bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery of Systolic and Diastolic Left Ventricular Function Early after Cardiopulmonary Bypass
Authors: De Hert Stefan G. , Rodrigus Inez E. , Haenen Luc R. , De Mulder Peter A. , Gillebert Thierry C.
Published: November 2003

Background

Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload.

Methods

Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml-1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12).

Results

In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml-1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ ml and Kc was 0.011 +/- 0.002 ml-1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period.

Conclusions

Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.
Volatile Anesthetics Reduce Low-voltage-activated Calcium Currents in a Thyroid C-Cell Line
Authors: McDowell Thomas S. , Pancrazio Joseph J. , Lynch Carl III
Published: November 2003

Background

Volatile anesthetics may act in part by inhibiting voltage-dependent calcium channels. The effects of several volatile agents on three types of calcium channels in a thyroid C-cell line were examined.

Methods

Whole-cell calcium currents were recorded using standard patch clamp techniques. Current-voltage relationships were derived before, during, and after application of isoflurane, enflurane, or halothane. Low-voltage-activated (LVA; T type) calcium currents were isolated based on the voltage range of activation. High-voltage-activated (HVA) calcium currents were separated into L and N types using omega-conotoxin GVIA (omega-CTX) and nicardipine.

Results

All three agents reversibly decreased both LVA and HVA currents at clinically relevant concentrations. Isoflurane and enflurane both reduced peak LVA current more than peak HVA current: -33 +/- 6% (mean +/- SE) versus -22 +/- 4% for 0.71 mM isoflurane (n = 6), and -46 +/- 6% versus -35 +/- 5% for 1.21 mM enflurane (n = 6). In contrast, halothane depressed LVA and HVA currents to a similar extent: -22 +/- 4% versus -29 +/- 3% for 0.65 mM halothane (n = 6). Isoflurane had no effect on LVA whole-cell current kinetics. Pretreatment with either omega-CTX (400 nM) or nicardipine (1 microM) did not change the sensitivity of HVA current to isoflurane.

Conclusions

Isoflurane and enflurane block LVA calcium channels more potently than either L-type or N-type calcium channels, but halothane shows no such preferential effect. These results may have implications for the mechanism action of volatile anesthetics.
Effect of Isoflurane on Motor-evoked Potentials Induced by Direct Electrical Stimulation of the Exposed Motor Cortex with Single, Double, and Triple Stimuli in Rats
Authors: Kawaguchi Masahiko , Shimizu Kiyoshi , Furuya Hitoshi , Sakamoto Takanori , Ohnishi Hideyuki , Karasawa Jun
Published: November 2003

Background

The clinical application of intraoperative motor-evoked potentials (MEPs) has been hampered by their sensitivity to anesthetics. Recently, to overcome anesthetic-induced depression of myogenic MEPs, multiple stimulus setups with a paired or a train of pulses for stimulation of the motor cortex were reported. However, the effects of anesthetics on MEPs induced by these stimulation techniques are unknown.

Methods

Bipolar electrical stimulation of the left motor cortex was carried out in 15 rats anesthetized with thiopental while the compound muscle action potentials were recorded from the contralateral hind limb. After recording of the MEP in response to the single-shock stimulation of the motor cortex, paired pulses (double pulses) or a train of three pulses (triple pulses) with an interstimulus interval of each pulse at 0.3, 0.5, 1.0, 1.5, and 2.0 ms were applied. After control MEP recording, isoflurane was administered at a concentration of 0.25 minimum alveolar anesthetic concentration (MAC), 0.5 MAC, 0.75 MAC, and 1.0 MAC, and the effects of isoflurane on the MEPs induced by single, double, and triple pulses were evaluated.

Results

In all animals, distinct baseline MEPs were recorded. During the administration of 0.25 MAC and 0.5 MAC isoflurane, MEPs induced by stimulation with a single pulse could be recorded in 87% and 33% of animals, respectively, and MEP amplitude was significantly reduced in a dose-dependent manner. During the administration of 0.75 MAC isoflurane, MEPs after single-pulse stimulation could not be recorded in any animals. By stimulating with paired or triple pulses, the success rate of MEP recording and MEP amplitude significantly increased compared with those after single pulse before and during the administration of isoflurane. Both the success rate of MEP recording and MEP amplitude after double- and triple-pulse stimulation decreased significantly in a dose-dependent manner during the administration of isoflurane.

