bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of the Intubating Laryngeal Mask Airway
Authors: van Vlymen Janet M. , Coloma Margarita , Tongier W. Kendall , White Paul F. 
Published: November 2003

Background
The intubating laryngeal mask airway (ILMA) is designed to facilitate blind tracheal intubation. The effect of a muscle relaxant on the ability to perform tracheal intubation through the ILMA device has not been previously evaluated. This randomized, double-blind, placebo-controlled study was designed to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the success rate and incidence of complications associated with ILMA-assisted tracheal intubation.

Methods
A total of 75 healthy patients were induced with propofol 2 mg/kg and fentanyl 1 microg/kg intravenously. After insertion of the ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of the study drug, tracheal intubation was attempted using a disposable polyvinyl tube. If unsuccessful, a reusable silicone tube was tried. In addition to recording the time and number of attempts required to secure the airway, the incidence of complications during placement of the tracheal tube and removal of the ILMA were noted.

Results
Tracheal intubation was successful in 76-96% of the patients. The overall success rates and times required to secure the airway were similar in all three treatment groups. The high-dose rocuronium group experienced less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than the low-dose rocuronium and saline groups, respectively. Use of rocuronium was also associated with a dose-related decrease in the requirement for supplemental bolus doses of propofol during intubation and removal of the ILMA device.

Conclusions
Use of rocuronium did not significantly improve the success rate in performing tracheal intubation through the ILMA. However, it produced dose-related decreases in coughing and movement after tracheal intubation and reduced difficulties associated with removal of the ILMA device.
Effects of Intravenous Zaprinast and Inhaled Nitric Oxide on Pulmonary Hemodynamics and Gas Exchange in an Ovine Model of Acute Respiratory Distress Syndrome
Authors: Adrie Christophe , Holzmann Alexandra , Hirani W. Mona , Zapol Warren M. , Hurford William E. 
Published: November 2003

Background
Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury.

Methods
The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH).

Results
After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control).

Conclusions
This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.
Anesthetic Effects on Cerebral Metabolic Rate Predict Histologic Outcome from Near-complete Forebrain Ischemia in the Rat
Authors: Nellgård Bengt , Mackensen G. Burkhard , Pineda Jose , Wellons John C. , Pearlstein Robert D. , Warner David S. 
Published: November 2003

Background
Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate.

Methods
Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later.

Results
With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration.

Conclusions
At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.
Effects of Radolmidine, A Novel α2-Adrenergic Agonist Compared with Dexmedetomidine in Different Pain Models in the Rat
Authors: Xu Mei , Kontinen Vesa K. , Kalso Eija 
Published: November 2003

Background
Intrathecally administered alpha2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha2-adrenoceptor agonist with a different pharmacokinetic profile compared with the well-researched dexmedetomidine. This study determined the antinociceptive and sedative effects of radolmidine in different models of acute and chronic pain. Dexmedetomidine and saline served as controls.

Methods
Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine and radolmidine were administered intrathecally in doses of 0.25 microg, 2.5 microg, 5 microg, and 10 microg.

Results
In the tail flick test, radolmidine showed a dose-dependent antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 microg or 5 microg of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 microg dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine.

Conclusions
Radolmidine and dexmedetomidine had equipotent antinociceptive effects in all tests studied. However, radolmidine caused significantly less sedation than dexmedetomidine, probably because of a different pharmacokinetic profile.
Pharmacokinetics and Pharmacodynamics of Inhaled versus Intravenous Morphine in Healthy Volunteers
Authors: Dershwitz Mark , Walsh John L. , Morishige Richard J. , Connors Patricia M. , Rubsamen Reid M. , Shafer Steven L. , Rosow Carl E. 
Published: November 2003

Background
A new pulmonary drug delivery system produces aerosols from disposable packets of medication. This study compared the pharmacokinetics and pharmacodynamics of morphine delivered by an AERx prototype with intravenous morphine.

Methods
Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models.

Results
The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1.

