bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids Prolong Rat Sciatic Nerve Blockade In Vivo from Bupivacaine Microspheres
Authors: Castillo Jenny , Curley Joanne , Hotz Joyce , Uezono Megumi , Tigner Joseph , Chasin Mark , Wilder Robert , Langer Robert , Berde Charles 
Published: November 2003

Background
Previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here.

Methods
Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres.

Results
Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively.

Conclusions
Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.
Intrathecal Catheterization in the Rat
Authors: Sakura Shinichi , Hashimoto Keishi , Bollen Andrew W. , Ciriales Ricardo , Drasner Kenneth 
Published: November 2003

Background
The authors previously described an in vivo model suitable for investigation of functional impairment induced by intrathecally injected local anesthetic. However, meaningful histologic analysis could not be performed because catheterization, per se, induced morphologic changes in control animals. In the current experiments, the authors sought to identify an alternative, less reactive, catheterization technique for intrathecal drug administration.

Methods
Twenty-five rats received an intrathecal infusion of normal saline through a catheter composed of either 28-gauge polyurethane, 32-gauge polyimide, 32-gauge polyurethane, PE-10 polyethylene, or PE-10 polyethylene that had been stretched to twice its original length. Seven days after infusion, sensory function was assessed using the tail-flick test, and the spinal cord and nerve roots were prepared for neuropathologic evaluation.

Results
There was no significant difference in sensory function among groups. Animals in which 28-gauge polyurethane, 32-gauge polyimide, PE-10, and double-stretched PE-10 had been implanted had moderate to severe nerve injury in 11%, 14%, 23%, and 8% of fascicles, respectively, whereas none of the animals in which 32-gauge polyurethane was implanted had any evidence of moderate or severe damage.

Conclusions
Morphologic changes induced by intrathecal catheterization in the rat can be minimized by the use of 32-gauge polyurethane tubing.
Effect of Diltiazem on Midazolam and Alfentanil Disposition in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Ahonen Jouni , Olkkola Klaus T. , Salmenpera Markku , Hynynen Markku , Neuvonen Pertti J. 
Published: November 2003

Background
Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia.

Methods
Thirty patients having coronary artery bypass grafting were randomly assigned to receive either diltiazem (60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg.kg-1.h-1 started at induction and continued for 23 h) or placebo in a double-blind study. Anesthesia was induced with 0.1 mg/kg midazolam, 50 micrograms/kg alfentanil, and 20 to 80 mg propofol and maintained with infusions of 1 microgram.kg-1.min-1 of both midazolam and alfentanil supplemented with isoflurane. Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined. The terminal half-life and the time for the drug plasma level to decrease 50% after cessation of the infusion (t50) were calculated for midazolam and alfentanil. Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol.

Results
Diltiazem increased the mean concentration-time curves (from end of anesthesia until 23 h) of midazolam by 24% (P < 0.05) and that of alfentanil by 40% (P < 0.05). The mean half-life of midazolam was 43% (P < 0.05) and that of alfentanil was 50% (P < 0.05) longer in patients receiving diltiazem. The mean t50 of alfentanil was 40% longer (P < 0.05) in patients receiving diltiazem, but the change in the mean t50 of midazolam (25%) was not statistically significant. In patients receiving diltiazem, tracheal extubation was performed on average 2.5 h later (P = 0.054) than in those receiving placebo.

Conclusions
Diltiazem slows elimination of midazolam and alfentanil and may delay tracheal extubation after large doses of these anesthetic adjuncts. CYP3A-mediated drug interactions should be considered as confounders when recovery from anesthesia with midazolam and alfentanil infusions is assessed.
Human Skin Flora as a Potential Source of Epidural Abscess
Authors: Sato Sukeyuki , Sakuragi Tadakazu , Dan Kenjiro 
Published: November 2003

Background
The mechanism of epidural infection associated with epidural block is not clearly understood. Resident organisms in skin specimens were studied after skin was prepared with disinfectants.

