bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric Oxide Mediates Hepatic Cytochrome P450 Dysfunction Induced by Endotoxin
Authors: Muller Claudia M. , Scierka Annette , Stiller Richard L. , Kim Yong-Myeong , Cook Ryan D. , Lancaster Jack R. , Buffington Charles W. , Watkins David W. 
Published: November 2003

Background
Animals subjected to immunostimulatory conditions (sepsis) exhibit decreased total cytochrome P450 content and decreased P450-dependent drug metabolism. Cytochrome P450 function is of clinical significance because it mediates the metabolism of some opioid and hypnotic drugs. The authors tested the hypothesis that reduced P450 function and decreased drug metabolism in sepsis are mediated by endotoxin-enhanced synthesis of nitric oxide.

Methods
Hepatic microsomes were prepared from male Sprague-Dawley rats in nontreated rats, rats pretreated with phenobarbital and rats receiving aminoguanidine or NG-L-monomethyl-arginine alone. Nitric oxide synthesis was augmented for 12 h with a single injection of bacterial lipopolysaccharides. Nitric oxide synthase was inhibited with aminoguanidine or N(G)-L-monomethyl-arginine during the 12 h of endotoxemia in some animals. Plasma nitrite and nitrate concentrations were measured in vivo, and total microsomal P450 content, and metabolism of ethylmorphine and midazolam in vitro.

Results
Administration of endotoxin increased plasma nitrite and nitrate concentrations, decreased total cytochrome P450 content, and decreased metabolism of ethylmorphine and midazolam. Inhibition of nitric oxide formation by aminoguanidine or N(G)-L-monomethyl-arginine partially prevented the endotoxin-induced effects in the nontreated and phenobarbital-treated groups. Aminoguanidine or N(G)-L-monomethyl-arginine alone did not have an effect on either total cytochrome P450 content or P450-dependent drug metabolism. Plasma nitrite and nitrate concentrations correlated significantly negatively with P450 content (nontreated r = -0.88, phenobarbital r = -0.91), concentrations of formed formaldehyde (nontreated r = -0.87, phenobarbital r = -0.95), and concentrations of midazolam metabolites (4-OH midazolam nontreated r = -0.88, phenobarbital r = -0.93, and 1'-OH midazolam nontreated r = -0.88, phenobarbital r = -0.97).

Conclusions
Altered hepatic microsomal ethylmorphine and midazolam metabolism during sepsis is mediated in large part by nitric oxide.
Exacerbation or Unmasking of Focal Neurologic Deficits by Sedatives
Authors: Thal Gary D. , Szabo Michele D. , Lopez-Bresnahan Maria , Crosby Gregory 
Published: November 2003

Background
Transient focal neurologic deficits have been observed in patients emerging from brain tumor or carotid surgery, and a pharmacologic effect of anesthetic agents has been proposed as the cause of such neurologic dysfunction. Therefore, the effect of sedation with midazolam or fentanyl on motor neurologic function was studied prospectively and preoperatively in patients with carotid disease or mass lesions of the brain.

Methods
Fifty-four unpremedicated adult patients with carotid disease or a brain tumor were given small intravenous doses of either 2.8 +/- 1.3 mg midazolam or 170 +/- 60 micrograms fentanyl in the preoperative period. A thorough motor examination was performed at baseline and after sedation by an individual who was unaware of the details of the patient's disease or symptoms. A mental status examination also was performed to control for the effects of inattentiveness or lack of cooperation during the neurologic examination.

Results
Patients were sedated mildly but were fully cooperative. Focal motor deterioration occurred after sedation in 30% of patients, and the incidence was similar in patients in the fentanyl and midazolam groups. Among patients with a focal motor abnormality on baseline examination or a resolved prior motor deficit, 73% had exacerbation or unmasking of these signs by sedation, whereas no patient without a prior history of motor dysfunction had a sedative-induced change. Sedative-induced changes in neurologic function ranged from unilateral mild weakness to complete plegia, but appeared to be transient in nature.

Conclusions
Sedation with midazolam or fentanyl can transiently exacerbate or unmask focal motor deficits in patients with prior motor dysfunction.
Influence of Volatile Anesthetics on Left Ventricular Afterload In Vivo
Authors: Lowe Dermot , Hettrick Douglas A. , Pagel Paul S. , Warltier David C. 
Published: November 2003

Background
This investigation examined the effects of desflurane and sevoflurane on quantitative indices of left ventricular afterload derived from aortic input impedance (Zin) interpreted using a three-element Windkessel model.

