Q) mismatch during lung injury.

Methods
Fourteen anesthetized dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before and after induction of lung injury with oleic acid. Gas exchange was assessed by blood gas analysis and by estimating the V(A)/Q distributions using the multiple inert gas elimination technique.

Results
Administration of oleic acid produced a lung injury with severe V(A)/Q mismatch and 38 +/- 4% intrapulmonary shunting of blood. During lung injury, isoflurane accounted for a dose-related increase in blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4% (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/- 0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a decrease in perfusion of normal V(A)/Q units from 58 +/- 5 to 55 +/- 4 (0.25 vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and 56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/- 19 ml. kg. min (0.25 vol%) and 505 +/- 22 ml. kg. min (0.5 vol%) (P < 0.05). Gas exchange, perfusion of shunt and normal V(A)/Q units, and pulmonary blood flow distribution was similar in absence of lung injury with and without isoflurane. Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05). CONCLUSIONS Inhalation of low concentrations of isoflurane contributed to increased V(A)/Q mismatch and decreased systemic blood flow and oxygen delivery in mechanically ventilated animals with injured lungs.
Changes in Regional Ventilation after Autologous Blood Clot Pulmonary Embolism
Authors: Vidal Melo Marcos F. , Harris R. Scott , Layfield Dominick , Musch Guido , Venegas Jose G. 
Published: November 2003

Background
Previous studies have suggested that pulmonary embolism (PE) and pulmonary artery occlusion result in a shift in alveolar ventilation away from unperfused regions. This study aimed to directly assess changes in regional specific ventilation (sV(A)) due to autologous blood clot PE using positron emission tomography.

Methods
Pulmonary embolism was created in six anesthetized, paralyzed, and mechanically ventilated sheep by injecting cylindrical clots of autologous blood (7 mm in diameter and height). Clots were progressively infused into a central vein until a stable mean pulmonary artery pressure between 30 and 40 mmHg was achieved. A multislice positron emission tomography camera was used to image 15 contiguous, 6.5-mm-thick transverse cross-sections of the chest beginning just above the diaphragm. sV(A) from perfused regions (sV(A),(p)) was assessed as the ventilatory turnover rate of the tracer NN after central venous injection of NN-labeled saline.

Results
Pulmonary embolism obstructed flow to 64% of imaged areas. Before PE, (sV(A),(p))was equivalent in areas that would remain perfused and those that would become embolized after PE (0.021 +/- 0.007 0.021 +/- 0.006 s(-1); P = nonsignificant). After PE, sV(A),(p) of areas remaining perfused increased to 0.033 +/- 0.011 s (-1) (P < 0.005). This effect on regional sV(A),(p) could have been caused by active redistribution of sV(A),(p) or by a reduction in tracer concentration of perfused areas due to the dead space common to perfused and embolized regions. Model simulations indicated that the common dead-space effect could only explain a small part of the sV(A),(p) increase.

Conclusions
An increase in sV(A),(p) of perfused regions occurs following PE with 7-mm autologous blood clots. This increase is most likely caused by a shift in ventilation away from embolized areas mediated by hypocapnic pneumoconstriction.
Carbon Monoxide Modulates Endotoxin-induced Microvascular Leukocyte Adhesion through Platelet-dependent Mechanisms
Authors: Morisaki Hiroshi , Katayama Tomihiro , Kotake Yoshifumi , Ito Masaharu , Handa Makoto , Ikeda Yasuo , Takeda Junzo , Suematsu Makoto 
Published: November 2003

Background
Although precise mechanisms remain to be determined, recent studies show that heme oxygenase-1 (HO-1), providing endogenous carbon monoxide (CO) and bilirubin, serves as an antiinflammatory enzyme. This study aimed to clarify roles of CO in regulation of microvascular adhesion of platelets and leukocytes in endotoxemia.

Methods
Rats pretreated with or without hemin were anesthetized with pentobarbital and received continuous infusion of endotoxin. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized using intravital ultra-high-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on platelet and leukocyte behavior during endotoxemia, these studies were repeated with superfusion of either CO, bilirubin, or zinc protoporphyrine-IX.

Results
Endotoxin caused a marked depression of platelet velocity traversing along periendothelial regions, accompanied by augmented rolling and adhesion of leukocytes in venules. The endotoxin-elicited changes were attenuated by the HO-1 induction with hemin and restored by blockade of the enzyme activity with zinc protoporphyrine-IX, a potent inhibitor of HO-1. Such an inhibitory action of HO-1 on microvascular cell adhesion was reproduced by local superfusion of the buffer containing CO at micromolar concentrations. Such antiadhesive actions of CO on leukocytes disappeared under immunoneutralization of glycoprotein Ibalpha, an adhesion molecule against platelets, but not against leukocytes. Platelets isolated from hemin-treated rats increased their ability to generate CO and displayed lesser sensitivity of agonist-induced aggregation than those from controls.

