bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Targeted Neuronal Nitric Oxide Synthase Gene Disruption and Nitro sup G -L-Arginine Methylester on the Threshold for Isoflurane Anesthesia
Authors: Ichinose Fumito , Huang Paul L. , Zapol Warren M. 
Published: November 2003

Background
Considerable evidence suggests that nitric oxide plays a role in synaptic transmission in the central and peripheral nervous system. Nonselective inhibition of nitric oxide synthase by nitroG-L-arginine methylester (L-NAME) reduces the minimum alveolar concentration of halothane anesthesia. The effects of selective neuronal nitric oxide synthase inhibition on the anesthetic requirements in mice congenitally deficient in neuronal nitric oxide synthase (knockout mice) were examined.

Methods
Isoflurane minimum alveolar concentration and righting reflex ED50 (RRED50) were determined in knockout and wild-type mice. Subsequently, the effects of intraperitoneal L-NAME on minimum alveolar concentration and RRED50 of knockout and wild-type mice were examined. In a separate experiment, the effects of week-long administration of L-NAME were examined in wild-type mice. Isoflurane minimum alveolar concentration and RRED50 were measured on the 8th day and were repeated after an acute intraperitoneal dose of L-NAME.

Results
Targeted disruption of the neuronal nitric oxide synthase gene did not modify isoflurane minimum alveolar concentration and RRED50 of knockout mice. Acute intraperitoneal L-NAME decreased the minimum alveolar concentration and RRED50 of wild-type but did not alter those values in knockout mice. The wild-type mice, when given L-NAME for a week, showed a minimum alveolar concentration and RRED50 identical to that of untreated wild-type mice.

Conclusions
Although acute nonselective inhibition of nitric oxide synthase reduces the anesthetic requirements of wild-type mice, a chronic congenital deficiency of neuronal nitric oxide synthase or a week of L-NAME treatment of wild-type mice does not produce a state of greater sensitivity to the effects of isoflurane anesthesia.
Amrinone Is Superior to Epinephrine in Reversing Bupivacaine-induced Cardiovascular Depression in Sevoflurane-anesthetized Dogs
Authors: Saitoh Kazuhiko , Hirabayashi Yoshihiro , Shimizu Reiju , Fukuda Hirokazu 
Published: November 2003

Background
Bupivacaine-induced cardiovascular depression is known to be difficult to treat, and the efficacy of epinephrine for treatment of bupivacaine-induced cardiovascular depression is in doubt. We compared the efficacy of amrinone with that of epinephrine for the treatment of bupivacaine-induced cardiovascular depression in anesthetized dogs.

Methods
In dogs receiving 1.5-2% sevoflurane anesthesia, 0.5% bupivacaine was infused at a rate of 0.5 mg.kg-1.min-1 intravenously until mean arterial blood pressure decreased to 40 mmHg or less. In the amrinone group (n = 9), amrinone (4 mg.kg-1, intravenously) was given immediately after cardiovascular depression, followed by intravenous infusion at a rate of 0.1 mg.kg-1.min-1. In the epinephrine group (n = 9), epinephrine (0.01 mg.kg-1, intravenously) was given as a bolus, and the same dose was given again as required.

Results
All nine dogs that received amrinone survived. Of the nine dogs that received epinephrine, five survived; fatal cardiovascular depression developed in the four remaining animals (P < 0.05). Only one animal in the amrinone group showed tachyrhythmia with wide QRS complexes during resuscitation, whereas all nine animals in the epinephrine group showed tachyrhythmia with wide QRS complexes during resuscitation.

Conclusions
Amrinone is superior to epinephrine for the treatment of bupivacaine-induced cardiovascular depression in sevoflurane-anesthetized dogs.
A Cost Analysis of the Laryngeal Mask Airway for Elective Surgery in Adult Outpatients
Authors: Macario Alex , Chang Pearl C. , Stempel Dan B. , Brock-Utne John G. 
Published: November 2003

Background
Since the introduction of the laryngeal mask airway (LMA) into the United States in 1991, the device has become widely used in anesthesia practice. The purpose of this economic analysis was to use existing data to evaluate the costs of the LMA relative to three other common airway management techniques and to identify the variables that had the greatest effect on cost efficiency.

