bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic-Pharmacodynamic Modeling of the Respiratory Depressant Effect of Alfentanil
Authors: Bouillon Thomas , Schmidt Christina , Garstka Gudrun , Heimbach Dirk , Stafforst Dieter , Schwilden Helmut , Hoeft Andreas
Published: November 2003

Background

Although respiratory depression is the most well-known and dangerous side effect of opioids, no pharmacokinetic-pharmacodynamic model exists for its quantitative analysis. The development of such a model was the aim of this study.

Methods

After institutional approval approval and informed consent were obtained, 14 men (American Society of Anesthesiologists physical status I or II; median age, 42 yr [range, 20-71 yr]; median weight, 82.5 kg [range, 68-108 kg]) were studied before they underwent major urologic surgery. An intravenous infusion of alfentanil (2.3 microg x kg(-1) x min(-1)) was started while the patients were breathing oxygen-enriched air (fraction of inspired oxygen [FIO2 = 0.5) over a tightly fitting continuous positive airway pressure mask. The infusion was discontinued when a cumulative dose of 70 microg/kg had been administered, the end-expiratory partial pressure of carbon dioxide (PE(CO2) exceeded 65 mmHg, or apneic periods lasting more than 60 s occurred During and after the infusion, frequent arterial blood samples were drawn and analyzed for the concentration of alfentanil and the arterial carbon dioxide pressure (PaCO2). A mamillary two-compartment model was fitted to the pharmacokinetic data. The PaCO2 data were described by an indirect response model The model accounted for the respiratory stimulation resulting from increasing PaCO2. The model parameters were estimated using NONMEM. Simulations were performed to define the respiratory response at steady state to different alfentanil concentrations.

Results

The indirect response model adequately described the time course of the PaCO2. The following pharmacodynamic parameters were estimated (population means and interindividual variability): EC50, 60.3 microg/l (32%); the elimination rate constant of carbon dioxide (Kel), 0.088 min(-1) (44%); and the gain in the carbon dioxide response, 4(28%) (fixed according to literature values). Simulations revealed the pronounced role of PaCO2 in maintaining alveolar ventilation in the presence of opioid.

Conclusions

The model described the data for the entire opioid-PaCo2 response surface examined. Indirect response models appear to be a promising tool for the quantitative evaluation of drug-induced respiratory depression.
Differential Effects of Sevoflurane, Isoflurane, and Halothane on Ca (2+) Release from the Sarcoplasmic Reticulum of Skeletal Muscle
Authors: Kunst Gudrun , Graf Bernhard M. , Schreiner Rupert , Martin Eike , Fink Rainer H. A.
Published: November 2003

Background

Although malignant hyperthermia after application of sevoflurane has been reported, little is known about its action on intracellular calcium homeostasis of skeletal muscle. The authors compared the effect of sevoflurane with that of isoflurane and halothane on Ca2+ release of mammalian sarcoplasmic reticulum and applied a novel method to quantify Ca2+ turnover in permeabilized skeletal muscle fibers.

Methods

Liquid sevoflurane, isoflurane, and halothane at 0.6 mM, 3.5 mM, and 7.6 mm were diluted either in weakly calcium buffered solutions with no added Ca2+ (to monitor Ca2+ release) or in strongly Ca2+ buffered solutions with [Ca2+] values between 3 nM and 24.9 microm for [Ca+]-force relations. Measurements were taken on single saponin skinned muscle fiber preparations of BALB/c mice. Individual [Ca2+]force relations were characterized by the Ca2+ concentration at half-maximal force that indicates the sensitivity of the contractile proteins and by the steepness. Each force transient was transformed directly into a Ca2+ transient with respect to the individual [Ca2+]-force relation of the fiber.

Results

At 0.6 mM, single force transients induced by sevoflurane were lower compared with equimolar concentrations of isoflurane and halothane (P < 0.05). Similarly, calculated peak Ca2+ transients of sevoflurane were lower than those induced by equimolar halothane (P < 0.05). The Ca2+ concentrations at half maximal force were decreased after the addition of sevoflurane, isoflurane, and halothane in a concentration-dependent manner (P < 0.05).

