bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of Three Different Doses of Epidural Neostigmine Coadministered with Lidocaine for Postoperative Analgesia
Authors: Lauretti Gabriela R. , de Oliveira Raquel , Reis Marlene P. , Juliao Maria-do-Carmo C. , Pereira Newton L. 
Published: November 2003

Background
Intrathecal neostigmine produces analgesia in volunteers and patients. However, the use of epidural neostigmine has not been investigated. The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures.

Methods
After Institutional Review Board approval and informed consent, 48 patients (n = 12) undergoing knee surgery were randomly allocated to one of four groups and studied in a prospective way. After 0.05-0.1 mg/kg intravenous midazolam premedication, patients were randomized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine (85 mg) with saline (control group); 1 microg/kg epidural neostigmine (1 microg group); 2 microg/kg epidural neostigmine (2 microg group); or 4 microg/kg epidural neostigmine (4 microg group). The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Postoperatively, pain was assessed using the visual analog scale, and intramuscular 75 mg diclofenac was available at patient request.

Results
Groups were demographically the same and did not differ in intraoperative characteristics (blood pressure, heart rate, ephedrine consumption, oxyhemoglobin saturation, sensory loss before start of surgery, or duration of sensory motor block). The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). The time (min +/- SD) to first rescue analgesic was as follows: control group: 205+/-48; 1-microg group: 529+/-314; 2-microg group: 504+/-284; 4-microg group: 547+/-263 (P < 0.05). The analgesic consumption (number of intramuscular diclofenac injections [mean, 25th-75th percentile]) in 24 h was as follows: control group: 3 [3 or 4]; 1-microg group: 1 [1 or 2]; 2-microg group: 2 [1 or 2]; 4-microg group: 2 [1-3] (P < 0.05). The 24-h-pain visual analog scale score (cm +/- SD) that represents the overall impression for the last 24 h was as follows: control group: 5+/-1.6; 1-microg group: 1.6+/-1.8; 2-microg group: 1.4+/-1.6; 4-microg group: 2.2+/-1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05).

Conclusion
Epidural neostigmine (1, 2, or 4 microg/kg) in lidocaine produced a dose-independent analgesic effect (approximately 8 h) compared to the control group (approximately 3.5 h), and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.
The Effect of Naloxone on Ketamine-induced Effects on Hyperalgesia and Ketamine-induced Side Effects in Humans
Authors: Mikkelsen Soren , Ilkjaer Susanne , Brennum Jannick , Borgbjerg Finn M. , Dahl Jorgen B. 
Published: November 2003

Background
The (NMDA) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia. Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans. Although it is disputed, the actions of ketamine have been ascribed not only to NMDA receptor antagonism, but also to opioid receptor agonism. A study therefore was designed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone.

Methods
Twenty-five volunteers were subjected to three treatment regimens. A standardized first-degree burn injury was induced. On appearance of primary and secondary hyperalgesia, one of the following infusion schemes was applied in a randomized, double-blind, cross-over fashion: (1) infusion of naloxone (0.8 mg/15 min followed by 0.4 mg/h), succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); (2) infusion of placebo, succeeded by infusion of ketamine (0.3 mg x kg(-1) x 15 min(-1) followed by 0.3 mg x kg(-1) x h(-1)); and (3) infusion of placebo, succeeded by infusion of placebo. Heat-pain detection thresholds, magnitude of secondary hyperalgesia around the burn injury, and side effects were determined.

Results
Ketamine reduced secondary hyperalgesia. Naloxone did not affect the action of ketamine. The magnitudes of side effects were equal if the subjects received ketamine, regardless of preceding infusion of naloxone.

Conclusions
In this experimental setting, opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia.
Phase-contrast MRI Measurement of Systolic Cerebrospinal Fluid Peak Velocity (CSFVPeak) in the Aqueduct of Sylvius
Authors: Kolbitsch Christian , Schocke Michael , Lorenz Ingo H. , Kremser Christian , Zschiegner Fritz , Pfeiffer Karl P. , Felber Stephan , Aichner Franz , Hormann Christoph , Benzer Arnulf 
Published: November 2003

Background
Cerebrospinal fluid (CSF) outflow to intra- and extracranial subarachnoid spaces caused by arterial inflow to the brain predominantly compensates systolic increases in cerebral blood volume. Phase-contrast magnetic resonance imaging is a new tool for noninvasive assessment of CSF displacement by measuring CSF peak velocity (CSFV(Peak)). The authors tested this new tool in an experimental human model of increased intracranial pressure and reduced cerebral capacity by means of continuous positive airway pressure (CPAP) breathing.

