bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of Halogenated Anesthetics with Dobutamine in Rat Myocardium
Authors: Gueugniaud Pierre-Yves , Hanouz Jean-Luc , Martino Jean-Marc , Lecarpentier Yves , Coriat Pierre , Riou Bruno 
Published: November 2003

Background
Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations, but their interactions with dobutamine remain unknown.

Methods
The effects of halothane, isoflurane, sevoflurane, and desflurane (1 and 2 minimum alveolar concentration) on the inotropic responses induced by dobutamine (10(-8)-10(-4) M) were studied in rat left ventricular papillary muscles in vitro. Inotropic effects were studied under low (isotony) and high (isometry) loads. The authors also studied the lusitropic effects in isotonic (R1) and isometric (R2) conditions. Data are the mean percentage of baseline +/- SD.

Results
Dobutamine induced a positive inotropic effect (active isometric force: 185+/-36%, P < 0.001) and a positive lusitropic effect under low load (R1: 78+/-9%, P < 0.001), but not under high load (R2: 95+/-21%, not significant). Halothane, isoflurane, and sevoflurane did not modify the positive inotropic effect of dobutamine. Even in the presence of alpha-adrenoceptor blockade, isoflurane did not potentiate the positive inotropic effect of dobutamine. Desflurane significantly enhanced the positive inotropic effect of dobutamine (active isometric force: 239+/-35%, P < 0.001), but this potentiation was abolished by pretreatment with reserpine. In contrast to halothane, isoflurane, sevoflurane, and desflurane did not significantly modify the lusitropic effects of dobutamine.

Conclusions
Halogenated anesthetics, except desflurane, did not modify the positive inotropic effects of dobutamine. Desflurane enhanced the positive inotropic effect of dobutamine, but this effect was related to the desflurane-induced release in intramyocardial catecholamine stores.
Effects of Halothane and Isoflurane on Fast and Slow Inactivation of Human Heart hH1a Sodium Channels
Authors: Stadnicka Anna , Kwok Wai-Meng , Hartmann Hali A. , Bosnjak Zeljko J. 
Published: November 2003

Background
Cloning and heterologous expression of ion channels allow biophysical and molecular studies of the mechanisms of volatile anesthetic interactions with human heart sodium channels. Volatile anesthetics may influence the development of arrhythmias arising from cardiac sodium channel dysfunction. For that reason, understanding the mechanisms of interactions between these anesthetics and cardiac sodium channels is important. This study evaluated the mechanisms of volatile anesthetic actions on the cloned human cardiac sodium channel (hH1a) alpha subunit.

Methods
Inward sodium currents were recorded from human embryonic kidney (HEK293) cells stably expressing hH1a channels. The effects of halothane and isoflurane on current and channel properties were evaluated using the whole cell voltage-clamp technique.

Results
Halothane at 0.47 and 1.1 mM and isoflurane at 0.54 and 1.13 mM suppressed the sodium current in a dose- and voltage-dependent manner. Steady state activation was not affected, but current decay was accelerated. The voltage dependence of steady state fast and slow inactivations was shifted toward more hyperpolarized potentials. The slope factor of slow but not fast inactivation curves was reduced significantly. Halothane increased the time constant of recovery from fast inactivation. The recovery from slow inactivation was not affected significantly by either anesthetic.

Conclusions
In a heterologous expression system, halothane and isoflurane interact with the hH1a channels and suppress the sodium current. The mechanisms involve acceleration of the transition from the open to the inactivated state, stabilization of the fast and slow inactivated states, and prolongation of the inactivated state by delayed recovery from the fast inactivated to the resting state.
4-Chloro-m-cresol is a Trigger of Malignant Hyperthermia in Susceptible Swine
Authors: Wappler Frank , Scholz Jens , Fiege Marko , Kolodzie Kerstin , Kudlik Christiana , Weibhorn Ralf , Schulte am Esch Jochen 
Published: November 2003

Background
4-Chloro-m-cresol (4-CmC) induces marked contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MHS). In contrast, 4-CmC induces only small contractures in specimens from normal (MHN) patients. 4-CmC is a preservative within a large number of commercially available drug-preparations (e.g., insulin, heparin, succinylcholine), and it has been suggested that 4-CmC might trigger malignant hyperthermia. This study was designed to investigate the effects of 4-CmC in vivo and in vitro in the same animals.

