bluuebunny/crossref_metadata_2025_split huggingface dataset:
Additive Inhibition of Nicotinic Acetylcholine Receptors by Corticosteroids and the Neuromuscular Blocking Drug Vecuronium
Authors: Kindler Christoph H. , Verotta Davide , Gray Andrew T. , Gropper Michael A. , Yost C. Spencer 
Published: November 2003

Background
Neuromuscular disorders associated with muscular weakness and prolonged paralysis are common in critically ill patients. Acute myopathy has been described in patients receiving a combination therapy of corticosteroids and nondepolarizing neuromuscular blocking drugs for treatment of acute bronchospasm. The cause of this myopathy is not fully established and may involve drug interactions that perturb neuromuscular transmission. To investigate the interaction of corticosteroids with neuromuscular blocking drugs, the authors determined the effects of methylprednisolone and hydrocortisone alone and in combination with vecuronium on fetal (gamma-subunit containing) and adult (epsilon-subunit containing) subtypes of the muscle-type nicotinic acetylcholine receptor.

Methods
Functional channels were expressed in Xenopus laevis oocytes and activated with 1 microM acetylcholine. The resulting currents were recorded using a whole cell two-electrode voltage clamp technique.

Results
Both forms of the muscle-type acetylcholine receptor were potently inhibited by methylprednisolone and hydrocortisone, with concentrations producing 50% inhibition in the range of 400-600 microM and 1-2 mM, respectively. The corticosteroids produced noncompetitive antagonism of the muscle-type nicotinic acetylcholine receptor at clinical concentrations. Both receptor forms were also inhibited, even more potently, by vecuronium, with a concentration producing 50% inhibition in the range of 1-2 nM. Combined application of vecuronium and methylprednisolone showed additive effects on both receptor forms, which were best described by a two-site model, with each site independent.

Conclusions
The enhanced neuromuscular blockade produced when corticosteroids are combined with vecuronium may augment pharmacologic denervation and contribute to the pathophysiology of prolonged weakness observed in some critically ill patients.
The Dose–Response of Intrathecal Sufentanil Added to Bupivacaine for Labor Analgesia
Authors: Wong Cynthia A. , Scavone Barbara M. , Loffredi Mariann , Wang Warren Y. , Peaceman Alan M. , Ganchiff Jeanne N. 
Published: November 2003

Background
Regional analgesia for labor often is initiated with an intrathecal injection of a local anesthetic and opioid. The purpose of this prospective, randomized, blinded study was to determine the optimal dose of intrathecal sufentanil when combined with 2.5 mg bupivacaine for labor analgesia.

Methods
One hundred seventy parous parturients with cervical dilation between 3-5 cm were randomized to receive intrathecal 0 (control), 2.5, 5.0, 7.5, or 10.0 microg sufentanil combined with 2.5 mg bupivacaine, followed by a lidocaine epidural test dose, for initiation of analgesia (34 patients in each group). Visual analog scores and the presence of nausea, vomiting, and pruritus were determined every 15 min until the patient requested additional analgesia. Fetal heart rate tracings were compared between groups.

Results
Groups were similar for age, height, weight, oxytocin dose, duration of labor, and baseline visual analog scores. Duration of action was significantly shorter for control patients (39 +/- 25 min [mean +/- SD]) compared with those administered sufentanil, all doses (93 +/- 32, 93 +/- 47, 94 +/- 33, 97 +/- 39 min), but was not different among groups administered 2.5, 5.0, 7.5, or 10.0 microg sufentanil. More patients who received 10 microg sufentanil reported nausea and vomiting than did control patients. The severity of pruritus increased with administration of 7.5 and 10.0 microg sufentanil. There was no difference in fetal heart rate changes among groups.

