bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Intubating LMA-Fastrach™ in 254 Patients with Difficult-to-manage Airways
Authors: Ferson David Z. , Rosenblatt William H. , Johansen Mary J. , Osborn Irene , Ovassapian Andranik
Published: November 2003

Background

The laryngeal mask airway (LMA; LMA North America, Inc., San Diego, CA) has a well-established role in the emergency and elective treatment of patients with difficult-to-manage airways (DA). In this study, the authors report their clinical experience with the intubating LMA (LMA-Fastrach; LMA North America, Inc., San Diego, CA) in 254 patients with different types of DA.

Methods

The authors reviewed the anesthetic and medical records of patients with DA in whom the LMA-Fastrach was used electively or emergently at four institutions from October 1997 through October 2000. In each case, the number of insertion and intubation attempts was recorded. Success rates for blind and fiber optically guided intubation through the LMA-Fastrach were calculated, up to a maximum of five attempts per patient.

Results

The LMA-Fastrach was used in 257 procedures performed in 254 patients with DA, including patients with Cormack-Lehane grade 4 views; patients with immobilized cervical spines; patients with airways distorted by tumors, surgery, or radiation therapy; and patients wearing stereotactic frames. Insertion of the LMA-Fastrach was accomplished in three attempts or fewer in all patients. The overall success rates for blind and fiber optically guided intubations through the LMA-Fastrach were 96.5% and 100.0%, respectively.

Conclusions

The LMA-Fastrach was used successfully in a high percentage of patients who presented with a variety of DA. The clinical experience presented herein indicates that this device may be particularly useful in the emergency and elective treatment of patients in whom intubation with a rigid laryngoscope has failed and in the treatment of patients with immobilized cervical spines.
Interaction of Protamine with α- and β-Adrenoceptor Stimulations in Rat Myocardium
Authors: David Jean-Stéphane , Vivien Benoît , Lecarpentier Yves , Coriat Pierre , Riou Bruno
Published: November 2003

Background

Protamine alters the inotropic responses to beta-adrenoceptor stimulation, but its mechanism of action is not well-understood. Moreover, its interaction with alpha-adrenoceptor stimulation and the lusitropic (relaxation) response to beta-adrenoceptor stimulation remain unknown.

Methods

The effects of protamine (10 or 100 microg/ml) on the responses induced by phenylephrine and isoproterenol were studied in rat left ventricular papillary muscles. Inotropic and lusitropic effects were studied under low and high loads. The authors also studied the interaction of protamine with forskolin (50 microm) and dibutyryl 3',5'-cAMP (0.5 mm). Data are mean percentage of baseline active force +/- SD.

Results

In control groups, phenylephrine (135 +/- 17%, P < 0.05) and isoproterenol (185 +/- 44%, P < 0.05) induced a positive inotropic effect. Isoproterenol induced positive lusitropic effects under low and high loads. Protamine abolished the inotropic responses to alpha- (102 +/- 23%, not significant) and beta-adrenoceptor stimulations (99 +/- 17%, not significant) but did not modify the lusitropic responses to isoproterenol. Protamine abolished the inotropic responses to forskolin (89 +/- 6 vs. 154 +/- 20%, P < 0.05) and markedly decreased that of dibutyryl 3',5'-cAMP (132 +/- 31 vs. 167 +/- 30%, P < 0.05) but did not modify their lusitropic responses.

Conclusions

Protamine abolished the inotropic responses to alpha- and beta-adrenoceptor stimulations but preserved the lusitropic responses to beta-adrenoceptor stimulation. Although protamine may act at several sites on the adrenoceptor stimulation cascade, one of its main sites of action is situated downstream from cAMP-mediated phosphorylation.
Differential Sensitivity of Abdominal Muscles and the Diaphragm to Mivacurium
Authors: Kirov Krassen , Motamed Cyrus , Dhonneur Gilles
Published: November 2003

Background

Respiratory muscles are considered to be more resistant to muscle relaxants as compared with peripheral muscles. However, the relative sensitivity of respiratory muscles participating to the pump function has not been compared. We used electromyography to compare pharmacodynamic parameters of the diaphragm and abdominal muscles after mivacurium.

Methods

Forty adults undergoing elective surgery were randomly allocated in five dosing groups of mivacurium (50, 100, 150, 200, and 250 microg/kg). Patients anesthetized with propofol and fentanyl underwent intubation without relaxants. Anesthesia was maintained with nitrous oxide and propofol. The right phrenic nerve, the left 10th intercostal nerve, and the ulnar nerve were stimulated. Electromyography of the diaphragm and abdominal muscles was recorded from surface electrodes. Mechanomyography was used to measure adductor pollicis evoked contraction. After a 5-min stable recording period, patients received a single intravenous bolus (20 s) dose of mivacurium. By using log dose-probit effect regression analysis, dose-response curves were constructed. Effective doses and 95% confidence intervals were derived for the diaphragm and abdominal muscles and were compared.

