bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-dependent Efficacy of Bacterial Filters and Infection Risk in Long-term Epidural Catheterization
Authors: De Cicco Marcello , Matovic Mira , Castellani Guiseppe Tarabini , Basaglia Giancarlo , Santini Gianfranco , Del Pup Carla , Fantin Dario , Testa Vinicio
Published: November 2003

Background

Epidural infection represents a serious albeit infrequent complication of long-term epidural catheterization. The catheter hub is regarded as the main point of entry for microorganisms among the three possible routes (hematogenous, insertion site, hub) of microbial colonization of the inserted catheter. The current study was aimed at evaluating whether frequent changing of antimicrobial filters carries an increased risk of catheter hub contamination and the time-dependent efficacy of commonly used antimicrobial filters after prolonged use.

Methods

In the first part of the study, a microbiologic survey (skin, filter, hub, and catheter tip) was performed weekly in a group of 47 patients with cancer bearing subcutaneously tunneled catheters managed at home. Subsequently, the time-dependent efficacy of 96 micropore filters (32 Portex, 32 Sterifix-Braun, 32 Encapsulon TFX-Medical) differing in surface areas and/or composition of the filtering membrane was evaluated in a laboratory study. Filters were perfused, under the usual conditions of clinical use (flow resistance, injection pressure, temperature), every 8 h up to 60 days, with 5 ml of two different analgesic solutions, either sterile or containing 1.5 x 10(5)/ml of Streptococcus milleri I. Eight filters of each type subsequently were flushed with a S. milleri suspension (0.5 McFarland) after 7, 14, 28, and 60 days of continuous perfusion, and the resulting filtrates were cultured.

Results

In 16 of 19 positive hub cultures, the same microorganisms (species, biotype, antibiotype) were cultured from skin and filters. A statistically significant positive trend was found between the number of filter changes and the rate of positive hub cultures (chi 1(2) trend 5.11; P = 0.02). A high correlation coefficient was found between number of positive skin cultures and number of positive filtrates (r = 0.88; P = 0.01) and between number of positive filtrates and number of positive hub cultures (r = 0.93; P = 0.003). Cultures obtained from Portex and Sterifix-Braun filters yielded no bacterial growth (64/64) throughout the study period. Cultures from Encapsulon TFX-Medical filters showed bacterial growth 2/8 at seventh day, 7/8 at the 14th day, and 16/16 from the 28th day onward.

Conclusions

Our data indicate significant correlation between the incidence of catheter hub colonization and the filter-change frequency, when the skin close to the filter-hub connection is contaminated. Our results also show that Portex and Sterifix-Braun bacterial filters, when perfused with reduced volumes at low injection pressures, maintain an unmodified antimicrobial function for at least 60 days. Based on these data, it appears clinically feasible to reduce the frequency of filter changes during long-term epidural catheterization, with a consequent possible decrease of epidural catheter colonization.
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.
Effects of Exogenous Intravenous Glucose on Plasma Glucose and Lipid Homeostasis in Anesthetized Infants
Authors: Nishina Kahoru , Mikawa Katsuya , Maekawa Nobuhiro , Asano Migiwa , Obara Hidefumi
Published: November 2003

Background

Whether intravenous glucose administration to infants during anesthesia is necessary remains to be resolved. The current study was designed to investigate the effect of exogenous glucose infusion on plasma glucose and lipid homeostasis in infants undergoing minor surgery.

Methods

Sixty infants (inpatients, ASA physical status 1) between 1 and 11 months of age were divided randomly into three groups as follows: LR group, lactated Ringer's solution (LR) alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. All fluids were infused at a rate of 6 ml.kg-1.h-1 until 1 h after surgery. Plasma concentrations of glucose, nonesterified fatty acids, ketone bodies, insulin, and cortisol were determined at induction of anesthesia, at the end of surgery, and 1 h after surgery.