Conclusions
Intrathecal bupivacaine (2.5 mg) without sufentanil did not provide satisfactory analgesia for parous patients. However, bupivacaine combined with 2.5 microg sufentanil provided analgesia comparable to higher doses, with a lower incidence of nausea and vomiting and less severe pruritus.
Pharmacokinetics of Human Cerebral Opioid Extraction
Authors: Metz Christoph , Göbel Lothar , Gruber Michael , Hoerauf Klaus H. , Taeger Kai 
Published: November 2003

Background
The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans.

Methods
After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia.

Results
Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90.

Conclusions
The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.
The Influence of Drug-induced Low Plasma Cholinesterase Activity on the Pharmacokinetics and Pharmacodynamics of Mivacurium
Authors: Østergaard Doris , Rasmussen Søren N. , Viby-Mogensen Jørgen , Pedersen Niels A. , Boysen Rikke 
Published: November 2003

Background
The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.

Methods
Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography.

Results
Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol.

Conclusion
A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.
Ropivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, versus Bupivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, Using Patient-controlled Epidural Analgesia for Labor
Authors: Fischer Catherine , Blanié Pierre , Jaouën Envel , Vayssière Christophe , Kaloul Ismaël , Coltat Jean-Claude 
Published: November 2003

Background
This study compared the administration of 0.1% ropivacaine and 0.5 microg/ml sufentanil with that of 0.1% bupivacaine and 0.5 microg/ml sufentanil via patient-controlled epidural analgesia route during labor.

Methods
Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 microg/ml sufentanil or 0.1% bupivacaine and 0.5 microg/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery.

Results
No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively; P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD]; P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm; P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses; P < 0.05).

Conclusions
Delivered as patient-controlled epidural analgesia, 0.1% ropivacaine and 0.5 microg/ml sufentanil produce less motor block but are clinically less potent than 0.1% bupivacaine and 0.5 microg/ml sufentanil.
Multiport Epidural Catheters
Authors: Leighton Barbara L. , Topkis William G. , Gross Jeffrey B. , Arkoosh Valerie A. , Lee Sung-Hee R. , Huffnagle H. Jane , Huffnagle Suzanne L. 
Published: November 2003

Background
Multiport epidural catheters are popular; however, the reliability of the air test has not been evaluated with this catheter design. The authors determined the effectiveness of aspirating for blood and the air test in detecting intravascular multiorifice epidural catheters.

Methods
Three hundred women in labor underwent placement of a blunt-tip, three-hole, 20-gauge, lumbar epidural catheter. If there were no signs of spinal anesthesia, 3 ml lidocaine or bupivacaine was injected and the patient was observed for signs of spinal anesthesia. If there were no signs of spinal anesthesia, the authors injected 1 ml air through the epidural catheter while listening to the maternal precordium using a Doppler fetal heart rate monitor. Catheters through which blood was aspirated were air-tested and replaced. Patients with air-test-positive, blood-aspiration-negative catheters received 100 mg lidocaine through the catheter and were questioned about toxicity symptoms. The authors injected bupivacaine-fentanyl through aspiration-negative,air-test-negative catheters and recorded the sensory analgesic level 20 min later.

Results
The authors aspirated cerebrospinal fluid through one catheter and documented intravascular placement in 11 catheters. Results of the air test and blood aspiration were positive for eight catheters. Blood could not be aspirated from one air-test-positive catheter; perioral numbness developed in the patient after lidocaine injection. Blood was freely aspirated from two air-test-negative catheters. In the remaining 288 catheters, bupivacaine-fentanyl injection produced epidural analgesia in 279 patients and no effect in 9 patients.

Conclusions
The authors obtained false-negative results with both catheter aspiration and the air test. Fractionating the local anesthetic dose is important when using multiorifice epidural catheters.
Pressure Support Ventilation versus Continuous Positive Airway Pressure with the Laryngeal Mask Airway
Authors: Brimacombe Joseph , Keller Christian , Hörmann Christoph 
Published: November 2003

Background
The authors tested the hypothesis that pressure support ventilation (PSV) provides more effective gas exchange than does unassisted ventilation with continuous positive airway pressure (CPAP) in anesthetized adult patients treated using the laryngeal mask airway.