Conclusions

Application of double or triple stimulation of the motor cortex increases the success rate of MEP recording and its amplitude during isoflurane anesthesia in rats. However, these responses are suppressed by isoflurane in a dose-dependent manner.
Early Tracheal Extubation after Coronary Artery Bypass Graft Surgery Reduces Costs and Improves Resource Use
Authors: Cheng Davy C. H. , Karski Jacek , Peniston Charles , Raveendran Ganesh , Asokumar Buvanendran , Carroll Jo , David Tirone , Sandler Alan
Published: November 2003

Background

Economics has caused the trend of early tracheal extubation after cardiac surgery, yet no prospective randomized study has directly validated that early tracheal extubation anesthetic management decreases costs when compared with late extubation after cardiac surgery.

Methods

This prospective, randomized, controlled clinical trial was designed to evaluate the cost savings of early (1-6 h) versus late tracheal extubation (12-22 h) in patients after coronary artery bypass graft (CABG) surgery. The total cost for the services provided for each patient was determined for both the early and late groups from hospital admission to discharge home. All costs applicable to each of the services were classified into direct variables, direct fixed costs, and overhead (an indirect cost). Physician fees and heart catheterization costs were included. The total service cost was the sum of unit workload and overhead costs.

Results

One hundred patients having elective CABG who were younger than 75 yr were studied. Including all complications, early extubation (n = 50) significantly reduced cardiovascular intensive care unit (CVICU) costs by 53% (P < 0.026) and the total CABG surgery cost by 25% (P < 0.019) when compared with late extubation (n = 50). Forty-one patients (82%) in each group were tracheally extubated within the defined period. In the early extubation group, the actual departmental cost savings in CVICU nursing and supplies was 23% (P < 0.005), in ward nursing and supplies was 11% (P < 0.05), and in respiratory therapy was 12% (P < 0.05). The total cost savings per patient having CABG was 9% (P < 0.001). Further cost savings using discharge criteria were 51% for CVICU nursing and supplies (P < 0.001), 9% for ward nursing and supplies (P < 0.05), and 29% for respiratory therapy (P < 0.001), for a total cost savings per patient of 13% (P < 0.001). Early extubation also reduced elective case cancellations (P < 0.002) without any increase in the number of postoperative complications and readmissions.

Conclusions

Early tracheal extubation anesthetic management reduces total costs per CABG surgery by 25%, predominantly in nursing and in CVICU costs. Early extubation reduces CVICU and hospital length of stay but does not increase the rate or costs of complications when compared with patients in the late extubation group. It shifts the high CVICU costs to the lower ward costs. Early extubation also improves resource use after cardiac surgery when compared with late extubation.
Effects of Eltanolone on Myocardial Performance and Coronary Flow in Intact and Catecholamine-depleted Isolated Rabbit Hearts
Authors: Mouren Stephane , Abdenour Lamine , Souktani Rachid , Coriat Pierre
Published: November 2003

Background

Experimental studies suggest that the new short-acting intravenous anesthetic agent eltanolone does not markedly alter hemodynamics or cardiac function. However, because its intrinsic effects on myocardial performance and coronary blood flow are not yet known, they were examined in isolated blood-perfused rabbit hearts.

Methods

Coronary blood flow, myocardial contractility, relaxation, and oxygen consumption were measured during perfusion of hearts with 0.1 to 10 micrograms/ml eltanolone (n = 7) or its vehicle (n = 7). To determine whether the cardiac effects of eltanolone are mediated by indirect sympathetic activation, the same dose-response curve was studied in another group of five hearts depleted of catecholamine with reserpine treatment.

Results

Coronary blood flow significantly increased with 10 micrograms/ml eltanolone and significantly decreased with 10 micrograms/ ml eltanolone vehicle. At eltanolone concentrations less than 10 micrograms/ml, myocardial contractility and relaxation remained unchanged but decreased at 10 micrograms/ml. Myocardial contractility and relaxation were not affected by perfusion of eltanolone vehicle alone. In eltanolone-perfused hearts, unchanged myocardial oxygen consumption was associated with significant increases in coronary venous oxygen content and tension, but in vehicle-perfused hearts, it was associated with reduced coronary venous oxygen content and tension. In catecholamine-depleted hearts, the variations in myocardial performance and coronary blood flow induced by eltanolone were similar to those observed in intact hearts.

Conclusions

Eltanolone (0.1 to 3 micrograms/ml) did not alter myocardial performance or coronary blood flow in isolated blood-perfused rabbit hearts. These effects were not due to an eltanolone-induced indirect sympathetic activation. Cardiac depression and coronary vasodilatation were only observed at concentrations of eltanolone far greater than those in clinical range.
Intraabdominal Carbon Dioxide Insufflation in the Pregnant Ewe
Authors: Cruz Antonio M. , Southerland Lucy C. , Duke Tanya , Townsend Hugh G. G. , Ferguson James G. , Crone Lesley-Ann L.
Published: November 2003

Background

Laparoscopic surgical procedures are being performed in pregnant women with increasing frequency. Maternal-fetal physiologic changes occurring during intraabdominal carbon dioxide insufflation are poorly understood, and maternal-fetal safety is of concern during carbon dioxide pneumoperitoneum. A previous pilot study using end-tidal carbon dioxide-guided ventilation resulted in maternal and fetal acidosis and tachycardia during carbon dioxide pneumoperitoneum. Using serial arterial PCO2 to guide ventilation, this study was designed to evaluate maternal-fetal cardiopulmonary status, uterine blood flow, and the intraamniotic pressure effects of intraabdominal carbon dioxide insufflation in singleton pregnant ewes between 120 and 135 days of gestation.

