bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonhalogenated Alkane Anesthetics Fail to Potentiate Agonist Actions on Two Ligand-gated Ion Channels
Authors: Raines Douglas E. , Claycomb Robert J. , Scheller Michaela , Forman Stuart A.
Published: November 2003

Background

Although ether, alcohol, and halogenated alkane anesthetics potentiate agonist actions or increase the apparent agonist affinity of ligand-gated ion channels at clinically relevant concentrations, the effects of nonhalogenated alkane anesthetics on ligand-gated ion channels have not been studied. The current study assessed the abilities of two representative nonhalogenated alkane anesthetics (cyclopropane and butane) to potentiate agonist actions or increase the apparent agonist affinity of two representative ligand-gated ion channels: the nicotinic acetylcholine receptor and y-aminobutyric acid type A (GABA(A)) receptor.

Methods

Nicotinic acetylcholine receptors were obtained from the electroplax organ of Torpedo nobiliana, and human GABA(A) receptors (alpha1beta2gamma2L) were expressed in human embryonic kidney 293 cells. The Torpedo nicotinic acetylcholine receptors apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the apparent rates of desensitization induced by a range of acetylcholine concentrations. The GABA(A) receptor's apparent agonist affinity in the presence and absence of anesthetic was assessed by measuring the peak currents induced by a range of GABA concentrations.

Results

Neither cyclopropane nor butane potentiated agonist actions or increased the apparent agonist affinity (reduced the apparent agonist dissociation constant) of the Torpedo nicotinic acetylcholine receptor or GABA(A) receptor. At clinically relevant concentrations, cyclopropane and butane reduced the apparent rate of Torpedo nicotinic acetylcholine receptor desensitization induced by low concentrations of agonist.

Conclusions

Our results suggest that the in vivo central nervous system depressant effects of nonhalogenated alkane anesthetics do not result from their abilities to potentiate agonist actions on ligand-gated ion channels. Other targets or mechanisms more likely account for the anesthetic activities of nonhalogenated alkane anesthetics.
Halothane but Not Isoflurane Attenuates Interleukin 1β– induced Nitric Oxide Synthase in Vascular Smooth Muscle
Authors: Maeda Hiroshi , Iranami Hiroshi , Yamamoto Manabu , Ogawa Koji , Morikawa Yoshihiro , Senba Emiko , Hatano Yoshio
Published: November 2003

Background

Inducible nitric oxide synthase (iNOS) is induced by endotoxin or cytokines, such as interleukin (IL)-1, through a protein synthesis pathway. Halothane reportedly inhibits protein synthesis in various tissues. The aim of the current study was to examine the effect of halothane on the IL-1beta-evoked induction of NOS in vascular smooth muscle.

Methods

After removal of the endothelium, arterial rings of rat aorta were mounted in an isometric force recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL-1beta (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mM) and phenylephrine (10(-9)-10(-5) M) were studied. The cyclic guanosine monophosphate and cyclic adenosine monophosphate contents were determined by radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or Northern blot analysis, respectively.

Results

Halothane (1.0-3.0%) but not isoflurane (3%) significantly reduced the ML-1beta-induced inhibition of contraction in a concentration-dependent manner. The cyclic guanosine monophosphate content of the vascular smooth muscle increased significantly after a 5-h exposure to IL-1beta. Halothane at 3.0% significantly inhibited the increase in cyclic guanosine monophosphate content induced by IL-1beta. Halothane had no effect on cyclic adenosine monophosphate content. IL-1beta-induced expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by halothane.

Conclusion

The current study demonstrated that halothane but not isoflurane inhibits IL-1beta-stimulated hyporesponsiveness to vasoconstrictive agents in vascular smooth muscle and that this inhibitory effect of halothane involves the inhibition of iNOS mRNA expression. Thus, these findings suggest that halothane may have some sites to affect nitric oxide-signaling pathway.
Opioid Peptide–expressing Leukocytes
Authors: Rittner Heike L. , Brack Alexander , Machelska Halina , Mousa Shaaban A. , Bauer Monika , Schäfer Michael , Stein Christoph
Published: November 2003

Background

Inflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify populations of opioid-containing cells during the course of Freund's complete adjuvant-induced hind paw inflammation in the rat. In parallel, we examined the development of stress-induced local analgesia in the paw.

Methods

At 2, 6, and 96 h after Freund's complete adjuvant inoculation, cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to beta-endorphin. After magnetic cell sorting, the beta-endorphin content was quantified by radioimmunoassay. Pain responses before and after cold water swim stress were evaluated by paw pressure thresholds.

Results

In early inflammation, 66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+ monocytes or macrophages (73%). During the 4 days after Freund's complete adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001, Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9-fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced analgesia increased by 160% (P < 0.01, analysis of variance).