Results

The dose-response regression line of abdominal muscles differed from that of the diaphragm. Calculated ED50 and ED90 were higher for the diaphragm than for the abdominal muscles (104 [82-127] and 196 [177-213] microg/kg, and 67 [51-82] and 161 [143-181] microg/kg, respectively). The onset of block was faster and recovery of control responses were shorter at the diaphragm than at the abdominal muscles.

Conclusion

Diaphragm and abdominal muscles have differential sensitivity to mivacurium. The diaphragm is more resistant to mivacurium than abdominal muscles are.
The Effect of Prone Positioning on Intraocular Pressure in Anesthetized Patients
Authors: Cheng Mary Ann , Todorov Alexandre , Tempelhoff René , McHugh Tom , Crowder C. Michael , Lauryssen Carl
Published: November 2003

Background

Ocular perfusion pressure is commonly defined as mean arterial pressure minus intraocular pressure (IOP). Changes in mean arterial pressure or IOP can affect ocular perfusion pressure. IOP has not been studied in this context in the prone anesthetized patient.

Methods

After institutional human studies committee approval and informed consent, 20 patients (American Society of Anesthesiologists physical status I-III) without eye disease who were scheduled for spine surgery in the prone position were enrolled. IOP was measured with a Tono-pen XL handheld tonometer at five time points: awake supine (baseline), anesthetized (supine 1), anesthetized prone (prone 1), anesthetized prone at conclusion of case (prone 2), and anesthetized supine before wake-up (supine 2). Anesthetic protocol was standardized. The head was positioned with a pinned head-holder. Data were analyzed with repeated-measures analysis of variance and paired t test.

Results

Supine 1 IOP (13 +/- 1 mmHg) decreased from baseline (19 +/- 1 mmHg) (P < 0.05). Prone 1 IOP (27 +/- 2 mmHg) increased in comparison with baseline (P < 0.05) and supine 1 (P < 0.05). Prone 2 IOP (40 +/- 2 mmHg) was measured after 320 +/- 107 min in the prone position and was significantly increased in comparison with all previous measurements (P < 0.05). Supine 2 IOP (31 +/- 2 mmHg) decreased in comparison with prone 2 IOP (P < 0.05) but was relatively elevated in comparison with supine 1 and baseline (P < 0.05). Hemodynamic and ventilatory parameters remained unchanged during the prone period.

Conclusions

Prone positioning increases IOP during anesthesia. Ocular perfusion pressure could therefore decrease, despite maintenance of normotension.
The Visual Analog Scale for Pain
Authors: Bodian Carol A. , Freedman Gordon , Hossain Sabera , Eisenkraft James B. , Beilin Yaakov
Published: November 2003

Background

The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established. This study defines changes in dosing of intravenous patient-controlled analgesia as a clinically relevant outcome and compares it with VAS measures of postoperative pain.

Methods

Visual analog scale measurements were obtained from 150 patients on the morning after intraabdominal surgery. On the same afternoon, 50 of the patients provided a VAS score on the same form used in the morning, 50 on a new form, and 50 were not asked for a second VAS measurement.

Results

Visual analog scale values and changes in value were similar for patients who were given a new VAS form in the afternoon and those who used the form that showed the morning value. The proportions of patients requesting additional analgesia were 4, 43, and 80%, corresponding to afternoon VAS scores of 30 or less, 31-70, and greater than 70, respectively. Change from morning VAS score had no apparent influence on patient-controlled analgesic dosing for patients with afternoon values of 30 or less or greater than 70, but changes in VAS scores of at least 10 did discriminate among patients whose afternoon values were between 31 and 70.

Conclusions

When pain is an outcome measure in research studies, grouping final VAS scores into a small number of categories provides greater clinical relevance for comparisons than using the full spectrum of measured values or changes in value. Seeing an earlier VAS form has no apparent influence on later values.
Brain Expression of Inducible Cyclooxygenase 2 Messenger RNA in Rats Undergoing Cardiopulmonary Bypass
Authors: Hindman Bradley J. , Moore Steven A. , Cutkomp Johann , Smith Tom , Ross-Barta Susan E. , Dexter Franklin , Brian Johnny E.
Published: November 2003

Background

We hypothesized that systemic proinflammatory cytokines or endotoxemia, or both, associated with cardiopulmonary bypass (CPB) would increase expression of inducible cyclooxygenase (COX-2) or inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), or both, in brain.

Methods

Isoflurane-anesthetized Sprague-Dawley rats were randomly selected for CPB (n = 6) or sham surgery (n = 6). All animals underwent tracheotomy and controlled ventilation, arterial and venous pressure monitoring, insertion of a jugular venous outflow catheter, insertion of a subclavian arterial inflow catheter, systemic anticoagulation (500 U/kg heparin) and, except during CPB, servoregulation of pericranial temperature at 37.5 degrees C. Animals selected for CPB underwent 1 h of CPB at 165 ml x kg(-1) x min(-1) (31.8 +/- 0.2 degrees C), whereas animals having sham surgery underwent no intervention during this interval. Thereafter, all animals were given protamine and remained anesthetized for 4 more h. Brain and liver COX-2 and iNOS mRNA expression were determined by a ribonuclease protection assay with ribosomal L32 mRNA as a loading control. Arterial blood was analyzed for interleukin 1beta, interleukin 6, and endotoxin concentrations.