Methods

In a prospective randomized cross-over study, nine ewes were to receive either abdominal insufflation with carbon dioxide to an intraabdominal pressure of 15 mmHg (n = 9; insufflation group) or receive no insufflation (n = 9; control group). Anesthesia was induced with thiopental and maintained with end-tidal halothane (1 to 1.5 minimum alveolar concentration/100% oxygen). Mechanical ventilation was guided by serial maternal arterial blood gas analysis to maintain PaCO2 between 35 and 40 mmHg. Data from insufflated animals were collected during insufflation (60 min) and after desufflation (30 min). Control group data were collected and matched to similar time intervals for 90 min. Ewes were allowed to recover, and after a rest period (48 h) they were entered in the cross-over study.

Results

During insufflation there was a significant increase (P < 0.05) in maternal PaCO2 to end-tidal carbon dioxide gradient and minute ventilation, with concomitant decreases in maternal end-tidal carbon dioxide and PaO2. Intraamniotic pressure increased significantly during insufflation. No significant changes were observed in maternal hemodynamic variables, fetal variables, or in uterine blood flow during the study. There were no fetal deaths or preterm labor in any of the animals during the experiment.

Conclusions

During the 1-h insufflation, a marked increase in PaCO2-to-end-tidal carbon dioxide gradient was observed, suggesting that capnography may be an inadequate guide to ventilation during carbon dioxide pneumoperitoneum in the pregnant patient. No other significant circulatory changes were observed.
Halothane Blocks Synaptic Excitation of Inhibitory Interneurons
Authors: Perouansky Misha , Kirson Eilon D. , Yaari Yoel
Published: November 2003

Background

Activation of principal hippocampal neurons is controlled by feedforward and feedback inhibition mediated by gamma-aminobutyric acidergic interneurons. The effects of halothane on glutamate receptor-mediated synaptic excitation of inhibitory interneurons have not been reported yet.

Methods

The effects of halothane on glutamatergic excitatory postsynaptic currents and on spike threshold in visually identified interneurons were studied with tight-seal, whole-cell voltage- and current-clamp recordings in thin slices from adult mouse hippocampus. The excitatory postsynaptic currents were pharmacologically isolated into their N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated components using selective antagonists.

Results

Halothane (0.37-2.78 mM) reversibly blocked non-N-methyl-D-aspartate and N-methyl-D-aspartate excitatory postsynaptic currents in hippocampal oriens-alveus interneurons. Half-maximal inhibition was observed at similar concentrations (0.59 mM and 0.50 mM, respectively). Halothane inhibited synaptically generated action potentials at concentrations that did not elevate the spike threshold.

Conclusions

Halothane blocks glutamate receptor-mediated synaptic activation of inhibitory interneurons in the mouse hippocampus.
Immediate-early Gene Expression in Ovine Brain after Cardiopulmonary Bypass and Hypothermic Circulatory Arrest
Authors: Bokesch Paula M. , Marchand James , Seirafi Peter A. , Deiss Judith M. , Warner Kenneth G. , Bronson Roderick T. , Kream Richard M.
Published: November 2003

Background

Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are associated with neurological injury. Altered immediate-early gene expression occurs rapidly in the brain in response to ischemia, hypoxia, and severe metabolic stress, which results in long-term changes in the molecular phenotype of neurons. This study determined the effects of CPB and HCA on the expression of the immediate-early gene c-fos.

Methods

Neonatal lambs were subjected to 2 h of CPB at 38 degrees C (n = 4) or 60 min (n = 6), 90 min (n = 7), and 120 min (n = 6) of HCA at 15 degrees C. One hour after terminating CPB at 38 degrees C, the brains were analyzed for FOS-encoding mRNA and FOS-like immunoreactivity in the hippocampal formation. Other animals (n = 15), subjected to the same CPB and HCA protocol, were allowed to survive 3-5 days before their brains were examined for dead neurons.

