bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway Anesthesia Alone Does Not Explain Attenuation of Histamine-induced Bronchospasm by Local Anesthetics
Authors: Groeben Harald , Großwendt Thorsten , Silvanus Marie-Theres , Pavlakovic Goran , Peters Jürgen
Published: November 2003

Background

Lidocaine inhalation attenuates histamine-induced bronchospasm while evoking airway anesthesia. Because this occurs at plasma concentrations much lower than those required for intravenous lidocaine to attenuate bronchial reactivity, this effect is likely related to topical airway anesthesia and presumably independent of the specific local anesthetic used. Therefore, the authors tested the effect of dyclonine, lidocaine, and ropivacaine inhalation on histamine-induced bronchospasm in 15 volunteers with bronchial hyperreactivity.

Methods

Bronchial hyperreactivity was verified by an inhalational histamine challenge. Histamine challenge was repeated after inhalation of dyclonine, lidocaine, ropivacaine, or placebo on 4 different days in a randomized, double-blind fashion. Lung function, bronchial hyperreactivity to histamine, duration of local anesthesia, and lidocaine and ropivacaine plasma concentrations were measured. Statistical analyses were performed with the Friedman and Wilcoxon rank tests. Data are presented as mean +/- SD.

Results

The inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s (PC20) was 7.0 +/- 5.0 mg/ml at the screening evaluation. Lidocaine and ropivacaine inhalation increased PC20 significantly to 16.1 +/- 12.9 and 16.5 +/- 13.6 mg/ml (P = 0.007), whereas inhalation of dyclonine and saline did not (9.1 +/- 8.4 and 6.1 +/- 5.0 mg/ml, P = 0.7268). Furthermore, in contrast to saline and lidocaine, inhalation of both ropivacaine and dyclonine significantly decreased forced expiratory volume in 1 s from baseline (P = 0.0016 and 0.0018, respectively). The longest lasting and most intense anesthesia developed after dyclonine inhalation (48 +/- 13 vs. 28 +/- 8 [lidocaine] and 25 +/- 4 min [ropivacaine]).

Conclusion

Both lidocaine and the new amide local anesthetic ropivacaine significantly attenuate histamine-induced bronchospasm. In contrast, dyclonine, despite its longer lasting and more intense local anesthesia, does not alter histamine-evoked bronchoconstriction and irritates the airways. Thus, airway anesthesia alone does not necessarily attenuate bronchial hyperreactivity. Other properties of inhaled local anesthetics may be responsible for attenuation of bronchial hyperreactivity.
Is Ventilator-associated Pneumonia an Independent Risk Factor for Death?
Authors: Bregeon Fabienne , Ciais Véronique , Carret Vincent , Gregoire Régine , Saux Pierre , Gainnier Marc , Thirion Xavier , Drancourt Michel , Auffray Jean-Pierre , Papazian Laurent
Published: November 2003

Background

Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation.

Methods

During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP.

Results

Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia.

Conclusion

Ventilator-associated pneumonia does not appear to be an independent risk factor for death.
Intrathecal Ropivacaine and Clonidine for Ambulatory Knee Arthroscopy
Authors: De Kock Marc , Gautier Philippe , Fanard Luc , Luc Hody Jean , Lavand’homme Patricia
Published: November 2003

Background

The aim of this study was to evaluate the association of a small dose of intrathecal ropivacaine with small doses of intrathecal clonidine for ambulatory surgery.

Methods

One hundred twenty patients, classified as American Society of Anesthesiologists physical status I and scheduled for knee arthroscopy, were studied. Patients were randomly assigned to receive 4 ml of one of the following double-blinded isobaric intrathecal solutions: 8 mg of ropivacaine (group 1; n =30); 8 mg ropivacaine plus 15 microg clonidine (group 2; n =30); 8 mg ropivacaine plus 45 microg clonidine (group 3; n =30); and 8 mg ropivacaine plus 75 microg clonidine (group 4; n =30). The level and duration of sensory anesthesia were recorded, along with the intensity and duration of motor block. Patient and surgeon were interviewed to evaluate the quality of anesthesia.

Results

Intrathecal ropivacaine (8 mg alone) produced short sensory anesthesia and motor blockade (132 +/- 38 min and 110 +/- 35 min; mean +/- SD). However, the quality of anesthesia was significantly lower than in any other group (P < 0.05). Ropivacaine (8 mg) plus 75 microg clonidine produced significantly longer sensory and motor anesthesia (195 +/- 40 min and 164 +/- 38 min; P < 0.05). However, this was associated with systemic effects, such as sedation and reduction of arterial blood pressure. Ropivacaine (8 mg) plus 15 microg clonidine did not prolong sensory or motor blockade, afforded high quality anesthesia, and was not associated with detectable systemic effects.

