bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous Anesthetics Attenuate Phenylephrine-induced Calcium Oscillations in Individual Pulmonary Artery Smooth Muscle Cells
Authors: Hamada Hiroshi , Damron Derek S. , Murray Paul A. 
Published: November 2003

Background
The authors investigated the effects of intravenous anesthetics on alpha-adrenergic-induced oscillations in intracellular free calcium concentration ([Ca2+]i) in individual pulmonary artery smooth muscle cells (PASMCs).

Methods
PASMCs were cultured from explants of canine intrapulmonary artery. Fura-2-loaded PASMCs were continuously superfused with phenylephrine (10 microM) at 37 degrees C on the stage of an inverted fluorescence microscope. Measurement of [Ca2+]i was via a dual wavelength spectrofluorometer. Intravenous anesthetics were added to the superfusate to assess their effects on the phenylephrine-induced [Ca2+]i oscillations.

Results
Resting [Ca2+]i was 103 +/- 6 nM. Phenylephrine stimulated [Ca2+]i oscillations, reaching a peak concentration of 632 +/- 20 nM and a frequency of 1.53 +/- 0.14 transients/min. The effects of phenylephrine were dose-dependent. The effects of intravenous anesthetics on phenylephrine-induced [Ca2+]i oscillations were dose-dependent. Ketamine (100 microM) reduced the amplitude (221 +/- 22 nM) but not the frequency (1.48 +/- 0.11/min) of the oscillations, whereas thiopental (100 microM) decreased the amplitude (270 +/- 20 nM) and the frequency (1.04 +/- 0.10/min). Propofol (100 microM) and the Intralipid vehicle inhibited the amplitude (274 +/- 11 nM) but not the frequency (1.39 +/- 0.11/min) of the oscillations. The effects of ketamine and thiopental, but not propofol, were evident at clinically relevant concentrations.

Conclusion
Ketamine, thiopental, and propofol exerted differential effects to inhibit the amplitude or the frequency of phenylephrine-induced [Ca2+]i oscillations in individual PASMCs. Thus, intravenous anesthetics may alter the pulmonary vascular response to alpha-adrenoreceptor activation by directly inhibiting [Ca2+]i signaling in PASMCs.
The Effect of Thiopental and Propofol on NMDA- and AMPA-mediated Glutamate Excitotoxicity
Authors: Zhu Hechen , Cottrell James E. , Kass Ira S. 
Published: November 2003

Background
Glutamate excitotoxicity has been implicated as an important cause of ischemic, anoxic, epileptic, and traumatic neuronal damage. Glutamate receptor antagonists have been shown to reduce anoxic, ischemic, and epileptic damage. The effects of thiopental and propofol on N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA)-induced neuronal damage were investigated in this study.

Methods
The Schaffer collateral pathway was stimulated, and a postsynaptic-evoked population spike was recorded from the CA1 pyramidal cell layer of rat hippocampal slices. The recovery of the population spike amplitude was an indicator of neuronal viability. The duration of NMDA (25 microM) or AMPA (15 or 10 microM) treatment was 10 min. Thiopental (600 microM), propofol (112 microM), or the vehicle was present 15 min before, during, and 10 min after the NMDA or AMPA treatment.

Results
Thiopental prolonged the time required to completely block the population spike after the addition of NMDA or AMPA. Thiopental improved the recovery of the population spike after 25 microM NMDA (79% vs. 44%) and 15 microM AMPA (50% vs. 15%). Propofol worsened the recovery of the population spike from NMDA-induced damage. The recovery was 8% with propofol compared with 40% with NMDA alone. Propofol did not significantly alter the AMPA-induced neuronal damage.

Conclusions
Thiopental attenuates NMDA- and AMPA-mediated glutamate excitotoxicity. This may be one way barbiturates reduce anoxic, ischemic, and epileptic damage. Propofol enhances NMDA-induced neuronal damage. These results demonstrate that thiopental and propofol have different properties with respect to glutamate excitotoxicity.
Isoflurane and Halothane Do Not Alter the Enhanced Afterload Sensitivity of Left Ventricular Relaxation in Dogs with Pacing-induced Cardiomyopathy
Authors: Pagel Paul S. , Hettrick Douglas A. , Kersten Judy R. , Tessmer John P. , Lowe Dermot , Warltier David C. 
Published: November 2003

Background
The afterload dependence of left ventricular (LV) relaxation is accentuated in the failing heart. The authors tested the hypothesis that isoflurane and halothane alter the afterload sensitivity of LV relaxation in dogs with pacing-induced cardiomyopathy.