Results

Minimal c-fos mRNA and FOS proteins were observed in neurons of animals subjected to normothermic bypass and of those that served as controls. Non-neuronal FOS proteins were observed in the choroid plexus, ependyma, and blood vessels at all times, including normothermic CPB, but not in the control animals without CPB. The magnitude of c-fos mRNA expression in hippocampal neurons increased directly with the duration of HCA. In contrast, expression of FOS proteins peaked after 90 min of HCA and declined significantly thereafter. Dead neurons were seen in surviving animals after 2 h of HCA only.

Conclusions

Cardiopulmonary bypass and HCA alter immediate-early gene expression in the brain. Translational processes are impaired after 120 min of HCA and correlate with neuron death in the hippocampus.
Cricoid Cartilage Pressure Decreases Lower Esophageal Sphincter Tone
Authors: Tournadre Jean-Pierre , Chassard Dominique , Berrada Khalid R. , Bouletreau Paul
Published: November 2003

Background

Cricoid cartilage pressure induced to prevent pulmonary aspiration from regurgitation of gastric contents has been recommended, and its efficacy requires a force greater than 40 Newtons. For regurgitation to occur, both an increase in gastric pressure and relaxation of the lower esophageal sphincter (LES) are necessary. However, the effect of cricoid cartilage pressure on the LES is unknown. This study evaluated the effects of cricoid cartilage pressure on LES in human volunteers.

Methods

Lower esophageal sphincter and esophageal barrier pressures (which equals LES pressure-gastric pressure) were measured using a manometric method in eight unanesthetized volunteers (4 men, 4 women) classified as American Society of Anesthesiologists physical status 1. The force applied to the cricoid cartilage was measured continuously, and LES pressure was recorded at a cricoid force of 20 and 40 Newtons.

Results

Cricoid pressure decreased LES pressure from 24 +/- 3 mmHg to 15 +/- 4 mmHg at a force of 20 Newtons (P < 0.05) and to 12 +/- 4 mmHg with a force of 40 Newtons (P < 0.01).

Conclusions

These findings may explain the occurrence of pulmonary aspiration before tracheal intubation despite application of cricoid cartilage pressure.
Influence of Age and Gender on the Pharmacokinetics and Pharmacodynamics of Remifentanil
Authors: Minto Charles F. , Schnider Thomas W. , Egan Talmage D. , Youngs Elizabeth , Lemmens Harry J. M. , Gambus Pedro L. , Billard Valerie , Hoke John F. , Moore Katherine H. P. , Hermann David J. , Muir Keith T. , Mandema Jaap W. , Shafer Steven L.
Published: November 2003

Background

Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil.

Methods

Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of 1 to 8 micrograms.kg-1.min-1 for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concentration. The electroencephalogram was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an additional 15 healthy participants ages 41 to 84 y.

Results

The parameters for the simple three-compartment pharmacokinetic model were V1 = 4.98 l, V2 = 9.01 l, V3 = 6.54 l, Cl1 = 2.46 l/min, Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 y, V1 and Cl1 decreased by approximately 25% and 33%, respectively. The parameters for the simple sigmoid Emax pharmacodynamic model were Ke0 = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz, EC50 = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC50 and Ke0, with both decreasing by approximately 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively.

Conclusions

This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter.
Changes in Cerebrospinal Fluid Pressure and Lactate Concentrations during Thoracoabdominal Aortic Aneurysm Surgery
Authors: Drenger Benjamin , Parker Stephen D. , Frank Steven M. , Beattie Charles
Published: November 2003

Background

Although ischemic injury to the spinal cord is a well-known complication of aortic surgery, no metabolic markers have been identified as predictors of an adverse outcome. This study evaluated the effect of cerebrospinal fluid (CSF) drainage, with and without distal femoral perfusion or moderate hypothermia on blood and CSF lactate concentrations and CSF pressure during thoracoabdominal aortic aneurysm surgery.

Methods

Three nonconcurrent groups of patients were studied prospectively: patients with normal body temperature (35 degrees C) but without distal femoral bypass (n = 6), patients with normal body temperature with bypass (n = 7), and patients with hypothermia (30 degrees C) and bypass (n = 8). In all patients, CSF pressure was recorded before, during, and after aortic cross-clamping. During the surgical repair, CSF drainage was performed using a 4-Fr intrathecal silicone catheter. Blood and CSF lactate concentrations were measured throughout the operation.

Results

Significant increases in blood (490%) and CSF (173%) lactate concentrations were observed during and after thoracic aortic occlusion in patients with normothermia and no bypass (P < 0.02 and 0.05, respectively). Distal perfusion attenuated the increase in both blood and CSF lactate (P < 0.01), and a further reduction was achieved with hypothermia of 30 degrees C (P < 0.001). Patients who became paraplegic showed a greater increase in CSF lactate concentrations after aortic clamp release compared with those who suffered no neurological damage (275% vs. 123% of baseline; P < 0.05). Increased CSF pressure of 42-60% (P < 0.005) was noted soon after thoracic aortic occlusion, both with and without distal femoral bypass.