Conclusion

Whereas sevoflurane, isoflurane, and halothane similarly increase the Ca2+ sensitivity of the contractile apparatus in skeletal muscle fibers, 0.6 mM sevoflurane induces smaller Ca2+ releases from the sarcoplasmic reticulum than does equimolar halothane.
Spinal Antinociceptive Effect of Epidural Nonsteroidal Antiinflammatory Drugs on Nitric Oxide-induced Hyperalgesia in Rats
Authors: Masue Tatsuhiko , Dohi Shuji , Asano Toshio , Shimonaka Hiroyuki
Published: November 2003

Background

Nonsteroidal antiinflammatory drugs (NSAIDs) suppress various hyperalgesia perhaps via inhibition of cyclooxygenase activity at the spinal cord. The present study aimed to examine whether epidural application of NSAIDs affects hyperalgesia induced by nitric oxide.

Methods

The authors studied the antinociceptive effects of epidurally administered NSAIDs in rats with a chronically in-dwelling epidural catheter by three hyperalgesic models, including nitric oxide-induced hyperalgesia by nitroglycerin (10 microg) or l-arginine (100 microg), and the biphasic response in the formalin test.

Results

Epidural, but not systemic, nitroglycerin induced hyperalgesia that was completely blocked by methylene blue but not by N(omega)-nitro-L-arginine methyl ester (L-NAME). Epidural l-arginine, but not d-arginine, also induced hyperalgesia that was completely blocked by L-NAME. Epidural S(+)ibuprofen (100-1,000 microg) suppressed the nitroglycerin- and l-arginine-induced thermal hyperalgesia and also the second phase response in the formalin test. Neither systemic S(+)ibuprofen nor epidural R(-)ibuprofen suppressed the hyperalgesia Epidural indomethacin (10-100 microg) or diclofenac (10-1,000 microg) dose-dependently suppressed nitroglycerin-induced thermal hyperalgesia The order of potency for this suppression (ID50 in microg) was indomethacin = didofenac > S(+)ibuprofen > R(-)ibuprofen.

Conclusions

The antinociceptive action of epidurally administered NSAIDs could be the result of suppression of spinal sensitization, perhaps induced with nitric oxide in the spinal cord. The ID50 values for epidural indomethacin, diclofenac, and S(+)ibuprofen were about 10 times higher than those reported in other studies for intrathecal NSAIDs in hyperalgesia models. (Key words: Cyclooxygenase inhibitors; NO donor; NO precursor; optical isomers; neuroplasticity.)
Inhibition of Nitric Oxide Synthase Prevents Hyporesponsiveness to Inhaled Nitric Oxide in Lungs from Endotoxin-challenged Rats
Authors: Holzmann Alexandra , Manktelow Claire , Taut Friedemann J. H. , Bloch Kenneth D. , Zapol Warren
Published: November 2003

Background

Inhalation of nitric oxide (NO) selectively dilates the pulmonary circulation and improves arterial oxygenation in patients with adult respiratory distress syndrome (ARDS). In approximately 60% of patients with septic ARDS, minimal or no response to inhaled NO is observed. Because sepsis is associated with increased NO production by inducible NO synthase (NOS2), the authors investigated whether NOS inhibition alters NO responsiveness in rats exposed to gram-negative lipopolysaccharide (LPS).

Methods

Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli O111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured.

Results

Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75+/-0.25, 1.25+/-0.25, 1.75+/-0.25 mmHg) than in lungs of control rats (3+/-0.5, 4.25+/-0.25, 4.5+/-0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75+/-0.25, 4.5+/-0.25, 4.5+/-0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0+/-1.0, 4.0+/-1.0, 4.0+/-0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75+/-0.25, 2.25+/-0.5, 2.75+/-0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness.

Conclusion

These observations demonstrate that LPS-mediated increases in pulmonary NOS2 are involved in decreasing responsiveness to inhaled NO.
Recovery Profile, Costs, and Patient Satisfaction with Propofol and Sevoflurane for Fast-track Office-based Anesthesia
Authors: Tang Jun , Chen Lei , White Paul F. , Watcha Mehernoor F. , Wender Ronald H. , Naruse Robert , Kariger Robert , Sloninsky Alexander
Published: November 2003

Background

Office-based surgery is becoming increasingly popular because of its cost-saving potential Both propofol and sevoflurane are commonly used in the ambulatory setting because of their favorable recovery profiles. This clinical investigation was designed to compare the clinical effects, recovery characteristics, and cost-effectiveness of propofol and sevoflurane when used alone or in combination for office-based anesthesia.

