bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketamine Inhibits Endotoxin-induced Shock in Rats
Authors: Taniguchi Takumi , Shibata Keizo , Yamamoto Ken
Published: November 2003

Background

Cytokines and nitric oxide are believed to participate importantly in the pathogenesis of endotoxin-induced shock. Several investigators have documented that ketamine attenuates production of cytokines and nitric oxide in endotoxemia, but little is known concerning hemodynamic effects of the drug in this state. The objective of the current study was to assess the potential modifying effects of ketamine in endotoxemia.

Methods

The authors randomly assigned 40 rats to one of four equal groups: endotoxin alone, receiving Escherichia coli endotoxin (15 mg/kg, administered intravenously); saline control, receiving saline only; ketamine alone, receiving ketamine (10 mg x kg(-1) x h(-1), administered intravenously); pretreatment, with ketamine administration initiated before the endotoxin exposure; and posttreatment, with ketamine initiated 2 h after endotoxin. During the 5 h after endotoxin injection, hemodynamics, acid-base status, and plasma concentrations of tumor necrosis factor alpha and interleukin 6 were assessed in each group.

Results

Endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increase in the plasma cytokine concentrations. This hemodynamic and cytokine responses to endotoxin were completely abolished in the pretreatment group and modestly suppressed in the posttreatment group. in the absence of endotoxin, ketamine did not modify these responses.

Conclusion

Ketamine administration inhibited hypotension, metabolic acidosis, and cytokine responses in rats injected with endotoxin. The results suggest that judicious use of ketamine as an anesthetic agent may offer advantages in endotoxemia.
Role of Potassium Channels in Isoflurane- and Sevoflurane-induced Attenuation of Hypoxic Pulmonary Vasoconstriction in Isolated Perfused Rabbit Lungs
Authors: Liu Renyu , Ueda Mayumi , Okazaki Naoto , Ishibe Yuichi
Published: November 2003

Background

Although potassium channels are thought to be responsible for the initiation of hypoxic pulmonary vasoconstriction (HPV), their role in the HPV-inhibitory effect of volatile anesthetics is unclear. The current study tested if the HPV-inhibitory effect of isoflurane and sevoflurane can be affected by changing the potassium-channel opening status with specific potassium-channel inhibitors in isolated rabbit lungs.

Methods

Isolated rabbit lungs were divided into eight groups (n = 6 each in isoflurane groups and n = 8 in sevoflurane groups): those receiving no inhibitor treatment = control-isoflurane and control-sevoflurane groups; those treated with an adenosine triphosphate-sensitive potassium (K(ATP))-channel inhibitor, glibenclamide = glibenclamide-isoflurane and glibenclamide-sevoflurane groups; those treated with a high-conductance calcium-activated potassium (K(Ca))-channel inhibitor, iberiotoxin = iberiotoxin-isoflurane and iberiotoxin-sevoflurane groups; and those treated with a voltage-sensitive potassium (Kv)-channel inhibitor, 4-aminopyridine = 4-aminopyridine-isoflurane and 4-aminopyridine-sevoflurane groups. The effect of anesthetic on HPV was tested by exposure of the lungs to isoflurane at a concentration of 0, 0.5, 1, or 2 minimum alveolar concentration, or to sevoflurane at a concentration of 0, 0.5, 1, or 1.62 minimum alveolar concentration. The relation between anesthetic concentrations and the HPV response was analyzed by the Wagner equation.

Results

The inhibition of Kv channels by 4-aminopyridine and K(Ca) channels by iberiotoxin augmented the HPV response. The isoflurane-induced attenuation of HPV was attenuated by voltage-sensitive potassium-channel inhibition with 4-aminopyridine, potentiated by K(Ca)-channel inhibition with iberiotoxin, but not affected by K(ATP)-channel inhibition with glibenclamide. The sevoflurane-induced attenuation of HPV was not affected by any of the potassium-channel inhibitors.

Conclusions

Isoflurane may modulate the HPV response partially through K(Ca) and Kv channels, but sevoflurane may attenuate the HPV response through other pathways rather than through the currently investigated potassium channels in isolated rabbit lungs.
Adenoviral Vector Transfection into the Pulmonary Epithelium after Cecal Ligation and Puncture in Rats
Authors: Weiss Yoram G. , Tazelaar John , Gehan Beth A. , Bouwman Arthur , Christofidou-Solomidou Melpo , Yu Qian-Chun , Raj Nichelle , Deutschman Clifford S.
Published: November 2003

Background

Adenoviral-targeted gene delivery to respiratory epithelium can augment production of specific proteins. Therefore, it may be valuable in treating the acute respiratory distress syndrome. The authors tested the hypothesis that adenoviral vector uptake after cecal ligation and double puncture in rats, an animal model of the acute respiratory distress syndrome, is higher than that observed in controls that did not undergo operation ("nonoperated") or those that underwent a sham operation ("sham-operated").