Conclusions

Incremental reductions in CSF lactate concentrations were achieved using distal femoral bypass and hypothermia. The reduction in CSF lactate correlated with the methods used to protect the spinal cord during thoracoabdominal aortic aneurysm surgery and was associated with better outcome. Decompression by distal bypass of the hemodynamic overload caused by aortic occlusion was insufficient to eliminate the acute increase in CSF pressure. Cerebrospinal fluid lactate measurements during high aortic surgery may accurately represent the spinal cord metabolic balance.
Incidence of Neurologic Complications Related to Thoracic Epidural Catheterization
Authors: Giebler Reiner M. , Scherer Ralf U. , Peters Jurgen
Published: November 2003

Background

Due to potential neurologic sequelae, the risk:benefit ratio of thoracic epidural analgesia is controversial. Surprisingly, however, few available data address neurologic complications. The incidence of neurologic complications occurring after thoracic epidural catheterization was studied in patients scheduled for abdominal or abdominothoracic surgery.

Methods

A total of 4,185 patients were studied, including 2,059 during the prospective phase of the study and 2,126 during the retrospective phase. After thoracic epidural catheterization, all patients received general anesthesia. Patients' neurologic status was assessed by an anesthesiologist using clinical criteria after operation and after epidural catheter removal. If neurologic complications were suspected, a neurologist was consulted. The incidence of specific complications was compared for different thoracic puncture sites: upper (T3/4-6/7), mid (T7/8-8/9), and lower (T9/10-11/12) catheter insertion levels.

Results

The overall incidence of complications after thoracic epidural catheterization was 3.1% (n = 128). This included dural perforation (0.7%; n = 30); unsuccessful catheter placement (1.1%; n = 45); postoperative radicular type pain (0.2%; n = 9), responsive to catheter withdrawal in all cases; and peripheral nerve lesions (0.6%; n = 24), 0.3% (n = 14) of which were peroneal nerve palsies probably related to surgical positioning or other transient peripheral nerve lesions (0.2%; n = 10). No signs suggesting epidural hematoma were recognized, and there were no permanent sensory or motor defects attributable to epidural catheterization. Unintentional dural perforation was observed significantly more often in the lower (3.4%) than in the mid (0.9%), or upper (0.4%) thoracic region. A single patient experienced severe respiratory depression after receiving epidural buprenorphine but recovered without sequelae.

Conclusions

Thoracic epidural catheterization for abdominal and thoracoabdominal surgery is not associated with a high incidence of serious neurologic complications. In fact, the incidence of puncture- and catheter-related complications is less in the mid and upper than in lower thoracic region, and the predicted maximum risk for permanent neurologic complications (upper bound of the 95% confidence interval) is 0.07%.
Decreased Thiopental Requirements in Early Pregnancy
Authors: Gin Tony , Mainland Phoebe , Chan Matthew T. V. , Short Timothy G.
Published: November 2003

Background

Anesthetic requirements for inhalational agents are decreased during pregnancy, but there are no data regarding requirements for intravenous agents. The quantal dose-response curves for thiopental were calculated for 70 nonpregnant women having gynecologic surgery and for 70 pregnant women of 7-13 weeks' gestation having elective abortions.

Methods

Groups of 10 patients were given 2, 2.4, 2.8, 3.3, 3.8, 4.5, or 5.3 mg/kg thiopental as a bolus dose during a period of 10 s. Two minutes later, patients were asked to open their eyes as a test for hypnosis. Patients who did not open their eyes were given a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical stimulus to the ulnar nerve as a test for anesthesia. Purposeful movement indicated that there was no anesthesia. Log dose-response curves for hypnosis and anesthesia were calculated after logit transformation.

Results

In the nonpregnant women, the median effective doses (ED50s) (95% confidence interval) for hypnosis and anesthesia were 3.1 (2.8-3.4) mg/kg and 4.9 (4.5-5.4) mg/kg, whereas in the pregnant women the corresponding ED50s were 2.6 (2.3-2.8) mg/kg and 4 (3.7-4.4) mg/kg. In the non-pregnant women, the ED95s (95% CI) for hypnosis and anesthesia were 4.4 (3.9-5.4) mg/kg and 6.4 (5.7-7.9) mg/kg, whereas in the pregnant women the corresponding ED95s were 3.7 (3.3-4.5) mg/kg and 5.2 (4.7-6.3) mg/kg. The pregnant to nonpregnant relative median potency (95% CI) ratio for hypnosis was 0.83 (0.67-0.96) and for anesthesia it was 0.82 (0.62-0.94).