Methods
The authors investigated systolic CSFV(Peak) in the aqueduct of Sylvius in 11 awake, normocapnic (end-tidal carbon dioxide [ET(CO2)] = 40 mmHg) volunteers without CPAP and at two different CPAP levels (6 and 12 cm H2O) by means of electroencephalography-gated phase-contrast magnetic resonance imaging.

Results
Administration of 6 cm H2O CPAP did not change systolic CSFV(Peak) (-4.9+/-2.8 cm/s vs. control: -5.1+/-2.7 cm/s), whereas 12 cm H2O CPAP significantly reduced systolic CSFV(Peak) (-4.0+/-1.8 cm/s vs. control: -5.1+/-2.7 cm/s; P < 0.05).

Conclusions
These findings in awake volunteers show that monitoring CSFV(Peak) in the aqueduct of Sylvius is a sensitive method for detecting even minor impairment of cerebral capacity caused by experimentally induced increases in intracranial pressure.
Clinical Effects and Maternal and Fetal Plasma Concentrations of 0.5% Epidural Levobupivacaine versus Bupivacaine for Cesarean Delivery
Authors: Bader Angela M. , Tsen Lawrence C. , Camann William R. , Nephew Elizabeth , Datta Sanjay 
Published: November 2003

Background
Bupivacaine exists as a mixture of two enantiomers, levobupivacaine and dexbupivacaine. Data suggest that levobupivacaine has equal local anesthetic potency, with reduced potential for central nervous system and cardiovascular toxicity. The present study compares the efficacy of 0.5% levobupivacaine with 0.5% bupivacaine for epidural anesthesia in parturients undergoing elective cesarean delivery.

Methods
Sixty healthy obstetric patients undergoing elective cesarean delivery with epidural anesthesia completed the study. Patients were randomized to receive 30 ml of either 0.5% levobupivacaine or 0.5% bupivacaine in a double-blind fashion. The efficacy endpoint measures included onset, offset, and quality of anesthesia. Neonatal blood gas analyses, Apgar score determinations, and neurobehavioral examinations were performed. Venous samples for pharmacokinetic studies and serial electrocardiograms were obtained in 10 patients in each group.

Results
Levels of sensory block, motor block, muscle relaxation, and overall quality of anesthesia did not differ between groups. The frequency of hypotension was 84.4% in the levobupivacaine group and 100% for the bupivacaine group (P < or = 0.053). No significant difference in observed maximum concentration of drug after dosing or area under the plasma drug concentration versus time curve were seen. The maximum concentrations were 1.017 and 1.053 microg/ml, and the areas were 4.082 and 3.765 h(microg/ml) for the levobupivacaine and bupivacaine groups, respectively. Umbilical vein-to-maternal vein ratios were 0.303 for the levobupivacaine group and 0.254 for the bupivacaine group.

Conclusions
The use of epidural 0.5% levobupivacaine for cesarean delivery results in equally efficacious anesthesia compared with 0.5% bupivacaine. Pharmacokinetic parameters were similar in the two groups.
The Effects of Two Antiinflammatory Pretreatments on Bacterial-induced Lung Injury
Authors: Miyazaki Hiroshi , Broaddus V. Courtney , Wiener-Kronish Jeanine P. , Sawa Teiji , Pittet Jean-Francois , Kravchenko Vladimir , Mathison John C. , Nishizawa Hideo , Hattori Satoshi , Yamakawa Tadashi , Yamada Hiroshi , Kudoh Ichidai 
Published: November 2003

Background
Two antiinflammatory therapies that have been effective in preventing acid-induced lung injury were evaluated. Specifically, their effects on a subsequent bacterial-airspace challenge were compared. Bacteria were instilled 24 h after acid-induced lung injury. Pseudomonas aeruginosa PAO-1 was used as the bacteria, because its effects in healthy lungs was documented previously.