Methods

Adenoviruses expressing green fluorescent protein or Lac-Z were delivered into the lungs of anesthetized rats via tracheal catheter. Animals were killed 24 or 48 h later. Histopathology and green fluorescent protein expression were examined using light of fluorescence microscopy. Cellular localization of Lac-Z was determined with electron microscopy or semithin sectioning. Viral receptor density and localization were determined using imunoblotting and immunohistochemistry.

Results

After cecal ligation and double puncture, rats were hypoxic and tachypneic. Alveoli were segmentally consolidated, contained proteinaceous debris and neutrophils, and had thickened septa. Administration of adenoviruses to rats that were sham-operated or underwent cecal ligation and double puncture resulted in high levels of marker protein expression in cells lining alveoli. Use of 3 x 10(11) plaque-forming units instead of 3 x 10(12) plaque-forming units resulted in similar levels of green fluorescent protein expression with negligible viral-mediated lymphocytic infiltration. Semithin section and electron microscopy revealed expression primarily localized to type II alveolar cells. Abundance of alpha(v)beta3 integrins and human coxsackie-adenovirus receptor (receptors that modulate viral attachment and internalization) was increased after cecal ligation and double puncture, predominantly in type II pneumocytes.

Conclusions

Cecal ligation and double puncture induces histologic and functional changes consistent with the acute respiratory distress syndrome, increases surface expression of viral receptors, and enhances adenoviral-mediated gene transfer.
Activation of μ-Opioid Receptor Induces Expression of c-fos and junB via Mitogen-activated Protein Kinase Cascade
Authors: Shoda Takehiro , Fukuda Kazuhiko , Uga Hisatoshi , Mima Hiroyuki , Morikawa Hitoshi
Published: November 2003

Background

Opioid-induced long-term functional alterations of the nervous system, such as tolerance, addiction, and dependence, conceivably involve changes in gene expression. The authors have previously reported that opioid receptors are functionally coupled to extracellular signal-regulated kinase, a class of the mitogen-activated protein kinase. To address whether activation of the opioid receptor induces changes in gene expression through the activation of extracellular signal-regulated kinase, the authors examined mu-opioid receptor (MOR)-induced immediate early gene expression.

Methods

Chinese hamster ovary cells stably expressing MOR were used. Cells were stimulated by MOR agonists after 24-h serum starvation. Expression of c-fos and junB genes was analyzed by RNA blot hybridization. To explore the mechanism of MOR-mediated c-fos and junB expression, activity of a transcription factor, Elk-1, was assessed by reporter assay. Furthermore, to investigate the functional consequences of c-fos and junB induction, MOR-mediated formation of the functional transcription factor complex AP-1 was examined by reporter assay and electrophoretic mobility shift assay.

Results

Mu-opioid receptor activation induced c-fos and junB messenger RNAs, which were inhibited by pretreatment of the cells with pertussis toxin and PD98059, an inhibitor of extracellular signal-regulated kinase cascade. MOR stimulation elevated Elk-1-mediated transcriptional activity by about 10-fold. AP-1-mediated transcriptional activity was stimulated by MOR agonists by about twofold. Electrophoretic mobility shift assay revealed that AP-1 binding activity in the nuclear extract was elevated by MOR activation and further showed that products of c-fos and junB genes are involved in formation of AP-1 complex.

Conclusions

Mu-opioid receptor activation induces c-fos and junB expression and elevates AP-1-mediated transcriptional activities via the mitogen-activated protein kinase cascade.
Role of Endothelium in the Action of Isoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries
Authors: Izumi Kaoru , Akata Takashi , Takahashi Shosuke
Published: November 2003

Background

It is believed that isoflurane decreases blood pressure predominantly by decreasing systemic vascular resistance with modest myocardial depression. Nevertheless, little information is available regarding the direct action of isoflurane on systemic resistance arteries.

Methods

With use of the isometric force recording method, the action of isoflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries.

Results

In the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2-5%), but it was subsequently almost normalized to the control level during exposure to isoflurane. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine response was gradually inhibited during exposure to isoflurane (> or = 3%), and the inhibition was prolonged after wash-out of isoflurane. The isoflurane-induced enhancement of norepinephrine response was still observed after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase.