Conclusion

Small-dose intrathecal clonidine (15 microg) plus 8 mg intrathecal ropivacaine produces adequate and short-lasting anesthesia for knee arthroscopy.
Ketamine, but Not S (+)-ketamine, Blocks Ischemic Preconditioning in Rabbit Hearts In Vivo
Authors: Müllenheim Jost , Fräßdorf Jan , Preckel Benedikt , Thämer Volker , Schlack Wolfgang
Published: November 2003

Background

Ketamine blocks KATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The authors investigated the effects of ketamine and S(+)-ketamine on ischemic preconditioning in the rabbit heart in vivo.

Methods

In 46 alpha-chloralose-anesthetized rabbits, left ventricular pressure (tip manometer), cardiac output (ultrasonic flow probe), and myocardial infarct size (triphenyltetrazolium staining) at the end of the experiment were measured. All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. The control group underwent the ischemia-reperfusion program without preconditioning. Ischemic preconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (preconditioning group). To test whether ketamine or S(+)-ketamine blocks the preconditioning-induced cardioprotection, each (10 mg kg(-1)) was administered 5 min before the preconditioning ischemia. To test any effect of ketamine itself, ketamine was also administered without preconditioning at the corresponding time point.

Results

Hemodynamic baseline values were not significantly different between groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardiac output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventricular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significantly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals without preconditioning (48 +/- 18%), but abolished the cardioprotective effects of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did not affect ischemic preconditioning (25 +/- 11%, P = 1.0).

Conclusions

Ketamine, but not S(+)-ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.
Effect of Increasing Perfluorocarbon Dose on ˙Va/˙Q Distribution during Partial Liquid Ventilation in Acute Lung Injury
Authors: Lim Chae-Man , Domino Karen B. , Glenny Robb W. , Hlastala Michael P.
Published: November 2003

Background

Although gas exchange during partial liquid ventilation (PLV) depends on perfluorocarbon liquid, the effect of perfluorocarbon dose on the ventilation-perfusion (VA/Q) distribution is not known. This study investigated how VA/Q distribution of an acutely injured lung is affected during PLV at increasing perfluorocarbon dose.

Methods

In eight rabbits (3.2 +/- 0.1 kg), acute lung injury (ALI) was created by repeated saline lavage (arterial oxygen partial pressure/fraction of inspired oxygen, 37 +/- 11 mm Hg). Three different doses of perfluorodecalin (9 ml/kg = low dose; 13.5 ml/kg = medium dose; 18 ml/kg = functional residual capacity [FRC] dose) were applied in random order during PLV. VA/Q distribution at different doses was evaluated by multiple inert gas elimination technique.

Results

Inert gas shunt (63 +/- 21% at ALI) decreased with increasing perfluorocarbon dose (43 +/- 21% at low dose, 29 +/- 10% at medium dose, 11 +/- 9% at FRC dose; P = 0.022). Compared with ALI (0%), the proportion of low VA/Q units was higher at all tested doses (19 +/- 10, 25 +/- 12, and 34 +/- 18%, respectively; all P < 0.05). Compared with ALI (27 +/- 14%), the proportion of normal VA/Q units was not increased at low or medium doses but was increased only at the FRC dose (45 +/- 13%; P = 0.027).

Conclusions

With increasing perfluorocarbon dose during PLV, shunt was reduced from a small dose. The majority shunt units were converted to units showing low VA/Q ratios rather than normal VA/Q ratios. The presence of considerable amount of low VA/Q units across the varying doses of perfluorocarbon suggested that additional measures are necessary during PLV to augment its effect on gas exchange.
Blockade and Activation of the Human Neuronal Nicotinic Acetylcholine Receptors by Atracurium and Laudanosine
Authors: Chiodini Florence , Charpantier Eric , Muller Dominique , Tassonyi Edomer , Fuchs-Buder Thomas , Bertrand Daniel
Published: November 2003

Background

Curaremimetic nondepolarizing muscle relaxants are widely used in clinical practice to prevent muscle contraction either during surgery or during intensive care. Although primarily acting at the neuromuscular junction, these compounds can cause adverse effects, including modification of cardiac rhythm, arterial blood pressure, and in the worst cases, triggering of seizures. In this study, we assessed the interaction of atracurium and its metabolite, laudanosine, with neuronal nicotinic receptors.

Methods

The human neuronal nicotinic receptors alpha4beta2, alpha3beta4, alpha3alpha5beta4, and alpha7 are heterologously expressed in Xenopus laevis oocytes, and the effect of atracurium and its degradation product, laudanosine, were studied on these receptors.