Methods
We evaluated four airway management techniques for healthy adults receiving an isoflurane-nitrous oxide-oxygen anesthetic for elective outpatient surgery: (1) LMA with spontaneous ventilation; (2) face mask with spontaneous ventilation; (3) tracheal intubation after succinylcholine with subsequent spontaneous ventilation; and (4) tracheal intubation after nondepolarizing neuromuscular blockade and controlled ventilation. We analyzed published clinical studies of the LMA and obtained cost data from Stanford University Medical Center. The best available estimates of the independent variables were incorporated into a baseline case. For each airway technique we derived cost equations that excluded costs common to all four techniques.

Results
Relative to airway management with an LMA, calculated values for the baseline analysis included additional isoflurane costs for use of a face mask ($ 0.12/min) and for tracheal intubation with ($ 0.043/min) and without neuromuscular blockade ($ 0.06/min). With a neuromuscular blocking drug cost of $ 0.21/min and an LMA cost per use of $ 20, the face mask with spontaneous ventilation was the cost-efficient airway choice for anesthetics lasting as long as 100 min. Increasing the LMA reuse rate from 10 to 25 made the LMA the least costly airway technique for cases lasting more than 70 min.

Conclusions
If the LMA is reused 40 times, the LMA is the cost-efficient airway choice for outpatients receiving an isoflurane-nitrous oxide-oxygen anesthetic lasting longer than 40 min. This finding does not change if the cost of neuromuscular blockade or the incidence of airway-related complications is varied over a clinically relevant range.
Preanesthetic Medication of Children with Midazolam Using the Biojector Jet Injector
Authors: Greenberg Robert S. , Maxwell Lynne G. , Zahurak Marianna , Yaster Myron 
Published: November 2003

Background
A rapid, dependable, and economical technique to atraumatically sedate children before anesthesia that does not prolong postanesthesia care unit time remains elusive. The Biojector jet injection system uses carbon dioxide rather than a needle to deliver an intramuscular injection. The dose-response relationship when midazolam is administered was studied using this jet injector.

Methods
Forty children (2.3 +/- 1.3 yr old) undergoing elective myringotomy and tube placement were randomly assigned to receive 0.05, 0.1, 0.15, 0.2, or 0.3 mg.kg-1 midazolam injected intramuscularly using the Biojector disposable syringe (0.006-inch orifice). Assessment of each child before, during, and 10 min after injection, on application of the anesthesia face mask, and every 15 min for 1 h after arrival to the postanesthesia care unit was made by an observer blinded to drug dosage.

Results
Face mask tolerance using doses > or = 0.1 mg.kg-1 midazolam was acceptable and statistically different from 0.05 mg/kg. Crying on injection tended to increase with increasing dose. All children were awake and arousable, meeting discharge criteria, after 30 min from arrival in the postanesthesia care unit.

Conclusions
Midazolam (0.1-0.15 mg.kg-1) administered using jet injection effectively and rapidly produces sedation, in a manner acceptable to parents, without delaying postanesthesia care unit discharge.
Contrasting Actions of Intrathecal U50, 488H, Morphine, or [D-Pen sup 2, D-Pen sup 5] Enkephalin or Intravenous U50, 488H on the Visceromotor Response to Colorectal Distension in the Rat
Authors: Harada Y. , Nishioka K. , Kitahata L. M. , Nakatani K. , Collins J. G. 
Published: November 2003

Background
Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model.

Methods
The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously.

Results
Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg.

Conclusions
The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.
Visceral Antinociceptive Effects of Spinal Clonidine Combined with Morphine, [D-Pen sup 2, D-Pen sup 5] Enkephalin, or U50,488H
Authors: Harada Y. , Nishioka K. , Kitahata L. M. , Kishikawa K. , Collins J. G. 
Published: November 2003

Background
Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H).

Methods
Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined.

Results
Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine.