Conclusions
These results suggest that CO desensitizes endotoxin-induced adhesive responses of leukocytes, mainly through its ability to ameliorate platelet activation.
Collapsibility of the Upper Airway during Anesthesia with Isoflurane
Authors: Eastwood Peter R. , Szollosi Irene , Platt Peter R. , Hillman David R. 
Published: November 2003

Background
The unprotected upper airway tends to obstruct during general anesthesia, yet its mechanical properties have not been studied in detail during this condition.

Methods
To study its collapsibility, pressure-flow relationships of the upper airway were obtained at three levels of anesthesia (end-tidal isoflurane = 1.2%, 0.8%, and 0.4%) in 16 subjects while supine and spontaneously breathing on nasal continuous positive airway pressure. At each level of anesthesia, mask pressure was transiently reduced from a pressure sufficient to abolish inspiratory flow limitation (11.8 +/- 2.7 cm H(2)O) to pressures resulting in variable degrees of flow limitation. The relation between mask pressure and maximal inspiratory flow was determined, and the critical pressure at which the airway occluded was recorded. The site of collapse was determined from simultaneous measurements of nasopharyngeal, oropharyngeal, and hypopharyngeal and esophageal pressures.

Results
The airway remained hypotonic (minimal or absent intramuscular genioglossus electromyogram activity) throughout each study. During flow-limited breaths, inspiratory flow decreased linearly with decreasing mask pressure (r(2) = 0.86 +/- 0.17), consistent with Starling resistor behavior. At end-tidal isoflurane of 1.2%, critical pressure was 1.1 +/- 3.5 cm H O; at 0.4% it decreased to -0.2 +/- 3.6 cm H(2)O ( < 0.05), indicating decreased airway collapsibility. This decrease was associated with a decrease in end-expiratory esophageal pressure of 0.6 +/- 0.9 cm H(2)O ( < 0.05), suggesting an increased lung volume. Collapse occurred in the retropalatal region in 14 subjects and in the retrolingual region in 2 subjects, and did not change with anesthetic depth.

Conclusions
Isoflurane anesthesia is associated with decreased muscle activity and increased collapsibility of the upper airway. In this state it adopts the behavior of a Starling resistor. The decreased collapsibility observed with decreasing anesthetic depth was not a consequence of neuromuscular activity, which was unchanged. Rather, it may be related to increased lung volume and its effect on airway wall longitudinal tension. The predominant site of collapse is the soft palate.
Effectiveness of Acute Normovolemic Hemodilution to Minimize Allogeneic Blood Transfusion in Major Liver Resections
Authors: Matot Idit , Scheinin Olga , Jurim Oded , Eid Ahmed 
Published: November 2003

Background
Liver resection is a major operation for which, even with the improvements in surgical and anesthetic techniques, the reported rate of blood transfusion was rarely less than 30%. About 60% of transfused patients require only 1 or 2 units of blood, a blood requirement that may be accommodated by the use of acute normovolemic hemodilution (ANH).

Methods
The efficacy, hemodynamic effects, and safety of ANH were investigated in a randomized, active-control study in patients with American Society of Anesthesiologists status I-II who were undergoing major liver resection with fentanyl-nitrous oxide-isoflurane anesthesia. Patients were randomized to the ANH (n = 39) or control group (n = 39). Patients in the ANH group underwent hemodilution to a target hematocrit of 24%. The indication for blood transfusion was standardized. In both groups transfusion was started at a hematocrit of 20%. The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery. Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population.

Results
During the perioperative period, 14 control patients (36%) received at least one unit of allogeneic blood compared with 4 patients (10%) in the ANH group ( < 0.05). The hemodilution process was not associated with significant changes in patients' hemodynamics. Morbidity was similar between the control and the ANH groups. Postoperative hematocrit levels and biochemical liver, renal, and standard coagulation test results were similar in both groups.

Conclusions
Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I-II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood.
Input Characteristics and Bioavailability after Administration of Immediate and a New Extended-release Formulation of Hydromorphone in Healthy Volunteers
Authors: Drover David R. , Angst Martin S. , Valle Marta , Ramaswamy Bhamini , Naidu Sujata , Stanski Donald R. , Verotta Davide 
Published: November 2003

Background
To compare the pharmacokinetics of intravenous, oral immediate-release (IR), and oral extended-release (OROS ) formulations of hydromorphone.

Methods
In this randomized, six-session, crossover-design study, 12 subjects received hydromorphone 8-mg intravenous, 8-mg IR oral, and 8-, 16-, and 32-mg OROS formulations or placebo orally followed by plasma sampling for hydromorphone determination. Pharmacokinetic analysis was performed using NONMEM. Using the disposition of hydromorphone from the intravenous administration, deconvolution was used to estimate the input rate function (release rate from the gut to the blood) for the IR and OROS formulations. A linear spline was used to describe the drug input rate function.

Results
The deconvolution using linear splines described the release characteristics of both the IR and OROS formulations. The mean absolute bioavailability for the 8-mg OROS formulation was significantly larger ( = 0.025) than for the 8-mg IR formulation: 0.24 (SD 0.059) versus 0.19 (SD 0.054), respectively. The bioavailability was the same for the three doses of the OROS formulation. Predicted degree of fluctuation of plasma concentrations would be expected to be 130% and 39% for the IR and OROS 8-mg doses, respectively.