Results

Atracurium and laudanosine inhibited in the micromolar range the major brain alpha4beta2 receptor and the ganglionic alpha3beta4 or alpha3beta4alpha5 and the homomeric alpha7 receptors. For all four receptors, inhibition was rapid and readily reversible within less than 1 min. Atracurium blockade was competitive at alpha4beta2 and alpha7 receptors but displayed a noncompetitive blockade at the alpha3beta4 receptors. Inhibition at this receptor subtype was not modified by alpha5. Laudanosine was found to have a dual mode of action; first, it competes with acetylcholine and, second, it blocks the ionic pore by steric hindrance. At low concentrations, these two drugs are able to activate both the alpha4beta2 and the alpha3beta4 receptors.

Conclusion

Adverse effects observed during atracurium administration may be attributed, at least partly, to an interaction with neuronal nicotinic receptors.
The Use of Intravenous Nitroglycerin in a Case of Spasm of the Sphincter of Oddi during Laparoscopic Cholecystectomy
Authors: Toyoyama Hirokatsu , Kariya Nobutaka , Hase Ichiro , Toyoda Yoshiro
Published: November 2003

Spasm of the sphincter of Oddi still occurs during cholecystectomy. Some reports indicate that the spasm, induced by morphine, can be reversed by injection of naloxone, nalbuphine, and glucagon. Others maintain that nitroglycerin or nifedipine can relax the sphincter of Oddi muscle. We recently encountered spasm of the sphincter of Oddi during a laparoscopic cholecystectomy and treated it successfully with intravenous nitroglycerin.
Tissue Injury and the Inflammatory Response to Pediatric Cardiac Surgery with Cardiopulmonary Bypass
Authors: Chew Michelle S. , Brandslund Ivan , Brix-Christensen Vibeke , Ravn Hanne B. , Hjortdal Vibeke E. , Pedersen Jens , Hjortholm Kirsten , Hansen Ole K. , Tønnesen Else
Published: November 2003

Background

There are few detailed descriptions of the inflammatory response to cardiac surgery with cardiopulmonary bypass (CPB) in children beyond 24 h postoperatively. This is especially true for the antiinflammatory cytokines and the extent of tissue injury. The aim of the current study was to describe the inflammatory and injury responses in uncomplicated pediatric cardiac surgery with CPB, where methylprednisolone and modified ultrafiltration (MUF) were used.

Methods

Blood samples were collected up to 48 h postoperatively. Cytokines (tumor necrosis factor-alpha and interleukin-6, -1beta, -10, and -1ra), complement (C3d and C4d) and coagulation system (prothrombin activation fragments 1 and 2 and antithrombin III) activation, neutrophil elastase, and the resulting tissue injury (creatine kinase, lactate dehydrogenase, alanine transaminase, amylase, and gamma-glutamyl transferase) were measured.

Results

The proinflammatory cytokine release varied widely, in contrast to a clear-cut antiinflammatory response. Cytokine concentrations did not decrease immediately after MUF, and no rebound increases later in the postoperative period were observed. The coagulation system, but not complement, was activated. There was a late release of C-reactive protein. Tissue injury could be quantified biochemically without evidence of hepatic or pancreatic dysfunction.

Conclusion

In this group of uncomplicated subjects, the antiinflammatory cytokine and tissue injury responses were well defined, in contrast to a variable proinflammatory cytokine release. This was accompanied by activation of the coagulation system but not of complement. Concentrations of inflammatory mediators did not decrease immediately after MUF, and there was no evidence for rebound release later in the postoperative period.
Dose–Response Study of Epidural Ropivacaine for Labor Analgesia
Authors: Lee Bee Beng , Ngan Kee Warwick D. , Wong Eliza L. Y. , Liu Justina Y. W.
Published: November 2003

Background

Ropivacaine has been introduced for use in epidural analgesia in labor. However, there have been few formal dose-response studies of ropivacaine in this setting.

Methods

The authors performed a prospective, randomized, double-blind study examining the effectiveness of five different doses of ropivacaine (10, 20, 30, 40, and 50 mg) administered epidurally in a volume of 10 ml to establish analgesia in 66 parturients who were in active labor with cervical dilatation less than 4 cm. A dose was considered effective when the visual analog scale pain score decreased by 50% or more from baseline.

Results

A sigmoid dose-response curve and a probit log dose-response plot (linear regression coefficient, r = 0.84; coefficient of determination, r2 = 0.71) were obtained. The ED50 (median effective dose) obtained based on the maximum likelihood estimation was 18.4 mg (95% confidence interval, 13.4-25.4 mg). Time to onset of analgesia, duration of analgesia, time to two-segment regression of sensory block level, and incidence of motor block were not affected by the dosage of ropivacaine administered (P = 0.93, 0.12, 0.55, and 0.39, respectively). However, the upper level of sensory block was dose-related (P < 0.01).