Results

Endotoxin concentrations did not increase above baseline values in either group. At 4 h after the CPB interval, interleukin 6 concentrations were significantly greater in CPB animals (101 +/- 45 pg/ml) versus sham animals (44 +/- 17 pg/ml) (P = 0.025). Brain COX-2 expression was significantly greater in CPB animals (0.36 +/- 0.11) versus shams (0.19 +/- 0.08) (P = 0.013). Brain COX-2 expression correlated with interleukin 6 concentration 4 h after CPB (r = 0.91; P = 5 x 10(-5)). In brain, iNOS mRNA was not detected in any animal. Cardiopulmonary bypass animals had only trace COX-2 and iNOS mRNA induction in liver.

Conclusions

Cardiopulmonary bypass was associated with increased systemic interleukin 6 concentrations and increased brain COX-2 expression.
Ketamine Blockade of Voltage-gated Sodium Channels
Authors: Wagner Larry E. , Gingrich Kevin J. , Kulli John C. , Yang Jay
Published: November 2003

Background

The general anesthetic ketamine is known to be an N-methyl-D-aspartate receptor blocker. Although ketamine also blocks voltage-gated sodium channels in a local anesthetic-like fashion, little information exists on the molecular pharmacology of this interaction. We measured the effects of ketamine on sodium channels.

Methods

Wild-type and mutant (F1579A) recombinant rat skeletal muscle sodium channels were expressed in Xenopus oocytes. The F1579A amino acid substitution site is part of the intrapore local anesthetic receptor. The effect of ketamine was measured in oocytes expressing wild-type or mutant sodium channels using two-electrode voltage clamp.

Results

Ketamine blocked sodium channels in a local anesthetic-like fashion, exhibiting tonic blockade (concentration for half-maximal inhibition [IC50] = 0.8 mm), phasic blockade (IC50 = 2.3 mm), and leftward shift of the steady-state inactivation; the parameters of these actions were strongly modified by alteration of the intrapore local anesthetic binding site (IC50 = 2.1 mm and IC50 = 10.3 mm for tonic and phasic blockade, respectively). Compared with lidocaine, ketamine showed greater tonic inhibition but less phasic blockade.

Conclusions

Ketamine interacts with sodium channels in a local anesthetic-like fashion, including sharing a binding site with commonly used clinical local anesthetics.
Anesthetic Effects on Mitochondrial ATP-sensitive K Channel
Authors: Kohro Shinji , Hogan Quinn H. , Nakae Yuri , Yamakage Michiaki , Bosnjak Zeljko J.
Published: November 2003

Background

Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation.

Methods

Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured.

Results

Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation.

Conclusions

Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.
Inhalation Anesthetics Induce Apoptosis in Normal Peripheral Lymphocytes In Vitro
Authors: Matsuoka Hiroshi , Kurosawa Shin , Horinouchi Takashi , Kato Masato , Hashimoto Yasuhiko
Published: November 2003

Background

The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes induced by inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes.

Methods

Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mm) and after 6, 12, and 24 h of exposure (1.5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 h of exposure (1.5 mm).

Results

The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mm], 9.1 +/- 1.5% [1.0 mm], 12.6 +/- 2.1% [1.5 mm]; isoflurane: 7.5 +/- 1.6% [0.5 mm], 10.5 +/- 1.5% [1.0 mm], 16.3 +/- 2.7% [1.5 mm]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mm. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%).

Conclusions

Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.
Closed-loop Control of Anesthesia Using Bispectral Index
Authors: Absalom Anthony R. , Sutcliffe Nicholas , Kenny Gavin N.
Published: November 2003

Background

The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. A closed-loop anesthesia system was built using BIS as the control variable, a proportional-integral-differential control algorithm, and a propofol target-controlled infusion system as the control actuator. Closed-loop performance was assessed in 10 adult patients.

Methods

Ten adult patients scheduled to undergo elective hip or knee surgery were enrolled. An epidural cannula was inserted, and 0.5% bupivacaine was used to provide anesthesia to T8 before general anesthesia was induced using the propofol target-controlled infusion system under manual control. After the start of surgery, when anesthesia was clinically adequate, automatic control of anesthesia was commenced using the BIS as the control variable. Adequacy of anesthesia during closed-loop control was assessed clinically and by calculating the median performance error, the median absolute performance error, and the mean offset of the control variable.