Methods

One hundred four outpatients undergoing superficial surgical procedures at an office-based surgical center were randomly assigned to one of three general anesthetic groups. In groups I and II, propofol 2 mg/kg was administered for induction followed by propofol 75-150 microg x kg(-1) x min(-1) (group I) or sevoflurane 1-2% (group II) with N2O 67% in oxygen for maintenance of anesthesia In group m, anesthesia was induced and maintained with sevoflurane in combination with N2O 67% in oxygen. Local anesthetics were injected at the incision site before skin incision and during the surgical procedure. The recovery profiles, costs of drugs, and resources used, as well as patient satisfaction, were compared among the three treatment groups.

Results

Although early recovery variables (e.g., eye opening, response to commands, and sitting up) were similar in all three groups, the times to standing up and to be "home ready" were significantly prolonged when sevoflurane-N2O was used for both induction and maintenance of anesthesia. The time to tolerating fluids, recovery room stay, and discharge times were significantly decreased when propofol was used for both induction and maintenance of anesthesia. Similarly, the incidence of postoperative nausea and vomiting and the need for rescue antiemetics were also significantly reduced after propofol anesthesia. Finally, the total costs and patient satisfaction were more favorable when propofol was used for induction and maintenance of office-based anesthesia

Conclusion

Compared with sevoflurane-N2O, use of propofol-N2O for office-based anesthesia was associated with an improved recovery profile, greater patient satisfaction, and lower costs. There were significantly more patients who were dissatisfied with the sevoflurane anesthetic technique.
Statistical Method to Evaluate Management Strategies to Decrease Variability in Operating Room Utilization
Authors: Dexter Franklin , Macario Alex , Lubarsky David A. , Burns David D.
Published: November 2003

Background

Operating room (OR) managers seeking to maximize labor productivity in their OR suite may attempt to reduce day-today variability in hours of OR time for which there are staff but for which there are no cases ("underutilized time"). The authors developed a method to analyze data from surgical services information systems to evaluate which management interventions can most effectively decrease variability in underutilized time.

Methods

The method uses seven summary statistics of daily workload in a surgical suite: daily allocated hours of OR time, estimated hours of elective cases, actual hours of elective cases, estimated hours of add-on cases, actual hours of add-on cases, hours of turnover time, and hours of underutilized time. Simultaneous linear statistical equations (a structural equation model) specify the relationship among these variables. Estimated coefficients are used in Monte Carlo simulations.

Results

The authors applied the analysis they developed to two OR suites: a tertiary care hospital's suite and an ambulatory surgery center. At both suites, the most effective strategy to decrease variability in underutilized OR time was to choose optimally the day on which to do each elective case so as to best fill the allocated hours. Eliminating all (1) errors in predicting how long elective or add-on cases would last, (2) variability in turnover or delays between cases, or (3) day-to-day variation in hours of add-on cases would have a small effect.

Conclusions

This method can be used for decision support to determine how to decrease variability in underutilized OR time.
Consistency, Inter-rater Reliability, and Validity of 441 Consecutive Mock Oral Examinations in Anesthesiology
Authors: Schubert Armin , Tetzlaff John E. , Tan Ming , Ryckman Victor J. , Mascha Edward
Published: November 2003

Background

Oral practice examinations (OPEs) are used extensively in many anesthesiology programs for various reasons, including assessment of clinical judgment. Yet oral examinations have been criticized for their subjectivity. The authors studied the reliability, consistency, and validity of their OPE program to determine if it was a useful assessment tool.

Methods

From 1989 through 1993, we prospectively studied 441 OPEs given to 190 residents. The examination format closely approximated that used by the American Board of Anesthesiology. Pass-fail grade and an overall numerical score were the OPE results of interest. Internal consistency and inter-rater reliability were determined using agreement measures. To assess their validity in describing competence, OPE results were correlated with in-training examination results and faculty evaluations. Furthermore, we analyzed the relationship of OPE with implicit indicators of resident preparation such as length of training.

Results

The internal consistency coefficient for the overall numerical score was 0.82, indicating good correlation among component scores. The interexaminer agreement was 0.68, indicating moderate or good agreement beyond that expected by chance. The actual agreement among examiners on pass-fail was 84%. Correlation of overall numerical score with in-training examination scores and faculty evaluations was moderate (r = 0.47 and 0.41, respectively; P < 0.01). OPE results were significantly (P < 0.01) associated with training duration, previous OPE experience, trainee preparedness, and trainee anxiety.