Methods
After approval of the animal care committee, six Pietrain MHS and six control (MHN) swine were anesthetized with azaperone 4 mg/kg intramuscularly and metomidate 10 mg/kg intraperitoneally. After endotracheal intubation, lungs were mechanically ventilated (inspired oxygen fraction 0.3) and anesthesia was maintained with etomidate 2.5 mg x kg(-1) x h(-1) and fentanyl 50 microg x kg(-1) x h(-1). Animals were surgically prepared with arterial and central venous catheters for measurement of hemodynamic parameters and to obtain blood samples. Before exposure to 4-CmC in vivo, muscle specimens were excised for in vitro contracture tests with 4-CmC in concentrations of 75 and 200 microM. Subsequently, pigs were exposed to cumulative administration of 3, 6, 12, 24, and 48 mg/kg 4-CmC intravenously. If an unequivocal episode of malignant hyperthermia occurred, as indicated by venous carbon dioxide concentration > or = 70 mmHg, pH < or = 7.25, and an increase of temperature > or = 2 degrees C, the animals were treated with dantrolene, 3.5 mg/kg.

Results
All MHS swine developed malignant hyperthermia after administration of 4-CmC in doses of 12 or 24 mg/kg. Venous carbon dioxide concentration significantly increased and pH significantly decreased. Temperature increased in all MHS animals more than 2 degrees C. Blood lactate concentrations and creatine kinase levels were significantly elevated. All MHS swine were treated successfully with dantrolene. In contrast, no MHN swine developed signs of malignant hyperthermia. After receiving 4-CmC in a concentration of 48 mg/kg, however, all MHN animals died by ventricular fibrillation. The in vitro experiments showed that both concentrations of 4-CmC produced significantly greater contractures in MHS than in MHN specimens.

Conclusions
4-CmC is in vivo a trigger of malignant hyperthermia in swine. However, the 4-CmC doses required for induction of malignant hyperthermia were between 12 and 24 mg/kg, which is about 150-fold higher than the 4-CmC concentrations within clinically used preparations.
Is Outpatient Laparoscopic Cholecystectomy Safe and Cost-effective?
Authors: Fleisher Lee A. , Yee Kelvin , Lillemoe Keith D , Talamini Mark A. , Yeo Charles J. , Heath Roberta , Bass Eric , Snyder Douglas S. , Parker Stephen D. 
Published: November 2003

Background
There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting.

Methods
Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed.

Results
Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient.

Conclusions
The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.
Effects of Perioperative Analgesic Technique on the Surgical Outcome and Duration of Rehabilitation after Major Knee Surgery
Authors: Capdevila Xavier , Barthelet Yves , Biboulet Philippe , Ryckwaert Yves , Rubenovitch Josh , d'Athis Francoise 
Published: November 2003

Background
Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.

Methods
Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 microg/ml clonidine administered at 0.1 ml x kg(-1) x h(-1). Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria

Results
The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 degrees (60-100 degrees)(median and 25th-75th percentiles) in the continuous epidural infusion group, 90 degrees (60-100 degrees) in the continuous femoral block group, and 80 degrees (60-100 degrees) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.

Conclusion
Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence.
Ultrasound-guided Internal Jugular Venous Cannulation in Infants
Authors: Verghese Susan T. , McGill Willis A. , Patel Ramesh I. , Sell Jeffrey E. , Midgley Frank M. , Ruttimann Urs E. 
Published: November 2003

Background
Percutaneous cannulation of the internal jugular vein in infants is technically more difficult and carries a higher risk of carotid artery puncture than in older children and adults. In this prospective study, the authors tested their hypothesis that using an ultrasound scanner would increase the success of internal jugular cannulation and decrease the incidence of carotid artery puncture in infants.