Results

No infants in the three groups had hypoglycemia (< 50 mg.dl-1) throughout the study. In the LR group, plasma glucose concentration remained unchanged perioperatively compared with the basal values (at induction), whereas in the D2LR group, it increased during surgery but remained normoglycemic. In the D5LR group, plasma glucose concentration increased markedly both during and after surgery. In 6 of 20 infants, plasma glucose was greater than 200 mg.dl-1 at the end of surgery. In 8 of 20 infants receiving glucose-free infusion, plasma glucose concentrations decreased at the end of surgery. In contrast, the plasma glucose concentration increased in infants receiving glucose infusion. In the LR group, plasma concentrations of nonesterified fatty acids and ketone bodies increased at the end of and after surgery, suggesting lipid mobilization. The base excess decreased in the LR groups as concentration of the ketone bodies increased. Plasma insulin concentrations increased in the D2LR and D5LR groups and decreased after surgery in infants receiving a glucose-free solution. No intergroup differences in plasma cortisol concentrations existed at any sample point.

Conclusions

These data indicate that, in otherwise healthy infants undergoing minor surgery, intravenous infusion of 2% glucose may be sufficient to maintain plasma glucose concentrations within physiologic ranges and to prevent a compensatory increase in lipid mobilization (lipolysis) when fluids are infused at a rate of 6 ml.kg-1.h-1. However, there are limitations in extrapolating the results to neonates.
Theoretical Analysis of Cerebral Venous Blood Hemoglobin Oxygen Saturation as an Index of Cerebral Oxygenation during Hypothermic Cardiopulmonary Bypass
Authors: Dexter Franklin , Hindman Bradley J.
Published: November 2003

Background

Jugular venous catheters and near-infrared spectroscopy can measure cerebral venous blood hemoglobin oxygen saturation (SvO2). We used computer simulation to characterize the relation between Sv02 and cerebral metabolic rate for oxygen (CMR02) during hypothermic cardiopulmonary bypass (CPB).

Methods

We developed a theoretical model of cerebral oxygen consumption and blood-brain oxygen transfer. Our model included the temperature dependence of blood and brain oxygen solubility; the temperature, age, and acid-base dependence of hemoglobin oxygen dissociation; and the temperature and age dependence of CMRO2. We simulated cerebral blood flow reductions that decreased Sv02 and CMR02.

Results

Our model predicts the relation between CMR02 and Sv02 to be dependent on temperature, because of a shift of the oxygen partial pressure at which hemoglobin oxygen saturation equals 0.50. For example, during normothermic CPB, Sv02 can decrease to 30% before CMR02 will decrease to less than 90% of normal. In contrast, for alpha-stat management of infants at 17 degrees C, Sv02 must be maintained at greater than 95% to maintain CMR02 at greater than 90% of its temperature appropriate value.

Conclusions

High Sv02 observed during hypothermic CPB may indicate impaired oxygen transfer from hemoglobin to brain, not "luxury perfusion." The relation between Sv02 and CMR02 depends dramatically on the temperature of the patient. Sv02 per se may not be reliable index of normal CMR02 during hypothermic CPB.
Renal Function in Patients with High Serum Fluoride Concentrations after Prolonged Sevoflurane Anesthesia
Authors: Higuchi Hideyuki , Sumikura Hiroyuki , Sumita Shinji , Arimura Shinya , Takamatsu Futoshi , Kanno Masuyuki , Satoh Tetsuo
Published: November 2003

Background

In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia.

Methods

Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group.

Results

The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups.

Conclusions

The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.
Morphine Inhibits Spontaneous and Cytokine-enhanced Natural Killer Cell Cytotoxicity in Volunteers
Authors: Yeager Mark P. , Colacchio Thomas A. , Yu Cecelia T. , Hildebrandt Laurie , Howell Alexandra L. , Weiss Julie , Guyre Paul M.
Published: November 2003

Background

Opioids are used by patients who have conditions ranging from the acute pain of surgery and chronic cancer pain to substance abuse. Despite their widespread use and considerable experimental data about them, little is known about how opioids may alter in vivo immunity in humans. This study was designed to evaluate the in vivo effect of morphine on human peripheral blood immune functions.

