bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidural Anesthesia and Acutely Increased Intracranial Pressure
Authors: Grocott H. P. , Mutch W. A. C.
Published: November 2003

Background

The effects of epidural injection on intracranial pressure (ICP), lumbar epidural pressure, cerebral blood flow (CBF), and spinal cord blood flow (SCBF) were studied after acutely increased ICP in swine.

Methods

Twenty pigs, anesthetized with isoflurane and mechanically ventilated to maintain normocarbia, had two Tuohy needles placed in the lumbar epidural space. The ICP, lumbar epidural pressure, heart rate, mean arterial pressure, and central venous pressure were monitored. All animals had a Fogarty catheter placed in the parietal epidural space. Six pigs were randomized to a normal ICP group (group N) and eight pigs to an increased ICP group by inflation of the Fogarty catheter balloon (group R). Each pig had 0.33 ml.kg-1 of 2.0% carbonated lidocaine injected over 20 s via an epidural needle placed at L3. The ICP and lumbar epidural pressure were then monitored continuously for 30 min. Pressure-time data were fit to traditional compartmental models. Epidural elastance and resistance were calculated using a derivation of the Windkessel theory. An additional six pigs had ICP elevated as in group R and CBF and SCBF measured using radioactive microspheres at five time periods: baseline, 0-60 s, 100-160 s, 200-260 s, and at 30 min after epidural injection.

Results

The animals did not differ with respect to heart rate, central venous pressure, or mean arterial pressure at baseline. The ICP was 10 +/- 2 mmHg in group N, and 24 +/- 2 mmHg after balloon inflation in group R. After epidural injection, peak ICP was significantly greater in group R (76 +/- 22 vs. 54 +/- 17 mmHg) but not different by 30 min (17 +/- 5 vs. 11 +/- 1 mmHg). Epidural elastance in group N was 8.3 +/- 3.1 mmHg.ml-1 and 12.8 +/- 3.0 mmHg.ml-1 in group R (P = 0.045). Epidural resistance was 1,330 +/- 590 mmHg.s.ml-1 in group N and 2,220 +/- 600 mmHg.s.ml-1 in group R (P = 0.038). The CBF and SCBF were less than 10% of baseline during the 0- to 60-s time period after epidural injection. Thereafter, CBF and SCBF did not differ from baseline values.

Conclusions

In this porcine model, epidural injection increased ICP. With increased ICP at baseline, more pronounced increases in ICP followed epidural injection. With increased baseline ICP, both epidural elastance and resistance increased compared with controls. The CBF and SCBF were markedly reduced immediately after local anesthetic injection into the epidural space.
Lack of Inhibition by Inhalational Anesthetics of Myocardial Contraction Dependent on Intracellular Sodium Activity
Authors: Komai Hirochika , Chiou Kenneth Y. , Rusy Ben F.
Published: November 2003

Background

When cardiac muscle is stimulated at a high frequency after rest, the peak force increases rapidly at first and then slowly. The slow phase reflects Ca2+ accumulation dependent on an increase in intracellular Na+ activity. The positive inotropic effect of high concentrations of cardiac glycosides also involves Ca2+ accumulation dependent on an increase in intracellular Na+ activity. The effect of isoflurane on the component of myocardial contraction dependent on an increase in intracellular Na+ activity is not well understood.

Methods

The isometric force of rabbit papillary muscle contractions was measured. The authors studied the effects of isoflurane on the force increase that occurs when the muscles are stimulated after a rest and on the force increase induced by ouabain.

Results

Isoflurane (1.5%, 2.4%) had no statistically significant effect on the magnitude of the slow phase of force increase when the muscles were stimulated at 2 Hz after a rest. Isoflurane (1.5%) did not decrease the magnitude of force increase induced by ouabain (1 microM).

