bluuebunny/crossref_metadata_2025 huggingface dataset:
A Direct Search Procedure to Optimize Combinations of Epidural Bupivacaine, Fentanyl, and Clonidine for Postoperative Analgesia
Authors: Curatolo Michele , Schnider Thomas W. , Petersen-Felix Steen , Weiss Susanne , Signer Christoph , Scaramozzino Pasquale , Zbinden Alex M.
Published: November 2003

Background

The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia.

Methods

One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained.

Results

Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (microg/h), clonidine dose (microg/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively.

Conclusions

Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.
Pharmacokinetics of Dopamine in Healthy Male Subjects
Authors: MacGregor Drew A. , Smith Timothy E. , Prielipp Richard C. , Butterworth John F. , James Robert L. , Scuderi Phillip E.
Published: November 2003

Background

Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model.

Methods

Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine.

Results

Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion.

Conclusions

Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.
Efficacy of Neurolytic Celiac Plexus Block in Varying Locations of Pancreatic Cancer
Authors: Rykowski Jan J. , Hilgier Maciej
Published: November 2003

Background

Neurolytic celiac plexus block (NCPB) is an effective way of treating severe pain in some patients with pancreatic malignancy. However, there are no studies to date that evaluate the effectiveness of NCPB related to the site of primary pancreas cancer. The aim of the study was to assess the effectiveness of NCPB in pancreatic cancer pain, depending on the location of the pancreatic tumor.

Methods

The prospective study was conducted in 50 consecutive patients diagnosed with pancreatic cancer. The patients were categorized into two different groups depending on tumor localization: group 1: patients with the cancer of the head of the pancreas and group 2: patients with the cancer of the body and tail of the pancreas. The qualitative and quantitative pain analyses were performed before and after NCPB. The patients underwent prognostic celiac plexus block with bupivacaine, followed by neurolysis during fluoroscopic control within the next 24 h.

Results

After NCPB, 37 patients (74%) had effective pain relief during the first 3 months or until death. Of the 37 patients who had effective pain relief, 33 (92%) were from group 1 and 4 (29%) were from group 2. In the remaining 13 patients (3 patients from group 1 and 10 patients from group 2), pain relief after NCPB was not satisfactory. Those patients were scheduled for repeated retrocrural neurolysis during computed tomography control. Computed tomography showed massive growth of the tumor around the celiac axis with metastases. After repeated neurolysis, pain relief clinically still was not satisfactory, necessitating additional opioid treatment.

Conclusion

In this study, unilateral transcrural celiac plexus neurolysis has been shown to provide effective pain relief in 74% of patients with pancreatic cancer pain. Neurolysis was more effective in cases with tumor involving the head of the pancreas. In the cases with advanced tumor proliferation, regardless of the technique used, the analgesic effects of NCPB were not satisfactory.
Female Gender Associates with Increased Duration of Intubation and Length of Stay after Coronary Artery Surgery
Authors: Butterworth John , James Robert , Prielipp Richard , Cerese Julie , Livingston Jean , Burnett David
Published: November 2003

Background

Females have worse outcome than do males after coronary artery bypass grafting; however, gender effects on length of stay (LOS) outcomes, such as duration of intubation or intensive care unit (ICU) LOS, have not been evaluated previously. The authors hypothesized that adjustment for pertinent preoperative covariates would eliminate any significant effect of gender on duration of intubation, LOS in the ICU after extubation, total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS.

Methods

Patients undergoing elective or urgent primary coronary artery bypass grafting surgery at 51 academic health centers in 1995 and 1997 were studied. Unique multivariable statistical models were developed for duration of intubation, ICU LOS after extubation, total ICU LOS, and postoperative (exclusive of ICU and total) LOS to test for independent associations with gender. Preoperative but not intraoperative or postoperative variables were included in the model. P> or =0.01 was considered significant.

Results

All LOSs were of significantly longer duration in females than in males in both the 1995 (n = 1,064) and 1997 (n = 910) data collections. After covariate adjustment, female sex remained associated with significantly longer duration ICU LOS and total postoperative LOS in both the 1995 (female:male ratios 1.30:1 and 1.13:1, respectively) and the 1997 (female:male ratios 1.19:1 and 1.12:1, respectively) data sets. After covariate adjustment, duration of intubation and ICU LOS after extubation were of significantly longer duration in women than men in 1995 (female:male ratios 1.22:1 and 1.39:1, respectively), but the differences were not significant in 1997.