Conclusion

In a traditional dose-response study, the ED50 of ropivacaine required to initiate epidural analgesia in early labor was found to be 18.4 mg (95% confidence interval, 13.4-25.4 mg).
The Midlatency Auditory Evoked Potentials Predict Responsiveness to Verbal Commands in Patients Emerging from Anesthesia with Xenon, Isoflurane, and Sevoflurane but Not with Nitrous Oxide
Authors: Goto Takahisa , Nakata Yoshinori , Saito Hayato , Ishiguro Yoshiki , Niimi Yoshinari , Morita Shigeho
Published: November 2003

Background

It has recently been demonstrated that the approximately 40-Hz spectral power of the midlatency auditory evoked potential (MLAEP) correlates well with wakefulness during desflurane or propofol anesthesia. The aim of this study was to characterize how other inhalational anesthetics affects the MLAEP as the patients regain responsiveness to simple verbal command during emergence from anesthesia.

Methods

Sixty patients were randomly assigned to receive xenon, isoflurane, sevoflurane, or nitrous oxide (N2O) supplemented with epidural anesthesia. During emergence, the concentration of an anesthetic was decreased in 0.1-minimum alveolar concentration (MAC) decrements from 0.8 MAC or from 70% in the case of N2O, and each new concentration was maintained for 15 min. Every 5 min during each equilibration period, the MLAEP was recorded and the patients were asked to open their eyes and squeeze and release the investigator's hand. This process was repeated until the first response to either of these commands was observed.

Results

Thirteen patients were excluded because of technical reasons. The preanesthetic MLAEP showed a periodic waveform, where the Na-Pa-Nb complex was the most prominent component contributing to the high energy around 29-39 Hz in the power spectrum. Emergence from xenon, isoflurane, and sevoflurane anesthesia produced similar changes in the MLAEP. The spectral power for the frequency 29 Hz or greater was severely suppressed at 0.8 MAC but significantly recovered between the concentration only 0.1 MAC higher that permitting the first response to command and that associated with the first response. In contrast, N2O hardly affected the MLAEPs, even at the concentrations producing unresponsiveness. Two patients did not lose responsiveness even at the highest concentration tested (70%).

Conclusions

The MLAEP is closely associated with responsiveness to verbal command during emergence from anesthesia with xenon, isoflurane, and sevoflurane but not with N2O.
Epidural Lidocaine Decreases Sevoflurane Requirement for Adequate Depth of Anesthesia as Measured by the Bispectral Index ® Monitor
Authors: Hodgson Peter S. , Liu Spencer S.
Published: November 2003

Background

Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS).

Methods

After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured.

Results

The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml).

Conclusions

Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural-general anesthesia.
Effects of Isoflurane on Intracellular Calcium and Myocardial Crossbridge Kinetics in Tetanized Papillary Muscles
Authors: Hannon James D. , Cody Mark J. , Housmans Philippe R.
Published: November 2003

Background

Isoflurane depresses the intracellular Ca2+ transient and force development during a twitch, but its effects on crossbridge cycling rates are difficult to predict because of the transient nature of the twitch. Measurements of the effects of isoflurane on crossbridge cycling kinetics during tetanic contractions, which provide a steady state level of activation in intact cardiac muscle, have not been previously reported.

Methods

Ferret right ventricular papillary muscles were isolated, and superficial cells were microinjected with the bioluminescent photoprotein aequorin to monitor the intracellular Ca2+ concentration. The rate of tension redevelopment (kTR) was measured during steady state isometric activation (tetanic stimulation, frequency 20 Hz, 1 microM ryanodine, temperature = 30 degrees C) in the absence of isoflurane (2, 6, and 12 mM extracellular [Ca2+]) and in the presence of 0.5, 1.0, and 1.5 minimum alveolar concentration isoflurane (12 mM extracellular [Ca2+]).

Results

Intracellular [Ca2+], isometric force, and kTR all increased when the extracellular [Ca2+] increased. Isoflurane (0.5, 1.0, and 1.5 minimum alveolar concentration) caused intracellular [Ca2+], isometric force, and kTR to decrease in a dose-dependent manner in the presence of 12 mM extracellular [Ca2+]. In the presence of increasing concentrations of isoflurane, the relation between intracellular [Ca2+] and force remained unchanged, whereas the relation between intracellular [Ca2+] and kTR was shifted toward higher [Ca2+].

Conclusions

These results indicate that isoflurane depresses myocardial crossbridge cycling rates. It appears that this effect is partially mediated by a decrease in the intracellular [Ca2+]. However, additional mechanisms must be considered to explain the shift of the relation between intracellular [Ca2+] and kTR toward higher [Ca2+].
Body Morphology and the Speed of Cutaneous Rewarming
Authors: Szmuk Peter , Rabb Mary F. , Baumgartner James E. , Berry James M. , Sessler Andrew M. , Sessler Daniel I.
Published: November 2003

Background

Infants and children cool quickly because their surface area (and therefore heat loss) is large compared with their metabolic rate, which is mostly a function of body mass. Rewarming rate is a function of cutaneous heat transfer plus metabolic heat production divided by body mass. Therefore, the authors tested the hypothesis that the rate of forced-air rewarming is inversely related to body size.

