bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fentanyl Enhancement of Carrageenan-induced Long-lasting Hyperalgesia in Rats
Authors: Rivat Cyril , Laulin Jean-Paul , Corcuff Jean-Benoît , Célèrier Evelyne , Pain Laure , Simonnet Guy 
Published: November 2003

Background
Tissue damage may produce hyperalgesia, allodynia, and persistent pain. The authors recently reported that fentanyl elicits analgesia but also activates N-methyl-D-aspartate-dependent pain facilitatory processes opposing analgesia. In nonsuffering rats, this leads to a long-lasting enhancement in pain sensitivity. The current study assessed whether fentanyl could amplify carrageenan-induced hyperalgesia.

Methods
First, rats were injected once with carrageenan in a hind paw, with fentanyl (60 or 100 microg/kg each given four times at 15-min intervals [4 x 60 or 4 x100]) or saline. Second, rats were injected with carrageenan twice without fentanyl (7-day interval), with the second injection either in the previously injected paw or in the other paw. Third, rats were injected twice with carrageenan in the same hind paw: the first ketamine injection was given (10 mg/kg each given three times at 5-h intervals) with or without fentanyl (4 x 60 microg/kg), and second injection was given without ketamine or fentanyl. The consequences of treatments on long-term hyperalgesia were examined by the paw-pressure vocalization test.

Results
The long-lasting hyperalgesia induced by the first carrageenan injection was dose-dependently enhanced in both duration and magnitude in 4 x 60 or 4 x 100 microg/kg fentanyl-treated rats: 5 or 10 days, respectively, as compared with 2 days in saline-treated rats. Hyperalgesia observed in the hind paw contralateral to the first carrageenan injection was enhanced in fentanyl-treated rats. The second carrageenan injection, performed in any hind paw, induced an exaggerated hyperalgesia, especially in fentanyl-treated rats. Pretreatment with ketamine totally prevented the carrageenan- and fentanyl-induced enhancement of the long-lasting hyperalgesia.

Conclusion
Central sensitization in inflammatory pain states is reinforced by an opiate treatment, which could be prevented by N-methyl-D-aspartate receptors blockade.
Lidocaine Induces a Reversible Decrease in Alveolar Epithelial Fluid Clearance in Rats
Authors: Laffon Marc , Jayr Christian , Barbry Pascal , Wang Ybing , Folkesson Hans G. , Pittet Jean-Francois , Clerici Christine , Matthay Michael A. 
Published: November 2003

Background
Lidocaine is widely used in patients with acute cardiac disorders and has also been recently implicated as a possible cause of pulmonary edema after liposuction. The objective of this study was to assess the effect of lidocaine on alveolar fluid clearance, the primary mechanism responsible for the resolution of alveolar edema.

Methods
Alveolar fluid clearance was measured in 29 ventilated rats using our well-validated method over 1 h using a 5% albumin solution instilled into the distal air spaces of the lung. Lidocaine was added to the instilled albumin solution (10(-5) M) or administered intravenously at a dose estimated to achieve a clinically relevant plasma concentration of 10(-5) M. Standard agonists and antagonists were used to determine the effect of lidocaine on alveolar fluid clearance. To determine whether lidocaine acted predominantly on the apical or basal surface, we also used QX314, lidocaine n-ethyl bromide quaternary salt, an analog of lidocaine, which is unable to cross the alveolar epithelium. The effect of lidocaine on the apical epithelial sodium channel transfected in Xenopus oocytes was also studied.

Results
Alveolar or intravenous lidocaine decreased alveolar fluid clearance by 50%, an effect that was reversible with the beta2 agonist, terbutaline. Lidocaine acted predominantly on the basal surface of the epithelium because n-ethyl bromide quaternary salt decreased alveolar fluid clearance only when it was given intravenously and because lidocaine did not inhibit the apical epithelial sodium channel when expressed in oocytes.