Methods
After Animal Care Committee approval, dogs (n = 8) were chronically instrumented for measurement of systemic hemodynamics including aortic blood pressure and flow. On separate days, aortic pressure and flow waveforms were recorded under steady-state conditions in the conscious state and after equilibration for 30 min at 1.1, 1.3, 1.5, and 1.7 minimum alveolar concentration of desflurane or sevoflurane. Aortic input impedance spectra were obtained via power spectral analysis of aortic pressure and flow waveforms. Characteristic aortic impedance (Zc) and total arterial resistance were calculated as the mean of the magnitude of Zin between 2 and 15 Hz and the difference between Zin at zero frequency and Zc, respectively. Total arterial compliance (C) was calculated from aortic pressure and flow waveforms using the Windkessel model.

Results
Desflurane and sevoflurane increased heart rate and decreased systolic, diastolic, and mean arterial pressure, left ventricular systolic pressure, left ventricular peak positive rate of increase in left ventricular pressure, percent segment shortening, and stroke volume. Sevoflurane, but not desflurane, decreased cardiac output. Desflurane, but not sevoflurane, decreased systemic vascular resistance. Desflurane decreased R (3,170 +/- 188 during control to 2441 +/- 220 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) and did not alter C and Zc. In contrast, sevoflurane increased C (0.57 +/- 0.05 during control to 0.79 +/- 0.05 ml/ mmHg at 1.7 minimum alveolar concentration) and Zc (139 +/- 10 during control to 194 +/- 14 dynes.second.centimeter-5 at 1.7 minimum alveolar concentration) but did not change R.

Conclusions
The results indicate that desflurane and sevoflurane produce substantially different effects on left ventricular afterload in chronically instrumented dogs. Desflurane-induced decreases in systemic vascular resistance occur primarily because of effects on arteriolar resistance vessels. In contrast, sevoflurane increased C and Zc concomitant with pressure-dependent reductions in aortic diameter, suggesting that this anesthetic may alter left ventricular afterload by affecting the mechanical properties of the aorta.
Volatile Anesthetics Depress Spinal Motor Neurons
Authors: Rampil Ira J. , King Bryan S. 
Published: November 2003

Background
Depression of spinal alpha-motor neurons apparently plays a role in the surgical immobility induced by isoflurane. Using the noninvasive technique of F-wave analysis, the authors tested the hypothesis that depressed motor neuron excitability is an effect common to other clinically relevant inhaled anesthetics.

Methods
The authors measured F-wave amplitude in rats anesthetized with desflurane, enflurane, halothane, or sevoflurane. Each animal received one anesthetic at five equipotent anesthetic concentrations (0.6, 0.8, 1.2, and 1.6 minimum alveolar concentration [MAC] and 0.8 MAC with 65% N2O). F waves were detected as late potentials in electromyographic responses evoked in the intrinsic muscles of the hind paw after monopolar stimulation of the ipsilateral posterior tibial nerve.

Results
All tested inhaled anesthetics depressed F-wave amplitude but not M-wave (orthodromic, early muscle activation) amplitude, and increased M-F latency in a dose-dependent manner. At 1.0 MAC, the estimated F/M ratio was 70 +/- 13% SD of that at baseline (0.6 MAC). Nitrous oxide added to 0.8 MAC of the potent vapors depressed F/M ratio by 63 +/- 17%.

Conclusions
All anesthetics tested appeared to depress the excitability of spinal motor neurons. This effect may contribute to surgical immobility, and its magnitude is comparable at equipotent concentrations of agents. The authors hypothesize that this effect is due to hyperpolarization, although, currently, there is insufficient information to discriminate between pre- and postsynaptic mechanisms.
Cardiac and Regional Hemodynamic Interactions between Halothane and Nitric Oxide Synthase Activity in Dogs
Authors: Chelly Jacques E. , Doursoot Marie-Francoise , Lechevalier Thierry , Liang Yang Yan , Chelly Frank , Hartley Craig , Kilbourn Robert G. 
Published: November 2003

Background
In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs.

Methods
Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA.

Results
In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction.

Conclusions
Halothane minimally interferes with the systemic and regional hemodynamic consequences of nitric oxide synthase blockade. The nature and magnitude of the interaction depend on the territory in which they occur.
Concomitant Administration of Morphine and an N-Methyl-D-Aspartate Receptor Antagonist Profoundly Reduces Inflammatory Evoked Spinal c-Fos Expression
Authors: Honore Prisca D. , Chapman Victoria , Buritova Jaroslava , Besson Jean-Marie 
Published: November 2003

Background
After intraplantar injection of carrageenin, peripheral inflammation and spinal c-Fos expression are extensive, with the latter being sensitive to both large doses of morphine or N-methyl-D-aspartate receptor antagonism. The authors investigated the effects of coadministered morphine and (+)-HA966, a functional antagonist at the glycine site of the N-methyl-D-aspartate receptor, on the two parameters.

