bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Depth of Anesthesia and Postoperative Respiratory Recovery after Remifentanil-versus Alfentanil-based Total Intravenous Anesthesia in Patients Undergoing Ear–Nose–Throat Surgery
Authors: Wuesten Rainer , Van Aken Hugo , Glass Peter S. A. , Buerkle Hartmut
Published: November 2003

Background

The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics.

Methods

Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 microg/kg; maintenance infusion, 0.25 microg x kg(-1) x min-1) or alfentanil (loading dose, 50 microg/kg; maintenance infusion, 1 microg x kg(-1) x min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 microg x kg(-1) min(-1)). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded.

Results

Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group.

Conclusions

When both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.
Nosocomial Infections and Outcome of Critically Ill Elderly Patients after Surgery
Authors: Stéphan François , Cheffi Ali , Bonnet Francis
Published: November 2003

Background

The relation between older age and nosocomial infection and mortality in the intensive care unit (ICU) is still a controversial issue.

Methods

The authors prospectively studied 406 patients admitted to a surgical ICU, 106 of whom were more than 75 yr old. Information concerning ICU-acquired nosocomial infections, severity of illness, therapeutic activity, and hospital outcome was collected. A Cox proportional hazard analysis was used to evaluate potential risk factors for ICU-acquired nosocomial infections, ICU, and hospital death.

Results

During their ICU stay, 23 elderly patients experienced 40 nosocomial infections, 28 "young" patients (< 60 yr) experienced 54 nosocomial infections, and 52 "intermediate age" patients (60-75 yr) experienced 98 nosocomial infections. Incidence density of nosocomial infections was 4.9% patient days for elderly patients, 4.7% for young patients, and 6.0% for intermediate age patients (no significance). The frequency distribution of the various microorganisms isolated was similar between the three groups. Compared with younger patients, elderly patients had a higher Acute Physiology and Chronic Health Evaluation II score and a higher ICU and hospital mortality rate. Despite a higher level of severity of illness, elderly patients had a reduction of therapeutic activity. However, Cox proportional hazard analysis showed that age more than 75 yr was not a risk factor for ICU-acquired nosocomial infection, ICU, or hospital death.

Conclusions

In patients referred to a surgical ICU after a surgical procedure, age more than 75 yr by itself does not appear to be a significant predictor of ICU-acquired nosocomial infection or mortality rate during the ICU stay. However, it appears that patients more than 60 yr have a higher incidence of nosocomial infection in ICU.
Efficacy of Acute Normovolemic Hemodilution Assessed as a Function of Fraction of Blood Volume Lost
Authors: Weiskopf Richard B.
Published: November 2003

Background

It has been recommended that intraoperative acute normovolemic hemodilution (ANH) be considered for patients expected to experience surgical blood loss of 20% or more of their blood volume. Previous mathematical analyses have not evaluated the potential efficacy of ANH in terms of fraction of blood volume lost. Since decrease of oxygen-carrying capacity is a function of erythrocyte loss relative to blood volume, the purpose of this analysis was to provide an assessment of ANH applicable to all blood volumes and to determine whether this recommendation is appropriate.

Methods

Equations were developed to describe the fractional blood volume loss (blood volume loss/blood volume; VReM/VBld) required to reduce hematocrit below a "trigger" hematocrit with maintenance of isovolemia. This is also the minimum fractional blood volume loss required for initial erythrocyte savings by any conservation technique. Equations were also developed to describe the fractional surgical blood volume loss for which ANH will obviate the need for transfusion of erythrocytes from any source other than those removed by ANH, and the fractional surgical blood volume loss required for ANH to save a defined volume of erythrocytes.

Results

Acute normovolemic hemodilution can extend the allowable fractional surgical blood loss before erythrocyte transfusion is required. The VRem/VBld required to initiate erythrocyte savings is approximately 0.5-0.9. The efficacy of ANH in terms of erythrocytes saved cannot be expressed as a function of the fractional blood volume lost alone. To save 1 unit of erythrocytes requires a fractional surgical blood loss of approximately 0.7-1.2 for the usual surgical patient when the transfusion trigger hematocrit is 0.18-0.21.

Conclusions

This analysis suggests that surgical blood loss should be 0.50 or more for ANH to begin to "save" erythrocytes and 0.70 or more of the patient's blood volume for ANH to save 1 unit erythrocytes, for the usual surgical patient with an initial hematocrit of 0.32-0.36 and a transfusion "trigger" hematocrit (the value at which transfusion is initiated) of 0.18-0.21.
Effect of Inhaled Prostacyclin in Combination with Almitrine on Ventilation–Perfusion Distributions in Experimental Lung Injury
Authors: Dembinski Rolf , Max Martin , López Frank , Kuhlen Ralf , Kurth Roland , Rossaint Rolf
Published: November 2003

Background

Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone.