Methods

Healthy volunteers underwent continuous exposure to morphine for 36 h including a 24-h intravenous infusion in the hospital. Peripheral blood was drawn for immune function studies at five measurement times before, during, and after morphine exposure. Peripheral blood mononuclear cells were tested for acute and gamma-interferon-stimulated natural killer cell cytotoxicity (NKCC), antibody-dependent cell cytotoxicity, antibody Fc receptor expression, and human immunodeficiency virus infectivity.

Results

Significant suppression of NKCC was observed at 2 and 24 h after the onset of intravenous morphine exposure. Suppression of NKCC persisted for 24 h after termination of morphine infusion in a "high"-dose study group. gamma-Interferon-stimulated NKCC and antibody-dependent cell cytotoxicity were also decreased after 24 h of intravenous morphine exposure. No effect on Fc receptor expression was observed. Mean virus antigen production after lymphocyte infection with human immunodeficiency virus was not increased (p24 100 ng/ml after morphine vs. 43 ng/ml before morphine; P = 0.17).

Conclusions

These results suggest that morphine administration, at doses within the range of analgesic use, can cause measurable suppression of some components of the human cellular immune system.
Combined Spinal-Epidural Anesthesia for Outpatient Surgery
Authors: Urmey William F. , Stanton Jennifer , Peterson Margaret , Sharrock Nigel E.
Published: November 2003

Background

Combined spinal-epidural anesthesia (CSE) may offer theoretic advantages for outpatient surgery, because it produces the rapid onset of spinal anesthesia, with the option to extend the blockade with an epidural catheter. In this study, the authors attempted to determine an appropriate initial dose of a short-acting local anesthetic, 2% lidocaine, to administer for outpatient knee arthroscopy using CSE.

Methods

Data were collected from 90 patients undergoing outpatient knee arthroscopy. Using a double-blinded, prospective study design, patients were randomly assigned to receive CSE with an initial dose of intrathecal 2% lidocaine of 40, 60, or 80 mg. A 27-G 4 11/16-inch Whitacre needle was placed through a 17-G Weiss needle. Onset and regression of sensory anesthesia and motor blockade were measured by a blinded observer at frequent intervals.

Results

All 90 patients had adequate anesthesia. Durations of thoracic and lumbar sensory and lower limb motor blockade were significantly shorter in the 40-mg group compared with the 60- or 80-mg groups (P < 0.0002 Mantel-Cox, Survivorship Analysis). Indices of neural blockade resolved 30-40 min more rapidly in the 40-mg group than in either the 60- or 80-mg group. Times to urinate, site upright in a chair, take oral fluids, and be discharged were all significantly shorter (between 30 and 60 min) in the 40-mg group compared with the 60- and 80-mg groups (P < 0.01). Seven patients required intraoperative epidural supplementation: three in the 40-mg group, three in the 60-mg group, and one in the 80-mg group.

Conclusions

Combined spinal-epidural anesthesia with a 40-mg initial intrathecal dose of lidocaine provided reliable anesthesia for knee arthroscopy. Duration of spinal anesthesia with lidocaine was dose related.
Desflurane Inhibits Hypoxic Pulmonary Vasoconstriction in Isolated Rabbit Lungs
Authors: Loer Stephan A. , Scheeren Thomas W. L. , Tarnow Jorg
Published: November 2003

Background

Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV) in vivo and in vitro with a half-maximum inhibiting effect (ED50) within concentrations applied for general anesthesia. Because it is unknown whether desflurane acts likewise, we studied its effect on HPV in isolated blood-perfused rabbit lungs and compared its ED50 with that of halothane.

Methods

Isolated blood-perfused rabbit lungs were randomly allocated to treatment with either desflurane (n = 6) or halothane (n = 6). HPV, defined as an increase in pulmonary arterial pressure (PAP) at constant flow, was elicited by decreasing inspiratory oxygen concentration from 20% to 3% for 4 min. This effect was determined without (control HPV) and with increasing concentrations of the anesthetics (fraction of inspired carbon dioxide kept constant at 4.8 +/- 0.2%, perfusate temperature at 37 degrees C, and blood flow at 100 ml.min-1).