Methods
Dogs (n = 6) were chronically instrumented for measurement of LV and aortic pressures and subendocardial segment length. Hemodynamics were recorded, and LV relaxation was evaluated with a time constant of isovolumic relaxation (tau) under control conditions and during decreases and increases in LV load produced by abrupt inferior vena caval (IVC) occlusion and phenylephrine (intravenous infusion), respectively, in the conscious state and during isoflurane and halothane anesthesia (1.5 MAC) on separate days before and after the development of pacing-induced cardiomyopathy. The slope (R) of the tau versus LV end-systolic pressure (P[es]) relation was also used to determine the afterload sensitivity of LV relaxation.

Results
IVC occlusion and phenylephrine produced similar or less profound changes in P(es), regional end-systolic force (an index of LV afterload), and end-systolic segment length in cardiomyopathic compared with healthy dogs. However, IVC occlusion and phenylephrine caused more pronounced alterations in tau in conscious and isoflurane- and halothane-anesthetized dogs after the development of cardiomyopathy. R was also greater in cardiomyopathic compared with healthy dogs (e.g., 0.32 +/- 0.03 before pacing to 1.00 +/- 0.13 ms/mmHg in conscious dogs). No differences in the load dependence of LV relaxation were observed between the conscious and anesthetized states before and after production of LV dysfunction.

Conclusions
The results indicate that isoflurane and halothane do not alter the afterload dependence of LV relaxation in the normal and cardiomyopathic heart. The lack of effect of the volatile anesthetics is probably related to anesthetic-induced reductions in the resistance to LV ejection concomitant with simultaneous negative inotropic effects.
Difficult or Impossible Ventilation after Sufentanil-induced Anesthesia Is Caused Primarily by Vocal Cord Closure
Authors: Bennett Joel A. , Abrams Jonathan T. , Van Riper Daniel F. , Horrow Jan C. 
Published: November 2003

Introduction
Opioid-induced rigidity often makes bag-mask ventilation difficult or impossible during induction of anesthesia. Difficult ventilation may result from chest wall rigidity, upper airway closure, or both. This study further defines the contribution of vocal cord closure to this phenomenon.

Methods
With institutional review board approval, 30 patients undergoing elective cardiac surgery participated in the study. Morphine (0.1 mg/kg) and scopolamine (6 microg/kg) given intramuscularly provided sedation along with intravenous midazolam as needed. Lidocaine 10% spray provided topical anesthesia of the oropharynx. A fiberoptic bronchoscope positioned in the airway photographed the glottis before induction of anesthesia A second photograph was obtained after induction with 3 microg/kg sufentanil administered during a period of 2 min. A mechanical ventilator provided 10 ml/kg breaths at 10/min via mask and oral airway with jaw thrust. A side-stream spirometer captured objective pulmonary compliance data. Subjective airway compliance was scored. Pancuronium (0.1 mg/kg) provided muscle relaxation. One minute after the muscle relaxant was given, a third photograph was taken and compliance measurements and scores were repeated. Photographs were scored in a random, blinded manner by one investigator. Wilcoxon signed rank tests compared groups, with Bonferroni correction. Differences were considered significant at P < 0.05.

Results
Twenty-eight of 30 patients exhibited decreased pulmonary compliance and closed vocal cords after opioid induction. Two patients with neither objective nor subjective changes in pulmonary compliance had open vocal cords after opioid administration. Both subjective and objective compliances increased from severely compromised values after narcotic-induced anesthesia to normal values (P = 0.000002) after patients received a relaxant. Photo scores document open cords before induction, progressing to closed cords after the opioid (P = 0.00002), and opening again after a relaxant was administered (P = 0.00005).