Methods

Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences.

Results

All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution.

Conclusions

The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.
Technique for Using Video Microscopy and Indicator Dilution for Repeated Measurements of Cardiac Output in Small Animals
Authors: Rivers Richard J. , Beckman Judy B. , Frame Mary D. S.
Published: November 2003

Background

The authors developed an indicator dilution technique for small animals to repeatedly determine cardiac output and blood volume without cardiac instrumentation or blood sampling.

Methods

Observations were made in the hamster (N = 32, 70 mg/kg pentobarbital) cremaster using in vivo fluorescence videomicroscopy. Fluorescein isothiocyanate-conjugated bovine serum albumin (10 mg/ml) was injected as a bolus dose (right jugular) while video recording the light intensity in a 20-microm arteriole (intensified charge-coupled device [CCD] camera at fixed gain). The intensity signal was analyzed over time (background subtracted) and calibrated to the dye concentration. The ex vivo calibration was performed using a constant optical path length (20 microm) and a range of dye and hematocrit concentrations. In vivo tube hematocrit was determined using standard methods with fluorescently labeled erythrocytes. Thus, quenching of the fluorescence signal by hemoglobin was corrected for the calibration, and the plasma space in the arteriole was determined. The steady state dye concentration measured by the light intensity at 2 min was not different from the dye concentration found by direct spectrophotometric analysis of the plasma.

Results

Cardiac index was calculated as milliliters of blood per minute per kilogram body weight. The calculated cardiac index was 359 +/- 18 ml.min(-1).kg(-1), which is not different from the reported values for hamsters. Cardiac output was increased twofold when enough intravenous nitroprusside or nitroglycerine was injected to decrease mean arterial pressure from 90 to 70 mmHg. Cardiac output was elevated during dobutamine infusion (16 microg.kg(-1).min(-1)) and decreased during esmolol infusion (50, 75.kg(-1).min(-1)). Blood volume determined from the steady state dye concentrations was 6.2 +/- 0.5 ml/100 g body weight, within the normal range for hamsters.

Conclusions

Fluorescent dye dilution and video microscopy can be used to repeatedly determine cardiac output or blood volume in small animals.
Automated Responsiveness Test (ART) Predicts Loss of Consciousness and Adverse Physiologic Responses during Propofol Conscious Sedation
Authors: Doufas Anthony G. , Bakhshandeh Maryam , Bjorksten Andrew R. , Greif Robert , Sessler Daniel I.
Published: November 2003

Background

The authors evaluated a device designed to provide conscious sedation with propofol (propofol-air), or propofol combined with 50% nitrous oxide (N2O; propofol-N2O). An element of this device is the automated responsiveness test (ART), a method for confirming that patients remain conscious. The authors tested the hypotheses that the ART predicts loss of consciousness and that failure to respond to the ART precedes sedation-induced respiratory or hemodynamic toxicity.

Methods

The protocol consisted of sequential 15-min cycles in 20 volunteers. After a 15-min control period, propofol was infused to an initial target effect-site concentration of 0.0 microg/ml with N2O or 1.5 microg/ml with air. Subsequently, the propofol target effect-site concentration was increased by a designated increment (0.25 and 0.5 microg/ml) and the process repeated. This sequence was continued until loss of consciousness, as defined by an Observer's Assessment of Alertness/Sedation (OAA/S) score of 10/20 or less, or until an adverse physiologic event was detected.

Results

The OAA/S score at which only 50% of the volunteers were able to respond to the ART (P50) during propofol-N2O was 11.1 of 20 (95% confidence interval [CI]: 10.6-11.8); the analogous P50 was 11.8 of 20 (95% CI: 11.4-12.3) with propofol-air. Failure to respond to the ART occurred at a plasma propofol concentration of 0.7 +/- 0.6 microg/ml with propofol-N2O and 1.6 +/- 0.6 microg/ml with propofol-air, whereas loss of consciousness occurred at 1.2 +/- 0.8 microg/ml and 1.9 +/- 0.7 microg/ml, respectively. There were no false-normal ART responses.

Conclusion

The ART can guide individual titration of propofol because failure to respond to responsiveness testing precedes loss of consciousness and is not susceptible to false-normal responses. The use of N2O with propofol for conscious sedation decreases the predictive accuracy of the ART.
Cardiovascular Responses to the Induction of Mild Hypothermia in the Presence of Epidural Anesthesia
Authors: Yoshida Masahiro , Shibata Keizo , Itoh Hironori , Yamamoto Ken
Published: November 2003

Background

The combining of epidural anesthesia with general anesthesia impairs central and peripheral thermoregulatory control and therefore is often accompanied by unintended intraoperative hypothermia. However, little is known about the cardiovascular response to hypothermia during combined epidural and general anesthesia. The authors assessed the effects of hypothermia during such combined anesthesia.