Results

Before exposure to the anesthetics, PAP increased by 8.6 +/- 1.9 cmH2O for all lungs within 4 min of hypoxia (control PAP for all lungs 19.6 +/- 2.5 cmH2O). Desflurane decreased this effect in a concentration-dependent fashion with an ED50 of 14.5%, compared with that of halothane, with an ED50 of 1.7%.

Conclusions

Assuming that 1 minimum alveolar concentration (MAC) values of desflurane and halothane for rabbits are 8.9% and 1.39%, respectively, this study yields ED50 values for the inhibition of HPV of approximately 1.6 MAC for desflurane and 1.2 MAC for halothane (P not statistically significant).
Effect of Aminophylline on High-energy Phosphate Metabolism and Fatigue in the Diaphragm
Authors: Ide Tohru , Nichols David G. , Buck James R. , Eleff Scott M. , Shungu Dikoma C. , Robotham James L. , Fitzgerald Robert S. , Traystman Richard J.
Published: November 2003

Background

Diaphragmatic fatigue causes respiratory failure, for which aminophylline has been used as therapy. Because the mechanism of action of aminophylline in reversing diaphragmatic fatigue is unclear, we used in vivo 31P magnetic resonance spectroscopy (MRS) to determine the relation between diaphragmatic activation, force output, and aerobic metabolism.

Methods

Bilateral phrenic stimulation was used to pace the diaphragm in pentobarbital-anesthetized piglets (6-10 weeks old; n = 44). Esophageal and abdominal pressures were measured to calculate transdiaphragmatic pressure (Pdi) (Pdi = abdominal pressure-esophageal pressure) as an index of force output. Activation was determined by the amplitude of the compound action potential of the diaphragmatic electromyogram. Aerobic metabolism was assessed with a 31P MRS surface coil on the right hemidiaphragm with the animal in a 4.7-T magnet. The animals were divided into four groups based on aminophylline loading dose: saline, aminophylline 10 mg/kg (A10), aminophylline 20 mg/kg (A20), and aminophylline 40 mg/kg (A40). After aminophylline loading the diaphragm was paced for 25 min followed by a 10-min recovery.

Results

Aminophylline concentrations were 12.2 +/- 0.7, 21.9 +/- 2.4, and 44.9 +/- 3.6 mg/l in the A10, A20, and A40 groups, respectively. Compound action potential amplitude decreased in all groups by 30% after 25 min of pacing. Conversely, Pdi remained at 100 +/- 3% of the initial value after 5 min of pacing in the A40 group but decreased to 75 +/- 3% in the saline group. Pdi recovered completely (103 +/- 17%) in the A40 group but remained depressed (72 +/- 6%) in the saline group. Pdi values were intermediate in the A10 and A20 groups. MRS data revealed inadequate energy supply/demand ratio in the saline group such that the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) increased to 1.01 +/- 0.09 after 5 min of pacing. Pi/PCr remained unchanged in the A40 group and was intermediate in the A10 and A20 groups. beta-Adenosine triphosphate and intracellular pH did not differ among groups or as a function of pacing. Diaphragmatic blood flow increased from a resting value of 35-60 to 300-410 ml.min-1 x 100 g-1 during pacing in all groups and was not affected by aminophylline dose.

Conclusions

Aminophylline, in a dose-dependent fashion, delays the onset of fatigue and improves recovery from fatigue. Delayed fatigue is associated with improved aerobic metabolism as reflected in a low Pi/PCr ratio.
Direct Cerebrovasodilatory Effects of Halothane, Isoflurane, and Desflurane during Propofol-induced Isoelectric Electroencephalogram in Humans
Authors: Matta Basil F. , Mayberg Teresa S. , Lam Arthur M.
Published: November 2003

Background

The effect of volatile anesthetics on cerebral blood flow depends on the balance between the agent's direct vasodilatory action and the indirect vasoconstrictive action mediated by flow-metabolism coupling. To compare the intrinsic action of volatile anesthetics, the effect of halothane, isoflurane, and desflurane on flow velocity in the middle cerebral artery during propofol-induced isoelectricity of the electroencephalogram was examined.
Desflurane and Isoflurane Exert Modest Beneficial Actions on Left Ventricular Diastolic Function during Myocardial Ischemia in Dogs
Authors: Pagel Paul S. , Hettrick Douglas A. , Lowe Dermot , Tessmer John P. , Warltier David C.
Published: November 2003