Conclusions

The degree of endogenous pain inhibition is proportional to the number of opioid peptide-producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation. These mechanisms may be important for understanding pain in immunosuppressed states such as cancer, diabetes, or AIDS and for the design of novel therapeutic strategies in inflammatory diseases.
Halothane-dependent Lipid Peroxidation in Human Liver Microsomes Is Catalyzed by Cytochrome P4502A6 (CYP2A6)
Authors: Minoda Yuko , Kharasch Evan D.
Published: November 2003

Background

Halothane is extensively (approximately 50%) metabolized in humans and undergoes both oxidative and reductive cytochrome P450-catalyzed hepatic biotransformation. Halothane is reduced under low oxygen tensions by CYP2A6 and CYP3A4 in human liver microsome to an unstable free radical, and then to the volatile metabolites chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE). The free radical is also thought to initiate lipid peroxidation. Halothane-dependent lipid peroxidation has been shown in animals in vitro and in vivo but has not been evaluated in humans. This investigation tested the hypothesis that halothane causes lipid peroxidation in human liver microsomes, identified P450 isoforms responsible for halothane-dependent lipid peroxidation, and tested the hypothesis that lipid peroxidation is prevented by inhibiting halothane reduction.

Methods

Halothane metabolism was determined using human liver microsomes or cDNA-expressed P450. Lipid peroxidation was quantified by malondialdehyde (MDA) formation using high-pressure liquid chromatography-ultraviolet analysis of the thiobarbituric acid-MDA adduct. CTE and CDE were determined by gas chromatography-mass spectrometry.

Results

Halothane caused MDA formation in human liver microsomes at rates much lower than in rat liver microsomes. Human liver microsomal MDA production exhibited biphasic enzyme kinetics, similar to CDE and CTE production. MDA production was inhibited by the CYP2A6 inhibitor methoxsalen but not by the CYP3A4 inhibitor troleandomycin. Halothane-dependent MDA production was catalyzed by cDNA-expressed CYP2A6 but not CYP3A4 or P450 reductase alone. CYP2A6-catalyzed MDA production was inhibited by methoxsalen or anti-CYP2A6 antibody.

Conclusions

Halothane causes lipid peroxidation in human liver microsomes, which is catalyzed by CYP2A6, and inhibition of halothane reduction prevents halothane-dependent lipid peroxidation in vitro.
Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide
Authors: Visser Klazina , Hassink Elly A. , Bonsel Gouke J. , Moen Jeroen , Kalkman Cor J.
Published: November 2003

Background

To assess the incidence of postoperative nausea and vomiting after total intravenous anesthesia (TIVA) with propofol versus inhalational anesthesia with isoflurane-nitrous oxide, the authors performed a randomized trial in 2,010 unselected surgical patients in a Dutch academic institution. An economic evaluation was also performed.

Methods

Elective inpatients (1,447) and outpatients (563) were randomly assigned to inhalational anesthesia with isoflurane-nitrous oxide or TIVA with propofol-air. Cumulative incidence of postoperative nausea and vomiting was recorded for 72 h by blinded observers. Cost data of anesthetics, antiemetics, disposables, and equipment were collected. Cost differences caused by duration of postanesthesia care unit stay and hospitalization were analyzed.

Results

Total intravenous anesthesia reduced the absolute risk of postoperative nausea and vomiting up to 72 h by 15% among inpatients (from 61% to 46%, P < 0.001) and by 18% among outpatients (from 46% to 28%, P < 0.001). This effect was most pronounced in the early postoperative period. The cost of anesthesia was more than three times greater for propofol TIVA. Median duration of stay in the postanesthesia care unit was 135 min after isoflurane versus 115 min after TIVA for inpatients (P < 0.001) and 160 min after isoflurane versus 150 min after TIVA for outpatients (P = 0.039). Duration of hospitalization was equal in both arms.

Conclusion

Propofol TIVA results in a clinically relevant reduction of postoperative nausea and vomiting compared with isoflurane-nitrous oxide anesthesia (number needed to treat = 6). Both anesthetic techniques were otherwise similar. Anesthesia costs were more than three times greater for propofol TIVA, without economic gains from shorter stay in the postanesthesia care unit
Ropivacaine 0.2% and Lidocaine 0.5% for Intravenous Regional Anesthesia in Outpatient Surgery
Authors: Atanassoff Peter G. , Ocampo Carlos A. , Castro Bande Marcos , Hartmannsgruber Maximilian W. B. , Halaszynski Thomas M.
Published: November 2003

Background

A longer-acting local anesthetic agent, such as ropivacaine, may offer advantages over lidocaine for intravenous regional anesthesia. The objectives of this study were to evaluate whether the findings of volunteer investigations with intravenous regional anesthesia with ropivacaine (which have shown prolonged analgesia after release of the tourniquet) translates into improved pain control after surgery.