Conclusion

Our results show the substantial internal consistency and reliability of OPE results at a single institution. The positive correlation of OPE scores with in-training examination scores, faculty evaluations, and other indicators of preparation suggest that OPEs are a reasonably valid tool for assessment of resident performance.
Nitecapone Reduces Cardiac Neutrophil Accumulation in Clinical Open Heart Surgery
Authors: Pesonen Eero J. , Vento Antti E. , Ramo Juhani O. , Vuorte Juha , Jansson Sten-Erik , Repo Heikki
Published: November 2003

Background

To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients.

Methods

In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping.

Results

Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range].

Conclusion

Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.
Anesthetic Doses of Sevoflurane To Block Cardiovascular Responses to Incision when Administered with Xenon or Nitrous Oxide
Authors: Nakata Yoshinori , Goto Takahisa , Ishiguro Yoshiki , Terui Katsuo , Niimi Yoshinari , Morita Shigeho
Published: November 2003

Background

The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2O.

Methods

Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.

Results

The MAC-BAR of sevoflurane, including the contribution of Xe or N2O, was 2.1+/-0.2 MAC and 2.7+/-0.2 MAC when administered with 1 MAC and 0.7 MAC Xe, respectively, and 2.6+/-0.4 MAC when administered with 0.7 MAC N2O (mean +/- SD).

Conclusions

Although 1 MAC Xe has a more potent suppressive effect on cardiovascular responses to incision than 0.7 MAC Xe or N2O, Xe and N2O have a similar suppressive effect at 0.7 MAC.
Analgesic and Hemodynamic Effects of Intrathecal Clonidine as the Sole Analgesic Agent during First Stage of Labor
Authors: Chiari Astrid , Lorber Christine , Eisenach James C. , Wildling Eckart , Krenn Claus , Zavrsky Ana , Kainz Christian , Germann Peter , Klimscha Walter
Published: November 2003

Background

Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances labor analgesia from intrathecal sufentanil. The authors evaluated the dose-response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects.

Methods

Thirty-six parturients requesting labor analgesia were included in this prospective, randomized, double-blind study. Parturients with < 6 cm cervical dilatation received either 50, 100, or 200 microg intrathecal clonidine. The authors recorded visual analog pain score (VAPS), maternal blood pressure and heart rate, ephedrine requirements, and sedation at regular intervals and fetal heart rate tracings continuously. Duration of analgesia was defined as time from intrathecal clonidine administration until request for additional analgesia.

Results

Clonidine produced a reduction in VAPS with all three doses. The duration of analgesia was significantly longer in patients receiving 200 microg (median, 143; range, 75-210 min) and 100 microg (median, 118; range, 60-180 min) than 50 microg (median, 45; range, 25-150 min), and VAPS was lower in the 200-microg than in the 50-microg group. In the 200-microg group, hypotension required significantly more often treatment with ephedrine than in the other groups. No adverse events or fetal heart rate abnormalities occurred.

Conclusions

Fifty to 200 microg intrathecal clonidine produces dose-dependent analgesia during first stage of labor. Although duration and quality of analgesia were more pronounced with 100 and 200 microg than with 50 microg, the high incidence of hypotension requires caution with the use of 200 microg for labor analgesia.
Adenosine
Authors: Weigand Markus A. , Michel Andre , Eckstein Hans-Henning , Martin Eike , Bardenheuer Hubert J.
Published: November 2003

Background

For the human brain, there are no data available concerning the significance of adenosine and its metabolites as biochemical indicators of cerebral ischemia. Since adenosine may counteract key pathogenetic mechanisms during cerebral ischemia, its sensitivity and specificity as a marker of cerebral ischemia was investigated in relation to hypoxanthine and lactate.

Methods

Arterial and jugular venous concentration changes of adenosine, hypoxanthine, and lactate were studied in 41 patients undergoing carotid endarterectomy. Cerebral tissue oxygenation was monitored continuously by somatosensory-evoked potentials. A carotid artery shunt (n = 6) was placed only after complete loss of somatosensory-evoked potentials.

Results

Before carotid artery clamping jugular venous concentrations of adenosine, hypoxanthine, and lactate in subsequently shunted patients were 229+/-88 nM, 1105+/-116 nM, and 0.85+/-0.52 mM, respectively (mean +/- SD). In patients who required shunting, carotid artery clamping induced a significant increase in jugular venous adenosine (389+/-114 nM) and jugular venous hypoxanthine (1444+/-168 nM). In contrast, the increase in jugular venous lactate (0.91+/-0.48 mM) did not reach statistical significance. Focal cerebral ischemia was indicated by jugular venous adenosine with a sensitivity and specificity of 0.83 and 0.71, respectively.