Methods
After approval from the institutional review board and receipt of written informed parental consent, 95 infants scheduled for cardiac surgery were randomized prospectively into two groups. In the landmarks group, the patients' internal jugular veins were cannulated using the traditional method of palpation of carotid pulsation and identification of other anatomic landmarks. In the ultrasound group, cannulation was guided using an ultrasound scanner image. The cannulation time, number of attempts, success rate, and incidence of complications were compared for the two groups.

Results
There were no significant differences between the two groups with regard to weight, age, and American Society of Anesthesiologists physical status classification. The success rate was 100% in the ultrasound group, with no carotid artery punctures, and 77% in the landmarks group, with a 25% incidence of carotid artery punctures. Both differences were significant (P > 0.0004). The cannulation time was less, the number of attempts was fewer, and the failure rate was significantly lower in the ultrasound group than in the landmark group.

Conclusion
Ultrasonographic localization of the internal jugular vein was superior to the landmarks technique in terms of overall success, speed, and decreased incidence of carotid artery puncture.
Bupivacaine Augments Intrathecal Fentanyl for Labor Analgesia
Authors: Palmer Craig M. , Van Maren Gretchen , Nogami Wallace M. , Alves Diane 
Published: November 2003

Background
fentanyl has been shown to be an effective analgesic for labor; this study investigated the analgesic effect of low-dose bpivacaine added to intrathecal fentanyl for labor analgesia

Methods
Ninety parturients in active labor who requested regional analgesia were randomized to receive an intrathecal injection of either fentanyl, 25 microg; bupivacaine, 1.25 mg, with fentanyl, 25 microg; or bupivacaine, 2.5 mg, with fentanyl, 25 microg, as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection until the patient requested further analgesia. Maternal blood pressure and fetal heart rate were recorded before and at intervals after injection. Lower-extremity muscle strength was tested before and 30 min after injection; anesthetic level to cold sensation and the presence and severity of pruritus were recorded.

Results
Duration of analgesia was longer in the group receiving bupivacaine, 2.5 mg, and fentanyl, 25 microg, than the group receiving plain fentanyl (108 vs. 92 min; P < 0.05). Onset of analgesia was faster in both groups receiving bupivacaine compared with plain fentanyl (P < 0.05). No differences in muscle strength after injection were found in any group, although anesthetic levels to cold were documented in all patients in the bupivacaine groups, and 21 of 30 in the plain fentanyl group. Baseline fetal heart rates did not change after injection in any group, and maternal blood pressure was unchanged.

Conclusions
The addition of 2.5 mg isobaric bupivacaine to 25 microg fentanyl for intrathecal labor analgesia modestly increases duration and speeds onset of analgesia compared with plain intrathecal fentanyl.
Can Postoperative Nausea and Vomiting Be Predicted?
Authors: Sinclair David R. , Chung Frances , Mezei Gabor 
Published: November 2003

Background
Iletrospective studies fail to identify predictors of postoperative nausea and vomiting (PONV). The authors prospectively studied 17,638 consecutive outpatients who had surgery to identify predictors.

Methods
Data on medical conditions, anesthesia, surgery, and PONV were collected in the post-anesthesia care unit, in the ambulatory surgical unit, and in telephone interviews conducted 24 h after surgery. Multiple logistic regression with backward stepwise elimination was used to develop a predictive model An independent set of patients was used to validate the model

Results
Age (younger or older), sex (female or male), smoking status (nonsmokers or smokers), previous PONV, type of anesthesia (general or other), duration of anesthesia (longer or shorter), and type of surgery (plastic, orthopedic shoulder, or other) were independent predictors of PONV. A 10-yr increase in age decreased the likelihood of PONV by 13%. The risk for men was one third that for women. A 30-min increase in the duration of anesthesia increased the likelihood of PONV by 59%. General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia. Patients with plastic and orthopedic shoulder surgery had a sixfold increase in the risk for PONV. The model predicted PONV accurately and yielded an area under the receiver operating characteristic curve of 0.785+/-0.011 using an independent validation set.

Conclusions
A validated mathematical model is provided to calculate the risk of PONV in outpatients having surgery. Knowing the factors that predict PONV will help anesthesiologists determine which patients will need antiemetic therapy.
Sevoflurane Increases Lumbar Cerebrospinal Fluid Pressure in Normocapnic Patients Undergoing Transsphenoidal Hypophysectomy
Authors: Talke Pekka , Caldwell James E. , Richardson Charles A. 
Published: November 2003

Background
The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations.