Methods

With Human Investigation Committee approval and a double-blind study design, 20 healthy patients with American Society of Anesthesiologists physical status I or II classification who were scheduled to undergo forearm and hand surgery were randomly assigned to administration of 40 ml of either 0.2% ropivacaine or 0.5% lidocaine for intravenous regional anesthesia. Evidence of central nervous system side effects, such as lightheadedness, tinnitus, and metallic taste, as well as cardiac arrhythmias, were evaluated and treated (if necessary) after local anesthetic administration, before and during surgery, and after release of the tourniquet until discharge from the postanesthesia care unit. Regression of sensory anesthesia in the nerve distributions of the forearm and hand was recorded. Verbal numerical pain scores were monitored and quantified until the patients were discharged to home from the postanesthesia care unit. Patient pain scores, side effect profiles, time to first oral intake, and total amount of oral analgesics were recorded 24 h postoperatively.

Results

Intravenous regional anesthesia with 0.2% ropivacaine and 0.5% lidocaine provided equivalent levels of surgical anesthesia. After release of the tourniquet, the first evidence for return of sensation in the distribution of the five peripheral nerves occurred later in the ropivacaine group (median, 20 min; range, 15-40 min) than in the lidocaine group (median, 1 min; range, 1-25 min). Verbal numerical pain scores were significantly lower at the time of admission, whereas during the remainder of the postanesthesia care unit stay and later at home, the difference in verbal numerical pain scores between the two groups was no longer statistically significant.

Conclusions

Ropivacaine 0.2% may be an alternative to 0.5% lidocaine for intravenous regional anesthesia in the outpatient surgical setting. Longer-lasting analgesia in the immediate postoperative period may be due to a more profound and prolonged tissue binding effect of ropivacaine.
Magnesium Sulfate Does Not Reduce Postoperative Analgesic Requirements
Authors: Ko Seong-Hoon , Lim Hye-Rin , Kim Dong-Chan , Han Young-Jin , Choe Huhn , Song He-Sun
Published: November 2003

Background

Because magnesium blocks the N-methyl-D-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans. The current study was designed to evaluate whether perioperative intravenous magnesium sulfate infusion affects postoperative pain.

Methods

Sixty patients undergoing abdominal hysterectomy received 50 mg/kg intravenous magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg x kg(-1) x h(-1) for 6 h (magnesium group) or the same volume of isotonic saline (control group). At the end of surgery, serum and CSF magnesium concentration were measured in both groups. The cumulative postoperative analgesic consumption was measured to assess the analgesic effect using a patient-controlled epidural analgesia device. Pain intensities at rest and during forced expiration were evaluated at 6, 24, 48, and 72 h postoperatively.

Results

At the end of surgery, patients in the magnesium group had significantly greater postoperative serum magnesium concentrations compared with both preoperative and control group values (P < 0.001). Despite significantly higher serum magnesium concentrations in the magnesium group, there was no significant difference in magnesium concentration measured in postoperative CSF. Cumulative postoperative analgesic doses were similar in both groups. However, there was observed an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration in both groups. Visual analog pain scores at rest and during forced expiration were similar and less than 4 in both groups.

Conclusions

Perioperative intravenous administration of magnesium sulfate did not increase CSF magnesium concentration and had no effects on postoperative pain. However, an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration was observed. These results suggest that perioperative intravenous magnesium infusion may not be useful for preventing postoperative pain.
Use of Intraoperative Transesophageal Echocardiography to Predict Atrial Fibrillation after Coronary Artery Bypass Grafting
Authors: Shore-Lesserson Linda , Moskowitz David , Hametz Craig , Andrews David , Yamada Tatsuya , Vela-Cantos Frances , Hossain Sabera , Bodian Carol , Lessen Ronald J. , Konstadt Steven N.
Published: November 2003

Background

Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital.

Methods

The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation.

Results

Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96).

Conclusions

Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.
Desflurane, Sevoflurane, and Isoflurane Affect Left Atrial Active and Passive Mechanical Properties and Impair Left Atrial–Left Ventricular Coupling In Vivo
Authors: Gare Meir , Schwabe David A. , Hettrick Douglas A. , Kersten Judy R. , Warltier David C. , Pagel Paul S.
Published: November 2003

Background

The effects of volatile anesthetics on left atrial function in vivo have not been described. The authors tested the hypothesis that desflurane, sevoflurane, and isoflurane alter left atrial mechanics evaluated with invasively derived pressure-volume relations.