Methods

The authors randomly assigned 30 mongrel dogs anesthetized with isoflurane (1.0%) to three groups of 10: control, receiving general anesthesia alone; thoracic injection, additionally receiving thoracic epidural anesthesia; and lumbar injection, additionally receiving thoracolumbar epidural anesthesia. Core temperature was lowered from 38.5 degrees C to approximately 34 degrees C (mild hypothermia) using a femoral arteriovenous shunt in an external cool water bath. During hypothermia, the authors measured heart rate, cardiac output, and plasma catecholamine concentrations in each group. Ejection fraction was also measured using echocardiography.

Results

Compared with measurements during baseline conditions (general anesthesia alone with no epidural injection and no hypothermia) in the control, thoracic, and lumbar injection groups, the injections followed by hypothermia produced 17, 32, and 41% decreases in heart rate; 22, 32, and 47% reductions in cardiac output; 66, 85, and 92% decreases in the epinephrine concentrations; and 27, 44, and 85% decreases in the norepinephrine concentrations. In contrast, ejection fraction did not change in any group.

Conclusion

Mild hypothermia during combined epidural anesthesia and general anesthesia markedly reduced cardiac output in dogs, mainly by decreasing heart rate.
Different Inhibitory Effects of Volatile Anesthetics on T- and L-type Voltage-dependent Ca2+Channels in Porcine Tracheal and Bronchial Smooth Muscles
Authors: Yamakage Michiaki , Chen Xiangdong , Tsujiguchi Naoki , Kamada Yasuhiro , Namiki Akiyoshi
Published: November 2003

Background

The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs).

Methods

Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution.

Results

The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle.

Conclusions

The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.
Pharyngolaryngeal Morbidity with the Laryngeal Mask Airway in Spontaneously Breathing Patients
Authors: Grady Deirdre M. , McHardy Fiona , Wong Jean , Jin Fengling , Tong Doris , Chung Frances
Published: November 2003

Background

Currently, the manufacturer of the laryngeal mask airway (LMA; Laryngeal Mask Company, Ltd., Northfield End, Henley on Thames, Oxon, United Kingdom) recommends using as large a mask size as possible. The aim of this study was to compare the incidence of pharyngolaryngeal morbidity after the use of a large (size 5 in males and size 4 in females) or small (size 4 in males and size 3 in females) LMA in spontaneously breathing patients.

Methods

A total of 258 male and female patients were randomly assigned to insertion of a large or small LMA while breathing spontaneously during general anesthesia. After insertion of the LMA, a "just-seal" cuff pressure was obtained, and intracuff pressure was measured at 10-min intervals until just before removal of the LMA. The 2- and 24-h incidence of postoperative sore throat, pain, hoarseness, dysphagia, and nausea and vomiting was assessed. Complications after LMA removal, including body movement, coughing, retching, regurgitation, vomiting, biting on the LMA, bronchospasm, laryngospasm, or the presence of blood on the LMA, were recorded.

Results

The use of a large LMA was associated with a higher incidence of sore throat in both sexes (20% vs. 7% in men, 21% vs. 5% in women; P < 0.05) and a higher incidence of hoarseness in male patients at 2 h postoperatively (21% vs. 9%, P < 0.05). There was a higher incidence of sore throat in male patients at 24 h postoperatively with the use of a large LMA (26% vs. 12%, P < 0.05). There was no difference in the incidence of complications of LMA removal orother pharyngolaryngeal morbidity, such as difficulty swallowing, drinking, and eating, or nausea and vomiting, between male or female groups at any time period with the use of a large LMA.

Conclusions

Selection of a small laryngeal mask airway (size 4) in spontaneously breathing male patients may be more appropriate to limit the occurrence of sore throat on the first postoperative day. All patients had a fourfold increased risk of developing sore throat when a large LMA was used.
Anesthetic Potency and Influence of Morphine and Sevoflurane on Respiration in μ-Opioid Receptor Knockout Mice
Authors: Dahan Albert , Sarton Elise , Teppema Luc , Olievier Cees , Nieuwenhuijs Diederik , Matthes Hans W. D. , Kieffer Brigitte L.
Published: November 2003

Background

The involvement of the mu-opioid receptor (muOR) system in the control of breathing, anesthetic potency, and morphine- and anesthesia-induced respiratory depression was investigated in mice lacking the muOR.

