bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic Neural Activation Evoked by μ-Receptor Blockade in Patients Addicted to Opioids Is Abolished by Intravenous Clonidine
Authors: Kienbaum Peter , Heuter Thorsten , Michel Martin C. , Scherbaum Norbert , Gastpar Markus , Peters Jürgen
Published: November 2003

Background

Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification.

Methods

Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration.

Results

Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P < 0.001) and catecholamine plasma concentrations (P < 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change.

Conclusions

Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.
Older Age Is the Strongest Predictor of Postoperative Atrial Fibrillation
Authors: Amar David , Zhang Hao , Y. Leung Denis H. , Roistacher Nancy , Kadish Alan H.
Published: November 2003

Background

Identification of patients vulnerable for atrial fibrillation (AF) after major thoracic surgery will allow targeting those most likely to benefit from prophylactic therapy. The goal of the current study was to evaluate the accuracy of easily available clinical characteristics for the prediction of this complication.

Methods

Patients undergoing major elective thoracic surgery were chosen from an ongoing prospective database.

Results

Postoperative in-hospital AF occurred in 79 (15%) of 527 patients Using cut-point methodology and logistic regression, the authors identified two preoperative risk factors independently associated with AF: age 60 yr or older (P = 0.0007) and heart rate 74 beats/min or greater on preadmission electrocardiogram (P = 0.005). The odds of developing AF increased by a factor of 2.5 (95% confidence interval, 1.7-3.4; P < 0.0001) between incremental age categories (< 60 yr, 60-69 yr, > or = 70 yr) and by a factor of 2.3 (95% confidence interval, 1.4-3.8; P < 0.0007) between heart rate categories (< 74 beats/min, > or = 74 beats/min). The combination of age 60 yr or older and preoperative heart rate 74 beats/min or greater predicted AF with a sensitivity of 73% and specificity of 57%. Maximum P-wave duration as measured from standard electrocardiogram did not differentiate patients who did or did not develop AF. Patients who developed AF had a higher incidence of postoperative pneumonia (14 vs. 4%; P = 0.001), acute respiratory failure (8 vs. 1.6%; P = 0.01), greater hospital stay (17 +/- 17 vs. 10 +/- 9 days; P = 0.001) and 30-day mortality (11 vs. 3%; P = 0.001) when compared with those who did not develop AF, respectively.

Conclusions

Advanced age and preoperative heart rate identify patients at high risk for development of AF after thoracic surgery. Postoperative AF occurs more frequently in patients with greater postoperative morbidity and length of hospitalization.
Estrogen Reduces Efficacy of μ- but Not κ-Opioid Agonist Inhibition in Response to Uterine Cervical Distension
Authors: Sandner-Kiesling Andreas , Eisenach James C.
Published: November 2003

Background

Although the uterine cervix is a common source of acute and chronic visceral pain in women, there is practically no neurobiological investigation of nociception from this visceral organ. With use of a novel model of uterine cervical distension nociception in rats, the estrogen dependency of opioid agonist-induced inhibition was investigated.

Methods

Sprague Dawley rats were anesthetized with halothane and bilateral ovariectomy was performed, after which placebo or estrogen treatment was administered for 1 week. Animals were reanesthetized and fine metal rods were inserted into the uterine cervix for manual distension. Reflex contraction of the rectus abdominis in response to distension was recorded before and after cumulative dosing with the mu-opioid agonist morphine and the kappa-opioid agonist (-)U50488.

Results

Uterine cervical distension increased reflex abdominal muscle contraction with a threshold of 75 g, regardless of estrogen treatment. Morphine and (-)U50488 reduced the reflex response to cervical distension in a dose-dependent manner. Estrogen reduced the inhibitory effect of morphine but not that of (-)U50488.