Methods

Barbiturate-anesthetized dogs (n = 24) were instrumented for measurement of aortic, left atrial, and left ventricular pressures (micromanometers) and left atrial volume (orthogonal sonomicrometers). Left atrial contractility and chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively, obtained from differentially loaded diagrams. Relaxation was determined from the slope of left atrial pressure decline after contraction. Stroke work and reservoir function were assessed by A and V loop areas, respectively. Left atrial-left ventricular coupling was determined by the ratio of left atrial contractility and left ventricular elastance. Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration desflurane, sevoflurane, or isoflurane in a random manner, and left atrial function was determined after 20-min equilibration at each dose.

Results

Desflurane, sevoflurane, and isoflurane decreased heart rate, mean arterial pressure, and maximal rate of increase of left ventricular pressure and increased left atrial end-diastolic, end-systolic, and maximum volumes. All three anesthetics caused dose-related reductions in left atrial contractility, relaxation, chamber stiffness, and stroke work. Administration of 0.6 and 0.9 minimum alveolar concentration desflurane, sevoflurane, and isoflurane increased V loop area. All three anesthetics decreased the ratio of stroke work to total left atrial pressure-volume diagram area, increased the ratio of conduit to reservoir volume, and reduced left atrial contractility-left ventricular elastance to equivalent degrees.

Conclusions

The results indicate that desflurane, sevoflurane, and isoflurane depress left atrial contractility, delay relaxation, reduce chamber stiffness, preserve reservoir and conduit function, and impair left atrial-left ventricular coupling in vivo.
Myocardial and Coronary Effects of Propofol in Rabbits with Compensated Cardiac Hypertrophy
Authors: Ouattara Alexandre , Langeron Olivier , Souktani Rachid , Mouren Stéphane , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts.

Methods

The effects of propofol (10-1,000 microM) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7).

Results

The cardiac hypertrophy model induced significant left ventricular hypertrophy (136+/-21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (> or = 300 microM) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157+/-23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group.

Conclusions

Propofol only decreased myocardial function at supratherapeutic concentrations. The myocardial and coronary effects of propofol were not significantly modified in cardiac hypertrophy.
Lidocaine and Mexiletine Inhibit Mitochondrial Oxidation in Rat Ventricular Myocytes
Authors: Tsutsumi Yasuo , Oshita Shuzo , Kawano Takashi , Kitahata Hiroshi , Tomiyama Yoshinobu , Kuroda Yasuhiro , Nakaya Yutaka
Published: November 2003

Background

Accumulating evidence suggests that mitochondrial rather than sarcolemmal adenosine triphosphate-sensitive K+ (K(ATP)) channels may have an important role in the protection of myocardium during ischemia. Because both lidocaine and mexiletine are frequently used antiarrhythmic drugs during myocardial ischemia, it is important to investigate whether they affect mitochondrial K(ATP) channel activities.

Methods

Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. The authors measured flavoprotein fluorescence to evaluate mitochondrial redox state. Lidocaine or mexiletine was applied after administration of diazoxide (25 microM), a selective mitochondrial K(ATP) channel opener. The redox signal was normalized to the baseline flavoprotein fluorescence obtained during exposure to 2,4-dinitrophenol, a protonophore that uncouples respiration from ATP synthesis and collapses the mitochondrial potential.

Results

Diazoxide-induced oxidation of flavoproteins and the redox changes were inhibited by 5-hydroxydecanoic acid, a selective mitochondrial K(ATP) channel blocker, suggesting that flavoprotein fluorescence can be used as an index of mitochondrial oxidation mediated by mitochondrial K(ATP) channels. Lidocaine (10(-3) to 10 mM) and mexiletine (10(-3) to 10 mM) reduced oxidation of the mitochondrial matrix in a dose-dependent manner with an EC50 of 98+/-63 microM for lidocaine and 107+/-89 microM for mexiletine.

Conclusions

Both lidocaine and mexiletine reduced flavoprotein fluorescence induced by diazoxide in rat ventricular myocytes, indicating that these antiarrhythmic drugs may produce impairment of mitochondrial oxidation mediated by mitochondrial K(ATP) channels.
Effect of Direct Fetal Opioid Analgesia on Fetal Hormonal and Hemodynamic Stress Response to Intrauterine Needling
Authors: Fisk Nicholas M. , Gitau Rachel , Teixeira Jeronima M. , Giannakoulopoulos Xenophon , Cameron Alan D. , Glover Vivette A.
Published: November 2003

Background

Whether the fetus can experience pain remains controversial. During the last half of pregnancy, the neuroanatomic connections for nociception are in place, and the human fetus mounts sizable stress responses to physical insults. Analgesia has been recommended for intrauterine procedures or late termination, but without evidence that it works. The authors investigated whether fentanyl ablates the fetal stress response to needling using the model of delayed interval sampling during intrahepatic vein blood sampling and transfusion in alloimmunized fetuses undergoing intravascular transfusion between 20 and 35 weeks.