Conclusions
The onset and duration of the effects of morphine are similar after intravenous administration or inhalation via this new pulmonary drug delivery system. Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form.
Predictive Accuracy of Target-controlled Propofol and Sufentanil Coinfusion in Long-lasting Surgery
Authors: Pandin Pierre C. , Cantraine Francis , Ewalenko Patricia , Deneu Stéphane C. , Coussaert Eddy , d’Hollander Alain A. 
Published: November 2003

Background
The predictive accuracy of target concentration infusions of propofol has been documented only for less than 4 h, and no prospective study of sufentanil target controlled infusion is available. The authors investigated the predictive accuracy of pharmacokinetic models for propofol and sufentanil coadministered during long-lasting surgery.

Methods
Ten patients, American Society of Anesthesiologists physical status I and II, were studied during extended cervicofacial surgery. Target controlled infusion of propofol and sufentanil was administered during surgery using decisional algorithms, taking into consideration pain assessment, hemodynamic changes, and peroperative blood losses. Intrasubject data analysis included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble.

Results
The range of plasma target concentrations was 2-5 microgram/ml for propofol and 0.2-1 ng/ml for sufentanil. Median performance error was -12.1% for propofol and -10% for sufentanil. The wobble values were 11.6% and 22.3% for propofol and sufentanil, respectively. The pharmacokinetic sets used slightly overpredicted the concentrations, with negative values of divergence of 2.92% and 0.22% units/h for propofol and sufentanil, for a mean infusion period of 762 min.

Conclusions
This prospective study demonstrates the predictive accuracy of the pharmacokinetic model for sufentanil infusion and confirms that for propofol during long-lasting surgery using standardized rules for the management of target controlled infusion and blood loss replacement.
Efficacy of Preoxygenation with Tidal Volume Breathing
Authors: Nimmagadda Usharani , Salem M. Ramez , Joseph Ninos J. , Lopez Gilbert , Megally Mahfouz , Lang David J. , Wafai Yaser 
Published: November 2003

Background
Preoxygenation before tracheal intubation is intended to increase oxygen reserves and delay the onset of hypoxemia during apnea. Various systems are used for preoxygenation. Designed specifically for preoxygenation, the NasOral system uses a small nasal mask for inspiration and a mouthpiece for exhalation. One-way valves in the nasal mask and the mouthpiece ensure unidirectional flow. This investigation compares the efficacy of preoxygenation using the standard circle system with the NasOral system and five different resuscitation bags.

Methods
Twenty consenting, healthy volunteers were studied in the supine position for 5-min periods of tidal volume breathing using the circle absorber system, the NasOral system, and five resuscitation bags in a randomized order. Data were collected during room air breathing and at 30-s intervals during 5 min of oxygen administration. Inspired oxygen, end-tidal oxygen, and end-tidal nitrogen were measured by mass spectrometry.

Results
At 2. 5 min of oxygenation, end-tidal oxygen plateaued at 88.1 +/- 4.8 and 89.3 +/- 6.4% (mean +/- SD) for the circle absorber and NasOral systems, respectively. This was associated with inverse decreases in end-tidal nitrogen. At no time did these end-tidal oxygen or nitrogen values differ from each other. Three of the resuscitation bags (one disk type and two duck-bill type with one-way exhalation valves) delivered inspired oxygen more than 90%, and the end-tidal oxygen plateaued between 77 and 89% at 2 min of tidal volume breathing. The other two resuscitation bags (both duck-bill bags without exhalation valves) delivered inspired oxygen less than 40%, and the end-tidal oxygen values ranged between 21.8 +/- 5.0 and 31.9 +/- 8.7%.