Conclusions

It has been suggested that mu-opioid agonists are less potent in females than males, whereas kappa-opioid agonists are more potent in females than males. These data suggest that estrogen may influence the action of opioids, at least against visceral pain, which may explain this sex difference. In addition, these data suggest that kappa-opioid agonists may be effective in the treatment of pain originating from the uterine cervix, regardless of estrogen status.
Fentanyl Enhancement of Carrageenan-induced Long-lasting Hyperalgesia in Rats
Authors: Rivat Cyril , Laulin Jean-Paul , Corcuff Jean-Benoît , Célèrier Evelyne , Pain Laure , Simonnet Guy
Published: November 2003

Background

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

Methods

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

Results

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

Conclusion

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Method

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusion

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

Background

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

Methods

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

Results

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

Conclusion

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

Background

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

Methods

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

Results

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

Conclusions

The addition of epidural epinephrine 1:300,000 (66 microg) resulted in a significant 29% reduction in the MLAC of bupivacaine. Coincident reductions in fetal heart rate and maternal blood pressure were also observed that were not clinically significant.
Assessment of the Intrarater and Interrater Reliability of an Established Clinical Task Analysis Methodology
Authors: Slagle Jason , Weinger Matthew B. , Dinh My-Than T. , Brumer Vanessa V. , Williams Kevin
Published: November 2003

Background

Task analysis may be useful for assessing how anesthesiologists alter their behavior in response to different clinical situations. In this study, the authors examined the intraobserver and interobserver reliability of an established task analysis methodology.

Methods

During 20 routine anesthetic procedures, a trained observer sat in the operating room and categorized in real-time the anesthetist's activities into 38 task categories. Two weeks later, the same observer performed task analysis from videotapes obtained intraoperatively. A different observer performed task analysis from the videotapes on two separate occasions. Data were analyzed for percent of time spent on each task category, average task duration, and number of task occurrences. Rater reliability and agreement were assessed using intraclass correlation coefficients.

Results

Intrarater reliability was generally good for categorization of percent time on task and task occurrence (mean intraclass correlation coefficients of 0.84-0.97). There was a comparably high concordance between real-time and video analyses. Interrater reliability was generally good for percent time and task occurrence measurements. However, the interrater reliability of the task duration metric was unsatisfactory, primarily because of the technique used to capture multitasking.

Conclusions

A task analysis technique used in anesthesia research for several decades showed good intrarater reliability. Off-line analysis of videotapes is a viable alternative to real-time data collection. Acceptable interrater reliability requires the use of strict task definitions, sophisticated software, and rigorous observer training. New techniques must be developed to more accurately capture multitasking. Substantial effort is required to conduct task analyses that will have sufficient reliability for purposes of research or clinical evaluation.
Frequency of Myocardial Infarction, Pulmonary Embolism, Deep Venous Thrombosis, and Death following Primary Hip or Knee Arthroplasty
Authors: Wood Margaret , Mantilla Carlos B. , Horlocker Terese T. , Schroeder Darrell R. , Berry Daniel J. , Brown David L.
Published: November 2003

Background

There is limited information about the frequency of perioperative complications after elective primary orthopedic total hip and knee arthroplasty in contemporary practice. The purpose of this study was to determine the frequency of clinically relevant myocardial infarction, pulmonary embolism, deep venous thrombosis, and death within 30 days after elective primary hip or knee arthroplasty treated according to contemporary perioperative management.

Methods

The authors examined the medical records of consecutive patients undergoing hip or knee arthroplasty at their institution in a 10-yr period. Prospectively collected databases were used to identify patients with the diagnosis of myocardial infarction, pulmonary embolism, deep venous thrombosis, or death using strict validation criteria and diagnostic-certainty categories.

Results

A total of 10,244 patients underwent primary total hip or knee arthroplasty in the period of study. Of these, 224 patients had one or more adverse events (overall event rate: 2.2%; myocardial infarction: 0.4%; pulmonary embolism: 0.7%; deep venous thrombosis: 1.5%; death: 0.5%). Most adverse events (myocardial infarction, pulmonary embolism, and death) increased in frequency with older age, particularly for patients aged 70 yr or older. Myocardial infarction occurred more frequently in male patients. There were no differences in the overall event frequency between types of procedure. However, pulmonary embolism was highest in patients undergoing bilateral knee operations.