Conclusions

Carotid artery clamping induced significant increases in jugular venous adenosine and hypoxanthine in patients with inadequate collateral blood flow. In addition, focal cerebral ischemia was reflected by changes in adenosine concentrations.
Relative Contribution of Skin and Core Temperatures to Vasoconstriction and Shivering Thresholds during Isoflurane Anesthesia
Authors: Lenhardt Rainer , Greif Robert , Sessler Daniel I. , Laciny Sonja , Rajek Angela , Bastanmehr Hiva
Published: November 2003

Background

Thermoregulatory control is based on both skin and core temperatures. Skin temperature contributes approximately 20% to control of vasoconstriction and shivering in unanesthetized humans. However, this value has been used to arithmetically compensate for the cutaneous contribution to thermoregulatory control during anesthesia--although there was little basis for assuming that the relation was unchanged by anesthesia. It even remains unknown whether the relation between skin and core temperatures remains linear during anesthesia. We therefore tested the hypothesis that mean skin temperature contributes approximately 20% to control of vasoconstriction and shivering, and that the contribution is linear during general anesthesia.

Methods

Eight healthy male volunteers each participated on 3 separate days. On each day, they were anesthetized with 0.6 minimum alveolar concentrations of isoflurane. They then were assigned in random order to a mean skin temperature of 29, 31.5, or 34 degrees C. Their cores were subsequently cooled by central-venous administration of fluid at approximately 3 degrees C until vasoconstriction and shivering were detected. The relation between skin and core temperatures at the threshold for each response in each volunteer was determined by linear regression. The proportionality constant was then determined from the slope of this regression. These values were compared with those reported previously in similar but unanesthetized subjects.

Results

There was a linear relation between mean skin and core temperatures at the vasoconstriction and shivering thresholds in each volunteer: r2 = 0.98+/-0.02 for vasoconstriction, and 0.96+/-0.04 for shivering. The cutaneous contribution to thermoregulatory control, however, differed among the volunteers and was not necessarily the same for vasoconstriction and shivering in individual subjects. Overall, skin temperature contributed 21+/-8% to vasoconstriction, and 18+/-10% to shivering. These values did not differ significantly from those identified previously in unanesthetized volunteers: 20+/-6% and 19+/-8%, respectively.

Conclusions

The results in anesthetized volunteers were virtually identical to those reported previously in unanesthetized subjects. In both cases, the cutaneous contribution to control of vasoconstriction and shivering was linear and near 20%. These data indicate that a proportionality constant of approximately 20% can be used to compensate for experimentally induced skin-temperature manipulations in anesthetized as well as unanesthetized subjects.
Cecal Ligation and Puncture Peritonitis Model Shows Decreased Nicotinic Acetylcholine Receptor Numbers in Rat Muscle
Authors: Tsukagoshi Hiroshi , Morita Toshihiro , Takahashi Kenichiro , Kunimoto Fumio , Goto Fumio
Published: November 2003

Background

Although systemic inflammation is believed to cause upregulation of nicotinic acetylcholine receptors (nAchRs) in muscle, chronic infections such as Chagas' disease occasionally are complicated by myasthenia gravis. The authors investigated how a nonlethal cecal ligation and puncture (CLP) peritonitis model in rats could affect muscle nAchR.

Methods

On day 1, 4, 7, 14, or 21 after CLP or sham operation, nAchR binding was assayed in the anterior tibial muscle and diaphragm using [125I]alpha-bungarotoxin. The presence or absence of weakness, in vivo dose-response relationships for d-tubocurarine, and serum anti-nAchR antibody titers were assayed in separate experiments.

Results

Systemic inflammation was most severe during the first 4 to 5 days. Numbers of nAchRs were decreased in anterior tibial muscle on days 7, 14, and 21 after CLP, and in the diaphragm on days 7 and 14 (P < 0.01). Both 50% and 90% blocking doses of d-tubocurarine) were lower in CLP rats than in sham-operated rats on days 7, 14, and 21 (P < .05). Weakness was overt in approximately half of CLP rats at these times. Serum anti-nAchR antibody (0.7-1.4 nM) was detectable beginning on day 4 and continuing throughout the 21-day observation period in 58-67% of CLP rats.