Methods

Experiments were performed in mice lacking exon 2 of the muOR gene (muOR-/-) and their wild-type littermates (muOR+/+). The influence of saline, morphine, naloxone, and sevoflurane on respiration was measured using a whole body plethysmographic method during air breathing and elevations in inspired carbon dioxide concentration. The influence of morphine and naloxone on anesthetic potency of sevoflurane was determined by tail clamp test.

Results

Relative to wild-type mice, muOR-deficient mice displayed approximately 15% higher resting breathing frequencies resulting in greater resting ventilation levels. The slope of the ventilation-carbon dioxide response did not differ between genotypes. In muOR+/+ but not muOR-/- mice, a reduction in resting ventilation and slope, relative to placebo, was observed after 100 mg/kg morphine. Naloxone increased resting ventilation and slope in both genotypes. Sevoflurane at 1% inspired concentration induced similar reductions in resting ventilation and slope in the two genotypes. Anesthetic potency was 20% lower in mutant relevant to wild-type mice. Naloxone and morphine caused an increase and decrease, respectively, in anesthetic potency in muOR+/+ mice only.

Conclusions

The data indicate the importance of the endogenous opioid system in the physiology of the control of breathing with only a minor role for the muOR. The muOR gene is the molecular site of action of the respiratory effects of morphine. Anesthetic potency is modulated by the endogenous mu-opioid system but not by the kappa- and delta-opioid systems.
Role of Heparin and Nitric Oxide in the Cardiac and Regional Hemodynamic Properties of Protamine in Conscious Chronically Instrumented Dogs
Authors: Oguchi Takeshi , Doursout Marie-Françoise , Kashimoto Satoshi , Yan Liang Yang , Hartley Craig J. , Chelly Jacques E.
Published: November 2003

Background

Because protamine is administered to reverse heparin, a drug that might itself affect the pharmacologic properties of protamine, this study was designed to assess the properties of protamine alone and in the presence of heparin in conscious dogs.

Methods

Twelve dogs were instrumented to continuously record cardiac and regional hemodynamics. On separate occasions, a dose of protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine (3 mg/kg) were administered in the presence of N-methyl-L-arginine, a specific nitric oxide synthase inhibitor. Identical experiments were performed with protamine (8 mg/kg) in the absence of heparin on a separate occasion.

Results

Protamine alone produced limited cardiac and regional changes. In the presence of heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3 and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5 mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg. Protamine produced an immediate increase followed by a secondary decrease in renal vascular resistance. Protamine-induced secondary pulmonary pressor effects were attenuated. In the presence of heparin, nitric oxide synthase blockade selectively attenuated protamine-induced immediate hypotension, systemic vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as the decrease in portal blood flow and accentuated the renal vasoconstriction.

Conclusions

The presence of heparin accentuated the decrease in cardiac function induced by protamine as well as its effects on regional circulation. The data provide evidence that the nitric oxide pathway is involved in the systemic and selective regional heparin-protamine-mediated vasodilatation in conscious dogs.
Divergence of Volatile Anesthetic Effects in Inhibitory Neurotransmitter Receptors
Authors: Greenblatt Eric P. , Meng Xin
Published: November 2003

Background

The mechanism of volatile anesthetic (VA) action is unknown. Inhibitory receptors for the neurotransmitters gamma-aminobutyric acid (GABA) or glycine are typically positively modulated by VAs and may be important targets for their action. The existence of a GABA receptor subtype (p), which is uniquely inhibited by VAs, suggested a chimeric receptor approach to identify portions of these proteins that may be necessary for anesthetic effects.

Methods

A silent mutation resulting in the addition of a unique restriction enzyme recognition site was introduced in GABA receptor type A alpha2, glycine alpha1, and p subunit cDNAs. Chimeras were constructed by rejoining restriction digest fragments and were expressed in Xenopus oocytes. Modulation of submaximal agonist-evoked peak currents by the VAs chloroform, enflurane, halothane, or isoflurane was measured using two-electrode voltage clamp.

Results

Four chimeras were constructed and designated glyrho, rhogly, alpha2rho, and rhoalpha2. Glyrho formed glycine-gated receptors with currents that were enhanced by chloroform or halothane but were inhibited by enflurane or isoflurane. Chimeras rhogly and rhoalpha2 each formed GABA-gated receptors with currents that were inhibited by chloroform or halothane but enhanced by enflurane or isoflurane.