Conclusions

The overall frequency of serious complications within 30 days after primary total hip or knee arthroplasty with contemporary practice was 2.2%. Accurate knowledge of the perioperative risks associated with widely performed elective operations can be used to implement management strategies that may further improve patient outcomes and decrease cost.
Spinal GABAAand GABABReceptor Pharmacology in a Rat Model of Neuropathic Pain
Authors: Malan T. Philip , Mata Heriberto P. , Porreca Frank
Published: November 2003

Background

This study tests the hypothesis that loss of spinal activity of gamma-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury.

Methods

Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52 degrees C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus.

Results

Spinal administration of the GABAA receptor antagonist bicuculline or the GABAB receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABAB receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABAA receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function.

Conclusions

Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABAA agonists may provide a specific therapy for neuropathic pain.
Intracerebroventricular Morphine Produces Antinociception by Evoking γ-Aminobutyric Acid Release through Activation of 5-Hydroxytryptamine 3 Receptors in the Spinal Cord
Authors: Kawamata Tomoyuki , Omote Keiichi , Toriyabe Masaki , Kawamata Mikito , Namiki Akiyoshi
Published: November 2003

Background

It has been generally considered that supraspinal morphine activates the serotonergic descending inhibitory system and releases serotonin (5-hydroxytryptamine [5-HT]) in the spinal cord, producing antinociception through activation of 5-HT receptors. The involvement of a spinal gamma-aminobutyric acid-mediated (GABAergic) system is also suggested in supraspinal morphine antinociception. It has been reported that spinal GABAergic system contributes to 5-HT3 receptor-mediated antinociception. In this study, the authors investigated the contribution of spinal 5-HT3 receptor and the GABAergic system in the intracerebroventricular morphine-induced antinociception.

Methods

Male Sprague-Dawley rats were used. Using the spinal microdialysis method, concentrations of 5-HT and GABA were measured after intracerebroventricular morphine administration. The effect of intracerebroventricular naloxone or spinal perfusion of a selective 5-HT3 receptor antagonist 3-tropanyl-indole-3-carboxylate methiodide on the spinal release of GABA after intracerebroventricular morphine administration was also examined. In the behavioral study, involvement of 5-HT3 receptors or GABAA receptors in the intracerebroventricular morphine-induced antinociceptive effect was investigated using the tail-flick test.

Results

Intracerebroventricular morphine (40 nmol) significantly increased spinal GABA and 5-HT release. Evoked spinal GABA release was reversed by intracerebroventricular naloxone (40 nmol) or spinal perfusion of 3-tropanyl-indole-3-carboxylate methiodide (1 mm). In the behavioral study, intracerebroventricular morphine produced significant antinociception. Intrathecal administration of either GABAA receptor antagonist bicuculine or 3-tropanyl-indole-3-carboxylate methiodide but not vehicle reversed the morphine-induced antinociceptive effect.

Conclusion

Intracerebroventricular morphine evokes spinal GABA release via the activation of 5-HT3 receptors in the spinal cord, resulting in antinociceptive effect.
Propofol Anesthesia Compared to Awake Reduces Infarct Size in Rats
Authors: Gelb Adrian W. , Bayona Nestor A. , Wilson John X. , Cechetto David F.
Published: November 2003

Background

Propofol has not been studied directly in animals subject to cerebral ischemia in the conscious state. Strokes are usually induced in animals while they are anesthetized, making it difficult to eliminate anesthetic interactions as a complicating factor. Therefore, to compare the neuroprotective effects of propofol to the unanesthetized state, experiments were performed using a model that induces a stroke in the conscious rat.

Methods

Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor endothelin. Four days before the strokes were induced, a guide cannula was implanted for the injection of endothelin. On the day of the experiment, endothelin (6.0 pmol in 3 microl) was injected into the striatum. Propofol (25 or 15 mg. kg-1. h-1) or intralipid (vehicle) were infused for 4 h starting immediately after the endothelin injection. In another series, the propofol infusion was begun 1 h after the endothelin injection and continued for 4 h. Three days later, the animals were killed, and the brains were sectioned and stained.