Conclusions
Lidocaine decreased alveolar fluid clearance by 50%, an effect that may have major clinical implications in the care of patients with cardiac disease or during the perioperative period in some patients. Importantly, the effect of lidocaine was completely reversible with beta2-adrenergic therapy.
Effect of Mannitol and Furosemide on Plasma Osmolality and Brain Water
Authors: Thenuwara Kokila , Todd Michael M. , Brian Johnny E. 
Published: November 2003

Background
Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might occur is via a reduction in brain water content. Although mannitol and furosemide are commonly used in combination, there has been no formal evaluation of the interactive effects of these two drugs on brain water. The effect of mannitol and furosemide alone and in combination on water content of normal rat brain was examined.

Methods
The lungs of rats anesthetized with halothane were mechanically ventilated to maintain normal physiologic parameters. After baseline measurement of plasma osmolality, mannitol (1, 4, or 8 g/kg), furosemide (2, 4, or 8 mg/kg), or a combination of furosemide (8 mg/kg) and mannitol (1, 4, or 8 g/kg) was administered intravenously over approximately 15 min. One hour later, plasma osmolality was measured, the animals were killed, and brain water content was determined by wet and dry weight measurements.

Results
Mannitol produced a dose-dependent increase in plasma osmolality and reduction of brain water content. There was a linear relation between plasma osmolality and brain water content. Furosemide alone did not affect plasma osmolality or brain water at any dose. The combination of furosemide with mannitol resulted in a greater increase in plasma osmolality than seen with mannitol alone and a greater decrease in brain water at 4 and 8 g/kg of mannitol.

Conclusions
The doses of mannitol and furosemide utilized were much larger than clinically applicable doses and were selected to maximize the ability to detect effect on brain water. The combination of mannitol and furosemide resulted in greater reduction of brain water content than did mannitol alone. Furosemide enhanced the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content. Potential interaction (if any) of smaller, clinically used doses of mannitol and furosemide cannot be surmised from the current study.
Xenon Does Not Impair the Responsiveness of Cardiac Muscle Bundles to Positive Inotropic and Chronotropic Stimulation
Authors: Schroth Sylvia C. , Schotten Ulrich , Alkanoglu Orkide , Reyle-Hahn Matthias S. , Hanrath Peter , Rossaint Rolf 
Published: November 2003

Background
Most volatile anesthetics exhibit a direct myocardial depressant effect. This side effect often limits their applicability in patients with impaired cardiac function. Xenon is a new gaseous anesthetic that did not show any adverse cardiovascular effects in clinical and experimental studies. The authors tested the hypothesis that xenon does not affect myocardial contractility or the positive inotropic effect of isoproterenol, calcium, and increase in pacing rate in isolated guinea pig ventricular muscle bundles.

Methods
Thin ventricular muscle bundles from guinea pig hearts with a mean diameter of 0.4-0.45 mm were prepared under stereomicroscopic control. Force of contraction and contraction times were studied in muscles superfused with medium equilibrated with either 65% xenon and 35% oxygen (xenon group), 1.2% isoflurane in oxygen (isoflurane group), or 65% nitrogen and 35% oxygen (control group). In addition, the positive inotropic effects of calcium, isoproterenol (10(-10)-3 x 10(-8) M) and increasing frequency (0.5-2 Hz) were studied during xenon and isoflurane exposure.

Results
In contrast to isoflurane, xenon did not alter myocardial force of contraction or contraction times. The positive inotropic effect of isoproterenol, calcium, and increasing pacing frequencies did not differ between the muscles exposed to xenon and the control group. Isoflurane elicited the expected negative inotropic effect (30% reduction of force of contraction) but did not impair the response to inotropic stimuli.

Conclusions
Xenon does not alter myocardial contractility and the response to inotropic stimuli such as calcium, isoproterenol, or increase in pacing frequency in isolated guinea pig ventricular muscle bundles.
Effects of Primary Alcohols on Airway Smooth Muscle
Authors: Sakihara Chie , Jones Keith A. , Lorenz Robert R. , Perkins William J. , Warner David O. 
Published: November 2003

Background
The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity).