Methods

Intravenous fentanyl (10 microg/kg estimated fetal weight x 1.25 placental correction) was given once at intrahepatic vein transfusion in 16 fetuses, and changes (posttransfusion - pretransfusion) in beta endorphin, cortisol, and middle cerebral artery pulsatility index were compared with intrahepatic vein transfusions without fentanyl and with control transfusions at the placental cord insertion.

Results

Fentanyl reduced the beta endorphin (mean difference in changes, -70.3 pg/ml; 95% confidence interval, -121 to -19.2; P = 0.02) and middle cerebral artery pulsatility index response (mean difference, 0.65; 95% confidence interval, 0.26-1.04; P = 0.03), but not the cortisol response (mean difference, -10.9 ng/ml, 95% confidence interval, -24.7 to 2.9; P = 0.11) in fetuses who had paired intrahepatic vein transfusions with and without fentanyl. Comparison with control fetuses transfused without fentanyl indicated that the beta endorphin and cerebral Doppler response to intrahepatic vein transfusion with fentanyl approached that of nonstressful placental cord transfusions.

Conclusions

The authors conclude that intravenous fentanyl attenuates the fetal stress response to intrahepatic vein needling.
Changes in Plasma Creatinine Concentration after Cardiac Anesthesia with Isoflurane, Propofol, or Sevoflurane
Authors: Story David A. , Poustie Stephanie , Liu Guoming , Larry McNicol P.
Published: November 2003

Background

Renal impairment often follows cardiac surgery. The authors investigated whether sevoflurane produces greater increases in plasma creatinine concentration than isoflurane or propofol after elective coronary artery surgery.

Methods

As part of maintenance anesthesia, including during cardiopulmonary bypass, patients were randomly allocated to receive one of three agents: isoflurane (n = 118), sevoflurane (n = 118), or propofol (n = 118). Fresh gas flows were 3 l/min. The preoperative plasma creatinine concentration was subtracted from the highest creatinine concentration in the first 3 postoperative days. A median maximum increase greater than 44 microM (0.5 mg/dl) was regarded as clinically important. Data were analyzed on an intention-to-treat basis. Subgroup analyses were performed on per-protocol patients and those with preoperative renal impairment (creatinine concentration > 130 microM [1.47 mg/dl] or urea > 7.7 mM [blood urea nitrogen, 21.6 mg/dl]).

Results

The differences between the groups were small, clinically unimportant, and not statistically significant for the primary analysis and subgroups. The proportions of patients with creatinine increases greater than 44 microM were 15% in the isoflurane group, 17% in the sevoflurane group, and 11% in the propofol group (P = 0.45). The median increases were 8 microM in the isoflurane group, 4 microM in the sevoflurane group, and 6 microM in the propofol group. The differences between the three median maximum increases were 1-4 microM (P > 0.45). In the subgroup with preoperative renal impairment, the median increases were 10 microM in the isoflurane group, 15 microM in the sevoflurane group, and 5 microM in the propofol group (P = 0.72).

Conclusions

Sevoflurane did not produce greater increases in creatinine than isoflurane or propofol after elective coronary artery surgery.
Changes in Blood Volume and Hematocrit during Acute Preoperative Volume Loading with 5% Albumin or 6% Hetastarch Solutions in Patients before Radical Hysterectomy
Authors: Rehm Markus , Haller Mathias , Orth Victoria , Kreimeier Uwe , Jacob Mathias , Dressel Holger , Mayer Sabine , Brechtelsbauer Heinz , Finsterer Udilo
Published: November 2003

Background

The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently.

Methods

Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion.

Results

More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume.

Conclusions

The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.
Effect of Epidural Analgesia with Ambulation on Labor Duration
Authors: Vallejo Manuel C. , Firestone Leonard L. , Mandell Gordon L. , Jaime Francisco , Makishima Sandra , Ramanathan Sivam
Published: November 2003

Background

Ambulatory epidural analgesia (AEA) is a popular choice for labor analgesia because ambulation reportedly increases maternal comfort, increases the intensity of uterine contractions, avoids inferior vena cava compression, facilitates fetal head descent, and relaxes the pelvic musculature, all of which can shorten labor. However, the preponderance of evidence suggests that ambulation during labor is not associated with these benefits. The purpose of this study is to determine whether ambulation with AEA decreases labor duration from the time of epidural insertion to complete cervical dilatation.