Conclusions
Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.
Postoperative Pain Control with a New Transdermal Fentanyl Delivery System
Authors: Miguel Rafael , Kreitzer Joel M. , Reinhart Douglas , Sebel Peter S. , Bowie Julius , Freedman Gordon , Eisenkraft James B. 
Published: November 2003

Background
A new transdermal delivery system for fentanyl is available in two strengths: 70-80 and 90-100 micrograms.kg-1.h-1 (40- and 60-cm2 patches, respectively). Their short onset and 24-h drug delivery make them attractive for postoperative pain control.

Methods
Both doses of the new transdermal fentanyl patches were evaluated for the relief of postoperative pain in 143 patients after gynecologic exploratory laparotomy. The study was conducted at four centers using a prospective, randomized, placebo-controlled, double-blind format. Patients were randomly assigned to one of three study groups: group 1 patients received two placebo patches: group 2 patients received a 40-cm2 fentanyl patch and a 60-cm2 placebo patch; and group 3 patients received a 60-cm2 fentanyl patch and a 40-cm2 placebo patch. Patient-controlled morphine use and pain, sedation, and comfort scores were assessed postoperatively every 4 h for 36 h after patch placement.

Results
Patients' assessment of their analgesia was significantly (P < or = 0.05) better in group 2 at 16 and 24 h and in group 3 at 8, 12, 16, 20, and 24 h postoperatively, compared with the patients in group 1. Patients in groups 2 and 3 required less supplemental morphine to maintain satisfactory analgesia than did the patients in group 1. Patients in groups 2 and 3 had greater incidences of pruritus, erythema, and respiratory depression than did those receiving placebo.

Conclusions
Concern exists regarding the side effects of this this new transdermal fentanyl patch. Therefore, this new patch will need further research before it can be recommended as an adjunct in controlling postoperative pain.
Influences of Subanesthetic Isoflurane on Ventilatory Control in Humans
Authors: van den Elsen Maarten , Dahan Albert , DeGoede Jacob , Berkenbosch Aad , van Kleef Jack 
Published: November 2003

Background
The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia.

Methods
Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and off-set (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane.

Results
Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001).

Conclusions
The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.
Heat Balance and Distribution during the Core-Temperature Plateau in Anesthetized Humans
Authors: Kurz Andrea , Sessler Daniel I. , Christensen Richard , Dechert Martha 
Published: November 2003

Background
Once triggered, intraoperative thermoregulatory vasoconstriction is remarkably effective in preventing further hypothermia. Protection results from both vasoconstriction-induced decrease in cutaneous heat loss and altered distribution of body heat. However, the independent contributions of each mechanism have not been quantified. Accordingly, we evaluated overall heat balance and distribution of heat within the body during the core-temperature plateau.

Methods
Nine minimally clothed male volunteers were anesthetized with propofol and isoflurane and maintained in an approximately 22 degrees C environment. They were monitored for approximately 2 h before vasoconstriction and for 3 h subsequently. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular temperatures, ten skin temperatures, and "deep" foot temperature. Heat constrained by vasoconstriction to the trunk and head was calculated by subtracting the expected change in that region (overall heat balance multiplied by the fractional weight of the trunk and head) from the actual change (change in distal esophageal temperature multiplied by the specific heat of human tissue and the weight of the trunk and head); the result represents the amount by which core heat exceeded that which would be expected based on overall heat balance, assuming that the change was evenly distributed throughout the body.

Results
Vasoconstriction and passive tissue cooling decreased heat loss but not to the level of heat production. Consequently, heat loss exceeded metabolic heat production throughout the study. Core temperature decreased approximately 1.3 C during the 2-h prevasoconstriction period; however, core temperature remained virtually constant during the subsequent 3 h. In the 3 h after vasoconstriction, arm and leg heat content decreased 57 +/- 9 kcal, and vasoconstriction constrained 22 +/- 8 kcal to the trunk and head.

Conclusions
These results confirm the efficacy of thermo-regulatory vasoconstriction in preventing additional core hypothermia. Decreased cutaneous heat loss and constraint of metabolic heat to the core thermal compartment contributed to the plateau.
Clinical Trial of a New Lightwand Device (Trachlight) to Intubate the Trachea
Authors: Hung Orlando R. , Pytka Saul , Morris Ian , Murphy Michael , Launcelott Gordon , Stevens Sarah , MacKay William , Stewart Ronald D. 
Published: November 2003

Background
Transillumination of the soft tissue of the neck using a lighted stylet (lightwand) is an effective and safe intubating technique. A newly designed lightwand (Trachlight) incorporates modifications to improve the brightness of the light source as well as flexibility. The goal of this study was to determine the effectiveness and safety of this device in intubating the trachea of elective surgical patients.