Results

The median performance error and the median absolute performance error were 2.2 and 8.0%, respectively. Mean offset of the BIS from the set point was 0.9. Cardiovascular parameters were stable during closed-loop control. Operating conditions were adequate in all patients but one, who began moving after 45 min of stable anesthesia. No patients reported awareness or recall of intraoperative events. In three patients, there was oscillation of the measured BIS around the set point.

Conclusions

The system was able to provide clinically adequate anesthesia in 9 of 10 patients. Further studies are required to determine whether control performance can be improved by alterations to the gain factors or by using an effect site-targeted, target-controlled infusion propofol system.
Alveolar and Serum Procalcitonin
Authors: Duflo Frédéric , Debon Richard , Monneret Guillaume , Bienvenu Jacques , Chassard Dominique , Allaouchiche Bernard
Published: November 2003

Background

The potential role of serum and alveolar procalcitonin as early markers of ventilator-associated pneumonia (VAP) and its prognostic value were investigated.

Methods

Ninety-six patients with a strong suspicion of VAP were prospectively enrolled. VAP diagnosis was based on a positive quantitative culture obtained via a mini-bronchoalveolar lavage of 103 colony-forming units/ml or more. Blood and alveolar samples were collected for procalcitonin measurement and analyzed for diagnostic and prognostic evaluation on days 0, 3, and 6. Sensitivity, specificity, positive likelihood ratio, and receiver-operating characteristic curves were analyzed to define ideal cutoff values and approach the decision analysis.

Results

Serum procalcitonin was significantly increased in the VAP group (n = 44) compared with the non-VAP group (n = 52): 11.5 ng/ml (95% confidence interval, 5.9-17.0) versus 1.5 ng/ml (1.1-1.9). A serum procalcitonin concentration greater than 3.9 ng/ml (best cutoff value) was considered positive for the VAP diagnosis (sensitivity, 41%; specificity, 100%). Serum procalcitonin was significantly increased in the non-survivors compared with the survivors for the VAP group: 16.5 ng/ml (95% confidence interval, 8.1-24.9) versus 2.9 ng/ml (1.2-4.7). The best cutoff value for serum procalcitonin of the nonsurvivors in the VAP group was 2.6 ng/ml (sensitivity, 74%; specificity, 75%; positive likelihood ratio, 2.96). Regarding VAP diagnosis and prognosis, no significant differences were found for alveolar procalcitonin in all groups.

Conclusions

Serum but not alveolar procalcitonin seems to be a helpful parameter in the early VAP diagnosis and an appropriate marker for predicting mortality.
Systemic Free Radical Activation Is a Major Event Involved In Myocardial Oxidative Stress Related to Cardiopulmonary Bypass
Authors: Clermont Gaëlle , Vergely Catherine , Jazayeri Saëd , Lahet Jean-Jacques , Goudeau Jean-Jacques , Lecour Sandrine , David Michel , Rochette Luc , Girard Claude
Published: November 2003

Background

Cardiopulmonary bypass (CPB) can induce deleterious effects that could be triggered in part by radical oxygen species; however, their involvement in the course of surgery has been elusive. The aim of this study was to evaluate the time course and origin of radical oxygen species release, myocardial or not, in patients undergoing coronary artery surgery involving CPB.

Methods

Blood samples were taken from periphery and coronary sinus of patients during CPB, and oxidative stress was evaluated by direct and indirect approaches. Direct detection of alkyl and alkoxyl radicals was assessed by electron spin resonance spectroscopy associated with the spin-trapping technique using alpha-phenyl-N-tert-butylnitrone.

Results

The authors showed that the spin adduct concentration was not influenced by anesthesia and pre-CPB surgery. A rapid systemic increase of plasma spin adduct concentration occurred after starting CPB, and it stayed at a high concentration until the end of CPB. At the beginning of reperfusion period, radical oxygen species release was accelerated in the coronary sinus; however, it was not significant. A positive correlation was found between alpha-phenyl-N-tert-butylnitrone adduct concentrations and (1) the duration of CPB and (2) concentration of postoperative creatine phosphokinase of muscle band (CPK MB). Plasma vitamin E and C, ascorbyl radical, uric acid, thiol, plasma antioxidant status, and thiobarbituric acid reacting substances were also measured but did not give relevant indications, except for uric acid, which seemed to be consumed by the heart during reperfusion.

Conclusion

The results indicate that a systemic production of free radicals occurs during CPB that may overwhelm the production related to reperfusion of the ischemic heart. This systemic oxidative stress is likely to participate in secondary myocardial damage.
Effects of Parecoxib, a Parenteral COX-2-specific Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Propofol
Authors: Ibrahim Andra , Park Sang , Feldman Jennifer , Karim Aziz , Kharasch Evan D.
Published: November 2003

Background

Parecoxib, a cyclooxygenase-2-specific inhibitor with intended perioperative analgesic and antiinflammatory use, is a parenterally administered inactive prodrug undergoing rapid hydrolysis in vivo to the active cyclooxygenase-2 inhibitor valdecoxib. Both parecoxib and valdecoxib inhibit human cytochrome P450 2C9 (CYP2C9) activity in vitro. Thus, a potential exists for in vivo interactions with other CYP2C9 substrates, including propofol. This investigation determined the influence of parecoxib on the pharmacokinetics and pharmacodynamics of bolus dose propofol in human volunteers.