Conclusions

Isoflurane has little effect on myocardial contractions that depend on Ca2+ accumulation after an increase in intracellular Na+ activity. This may partly account for the smaller cardiac depressant effect of isoflurane observed at high frequencies rather than at low frequencies. The results of the present study and an earlier study with halothane suggest that the lack of inhibition of contractions dependent on Ca2+ accumulation after an increase in intracellular Na+ activity may be a common property of inhalational anesthetics.
Volatile Anesthetics Affect Calcium Mobilization in Bovine Endothelial Cells
Authors: Pajewski Thomas N. , Miao Ning , Lynch Carl III , Johns Roger A.
Published: November 2003

Background

The site where volatile anesthetics inhibit endothelium-dependent, nitric oxide-mediated vasodilation is unclear. To determine whether anesthetics could limit endothelium-dependent nitric oxide production by inhibiting receptor-mediated increases in cytosolic Ca2+, experiments were performed to see if the inhalational anesthetics halothane, isoflurane, and enflurane affect intracellular Ca2+ ([Ca2+]i) transients induced by the agonists bradykinin and adenosine triphosphate in cultured bovine aortic endothelial cells.

Methods

Bovine aortic endothelial cells, which had been loaded with the fluorescent Ca2+ indicator Fura-2, were added to medium preequilibrated with volatile anesthetic (1.25% and 2.5% for isoflurane, 1.755 and 3.5% for enflurane, and 0.75% and 1.5% for halothane). In Ca(2+)-containing medium, intracellular Ca2+ transients were elicited in response to bradykinin (10 nM and 1 microM) or adenosine triphosphate (1 microM and 100 microM).

Results

Both bradykinin and adenosine triphosphate triggered a rapid rise to peak [Ca2+]i followed by a gradual decline to a plateau above the resting level. Although basal [Ca2+]i was unaltered by the anesthetics, both halothane and enflurane, in a dose-dependent manner, depressed the peak and plateau of the [Ca2+]i transient elicited by 10 nM bradykinin, whereas isoflurane had no effect. When [Ca2+]i transients were elicited by 1 microM bradykinin, halothane (1% and 5%) did not alter peak and plateau levels. Halothane and enflurane also decreased [Ca2+]i transients evoked by 1 microM and 100 microM adenosine triphosphate, whereas isoflurane also had no effect in this setting.

Conclusions

Halothane and enflurane, but not isoflurane, inhibit bradykinin- and adenosine triphosphate-stimulated Ca2+ transients in endothelial cells. Limitations of Ca2+ availability to activate constitutive endothelial nitric oxide synthase could allow for part, but not all, of the inhibition of endothelium-dependent nitric oxide-mediated vasodilation by inhalational anesthetics.
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.
Effect of Sympathetic Nerve Block on Acute Inflammatory Pain and Hyperalgesia
Authors: Pedersen Juri L. , Rung George W. , Kehlet Henrik
Published: November 2003

Background

Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers.

Methods

The study was made as a randomized, single blinded investigation, in which the volunteers served as their own controls. A lumbar sympathetic nerve block and a contralateral placebo block were performed in 24 persons by injecting 10 ml bupivacaine (0.5%) and 10 ml saline, respectively. The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds to thermal and mechanical stimulation, and secondary hyperalgesia were assessed before block, after block, and 1, 2, 4, and 6 h after the heat injuries.

Results

Of the 24 volunteers, eight were excluded because of somatic block or incomplete sympathetic block. The study revealed no significant differences between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective.

Conclusion

Sympathetic nerve block did not change acute inflammatory pain or hyperalgesia after a heat injury in human skin.
Spinal Cord Motoneuron Excitability during Isoflurane and Nitrous Oxide Anesthesia
Authors: Zhou Henry H. , Mehta Mahesh , Leis Arturo A.
Published: November 2003

Background

Recent evidence suggests that the spinal cord is an important site of anesthesia that is necessary for surgical immobility, but the specific effect of anesthetics within the spinal cord is unclear. This study assessed the effect of isoflurane and nitrous oxide on spinal motoneuron excitability by monitoring the H-reflex and the F wave.