Conclusions

The dose of thiopental for hypnosis was 17% less and that for anesthesia was 18% less in pregnant women of 7-13 weeks' gestation compared with that in nonpregnant women.
Hospital Costs and Severity of Illness in Three Types of Elective Surgery
Authors: Macario Alex , Vitez Terry S. , Dunn Brian , McDonald Tom , Brown Byron
Published: November 2003

Background

If patients who are more severely ill have greater hospital costs for surgery, then health-care reimbursements need to be adjusted appropriately so that providers caring for more seriously ill patients are not penalized for incurring higher costs. The authors' goal for this study was to determine if severity of illness, as measured by either the American Society of Anesthesiologists Physical Status (ASA PS) or the comorbidity index developed by Charlson, can predict anesthesia costs, operating room costs, total hospital costs, or length of stay for elective surgery.

Methods

The authors randomly selected 224 inpatients (60% sampling fraction) having either colectomy (n = 30), total knee replacement (n = 100), or laparoscopic cholecystectomy (n = 94) from September 1993 to September 1994. For each surgical procedure, backward-elimination multiple regression was used to build models to predict (1) total hospital costs, (2) operating room costs, (3) anesthesia costs, and (4) length of stay. Explanatory candidate variables included patient age (years), sex, ASA PS, Charlson comorbidity index (which weighs the number and seriousness of coexisting diseases), and type of insurance (Medicare/Medicaid, managed care, or indemnity). These analyses were repeated for the pooled data of all 224 patients. Costs (not patient charges) were obtained from the hospital cost accounting software.

Results

Mean total hospital costs were $3,778 (95% confidence interval +/- 299) for laparoscopic cholecystectomy, $13,614 (95% CI +/- 3,019) for colectomy, and $18,788 (95% CI +/- 573) for knee replacement. The correlation (r) between ASA PS and Charlson comorbidity scores equaled 0.34 (P < .001). No consistent relation was found between hospital costs and either of the two severity-of-illness indices. The Charlson comorbidity index (but not the ASA PS) predicted hospital costs only for knee replacement (P = .003). The ASA PS, but not the Charlson index, predicted operating room and anesthesia costs only for colectomy (P < .03).

Conclusions

Severity of illness, as categorized by ASA PS categories 1-3 or by the Charlson comorbidity index, was not a consistent predictor of hospital costs and lengths of stay for three types of elective surgery. Hospital resources for these lower-risk elective procedures may be expended primarily to manage the consequences of the surgical disease, rather than to manage the patient's coexisting diseases.
Interaction of Halothane with α- and β-Adrenoceptor Stimulations in Rat Myocardium
Authors: Hanouz Jean-Luc , Riou Bruno MD , Massias Laurent , Lecarpentier Yves , Coriat Pierre
Published: November 2003

Background

Halothane induces negative inotropic and lusitropic effects in myocardium. It has been suggested that halothane potentiates beta-adrenoceptor stimulation. However, its effects on the inotropic response to alpha-adrenoceptor stimulation and its effects on the lusitropic effects of alpha- and beta-adrenoceptor stimulation are unknown.

Methods

The effects of halothane (0.5 and 1 minimum alveolar concentration [MAC]) on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit solution at 29 degrees C, pH 7.40, with 0.5 mM calcium and stimulation frequency at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and isometric (R2) conditions.

Results

One MAC halothane induced a negative inotropic effect (54 +/- 3%, P < 0.05), increased R1 (109 +/- 3%, P < 0.05), and decreased R2 (88 +/- 2%, P < 0.05). In control groups, phenylephrine (137 +/- 7%, P > 0.05) and isoproterenol (162 +/- 6%, P < 0.05) induced a positive inotropic effect. Halothane did not significantly modify the positive inotropic effect of calcium, suggesting that it did not modify the inotropic reserve of papillary muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of phenylephrine (237 +/- 19%, P < 0.05) and isoproterenol (205 +/- 11%, P < 0.05). Halothane did not modify the lusitropic effect of phenylephrine under high or low load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of isoproterenol under low load (P < 0.05), whereas it did not modify the positive lusitropic effect of isoproterenol under high load.

Conclusions

At clinically relevant concentrations, halothane potentiated the positive inotropic effects of both alpha- and beta-adrenoceptor stimulation. Furthermore, halothane alters the positive lusitropic-effect of beta-adrenoceptor stimulation under low load.
Epidural and Intrathecal n-Butyl-p-Aminobenzoate Solution in the Rat
Authors: Grouls R. J. E. , Meert T. F. , Korsten H. H. M. , Hellebrekers L. J. , Breimer D. D.
Published: November 2003

Background

Epidural administration of an aqueous suspension of n-butyl-p-aminobenzoate (BAB) to humans results in long-lasting sensory blockade without motor block. The dose-response of BAB administered epidurally and intrathecally as a solution was studied in rats to define the local anesthetic properties in an established animal model.