Conclusions

These data show, for the first time, functional divergence of VA action on a single protein target. The VAs in this study fall into two distinct groups with respect to their effects on these receptors. This grouping parallels the chemistry of these compounds. Our results support the involvement of multiple protein domains in the mechanism of VA modulation of GABA and glycine receptors.
An Obligatory Role for Spinal Cholinergic Neurons in the Antiallodynic Effects of Clonidine after Peripheral Nerve Injury
Authors: Paqueron Xavier , Li Xinhui , Bantel Carsten , Tobin Joseph R. , Voytko Mary Lou , Eisenach James C.
Published: November 2003

Background

Indirect evidence supports a role of spinal cholinergic neurons in tonically reducing response to noxious mechanical stimulation and in effecting analgesia from alpha2-adrenergic agonists. This study directly assessed the role of cholinergic neurons in regulating the level of mechanical allodynia and in participating in the antiallodynic effect of the clinically used alpha2-adrenergic agonist, clonidine, in an animal model of neuropathic pain.

Methods

Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Rats received a single intrathecal injection of saline or one of three different doses of the cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64-A; 2, 5, and 15 nmol). Seven days later, allodynia was assessed before and after intrathecal injection of 15 microg clonidine. The spinal cord was removed, and spinal cord acetylcholine content, cholinergic neuron number and distribution, and alpha2-adrenergic receptor expression were determined.

Results

AF64-A administration reduced both the number of cholinergic cells and the acetylcholine content of the lumbar dorsal spinal cord by 20-50% but did not affect level of mechanical allodynia. AF64-A did, however, completely block the anti-allodynic effect of clonidine. AF64-A did not reduce alpha2-adrenergic ligand binding in dorsal lumbar cord.

Conclusions

These data suggest that spinal cholinergic tone does not affect the level of mechanical allodynia after peripheral nerve injury. There is a quantitative reliance on spinal cholinergic neurons in the allodynia relieving properties of intrathecal clonidine, and this reliance does not depend on alpha2-adrenergic receptors colocalized on spinal cholinergic interneurons.
Signal Transduction of Opioid-induced Cardioprotection in Ischemia-Reperfusion
Authors: McPherson Bradley C. , Yao Zhenhai
Published: November 2003

Background

Morphine reduces myocardial ischemia-reperfusion injury in vivo and in vitro. The authors tried to determine the role of opioid delta1 receptors, oxygen radicals, and adenosine triphosphate-sensitive potassium (KATP) channels in mediating this effect.

Methods

Chick cardiomyocytes were studied in a flow-through chamber while pH, flow rate, oxygen, and carbon dioxide tension were controlled. Cell viability was quantified by nuclear stain propidium iodide, and oxygen radicals were quantified using molecular probe 2',7'-dichlorofluorescin diacetate.

Results

Morphine (1 microM) or the selective delta-opioid receptor agonist BW373U86 (10 pM) given for 10 min before 1 h of ischemia and 3 h of reoxygenation reduced cell death (31 +/- 5%, n = 6, and 28 +/- 5%, n = 6 [P < 0.05], respectively, 53 +/- 6%, n = 6, in controls) and generated oxygen radicals before ischemia (724 +/- 53, n = 8, and 742 +/- 75, n = 8 [P < 0.05], respectively, vs. 384 +/- 42, n = 6, in controls, arbitrary units). The protection of morphine was abolished by naloxone, or the selective delta1-opioid receptor antagonist 7-benzylidenenaltrexone. Reduction in cell death and increase in oxygen radicals with BW373U86 were blocked by the selective mitochondrial KATP channel antagonist 5-hydroxydecanoate or diethyldithiocarbamic acid (1,000 microM), which inhibited conversion of O2- to H2O2. The increase in oxygen radicals was abolished by the mitochondrial electron transport inhibitor myxothiazoL Reduction in cell death was associated with attenuated oxidant stress at reperfusion.

Conclusion

Stimulation of delta1-opioid receptors generates oxygen radicals via mitochondrial KATP channels. This signaling pathway attenuates oxidant stress and cell death in cardiomyocytes.
Propofol Increases Myofilament Ca2+Sensitivity and Intracellular pH via Activation of Na+–H+Exchange in Rat Ventricular Myocytes
Authors: Kanaya Noriaki , Murray Paul A. , Damron Derek S.
Published: November 2003

Background

The objectives were to determine the extent and mechanism of action by which propofol increases myofilament Ca2+ sensitivity and intracellular pH (pHi) in ventricular myocytes.

Methods

Freshly isolated adult rat ventricular myocytes were used for the study. Cardiac myofibrils were extracted for assessment of myofibrillar actomyosin adenosine triphosphatase (ATPase) activity. Myocyte shortening (video edge detection) and pHi (2',7'-bis-(2-carboxyethyl)-5(6')-carboxyfluorescein, 500/440 ratio) were monitored simultaneously in individual cells field-stimulated (0.3 Hz) and superfused with HEPES-buffered solution (pH 7.4, 30 degrees C).