Conclusions

Even in the context of accelerated recovery programs, these analyses show that female sex has powerful associations with increased LOS intervals for coronary artery bypass grafting surgery, even after adjustment for preoperative covariates. These effects could result from differences in the ways in which men and women respond to coronary artery disease, anesthesia, and coronary artery bypass grafting surgery, or to bias on the part of healthcare workers.
Efficacy of Two Methods for Reducing Postbypass Afterdrop
Authors: Rajek Angela , Lenhardt Rainer , Sessler Daniel I. , Brunner Gabriele , Haisjackl Markus , Kastner Johannes , Laufer Günther
Published: November 2003

Background

Afterdrop, defined as the precipitous reduction in core temperature after cardiopulmonary bypass, results from redistribution of body heat to inadequately warmed peripheral tissues. The authors tested two methods of ameliorating afterdrop: (1) forced-air warming of peripheral tissues and (2) nitroprusside-induced vasodilation.

Methods

Patients were cooled during cardiopulmonary bypass to approximately 32 degrees C and subsequently rewarmed to a nasopharyngeal temperature near 37 degrees C and a rectal temperature near 36 degrees C. Patients in the forced-air protocol (n = 20) were assigned randomly to forced-air warming or passive insulation on the legs. Active heating started with rewarming while undergoing bypass and was continued for the remainder of surgery. Patients in the nitroprusside protocol (n = 30) were assigned randomly to either a control group or sodium nitroprusside administration. Pump flow during rewarming was maintained at 2.5 l x m(-2) x min(-1) in the control patients and at 3.0 l x m(-2) x min(-1) in those assigned to sodium nitroprusside. Sodium nitroprusside was titrated to maintain a mean arterial pressure near 60 mm Hg. In all cases, a nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 18 intramuscular needle thermocouples, nine skin temperatures, and "deep" hand and foot temperature.

Results

In patients warmed with forced air, peripheral tissue temperature was higher at the end of warming and remained higher until the end of surgery. The core temperature afterdrop was reduced from 1.2+/-0.2 degrees C to 0.5+/-0.2 degrees C by forced-air warming. The duration of afterdrop also was reduced, from 50+/-11 to 27+/-14 min. In the nitroprusside group, a rectal temperature of 36 degrees C was reached after 30+/-7 min of rewarming. This was only slightly faster than the 40+/-13 min necessary in the control group. The afterdrop was 0.8+/-0.3 degrees C with nitroprusside and lasted 34+/-10 min which was similar to the 1.1+/-0.3 degrees C afterdrop that lasted 44+/-13 min in the control group.

Conclusions

Cutaneous warming reduced the core temperature afterdrop by 60%. However, heat-balance data indicate that this reduction resulted primarily because forced-air heating prevented the typical decrease in body heat content after discontinuation of bypass, rather than by reducing redistribution. Nitroprusside administration slightly increased peripheral tissue temperature and heat content at the end of rewarming. However, the core-to-peripheral temperature gradient was low in both groups. Consequently, there was little redistribution in either case.
Relative Importance of Flow versus Pressure in Splanchnic Perfusion during Cardiopulmonary Bypass in Rabbits
Authors: Bastien Olivier , Piriou Vincent , Aouifi Abdellah , Flamens Claire , Evans Rhys , Lehot Jean Jacques
Published: November 2003

Background

Decreased gastrointestinal perfusion has been reported during cardiopulmonary bypass (CPB). Conflicting results have been published concerning thresholds of pressure and flow to avoid splanchnic ischemia during CPB. This study compared splanchnic perfusion during independent and randomized variations of CPB pump flow or arterial pressure.

Methods

Ten rabbits were studied during mild hypothermic (36 degrees C) nonpulsatile CPB using neonatal oxygenators. Simultaneous measurements of tissue blood flow in four different splanchnic areas (gastric, jejunum, ileum, and liver) were performed by laser Doppler flowmetry (LDF) before CPB (T0) and during a 4-step factorial experimental block design. Pressure and flow were alternatively high or low in random order.

Results

Laser Doppler flowmetry was significantly lower than pre-CPB value but was better preserved (analysis of covariance) in all organs, except liver, when CPB flow was high, whatever the pressure. Splanchnic LDF values in the low- versus high-flow groups expressed as perfusion unit were (mean +/- SD): stomach, 94+/-66 versus 137+/-75; jejunum, 118+/-78 versus 172+/-75; ileum, 95+/-72 versus 146+/-83; and liver, 79+/-72 versus 108+/-118. No significant difference of LDF was observed between the high- and low-pressure groups, whatever the flow, except for liver: stomach, 115+/-64 versus 117+/-83; jejunum, 141+/-80 versus 148+/-83; ileum, 127+/-87 versus 114+/-76; liver, 114+/-88 versus 73+/-70.