Methods

Isoflurane, nitrous oxide, and fentanyl anesthesia were administered to infants, children, and adults scheduled to undergo hypothermic neurosurgery. All fluids were warmed to 37 degrees C and ambient temperature was maintained near 21 degrees C. Patients were covered with a full-body, forced-air cover of the appropriate size. The heater was set to low or ambient temperature to reduce core temperature to 34 degrees C in time for dural opening. Blower temperature was then adjusted to maintain core temperature at 34 degrees C for 1 h. Subsequently, the forced-air heater temperature was set to high (approximately 43 degrees C). Rewarming continued for the duration of surgery and postoperatively until core temperature exceeded 36.5 degrees C. The rewarming rate in individual patients was determined by linear regression.

Results

Rewarming rates were highly linear over time, with correlations coefficients (r2) averaging 0.98+/-0.02. There was a linear relation between rewarming rate (degrees C/h) and body surface area (BSA; m2): Rate (degrees C/h) = -0.59 x BSA (m2) + 1.9, r2 = 0.74. Halving BSA thus nearly doubled the rewarming rate.

Conclusions

Infants and children rewarm two to three times faster than adults, thus rapidly recovering from accidental or therapeutic hypothermia.
The Corrugator Supercilii, Not the Orbicularis Oculi, Reflects Rocuronium Neuromuscular Blockade at the Laryngeal Adductor Muscles
Authors: Plaud Benoît , Debaene Bertrand , Donati François
Published: November 2003

Background

Some studies suggest that the orbicularis oculi is resistant to neuromuscular blocking drugs and behaves like laryngeal muscles. Others report little or no difference between the orbicularis oculi and the adductor pollicis. These discrepancies could be related to the exact site of recording. The purpose of this study was to compare two monitoring sites around the eye with the adductor pollicis and the laryngeal adductor muscles.

Methods

After institutional approval and informed consent, the evoked response to train-of-four stimulation was measured in 12 patients by acceleromyography at the thumb (adductor pollicis), the eyelid (orbicularis oculi), and the superciliary arch (corrugator supercilii) after 0.5 mg/kg rocuronium during propofol-fentanyl-nitrous oxide anesthesia. In 12 other patients, laryngeal adductor neuromuscular blockade was assessed via the cuff of the tracheal tube and compared with the adductor pollicis and the corrugator supercilii after 0.6 mg/kg rocuronium.

Results

After 0.5 mg/kg, maximum blockade (%T1, mean +/- SD) was less at the corrugator supercilii (80+/-20%) than at the adductor pollicis (100+/-1%) and the orbicularis oculi (93+/-8%) (P < 0.01). Clinical duration (25%T1) was shorter at the corrugator supercilii (12+/-7 min) than at the adductor pollicis (25+/-4 min) and orbicularis oculi (24+/-10 min) (P < 0.01). After 0.6 mg/kg, maximum blockade was similar at the corrugator supercilii (88+/-8%) and the laryngeal adductor muscles (89+/-11%). Clinical duration at the corrugator supercilii and the laryngeal adductors was 17+/-7 and 17+/-10 min, respectively.

Conclusions

Muscles around the eye vary in their response to rocuronium. The response of the superciliary arch (corrugator supercilii) reflects blockade of laryngeal adductor muscles. However, the eyelid (orbicularis oculi) and thumb (adductor pollicis) have similar sensitivities.
Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation
Authors: Hambraeus-Jonzon Kristina , Chen Luni , Fredén Filip , Wiklund Peter , Hedenstierna Göran
Published: November 2003

Background

Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect.

Methods

Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO.

Results

Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions.

Conclusions

Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.
The γ Subunit Determines Whether Anesthetic-induced Leftward Shift Is Altered by a Mutation at α1S270 in α1β2γ2LGABAAReceptors
Authors: Scheller Michaela , Forman Stuart A.
Published: November 2003

Background

A major action of volatile anesthetics is enhancement of gamma-aminobutyric acid receptor type A (GABA(A)R) currents. In recombinant GABA(A)Rs consisting of several subunit mixtures, mutating the alpha1 subunit serine at position 270 to isoleucine [alpha1(S270I)] was reported to eliminate anesthetic-induced enhancement at low GABA concentrations. In the absence of studies at high GABA concentrations, it remains unclear whether alpha1(S270I) affects enhancement versus inhibition by volatile anesthetics. Furthermore, the majority of GABA(A)Rs in mammalian brain are thought to consist of alpha1, beta2, and gamma2 subunits, and the alpha1(S270I) mutation has not been studied in the context of this combination.