Methods

This was a randomized, balanced crossover, placebo-controlled, double-blind, clinical investigation. Twelve healthy 21- to 37-yr-old subjects were studied after providing institutional review board-approved written informed consent. Each subject received a 2-mg/kg intravenous propofol bolus 1 h after placebo (control) or 40 mg intravenous parecoxib on two occasions. Venous concentrations of propofol, parecoxib, and parecoxib metabolites were determined by mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental analysis. Pharmacodynamic measurements included clinical endpoints, cognitive function (memory, Digit-Symbol Substitution Tests), subjective self-assessment of recovery (Visual Analog Scale) performed at baseline, 15, 30, 60 min after propofol, and sedation depth measured by Bispectral Index.

Results

Propofol plasma concentrations were similar between placebo- and parecoxib-treated subjects. No significant differences were found in pharmacokinetic parameters (Cmax, clearance, elimination half-life, volume of distribution) or pharmacodynamic parameters (clinical endpoints [times to: loss of consciousness, apnea, return of response to voice], Bispectral Index scores, Digit-Symbol Substitution Test scores, memory, Visual Analog Scale scores, propofol EC(50)).

Conclusions

Single-bolus parecoxib, in doses to be used perioperatively, does not alter the disposition or the magnitude or time course of clinical effects of bolus propofol. Effects on a propofol infusion were not evaluated.
Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2Rebreathing
Authors: Tachibana Kazuya , Imanaka Hideaki , Miyano Hiroshi , Takeuchi Muneyuki , Kumon Keiji , Nishimura Masaji
Published: November 2003

Background

Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO(2)) rebreathing. Because this technique uses CO(2) rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement.

Methods

The authors enrolled 25 pharmacologically paralyzed adult post-cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (V(T)) of 12 ml/kg; (2) volume-controlled ventilation with V(T) of 6 ml/kg; (3) pressure-controlled ventilation with V(T) of 12 ml/kg; (4) pressure-controlled ventilation with V(T) of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with V(T) set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO(2) rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis.

Results

When VT was set at 12 ml/kg, cardiac output with the CO(2) rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, -1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO(2) rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, -1.66 l/min; limits of agreement, -3.90 to +0.58 l/min). When the loop was fully retracted, the CO(2) rebreathing technique overestimated cardiac output.

Conclusions

Although cardiac output was underreported at small VT values, cardiac output measured by the CO(2) rebreathing technique correlates fairly with that measured by the thermodilution method.
Amitriptyline for Prolonged Cutaneous Analgesia in the Rat
Authors: Khan Mohammed A. , Gerner Peter , Kuo Wang Ging
Published: November 2003

Background

Amitriptyline has been reported to be a more potent local anesthetic than bupivacaine. In keeping with the objective of identifying drugs for prolonged cutaneous analgesia, the authors compared the cutaneous analgesic effectiveness of amitriptyline and bupivacaine in rats.

Methods

Rats were subcutaneously injected on shaved dorsal skin. The skin wheal raised after injection of 0.6 ml of various concentrations of either amitriptyline or bupivacaine with and without epinephrine (1:200,000) was marked. Inhibition of the cutaneous trunci muscle reflex was evaluated quantitatively by the fraction of times a total of six pinpricks applied to the marked area failed to elicit a nocifensive motor response compared with control responses. No responses out of six pinpricks was defined as 100% maximum possible effect.

Results

Complete recovery from the cutaneous analgesia elicited by 0.05% and 0.5 amitriptyline versus 0.05 and 0.5% bupivacaine occurred in 9.9 +/- 0.2 and 19.3 +/- 0.4 h versus 2.2 +/- 0.1 and 16.1 +/- 0.2 h, respectively (mean +/- SE). Addition of epinephrine increased this duration to 14.1 +/- 0.1 and 21.4 +/- 0.2 h versus 3.2 +/- 0.1 and 17.0 +/- 0.3 h, respectively. Complete nociceptive blockade after coinjection of 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine lasted 24 +/- 0.5 h, and complete recovery from this block took 33 +/- 0.5 h. Areas under the percent maximum possible effect versus time curve were 1,770 +/- 24 and 1,471 +/- 50% h for 0.5% amitriptyline and bupivacaine with epinephrine, respectively, whereas this value was 2,836 +/- 62% h for the coinjected 0.25% amitriptyline, 0.25% bupivacaine, and epinephrine admixture.