Methods

Eight adult patients, categorized as American Society of Anesthesiologists physical status 1 or 2, who were undergoing elective orthopaedic surgery were anesthetized with 0.6, 0.8, 1.0, and 1.2 times the estimated minimum alveolar concentration (MAC) of isoflurane. Nitrous oxide was added in graded concentrations of 30%, 50%, and 70%, whereas the isoflurane concentration was decreased to maintain a total MAC of 1. The H-reflex of the soleus muscle and the F wave of the abductor hallucis muscle were measured before anesthesia and 15 min after each change of anesthetic concentration. Four or more trials of the H-reflex and 18 trials of the F wave were recorded at each concentration of anesthesia. The effect of the anesthetics on the H-reflex and F wave was analyzed using. Dunnett's test.

Results

H-reflex amplitude was decreased to 48.4 +/- 18.6% of preanesthesia level at 0.6 MAC isoflurane and to 33.8 +/- 19.1% when isoflurane concentration increased from 0.6 MAC to 1.2 MAC. F wave amplitude and persistence decreased to 52.2 +/- 33.6% and 44.4 +/- 26% of baseline at 0.6 MAC isoflurane, and to 33.8 +/- 26% and 21.7 +/- 22.8% at 1.2 MAC isoflurane. Isoflurane plus nitrous oxide (total 1 MAC) decreased H-reflex amplitude to 30.4-33.3% and decreased F wave persistence to 42.8-56.3% of baseline.

Conclusions

Both isoflurane alone and isoflurane plus nitrous oxide decrease H-reflex and F-wave amplitude and F-wave persistence. These effects suggest that isoflurane and nitrous oxide decrease motoneuronal excitability in the human spinal cord. This may play an important role in producing surgical immobility.
Esmolol Reduces Anesthetic Requirement for Skin Incision during Propofol/Nitrous Oxide/Morphine Anesthesia
Authors: Johansen Jay W. , Flaishon Ronald , Sebel Peter S.
Published: November 2003

Background

Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta 1-receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision.

Methods

Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micrograms.kg-1.min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micrograms.kg-1.min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression.

Results

The propofol Cp50 with nitrous oxide was 3.85 micrograms/ ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micrograms/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive blas. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found.

Conclusions

Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic-sparing effect of a beta-adrenergic antagonist in humans under clinically relevant conditions.
Microvascular Oxygen Delivery and Interstitial Oxygenation during Sodium Pentobarbital Anesthesia
Authors: Kerger Heinz , Saltzman Darin J. , Gonzales Armando , Tsai Amy G. , Ackern Klaus van , Winslow Robert M. , Intaglietta Marcos
Published: November 2003

Background

Anesthesia may represent a considerable bias in experimental medicine, particularly in conditions of stress (such as hemorrhage). Sodium pentobarbital (PB), widely used for cardiovascular investigations, may impair oxygen delivery by hemodynamic and respiratory depression. The critical issue, however, is whether the microcirculation can still maintain tissue oxygenation during anesthesia. To answer this question, the authors studied the effect of PB anesthesia on subcutaneous microvascular oxygen delivery and interstitial oxygenation in Syrian golden hamsters.

Methods

Sodium pentobarbital anesthesia was induced by intravenous injection (30 mg/kg body weight) and maintained by a 15-min infusion (2 mg.kg-1.min-1), with animals breathing spontaneously (PB-S) or ventilated with air (PB-V). Systemic parameters evaluated were mean arterial pressure (MAP), heart rate, cardiac index (CI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), base excess, and pH. Microvascular and interstitial oxygen tension (PO2), vessel diameter, red blood cell velocity (vRBC), and blood flow (Qb) were measured in a dorsal skinfold preparation. Microcirculatory PO2 values were determined by phosphorescence decay.