Conclusions

During the recovery phase of injury, nonlethal CLP peritonitis resulted in downregulation of nAchR. However, further study is needed to determine the role of anti-nAchR antibodies in the development of decreased receptor numbers and impaired neuromuscular function.
Vaporized Perfluorocarbon Improves Oxygenation and Pulmonary Function in an Ovine Model of Acute Respiratory Distress Syndrome
Authors: Bleyl Jorg U. , Ragaller Maximilian , Tscho Uwe , Regner Mike , Kanzow Maria , Hubler Matthias , Rasche Stefan , Albrecht Michael
Published: November 2003

Background

Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury.

Methods

Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals.

Results

Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376+/-182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward.

Conclusion

Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury.
Specific Actions of Halothane, Isoflurane, and Desflurane on Sympathetic Activity and A [Greek small letter delta] and C Somatosympathetic Reflexes Recorded in Renal Nerves in Dogs
Authors: Pac-Soo Chen K. , Ma Daqing , Wang Chen , Chakrabarti Mihir K. , Whitwam James G.
Published: November 2003

Background

This was a study of the relative effects on directly recorded sympathetic activity of desflurane, isoflurane, and halothane.

Methods

Renal sympathetic nerve activity (RSNA) was recorded with bipolar electrodes in renal nerves exposed retroperitoneally in anesthetized (alpha-chloralose), paralyzed (succinylcholine), and artificially ventilated dogs. Somatosympathetic responses were evoked by supramaximal electrical stimulation of radial nerves (0.33 Hz, 30 V, 0.5 ms). Spontaneous and evoked activity were rectified, averaged, and integrated to allow quantitative comparison of the effects of 3-12% desflurane, 0.6-2.4% isoflurane, and 0.4-1.6% halothane.

Results

Increasing concentrations of isoflurane progressively depressed mean RSNA, Adelta, and C reflexes by 40% (P < 0.01), 50% (P < 0.01) and 70% (P < 0.001) respectively at 2.4% concentration. Halothane depressed both reflexes equally by approximately 60% (P < 0.01) at 1.6% concentration, without significant depression of spontaneous RSNA. Desflurane increased and subsequently decreased RSNA by 37% (P < 0.02) and 65% (P < 0.001) at concentrations of 6% and 12% respectively, and although somatosympathetic reflexes remained unchanged up to 9%, both were depressed equally by 70% (P < 0.01) at 12% concentration.

Conclusion

After equilibration, lower concentrations of desflurane remained excitatory, but, like isoflurane, higher concentrations depressed RSNA. The effect of halothane on RSNA was insignificant. Isoflurane depressed C more than Adelta somatosympathetic reflexes, which is uncorrelated with lipid solubility because desflurane and halothane, which have the highest and lowest minimum alveolar concentration, respectively, depressed both equally.
Direct Effects of α1-and α2-AdrenergicAgonists on Spinal and Cerebral Pial Vessels in Dogs
Authors: Iida Hiroki , Ohata Hiroto , Iida Mami , Watanabe Yukinaga , Dohi Shuji
Published: November 2003

Background

The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of alpha2- and alpha1-adrenergic agonists on spinal and cerebral pial vessels in vivo.

Methods

Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 microg/ml; [2.1, 1.9, 2.5, and 2.3] x [10(-6), 10(-5), and 10(-4)] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window.

Results

On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 microg/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels).

Conclusion

Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.
Tourniquet Constriction Exacerbates Hyperalgesia-related Pain Induced by Intradermal Capsaicin Injection
Authors: Byas-Smith Michael G. , Bennett Gary J. , Gracely Richard H. , Max Mitchell B. , Robinovitz Elaine , Dubner Ronald
Published: November 2003

Background

When capsaicin is injected intradermally, hyperalgesia develops around the injection site. The authors observed that volunteers report painful sensations in the skin remote from the injection site during tourniquet constriction of the affected extremity.

Methods

Each volunteer received an intradermal injection of capsaicin on the volar forearm, followed by intermittent tourniquet constriction of the extremity. In some participants, the tourniquet position was rotated between different sites on the upper extremities. Laser Doppler measurements were made in the skin to measure capillary blood flow during pain magnification.