Methods

Recombinant GABA(A)Rs composed of alpha1beta2 or alpha1beta2gamma2L subunit mixtures were studied electrophysiologically in whole Xenopus oocytes in the voltage clamp configuration. Currents elicited by GABA (0.03 microM to 1 mM) were measured in the absence and presence of isoflurane or halothane. Anesthetic effects on GABA concentration responses were evaluated for individual oocytes.

Results

In wild-type alpha1beta2gamma2L GABA(A), anesthetics at approximately 2 minimum alveolar concentration (MAC) shifted GABA concentration response curves to the left approximately threefold, decreased the Hill coefficient, and enhanced currents at all GABA concentrations. The alpha1(S270I) mutation itself rendered the GABA(A)R more sensitive to GABA and reduced the Hill coefficient. At low GABA concentrations (EC5), anesthetic enhancement of peak current was much smaller in alpha1(S270I)beta2gamma2L versus wild-type channels. Paradoxically, the leftward shift of the whole GABA concentration-response relation by anesthetics was the same in both mutant and wild-type channels. At high GABA concentrations, volatile anesthetics reduced currents in alpha1(S270I)beta2gammaL GABA(A)Rs. In parallel studies on alpha1beta2 (gamma-less) GABA(A)Rs, anesthetic-induced leftward shifts in wild-type receptors were more than eightfold at 2 MAC, and the alpha1(S270I) mutation nearly eliminated anesthetic-induced leftward shift.

Conclusions

The results support a role for alpha1S270 in alpha1beta2gamma2L GABA(A)R gating and sensitivity to inhibition by volatile anesthetics. The alpha1S270 locus also modulates anesthetic enhancement in alpha1beta2 GABA(A)R. The presence of the gamma2L subunit reduces anesthetic-induced left shift of wild-type GABA(A)R and nullifies the impact of the alpha1(S2701) mutation on anesthetic modulation. Thus, the gamma2L subunit plays a significant role in GABA(A)R modulation by volatile anesthetic compounds.
Enflurane Actions on Spinal Cords from Mice That Lack the β3Subunit of the GABAAReceptor
Authors: E. Wong Shirley M. , Cheng Gong , Homanics Gregg E. , Kendig Joan J.
Published: November 2003

Background

Gamma-aminobutyric acid type A (GABA(A)) receptors are considered important in mediating anesthetic actions. Mice lacking the beta3 subunit of this receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC) than wild types (+/+). MAC is predominantly determined in spinal cord.

Methods

The authors measured three population-evoked responses in whole spinal cords, namely, the excitatory postsynaptic potential (pEPSP), the slow ventral root potential (sVRP), and the dorsal root potential. Synaptic and glutamate-evoked currents from motor neurons in spinal cord slices were also measured.

Results

Sensitivity of evoked responses to enflurane did not differ between +/+ and -/- cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05) attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate-evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords, but the interactions between strychnine and enflurane did not differ between -/- and +/+ cords.

Conclusions

Similar enflurane sensitivity in spinal cords from -/- and +/+ mice was coupled with a decreased role for GABA(A) receptors in mediating the actions of enflurane in the former. This finding implies that other anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor-mediated inhibition was found in -/- cords, but the glycine receptor does not appear to be a substitute anesthetic target. This mutation thus led to a quantitative change in the molecular basis for anesthetic depression of spinal neurotransmission in a fashion not predicted by the mutation itself. The results argue against an immutable dominant role for GABA(A) receptors in mediating spinal contributions to MAC.
Characterization of Thioether Compounds Formed from Alkaline Degradation Products of Enflurane
Authors: Orhan Hilmi , E. Vermeulen Nico P. , Sahin Gonul , M. Commandeur Jan N.
Published: November 2003

Background

Renal toxicity has occasionally been observed after enflurane anesthesia. Although originally attributed to its oxidative metabolism to inorganic fluoride, serum levels of inorganic fluoride appear to be small to explain these renal effects. Formation of potentially nephrotoxic halogenated alkenes during alkaline degradation in carbon dioxide absorbers and subsequent bioactivation via the glutathione conjugation pathway may be considered as an alternative mechanism for renal toxicity. The aim of this study was to characterize the thioethers formed chemically and biosynthetically.

Methods

Alkaline degradation of enflurane was achieved by stirring with pulverized potassium hydroxide. Volatile degradation products were analyzed by 19F nuclear magnetic resonance (NMR) analysis of head space gasses trapped in dimethyl sulfoxide (DMSO). Thioethers were generated chemically by trapping head space gasses in DMSO containing N-acetyl-L-cysteine or 2-mercaptoacetic acid as model thiol compounds. Glutathione conjugates were generated biosynthetically by passing head space through rat liver fractions in presence of glutathione. Products formed were analyzed by gas chromatography-mass spectroscopy and 19F-NMR.