Conclusions
The OROS formulation of hydromorphone produced continued release of medication over 24 h, which should allow for once-daily oral dosing. The extended release of hydromorphone will produce less fluctuation of plasma concentrations compared with IR formulations, which should provide for more constant pain control. The in vivo release of hydromorphone from both IR and OROS formulations were adequately described using a linear spline deconvolution approach. The increased bioavailability from the OROS formulation may be related to decreased metabolism by a first-pass effect or enterohepatic recycling of hydromorphone.
Hemostatic Activation and Inflammatory Response during Cardiopulmonary Bypass
Authors: Koster Andreas , Fischer Thomas , Praus Michael , Haberzettl Helmut , Kuebler Wolfgang M. , Hetzer Roland , Kuppe Herman 
Published: November 2003

Background
Cardiac surgery involving cardiopulmonary bypass (CPB) leads to fulminant activation of the hemostatic-inflammatory system. The authors hypothesized that heparin concentration-based anticoagulation management compared with activated clotting time-based heparin management during CPB leads to more effective attenuation of hemostatic activation and inflammatory response. In a randomized prospective study, the authors compared the influence of anticoagulation with a heparin concentration-based system (Hepcon HMS; Medtronic, Minneapolis, MN) to that of activated clotting time-based management on the activation of the hemostatic-inflammatory system during CPB.

Methods
Two hundred elective patients (100 in each group) undergoing standard cardiac surgery in normothermia were enrolled. No antifibrinolytic agents or aprotinin and no heparin-coated CPB systems were used. Samples were collected after administration of the heparin bolus before initiation of CPB and after conclusion of CPB before protamine infusion.

Results
There were no differences in the pre-CPB values between both groups. After CPB there were significantly higher concentrations ( < 0.05) for heparin and a significant reduction in thrombin generation (25.2 +/- 21.0 SD vs. 34.6 +/- 25.1), d-dimers (1.94 +/- 1.74 SD vs. 2.58 +/- 2.1 SD), and neutrophil elastase (715.5 +/- 412 SD vs. 856.8 +/- 428 SD), and a trend toward lower beta-thromboglobulin, C5b-9, and soluble P-selectin in the Hepcon HMS group. There were no differences in the post-CPB values for platelet count, adenosine diphosphate-stimulated platelet aggregation, antithrombin III, soluble fibrin, Factor XIIa, or postoperative blood loss.

Conclusion
Compared with heparin management with the activated clotting time, heparin concentration-based anticoagulation management during CPB leads to a significant reduction of thrombin generation, fibrinolysis, and neutrophil activation, whereas there is no difference in the effect on platelet activation. The generation of fibrin even in the presence of high heparin concentrations most likely has to be attributed to the reduced antithrombin III concentrations or reduced inhibition of clot-bound thrombin. Therefore, in addition to maintenance of higher heparin concentrations, monitoring and substitution of antithrombin III should be considered to ensure more efficient antithrombin activity during CPB.
Ischemic Preconditioning Is Capable of Inducing Mitochondrial Tolerance in the Rat Brain
Authors: Zhan Ren-Zhi , Fujihara Hideyoshi , Baba Hiroshi , Yamakura Tomohiro , Shimoji Koki 
Published: November 2003

Background
Preconditioning to ischemia is a phenomenon whereby a brief episode of sublethal ischemia and other nonlethal stressors produce protection against a subsequent detrimental ischemic insult. As mitochondrial dysfunction is related to necrotic and apoptotic neuronal death after cerebral ischemia, the authors examined if ischemic preconditioning is capable of inducing mitochondrial tolerance.

Methods
Forebrain ischemia was induced by bilateral common carotid artery occlusion with simultaneous hypotension for 8 min in Wistar rats (275-300 g). A 3-min ischemic episode performed 48 h before the 8-min ischemia was used for preconditioning. The extents of hippocampal CA1 neuronal damage were evaluated 7 days after reperfusion by neuro-specific nuclear protein immunostaining. Brain mitochondria were isolated 48 h after animals were subjected to the sham operation or the 3-min conditioning ischemia. Loss of cytochrome c from mitochondria after cerebral ischemia in vivo and after exposure of brain mitochondria to calcium in vitro was used as an indication of mitochondrial dysfunction.

Results
Results showed that ischemic preconditioning induced by a 3-min ischemic episode dramatically reduced the loss of hippocampal CA1 neurons resulting from a subsequent 8-min ischemia 7 days after reperfusion, and this protection was associated with a preservation of mitochondrial cytochrome c as examined after early reperfusion. Exposure of isolated brain mitochondria to calcium produced a dose-dependent increase in cytochrome c release either at 30 degrees C or at 37 degrees C. Compared with those animals receiving only sham operation, cytochrome c release caused by 100 microm calcium was significantly reduced in conditioned animals.

Conclusion
Regarding the importance of mitochondrial dysfunction in mediating ischemic neuronal death, the above results indicate that mitochondria may serve as end-effecting organelles to ischemic preconditioning.