Methods

In this prospective, randomized study, 160 nulliparous women with AFA were randomly assigned to one of two groups: AEA with ambulation and AEA without ambulation. AEA blocks were initiated with 15-20 ml ropivacaine (0.07%) plus 100 microg fentanyl, followed by a continuous infusion of 0.07% ropivacaine plus 2 microg/ml fentanyl at 15-20 ml/h. Maternal measured variables included ambulation time, time from epidural insertion to complete dilatation, stage II duration, pain Visual Analogue Scale scores, and mode of delivery. APGAR scores were recorded at 1 and 5 min. Results are expressed as mean +/- SD or median and analyzed using the t test, chi-square, or the Mann-Whitney test at P < or = 0.05.

Results

The ambulatory group walked 25.0 +/- 23.3 min, sat upright 40.3 +/- 29.7 min, or both. Time from epidural insertion to complete dilatation was 240.9 +/- 146.1 min in the ambulatory group and 211.9 +/- 133.9 min in the nonambulatory group (P = 0.206).

Conclusion

Ambulatory epidural analgesia with walking or sitting does not shorten labor duration from the time of epidural insertion to complete cervical dilatation.
Relation between Quality of Recovery in Hospital and Quality of Life at 3 Months after Cardiac Surgery
Authors: Myles Paul S. , Hunt Jennifer O. , Fletcher Helen , Solly Robert , Woodward David , Kelly Susan
Published: November 2003

Background

Improved quality of life (QoL) is a desirable outcome of cardiac surgery. The aim of the current study was to measure the association between quality of recovery 3 days after surgery and QoL measured 3 months later.

Methods

After obtaining ethics committee approval and consent, 120 adult cardiac surgical patients were studied. A 40-item quality of recovery score (QoR-40) was used to measure postoperative health status on days 1-3 and 1 month after surgery. QoL was measured using the short-form health survey (SF-36) at 1 and 3 months after surgery. The effect size (delta mean/SD) was used to define responsiveness, a clinically important difference in health. Associations were measured using correlation and reliability coefficients.

Results

There was a significant change in the mean QoR-40 for up to 1 month after surgery (P < 0.0005). QoL was improved at 3 months (P < 0.0005) but not 1 month (P = 0.29) after surgery. There was a moderate correlation between day-3 QoR-40 and 3-month SF-36 (r = 0.39; P < 0.0005). A poor-quality recovery in hospital predicted a poor QoL at 3 months (adjusted odds ratio, 4.20; 95% confidence interval, 1.41-12.5; P = 0.01).

Conclusions

The QoR-40 is a valid measure of quality of recovery after surgery and anesthesia. When compared with the SF-36, it is a better measure of early postoperative recovery. A poor-quality recovery on the days after surgery can predict a poor QoL at 3 months after surgery. This may allow earlier and more effective support strategies while patients are still in the hospital (counseling, home assistance, local doctor notification, cardiac rehabilitation).
Acute and Nonacute Complications Associated with Interscalene Block and Shoulder Surgery
Authors: Borgeat Alain , Ekatodramis Georgios , Kalberer Fabian , Benz Cedric
Published: November 2003

Background

The incidence, etiology, and evolution of complications after interscalene brachial plexus block (ISB) are not well-known. The authors prospectively monitored 521 patients for complications during the first 9 months after ISB.

Methods

A total of 521 adults scheduled for elective shoulder surgery performed with an ISB were included in this prospective study. The ISB procedure was standardized for all patients Acute complications were recorded. Patients were observed daily (for 10 days) for paresthesias, dysesthesias, pain not related to surgery, and muscular weakness and were evaluated at 1, 3, 6, and 9 months after surgery. Persistence of paresthesias dysesthesias, pain not related to surgery, or muscular weakness was investigated at 1 or 3 months by means of electroneuromyography. Final evaluation was performed at 9 months.

Results

A total of 520 patients completed the study; one was excluded after surgical axillary nerve damage. Two hundred thirty-four patients had an interscalene catheter. Acute complications consisted of one pneumothorax (0.2%) and one episode of central nervous system toxicity (incoherent speech; 0.2%). A 10 days, 74 patients (14%) were symptomatic, and none had muscular weakness. At 1 month, 41 patients (7.9%) had symptoms, and none had muscular weakness. Thirty patients under went electroneuromyography; sulcus ulnaris syndrome (n = 8) carpal tunnel syndrome (n = 2), and complex regional pain syndrome (n = 1) were diagnosed. At 3 months 20 patient (3.9%) were symptomatic, and none had muscular weakness All underwent electroneuromyography; carpal tunnel syndrome (n = 2), complex regional pain syndrome (n = 4), plexus neuropathy (n = 1), and plexus damage (n = 1) were diagnosed. At 6 months, 5 patients (0.9%) were symptomatic. At 9 months 1 patient (0.2%) had persistence of dysesthesia.