Results

Direct analysis of head space gasses showed formation of 1-chloro-1,2-difluorovinyl difluoromethyl ether and two unidentified fluorine-containing products as alkaline degradation products of enflurane. When trapped in DMSO-N-acetyl-L-cysteine-triethylamine, N-acetyl-S-(2-chloro-1,2-difluoro-1-(difluoromethoxy)ethyl)-L-cysteine was identified as the major product. Another N-acetyl-L-cysteine S-conjugate formed was N-acetyl-S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine, a potent nephrotoxin in rats. 19F-NMR analysis of glutathione conjugates formed after incubation with rat liver fractions resulted in formation of corresponding S-conjugates.

Conclusions

The current study demonstrates that alkaline degradation products of enflurane can be conjugated to thiol compounds, forming S-conjugates that could theoretically contribute to adverse renal effects observed occasionally with enflurane anesthesia. The N-acetyl-L-cysteine S-conjugates identified may be biomarkers to assess exposure of humans to alkaline degradation products of enflurane.
Roles of Carbon Monoxide in Leukocyte and Platelet Dynamics in Rat Mesentery during Sevoflurane Anesthesia
Authors: Morisaki Hiroshi , Katayama Tomihiro , Kotake Yoshifumi , Ito Masaharu , Tamatani Takuya , Sakamoto Shinji , Ishimura Yuzuru , Takeda Junzo , Suematsu Makoto
Published: November 2003

Background

Heme oxygenase 1 (HO-1), induced by a variety of stressors, provides endogenous carbon monoxide (CO) and bilirubin, both of which play consequential roles in organs. The current study aimed to examine whether induction of HO-1 and its by-products modulated endothelial interaction with circulating leukocytes and platelets evoked by sevoflurane anesthesia in vivo.

Methods

Rats, pretreated with or without hemin, were anesthetized with sevoflurane in 100% O2, and lungs were mechanically ventilated. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized during sevoflurane anesthesia at 1,000 frames/s using intravital ultrahigh-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on leukocyte and platelet behavior, these studies were repeated with superfusion of either CO, bilirubin, or Nomega-nitro-L-arginine methyl ester (L-NAME).

Results

As reported previously, the elevation of sevoflurane concentration evoked adhesive responses of leukocytes, concurrent with platelet margination and rolling. Pretreatment with hemin, a HO-1 inducer, prevented such sevoflurane-elicited changes in the microvessels. These changes were restored by zinc protoporphyrin IX, a HO inhibitor, and repressed by CO but not by bilirubin. During sevoflurane anesthesia, however, nitric oxide suppression by L-NAME deteriorated microvascular flows irrespective of the presence or absence of the HO-1 induction.

Conclusions

These results indicate that endogenous CO via HO-1 induction attenuates sevoflurane-induced microvascular endothelial interactions with leukocytes and platelets, although local nitric oxide levels appear to dominate microvascular flow in situ.
Effects of Halothane on Sarcoplasmic Reticulum Calcium Release Channels in Porcine Airway Smooth Muscle Cells
Authors: Pabelick Christina M. , Prakash Yedatore S. , Kannan Mathur S. , Warner David O. , Sieck Gary C.
Published: November 2003

Background

Volatile anesthetics relax airway smooth muscle (ASM) by altering intracellular Ca2+ concentration ([Ca2+]i). The authors hypothesized that relaxation is produced by decreasing sarcoplasmic reticulum Ca2+ content via increased Ca2+ "leak" through both inositol trisphosphate (IP3) and ryanodine receptor channels.

Methods

Enzymatically dissociated porcine ASM cells were exposed to acetylcholine in the presence or absence of 2 minimum alveolar concentration (MAC) halothane, and IP3 levels were measured using radioimmunoreceptor assay. Other cells were loaded with the Ca2+ indicator fluo-3 and imaged using real-time confocal microscopy.

Results

Halothane increased IP3 concentrations in the presence and absence of acetylcholine. Inhibition of phospholipase C blunted the IP3 response to halothane. Exposure to 2 MAC halothane induced a transient [Ca2+]i response, suggesting depletion of sarcoplasmic reticulum Ca2+. Exposure to 20 microM Xestospongin D, a cell-permeant IP3 receptor antagonist, resulted in a 45+/-13% decrease in the [Ca2+]i response to halothane compared with halothane exposure alone. In permeabilized cells, Xestospongin D or 0.5 mg/ml heparin decreased the [Ca2+]i response to halothane by 65+/-13% and 68+/-22%, respectively, compared with halothane alone. In both intact and permeabilized cells, 20 microM ryanodine blunted the [Ca2+]i response to halothane by 32+/-13% and 39+/-21%, respectively, compared with halothane alone. Simultaneous exposure to Xestospongin D and ryanodine completely inhibited the [Ca2+]i response to halothane.