Results

Hyperalgesia developed in the volunteers who were tested after the capsaicin injection. Blood flow increased three times in the dermal capillaries remote from the injection site after capsaicin injection. The tourniquet-induced pain reached peak intensity soon after tourniquet inflation. Tourniquet constriction of the arm on the affected side reliably induced painful exacerbation in each person tested. The quality of the sensation was described as burning and extended across the arm in most volunteers. Only when pinprick hyperalgesia was detectable did the volunteers experience the diffuse, immediate pain sensation. The pain initiated by the tourniquet constriction likely is related to changes in skin capillary blood flow.

Conclusions

Low cutaneous blood perfusion is related to the intensity of ongoing, spontaneous pain when secondary hyperalgesia is present. The specific trigger(s) have yet to be identified.
Intramuscular Rocuronium in Infants and Children
Authors: Kaplan Richard F. , Uejima T. , Lobel G. , Goudsouzian N. , Ginsberg B. , Hannallah Raafat , Coté Charles J. , Denman William , Griffith Renny , Clarke Chris , Hummer Kelly
Published: November 2003

Background

This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia.

Methods

Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if <2.5 yr; 0.80% end-tidal concentration if >2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed.

Results

The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children).

Conclusions

Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.
Clinical Assessment of a Plastic Optical Fiber Stylet for Human Tracheal Intubation
Authors: Gravenstein Dietrich , Melker Richard J. , Lampotang Samsun
Published: November 2003

Background

The authors compared the performance of a prototype intubation aid that incorporated plastic illumination and image guides into a stylet with fiberoptic bronchoscopy and direct laryngoscopy for tracheal intubation by novice users.

Methods

In a randomized, nonblinded design, patients were assigned to direct laryngoscopy, fiberoptic bronchoscopy, or imaging stylet intubation groups. The quality of laryngeal view and ease with which it was attained for each intubation was graded by the laryngoscopist. Time to intubation was measured in 1-min increments. A sore-throat severity grade was obtained after operation.

Results

There were no differences in demographic, physical examination, or surgical course characteristics among the groups. The laryngoscope produced an adequate laryngeal view more easily than did the imaging stylet or bronchoscope (P = 0.001) but caused the highest incidence of postoperative sore throat (P<0.05). Although the time to intubation for direct laryngoscopy was shorter than for imaging stylet, which was shorter than fiberoptic bronchoscopy (P<0.05), the quality of laryngeal view with the imaging stylet was inferior to both direct laryngoscopy and fiberoptic bronchoscopy techniques (P<0.05).

Conclusions

Novices using the imaging stylet produce fewer cases of sore throat (compared with direct laryngoscopy) and can intubate faster than when using a bronchoscope in anesthetized adult patients. The imaging stylet may be a useful aid for tracheal intubation, especially for those unable to maintain skills with a bronchoscope.
Cerebral Microembolism Diagnosed by Transcranial Doppler during Total Knee Arthroplasty
Authors: Sulek Cheri A. , Davies Laurie K. , Enneking Kayser F. , Gearen Peter A. , Lobato Emilio B.
Published: November 2003

Background

Tourniquet deflation following total knee arthroplasty (TKA) frequently results in release of emboli into the pulmonary circulation. Small emboli may gain access to the systemic circulation via a transpulmonary route or through a patent foramen ovale. This study examined the incidence of cerebral microembolism after tourniquet release by transcranial Doppler (TCD) ultrasonography and its correlation with echogenic material detected in the left atrium.

Methods

Twenty-two adult patients (9 men, 13 women) undergoing TKA were studied with simultaneous TCD ultrasonography and transesophageal echocardiography. Data were recorded after anesthesia induction and tourniquet inflation and during tourniquet deflation. Emboli counts were performed manually off-line. Echogenic material in the left atrium was qualitatively assessed and correlated with TCD data. Patients were examined postoperatively for focal neurologic deficits.

Results

Fifteen patients had unilateral TKA (six left, nine right) and seven had bilateral TKA. Cerebral emboli were detected in 9 of 15 patients (60%) with unilateral TKA and in 4 of 7 patients (57%) with bilateral TKA. Echogenic material was identified in the left atrium in eight patients (two through a patent foramen ovale and six from the pulmonary veins). Emboli counts were significantly higher in patients with bilateral TKA compared with those with unilateral TKA (P<0.05). Duration of tourniquet time in patients with emboli was longer only during bilateral TKA (P<0.05). All patients with echogenic material in the left atrium detected by transesophageal echocardiography had emboli as assessed by TCD ultrasonography. No focal neurologic deficits were identified.