Conclusion

Prevention of splanchnic ischemia during CPB should focus on preservation of high CPB blood flow rather than on high pressure.
Actions of Midazolam on GABAergic Transmission in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices
Authors: Kohno Tatsuro , Kumamoto Eiichi , Baba Hiroshi , Ataka Toyofumi , Okamoto Manabu , Shimoji Koki , Yoshimura Megumu
Published: November 2003

Background

Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord.

Methods

The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique.

Results

Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam.

Conclusions

Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.
Differential Effects of Anesthetic and Nonanesthetic Cyclobutanes on Neuronal Voltage-gated Sodium Channels
Authors: Ratnakumari Lingamaneni , Vysotskaya Tatyana N. , Duch Daniel S. , Hemmings Hugh C.
Published: November 2003

Background

Despite their key role in the generation and propagation of action potentials in excitable cells, voltage-gated sodium (Na+) channels have been considered to be insensitive to general anesthetics. The authors tested the sensitivity of neuronal Na+ channels to structurally similar anesthetic (1-chloro-1,2,2-trifluorocyclobutane; F3) and nonanesthetic (1,2-dichlorohexafluorocyclobutane; F6) polyhalogenated cyclobutanes by neurochemical and electrophysiologic methods.

Methods

Synaptosomes (pinched-off nerve terminals) from adult rat cerebral cortex were used to determine the effects of F3 and F6 on 4-aminopyridine- or veratridine-evoked (Na+ channel-dependent) glutamate release (using an enzyme-coupled spectrofluorimetric assay) and increases in intracellular Ca2+ ([Ca2+]i) (using ion-specific spectrofluorimetry). Effects of F3 and F6 on Na+ currents were evaluated directly in rat lumbar dorsal root ganglion neurons by whole-cell patch-clamp recording.

Results

F3 inhibited glutamate release evoked by 4-aminopyridine (inhibitory concentration of 50% [IC50] = 0.77 mM [approximately 0.8 minimum alveolar concentration (MAC)] or veratridine (IC50 = 0.42 mM [approximately 0.4 MAC]), and veratridine-evoked increases in [Ca2+]i (IC50 = 0.5 mM [approximately 0.5 MAC]) in synaptosomes; F6 had no significant effects up to 0.05 mM (approximately twice the predicted MAC). F3 caused reversible membrane potential-independent inhibition of peak Na+ currents (70+/-9% block at 0.6 mM [approximately 0.6 MAC]), and a hyperpolarizing shift in the voltage-dependence of steady state inactivation in dorsal root ganglion neurons (-21+/-9.3 mV at 0.6 mM). F6 inhibited peak Na+ currents to a lesser extent (16+/-2% block at 0.018 mM [predicted MAC]) and had minimal effects on steady state inactivation.

Conclusions

The anesthetic cyclobutane F3 significantly inhibited Na+ channel-mediated glutamate release and increases in [Ca2+]i. In contrast, the nonanesthetic cyclobutane F6 had no significant effects at predicted anesthetic concentrations. F3 inhibited dorsal root ganglion neuron Na+ channels with a potency and by mechanisms similar to those of conventional volatile anesthetics; F6 was less effective and did not produce voltage-dependent block. This concordance between anesthetic activity and Na+ channel inhibition supports a role for presynaptic Na+ channels as targets for general anesthetic effects and suggests that shifting the voltage-dependence of Na+ channel inactivation is an important property of volatile anesthetic compounds.
Isoflurane Action in the Spinal Cord Blunts Electroencephalographic and Thalamic–Reticular Formation Responses to Noxious Stimulation in Goats
Authors: Antognini Joseph F. , Wang Xiao Wei , Carstens E.
Published: November 2003

Background

Isoflurane depresses the electroencephalographic (EEG) activity and exerts part of its anesthetic effect in the spinal cord. The authors hypothesized that isoflurane would indirectly depress the EEG and subcortical response to noxious stimulation in part by a spinal cord action.

Methods

Depth electrodes were inserted into the midbrain reticular formation (MRF) and thalamus of six of seven isoflurane-anesthetized goats, and needle-electrodes were placed into the skull periosteum. In five of seven goats, an MRF microelectrode recorded single-unit activity. The jugular veins and carotid arteries were isolated to permit cranial bypass and differential isoflurane delivery. A noxious mechanical stimulus (1 min) was applied to a forelimb dewclaw at each of two cranial-torso isoflurane combinations: 1.1+/-0.3%-1.2+/-0.3% and 1.1+/-0.3-0.3+/-0.1% (mean +/- SD).