Conclusions

In isolated mesenteric resistance artery, the action of isoflurane on contractile response to norepinephrine consists of two distinct components: an endothelium-dependent enhancing component and an endothelium-independent inhibitory component. During exposure to isoflurane, the former counteracted the latter, preventing the norepinephrine response from being strongly inhibited. However, only the endothelium-independent component persists after washout of isoflurane, causing prolonged inhibition of the norepinephrine response. Superoxide anions may be involved in the enhanced response to norepinephrine.
Effects of the Anesthetic Gases Xenon, Halothane, and Isoflurane on Calcium and Potassium Currents in Human Atrial Cardiomyocytes
Authors: Hüneke Rocco , Jüngling Eberhard , Skasa Marius , Rossaint Rolf , Lückhoff Andreas
Published: November 2003

Background

Negative inotropic and proarrhythmic side effects on the heart are well known for the volatile anesthetics halothane and isoflurane but not for the noble gas xenon. We investigated the effects of halothane, isoflurane, and xenon on calcium and potassium currents in human atrial myocytes to elucidate the cellular and molecular basis of their cardiac actions.

Methods

Atrial myocytes were prepared from the right auricles obtained from patients undergoing heart surgery. Ion currents were measured with the whole cell patch clamp technique during superfusion of the cells with solutions that contained halothane, isoflurane, or xenon at concentrations corresponding to their respective minimum alveolar concentration (MAC); gas concentrations were determined with the head space-gas chromatography/mass spectrometry/selected ion monitoring method.

Results

L-type calcium currents were significantly depressed by 31.9 +/- 4.1%, from -1.8 +/- 0.3 to -1.2 +/- 0.4 picoampere (pA)/picofarad (pF) (n = 4; P < 0.05) at 1 MAC halothane and by 21.7 +/- 9.2%, from -1.6 +/- 0.7 to -1.2 +/- 0.6 pA/pF (n = 7; P < 0.05) at 1 MAC isoflurane, but not affected by 70% xenon (1 MAC). Inwardly rectifying potassium currents were not influenced by any anesthetic. Halothane (1 MAC) significantly inhibited the transient as well as the sustained part of voltage-gated potassium outward currents, by 19.4 +/- 6.7%, from 6.7 +/- 2.1 to 5.4 +/- 1.6 pA/pF (n = 8; P < 0.05), and by 8.6 +/- 4.8%, from 5.5 +/- 1.7 to 5.0 +/- 1.5 pA/pF (n = 8; P < 0.05), respectively. Transient K+ outward currents were even more inhibited, by 25.8 +/- 4.8%, from 9.8 +/- 3.1 to 7.3 +/- 2.1 pA/pF (n = 5; P < 0.05) at 1 MAC isoflurane, whereas xenon evoked only a slight (albeit significant) inhibition, by 6.1 +/- 3.7%, from 8.2 +/- 6.0 to 7.7 +/- 5.8 pA/pF (n = 10; P < 0.05). Isoflurane and xenon did not affect sustained potassium currents. All effects of the anesthetics were fully reversible after washout.

Conclusions

Halothane and isoflurane exhibited considerable inhibitory effects on voltage-gated cardiac Ca2+ and K+ currents important for the duration of action potentials and the repolarization. Xenon, in contrast, did not affect Ca2+ currents and only slightly inhibited transient K+ outward currents, in line with the almost absent cardiac side effects of the noble gas.
Double-masked Randomized Trial Comparing Alternate Combinations of Intraoperative Anesthesia and Postoperative Analgesia in Abdominal Aortic Surgery
Authors: Norris Edward J. , Beattie Charles , Perler Bruce A. , Martinez Elizabeth A. , Meinert Curtis L. , Anderson Gerald F. , Grass Jeffrey A. , Sakima Neil T. , Gorman Randolph , Achuff Stephen C. , Martin Barbara K. , Minken Stanley L. , Williams G. Melville , Traystman Richard J.
Published: November 2003

Background

Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta.

Methods

One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones.

Results

Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups.

Conclusions

In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.
An Evaluation of the Quality of Clinical Trials in Anesthesia
Authors: Pua Hwee Leng , Lerman Jerrold , Crawford Mark W. , Wright James G.
Published: November 2003

Background

The authors evaluated the quality of clinical trials published in four anesthesia journals during the 20-yr period from 1981-2000.