Conclusions

Interscalene brachial plexus block performed with a standardized technical approach, material, and drugs is associated with an incidence of short- and severe long-term complications of 0.4%. In case of persistent paresthesia, dysesthesia, or pain not related to surgery after ISB, sulcus ulnaris syndrome, carpal tunnel syndrome, or complex regional pain syndrome should be excluded since specific treatment may be required.
Effect of Synchronized Intermittent Mandatory Ventilation on Respiratory Workload in Infants after Cardiac Surgery
Authors: Imanaka Hideaki , Nishimura Masaji , Miyano Hiroshi , Uemura Hideki , Yagihara Toshikatsu
Published: November 2003

Background

Synchronized intermittent mandatory ventilation (SIMV) is commonly used in infants and adults. However, few investigations have examined how SIMV reduces respiratory workload in infants. The authors evaluated how infants' changing respiratory patterns when reducing SIMV rate increased respiratory load. The authors also investigated whether SIMV reduces infant respiratory workload in proportion to the rate of mandatory breaths and which rate of SIMV provides respiratory workloads similar to those after tracheal extubation.

Methods

When 11 post-cardiac surgery infants aged 2-11 months were to be weaned with SIMV, the authors randomly applied five levels of mandatory breathing: 0, 5, 10, 15, and 20 breaths/min. All patients underwent ventilation with SIMV mode: pressure control ventilation, 16 cm H2O; inspiratory time, 0.8 s; triggering sensitivity, 0.6 l/min; and positive endexpiratory pressure, 3 cm H2O. After establishing steady-state conditions at each SIMV rate, arterial blood gases were analyzed, and esophageal pressure, airway pressure, and airflow were measured. Inspiratory work of breathing, pressure-time products, and the negative deflection of esophageal pressure were calculated separately for assisted breaths, for spontaneous breaths, and for total breaths per minute. Measurements were repeated after extubation.

Results

As the SIMV rate decreased, although minute ventilation and arterial carbon dioxide tension were maintained at constant values, spontaneous breathing rate and tidal volume increased. Work of breathing, pressure-time products, and negative deflection of esophageal pressure increased as the SIMV rate decreased. Work of breathing and pressure-time products after extubation were intermediate between those at a SIMV rate of 5 breaths/min and those at 0 breaths/min.

Conclusion

When the load to breathing was increased progressively by decreasing the SIMV rate in post-cardiac surgery infants, tidal volume and spontaneous respiratory rate both increased. In addition, work of breathing and pressure-time products were increased depending on the SIMV rate.
Effects of Rapacuronium on Respiratory Function during General Anesthesia
Authors: Tobias Joseph D. , Johnson Joel O. , Sprague Kelly , Johnson Garry
Published: November 2003

Background

With its introduction for widespread clinical use, there has been an increase in reports of bronchospasm related to the administration of rapacuronium. As it is commonly used for rapid sequence intubation, it has been suggested that these effects may be related to an inadequate depth of anesthesia. The current study examines the airway effects of rapacuronium in tracheally intubated, anesthetized adults.

Methods

Endotracheal intubation was accomplished without the use of neuromuscular blocking agents. Dynamic compliance, tidal volume, peak inspiratory flow rate, peak expiratory flow rate, and peak inflating pressure were measured after administration of either rapacuronium (1.5 mg/kg) or cis-atracurium (0.2 mg/kg) to 20 adult patients (10 received rapacuronium and 10 received cis-atracurium) anesthetized with propofol-remifentanil.

Results

Statistically significant increases in peak inflating pressure (22 +/- 6 to 28 +/- 9 cm H2O, P = 0.0012) and decreases in dynamic compliance (108 +/- 43 to 77 +/- 41 ml/cm H2O, P = 0.0001), peak inspiratory flow rate (0.43 +/- 0.11 to 0.39 +/- 0.09 l/s, P = 0.0062), peak expiratory flow rate (0.67 +/- 0.10 to 0.59 +/- 0.09 l/s, P = 0.0015), and tidal volume (744 +/- 152 to 647 +/- 135 ml, P = 0.0293) occurred after administration of rapacuronium. No changes were seen after administration of cis-atracurium.

Conclusion

These data demonstrate that rapacuronium, but not cis-atracurium, has significant airway effects in intubated, mechanically ventilated adults.
Nitrogen at Raised Pressure Interacts with the GABAAReceptor to Produce Its Narcotic Pharmacological Effect in the Rat
Authors: David Hélène N. , Balon Norbert , Rostain Jean-Claude , Abraini Jacques H.
Published: November 2003

Background

Strong evidence supports the concept that conventional anesthetics, including inhalational agents and inert gases, such as xenon and nitrous oxide, interact directly with ion channel neurotransmitter receptors. However, there is no evidence that nitrogen, which only exhibits narcotic potency at increased pressure, may act by a similar mechanism.