Results
Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group.

Conclusions
Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.
Rapid Tracheal Intubation with Rocuronium
Authors: Kirkegaard-Nielsen Hans , Caldwell James E. , Berry Peter D. 
Published: November 2003

Background
Rapid tracheal intubation with rocuronium has not been studied using a probability-based approach. The authors aimed to predict doses of rocuronium giving 90% and 95% probability of in intubation within 60 s and to estimate their durations of action.

Methods
After premedication with midazolam, 2 mg, anesthesia was induced in 80 subjects with fentanyl, 2 microg/kg, followed 3 min later by propofol, 2 mg/kg. Patients received randomly rocuronium, 0.0, 0.4, 0.8, or 1.2 mg/kg (n = 20/ dose). Laryngoscopy began 40 s later, aiming for intubation at 60 s, and conditions were graded perfect, acceptable, or unacceptable, with the first two conditions being successful intubation. Anesthesia was maintained with isoflurane 0.5-1.0% (end-tidal) and fentanyL Duration of action was time until reappearance of the first tactile train-of-four response. The dose versus fraction of patients with successful intubation was analyzed by logistic regression. Doses giving 90% and 95% (D90 and D95) probability of successful intubation were calculated.

Results
intubation was successful in 7, 11, 18, and 19 patients in the 0.0, 0.4, 0.8, and 1.2 mg/kg groups, respectively. The D90 and D95 doses (95% confidence limits in parentheses) were 0.83 (0.59-1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D90 and D95 doses was 32 and 46 min, respectively.

Conclusions
After induction with fentanyl and propofol, rocuronium, 1.04 mg/kg gives 95% probability of successful intubation at 60 s.
Pharmacokinetic-Pharmacodynamic Modeling of the Respiratory Depressant Effect of Alfentanil
Authors: Bouillon Thomas , Schmidt Christina , Garstka Gudrun , Heimbach Dirk , Stafforst Dieter , Schwilden Helmut , Hoeft Andreas 
Published: November 2003

Background
Although respiratory depression is the most well-known and dangerous side effect of opioids, no pharmacokinetic-pharmacodynamic model exists for its quantitative analysis. The development of such a model was the aim of this study.

Methods
After institutional approval approval and informed consent were obtained, 14 men (American Society of Anesthesiologists physical status I or II; median age, 42 yr [range, 20-71 yr]; median weight, 82.5 kg [range, 68-108 kg]) were studied before they underwent major urologic surgery. An intravenous infusion of alfentanil (2.3 microg x kg(-1) x min(-1)) was started while the patients were breathing oxygen-enriched air (fraction of inspired oxygen [FIO2 = 0.5) over a tightly fitting continuous positive airway pressure mask. The infusion was discontinued when a cumulative dose of 70 microg/kg had been administered, the end-expiratory partial pressure of carbon dioxide (PE(CO2) exceeded 65 mmHg, or apneic periods lasting more than 60 s occurred During and after the infusion, frequent arterial blood samples were drawn and analyzed for the concentration of alfentanil and the arterial carbon dioxide pressure (PaCO2). A mamillary two-compartment model was fitted to the pharmacokinetic data. The PaCO2 data were described by an indirect response model The model accounted for the respiratory stimulation resulting from increasing PaCO2. The model parameters were estimated using NONMEM. Simulations were performed to define the respiratory response at steady state to different alfentanil concentrations.

Results
The indirect response model adequately described the time course of the PaCO2. The following pharmacodynamic parameters were estimated (population means and interindividual variability): EC50, 60.3 microg/l (32%); the elimination rate constant of carbon dioxide (Kel), 0.088 min(-1) (44%); and the gain in the carbon dioxide response, 4(28%) (fixed according to literature values). Simulations revealed the pronounced role of PaCO2 in maintaining alveolar ventilation in the presence of opioid.

Conclusions
The model described the data for the entire opioid-PaCo2 response surface examined. Indirect response models appear to be a promising tool for the quantitative evaluation of drug-induced respiratory depression.