Methods

Trials published in four major anesthesia journals during the periods 1981-1985, 1991-1995, and the first 6 months of 2000 were grouped according to journal and year. Using random number tables, four trials were selected from all of the eligible clinical trials in each journal in each year for the periods 1981-1985 and 1991-1995, and five trials were selected from all of the trials in each journal in the first 6 months of 2000. Methods and results sections from the 160 trials from 1981-1985 and 1991-1995 were randomly ordered and distributed to three of the authors for blinded review of the quality of the study design according to 10 predetermined criteria (weighted equally, maximum score of 10): informed consent and ethics approval, eligibility criteria, sample size calculation, random allocation, method of randomization, blind assessment of outcome, adverse outcomes, statistical analysis, type I error, and type II error. After these trials were evaluated, 20 trials from the first 6 months of 2000 were randomly ordered, distributed, and evaluated as described.

Results

The mean (+/- SD) analysis scores pooled for the four journals increased from 5.5 +/- 1.4 in 1981-1985 to 7.0 +/- 1.1 in 1991-1995 (P < 0.00001) and to 7.8 +/- 1.5 in 2000. For 7 of the 10 criteria, the percentage of trials from the four journals that fulfilled the criteria increased significantly between 1981-1985 and 1991-1995. During the 20-yr period, the reporting of sample size calculation and method of randomization increased threefold to fourfold, whereas the frequency of type I statistical errors remained unchanged.

Conclusion

Although the quality of clinical trials in four major anesthesia journals has increased steadily during the past two decades, specific areas of trial methodology require further attention.
Shiver Suppression Using Focal Hand Warming in Unanesthetized Normal Subjects
Authors: Sweney Matthew T. , Sigg Daniel C. , Tahvildari Samira , Iaizzo Paul A.
Published: November 2003

Background

A decrease of 1 or 2 degrees C in core temperature may provide protection against cerebral ischemia. However, during corporeal cooling of unanesthetized patients, the initiation of involuntary motor activity (shiver) prevents the reduction of core temperature. The authors' laboratory previously showed that focal facial warming suppressed whole-body shiver. The aim of the current study was to determine whether the use of hand warming alone could suppress shiver in unanesthetized subjects and hence potentiate core cooling.

Methods

Subjects (n = 8; healthy men) were positioned supine on a circulating water mattress (8-15 degrees C) with a convective-air coverlet (14 degrees C) extending from their necks to their feet. A dynamic protocol was used in which focal hand warming was used to suppress involuntary motor activity, enabling noninvasive cooling to decrease core temperatures. The following parameters were monitored: (1) heart rate; (2) blood pressure; (3) core temperature (rectal, tympanic); (4) cutaneous temperature and heat flux; (5) subjective shiver level (SSL scale 0-10) and thermal comfort index (scale 0-10); (6) metabolic data (n = 6); and (7) electromyograms.

Results

During cooling without hand warming, involuntary motor activity increased until it was widespread. After subjects reported whole-body shiver (SSL > or = 7), applied hand warming, in all cases, reduced shiver levels (SSL < o r= 3), decreased electromyographic root mean square amplitudes, and allowed core temperature to decrease from 37.0 +/- 0.2 to 35.9 +/- 0.5 degrees C (measured rectally).

Conclusions

Focal hand warming seems to be valuable in minimizing or eliminating the need to suppress involuntary motor activity pharmacologically when it is desired to induce or maintain mild hypothermia; it may be used in conjunction with facial warming or in cases in which facial warming is contraindicated.
Activation of Coagulation and Fibrinolysis during Coronary Surgery
Authors: Casati Valter , Gerli Chiara , Franco Annalisa , Della Valle Patrizia , Benussi Stefano , Alfieri Ottavio , Torri Giorgio , D’Angelo Armando
Published: November 2003

Background

The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques.

Methods

Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, alpha(2) antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively.

Results

Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas alpha(2)-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups.

Conclusions

Coronary surgery causes a net consumption of antithrombin and fibrinogen. A transient decrease in platelet counts, with plasminogen activation and increased D-dimer formation, however, is only observed with CABG. Twenty-four hours after surgery, the hemostatic profiles of patients in both groups are similar.
Prospective Randomized Trial of Normothermic versus Hypothermic Cardiopulmonary Bypass on Cognitive Function after Coronary Artery Bypass Graft Surgery
Authors: Grigore Alina M. , Mathew Joseph , Grocott Hilary P. , Reves Joseph G. , Blumenthal James A. , White William D. , Smith Peter K. , Jones Robert H. , Kirchner Jerry L. , Mark Daniel B. , Newman Mark F.
Published: November 2003

Background

Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery.

Methods

Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale.

Results

Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment.