Results

Propofol (100 microM) reduced the Ca2+ concentration required for activation of myofibrillar actomyosin ATPase from pCa 5.7 +/- 0.01 to 6.6 +/- 0.01. Increasing pHi (7.05 +/- 0.03 to 7.39 +/- 0.04) with NH4Cl increased myocyte shortening by 35 +/- 12%. Washout of NH4Cl decreased pHi to 6.82 +/- 0.03 and decreased myocyte shortening to 52 +/- 10% of control. Propofol caused a dose-dependent increase in pHi but reduced myocyte shortening. The propofol-induced increase in pHi was attenuated, whereas the decrease in myocyte shortening was enhanced after pretreatment with ethylisopropyl amiloride, a Na+-H+ exchange inhibitor, or bisindolylmaleimide I, a protein kinase C inhibitor. Propofol also attenuated the NH4Cl-induced intracellular acidosis, increased the rate of recovery from acidosis, and attenuated the associated decrease in myocyte shortening. Propofol caused a leftward shift in the extracellular Ca2+-shortening relation, and this effect was attenuated by ethylisopropyl amiloride.

Conclusions

These results suggest that propofol increases the sensitivity of myofibrillar actomyosin ATPase to Ca2+ (ie., increases myofilament Ca2+ sensitivity), at least in part by increasing pHi via protein kinase C-dependent activation of Na+-H+ exchange.
Inhaled Nitric Oxide Improves Survival Rates during Hypoxia in a Sickle Cell (SAD) Mouse Model
Authors: Martinez-Ruiz Ricardo , Montero-Huerta Pedro , Hromi Jonathan , Head C. Alvin
Published: November 2003

Background

The hallmark of sickle cell disease (SCD) is erythrocyte sickling during deoxygenation of the abnormal hemoglobin S (HbS). When HbS is deoxygenated, it aggregates into polymers, resulting in distortion of the erythrocyte structure, producing microvascular thrombosis and ischemia. The transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D-Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of nitric oxide (NO) breathing at various doses and time regimens in the presence of severe hypoxia (6% oxygen) using the SAD mouse model.

Methods

Age- and sex-matched control and SAD mice were exposed to 6% oxygen breathing in an environmental chamber and assessed for survival up to 1 h. Animals received different inhaled NO concentrations before and/or during hypoxia. Blood was obtained to evaluate the oxyhemoglobin dissociation curve and measure methemoglobinemia.

Results

Pretreatment by breathing NO at 20 ppm by volume in air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in improvement in survival rates in the SAD mouse (75%, n = 8) as compared with control SAD mice (11%, n = 9; P < 0.001). Pretreatment alone or breathing lower doses of NO were not protective. Changes in HbSAD oxygen affinity were not detected with NO breathing, and methemoglobin levels were low in all surviving mice.

Conclusions

Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice. There appears to be a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.
Comparison of Closed-loop Controlled Administration of Propofol Using Bispectral Index as the Controlled Variable versus “Standard Practice” Controlled Administration
Authors: Struys Michel M. R. F. , De Smet Tom , Versichelen Linda F. M. , Van de Velde Stijn , Van den Broecke Rudy , Mortier Eric P.
Published: November 2003

Background

This report describes a new closed-loop control system for propofol that uses the Bispectral Index (BIS) as the controlled variable in a patient-individualized, adaptive, model-based control system, and compares this system with manually controlled administration of propofol using hemodynamic and somatic changes to guide anesthesia.

Methods

Twenty female patients, American Society of Anesthesiologists physical status I or II, who were scheduled for gynecologic laparotomy were included to receive propofolremifentanil anesthesia. In group I, propofol was titrated using a BIS-guided, model-based, closed-loop system. The BIS target was set at 50. In group II, propofol was titrated using classical hemodynamic signs of (in)adequate anesthesia. Performance of control during induction and maintenance of anesthesia were compared between both groups using BIS as the controlled variable in group I and the reference variable in group II, and, conversely, the systolic blood pressure as the controlled variable in group II and the reference variable in group I. At the end of anesthesia, recovery profiles between groups were compared.

Results

Although patients undergoing manual induction of anesthesia in group II at 300 ml/h reached a BIS level of 50 faster than patients undergoing open-loop, computer-controlled induction in group I, manual induction caused a more pronounced initial overshoot of the BIS target. This resulted in a more pronounced decrease in blood pressure in group II. During the maintenance phase, better control of BIS and systolic blood pressure was found in group I compared with group II. Recovery was faster in group I.