Results

Sodium pentobarbital anesthesia significantly decreased CI, MAP, vRBC, and Qb. During PB infusion, PaO2 values were 56 +/- 12.8 mmHg (PB-S) and 115.9 +/- 14.6 mmHg (PB-V) compared with 69.4 +/- 18.2 mmHg and 61.4 +/- 12.6 mmHg at baseline. However, microvascular PO2 was reduced by 25-55% in both groups, resulting in an interstitial PO2 decrease from 23.9 +/- 5.6 mmHg (control) to 13.1 +/- 9.1 mmHg (PB-S) and 15.2 +/- 7 mmHg (PB-V). Microcirculatory PO2 values were restored 30 min after PB infusion, even though hemodynamic depression and a light anesthetic plane were maintained.

Conclusions

Sodium pentobarbital anesthesia caused impairment of microvascular oxygen delivery and interstitial oxygenation, effects that were not prevented by mechanical ventilation. Although these effects were restricted to deep anesthetic planes, prolonged hemodynamic depression suggests that caution is warranted when using PB as an anesthetic in cardiovascular investigations.
Stereospecific Effect of Bupivacaine Isomers on Atrioventricular Conduction in the Isolated Perfused Guinea Pig Heart
Authors: Graf Bernhard M. , Martin Eike , Bosnajak Zeliko J. , Stowed David F.
Published: November 2003

Background

The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms of bupivacaine may have differential effects on cardiovascular function, specifically on cardiac electrophysiology. The authors' aim was to determine if there were any direct functional differences in the cardiac effects of bupivacaine isomers. The isolated heart was used to avoid possible indirect cardiac effects of bupivacaine, such as autonomic nervous and hormonal influences, as well as preload and afterload factors.

Methods

The hearts of 12 ketamine-anesthetized guinea pigs were perfused with Krebs-Ringer's solution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electrodes were placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and inflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO2), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concentrations (0.5, 1, 5, 10 microM) of both isomers and the racemate of bupivacaine.

Results

Racemic and isomeric bupivacaine equally and dose dependently decreased cardiac function. At 10 microM bupivacaine these changes were HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 4%; and MVO2, -46 +/- 4%. The (+) isomer significantly prolonged AV conduction compared with the racemate and the (-) isomer at all concentrations. At 10 microM, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. The greater delay in AV time with the (+) than the racemate or (-) isomer led to a second-degree AV dissociation in 10 of 12 of hearts treated with (+) bupivacaine.

Conclusions

This study shows that bupivacaine has an enatiomer-specific effect to delay AV conduction and to produce second-degree AV dissociation in the isolated perfused heart. This suggests that bupivacaine isomers probably have differential effects on one or more ion-specific channels regulating AV conduction. Other measured direct cardiac effects of bupivacaine appear to be independent of the isomeric form.
Halothane Prevents Postischemic Production of Hydroxyl Radicals in the Canine Heart
Authors: Glantz Lucio , Ginosar Yehuda , Chevion Mordechai , Gozal Yaacov , Elami Amir , Navot Nahum , Kitrossky Nahum , Drenger Benjamin
Published: November 2003

Background

Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored.

Methods

Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored.

Results

An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion.

Conclusions

Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.
In Vivo Imaging of Nitrous Oxide-induced Changes in Cerebral Activation during Noxious Heat Stimuli
Authors: Gyulai Ferenc E. , Firestone Leonard L. , Mintun Mark A. , Winter Peter M.
Published: November 2003

Background

Although previous studies have provided some insight into the pharmacologic aspects of nitrous oxide analgesia, the neural circuits mediating its antinociceptive effect remain relatively unexplored. Position emission tomography was used in nine volunteers to identify the loci of nitrous oxide-modulated cerebral responses to a peripheral noxious stimulus.