Methods
New Zealand white rabbits were anesthetized and three pretreatments were administered: (1) pentoxifylline pretreatment (a 20-mg/kg bolus dose and then 6 mg x kg(-1) x h(-1) given intravenously), (2) 1 ml anti-tumor necrosis factor alpha antiserum given intravenously, or (3) normal saline given intravenously. The pretreatment doses were shown previously to prevent acid-induced lung injury. Then 1.2 ml/kg hydrochloric acid (HCl), pH 1.25, was instilled into the rabbits' right lungs. All the animals underwent mechanical ventilation for 8 h. Twenty-four hours after the acid instillation, the rabbits were anesthetized again and 2 ml/kg (10(9) colony forming units/ml) PAO-1 was instilled into their left lungs. The rabbits' breathing was aided by mechanical ventilation for another 8 h, and then they were killed and exsanguinated.

Results
Both pretreatments attenuated the acid-induced lung injury of the noninstilled left lungs. Arterial oxygen tension and the lung edema of pretreated, acid-exposed animals were significantly and almost equally improved (compared with no pretreatments) by either of the pretreatments. However, when the bacteria were instilled into the left lungs 24 h after the acid injury, the pentoxifylline pretreatment but not the anti-tumor necrosis factor alpha pretreatment prevented much of the bacteria-induced lung injury. Pentoxifylline pretreatment significantly improved the measurements of left lung edema and epithelial and endothelial permeability. There was also a trend for improved oxygenation in the pentoxifylline-pretreated and infected animals. In contrast, the anti-tumor necrosis factor alpha pretreatment did not prevent the bacteria-induced lung injury and increased some of the measurements of lung injury.

Conclusions
Two antiinflammatory therapies that prevented acid-induced lung injury to the noninstilled left lungs had significantly different effects on a subsequent bacteria-induced lung injury to the left lungs. The therapies differed in their mechanism of tumor necrosis factor alpha blockade, and this may have affected the bacteria-induced injury to the lungs.
The Comparative Toxicity of Cocaine and Its Metabolites in Conscious Rats
Authors: Morishima Hisayo O. , Whittington Robert A. , Iso Ayako , Cooper Thomas B. 
Published: November 2003

Background
The metabolites of cocaine, benzoylecgonine and ecgonine methyl ester, have been considered pharmacologically inactive when administered systemically. However, recent in vitro studies suggest that this may not be true. The current study was designed to evaluate the systemic toxicity of cocaine and its metabolites when administered systemically to awake rats fitted with catheters for long-term monitoring.

Methods
Cocaine, norcocaine, cocaethylene, benzoylecgonine, and ecgonine methyl ester were infused intravenously to produce sequential behavioral alterations and central nervous system and cardiovascular toxic effects. Arterial blood pressure and heart rate were monitored continuously. Plasma and tissue samples were analyzed for all compounds by capillary gas chromatography-mass spectrometry.

Results
The dose of norcocaine necessary to produce toxic effects was smaller than that of cocaine and cocaethylene. Benzoylecgonine and ecgonine methyl ester did not produce toxic manifestations at infusion rates that produced toxicity in the cocaine, norcocaine, and cocaethylene groups. Furthermore, 30- and 60-fold higher doses of benzoylecgonine and ecgonine methyl ester, respectively, were necessary to produce only mild neurobehavioral changes. Benzoylecgonine was not lethal even at doses 100 times greater than cocaine.

Conclusions
These results indicate that benzoylecgonine and ecgonine methyl ester are not as toxic as cocaine, norcocaine, or cocaethylene when administered intravenously to pharmacologically naive rats.
Preparation of Barbiturate Optical Isomers and Their Effects on GABA (A) Receptors
Authors: Tomlin Sarah L. , Jenkins Andrew , Lieb William R. , Franks Nicholas P. 
Published: November 2003

Background
Barbiturate anesthetics are optically active and usually exist in two mirror-image enantiomeric forms. Their stereoselective effects in mammals are well known, but remarkably few data are available concerning their effects on anesthetic targets in vitro. This is in part because of the lack of availability of pure barbiturate enantiomers. Such in vitro data could be used to test the relevance of putative molecular targets.