Results

The propofol group (25 mg. kg-1. h-1) had a significantly reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53 mm3). To exclude a direct interaction between propofol and endothelin, in thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction was examined using videomicroscopy, with or without propofol. Propofol had no effect on the magnitude or time course of the endothelin-induced vasoconstriction.

Conclusions

The results show that concurrent or delayed administration of propofol is neuroprotective.
Involvement of the Mitogen-activated Protein Kinase Family in Tetracaine-induced PC12 Cell Death
Authors: Tan Zhiming , Dohi Shuji , Chen Jinen , Banno Yosiko , Nozawa Yoshinori
Published: November 2003

Background

To explore whether cytotoxicity of local anesthetics is related to apoptosis, the authors examined how local anesthetics affect mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)-stress-activated protein kinases, and p38 kinase, which are known to play important roles in apoptosis.

Methods

Cell death was evaluated using PC12 cells. Morphologic changes of cells, cellular membrane, and nuclei were observed. DNA fragmentation was electrophoretically assayed. Western blot analysis was performed to analyze phosphorylation of the MAPK family, cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase. Intracellular Ca2+ concentration was measured using a calcium indicator dye.

Results

Tetracaine-induced cell death was shown in a time- and concentration-dependent manner and characterized by nuclear condensation or fragmentation, membrane blebbing, and internucleosomal DNA fragmentation. Caspase-3 activation and phosphorylation of ERK, JNK, and p38 occurred in the cell death. PD98059, an inhibitor of ERK, enhanced tetracaine-induced cell death and JNK phosphorylation, whereas ERK phosphorylation was inhibited. Curcumin, an inhibitor of JNK pathway, attenuated the cell death. Increase of intracellular Ca2+ concentration was detected. In addition to the increase of ERK phosphorylation and the decrease of JNK phosphorylation, two Ca2+ chelators protected cells from death. Neither cell death nor phosphorylation of the MAPK family was caused by tetrodotoxin. Nifedipine did not affect tetracaine-induced apoptosis.

Conclusions

Tetracaine induces apoptosis of PC12 cells via the MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca2+ influx caused by tetracaine seems to be responsible for the cell death, but blocking of Na+ channels or L-type Ca2+ channels is unlikely involved in the tetracaine's action for apoptosis.
Isoflurane Causes Anterograde but Not Retrograde Amnesia for Pavlovian Fear Conditioning
Authors: Dutton Robert C. , Maurer Anya J. , Sonner James M. , Fanselow Michael S. , Laster Michael J. , Eger Edmond I
Published: November 2003

Background

Production of retrograde amnesia by anesthetics would indicate that these drugs can disrupt mechanisms that stabilize memory. Such disruption would allow suppression of memory of previous untoward events. The authors examined whether isoflurane provides retrograde amnesia for classic (Pavlovian) fear conditioning.

Methods

Rats were trained to fear tone by applying three (three-trial) or one (one-trial) tone-shock pairs while breathing various constant concentrations of isoflurane. Immediately after training, isoflurane administration was either discontinued, maintained unchanged, or rapidly increased to 1.0 minimum alveolar concentration for 1 h longer. Groups of rats were similarly trained to fear context while breathing isoflurane by applying shocks (without tones) in a distinctive environment. The next day, memory for the conditioned stimuli was determined by presenting the tone or context (without shock) and measuring the proportion of time each rat froze (appeared immobile). For each conditioning procedure, the effects of the three posttraining isoflurane treatments were compared.

Results

Rapid increases in posttraining isoflurane administration did not suppress conditioned fear for any of the training procedures. In contrast, isoflurane administration during conditioning dose-dependently suppressed conditioning (P < 0.05). Training to tone was more resistant to the effects of isoflurane than training to context (P < 0.05), and the three-trial learning procedure was more was more resistant than the one-trial procedure (P < 0.05).