Background

Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia.
Further Characterization of the Receptor Mechanism Involved in the Antidysrhythmic Effect of Dexmedetomidine on Halothane/Epinephrine Dysrhythmias in Dogs
Authors: Kamibayashi Takahiko , Mammoto Tadanori , Hayashi Yukio , Yamatodani Atsushi , Takada Koji , Sasaki Shigeta , Yoshiya Ikuto
Published: November 2003

Background

alpha2Adrenoceptors in the central nervous system mediate various physiologic processes, including cardiovascular control. Recently, some of these actions have been reported to be mediated by a nonadrenergic receptor, namely an imidazoline receptor. The authors previously reported that dexmedetomidine, a selective alpha2agonist, prevents the genesis of halothane-epinephrine dysrhythmias through a central mechanism. Because dexmedetomidine also binds to imidazoline receptors, we performed the current study to examine the precise receptor mechanism involved in the antidysrhythmic property of dexmedetomidine.
Technique for Quantifying the Duration of Intravenous Anesthetic Effect
Authors: Bailey James M.
Published: November 2003

Background

Several recent studies have analyzed the relationship between pharmacokinetic parameters and the rate of decrease in concentration after discontinuation of a continuous drug infusion. Although these studies have clarified our understanding of those aspects of pharmacokinetics most relevant to anesthesia practice, they do not directly address the issue of the duration of drug effect, which will be a function of both pharmacokinetic and pharmacodynamic variables. This paper extends these concepts by presenting a method to unify pharmacokinetics and pharmacodynamics in a measure of duration of drug effect that is applicable when the drug effect is assessed in a binary, response/no response fashion.
Nitroprusside Inhibition of Platelet Function Is Transient and Reversible by Catecholamine Priming
Authors: Harris Stephen N. , Rinder Christine S. , Rinder Henry M. , Tracey Jayne B. , Smith Brian R. , Hines Roberta
Published: November 2003

Background

The time course and reversibility of sodium nitroprusside's in vivo inhibition of platelet function are unclear.
Inhaled Nitric Oxide Reduces Pulmonary Transvascular Albumin Flux in Patients with Acute Lung Injury
Authors: Benzing A. , Brautigam P. , Geiger K. , Loop T. , Beyer U. , Moser E.
Published: November 2003

Background

In acute lung injury, when pulmonary microvascular permeability is enhanced, transvascular fluid filtration mainly depends on pulmonary capillary pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40 ppm on pulmonary transvascular albumin flux was studied in nine patients with acute lung injury.
Desflurane Reduces the Gain of Thermoregulatory Arteriovenous Shunt Vasoconstriction in Humans
Authors: Kurz Andrea , Xiong Junyu , Sessler Daniel I. , Dechert Martha , Noyes Katherine , Belani Kumar
Published: November 2003

Background

Thermoregulatory responses, such as arteriovenous shunt vasoconstriction, provide substantial protection against core hypothermia. A response can be characterized by its threshold (core temperature triggering response), gain (rate at which response intensity increases, once triggered), and maximum response intensity. Reduced gain decreases the efficacy of a thermoregulatory response at a given threshold because response intensity will increase more slowly than usual. The effects of general anesthesia on the gain of arteriovenous shunt vasoconstriction have not been reported. Accordingly, we tested the hypothesis that desflurane decreases the gain of centrally mediated vasoconstriction.
Halothane Modulates Thermosensitive Hypothalamic Neurons in Rat Brain Slices
Authors: Farber Neil E. , Schmidt Jeffrey E. , Kampine John P. , Schmeling William T.
Published: November 2003

Background

In vivo, halothane alters spontaneous firing in and thermosensitivity of neurons in the preoptic region of the anterior hypothalamus. To better understand the mechanisms by which halothane specifically disrupts normal thermoregulation, this investigation examined the effects of halothane on thermosensitive preoptic region neurons in isolated hypothalamic tissue slices.