Methods
A high-performance liquid chromatography technique using a permethylated beta-cyclodextrin column was used to separate the optical isomers of three barbiturates in preparative quantities. The effects of the isomers on GABA-induced currents in stably transfected mouse fibroblast cells were investigated using the whole-cell patch-clamp technique.

Results
Highly purified optical isomers of hexobarbital, pentobarbital, and thiopental were prepared, and their effects were studied on a gamma-aminobutyric acid type A receptor of defined subunit composition. For each of the three barbiturates, both enantiomers potentiated gamma-aminobutyric acid-induced currents at pharmacologically relevant concentrations, with the S-enantiomer being more potent than the R-enantiomer by a factor of between 1.7 and 3.5. The degree of stereoselectivity did not vary greatly with anesthetic concentration.

Conclusions
The rank order and degree of stereoselectivity that we have observed for the enantiomers of hexobarbital, pentobarbital, and thiopental acting on the gamma-aminobutyric acid type A receptor are entirely consistent with this receptor playing a central role in the anesthetic actions of barbiturates.
4-Chloro-m-cresol Triggers Malignant Hyperthermia in Susceptible Swine at Doses Greatly Exceeding Those Found in Drug Preparations
Authors: Iaizzo Paul A. , Johnson Brooks A. , Nagao Kaoru , Gallagher William J. 
Published: November 2003

Background
Chlorocresols are used as preservatives in numerous commercial drugs that have been shown to induce myoplasmic Ca2+ release; the most potent isoform is 4-chloro-m-cresol. The aims of this study were to (1) examine the in vivo effects of 4-chloro-m-cresol on swine susceptible to malignant hyperthermia and (2) contrast in vivo versus in vitro dose-response curves.

Methods
Susceptible swine (weight: 38.5 kg+/-3.55 kg) were anesthetized and monitored for variations in physiological responses, including end-tidal CO2, heart rate, blood pressure, blood chemistry, and temperatures. In the first animals studied, 4-chloro-m-cresol, at equivalent cumulative doses of 0.14, 0.28, 0.57, 1.14, 2.27, 4.54, and 9.08 mg/kg (n = 3; 12.5, 25, 50, 100, 200, 400, and 800 micromol) were administered, and in a second group, larger doses were used: 1.14, 3.41, 7.95, 17.04 (n = 4), and/or 35.22 (n = 1) mg/kg (100, 300, 700, 1,500, and/or 3,100 micromol). For comparison, in vitro rectus abdominis muscle preparations obtained from normal and susceptible swine were exposed to 4-chloro-m-cresol, at cumulative concentrations of 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1,600 micromol; standard caffeine and halothane contracture testing was also performed.

Results
Episodes of malignant hyperthermia were not triggered in response to administration of low doses of 4-chloro-m-cresol, but transient cardiovascular reactions (e.g., tachycardia, arrhythmias, and hypotension) were observed. Subsequently, episodes in these animals were triggered when halothane (0.87; 1 MAC) and succinylcholine (2 mg/kg) were given. Animals administered the higher doses of 4-chloro-m-cresol all had fulminant episodes of malignant hyperthermia that were fatal, when equivalent cumulative concentrations were greater than 1,500 micromol. The levels of 4-chloro-m-cresol in the plasma rapidly decreased: e.g., 5 min postadministration of the 1,500-micromol dose, the mean plasma level was only 52+/-18 micromol (n = 4). Hemolysis was detected following 4-chloro-m-cresol administration at concentrations > 200 micromol. In vitro, muscle from susceptible animals elicited contractures > 200 mg at 50-micromol bath concentrations of 4-chloro-m-cresol (n = 29), whereas normal muscle did not elicit such contractures until bath concentrations were > 800 micromol (n = 10).

Conclusions
4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine, but only when serum concentrations are far above those likely to be encountered in humans. A relatively low concentration of 4-chloro-m-cresol, 50 micromol, is sufficient to activate sarcoplasmic [Ca+2] release in vitro (e.g., contractures); this same bolus dose administered in vivo (0.57 mg/kg) has minimal effects due to the rapid decrease in its plasma levels.
Deep Sedation and Mechanical Ventilation without Paralysis for 3 Weeks in Normal Beagles
Authors: Gronert Gerald A. , Fung Dennis L. , Haskins Steve C. , Steffey Eugene P. 
Published: November 2003

Background
Patients in the intensive care unit may have muscle weakness in the recovery phase, and disuse atrophy may play a role in this weakness. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation.