Methods
Sixty-nine paired skin specimens were excised at incisional sites after skin disinfection with 10% povidone-iodine (10% PVP-I) or 0.5% chlorhexidine in 80% ethanol (0.5% CHE) from 60 patients having back surgery. One of the specimen pairs was placed in 10 ml brain-heart infusion broth and incubated in air at 37 degrees C for 96 h. The other specimen was sectioned at 3 microns and prepared with Gram's stain for examination with the microscope.

Results
Thirteen gram-positive staphylococcal species (Staphylococcus epidermidis, 69.2%; S. hyicus, 15.4%; and S. capitis, 15.4%) were isolated from cultures. The isolates were found in a significantly greater proportion of the skin specimens disinfected with 10% PVP-I than in those disinfected with 0.5% CHE (11 of 34 cultures [32.4%] vs. 2 of 35 cultures [5.7%]; P < 0.01). Many gram-positive cocci were observed with the microscope in 4 (11.8%) and 5 (14.3%) of 34 and 35 skin specimens disinfected with 10% PVP-I and 0.5% CHE, respectively. The cocci formed a dense colony in each follicle and in the stratum corneum. No organism was present in any of 17,584 sweat glands examined.

Conclusions
In a large proportion of patients, isolation of viable organisms from excised skin specimens after disinfection with 10% PVP-I suggests that contamination of the epidural space by the skin flora may be a potential mechanism of epidural infection associated with epidural block.
Evaluation of a New Point-of-care Test that Measures PAF-mediated Acceleration of Coagulation in Cardiac Surgical Patients
Authors: Despotis George J. , Levine Vladimir , Filos Kriton S. , Santoro Samuel A. , Joist J. Heinrich , Spitznagel Edward , Goodnough Lawrence T. 
Published: November 2003

Background
This study was designed to evaluate a new point-of-care test (HemoSTATUS) that assesses acceleration of kaolin-activated clotting time (ACT) by platelet activating factor (PAF) in patients undergoing cardiac surgery. Our specific objectives were to determine whether HemoSTATUS-derived measurements correlate with postoperative blood loss and identify patients at risk for excessive blood loss and to characterize the effect of desmopressin acetate (DDAVP) and/or platelet transfusion on these measurements.

Methods
Demographic, operative, blood loss and hematologic data were recorded in 150 patients. Two Hepcon instruments were used to analyze ACT values in the absence (channels 1 and 2: Ch1 and Ch2) and in the presence of increasing doses of PAF (1.25, 6.25, 12.5, and 150 nM) in channels 3-6 (Ch3-Ch6). Clot ratio (CR) values were calculated with the following formula for each respective PAF concentration: clot ratio = 1-(ACT/control ACT). These values also were expressed as percent of maximal (%M = clot ratio/0.51 x 100) using the mean CRCh6 (0.51) obtained in a reference population.

Results
When compared with baseline clot ratios before anesthetic induction, a marked reduction in clot ratios was observed in both Ch5 and Ch6 after protamine administration, despite average platelet counts greater than 100 K/microliter. There was a high degree of correlation between clot ratio values and postoperative blood loss (cumulative chest tube drainage in the first 4 postoperative hours) with higher concentrations of PAF: CRCh6 (r = -0.80), %M of CRCh6 (r = -0.82), CRCh5 (r = -0.70), and %M of CRCh5 (r = -0.85). A significant (P < 0.01) improvement in clot ratios was observed with time after arrival in the intensive care unit in both Ch5 and Ch6, particularly in patients receiving DDAVP and/or platelets.