Conclusions

Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.
Coronary Artery Plaque Burden and Perioperative Cardiac Risk
Authors: Mahla Elisabeth , Vicenzi Martin N. , Schröttner Brigitte , Maier Robert , Tiesenhausen Kurt , Watzinger Norbert , Rienmüller Rainer , Moser Rita L. , Metzler Helfried
Published: November 2003

Background

Electron-beam computed tomography-derived coronary calcium score correlates with the morphologic severity of coronary artery disease, reflecting both global atherosclerotic plaque formation and coronary artery luminal narrowing. The current study examines the impact of coronary atherosclerotic plaque burden, measured by coronary calcium score, on the potential for perioperative myocardial cell injury, as assessed by cardiac troponin T elevations in patients undergoing elective vascular surgery. The authors further investigated whether perioperative myocardial cell injury in those patients adversely affects noninvasive measures of left ventricular systolic function, such as ejection fraction and wall motion score.

Methods

Fifty-one consecutive patients scheduled for vascular surgery were enrolled in this prospective study. In addition to standard preoperative evaluation, including patient history and physical examination, electron-beam computed tomography scan, 12-lead electrocardiography, and transthoracic echocardiography were performed on the day before surgery. Subsequent evaluations on postoperative days 2 and 7 included transthoracic echocardiography and 12-lead electrocardiography. Cardiac troponin T determinations were performed on the day before surgery, immediately preoperatively, and on postoperative days 1, 2, 3, and 7.

Results

The median coronary calcium score of the 51 patients was 997.0 (25th percentile, 202.5; 75th percentile, 1,949.5). Cardiac troponin T elevations exclusively occurred in patients with a coronary calcium score greater than 1,000. The six patients (12%) with perioperative cardiac troponin T elevations had a 2.5-fold higher coronary calcium score than those without cardiac troponin T elevation (P = 0.021). In these patients, the ejection fraction decreased from 61 +/- 10% to 52 +/- 13% (mean +/- SD) on postoperative day 2 and was 54 +/- 16% on postoperative day 7 (P = 0.022).

Conclusion

A high electron-beam computed tomography coronary calcium score, reflecting substantial coronary plaque burden, carries an increased risk for myocardial cell injury after vascular surgery. In these patients, myocardial damage may result in deterioration of global systolic left ventricular function.
Wavelet Analysis of Middle Latency Auditory Evoked Responses
Authors: Kochs Eberhard , Stockmanns Gudrun , Thornton Christine , Nahm Werner , Kalkman Cor J.
Published: November 2003

Background

Middle latency auditory evoked responses (MLAER) as a measure of depth of sedation are critically dependent on data quality and the analysis technique used. Manual peak labeling is subject to observer bias. This study investigated whether a user-independent index based on wavelet transform can be derived to discriminate between awake and unresponsive states during propofol sedation.

Methods

After obtaining ethics committee approval and written informed consent, 13 volunteers and 40 patients were studied. In all subjects, propofol was titrated to loss of response to verbal command. The volunteers were allowed to recover, then propofol was titrated again to the same end point, and subjects were finally allowed to recover. From three MLAER waveforms at each stage, latencies and amplitudes of peaks Pa and Nb were measured manually. In addition, wavelet transform for analysis of MLAER was applied. Wavelet transform gives both frequency and time information by calculation of coefficients related to different frequency contents of the signal. Three coefficients of the so-called wavelet detail level 4 were transformed into a single index (Db3d4) using logistic regression analysis, which was also used for calculation of indices for Pa, Nb, and Pa/Nb latencies. Prediction probabilities for discrimination between awake and unresponsive states were calculated for all MLAER indices.

Results

During propofol infusion, subjects were unresponsive, and MLAER components were significantly depressed when compared with the awake states (P < 0.001). The wavelet index Db3d4 was positive for awake and negative for unresponsive subjects with a prediction probability of 0.92.

Conclusion

These data show that automated wavelet analysis may be used to differentiate between awake and unresponsive states. The threshold value for the wavelet index allows easy recognition of awake versus unresponsive subjects. In addition, it is independent of subjective peak identification and offers the advantage of easy implementation into monitoring devices.
Bispectral Index Monitoring during Sedation with Sevoflurane, Midazolam, and Propofol
Authors: Ibrahim Andra E. , Taraday Julie K. , Kharasch Evan D.
Published: November 2003

Background

Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed ability of BIS to predict sedation depth between sevoflurane, propofol, and midazolam. Quality of recovery was also compared.

Methods

Patients undergoing surgery with local or regional anesthesia and sedation were randomized to sevoflurane (n = 23), midazolam (n = 21), or propofol (n = 22). Sedation was titrated to Observers's Assessment of Alertness-Sedation score of 3 (responds slowly to voice). BIS and Observers's Assessment of Alertness-Sedation were measured every 5 min. BIS prediction probability (PK) was compared between drugs. Recovery was assessed by BIS and Digit Symbol Substitution and memory tests.