Conclusions
The circle absorber and NasOral systems were equally effective in achieving maximal preoxygenation during tidal volume breathing. Resuscitation bags differed markedly in effectiveness during preoxygenation; those with duck-bill valves without one-way exhalation valves were the least effective. Thus, the use of these bags should be avoided for preoxygenation.
Facilitated Uptake of Fentanyl, but Not Alfentanil, by Human Pulmonary Endothelial Cells
Authors: Waters Christopher M. , Krejcie Tom C. , Avram Michael J. 
Published: November 2003

Background
Extensive pulmonary uptake of lipophilic basic amines, such as fentanyl, attenuates early blood drug concentrations after rapid intravenous administration. The basis of this phenomenon is poorly understood. The authors tested the hypothesis that fentanyl uptake into cultured human lung microvascular endothelial (HMVE-L) cells occurs by facilitated uptake in addition to passive diffusion. The authors compared fentanyl and alfentanil uptake with that of antipyrine, a diffusible marker of pulmonary tissue water. In addition, the authors determined the effect of verapamil, a nonspecific inhibitor of drug transport, and UIC2, a blocking antibody of the P-glycoprotein drug transporter, on the uptake of these drugs.

Methods
Human lung microvascular endothelial cells were incubated, with varying concentrations of antipyrine and fentanyl or alfentanil in the absence or presence of varying verapamil concentrations or of UIC2. Supernatants were collected and cells were rinsed and dissolved. Supernatant and cell-associated antipyrine, fentanyl, and alfentanil concentrations were measured. The data were fit to a model of cellular uptake that allowed for passive diffusion and facilitated uptake.

Results
Alfentanil uptake by HMVE-L cells was indistinguishable from that of antipyrine for the concentration ranges studied. In contrast, at low concentrations, fentanyl sequestration into HMVE-L cells was substantially greater than that of antipyrine. Facilitated fentanyl uptake was blocked by verapamil, but not by UIC2, in a concentration-dependent manner.

Conclusions
The differential HMVE-L uptake of fentanyl and alfentanil is consistent with the observed differences in the pulmonary uptake of these drugs. This suggests that specific fentanyl uptake and sequestration by HMVE-L cells may be the mechanisms of its extensive pulmonary uptake.
Cause-specific Mortality Risks of Anesthesiologists
Authors: Alexander Bruce H. , Checkoway Harvey , Nagahama Sonia I. , Domino Karen B. 
Published: November 2003

Background
The health-related effects of the operating room environment are unclear. The authors compared mortality risks of anesthesiologists to those of internal medicine physicians between 1979 and 1995.

Methods
The Physician Master File database, a listing of all US physicians, was used to identify anesthesiologists and general internists. The cohort of internists (n = 40,211) was a stratified random sample of all internists, frequency-matched to the cohort of anesthesiologists (n = 40,242) by gender, decade of birth, and US citizenship. The National Death Index was used to confirm death status and to determine specific causes of death. Mortality risks, adjusted for age, gender, and race, were compared using the Cox proportional hazards regression model.

Results
The standardized mortality ratios for all physicians were well below 1.0, except for suicide. The all-cause mortality ratios, and the risks of death caused by cancer and heart disease, did not differ between anesthesiologists and internists. Anesthesiologists had an increased risk of death from suicide (rate ratio [RR] = 1.45, 95% confidence interval [CI] = 1.07 - 1.97), drug-related death (RR = 2.79, 95% CI = 1.87 - 4.15), death from other external causes (RR = 1.53, 95% CI = 1.05 - 2.22), and death from cerebrovascular disease (RR = 1.39, 95% CI = 1.08 - 1.79). Male anesthesiologists had an increased risk of death from HIV (RR = 1.82, 95% CI = 1.09 - 3.02) and viral hepatitis (RR = 7.98, 95% CI = 1.0 - 63.84). Although the risk to anesthesiologists of drug-related deaths was highest in the first 5 years after medical school graduation, it remained increased over that of internists throughout the career.

Conclusions
Substance abuse and suicide represent significant occupational hazards for anesthesiologists. New methods to combat substance abuse among anesthesiologists should be developed.
Transdermal Nitroglycerine Enhances Spinal Neostigmine Postoperative Analgesia following Gynecological Surgery
Authors: Lauretti Gabriela R. , Oliveira Ana-Paula M. , Julião Maria-do-Carmo C. , Reis Marlene P. , Pereira Newton L. 
Published: November 2003

Background
Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia.

Methods
Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale.

Results
Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05).

Conclusion
Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.