Conclusion

A closed-loop system for propofol administration using the BIS as a controlled variable together with a model-based controller is clinically acceptable during general anesthesia.
Failure of Autologous Fresh Frozen Plasma to Reduce Blood Loss and Transfusion Requirements in Coronary Artery Bypass Surgery
Authors: Kasper Stefan-Mario , Giesecke Thorsten , Limpers Peter , Sabatowski Rainer , Mehlhorn Uwe , Diefenbach Christoph
Published: November 2003

Background

Previous studies failed to demonstrate any benefit from prophylaxis with fresh frozen plasma (FFP) after cardiopulmonary bypass (CPB). The results, however, were limited by either retrospective study design or use of FFP in subtherapeutic doses (2-3 units). The authors evaluated whether a therapeutic dose (15 ml/kg) of FFP reduces blood loss and transfusion requirements in elective coronary artery bypass surgery. The risks of multiple allogeneic blood donor exposure were circumvented by using autologous plasma.

Methods

Sixty adult patients scheduled for elective primary coronary artery bypass grafting were randomized to receive, after CPB, an intravenous infusion of 15 ml/kg of either autologous FFP (30 patients) or 6% hydroxyethyl starch 450/0.7 (HES; 30 patients). Autologous plasma was obtained by platelet-poor plasmapheresis several weeks before surgery. Perioperative blood transfusions were administered per protocol. Postoperative blood loss was defined as the chest tube drainage during the first 24 h after surgery.

Results

The data from 56 patients (FFP group, 27 patients; HES group, 29 patients) who completed the study according to protocol were analyzed. Median postoperative blood loss was 630 ml (range, 450-1,840 ml) and 830 ml (range, 340-1,980 ml) in the FFP and HES groups, respectively (P = 0.08). Both postoperative (0-24 h) and total perioperative erythrocyte transfusion requirements did not differ significantly between the groups (P = 0.32 and 0.14, respectively).

Conclusion

The prophylactic administration of a therapeutic dose (15 ml/kg) of autologous FFP after CPB failed to reduce blood loss and transfusion requirements in patients undergoing uncomplicated, elective, primary coronary artery bypass surgery.
Effects of Bupivacaine and Ropivacaine on High-voltage–activated Calcium Currents of the Dorsal Horn Neurons in Newborn Rats
Authors: Liu Bao-Gang , Zhuang Xin-Liang , Li Shi-Tong , Xu Guo-Hui , Brull Sorin J. , Zhang Jun-Ming
Published: November 2003

Background

Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons.

Methods

Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV.

Results

Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations.

Conclusions

The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).
Mild Alkalinization and Acidification Differentially Modify the Effects of Lidocaine or Mexiletine on Vasorelaxation Mediated by ATP-sensitive K+Channels
Authors: Kinoshita Hiroyuki , Iranami Hiroshi , Kimoto Yoshiki , Dojo Mayuko , Hatano Yoshio
Published: November 2003

Background

The previous study by the authors showed that the class Ib antiarrhythmic drug lidocaine impairs but mexiletine augments vasorelaxation mediated by adenosine triphosphate-sensitive K+ channels. Lidocaine and mexiletine have different values of the negative logarithm of the drug-proton dissociation constant, indicating that the ion channel-blocking effects of these drugs under different pH levels may vary. However, the role of pH in the effects of lidocaine and mexiletine on vasodilation mediated by K+ channels has not been studied. Therefore, the current study was designed to examine whether the inhibition and augmentation of vasorelaxation in response to an adenosine triphosphate-sensitive K+ channel opener, levcromakalim, by the clinically relevant concentrations of lidocaine or mexiletine are modified by mild alkalinization or acidification in the isolated rat aorta.

Methods

Rings of the rat aorta without endothelium were suspended for isometric force recording. Three types of modified Krebs-Ringer solutions (pH 7.2, 7.4, and 7.6) were prepared by changing the composition of NaCl and NaHCO3. During contractions in response to phenylephrine (3 x 10(-7) M), relaxations in response to levcromakalim (10(-8) to 10(-5) M) were obtained. Lidocaine (10(-5) to 10(-4) M), mexiletine (10(-5) to 10(-4) M), or glibenclamide (10(-5) M) was applied 15 min before addition of phenylephrine.

Results

Relaxations in response to levcromakalim, which are abolished by the selective adenosine triphosphate-sensitive K+ channel antagonist glibenclamide (10(-5) M), were not different among the three pH groups. In the normal Krebs-Ringer solution of pH 7.4, lidocaine significantly reduced these relaxations in a concentration-dependent fashion. Alkalinization of pH 7.6 augmented the inhibitory effect of lidocaine on these relaxations, whereas acidification of pH 7.2 substantially abolished this effect. In contrast, mexiletine pH independently augmented relaxations in response to levcromakalim. Glibenclamide (10(-5) M) abolished these relaxations in arteries treated with mexiletine (10(-4) M) in any pH group.