Results

Bispectral Index of responders to voice was significantly different from nonresponders (86 +/- 10 vs. 74 +/- 14, mean +/- SD; P < 0.001) However, wide variability and overlap in BIS were observed (25th-75th percentile, responders vs. non-responders: 79-96 vs. 65-83). BIS of responders was different for sevoflurane versus propofol and midazolam. BIS was a better predictor of propofol sedation than sevoflurane or midazolam (PK = 0.87 +/- 0.11, 0.76 +/- 0.01, and 0.69 +/- 0.02, respectively; P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement-disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05).

Conclusion

Individual BIS scores demonstrate significant variability, making it difficult to predict sedation depth. The relation between BIS and sedation depth may not be independent of anesthetic agent. Quality of recovery was similar between drugs, but excitement occurred frequently with sevoflurane.
The Effects of Aprotinin on Thromboelastography with Three Different Activators
Authors: Avidan Michael S. , Da Fonseca Jorge , Parmar Kiran , Alcock Emma , Ponte José , Hunt Beverley J.
Published: November 2003

Background

Thromboelastography is used for assessment of hemostasis. Adherence to thromboelastography-guided algorithms and aprotinin administration each decrease bleeding and blood product usage after cardiac surgery. Aprotinin, through inhibition of kallikrein, causes prolongation of the celite-activated clotting time and the activated partial thromboplastin ratio. The aim of this study was to assess the effects of aprotinin on the thromboelastography trace.

Methods

Three activators were used in the thromboelastography: celite (which is widely established), kaolin, and tissue factor. Assessment was performed on blood from volunteers and from patients before and after cardiac surgery.

Results

The tissue factor-activated thromboelastography trace was unaffected by the addition of aprotinin. When celite and kaolin were used as activators in the presence of aprotinin, the reaction time (time to clot formation) of the thromboelastography trace was prolonged (P < 0.0001) and the maximum amplitude (clot strength) was decreased (P < 0.05). With celite as an activator, the addition of aprotinin decreased (P < 0.05) the thromboelastography alpha angle (rate of clot extension). The reaction time of the celite-activated trace correlated with the activated partial thromboplastin ratio (P < 0.01). The reaction time of the tissue factor-activated trace correlated with the international normalized ratio (P < 0.01).

Conclusion

The thromboelastography trace is altered in the presence of aprotinin when celite and kaolin are used as activators but not when tissue factor is the activator.
Influence of Voltage-sensitive Ca++Channel Drugs on Bupivacaine Infiltration Anesthesia in Mice
Authors: Smith Forrest L. , Davis Richard W. , Carter Richard
Published: November 2003

Background

Local anesthesia has been traditionally associated with blockade of voltage-sensitive sodium (Na(+)) channels. Yet in vitro evidence indicates that local anesthetic mechanisms are more complex than previously understood. For example, local anesthetics bind and allosterically modify 1,4-dihydropyridine-sensitive Ca(++) channels and can reduce Ca(++) influx in tissues. The current study examines the influence of voltage-sensitive Ca(++) channels in bupivacaine infiltration anesthesia.

Methods

Baseline tail-flick latencies to radiant heat nociception were obtained before subcutaneous infiltration of bupivacaine and Ca(++)-modulating drugs in the tails of mice. No musculature is contained in the tail that could result in motor block. The magnitude of infiltration anesthesia over time, as well as the potency of bupivacaine alone or in the presence of Ca(++)-modulating drug, was assessed by obtaining test latencies.

Results

The 1,4-dihydropyridine L-type Ca(++) channel agonist S(-)-BayK-8644 reduced the duration of action and potency of bupivacaine anesthesia. In opposite fashion, nifedipine and nicardipine increased the effects of bupivacaine. Neither nifedipine nor nicardipine alone elicited anesthesia. Alternatively, the phenylalkylamine L-type blocker verapamil elicited concentration-dependent anesthesia. Other Ca(++) channel subtype blockers were investigated as well. The N-, T-, P-, and Q-type channel blockers, omega-conotoxin GVIA, flunarizine, omega-agatoxin IVA, and omega-conotoxin MVIIC, respectively, were unable to modify bupivacaine anesthesia.

Conclusions

These results indicate that heat nociception stimulates Ca(++) influx through L-type channels on nociceptors in skin. Although other voltage-sensitive Ca(++) channels may be located on skin nociceptors, only the L-type channel drugs affected bupivacaine in the radiant heat test.
Local Anesthetic Properties of Prenylamine
Authors: Mujtaba Mustafa G. , Gerner Peter , Kuo Wang Ging
Published: November 2003

Background

Local anesthetics that produce analgesia of long duration with minimal impairment of autonomic functions are highly desirable for pain management in the clinic. Prenylamine is a known calcium channel blocker, but its local anesthetic blocking effects on voltage-gated sodium channels have not been studied thus far.