Conclusion

Amitriptyline is a longer-acting local anesthetic compared with bupivacaine for cutaneous infiltration. Its analgesic effectiveness is significantly enhanced by epinephrine. Coinjection of amitriptyline and bupivacaine with epinephrine enhances the analgesic duration of both drugs.
Sevoflurane before or after Ischemia Improves Contractile and Metabolic Function while Reducing Myoplasmic Ca2+Loading in Intact Hearts
Authors: Varadarajan Srinivasan G. , An Jianzhong , Novalija Enis , Stowe David F.
Published: November 2003

Background

Ca(2+) loading occurs during myocardial reperfusion injury. Volatile anesthetics can reduce reperfusion injury. The authors tested whether sevoflurane administered before index ischemia in isolated hearts reduces myoplasmic diastolic and systolic [Ca(2+)] and improves function more so than when sevoflurane is administered on reperfusion.

Methods

Four groups of guinea pig hearts were perfused with crystalloid solution (55 mmHg, 37 degrees C): (1) no treatment before 30 min global ischemia and 60 min reperfusion (CON); (2) 3.5 vol% sevoflurane administered for 10 min before ischemia (SBI); (3) 3.5 vol% sevoflurane administered for 10 min after ischemia (SAI); and (4) 3.5 vol% sevoflurane administered for 10 min before and after ischemia (SBAI). Phasic myoplasmic diastolic and systolic [Ca(2+)] were measured in the left ventricular free wall with the fluorescence probe indo-1.

Results

Ischemia increased diastolic [Ca(2+)] and diastolic left ventricular pressure (LVP). In CON hearts, initial reperfusion greatly increased diastolic [Ca2+] and systolic [Ca(2+)] and reduced contractility (systolic-diastolic LVP, dLVP/dt(max)), relaxation (diastolic LVP, dLVP/dt(min)), myocardial oxygen consumption (MvO(2)), and cardiac efficiency. SBI, SAI, and SBAI each reduced ventricular fibrillation, attenuated increases in systolic and systolic-diastolic [Ca(2+)], improved contractile and relaxation indices, and increased coronary flow, percent oxygen extraction, MvO(2), and cardiac efficiency during 60 min reperfusion compared with CON. SBI was more protective than SAI, and SBAI was generally more protective than SAI.

Conclusions

Sevoflurane improves postischemic cardiac function while reducing Ca(2+) loading when it is administered before or after ischemia, but protection is better when it is administered before ischemia. Reduced Ca(2+) loading on reperfusion is likely a result of the anesthetic protective effect.
Effects of α2-Adrenoceptor Agonists on Perinatal Excitotoxic Brain Injury
Authors: Laudenbach Vincent , Mantz Jean , Lagercrantz Hugo , Desmonts Jean-Marie , Evrard Philippe , Gressens Pierre
Published: November 2003

Background

A growing number of children have severe neurologic impairment related to very premature birth. Experimental data suggest that overstimulation of cerebral N-methyl-d-aspartate (NMDA) receptors caused by excessive glutamate release may be involved in the genesis of perinatal hypoxic-ischemic brain injury. alpha(2)-Adrenoceptor agonists are protective in models of brain ischemia in adults. The authors sought to determine whether they prevent perinatal excitotoxic neuronal damage.

Methods

Five-day-old mice were allocated at random to clonidine (4-400 microg/kg), dexmedetomidine (1-30 microg/kg), or saline injected intraperitoneally before an intracerebral stereotactic injection of the NMDA receptor agonist ibotenate; cortical and white matter lesions were quantified 5 days later by histopathologic examination. Cortical neuron cultures exposed to 300 microm NMDA were used to evaluate the effects of clonidine or dexmedetomidine on neuronal death assessed by counting the number of pycnotic nuclei after fluorescent chromatin staining.

Results

In vivo, both clonidine and dexmedetomidine induced significant concentration-dependent reductions in the size of ibotenate-induced lesions in the cortex and white matter. In vitro, the number of neurons damaged by NMDA exposure was significantly decreased by both dexmedetomidine (-28 +/- 12% at 10 microm; P < 0.01) and clonidine (-37 +/- 19% at 100 microm; P < 0.01) as compared with controls. In both models, the selective alpha2-adrenoceptor antagonist yohimbine abolished the neuroprotective effect of clonidine and dexmedetomidine.

Conclusions

Clonidine and dexmedetomidine are potent neuroprotectors that act by stimulating the alpha(2) adrenoceptors. These results obtained in a murine model of perinatal excitotoxic injury may be relevant to some forms of neonatal brain damage in humans.
Isoflurane Activates PKC and Ca2+-Calmodulin-dependent Protein Kinase II via MAP Kinase Signaling in Cultured Vascular Smooth Muscle Cells
Authors: Zhong Li , Su Judy Y.
Published: November 2003

Background

Protein kinase C (PKC) and Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) have been implicated in isoflurane-increased force in skinned femoral arterial strips. The extracellular signal-regulated kinases (ERK1/2) of mitogen-activated protein kinase have been shown to be target effectors of PKC and CaMKII. This study examined the role of the ERK1/2 signaling pathway in isoflurane activation of PKC and CaMKII using cultured vascular smooth muscle cells.