Results

When cranial-torso isoflurane was 1.1-1.2%, the noxious stimulus did not alter the EEG. When torso isoflurane was decreased to 0.3%, the noxious stimulus activated the MRF, thalamic, and bifrontal-hemispheric regions (decreased high-amplitude, low-frequency power). For all channels combined, total (-33+/-15%), delta(-51+/-22%), theta (-33+/-19%), and alpha (-26+/-16%) power decreased after the noxious stimulus (P<0.05); beta power was unchanged. The MRF unit responses to the noxious stimulus were significantly higher when the spinal cord isoflurane concentration was 0.3% (1,286+/-1,317 impulses/min) as compared with 1.2% (489+/-437 impulses/min, P<0.05).

Conclusions

Isoflurane blunted the EEG and MRF-thalamic response to noxious stimulation in part via an action in the spinal cord.
Role of K+Channels in Augmented Relaxations to Sodium Nitroprusside Induced by Mexiletine in Rat Aortas
Authors: Kinoshita Hiroyuki , Ishikawa Toshizo , Hatano Yoshio
Published: November 2003

Background

A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation.

Methods

Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin).

Results

Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M).

Conclusions

These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.
Amniotic Fluid Removal during Cell Salvage in the Cesarean Section Patient
Authors: Waters Jonathan H , Biscotti Charles , Potter Paul S , Phillipson Eliot
Published: November 2003

Background

Cell salvage has been used in obstetrics to a limited degree because of a fear of amniotic fluid embolism. In this study, cell salvage was combined with blood filtration using a leukocyte depletion filter. A comparison of this washed, filtered product was then made with maternal central venous blood.

Methods

The squamous cell concentration, lamellar body count, quantitative bacterial colonization, potassium level, and fetal hemoglobin concentration were measured in four sequential blood samples collected from 15 women undergoing elective cesarean section. The blood samples collected included (1) unwashed blood from the surgical field (prewash), (2) washed blood (postwash), (3) washed and filtered blood (postfiltration), and (4) maternal central venous blood drawn from a femoral catheter at the time of placental separation.

Results

Significant reductions in the following parameters were seen when the postfiltration samples were compared to the prewash samples (median [25th-75th percentile]): squamous cell concentration (0.0 [0.0-0.1 counts/high-powered field (HPF)] vs. 8.3 counts/HPF [4. 0-10.5 counts/HPF], P < 0.05); bacterial contamination (0.1 [0.0-0. 2] vs. 3.0 [0.6-7.7] colony-forming units (CFU)/ml, P < 0.01); and lamellar body concentration (0.0 [0.0-1.0] vs. 22.0 [18.5-29.5] thousands/microl, P < 0.01). No significant differences existed between the postfiltration and maternal samples for each of these parameters. Fetal hemoglobin was in higher concentrations in the postfiltration sample when compared with maternal blood (1.9 [1.1-2. 5] vs. 0.5% [0.3-0.7] ). Potassium levels were significantly less in the postfiltration sample when compared with maternal (1.4 [1.0-1.5] vs. 3.8 mEq/l [3.7-4.0]).

Conclusions

Leukocyte depletion filtering of cell-salvaged blood obtained from cesarean section significantly reduces particulate contaminants to a concentration equivalent to maternal venous blood.
Topography of Clonidine-induced Electroencephalographic Changes Evaluated by Principal Component Analysis
Authors: Bischoff Petra , Scharein Eckehard , Schmidt Gunter N. , von Knobelsdorff Georg , Bromm Burkhart , Esch Jochen Schulte am
Published: November 2003

Background

Principal component analysis is a multivariate statistical technique to facilitate the evaluation of complex data dimensions. In this study, principle component analysis was used to reduce the large number of variables from multichannel electroencephalographic recordings to a few components describing changes of spatial brain electric activity after intravenous clonidine.

Methods

Seven healthy volunteers (age, 26 +/- 3 [SD] yr) were included in a double-blind crossover study with intravenous clonidine (1.5 and 3.0 microg/kg). A spontaneous electroencephalogram was recorded by 26 leads and quantified by standard fast Fourier transformation in the delta, theta, alpha, and beta bands. Principle component analysis derived from a correlation matrix calculated between all electroencephalographic leads (26 x 26 leads) separately within each classic frequency band. The basic application level of principle component analysis resulted in components representing clusters of electrodes positions that were differently affected by clonidine. Subjective criteria of drowsiness and anxiety were rated by visual analog scales.