Methods

Nitrous oxide-pain interactions were studied by comparing regional cerebral blood flow responses to a 48 degrees C tonic heat stimulus, applied to each volunteer's left forearm, during room air inhalation with those obtained while 20% nitrous oxide was administered. Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. Locations of specific regional activation related to pain, and nitrous oxide, were identified using the statistical parametric mapping method, with a significance level of P < 0.01. Pain was rated by visual analog scale and the values were compared using Wilcoxon rank sum analysis.

Results

Pain produced cerebral activation in the contralateral thalamus, anterior cingulate, and supplementary motor area. Adding nitrous oxide during pain stimulation abolished activation in these areas but was associated with activation in the contralateral infralimbic and orbitofrontal cortices. In parallel, mean visual analog scale scores decreased significantly from 67 +/- 4 (SEM) to 54 +/- 5 (P < 0.05).

Conclusions

Nitrous oxide, at 20% concentration, appears to modulate pain processing in the brain's medial pain system, and also activates the infralimbic and orbitofrontal cortices. The potential contribution of the affected brain areas to nitrous oxide analgesia is discussed.
Positron Emission Tomography Study of Regional Cerebral Metabolism in Humans during Isoflurane Anesthesia
Authors: Alkire Michael T. MD , Haier Richard J. PhD , Shah Nitin K. MD , Anderson Cynthia T. MD
Published: November 2003

Background

Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on human cerebral glucose metabolism using positron emission tomography (PET).

Methods

Five volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/- SD; expired = 0.5 +/- 0.1%). Scans were obtained with a GE2048 scanner (4.5-mm resolution-FWHM) using the 18fluorodeoxyglucose technique.

Results

Awake whole-brain glucose metabolism averaged 6.9 +/- 1.5 mg.100 g-1.min-1 (means +/- SD). Isoflurane reduced whole-brain metabolism 46 +/- 11% to 3.6 +/- 0.3 mg.100 g-1.min-1 (P < or = 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region-of-interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake.

Conclusion

These data clarify that the anesthetic state evident in the living human brain during unresponsiveness induced with isoflurane is associated with a global, fairly uniform, whole-brain glucose metabolic reduction of 46 +/- 11%.
Baricity, Needle Direction, and Intrathecal Sufentanil Labor Analgesia
Authors: Ferouz Fazeela , Norris Mark C. , Arkoosh Valerie A. , Leighton Barbara L. , Boxer Louis M. , Corba Robert J.
Published: November 2003

Background

Intrathecal sufentanil relieves labor pain but centrally mediated side effects are common. Preventing rostral spread of intrathecal sufentanil should limit these side effects. Both direction of the lateral opening of a pencil-point needle and drug baricity modify the spread of intrathecal local anesthetics. This randomized, prospective, double-blind study examines the effects of these variables on intrathecal sufentanil labor analgesia.

Methods

Forty laboring, full-term parturients, whose cervixes were dilated less than 5 cm and who requested analgesia for labor were enrolled. Combined spinal epidural analgesia was induced in patients in the sitting position. They were allocated to receive 10 micrograms intrathecal sufentanil diluted with either normal saline or dextrose with the aperture of the pencil-point needle directed cephalad or caudad during drug injection. Thus there were four groups of ten patients: dextrose up, dextrose down, saline up, and saline down. Sufentanil was diluted with normal saline to a concentration of 10 micrograms/ml. The study drug was made by mixing 1 ml sufentanil solution with either 1 ml 10% dextrose or 1 ml normal saline. Visual analog scores for pain, pruritus, nausea, and pain relief were recorded before and 5, 10, 15, and 30 min after drug injection.

Results

Baricity, but not needle orientation, influenced pain relief and pruritus. Sufentanil in dextrose produced less itching but also less analgesia. Nine of 20 women in the dextrose groups compared with 1 of 20 in the saline groups requested additional analgesia by 30 min.

Conclusions

Little or no labor analgesia developed for patients receiving sufentanil with dextrose. A supraspinal action may contribute to intrathecal sufentanil's analgesic efficacy.