Conclusion
Closure of vocal cords is the major cause of difficult ventilation after opioid-induced anesthesia.
Efficacy of Intraoperative Cooling Methods
Authors: Plattner Olga , Kurz Andrea , Sessler Daniel I. , Ikeda Takehiko , Christensen Richard , Marder Danielle , Clough David 
Published: November 2003

Background
Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods.

Methods
Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 degrees C, full-length mattress and cover), 2) forced air (10 degrees C, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 degrees C. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression.

Results
The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss approximately 10 W and decreased core temperature 0.8 +/- 0.3 degrees C/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, approximately 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 degrees C/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 degrees C/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss approximately 600-800 W and decreased core temperature 9.7 +/- 4.4 degrees C/h (r2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of approximately 2 degrees C.

Conclusions
Bladder lavage provided only trivial cooling and gastric lavage provoked complications. Forced-air and circulating-water cooling transferred relatively little heat but are noninvasive and easy to implement. Forced-air or circulating-water cooling, perhaps combined with intravenous administration of refrigerated fluids, may be sufficient in some patients. When noninvasive methods prove insufficient for rapid cooling, ice-water immersion or peritoneal lavage probably should be the next lines of defense.
Bioavailability of Intramuscular Rocuronium in Infants and Children
Authors: Reynolds Lynne M. , Lau Marie , Luks Andrew , Sharma Manohar , Fisher Dennis M. 
Published: November 2003

Background
Intramuscular rocuronium, in doses of 1,000 microg/kg in infants and 1,800 microg/kg in children, produces complete twitch depression in 5-6 min. To determine the rate and extent of absorption of rocuronium after intramuscular administration, blood was sampled at various intervals after rocuronium administration by both intramuscular and intravenous routes to determine plasma concentrations (Cp) of rocuronium.

Methods
Twenty-nine pediatric patients ages 3 months to 5 yr were anesthetized with N2O and halothane. The trachea was intubated, ventilation was controlled, and adductor pollicis twitch tension was measured. When anesthetic conditions were stable, rocuronium (1,000 microg/kg for infants and 1,800 microg/kg for children) was injected either intramuscularly (in the deltoid muscle) or intravenously. Four venous plasma samples were obtained from each child 2-240 min after rocuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak Cp with intramuscular administration.

Results
With intramuscular administration, rocuronium's bioavailability averaged 82.6% and its absorption rate constant was 0.105 min(-1). Simulation indicated that Cp peaked 13 min after rocuronium was given intramuscularly, and that 30 min after intramuscular administration, less than 4% of the administered dose remained to be absorbed from the intramuscular depot.

Conclusions
After rocuronium is administered into the deltoid muscle, plasma concentrations peak at 13 min, and approximately 80% of the administered drug is absorbed systemically.
Region-specific and Agent-specific Dilation of Intracerebral Microvessels by Volatile Anesthetics in Rat Brain Slices
Authors: Farber Neil E. , Harkin Christopher P. , Niedfeldt Jennifer , Hudetz Antal G. , Kampine John P. , Schmeling William T. 
Published: November 2003

Background
Volatile anesthetics are potent cerebral vasodilators. Although the predominant site of cerebrovascular resistance is attributed to intracerebral arterioles, no studies have compared the actions of volatile anesthetics on intraparenchymal microvessels. The authors compared the effects of halothane and isoflurane on intracerebral arteriolar responsiveness in hippocampal and neocortical microvessels using a brain slice preparation.

Method
After Institutional Review Board approval, hippocampal or neocortical brain slices were prepared from anesthetized Sprague-Dawley rats and placed in a perfusion-recording chamber, superfused with artificial cerebrospinal fluid. Arteriolar diameters were monitored with videomicroscopy before, during, and after halothane or isoflurane were equilibrated in the perfusate. PGF2alpha preconstricted vessels before anesthetic administration. A blinded observer using a computerized videomicrometer analyzed diameter changes.

Results
Baseline microvessel diameter and the degree of preconstriction were not different between groups. In the hippocampus, the volatile agents produced similar, concentration-dependent dilation (expressed as percent of preconstricted control +/- SEM) of 68 +/- 6% and 79 +/- 9% (1 MAC) and 120 +/- 3% and 109 +/- 5% (2 MAC) (P < 0.05) during halothane and isoflurane, respectively. In the cerebral cortex, isoflurane caused significantly less vasodilation than did similar MAC levels of halothane (84 +/- 9% vs. 42 +/- 5% dilation at 1 MAC; 121 +/- 4% vs. 83 +/- 5% dilation at 2 MAC halothane vs. isoflurane, respectively).