Methods

The time course of changes in tail withdrawal latency and motor function were determined in rats after epidural or intrathecal administration of solutions of BAB or bupivacaine. The dose-response relation was determined and median effective dose values were calculated.

Results

After epidural and intrathecal administration of BAB solutions, the onset and duration of the antinociceptive action were comparable to bupivacaine. Median effective dose values for tail-withdrawal latency of 6 s or more were significantly greater for BAB. After both routes of administration, BAB clearly affected motor function.

Conclusions

When administered epidurally and intrathecally as a solution, BAB is a local anesthetic of relative low potency with onset and duration of action comparable to those of bupivacaine. These findings suggest that the long-lasting action obtained after applying BAB suspension results from the slow dissolution (continuous release) of the solid BAB deposited in the epidural space.
Anesthesia-related Deaths during Obstetric Delivery in the United States, 1979–1990
Authors: Hawkins Joy L. , Koonin Lisa M. , Palmer Susan K. , Gibbs Charles P.
Published: November 2003

Background

Anesthesia-related complications are the sixth leading cause of pregnancy-related death in the United States. This study reports characteristics of anesthesia-related deaths during obstetric delivery in the United States from 1979-1990.

Methods

Each state reports deaths that occur within 1 yr of delivery to the Centers for Disease Control and Prevention as part of the ongoing Pregnancy Mortality Surveillance. Maternal death certificates (with identifiers removed) matched with live birth or fetal death certificates when available from 1979-1990 were reviewed to identify deaths due to anesthesia, the cause of death, the procedure for delivery, and the type of anesthesia provided. Maternal mortality rates per million live births were calculated. Case fatality rates and risk ratios were computed to compare general to regional anesthesia for cesarean section deliveries.

Results

The anesthesia-related maternal mortality rate decreased from 4.3 per million live births in the first triennium (1979-1981) to 1.7 per million in the last (1988-1990). The number of deaths involving general anesthesia have remained stable, but the number of regional anesthesia-related deaths have decreased since 1984. The case-fatality risk ratio for general anesthesia was 2.3 (95% confidence interval [CI], 1.9-2.9) times that for regional anesthesia before 1985, increasing to 16.7 (95% CI, 12.9-21.8) times that after 1985.

Conclusions

Most maternal deaths due to complications of anesthesia occurred during general anesthesia for cesarean section. Regional anesthesia is not without risk, primarily because of the toxicity of local anesthetics and excessively high regional blocks. The incidence of these deaths is decreasing, however, and deaths due to general anesthesia remain stable in number and hence account for an increased proportion of total deaths. Heightened awareness of the toxicity of local anesthetics and related improvements in technique may have contributed to a reduction in complications of regional anesthesia.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Authors: Lacroix M. , Donati F. , Varin F.
Published: November 2003

Background

Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma.

Methods

Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters.

Results

Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed.

Conclusions

Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.
Inhaled Nitric Oxide Inhibits Platelet Aggregation after Pulmonary Embolism in Pigs
Authors: Gries Andre , Bottiger Bernd W. , Dorsam Joachim , Bauer Harry , Weimann Jorg , Bode Christoph , Martin Eike , Motsch Johann
Published: November 2003

Background

Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in persons with acute respiratory distress syndrome. In pulmonary embolism (PE), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that results in circulatory failure. In the present study, the effect of inhaled NO on platelet aggregation after acute massive PE was investigated.

Methods

After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14). NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (10), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively.

Results

Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (-13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure.

Conclusions

Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs. This may be beneficial in treating acute massive PE.
Blocking Mechanisms of Ketamine and Its Enantiomers in Enzymatically Demyelinated Peripheral Nerve as Revealed by Single-channel Experiments
Authors: Brau Michael E. , Sander Frank , Vogel Werner , Hempelmann Gunter
Published: November 2003

Background

Ketamine shows, besides its general anesthetic effect, a local anesthetic-like action that is due to blocking of peripheral nerve sodium currents. In this study, the stereoselectivity of the blocking effects of the ketamine enantiomers S(+) and R(-) was investigated in sodium and potassium channels in peripheral nerve membranes.

Methods

Ion channel blockade of ketamine was investigated in enzymatically dissociated Xenopus sciatic nerves in multiple-channel and in single-channel outside-out patches.