Methods

Vascular smooth muscle cells were prepared by cell migration from isolated rabbit femoral arterial segments. Growth of passage of vascular smooth muscle cells (80-90% confluence, passage 5-10) was arrested for 48 h before experiments, during which time phorbol 1,3-diaceylester treatment was used to down-regulate PKC. Cells were treated for 30 min with one of the inhibitors of mitogen-activated protein kinase kinase (PD98059), PKC (Go6976 and bisindolylmaleimide), or CaMKII (KN-93 and KN-62) at 10 microm. After administration of isoflurane, vascular smooth muscle cells were frozen rapidly, homogenized, and centrifuged. The homogenates were used for identification of phosphorylated ERK1/2 or for further centrifugation to separate the membrane from the cytosol for identification of PKC isoforms (alpha and epsilon) by Western blotting.

Results

Isoflurane increased ERK1/2 phosphorylation in a dose-dependent manner and reached a plateau at 10 min. PD98059 or down-regulated PKC blocked the increase of phosphorylated ERK1/2 levels by isoflurane, and bisindolylmaleimide, KN-93, or KN-62, but not by Go6976 reduced levels of phosphorylated ERK1/2. The membrane fraction of PKC epsilon but not of PKC alpha was increased by isoflurane.

Conclusions

ERK1/2 signaling is downstream of PKC and CaMKII activated by isoflurane in vascular smooth muscle cells.
Isoflurane Prevents Delayed Cell Death in an Organotypic Slice Culture Model of Cerebral Ischemia
Authors: Sullivan Breandan L. , Leu David , Taylor Donald M. , Fahlman Christian S. , Bickler Philip E.
Published: November 2003

Background

General anesthetics reduce neuronal death caused by focal cerebral ischemia in rodents and by in vitro ischemia in cultured neurons and brain slices. However, in intact animals, the protective effect may enhance neuronal survival for only several days after an ischemic injury, possibly because anesthetics prevent acute but not delayed cell death. To further understand the mechanisms and limitations of volatile anesthetic neuroprotection, the authors developed a rat hippocampal slice culture model of cerebral ischemia that permits assessment of death and survival of neurons for at least 2 weeks after simulated ischemia.

Methods

Survival of CA1, CA3, and dentate gyrus neurons in cultured hippocampal slices (organotypic slice culture) was examined 2-14 days after 45 min of combined oxygen-glucose deprivation at 37 degrees C (OGD). Delayed cell death was serially measured in each slice by quantifying the binding of propidium iodide to DNA with fluorescence microscopy.

Results

Neuronal death was greatest in the CA1 region, with maximal death occurring 3-5 days after OGD. In CA1, cell death was 80 +/- 18% (mean +/- SD) 3 days after OGD and was 80-100% after 1 week. Death of 70 +/- 16% of CA3 neurons and 48 +/- 28% of dentate gyrus neurons occurred by the third day after OGD. Both isoflurane (1%) and the N-methyl-D-aspartate antagonist MK-801 (10 microm) reduced cell death to levels similar to controls (no OGD) for 14 days after the injury. Isoflurane also reduced cell death in CA1 and CA3 caused by application of 100 but not 500 microm glutamate. Cellular viability (calcein fluorescence) and morphology were preserved in isoflurane-protected neurons.

Conclusions

In an in vitro model of simulated ischemia, 1% isoflurane is of similar potency to 10 microm MK-801 in preventing delayed cell death. Modulation of glutamate excitotoxicity may contribute to the protective mechanism.
Effects of Inspired Hypoxic and Hypercapnic Gas Mixtures on Cerebral Oxygen Saturation in Neonates with Univentricular Heart Defects
Authors: Ramamoorthy Chandra , Tabbutt Sarah , Dean Kurth C. , Steven James M. , Montenegro Lisa M. , Durning Suzanne , Wernovsky Gil , William Gaynor J. , Spray Thomas L. , Nicolson Susan C.
Published: November 2003

Background

Neonates with functional single ventricle often require hypoxic or hypercapnic inspired gas mixtures to reduce pulmonary overcirculation and improve systemic perfusion. Although the impact of these treatments on arterial oxygen saturation has been described, the effects on cerebral oxygenation remain uncertain. This study examined the effect of these treatments on cerebral oxygen saturation and systemic hemodynamics.

Methods

Neonates with single ventricle mechanically ventilated with room air were enrolled in a randomized crossover trial of 17% inspired oxygen or 3% inspired carbon dioxide. Each treatment lasted 10 min, followed by a 10-20-min washout period. Cerebral and arterial oxygen saturation were measured by cerebral and pulse oximetry, respectively. Cerebral oxygen saturation, arterial oxygen saturation, and other physiologic data were continuously recorded.