Conclusions
Activated clotting time-based clot ratio values correlate significantly with postoperative blood loss and detect recovery of PAF-accelerated coagulation after administration of DDAVP or platelet therapy. The HemoSTATUS assay may be useful in the identification of patients at risk for excessive blood loss and who could benefit from administration of DDAVP and/or platelet transfusion.
Noninvasive Estimate of Work of Breathing Due to the Endotracheal Tube
Authors: Heyer Laurent , Louis Bruno , Isabey Daniel , Lofaso Frederic , Brochard Laurent , Fredberg Jeffrey J. , Harf Alain 
Published: November 2003

Background
Although evidence suggests that secretions lining the inner wall of the endotracheal tube (ETT) often reduce its cross-sectional area, no data are available on the work of breathing as affected by the ETT. A noninvasive method is proposed for estimating the additional work of breathing necessitated by the ETT in patients whose lungs are mechanically ventilated. This method (the acoustic-Blasius method) involves (1) determining the inner geometry of the ETT using the acoustic reflection method and (2) using these geometric data to solve the Blasius equation that characterizes the ETT pressure drop-flow relation.

Methods
To evaluate the acoustic-Blasius method in vivo, the authors computed the work of breathing due to the ETT in four healthy persons breathing through an ETT connected to a pressure-support device and in five tracheally intubated patients receiving mechanical assistance in the pressure-support mode. For the tracheally intubated patients, the reference value was the work calculated from the ETT pressure drop measured between the two ends of the ETT using a pressure catheter.

Results
In the healthy participants and the tracheally intubated patients, there was close agreement between inspiratory work per cycle values estimated by directly measuring the ETT pressure drop and calculated using the acoustic-Blasius method: The difference was consistently less than 0.08 joules (< 10% of the reference value).

Conclusions
The data show that the acoustic-Blasius method allows noninvasive quantification of the ETT-related work of breathing in situ.
Gradual Reduction of Endotracheal Tube Diameter during Mechanical Ventilation via Different Humidification Devices
Authors: Villafane Maria Cristina , Cinnella Gilda , Lofaso Frederic , Isabey Daniel , Harf Alain , Lemaire Francois , Brochard Laurent 
Published: November 2003

Background
Limited data suggest that increased resistance to flow within endotracheal tubes (ETT) may occur in patients whose lungs are mechanically ventilated for more than 48 h, especially when airway humidification is inadequate. This could lead to sudden ETT obstruction or induce excessive loading during spontaneous breathing.

Methods
Twenty-three such patients were randomly assigned to three types of airway humidifier based on three different working principles: a Fisher Paykell hot water system (n = 7), a Pall BB2215 heat and moisture exchanger (HME) hydrophobic filter (n = 8), and a Dar Hygrobac 35254111 HME hygroscopic filter (n = 8). The decrease in internal pressure along the ETT and the flow rate were measured in each patient every 2 days. An "effective inner diameter" was derived from these measurements and allowed the inner ETT configuration to be monitored.

Results
On the first day of intubation, the mean diameter was similar in the three groups, and was slightly smaller than the in vitro diameter (mean +/- SD: 7.6 +/- 0.6 mm for Fisher-Paykell, 7.7 +/- 0.4 for Pall, and 7.5 +/- 0.4 for Dar). The mean diameter tended to decrease from day to day. At the end of the study, the overall reduction in mean diameter was significantly greater with the hydrophobic HME (Pall) than with the two other systems (Pall: -6.5 +/- 4% vs. 2.5 +/- 2.5% for Dar and 1.5 +/- 3% for Fisher-Paykell; P < 0.01 with analysis of variance). The same was true of the mean reduction in effective inner ETT diameter expressed per day of ventilation (-1.6 +/- 1.5% per day for Pall vs. -0.5 +/- 0.4% for Dar and -0.2 +/- 0.4% for Fisher-Paykell; P < 0.01). In four patients, the ETT became obstructed and emergency repeated tracheal intubation was required. The Pall HME and the Fisher-Paykell system were being used in three and one patient, respectively. Before obstruction, the reduction in ETT diameter was significantly greater for these four patients than for the remaining 23 patients (7.8 +/- 1.4% vs. 3.1 +/- 4.1%; P < 0.01).