Methods

We compared the inhibitory and sedative effects of gamma-aminobutyric acid (GABA) and nitrogen pressure on locomotor activity and striatal dopamine release in freely moving rats and investigated the pharmacologic properties of the GABA-induced and nitrogen pressure-induced narcotic action using the highly selective competitive GABA(A) receptor antagonist bicuculine.

Results

Intracerebroventricular GABA infusion up to 60 micromol or exposure to nitrogen pressure up to 3 MPa decreased to a similar extent striatal dopamine release (r2= 0.899, df = 4, P < 0.01) and locomotor activity (r2 = 0.996, df = 28, P < 0.001). However, both agents only showed small effects on striatal dopamine release, reducing dopamine currents by only 12-13% at sedative concentrations. Pretreatment with bicuculline at 0.5, 1, and 2.5 pmol reduced the sedative action of GABA on locomotor activity by 10, 20, and 41%, respectively. Bicuculline in the nanomole range at 1, 2.5, and 5 nmol but not in the picomole range reduced the sedative action of nitrogen pressure by 5, 37, and 73%, respectively. Schild plot analysis is consistent with the fact that bicuculline is a competitive antagonist of both GABA and nitrogen at pressure.

Conclusions

These results suggest (1) that the presynaptic effects of both GABA and nitrogen pressure on striatal dopamine transmission are modest and not mainly involved in their sedative action and (2) that nitrogen at increased pressure may interact directly with the GABA(A) receptor. However, because the antagonistic effect of bicuculline on nitrogen sedation only occurred at much higher bicuculline concentrations than seen with GABA, it is suggested that nitrogen does not compete for the same site as GABA.
Cerebral Blood Volume (CBV) in Humans during Normo- and Hypocapnia
Authors: Reinstrup Peter , Ryding Erik , Ohlsson Tomas , Dahm Peter Lee , Uski Tore
Published: November 2003

Background

It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia.

Methods

Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning.

Results

Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects.

Conclusions

Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.
Relation of the Static Compliance Curve and Positive End-expiratory Pressure to Oxygenation during One-lung Ventilation
Authors: Slinger Peter D. , Kruger Marelise , McRae Karen , Winton Timothy
Published: November 2003

Background

Positive end-expiratory pressure (PEEP) is commonly applied to the ventilated lung to try to improve oxygenation during one-lung ventilation but is an unreliable therapy and occasionally causes arterial oxygen partial pressure (PaO(2)) to decrease further. The current study examined whether the effects of PEEP on oxygenation depend on the static compliance curve of the lung to which it is applied.

Methods

Forty-two adults undergoing thoracic surgery were studied during stable, open-chest, one-lung ventilation. Arterial blood gases were measured during two-lung ventilation and one-lung ventilation before, during, and after the application of 5 cm H(2)O PEEP to the ventilated lung. The plateau end-expiratory pressure and static compliance curve of the ventilated lung were measured with and without applied PEEP, and the lower inflection point was determined from the compliance curve.

Results

Mean (+/- SD) PaO(2) values, with a fraction of inspired oxygen of 1.0, were not different during one-lung ventilation before (192 +/- 91 mmHg), during (190 +/- 90), or after ( 205 +/- 79) the addition of 5 cm H(2)O PEEP. The mean plateau end-expiratory pressure increased from 4.2 to 6.8 cm H(2)O with the application of 5 cm H(2)O PEEP and decreased to 4.5 cm H(2)O when 5 cm H(2)O PEEP was removed. Six patients showed a clinically useful (> 20%) increase in PaO(2) with 5 cm H(2)O PEEP, and nine patients had a greater than 20% decrease in PaO(2). The change in PaO(2) with the application of 5 cm H(2)O PEEP correlated in an inverse fashion with the change in the gradient between the end-expiratory pressure and the pressure at the lower inflection point (r = 0.76). The subgroup of patients with a PaO(2) during two-lung ventilation that was less than the mean (365 mmHg) and an end-expiratory pressure during one-lung ventilation without applied PEEP less than the mean were more likely to have an increase in PaO(2) when 5 cm H(2)O PEEP was applied.

Conclusions

The effects of the application of external 5 cm H(2)O PEEP on oxygenation during one-lung ventilation correspond to individual changes in the relation between the plateau end-expiratory pressure and the inflection point of the static compliance curve. When the application of PEEP causes the end-expiratory pressure to increase from a low level toward the inflection point, oxygenation is likely to improve. Conversely, if the addition of PEEP causes an increased inflation of the ventilated lung that raises the equilibrium end-expiratory pressure beyond the inflection point, oxygenation is likely to deteriorate.