Methods
The effects of morphine, (+)-HA966 and coadministration of morphine and (+)-HA966 on spinal c-Fos expression in segments L4-L5 of the spinal cord and peripheral edema, induced at 1.5 h and 3 h after intraplantar carrageenin (6 mg/150 microliters) were studied.

Results
Previous coadministration of 0.3 mg/kg systemic morphine and 2.5 mg/kg subcutaneous (+)-HA966 significantly reduced c-Fos expression induced 1.5 h, but not 3 h, after carrageenin administration. However, coadministration of a larger dose of morphine (3 mg/kg) with (+)-HA966 (2.5 mg/kg) reduced c-Fos expression at 3 h after carrageenin administration, in a partially naloxone-reversible manner.

Conclusions
Concurrent mu-opioid receptor activation and N-methyl-D-aspartate receptor antagonism reduces nociceptive transmission at the level of the spinal cord, as shown by the reduction of carrageenin-evoked c-Fos expression.
Intramuscular Rocuronium in Infants and Children
Authors: Reynolds Lynne M. , Lau Marie , Brown Ronald , Luks Andrew , Fisher Dennis M. 
Published: November 2003

Background
Rocuronium's rapid onset and intermediate duration of action with intravenous administration suggests that intramuscular administration might facilitate tracheal intubation without producing prolonged paralysis. Accordingly, in infants and children, the authors measured onset at the adductor pollicis and respiratory muscles to determine the optimal dose (phase I), then gave this optimal dose to determine the optimal time for tracheal intubation (phase II).

Methods
The authors studied 45 unpremedicated patients aged 3 months to 5 yr. In phase I, 25 patients were anesthetized with nitrous oxide and halothane and breathed spontaneously; twitch tension and minute ventilation were measured. Rocuronium (800-2,400 micrograms/kg) was injected into the quadriceps or deltoid muscle; doses varied, using an "up-down" technique, the goal being to bracket the dose depressing twitch 75-90% within 5 min. In phase II, deltoid injections of the optimal dose from phase I (infants: 1,000 micrograms/kg; children: 1,800 micrograms/kg) were given to 20 patients anesthetized with 0.82-1.0% halothane. Tracheal intubation was attempted 1.5-3.0 min later; time to tracheal intubation was varied, using an "up-down" technique.

Results
In phase I, 5 of 7 patients given quadriceps injections (1,200-2,200 micrograms/kg) had slow onset of twitch and ventilatory depression. With deltoid injections (800-2,400 micrograms/kg), all patients developed complete twitch depression; median time to 50% depression of minute ventilation was 3.2 min in infants and 2.8 min in children. In phase II, intubating conditions were consistently adequate or good-excellent at 2.5 min in infants and 3.0 min in children. Initial twitch recovery was at 57 +/- 13 min (mean +/- SD) in infants and 70 +/- 23 min in children.

Conclusions
Deltoid injections of rocuronium, 1,000 micrograms/kg in infants and 1,800 micrograms/kg in children, rapidly permit tracheal intubation in infants and children, despite a light plane of anesthesia. Duration of action of these large doses might limit clinical utility.
Changing Anesthesiologists' Practice Patterns
Authors: Cohen Marsha M. , Rose Keith D. , Yee D. A. 
Published: November 2003

Background
Because the ultimate purpose of new medical knowledge is to achieve improved health outcomes, physicians need to possess and use this knowledge in their practice. The authors introduced enhanced education and individualized feedback to reduce postoperative nausea and vomiting (PONV). The primary objective was to increase anesthesiologists' use of preventive measures to reduce PONV, and the secondary objective was to determine whether patient outcomes were improved.

Methods
After obtaining hospital ethics committee approval, the effect of education and feedback on anesthesiologist performance and the rate of PONV in major surgery elective inpatients during a 2-yr period was assessed. After baseline data collection (6 months), anesthesiologists at the study hospital received enhanced education (8 months) and individualized feedback (10 months). Parallel data collection was performed at a control hospital at which practice was continued as usual. The education promoted preventive measures (antiemetic premedication, nasogastric tubes, droperidol, metoclopramide). Individualized feedback provided the number of patients receiving promoted measures and the rate of PONV. The mean percentage of anesthesiologists' patients receiving at least one promoted measure and the rate of PONV were compared with baseline levels.