Method
The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine.

Results
The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence.

Conclusions
Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.
Volume Kinetic Analysis of the Distribution of 0.9% Saline in Conscious versus Isoflurane-anesthetized Sheep
Authors: Brauer Kirk I. , Svensén Christer , Hahn Robert G. , Traber Lilian D. , Prough Donald S. 
Published: November 2003

Background
The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia.

Methods
Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes.

Results
The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma.

Conclusions
In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.
Inhibitory Effects of Volatile Anesthetics on K+and Cl−Channel Currents in Porcine Tracheal and Bronchial Smooth Muscle
Authors: Chen Xiangdong , Yamakage Michiaki , Namiki Akiyoshi 
Published: November 2003

Background
K+ and Ca2+-activated Cl- (ClCa) channel currents have been shown to contribute to the alteration of membrane electrical activity in airway smooth muscle. This study was conducted to investigate the effects of volatile anesthetics, which are potent bronchodilators, on the activities of these channels in porcine tracheal and bronchial smooth muscles.

Methods
Whole-cell patch clamp recording techniques were used to investigate the effects of superfused isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) on K+ and ClCa channel currents in dispersed smooth muscle cells.

Results
Isoflurane and sevoflurane inhibited whole-cell K+ currents to a greater degree in tracheal versus bronchial smooth muscle cells. More than 60% of the total K+ currents in tracheal smooth muscle appeared to be mediated through delayed rectifier K+ channels compared with less than 40% in bronchial smooth muscle. The inhibitory effects of the anesthetics were greater on the delayed rectifier K+ channels than on the remaining K+ channels. Cl- currents through ClCa channels were significantly inhibited by the anesthetics. The inhibitory potencies of the anesthetics on the ClCa channels were not different in tracheal and bronchial smooth muscle cells.

Conclusions
Volatile anesthetics isoflurane and sevoflurane significantly inhibited Cl- currents through ClCa channels, and the inhibitory effect is consistent with the relaxant effect of volatile anesthetics in airway smooth muscle. Different distributions and different anesthetic sensitivities of K+ channel subtypes could play a role in the different inhibitory effects of the anesthetics on tracheal and bronchial smooth muscle contractions.
Anesthesiologist Board Certification and Patient Outcomes
Authors: Silber Jeffrey H. , Kennedy Sean K. , Even-Shoshan Orit , Chen Wei , Mosher Rachel E. , Showan Ann M. , Longnecker David E. 
Published: November 2003

Background
Board certification is often used as a surrogate indicator of provider competence, although few outcome studies have demonstrated its validity. The aim of this study was to compare the outcomes of patients who underwent surgical procedures under the care of an anesthesiologist with or without board certification.

Methods
Medicare claims records for 144,883 patients in Pennsylvania who underwent general surgical or orthopedic procedures between 1991 and 1994 were used to determine provider-specific outcome rates adjusted to account for patient severity and case mix, and hospital characteristics. Outcomes of 8,894 cases involving midcareer anesthesiologists, 11-25 yr from medical school graduation, who lacked board certification were compared with all other cases. Midcareer anesthesiologist cases were studied because this group had sufficient time to become certified during an era when obtaining certification was already considered important, and consequently had the highest rate of board certification. Mortality within 30 days of admission and the failure-to-rescue rate (defined as the rate of death after an in-hospital complication) were the two primary outcome measures.

Results
Adjusted odds ratios for death and failure to rescue were greater when care was delivered by noncertified midcareer anesthesiologists (death = 1.13 [95% confidence interval, 1.00, 1.26], P < 0.04; failure to rescue = 1.13 [95% confidence interval, 1.01, 1.27], P < 0.04). Adjusting for international medical school graduates did not change these results.