Conclusions

The authors conclude that halothane reduces sarcoplasmic reticulum Ca2+ content in ASM cells via increased Ca2+ leak through both IP3 receptor and ryanodine receptor channels. Effects on IP3 receptor channels are both direct and indirect via elevation of IP3 levels.
A Double-blind, Randomized Comparison of IV Lorazepam versus Midazolam for Sedation of ICU Patients via a Pharmacologic Model
Authors: Barr Juliana , Zomorodi Katayoun , Bertaccini Edward J. , Shafer Steven L. , Geller Eran
Published: November 2003

Background

Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients.

Methods

With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling.

Results

A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively.

Conclusions

The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.
Fiberoptic Orotracheal Intubation on Anesthetized Patients
Authors: Naik Viren N. , Matsumoto Edward D. , Houston Patricia L. , Hamstra Stanley J. , Yeung Raymond Y.-M. , Mallon Joseph S. , Martire Terry M.
Published: November 2003

Background

With increasing pressure to use operating room time efficiently, opportunities for residents to learn fiberoptic orotracheal intubation in the operating room have declined. The purpose of this study was to determine whether fiberoptic orotracheal intubation skills learned outside the operating room on a simple model could be transferred into the clinical setting.

Methods

First-year anesthesiology residents and first- and second-year internal medicine residents were recruited. Subjects were randomized to a didactic-teaching-only group (n = 12) or a model-training group (n = 12). The didactic-teaching group received a detailed lecture from an expert bronchoscopist. The model-training group was guided, by experts, through tasks performed on a simple model designed to refine fiberoptic manipulation skills. After the training session, subjects performed a fiberoptic orotracheal intubation on healthy, consenting, anesthetized, paralyzed female patients undergoing elective surgery with predicted "easy" laryngoscopic intubations. Two blinded anesthesiologists evaluated each subject.

Results

After the training session, the model group significantly outperformed the didactic group in the operating room when evaluated with a global rating scale (P < 0.01)and checklist (P0.05). Model-trained subjects completed the fiberoptic orotracheal intubation significantly faster than didactic-trained subjects (P < 0.01). Model-trained subjects were also more successful at achieving tracheal intubation than the didactic group (P < 0.005).

Conclusion

Fiberoptic orotracheal intubation skills training on a simple model is more effective than conventional didactic instruction for transfer to the clinical setting. Incorporating an extraoperative model into the training of fiberoptic orotracheal intubation may greatly reduce the time and pressures that accompany teaching this skill in the operating room.
Effects of Desflurane and Sevoflurane on Length-dependent Regulation of Myocardial Function in Coronary Surgery Patients
Authors: De Hert Stefan G. , Van der Linden Philippe J. , ten Broecke Pieter W. , Vermeylen Kris T. , Rodrigus Inez E. , Stockman Bernard A.
Published: November 2003

Background

Desflurane and sevoflurane have negative inotropic effects. The current study investigated whether these effects resulted in an altered left ventricular response to increased cardiac load and affected length-dependent regulation of myocardial function. Length-dependent regulation of myocardial function refers to the ability of the heart to improve its performance when preload is increased.

Methods

A high-fidelity pressure catheter was positioned in the left ventricle and left atrium in 20 coronary surgery patients with a preoperative ejection fraction greater than 40%. Studies were performed before the initiation of cardiopulmonary bypass. Left ventricular response to increased cardiac load, obtained by leg elevation, was assessed during control conditions and during increasing concentrations of desflurane (2, 4, and 6% end tidal; n = 10) or sevoflurane (1, 2, and 3% end tidal; n = 10). Effects on contraction were evaluated by analysis of changes in maximal rate of pressure development. Effects on relaxation were assessed by analysis of changes in minimum rate of pressure development and by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant tau of isovolumic relaxation and end-systolic pressure). Peak left atrial-left ventricular pressure gradients were analyzed during early left ventricular filling.

Results

With both desflurane and sevoflurane, maximal and minimum rates of pressure development decreased while tau increased. Peak left atrial-left ventricular pressure gradients remained unchanged. The hemodynamic effects of leg elevation were similar at the different concentrations. Changes in parameters of contraction and relaxation during leg elevation were coupled and were not altered by desflurane or sevoflurane.

Conclusions

Despite their negative inotropic and lusitropic effects, neither desflurane nor sevoflurane adversely affect length-dependent regulation of left ventricular function. In the conditions of our study, the ability of the left ventricular to respond to increased cardiac load is not altered by the use of desflurane or sevoflurane.