Conclusion
Halothane and isoflurane differentially produce dose-dependent dilation of intraparenchymal cerebral microvessels. These findings suggest that local effects of the volatile anesthetics on intracerebral microvessel diameter contribute significantly to alterations in cerebrovascular resistance and support previously described heterogeneous actions on cerebral blood flow produced by these agents.
Efficacy, Dose-Response, and Safety of Ondansetron in Prevention of Postoperative Nausea and Vomiting
Authors: Tramer Martin R. , Reynolds D. John M. , Moore R. Andrew , McQuay Henry J. 
Published: November 2003

Objective
The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV).

Methods
Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo.

Results
Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36).

Conclusions
If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.
Oral Clonidine Premedication Reduces Minimum Alveolar Concentration of Sevoflurane for Tracheal Intubation in Children
Authors: Nishina Kahoru , Mikawa Katsuya , Shiga Makoto , Maekawa Nobuhiro , Obara Hidehumi 
Published: November 2003

Background
Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MAC(TI)) of sevoflurane was assessed with and without N2O and clonidine premedication.

Methods
Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 microg/kg oral clonidine or 4 microg/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial

Results
The MAC(TI) of sevoflurane in the absence of N2O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MAC(TI) of sevoflurane by 26%, 24%, and 27% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups.

Conclusions
Oral clonidine premedication decreased the MAC(TI) of sevoflurane. Nitrous oxide also decreased the MAC(TI). The combination of clonidine and N2O lessened the MAC(TI) of sevoflurane more than did either drug alone.
Patient-controlled Analgesia after Major Shoulder Surgery
Authors: Borgeat Alain , Schappi Beatrice , Biasca Nicola , Gerber Christian 
Published: November 2003

Background
The authors compared patient-controlled interscalene analgesia (PCIA) with local anesthetics with intravenous patient-controlled analgesia (PCA) with opioids to manage postoperative pain after major shoulder surgery.

Methods
Forty patients scheduled for elective major shoulder surgery were prospectively randomized to receive either PCIA or PCA. Before surgery, all patients had an interscalene block. In the PCIA group, a catheter was introduced within the interscalene sheath. Six hours after the initial block, patients received for 48 h either a continuous infusion of 0.15% bupivacaine through the interscalene catheter at a rate of 5 ml/h plus a bolus of 3 or 4 ml with a lock-time of 20 min (group PCLA) or a continuous intravenous infusion of nicomorphine at a rate of 0.5 mg/h plus a bolus of 2 or 3 mg with a lock-time of 20 min (group PCA). Pain relief was regularly assessed using a visual analog scale, side effects were noted, and the patients were asked to rate their satisfaction at the end of the study.

Results
Pain relief was significantly better controlled in the PCIA group at t = 12 and 18 h (P < 0.05). Vomiting and pruritus were 0 versus 25% and 0 versus 25% for the PCIA and PCA groups, respectively (P < 0.05). Patient satisfaction was greater in the PCIA group (P < 0.05). Time of first bolus administration and paracetamol supplement were similar in both groups.

Conclusions
The use of the PCIA technique was uncomplicated and provided better pain relief than PCA during the first 18 h after operation. The incidence of side effects such as vomiting and pruritus was significantly decreased with the use of PCIA, and patient satisfaction was superior in the PCIA group.
Cost-Benefit and Efficacy of Aprotinin Compared with ε-Aminocaproic Acid in Patients Having Repeated Cardiac Operations
Authors: Bennett-Guerrero Elliott , Sorohan Jonathan G. , Gurevich Miguel L. , Kazanjian Paul E. , Levy Roberto R. , Barbera Alberto V. , White William D. , Slaughter Thomas F. , Sladen Robert N. , Smith Peter K. , Newman Mark F. 
Published: November 2003

Background
Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs.

Methods
In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg).

Results
Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction.

Conclusions
Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).