Conclusions
When anesthesiology board certification is very common, as in midcareer practitioners, the lack of board certification is associated with worse outcomes. However, the poor outcomes associated with noncertified providers may be a result of the hospitals at which they practice and not necessarily their manner of practice.
Clevidipine in Adult Cardiac Surgical Patients
Authors: Bailey James M. , Lu Wei , Levy Jerrold H. , Ramsay James G. , Shore-Lesserson Linda , Prielipp Richard C. , Brister Neil W. , Roach Gary W. , Jolin-Mellgard Ase , Nordlander Margareta 
Published: November 2003

Background
Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients.

Methods
Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration-response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis.

Results
There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration.

Conclusion
Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.
Effects of Clonidine on Postoperative Nausea and Vomiting in Breast Cancer Surgery
Authors: Oddby-Muhrbeck Eva , Eksborg Staffan , Bergendahl Henrik T. G. , Muhrbeck Olle , Lönnqvist Per Arne 
Published: November 2003

Background
Postoperative nausea and vomiting (PONV) is still common, especially among female patients. Our hypothesis is that coinduction with clonidine reduces the incidence of PONV in adult patients undergoing breast cancer surgery.

Methods
Sixty-eight women premedicated with midazolam were randomly allocated to coinduction with intravenous clonidine (group C) or placebo (group P) in this prospective, double-blind study. Anesthesia was standardized (laryngeal mask airway, fentanyl, propofol, sevoflurane, nitrous oxide, and oxygen). Hemodynamic parameters and the requirements for propofol, sevoflurane, and the postoperative need for ketobemidone were noted. The primary endpoints studied were the number of PONV-free patients and patient satisfaction with respect to PONV.

Results
Patients in group C had a significantly reduced need for propofol (P < 0.04) and sevoflurane (P < 0.01) and a reduced early need for ketobemidone (P < 0.04). There were significantly more PONV-free patients in group C compared with group P (20 and 11 of 30, respectively; P < 0.04). The number needed to treat was 3.3 (95% confidence interval, 1.8, 16.9). Intraoperative blood pressure, postoperative heart rate, and postoperative blood pressure were all significantly lower in group C compared with group P, but were not considered to be of clinical importance. No negative side effects were recorded.

Conclusion
Coinduction with clonidine significantly increased the number of PONV-free patients after breast cancer surgery with general anesthesia.
Effect of Epidural Epinephrine on the Minimum Local Analgesic Concentration of Epidural Bupivacaine in Labor
Authors: Polley Linda S. , Columb Malachy O. , Naughton Norah N. , Wagner Deborah S. , M. van de Ven Cosmas J. 
Published: November 2003

Background
The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the local anesthetic-sparing efficacy of epidural epinephrine by its effect on the MLAC of bupivacaine.

Methods
In this double-blind, randomized, prospective study, 70 parturients who were at 7 cm or less cervical dilation and who requested epidural analgesia were allocated to one of two groups. After lumbar epidural catheter placement, 20 ml bupivacaine (n = 35) or bupivacaine with epinephrine 1:300,000 (n = 35) was administered. The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores, with 10 mm or less within 30 min defined as effective.

Results
The MLAC of bupivacaine alone was 0.091% wt/vol (95% confidence interval, 0.081-0.102). The addition of epinephrine 1:300,000 (66.7 microg) resulted in a significant reduction (P < 0.01) in the MLAC of bupivacaine to 0.065% wt/vol (95% confidence interval, 0.047-0.083). The lowest maternal blood pressure was significantly lower in the bupivacaine-epinephrine group (P = 0.03). There were statistically significant reductions in fetal heart rate (P = 0.011) in the bupivacaine-epinephrine group that were not clinically significant.

Conclusions
The addition of epidural epinephrine 1:300,000 (66 microg) resulted in a significant 29% reduction in the MLAC of bupivacaine. Coincident reductions in fetal heart rate and maternal blood pressure were also observed that were not clinically significant.