bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Maximum Depth of an Atracurium Neuromuscular Block Antagonized by Edrophonium to Effect Adequate Recovery
Authors: Beemer Geoffrey H. , Goonetilleke Patricia H. , Bjorksten Andrew R. 
Published: November 2003

Background
The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium.

Methods
In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio > or = 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium.

Results
In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio > or = 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > or = 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 +/- 3% (mean +/- SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 +/- 0.33 mg.kg-1 (mean +/- SD).

Conclusions
There is a maximum level of neuromuscular block that can be antagonized by edrophonium to effect adequate recovery. The level corresponds approximately to the reappearance of the fourth response to TOF stimulation. It is probably safest to wait until this level of block occurs before edrophonium is given for reversal. Earlier administration will not hasten recovery.
Triiodothyronine Increases Contractility Independent of β-Adrenergic Receptors or Stimulation of Cyclic-3',5'-Adenosine Monophosphate
Authors: Ririe Douglas G. , Butterworth John F. IV , Royster Roger L. , MacGregor Drew A. , Zaloga Gary P. 
Published: November 2003

Background
Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP).

Methods
A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol. cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol.

Results
T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 +/- 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 mumol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production.

Conclusions
These results demonstrate that the acute inotropic effects of T3 are not shared by T4 and appear unrelated to beta-adrenergic receptor mechanisms or to generation of cAMP. Thus, T3 acutely stimulates cardiac contraction by mechanisms that differ from those of the more commonly used beta-adrenergic receptor agonists and phosphodiesterase inhibitors. Further studies are needed to identify the mechanisms underlying the acute contractile effects of T3 and to determine whether T3 will prove useful for increasing ventricular function in patients.
The Clinical Neuromuscular Pharmacology of 51W89 in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia
Authors: Belmont Matthew R. , Lien Cynthia A. , Quessy Steve , Abou-Donia Martha M. , Abalos Amy , Eppich Larissa , Savarese John J. 
Published: November 2003

Background
Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures.

Methods
Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length.

Results
The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min.

Conclusions
51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.
The Effect of Intrinsic Efficacy on Opioid Tolerance
Authors: Duttaroy Alokesh , Yoburn Byron C. 
Published: November 2003

Background
The intrinsic efficacy of opioid analgesics has been suggested to play a role in the development of tolerance to these agents. However, the effect of differences in dosing protocol on tolerance to opioid analgesics of high or low efficacy has not been addressed. Therefore, the effect of opioid intrinsic efficacy on tolerance in mice was determined in protocols of continuous and intermittent administration of equieffective doses of opioid agonists.

Methods
Initial antinociceptive median effective doses (ED50s) for five opioid agonists that vary in intrinsic efficacy were estimated in untreated mice. Groups of mice received continuous infusions of morphine, fentanyl, or etorphine for 72 h or 7 days from osmotic minipumps implanted subcutaneously. The infusion doses were calculated as multiples of the initial antinociceptive ED50. An inert placebo was implanted subcutaneously in controls. At the end of treatment, the pumps and placebos were removed, and 4-24 h later, mice were tested in dose-response studies (tail flick) using the same drug that had been chronically administered. In another study using intermittent dosing, mice received subcutaneous injections every 24 h for 3 days of saline or morphine, etorphine, fentanyl, oxycodone, or meperidine, or received subcutaneous injections every 24 h for 7 days of saline or morphine, etorphine, or fentanyl. Daily doses were calculated as multiples of the initial antinociceptive ED50. Twenty-four hours after the last injection, mice were tested in dose-response studies.

Results
High-intrinsic-efficacy compounds (e.g., etorphine and fentanyl) produced less tolerance than a lower-intrinsic-efficacy drug (morphine) in 72-h and 7-day infusion studies. Tolerance for all compounds after intermittent treatment with equieffective doses was similar, and intrinsic efficacy had no effect on the magnitude of tolerance after intermittent dosing.

Conclusions
These results indicate that the intrinsic efficacy of opioid analgesics is inversely related to the degree of tolerance after continuous infusion, but that intrinsic efficacy does not significantly affect tolerance after once-daily intermittent administration of these agents. These findings may be of clinical utility in understanding the development of tolerance to the antinociceptive effects of opioids.
Pharmacokinetic Model Selection for Target Controlled Infusions of Propofol
Authors: Coetzee J. F , MBChB MMed (Anes.) , Glen J. B. , Boshoff L. 
Published: November 2003

Background
Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability.

Methods
Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data.

Results
Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time.