Results

Concentration-effect curves for the Na+ peak current revealed half-maximal inhibiting concentrations (IC50) of 347 microM and 291 microM for S(+) and R(-) ketamine, respectively. The potential-dependent K+ current was less sensitive than the Na+ current with IC50 values of 982 microM and 942 microM. The most sensitive ion channel was the flickering background K+ channel, with IC50 values of 168 microM and 146 microM for S(+) and R(-) ketamine. Competition experiments suggest one binding site at the flicker K+ channel, with specific binding affinities for each of the enantiomers. For the Na+ channel, the block was weaker in acidic (pH = 6.6) than in neutral (pH = 7.4) and basic (pH = 8.2) solutions; for the flicker K+ channel, the block was weaker in acidic and stronger in basic solutions.

Conclusions

Ketamine blockade of sodium and potassium channels in peripheral nerve membranes shows no stereoselectivity except for the flicker K+ channel, which showed a very weak stereoselectivity in favor of the R(-) form. This potential-insensitive flicker K+ channel may contribute to the resting potential. Block of this channel and subsequent depolarization of the resting membrane potential leads, besides to direct Na+ channel block, to inexcitability via Na+ channel inactivation.
Ascorbic Acid Inhibits Spinal Meningeal Catechol-o-Methyl Transferase in Vitro, Markedly Increasing Epinephrine Bioavailability
Authors: Kern C. , Bernards C. M.
Published: November 2003

Background

The spinal menings have previously been shown to contain catechol-o-methyl transferase (COMT), the enzyme that metabolizes epinephrine to the inactive metabolite metanephrine. The authors of this study aimed to quantitate the metabolism of epinephrine traversing the spinal meninges and to determine if that metabolism could be inhibited. In addition, they tried to determine the meningeal permeability of epinephrine.

Methods

Macca nemestrina spinal meninges were mounted in a diffusion cell and epinephrine was added to the donor reservoir at time 0. Three hundred minutes later, all buffer in the recipient reservoir was collected and analyzed for epinephrine metabolites. The experiments were conducted with either ascorbic acid (1 mM) or sodium metabisulfite (5.3 mM) added as antioxidants.

Results

In the presence of sodium metabisulfite, 60 +/- 6% of the epinephrine traversing the meningeal specimens was metabolized by COMT. In contrast, in the presence of ascorbic acid, less than 3% of the epinephrine traversing the spinal meninges was metabolized by COMT (P = 0.0001). The meningeal permeability coefficient for epinephrine was 0.38 +/- 0.08 cm/min x 10(-3).

Conclusions

Epinephrine permeability through the spinal meninges is low, and meningeal COMT markedly reduces the bioavailability of what little epinephrine can traverse the meninges. However, a clinically relevant concentration of ascorbic acid, a competitive inhibitor of COMT, almost completely blocks epinephrine metabolism and increases the bioavailability of epinephrine.
How Much Oxygen Does the Human Lung Consume?
Authors: Loer Stephan A. , Scheeren Thomas W. L. , Tarnow Jorg
Published: November 2003

Background

The amount of oxygen consumed by the lung itself is difficult to measure because it is included in whole-body gas exchange. It may be increased markedly under pathological conditions such as lung infection or adult respiratory distress syndrome. To estimate normal oxygen consumption of the human lung as a basis for further studies, respiratory gas analysis during total cardiopulmonary bypass may be a simple approach because the pulmonary circulation is separated from systemic blood flow during this period.

Methods

Lung oxygen consumption was determined in 16 patients undergoing cardiac surgery. During total cardiopulmonary bypass their lungs were ventilated with low minute volumes (tidal volume, 150 ml; rate, 6 min-1; inspiratory oxygen fraction, 0.5; positive end-expiratory pressure, 3 mmHg). All expiratory gas was collected and analyzed by indirect calorimetry. As a reference value also, whole-body oxygen consumption of these patients was determined before total cardiopulmonary bypass. In a pilot study of eight additional patients (same ventilatory pattern), the contribution of systemic (bronchial) blood flow to pulmonary gas exchange during cardiopulmonary bypass was assessed. For this purpose, the amount of enflurance diffusing from the systemic blood into the bronchial system was measured.

Results

The human lung consumes about 5-6 ml oxygen per minute at an esophageal temperature of 28 degrees C. Prebypass whole-body oxygen consumption measured at nearly normothermic conditions was 198 +/- 28 ml/min. Mean lung and whole-body respiratory quotients were similar (0.84 and 0.77, respectively). Extrapolating lung oxygen consumption to 36 degrees C suggests that the lung consumes about 11 ml/min or about 5% of total body oxygen consumption. Because the amount of enflurane diffused from the systemic circulation into the bronchial system during cardiopulmonary bypass was less than 0.1%, the contribution of bronchial blood flow to lung gas exchange can be assumed to be negligible.

Conclusions

The lung consumes about 5% of whole-body oxygen uptake.