Methods

The authors characterized the tonic and use-dependent prenylamine block of native Na(+) channels in cultured rat neuronal GH3 cells during whole cell voltage clamp conditions and the local anesthetic effect of prenylamine by neurologic evaluation of sensory and motor functions of sciatic nerve during neural block in rats.

Results

Prenylamine elicits both use-dependent block of Na(+) channels during repetitive pulses (3 microm prenylamine produced 50% block at 5 Hz) and tonic block for both resting and inactivated Na(+) channels. The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 microm for resting channels and 0.75 +/- 0.02 microm for inactivated channels. Furthermore, in vivo data show that 10 mm prenylamine produced a complete sciatic nerve block of motor function, proprioceptive responses, and nociceptive responses that lasted approximately 27, 34, and 24 h, respectively. Rats injected with 15.4 mm bupivacaine, a known local anesthetic currently used for pain management, had a significantly shorter duration of blockade (< 2 h) compared with rats injected with prenylamine.

Conclusions

The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo.
Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime
Authors: Wissing Heimo , Kuhn Iris , Warnken Uwe , Dudziak Rafael
Published: November 2003

Background

Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers.

Methods

Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Dräger absorber canister (bottom to top) filled with dried soda lime (Drägersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19-20 degrees C). The absorbent temperature was not controlled.

Results

Carbon monoxide production peaked initially and was highest with desflurane (507 +/- 70, 656 +/- 59 ml CO), followed by enflurane (460 +/- 41, 475 +/- 99 ml CO), isoflurane (176 +/- 2.8, 227 +/- 21 ml CO), sevoflurane (34 +/- 1, 104 +/- 4 ml CO), and halothane (22 +/- 3, 20 +/- 1 ml CO) (mean +/- SD at 2.5 and 5%, respectively).

Conclusions

The absorbent temperature increased with all anesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO hemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.
Halothane Inhibits Contraction and Action Potential Duration to a Greater Extent in Subendocardial than Subepicardial Myocytes from the Rat Left Ventricle
Authors: Rithalia Amber , Gibson Clare N. , Hopkins Philip M. , Harrison Simon M.
Published: November 2003

Background

Halothane inhibits the 4-aminopyridine-sensitive transient outward K(+) current (I(to)) which in many species, including humans, plays an important role in determining action potential duration. As I(to) is greater in the ventricular subepicardium than subendocardium, halothane may have differential effects on action potential duration and, therefore, contraction in cells isolated from these two regions.

Methods

Myocytes were isolated from the subendocardium and subepicardium of the rat left ventricle. Myocytes from each region were electrically stimulated at 1 Hz to measure contractions and action potentials and exposed to 0.6 mm halothane (approximately 2 x minimum alveolar concentration(50) for the rat) for 1 min. The time from the peak of the action potential to repolarization at 0 and -50 mV was measured to assess the effects of halothane on action potential duration.

Results

Halothane inhibited contraction to a significantly (P = 0.002) greater extent in subendocardial myocytes than in subepicardial myocytes: the amplitude of contraction during control conditions was 3.6 +/- 0.4 microm and 3.2 +/- 0.7 microm in subendocardial and subepicardial cells, respectively, and this was reduced to 1.1 +/- 0.2 microm (29 +/- 2% of control, P < 0.0001, n = 10) and 1.4 +/- 0.3 microm (46 +/- 3% of control, P = 0.007, n = 7), respectively, after a 1-min exposure to 0.6 mm halothane. Control action potential duration (at -50 mV) was 67 +/- 10 and 28 +/- 4 ms in subendocardial and subepicardial myocytes, respectively, and these values were reduced to 39 +/- 6 ms (58 +/- 3% of control, P < 0.001) and 20 +/- 3 ms (73 +/- 5% of control, P = 0.009) by halothane, respectively.

Conclusions

Action potential duration was reduced to a greater extent in subendocardial than subepicardial myocytes, which would contribute to the greater negative inotropic effect of halothane in the subendocardium. Furthermore, the transmural difference in action potential duration was reduced by halothane, which could contribute to its arrhythmogenic properties.
Consumption of Soy Diet before Nerve Injury Preempts the Development of Neuropathic Pain in Rats
Authors: Shir Yoram , Raja Srinivasa N. , Weissman Charles S. , Campbell James N. , Seltzer Ze’ev
Published: November 2003

Background

A previous report using a partial sciatic nerve ligation (PSL) model for neuropathic pain in rats demonstrated that consumption of soy-containing diets preoperatively and postoperatively suppressed development of mechanical and heat allodynia, as well as hyperalgesia. The current study examined whether dietary soy suppresses these neuropathic sensory disorders when consumed either before or after PSL injury.