Conclusions
Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.
The Effects of Epidural Ropivacaine and Bupivacaine for Cesarean Section on Uteroplacental and Fetal Circulation
Authors: Alahuhta Seppo , Rasanen Juha , Jouppila Pentti , Kangas-Saarela Tuula , Jouppila Riitta , Westerling Peter , Hollmen Arno I. 
Published: November 2003

Background
Ropivacaine is a new long-acting amide local anesthetic that has been shown in animal studies to have less dysrhythmogenic and cardiotoxic potential than bupivacaine. The intravenous administration of ropivacaine has not been associated with any detrimental effects on uterine blood flow in pregnant ewes. The purpose of this randomized, double-blind study was to examine the effects of epidural ropivacaine for cesarean section on blood flow velocity waveforms in uteroplacental and fetal arteries with color Doppler ultrasound and to assess whether the block modified fetal myocardial function.

Methods
Healthy parturient women with singleton, uncomplicated pregnancies at term received 115-140 mg 0.5% ropivacaine (n = 11) or 0.5% bupivacaine (n = 10) in incremental epidural doses. The first ultrasound measurement was performed before injection of the study drug. Pulsatility indexes (PI) were derived for the blood flow velocity waveforms of the maternal placental and nonplacental uterine arteries; the placental arcuate artery; and the fetal umbilical, middle cerebral, and renal arteries. The fetal heart then was examined by echocardiography. The PI of the maternal uterine arteries and the fetal umbilical artery were measured 5 min after the injection of the local anesthetic. When sensory analgesia had reached the T6-T4 level, the ultrasound measurement was repeated with the same methods and targets as in the baseline measurement.

Results
Both drugs provided adequate surgical anesthesia for cesarean section. In the bupivacaine group, the PI values for the maternal placental and nonplacental uterine arteries increased significantly 5 min after the main dose (P = 0.01, P = 0.002) and when sensory analgesia had reached the T6-T4 level (P = 0.004, P = 0.01) as compared with the baseline measurement. Simultaneously, the PI in the fetal middle cerebral artery decreased significantly (P = 0.02). The PI for the maternal uterine artery increased significantly (P = 0.01) after ropivacaine administration but only on the nonplacental side and not until sensory analgesia had reached the T6-T4 level. No effect on the Doppler indexes obtained from the umbilical artery was observed in either group. There were no significant differences relative to baseline values in any fetal myocardial measurement or in any ultrasound measurement between the groups. Neither drug had any detrimental effect on Apgar scores or umbilical cord acid-base status. None of the neonates' conditions was markedly depressed according to neurobehavioral testing.

Conclusions
Within this small study, epidural 0.5% ropivacaine for cesarean section did not compromise the utero-placental circulation in healthy parturient women with uncomplicated pregnancies. It provided surgical anesthesia that was equally effective as that provided by 0.5% bupivacaine.
Effects of Interpleural Bupivacaine on Respiratory Muscle Strength and Pulmonary Function
Authors: Gallart Lluis , Gea Joaquim , Aguar M. Carmen , Broquetas Joan M. , Puig Margarita M. 
Published: November 2003

Background
Several reports suggest that interpleural local anesthetics may have deleterious effects on respiratory function. The current study investigated the effects of interpleural bupivacaine on human respiratory muscles and lung function.

Methods
Thirteen patients (55 +/- 4 yr old) with normal respiratory function and scheduled for cholecystectomy entered the study before surgery. Respiratory parameters were compared before and after the interpleural administration of 20 ml 0.5% bupivacaine plus 1:200,000 epinephrine while patients were supine; we evaluated breathing pattern, dynamic and static lung volumes, airway conductance, maximal inspiratory pressures (at the mouth; at the esophagus [Pessniff]; at the abdomen [Pgasniff]; and transdiaphragmatic [Pdisniff]), functional reserve (tension-time index) of the diaphragm, and maximal expiratory pressures (at the mouth; at the esophagus [Pescough]; and at the abdomen [Pgacough]). Hemoglobin oxygen saturation by pulse oximetry, heart rate, and mean arterial pressure were continuously monitored.

Results
Respiratory rate (15 +/- 1 to 19 +/- 1 breaths/min; P < 0.01) and heart rate (78 +/- 3 to 83 +/- 3 beats/min; P < 0.01) were slightly increased. Dynamic and static lung volumes, airway conductance, hemoglobin saturation, and the remaining breathing pattern parameters were unchanged. Regarding respiratory muscles, maximal inspiratory pressure at the mouth, Pessniff, and tension-time index of the diaphragm did not change. Pdisniff decreased slightly (102 +/- 10 to 92 +/- 10 cmH2O; P < 0.05) because of a change in Pgasniff (24.2 +/- 7.4 to 18.4 +/- 6.8 cmH2O; P < 0.05). Maximal expiratory pressure at the mouth remained unaltered, but Pgacough decreased (108 +/- 10 to 92 +/- 8 cmH2O; P < 0.01), and Pescough showed a trend to decrease (92 +/- 13 to 78 +/- 10 cmH2O; P = 0.074).