Conclusions
During prolonged mechanical ventilation, significant alterations in inner ETT configuration occur frequently and are influenced by the type of humidification device used. In vivo monitoring of ETT mechanical properties might be clinically useful.
Nitric Oxide Involvement in Hypoxic Dilation of Pial Arteries in the Cat
Authors: Ishimura Naoko , Kitaguchi Katsuyasu , Tatsumi Kazuyuki , Furuya Hitoshi 
Published: November 2003

Background
The reactivity of cerebral arteries to different stimuli varies according to vessel size. Whether nitric oxide mediates hypoxic vasodilation is controversial. The authors considered this question by measuring the diameter of pial arteries and arterioles with or without exposure to the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME).

Methods
The cranial window technique, combined with microscopic video recording, was used in an experiment involving 20 cats anesthetized with fentanyl and midazolam. The diameters of pial arteries and arterioles were measured under the following conditions: (1) normoxia (PaO2 > 100 mmHg); (2) hypoxia (PaO2 < 45 mmHg); (3) normoxia with L-NAME infusion; and (4) hypoxia with L-NAME infusion. Changes in vessel diameter were analyzed with respect to artery size.

Results
Under hypoxic conditions, arteries and arterioles smaller than 200 microns were dilated significantly (P < 0.05). In arterioles smaller than 200 microns, L-NAME attenuated this hypoxic vasodilation (P < 0.05). In contrast, under normoxic conditions, L-NAME caused significant vasoconstriction in arteries larger than 100 microns but not in arteries smaller than 100 microns.

Conclusions
Arteries and arterioles smaller than 200 microns are dilated by hypoxia, and nitric oxide contributes to this process. Nitric oxide synthesis may also be related to the regulation of resting vascular tone in arteries larger than 100 microns.
Improving the Design of Muscle Relaxant Studies
Authors: Lee George C. , Iyengar Shuba , Szenohradszky Janos , Caldwell James E. , Wright Peter M. C. , Brown Ronald , Lau Marie , Luks Andrew , Fisher Dennis M. 
Published: November 2003

Background
The results from studies of muscle relaxants show wide variations among institutions. The authors hypothesized that some of this variability could be explained by differences in duration of nerve stimulation before drug administration (stabilization period).

Methods
Train-of-four stimulation was applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase 1, the stabilization period was > 30 min for both extremities. In phase 2-4, stabilization period was 20 min for one extremity and 2 min for the other. In addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period; in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until stable for more than 15 min. Time to 25% recovery (clinical duration) was calculated based on two indices: predrug and final (recovery) twitch tension. Values for onset and clinical duration were compared by paired parametric and nonparametric tests.

Results
In phase 1, predrug and recovery twitch tension were similar in each extremity, and onset and clinical duration did not differ between extremities, permitting paired comparisons in remaining studies. In phase 2, onset was more rapid with 20-min of prestimulation. With 20-min prestimulation, predrug and recovery twitch tension were similar; with 2-min prestimulation, recovery twitch tension exceeded predrug values. When referenced to predrug twitch tension, clinical duration was shorter with 2-min, that with 20-min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases 3, 4) abolished differences between extremities in onset and recovery.

Conclusions
With only train-of-four stimulation (no tetani), onset and clinical duration vary with duration of prestimulation, suggesting that a brief period of predrug stimulation is inadequate. However, lengthy prestimulation may be impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the need for prolonged stabilization during studies of muscle relaxants.
Bupivacaine Preferentially Blocks Ventral Root Axons in Rats
Authors: Dietz Friederike B. , Jaffe Richard A. 
Published: November 2003

Background
Clinically, bupivacaine can provide excellent sensory anesthesia with minimal impairment of motor function. However, the mechanisms by which local anesthetics produce differential sensory-motor nerve block is still unknown. The primary site of action for spinal and epidural anesthetics is thought to be the intradural segment of the spinal root. To determine the differential susceptibility of single motor and sensory nerve fibers to local anesthetic conduction block, bupivacaine effects on individual dorsal root (DR) and ventral root (VR) axons were studied.