Conclusions

These results suggest that even under conditions of such mild alkalosis or acidosis, vasorelaxation via adenosine triphosphate-sensitive K+ channels is dependent on pH in the presence of clinically relevant concentrations of lidocaine but not mexiletine.
Comparison of Metaraminol and Ephedrine Infusions for Maintaining Arterial Pressure during Spinal Anesthesia for Elective Cesarean Section
Authors: Ngan Kee Warwick D. , Lau Tze K. , Khaw Kim S. , Lee Bee B.
Published: November 2003

Background

Although ephedrine is usually recommended as the first-line vasopressor in obstetrics, its superiority over other vasopressors has not been proven in humans.

Methods

In a double-blind study, the authors randomized women having elective cesarean section with spinal anesthesia to receive an intravenous infusion of ephedrine, starting at 5 mg/min (n = 25), or metaraminol, starting at 0.25 mg/min (n = 25), titrated to maintain systolic arterial pressure in the target range 90-100% of baseline. Umbilical cord gases, maternal hemodynamics, uterine artery puLsatility index, and Apgar scores were compared.

Results

Systolic arterial pressure was maintained more closely in the target range in the metaraminol group compared with the ephedrine group. In the metaraminol group, umbilical arterial pH was greater (median and interquartile range, 7.31 and 7.31-7.33 vs. 7.24 and 7.14-7.29; P < 0.0001), and umbilical venous pH was greater (7.36 and 7.35-7.38 vs. 7.33 and 7.26-7.34; P < 0.0001) compared with the ephedrine group. No patient in the metaraminol group had umbilical arterial pH less than 7.2, compared with nine patients (39%) in the ephedrine group (P = 0.0005). Apgar scores were similar between groups. Changes in uterine artery pulsatility index were similar between groups.

Conclusions

When used by infusion to maintain arterial pressure during spinal anesthesia for cesarean section, metaraminol was associated with less neonatal acidosis and more closely controlled titration of arterial pressure compared with ephedrine.
Propofol Dosing Regimens for ICU Sedation Based upon an Integrated Pharmacokinetic– Pharmacodynamic Model
Authors: Barr Juliana , Egan Talmage D. , Sandoval Nancy F. , Zomorodi Katayoun , Cohane Carol , Gambus Pedro L. , Shafer Steven L.
Published: November 2003

Background

The pharmacology of propofol infusions administered for long-term sedation of intensive care unit (ICU) patients has not been fully characterized. The aim of the study was to develop propofol dosing guidelines for ICU sedation based on an integrated pharmacokinetic-pharmacodynamic model of propofol infusions in ICU patients.

Methods

With Institutional Review Board approval, 30 adult male medical and surgical ICU patients were given target-controlled infusions of propofol for sedation, adjusted to maintain a Ramsay sedation scale score of 2-5. Propofol administration in the first 20 subjects was based on a previously derived pharmacokinetic model for propofol. The last 10 subjects were given propofol based on a pharmacokinetic model derived from the first 20 subjects. Plasma propofol concentrations were measured, together with sedation score. Population pharmacokinetic and pharmacodynamic parameters were estimated by means of nonlinear regression analysis in the first 20 subjects, then prospectively tested in the last 10 subjects. An integrated pharmacokinetic-pharmacodynamic model was used to construct dosing regimens for light and deep sedation with propofol in ICU patients.

Results

The pharmacokinetics of propofol were described by a three-compartment model with lean body mass and fat body mass as covariates. The pharmacodynamics of propofol were described by a sigmoid model, relating the probability of sedation to plasma propofol concentration. The pharmacodynamic model for propofol predicted light and deep levels of sedation with 73% accuracy. Plasma propofol concentrations corresponding to the probability modes for sedation scores of 2, 3, 4, and 5 were 0.25, 0.6, 1.0, and 2.0 microg/ml. Predicted emergence times in a typical subject after 24 h, 72 h, 7 days, and 14 days of light sedation (sedation score = 3 --> 2) with propofol were 13, 34, 198, and 203 min, respectively. Corresponding emergence times from deep sedation (sedation score = 5 --> 2) with propofol were 25, 59, 71, and 74 h.

Conclusions

Emergence time from sedation with propofol in ICU patients varies with the depth of sedation, the duration of sedation, and the patient's body habitus. Maintaining a light level of sedation ensures a rapid emergence from sedation with long-term propofol administration.