Methods
Six dogs were anesthetized with pentobarbital to a sufficient depth that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks. Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 microg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NONMEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment.

Results
The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716+/-1,208 ng/ml (mean +/- SD), which was significantly different from 257+/-34 ng/ml, the value on day 0. There were no pharmacokinetic differences.

Conclusion
The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.
The Relationship between the Visual Analog Pain Intensity and Pain Relief Scale Changes during Analgesic Drug Studies in Chronic Pain Patients
Authors: Angst Martin S. , Brose William G. , Dyck John B. 
Published: November 2003

Background
Most analgesic drug studies in humans quantify drug action based on verbal reports of pain intensity and pain relief. Although measures of pain intensity and pain relief show a good overall correlation, it is not known if they relate to each other consistently over time Such consistency is necessary if both measures are used to depict analgesic drug action versus time. This study examined in chronic pain patients if the relationship between visual analog pain intensity and pain relief scores was consistent during two analgesic drug studies.

Methods
Data from two independently performed analgesic drug studies were analyzed using linear regression. Data were split into pain intensity and pain relief scores recorded before and after patients' experience of maximum analgesia (>90% of maximum pain relief). The slopes of the linear regression line depicting pain intensity versus pain relief scores before and after maximum analgesia were statistically compared.

Results
The slope of the linear regression line before and after maximum analgesia was significantly different in both drug studies (nonoverlapping 95% confidence intervals), -2.16+/-0.57 versus -1.05+/-0.10 and -1.47+/-0.26 versus -1.09+/-0.07, respectively. These results are compatible with the observation that patients indicating the same pain intensity before and after maximum analgesia reported a different magnitude of pain relief.

Conclusions
The relationship between visual analog pain intensity and pain relief scores changed systematically during both analgesic drug studies. The authors hypothesize that patients' interpretation of the pain relief scale had changed during the studies and therefore suggest using the pain intensity scale to quantify analgesic drug action over time.
Pharmacodynamics and the Plasma Concentration of Mivacurium during Spontaneous Recovery and Neostigmine-facilitated Recovery
Authors: Lien Cynthia A. , Belmont Matthew R. , Roth Doreen L. Wray , Okamoto Michiko , Abalos Amy , Savarese John J. 
Published: November 2003

Background
The authors examined the plasma concentrations of the isomers of mivacurium and its pharmacodynamics during spontaeous and neostigmine-facilitated recovery after a mivacurium infusion.

Methods
Sixteen patients receiving nitrous oxide-opioid anesthesia received 0.25 mg/kg mivacurium. Patient response to neuromuscular stimulation was determined using a mechanomyograph Once T1 had recovered to 25% of its baseline height, a mivacurium infusion was begun and adjusted to maintain 95-99% neuromuscular block. The infusion was discontinued after 90 min and muscle strength allowed to recover either spontaneously or after neostigmine/glycopyrrolate (0.05/0.01 mg/kg). Plasma concentrations of the isomers of mivacurium after discontinuation of the infusion were determined using an HPLC assay. Differences between the groups were determined using a one-way analysis of variance with a Bonferroni-corrected t test or Student t test as appropriate. P < or = 0.05 was considered significant.

Results
Differences in the times for recovery to a train-of-four ratio of 70% did not achieve statistical significance (mean+/-SD, 13.3+/-6.0 vs. 16.3+/-2.5 min for the neostigmine and spontaneous groups, respectively). Plasma cholinesterase activity decreased significantly from baseline values after administration of neostigmine (5.88+/-0.21 vs. 0.43+/-0.04 U/ml plasma). Plasma concentrations of the trans-trans isomer were significantly greater in the neostigmine group than in the spontaneous recovery group 5, 6, 8, and 10 min after discontinuation of the infusion. Differences in the plasma concentration of the cis-trans isomer did not achieve statistical significance.

Conclusions
Although administration of neostigmine decreased plasma cholinesterase activity and caused the trans-trans isomer to remain in the plasma at higher concentration, it did not delay recovery from mivacurium-induced block.