Methods
Lumbar DRs and VRs were excised from anesthetized adult male rats. Single-fiber dissection and recording techniques were used to isolate activity in individual axons. Supramaximal constant-voltage stimuli at 0.3 Hz were delivered to the root. During in vitro perfusion, each root was exposed to increasing concentrations of bupivacaine, and the minimum blocking concentration (C(m)) and the concentration that increased conduction latency by 50% (latency EC50) were measured.

Results
Ventral root axons were significantly more sensitive to the steady-state conduction blocking effects of bupivacaine than were either myelinated or unmyelinated DR axons (DR-C(m), 32.4 microM; VR-C(m), 13.8 microM; P < 0.0001). In addition, VR axons were more susceptible to the latency-increasing effects of bupivacaine than were DR axons (DR-EC50 = 20.7 microM; VR-EC50 = 8.5 microM; P < 0.0001). Within axon groups, differential sensitivity as a function of conduction velocity (axon diameter), or length of nerve exposed to the anesthetic could not be demonstrated.

Conclusions
In contrast to clinical expectations, low concentrations of bupivacaine preferentially block motor (VR) axons in the rat.
Epidural Clonidine Used as the Sole Analgesic Agent during and after Abdominal Surgery
Authors: De Kock M. , Wiederkher P. , Laghmiche A. , Scholtes J. -L. 
Published: November 2003

Background
Many studies have shown the beneficial effect of epidural clonidine in postoperative pain management. In these studies, the patients received local anesthetics, opioids, or both in combination with clonidine. Due to the interactive potentiation of those drugs, the importance of the intrinsic analgesic properties of the alpha 2-adrenoceptor agonist is difficult to establish. The authors investigated the analgesic potency of epidural clonidine when used as the sole analgesic agent during and after major abdominal surgery.

Methods
Fifty young adult patients undergoing intestinal surgery under general anesthesia with propofol were studied. At induction, the patients received epidurally either an initial dose of 2 micrograms/kg clonidine followed by an infusion of 0.5 microgram.kg-1.h-1 (group 1, n = 10) or 4 micrograms/kg followed by 1 microgram.kg-1.h-1 (group 2, n = 20) or 8 micrograms.kg-1.h-1 followed by an infusion of 2 micrograms.kg-1.h-1 (group 3, n = 20). During the operation, increases in arterial blood pressure or heart rate that did not respond to a propofol bolus (0.5 mg/kg) were treated with a bolus of intravenous lidocaine (1 mg/kg). Three successive injections were allowed. When baseline values were not restored, opioids were added and the patient was removed from the study. After operation, the clonidine infusions were maintained for 12 h. During this period and at every 30 min, sedation scores and visual analog scale values at rest and at cough were noted. In case of subjective scores up to 5 cm at rest or up to 8 cm at cough, the patients were given access to a patient-controlled analgesia device that delivered epidural bupivacaine. The end point of the study was reached once the patient activated the analgesic delivery button.

Results
During surgery, 60% of patients in group 1 compared with 33% of patients in group 2 and only 5% of patients in group 3 were removed from the study protocol because of inadequate anesthesia (P < 0.05). After operation, epidural clonidine provided complete analgesia lasting 30 +/- 21 min in group 1 compared with 251 +/- 237 min in group 2 or 369 +/- 256 min in group 3 (P < 0.05 for group 1 vs. groups 2 and 3 and group 2 vs. group 3).

Conclusions
Epidural clonidine used as the sole analgesic agent provided dose-dependent control of the hemodynamic changes associated with surgical stimulation. It also produced dose-dependent postoperative analgesia without major side effects.