Methods
Healthy surgical patients were studied. Patients with known or potential problems with intubation were excluded. During general anesthesia, the tracheas were intubated randomly using either the Trachlight or the laryngoscope. Failure to intubate was defined as lack of successful intubation after three attempts. The duration of each attempt was recorded as the time from insertion of the device into the oropharynx to the time of its removal. The total time to intubation (TTI), an overall measure of the ease of intubation, was defined as the sum of the durations of all (as many as three) intubation attempts. Complications, such as mucosal bleeding, lacerations, dental injury, and sore throat, were recorded.

Results
Nine hundred fifty patients (479 in the Trachlight group and 471 in the laryngoscope group) were studied. There was a 1% failure rate with the Trachlight, and 92% of intubations were successful on the first attempt, compared with a 3% failure rate and an 89% success rate on the first attempt with the laryngoscope (P not significant). All failures were followed by successful intubation using the alternate device. The TTI was significantly less with the Trachlight compared with the laryngoscope (15.7 +/- 10.8 vs. 19.6 +/- 23.7 s). For laryngoscopic intubation, the TTI was longer for patients with limited mandibular protrusion and mentohyoid distance, with a larger circumference of the neck, and with a high classification according to Mallampatti et al. However, there was no relation between the TTI and any of the airway parameters for Trachlight. There were significantly fewer traumatic events in the Trachlight group than in the laryngoscope group (10 vs. 37). More patients complained of sore throat in the laryngoscope group than in the Trachlight group (25.3% vs. 17.1%).

Conclusions
In contrast to laryngoscopy, the ease of intubation using the Trachlight does not appear to be influenced by anatomic variations of the upper airway. Intubation occasionally failed with the Trachlight but in all cases was resolved with direct laryngoscopy. The failures of direct laryngoscopy were resolved with Trachlight. Thus the combined technique was 100% successful in intubating the tracheas of all patients.
A System Model for Halothane Closed-Circuit Anesthesia
Authors: Vermeulen P. M. , Lerou J. G. C. , Dirksen R. , Booij L. H. D. J. , Borm G. F. 
Published: November 2003

Background
Previously, the authors described a physiologic model for closed-circuit inhalational anesthesia. The basic version of this system model was clinically validated for isoflurane. An extended version adopted nonpulmonary elimination causing a constant fraction of anesthetic to be irreversibly lost. This version improved the accuracy of the model for enflurane. The model's performance for other inhalational anesthetics that are not biochemically inert, such as halothane, remained to be evaluated.

Methods
The current study quantified the predictive performance of four versions of the model by comparison of the predicted and measured alveolar halothane concentration-time profiles in 53 patients. Version A did not incorporate nonpulmonary elimination, whereas version D adopted a nonlinear hepatic nonpulmonary elimination following Michaelis-Menten kinetics. A and D used fixed partition coefficients. Their counterparts, A' and D', were formulated to examine the impact of age-adjusted partition coefficients on the accuracy of our model. Each concentration measured by mass spectrometry was compared to four predicted concentrations calculated by four computer simulations (one per version). For each patient, the authors calculated the root mean squared error (rmse; typical error size), bias (systematic component), and scatter of the prediction errors.

Results
Fifty-three patients were anesthetized with 330 ml of liquid halothane via 426 bolus injections during more than 61 h; 21,890 alveolar concentrations (average 0.6 vol%) were measured. Version D' showed the best overall performance with an rmse of 19.6 +/- 7.2%, a bias of 0.5 +/- 15.9%, and a scatter of 13.2 +/- 3.5% (mean +/- SD).

Conclusions
The model incorporating nonpulmonary elimination and age-adjusted partition coefficients (D') is sufficiently reliable and accurate to represent halothane closed-circuit anesthesia. This system model, with its various versions, is a valuable tool to predict the dynamics of isoflurane, enflurane, and halothane for clinical, educational, and research purposes.