Results
At the study hospital, there was a significant increase in the mean percentage of the anesthesiologists' female patients receiving a preventive measure as well as a significant increase in the use of droperidol > or = 1 mg (P < 0.05) for all patients. The use of other promoted measures was unaffected. Absolute rates of PONV were unaffected at the study hospital until the post-feedback period (decrease of 8.8% between baseline and post-feedback (P = 0.015)).

Conclusion
It was demonstrated that enhanced education and individualized feedback can change anesthesiologists' practice patterns. The actual benefit to patients from use of preventive measures was limited when used in the everyday clinical situation. Therefore, only modest decreases in PONV were achieved, despite the use of preventive measures.
Perioperative Respiratory Complications in Patients with Asthma
Authors: Warner David O. , Warner Mark A. , Barnes Roxann D. , Offord Kenneth P. , Schroeder Darrell R. , Gray Darryl T. , Yunginger John W. 
Published: November 2003

Background
Patients with asthma are thought to be at high risk for pulmonary complications to develop during the perioperative period, and these complications may lead to serious morbidity. Existing medical records were reviewed to determine the frequency of and risk factors for perioperative pulmonary complications in a cohort of residents of Rochester, Minnesota, who had asthma and who underwent anesthesia and surgery at the Mayo Clinic in Rochester.

Methods
Medical records were reviewed for all residents of Rochester, Minnesota, who were initially diagnosed as having definite asthma according to strict criteria from 1 January 1964 through 31 December 1983 who subsequently had at least one surgical procedure involving a general anesthetic or central neuroaxis block at the Mayo Clinic (n = 706).

Results
Bronchospasm was documented in the perioperative records of 12 patients (1.7% [exact 95% confidence interval, 0.9 to 3%]). Postoperative respiratory failure developed in one of these patients. Laryngospasm developed in two additional patients during operation. All episodes of bronchospasm and laryngospasm in the immediate perioperative period were treated successfully. No episodes of pneumothorax, pneumonia, or death in the hospital were noted. For univariate analysis, characteristics associated with complications included the recent use of antiasthmatic drugs, recent asthma symptoms, and recent therapy in a medical facility for asthma. Patients in whom complications developed were significantly older at diagnosis and at surgery.

Conclusions
The frequency of perioperative bronchospasm and laryngospasm was surprisingly low in this cohort of persons with asthma. These complications did not lead to severe respiratory outcomes in most patients. The frequency of complications was increased in older patients and in those with active asthma.
Do Children Who Experience Laryngospasm Have an Increased Risk of Upper Respiratory Tract Infection?
Authors: Schreiner Mark S. , O'Hara Irene , Markakis Dorothea A. , Politis George D. 
Published: November 2003

Background
Laryngospasm is the most frequently reported respiratory complication associated with upper respiratory infection and general anesthesia in retrospective studies, but prospective studies have failed to demonstrate any increase in risk.

Methods
A case-control study was performed to examine whether children with laryngospasm were more likely to have an upper respiratory infection on the day of surgery. The parents of all patients (N = 15,183) who were admitted through the day surgery unit were asked if their child had an active or recent (within 2 weeks of surgery) upper respiratory infection and were questioned about specific signs and symptoms to determine if the child met Tait and Knight's definition of an upper respiratory infection. Control subjects were randomly selected from patients whose surgery had occurred within 1 day of the laryngospasm event.

Results
Patients who developed laryngospasm (N = 123) were 2.05 times (95% confidence interval 1.21-3.45) more likely to have an active upper respiratory infection as defined by their parents than the 492 patients in the control group (P < or = 0.01). The development of laryngospasm was not related to Tait and Knight's definition for an upper respiratory infection or to recent upper respiratory infection. Children with laryngospasm were more likely to be younger (odds ratio = 0.92, 95% confidence interval 0.87-0.99), to be scheduled for airway surgery (odds ratio = 2.08, 95% confidence interval 1.21-3.59), and to have their anesthesia supervised by a less experienced anesthesiologist (odds ratio = 1.69, 95% confidence interval 1.04-2.7) than children in the control group.

Conclusion
Laryngospasm was more likely to occur in children with an active upper respiratory infection, children who were younger, children who were undergoing airway surgery, and children whose anesthesia were supervised by less experienced anesthesiologists. Understanding the risk factors and the magnitude of the likely risk should help clinicians make the decision as to whether to anesthetize children with upper respiratory infection.
Single Injection Thermodilution
Authors: Jansen Jos R. C. , Schreuder Jan J. , Settels Jos J. , Kornet Lilian , Penn Olaf C. K. M. , Mulder Paul G. H. , Versprille Adrian , Wesseling Karel H. 
Published: November 2003

Background
Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output.

Methods
To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle.

Results
A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction.

Conclusion
It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.