Conclusions

Isoflurane provided intense dose-dependent anterograde but not retrograde amnesia for classic fear conditioning. Isoflurane appears to disrupt memory processes that occur at or within a few minutes of the conditioning procedure.
Continuous Infraclavicular Brachial Plexus Block for Postoperative Pain Control at Home
Authors: Ilfeld Brian M. , Morey Timothy E. , Enneking F. Kayser
Published: November 2003

Background

This randomized, double-blinded, placebo-controlled study investigated the efficacy of patient-controlled regional analgesia using an infraclavicular brachial plexus perineural catheter and a portable infusion pump for outpatients undergoing moderately painful, upper extremity orthopedic surgery.

Methods

Preoperatively, patients (n = 30) received an infraclavicular nerve block and perineural catheter. Postoperatively, patients were discharged home with oral narcotics and a portable infusion pump delivering study solution (0.2% ropivacaine or 0.9% saline) via the catheter for 3 days. Investigators and patients were blinded to random group assignment. Daily end points included pain scores at rest and with limb movement, narcotic use and side effects, sleep quality, patient satisfaction, and symptoms of catheter- or local anesthetic-related complications.

Results

Ropivacaine (n = 15) infusion significantly reduced pain compared with saline (n = 15) infusion (P < 0.001). For example, the average pain with movement (scale, 0-10) on postoperative day 1 was 6.1 +/- 2.3 for the saline group versus 2.5 +/- 1.6 for the ropivacaine group (P < 0.001). Oral narcotic use and related side effects were significantly decreased in the ropivacaine group. For example, on postoperative day 1, mean tablet consumption was 5.5 +/- 2.4 and 1.7 +/- 1.6 for the saline and ropivacaine groups, respectively (P < 0.001). Sleep disturbance scores were 10-fold greater for saline administration than for ropivacaine infusion (P < 0.001). Overall satisfaction was significantly greater in the ropivacaine group. No catheter- or local anesthetic-related complications occurred.

Conclusion

After moderately painful orthopedic surgery of the upper extremity, ropivacaine infusion using a portable, mechanical pump and an infraclavicular brachial plexus perineural catheter at home decreased pain, sleep disturbances, narcotic use and related side effects, and improved overall satisfaction.
The Epidural “Top-up”
Authors: Leeda Michal , Stienstra Rudolf , Arbous M. Sesmu , Verschure Maarten J. M. , Dahan Albert , Veering Bernadette Th. , van Kleef Jack W. , Burm Anton G. L.
Published: November 2003

Background

Extension of sensory blockade after an epidural top-up in combined spinal epidural (CSE) anesthesia is partly attributed to compression of the dural sac by the injected volume. This study investigated whether a volume effect plays a significant role when administering an epidural top-up after an initial epidural loading dose and assessed the predictive value of different factors with respect to the increase in sensory blockade.

Methods

After an epidural loading dose of 75 mg ropivacaine, 0.75%, 30 patients were randomly assigned to one of three groups. After the maximum level of sensory blockade (MLSB) had been established, patients received either an epidural top-up with 10 ml ropivacaine, 0.75% (group 1, n = 10) or saline (group 2, n = 10), or no epidural top-up (group 3, n = 10). Subsequently, sensory blockade was assessed at 5-min intervals for a further 30 min by a blinded observer.

Results

The MLSB increased significantly in the patients receiving an epidural top-up with ropivacaine but not in the patients receiving normal saline. Sensory block extension was inversely related to the number of segments blocked at the time of the epidural top-up, and female gender was associated with a smaller increase in MLSB.

Conclusions

When using epidural ropivacaine, the extension of sensory blockade after administering an epidural top-up is caused by a local anesthetic effect and not by a volume effect. Under the conditions of this study, predictors of the increase in sensory blockade are the presence of ropivacaine in the top-up injectate, the number of segments blocked at the time of epidural top-up, and gender.