Conclusions
In our experimental conditions, interpleural bupivacaine did not significantly change lung function or inspiratory muscle strength but induced a slight decrease in abdominal muscle strength. Although this effect was minimal, its clinical relevance needs to be evaluated further in patients with impaired respiratory function.
Local Cerebral Glucose Utilization in Stimulated Rats Sedated with Thiopental
Authors: Archer David P. , Froelich Jennifer , McHugh Michael , Pappius Hanna M. 
Published: November 2003

Background
Recent studies have suggested that supraspinal structures are involved in barbiturate-induced enhancement of nociceptive processing. The goal of the study was to determine whether cortical and subcortical regions involved in nociception were relatively activated or depressed by noxious stimulation during infusion of small doses of thiopental.

Methods
Local cerebral glucose utilization (LCGU) was measured with the 14C-2-deoxyglucose radioautographic technique in 14 rats. During the LCGU experiment, pressure was applied to the tail every 2 min, and the somatic motor response threshold was recorded. Seven animals received thiopental infusions to produce a steady-state plasma concentration (target concentrations of 10 micrograms/ml), and seven untreated animals served as controls.

Results
A steady-state plasma thiopental concentration (11.1 +/- 1.8 to 13.0 +/- 2.1 micrograms/ml) was accompanied by a decrease in the somatic motor response threshold from 277 +/- 32 g (before thiopental) to 215 +/- 41 g (P < 0.001). The somatic motor response threshold remained unchanged in the control group. Average LCGU was 29% less in the thiopental-treated animals than in the untreated controls (P < 0.001). In cortical regions associated with nociception, LCGU was relatively increased (+3% +/- 14%) during the thiopental infusion in comparison to the visual and auditory cortices (-18% +/- 13%; P < 0.001). Individual structures that showed relative changes during thiopental infusion included the nucleus accumbens (+17%, P < 0.05) and the habenula (-17%, P < 0.05). Heterogenous relative changes (P < 0.05) in LCGU were observed in the auditory system: auditory cortex (-22%), medial geniculate (-16%), lateral lemniscus (+26%), superior olive (+38%).

Conclusions
Noxious stimulation during low-dose thiopental infusions relatively increased LCGU in cortical regions postulated to be responsible for processing of noxious stimuli. Nuclei in the descending pain modulating system were not relatively depressed.
Does Early Posttreatment with Lidocaine Attenuate Endotoxin-induced Acute Lung Injury in Rabbits?
Authors: Nishina Kahoru , Mikawa Katsuya , Maekawa Nobuhiro , Takao Yumiko , Obara Hidefumi 
Published: November 2003

Background
It is well known that endotoxin causes acute lung injury, resulting in adult respiratory distress syndrome. Lidocaine pretreatment has recently been shown to attenuate endotoxin-induced lung injury in rabbits. The aim of the current study was to determine whether early postinjury treatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits.

Methods
Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline (group S-S), infusion of saline with lidocaine treatment (group S-L), infusion of Escherichia coli endotoxin (100 micrograms.kg-1 over a 60-min period) without lidocaine treatment (group E-S), or infusion of endotoxin with lidocaine treatment (group E-L). Ten minutes after the end of infusion of endotoxin (groups E-L and E-S) or saline (groups S-S and S-L), the animals received a bolus injection followed by continuous infusion of lidocaine (2 mg.kg-1 + 2 mg.kg-1.h-1 in groups S-L and E-L) or saline (groups S-S and E-S). The rabbits' lungs were ventilated with 40% O2. Hemodynamics, peripheral leukocyte and platelet counts, and arterial O2 tension (PaO2) were recorded during the ventilation period (6 h). After the observation, lung mechanics; the cell fraction of bronchoalveolar lavage fluid (BALF); and concentrations of activated complement components C3a and C5a, cytokines, and arachidonic acid metabolites in BALF were measured and analyzed. The ratio of lung wet weight to dry weight (W/D weight ratio) and albumin concentrations in BALF were analyzed as indexes of pulmonary edema. The Cypridina luciferin analogue-dependent chemiluminescence (representing O2 production) by neutrophils isolated from the pulmonary artery and light-microscopic findings of the lung were compared among the four groups.

Results
Endotoxin caused decreases in peripheral leukocyte and platelet counts, lung compliance, and PaO2. It caused increases in lung W/D weight ratio; polymorphonuclear cell counts in BALF; and albumin, C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and thromboxane B2 concentrations in BALF. Lidocaine attenuated the changes in W/D weight ratio and morphologic lung damage. The change in compliance, decrease in PaO2, and albumin concentrations in BALF were slightly but significantly less in rabbits receiving lidocaine after injury. The Cypridina luciferin analogue-dependent chemiluminescence by neutrophils was greater in rabbits receiving endotoxin without lidocaine than in those receiving endotoxin with lidocaine.

Conclusions
These results indicate that early treatment with lidocaine attenuates endotoxin-induced lung edema in rabbits without affecting chemical mediators in BALF. However, the improvement is slight and likely to be of little clinical significance.