Methods
Forty patients were randomized to two equal-sized crossover groups, and data were collected before surgery. In group 1, patients underwent CPAP, PSV, and CPAP in sequence. In group 2, patients underwent PSV, CPAP, and PSV in sequence. PSV comprised positive end expiratory pressure set at 5 cm H2O and inspiratory pressure support set at 5 cm H2O above positive end expiratory pressure. CPAP was set at 5 cm H2O. Each ventilatory mode was maintained for 10 min. The following data were recorded every minute for the last 5 min of each ventilatory mode and the average reading taken: end tidal carbon dioxide, oxygen saturation, expired tidal volume, leak fraction, respiratory rate, noninvasive mean arterial pressure, and heart rate.

Results
In both groups, PSV showed lower end tidal carbon dioxide (P < 0.001), higher oxygen saturation, (P < 0.001), and higher expired tidal volume (P < 0.001) compared with CPAP. In both groups, PSV had similar leak fraction, respiratory rate, mean arterial pressure, and heart rate compared with CPAP. In group 1, measurements for CPAP were similar before and after PSV. In group 2, measurements for PSV were similar before and after CPAP.

Conclusion
The authors concluded that PSV provides more effective gas exchange than does unassisted ventilation with CPAP during LMA anesthesia while preserving leak fraction and hemodynamic homeostasis.
The Fiberscopic Findings of the Epidural Space in Pregnant Women
Authors: Igarashi Takashi , Hirabayashi Yoshihiro , Shimizu Reiju , Saitoh Kazuhiko , Fukuda Hirokazu , Suzuki Hideo 
Published: November 2003

Background
The spread of epidural analgesia is facilitated by pregnancy. Changes in the epidural structure during pregnancy may affect the spread of analgesia in pregnant women. To investigate the changes in the epidural space produced by pregnancy, the authors performed epiduroscopy in pregnant women.

Methods
Using a flexible fiberscope, the authors evaluated the epidural space in 73 women undergoing lumbar epidural anesthesia. Patients were classified into three groups: a nonpregnant group (n = 21), a first trimester pregnant group (8-13 weeks, n = 23), and a third-trimester pregnant group (27-39 weeks, n = 29). A 17-gauge Tuohy needle was inserted using the paramedian technique and the loss-of-resistance method with 5 ml air. The epiduroscope was introduced into the lumbar epidural space via the Tuohy needle and was advanced approximately 10 cm in a cephalad direction from the needle tip within the epidural space. The differences in the epidural space among the three groups then was evaluated.

Results
The epiduroscopy showed that the epidural pneumatic space, after injection of a given amount of air, was narrower and the density of the vascular network greater in the third-trimester group than in the other two groups. The amount of engorged blood vessels was greater in the third and first trimester groups than in the nonpregnant group. The amount of bleeding at the needle tip and the amount of fatty and fibrous connective tissue did not differ among the three groups.

Conclusions
Epidural blood vessels become engorged in the first trimester; the density of the vascular networks increase in the third trimester. These changes in the epidural space during pregnancy may affect the spread of epidural analgesia in pregnant women.
Port-access Minimally Invasive Cardiac Surgery Increases Surgical Complexity, Increases Operating Room Time, and Facilitates Early Postoperative Hospital Discharge
Authors: Chaney Mark A. , Durazo-Arvizu Ramón A. , Fluder Elaine M. , Sawicki Kristina J. , Nikolov Mihail P. , Blakeman Bradford P. , Bakhos Mamdouh 
Published: November 2003

Background
Proposed advantages of port-access cardiac surgery have yet to be substantiated. The authors retrospectively compared patients undergoing port-access cardiac surgery with a matched group undergoing conventional cardiac surgery.

Methods
Forty-six patients who underwent port-access cardiac surgery were matched with 46 who underwent conventional cardiac surgery. Absolute criteria for matching included morning-of-surgery admission, procedure undergone, and care being delivered by one of two surgeons. If possible, matching included care delivered by one of two anesthesiologists. Patients were matched as closely as possible for preoperative demographic and clinical characteristics.