Results

Three percent inspired carbon dioxide increased cerebral oxygen saturation (56 +/- 13 to 68 +/- 13%; P < 0.01), whereas 17% inspired oxygen had no effect (53 +/- 13 to 53 +/- 14%; P = 0.8). Three percent inspired carbon dioxide increased the mean arterial pressure (45 +/- 8 to 50 +/- 9 mmHg; P < 0.01), whereas 17% inspired oxygen had no effect. And 3% inspired carbon dioxide decreased arterial pH and increased arterial carbon dioxide and oxygen tensions.

Conclusions

Inspired 3% carbon dioxide improved cerebral oxygenation and mean arterial pressure. Treatment with 17% inspired oxygen had no effect on either.
A Multicenter Study Comparing the ProSeal TMand Classic TMLaryngeal Mask Airway in Anesthetized, Nonparalyzed Patients
Authors: Brimacombe Joseph , Keller Christian , Fullekrug Bernd , Agrò Felice , Rosenblatt William , Dierdorf Stephen F. , Garcia de Lucas Elvira , Capdevilla Xavier , Brimacombe Nick
Published: November 2003

Background

The laryngeal mask airway ProSeal (PLMA), a new laryngeal mask device, was compared with the laryngeal mask airway Classic (LMA) with respect to: (1) insertion success rates and times; (2) efficacy of seal; (3) fiberoptically determined anatomic position; (4) orogastric tube insertion success rates and times; (5) total intraoperative complications; and (6) postoperative sore throat in nonparalyzed adult patients undergoing general anesthesia, hypothesizing that these would be different.

Methods

Three hundred eighty-four nonparalyzed anesthetized adult patients (American Society of Anesthesiologists physical status I-II) were randomly allocated to the PLMA or LMA for airway management. In addition, 50% of patients were randomized for orogastric tube placement. Unblinded observers collected intraoperative data, and blinded observers collected postoperative data.

Results

First-attempt insertion success rates (91 vs. 82%, P = 0.015) were higher for the LMA, but after three attempts success rates were similar (LMA, 100%; PLMA, 98%). Less time was required to achieve an effective airway with the LMA (31 +/- 30 vs. 41 +/- 49 s; P = 0.02). The PLMA formed a more effective seal (27 +/- 7 vs. 22 +/- 6 cm H2O; P < 0.0001). Fiberoptically determined anatomic position was better with the LMA (P < 0.0001). Orogastric tube insertion was more successful after two attempts (88 vs. 55%; P < 0.0001) and quicker (22 +/- 18 vs. 38 +/- 56 s) with the PLMA. During maintenance, the PLMA failed twice (leak, stridor) and the LMA failed once (laryngospasm). Total intraoperative complications were similar for both groups. The incidence of postoperative sore throat was similar.

Conclusion

In anesthetized, nonparalyzed patients, the LMA is easier and quicker to insert, but the PLMA forms a better seal and facilitates easier and quicker orogastric tube placement. The incidence of total intraoperative complications and postoperative sore throat are similar.
Efficacy of Clonidine for Prevention of Perioperative Myocardial Ischemia
Authors: Nishina Kahoru , Mikawa Katsuya , Uesugi Takanobu , Obara Hidefumi , Maekawa Munetaka , Kamae Isao , Nishi Nobuo
Published: November 2003

Background

There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard.

Methods

Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval.

Results

Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34-0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups.

Conclusion

The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.
Use of Dynamic Negative Airway Pressure (DNAP) to Assess Sedative-induced Upper Airway Obstruction
Authors: Litman Ronald S. , Hayes Jennifer L. , Basco Matthew G. , Schwartz Alan R. , Bailey Peter L. , Ward Denham S.
Published: November 2003

Background

Traditional methods of assessing ventilatory effects of sedative agents do not measure their propensity to cause upper airway obstruction (UAO). The primary objective of this study was to develop a method, using dynamic negative airway pressure (DNAP), for replicating UAO during deep sedation.

Methods

A state of deep sedation (defined as an Observer Assessment of Alertness and Sedation score of 3 and a bispectral index < 80) was attained in 10 healthy volunteers, aged 19-41, using midazolam. Volunteers breathed through a chamber connected to a regulated source of negative pressure that was gradually adjusted downward to produce UAO based on maximal inspiratory flow. The study consisted of three phases: A control phase while awake, a study phase during midazolam deep sedation, and a recovery phase after flumazenil administration.

Results

During the control phase no subject demonstrated airway obstruction at negative pressures to -30-cm H2O. All subjects exhibited complete UAO during DNAP episodes while sedated. Negative pressures required to cause complete UAO (Pcrit) ranged from -2 to -14 cm H2O. After administration of flumazenil, all subjects attained full consciousness within 5 min and did not demonstrate UAO at negative pressures to -30-cm H2O.

Conclusions

Dynamic Negative Airway Pressure is a useful method for provoking midazolam-induced UAO, and may potentially be used to compare the potential for different sedatives and patient factors to cause UAO. Flumazenil was completely effective in reversing the potential for midazolam to cause UAO.