Methods

Male Wistar rats were grouped into seven different feeding regimens. These rats were fed SOY (RMH-1000, PMI Feeds, St. Louis, MO), a diet containing 85% soy protein since weaning, and were then switched to noSOY (Bio-Serv Co., Frenchtown, NJ), a diet devoid of soy at certain time points before PSL injury (14, 7, 1 days, or 15 and 0 h). Postoperatively, these rats were fed SOY or noSOY diets. Levels of mechanical and heat allodynia and hyperalgesia were determined preoperatively and 3, 8, and 14 days after PSL injury.

Results

Compared with groups fed preoperative noSOY, consumption of SOY before PSL injury significantly blunted postoperative levels of allodynia and hyperalgesia. Administering the SOY diet both before and after PSL injury provided no additional suppression of neuropathic pain. No pain suppression was noted in rats fed a noSOY diet preoperatively and SOY diet after PSL injury. Switching from SOY to noSOY feeding within 15 h of PSL injury was sufficient to allow for the full development of allodynia and hyperalgesia.

Conclusions

Consumption of a soy-containing diet suppressed the development of neuropathic pain after PSL injury. The pain-suppressing properties of dietary soy were the result of a preemptive effect (i.e., when consumed preoperatively), but not a palliative effect (i.e., when consumed postoperatively). This effect of soy-containing diets appears to be short-lived, since switching to a noSOY diet 15 h before ligation abrogated the suppressive effect of soy.
Are Estimates of MAC Reliable?
Authors: Paul Matthias , Fisher Dennis M.
Published: November 2003

Background

Potency of inhaled anesthetics (minimum alveolar concentration [MAC]) is typically studied in humans using an "up-down" approach in which the (quantal) response to skin incision is assessed only once for each individual, so that each individual's MAC is never determined. The authors examined the influence of interindividual variability and study design issues (e.g., the number of patients enrolled in a study) on the accuracy of MAC estimates.

Methods

The typical sequence of a MAC study was simulated. The authors varied and tested the impact of several factors: anesthetic concentration used to start a study; number of "crossovers" (successive patients having different responses to skin incision) to terminate a study; concentration increment between consecutive patients; interindividual variability; and "measurement error." For each factor, simulations were replicated 500 times, and the resulting estimates were summarized.

Results

Starting an experiment below or above the "true" value led to slightly biased MAC estimates; in contrast, variability was underestimated with starting concentrations close to the true value. More than six crossovers improved MAC estimates minimally but increased variability estimates toward true values. A larger increment size affected MAC minimally and increased variability estimates toward true values. A larger interindividual variability led to more "outlier" estimates for MAC. Under many conditions, several of 500 replicates yielded MAC estimates that deviated more than 10% or even more than 25% from the "true" value.

Conclusion

Individual experiments may yield inaccurate MAC estimates. This inaccuracy is minimized as the number of crossovers increases; however, improvement diminishes as the number of crossovers exceeds six.
Effect of Clonidine on Lidocaine Clearance In Vivo
Authors: Kopacz Dan J. , Bernards Christopher M.
Published: November 2003

Background

The addition of clonidine to local anesthetics has been shown to prolong both peripheral and central neuraxial local anesthetic blocks. Whether clonidine prolongs local anesthetic block by a pharmacokinetic effect or a pharmacodynamic effect is unclear. By directly measuring lidocaine tissue concentrations at the site of injection in the presence and absence of clonidine, this study was designed to address this question.

Methods

Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of seven volunteers. Plain lidocaine (1%) was injected along one nerve, and lidocaine with clonidine (10 microg/ml) was injected along the other nerve in a double-blind, randomized manner. The extracellular fluid was then sampled for lidocaine concentration at 5-min intervals using microdialysis, cutaneous blood flow was assessed by laser Doppler at 10-min intervals, and sensory block was assessed every 10 min until resolution.

Results

Consistent with previous studies, clonidine prolonged lidocaine sensory block. Blood flow increased in both groups but was significantly lower in the clonidine group, especially during the first 60 min. Consistent with the lower blood flow, the area under the lidocaine concentration-versus-time curve was significantly greater in the clonidine group during the first 60 min.

Conclusion

When added to lidocaine, clonidine prolonged peripheral nerve block. The pharmacokinetic data suggest that the mechanism of prolongation is at least in part pharmacokinetic.