Results
All 46 pairs of patients were matched for procedure and admitted the morning of surgery. All 92 operations were performed by one of two surgeons, and 89% were performed by one of two anesthesiologists. Preoperative demographic and clinical characteristics were equivalent between groups. Compared with conventional cardiac surgery, port-access cardiac surgery increased surgical complexity (it almost tripled cardiopulmonary bypass time during coronary artery bypass grafting and increased it almost 40% during mitral valve procedures) and increased total operating room time (P < 0.0001). Port-access cardiac surgery had no beneficial effect on earlier postoperative extubation, decreased incidence of atrial fibrillation, or intensive care unit time, yet it decreased postoperative duration of stay (P = 0.029, all patients), a benefit observed primarily in patients undergoing coronary artery bypass grafting (P = 0.002).

Conclusions
This retrospective analysis revealed that port-access cardiac surgery increases surgical complexity, increases operating room time, has no effect on earlier postoperative extubation or decreased incidence of atrial fibrillation or intensive care unit time, and may facilitate postoperative hospital discharge (primarily in patients undergoing coronary artery bypass grafting). Properly designed prospective investigation is necessary to ascertain whether port-access cardiac surgery truly offers any benefits over conventional cardiac surgery.
Pain Relief in Complex Regional Pain Syndrome due to Spinal Cord Stimulation Does Not Depend on Vasodilation
Authors: Kemler Marius A. , Barendse Gerard A. M. , van Kleef Maarten , Egbrink Mirjam G. A. oude 
Published: November 2003

Background
Spinal cord stimulation (SCS) is known to relieve pain in patients with complex regional pain syndrome (CRPS) and, in general, to cause vasodilation. The vasodilatory effect of SCS is hypothesized to be secondary to inhibition of sympathetically mediated vasoconstriction, or through antidromic impulses resulting in release of vasoactive substances. The aim of the present study was to assess whether pain relief in CRPS after SCS is, in fact, dependent on vasodilation. In addition, we tried to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS.

Methods
Twenty-four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty-two of these 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled for the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects (n = 20) were tested once only. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstriction index.

Results
Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with baseline or the contralateral clinically unaffected side.

Conclusions
The current study failed to show that SCS influences skin microcirculation in patients with CRPS and a low sympathetic tone. Therefore, we may conclude that pain relief in CRPS due to SCS is possible without vasodilation. Because sympathetic activity was greatly decreased in our patients, these results support the hypothesis that the vasodilation that is normally found with SCS is due to an inhibitory effect on sympathetically maintained vasoconstriction.
Differential Block of Fast and Slow Inactivating Tetrodotoxin-sensitive Sodium Channels by Droperidol in Spinal Dorsal Horn Neurons
Authors: Olschewski Andrea , Bräu Michael E. , Hempelmann Gunter , Vogel Werner , Safronov Boris V. 
Published: November 2003

Background
Dorsal horn neurons of the spinal cord participate in neuronal pain transmission. During spinal and epidural anesthesia, dorsal horn neurons are exposed to local anesthetics and opioids. Droperidol is usually given with opioids to avoid nausea and vomiting. A recently developed method of "entire soma isolation" has made it possible to study directly the action of droperidol on different components of Na+ current in dorsal horn neurons.

Methods
Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats.

Results
The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating (tauF, 0.5-2 ms; 80-90% of the total amplitude) and a slow inactivating (tauS, 6-20 ms; 10-20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 microm. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 microm.

Conclusions
Droperidol selectively blocks fast Na+ channels, the fast and slow components of the Na+ current in dorsal horn neurons are carried through pharmacologically distinct types of Na+ channels, and the effects of droperidol differ from those of local anesthetics and tetrodotoxin, which equipotently suppress both components. Droperidol may be suggested as a pharmacologic tool for separation of different types of inactivating tetrodotoxin-sensitive Na+ channel.