Conclusions

Cerebral microembolism occurs frequently during tourniquet release, even in the absence of a patient foramen ovale. This passage most likely occurs through the pulmonary capillaries or the opening of recruitable pulmonary vessels.
Ritonavir's Role in Reducing Fentanyl Clearance and Prolonging Its Half-life
Authors: Olkkola Klaus T. , Palkama Vilja J. , Neuvonen Pertti J.
Published: November 2003

Background

The human immunodeficiency virus protease inhibitor ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme, and ritonavir's concomitant administration with the substrates of this enzyme may lead to dangerous drug interactions.

Methods

The authors investigated possible interactions between ritonavir and intravenously administered fentanyl in a double-blind, placebo-controlled, cross-over study in two phases. Twelve healthy volunteers received orally ritonavir or placebo for 3 days; the dose of ritonavir was 200 mg three times on the first day and 300 mg three times on the second. The last dose of ritonavir 300 mg or placebo was given on the morning of the third day. On the second day, 2 h after the afternoon pretreatment dose, fentanyl 5 microg/kg was injected intravenously in 2 min with naloxone to moderate its effects, and 15 timed venous blood samples were collected for 18 h.

Results

Ritonavir reduced the clearance of fentanyl by 67% from 15.6+/-8.2 to 5.2+/-2.0 ml x min(-1) x kg(-1) (P<0.01). The area under the fentanyl plasma concentration-time curve from 0 to 18 h was increased from 4.8+/-2.7 to 8.8+/-2.3 ng x ml(-1) x h(-1) by ritonavir (P<0.01). Ritonavir did not affect the initial concentrations and the steady-state volume of distribution of fentanyl. One subject discontinued participation before fentanyl administration because of severe side effects, and during the study 8 of the remaining 11 subjects reported nausea.

Conclusions

Ritonavir can inhibit the metabolism of fentanyl significantly, so caution should be exercised if fentanyl is given to patients receiving ritonavir medication.
A Simplified Risk Score for Predicting Postoperative Nausea and Vomiting
Authors: Apfel Christian C. , Läärä Esa , Koivuranta Merja , Greim Clemens-A. , Roewer Norbert
Published: November 2003

Background

Recently, two centers have independently developed a risk score for predicting postoperative nausea and vomiting (PONV). This study investigated (1) whether risk scores are valid across centers and (2) whether risk scores based on logistic regression coefficients can be simplified without loss of discriminating power.

Methods

Adult patients from two centers (Oulu, Finland: n = 520, and Wuerzburg, Germany: n = 2202) received inhalational anesthesia (without antiemetic prophylaxis) for various types of surgery. PONV was defined as nausea or vomiting within 24 h of surgery. Risk scores to estimate the probability of PONV were obtained by fitting logistic regression models. Simplified risk scores were constructed based on the number of risk factors that were found significant in the logistic regression analyses. Original and simplified scores were cross-validated. A combined data set was created to estimate a potential center effect and to construct a final risk score. The discriminating power of each score was assessed using the area under the receiver operating characteristic curves.

Results

Risk scores derived from one center were able to predict PONV from the other center (area under the curve = 0.65-0.75). Simplification did not essentially weaken the discriminating power (area under the curve = 0.63-0.73). No center effect could be detected in a combined data set (odds ratio = 1.06, 95% confidence interval = 0.71-1.59). The final score consisted of four predictors: female gender, history of motion sickness (MS) or PONV, nonsmoking, and the use of postoperative opioids. If none, one, two, three, or four of these risk factors were present, the incidences of PONV were 10%, 21%, 39%, 61% and 79%.

Conclusions

The risk scores derived from one center proved valid in the other and could be simplified without significant loss of discriminating power. Therefore, it appears that this risk score has broad applicability in predicting PONV in adult patients undergoing inhalational anesthesia for various types of surgery. For patients with at least two out of these four identified predictors a prophylactic antiemetic strategy should be considered.
Isoflurane-enhanced Recovery of Canine Stunned Myocardium
Authors: Toller Wolfgang G. , Montgomery Matthew W. , Pagel Paul S. , Hettrick Douglas A. , Warltier David C. , Kersten Judy R.
Published: November 2003

Background

Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs.

Methods

Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals.

Results

There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs.

Conclusions

The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.