Results

Topography of clonidine-induced electroencephalographic changes could be attributed to two independent spatial components in each classic frequency band, explaining at least 85% of total variance. The most prominent effects of clonidine were increases in the delta band over centroparietooiccipital areas and decreases in the alpha band over parietooccipital regions. Clonidine administration resulted in subjective drowsiness.

Conclusions

Data from the current study supported the fact that spatial principle component analysis is a useful multivariate statistical procedure to evaluate significant signal changes from multichannel electroencephalographic recordings and to describe the topography of the effects. The clonidine-related changes seen here were most probably results of its sedative effects.
Reliability of the Heparin Management Test for Monitoring High Levels of Unfractionated Heparin
Authors: Mertzlufft Fritz , Koster Andreas , Hansen Roland , Risch Anne , Kuppe Herrmann , Kübel Bernhard , Crystal George J.
Published: November 2003

Background

The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass.

Methods

In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass </= 90 min, n = 40), anticoagulation was performed according to the activated clotting time (with or without aprotinin); in group II (cardiopulmonary bypass >/= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma).

Results

In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%).

Conclusions

The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.
Preemptive Analgesia by Intravenous Low-dose Ketamine and Epidural Morphine in Gastrectomy
Authors: Aida Sumihisa , Yamakura Tomohiro , Baba Hiroshi , Taga Kiichiro , Fukuda Satoru , Shimoji Koki
Published: November 2003

Background

Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial.

Methods

Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.

Results

Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups.

Conclusion

The results suggest that for definitive preemptive analgesia, blockade of opioid and N-methyl-d-aspartate receptors is necessary for upper abdominal surgery such as gastrectomy; singly, either treatment provided significant, but not definitive, postsurgical pain relief. Epidural morphine may affect the spinal cord segmentally, whereas intravenous ketamine may block brain stem sensitization via the vagus nerve during upper abdominal surgery.
Area under the Plasma Concentration–Time Curve of Inorganic Fluoride following Sevoflurane Anesthesia Correlates with CYP2E1 mRNA Level in Mononuclear Cells
Authors: Hase Ichiro , Imaoka Susumu , Oda Yutaka , Hiroi Toyoko , Nakamoto Tatsuo , Asada Akira , Funae Yoshihiko
Published: November 2003

Background

Because the amount of inorganic fluoride released after anesthesia with sevoflurane depends on the dose of administered sevoflurane and cytochrome P450 (CYP) 2E1 activity in the liver, a reliable and noninvasive probe for CYP2E1 would be useful for predicting plasma inorganic fluoride levels after anesthesia. In this study, the authors evaluated the relation between plasma concentration of inorganic fluoride after sevoflurane anesthesia and CYP2E1 mRNA level in mononuclear cells.

Methods

Twenty patients (American Society of Anesthesiologists physical status I), aged 20-68 yr undergoing body surface surgery with general anesthesia with sevoflurane were enrolled. One milliliter of blood was obtained before administration of sevoflurane and mononuclear cells were obtained. Levels of CYP2E1 mRNA in mononuclear cells were measured by competitive reverse transcription polymerase chain reaction with a specific primer and competitor for CYP2E1 mRNA.

Results

There was a significant correlation between level of CYP2E1 mRNA in mononuclear cells and the area under the plasma concentration-time curve of plasma inorganic fluoride from the beginning of sevoflurane administration to infinity in uninduced and uninhibited patients (r2 = 0.56; P < 0.01).

Conclusions

Area under the plasma concentration-time curve of inorganic fluoride after sevoflurane anesthesia correlates with CYP2E1 mRNA in mononuclear cells in peripheral blood.
The Mechanical Antihyperalgesic Effect of Intrathecally Administered MPV-2426, a Novel α2-Adrenoceptor Agonist, in a Rat Model of Postoperative Pain
Authors: Onttonen Tiina , Pertovaara Antti
Published: November 2003

Background

MPV-2426 is a novel alpha2-adrenoceptor agonist developed for spinal pain therapy. It has proved to be effective in physiologic and neuropathic conditions. In the current study its effectiveness on mechanical hyperalgesia was assessed in a rat model of postoperative pain.

Methods

Rats with intrathecal catheters were anesthetized with pentobarbital, and a 1-cm incision was made in the plantar aspect of the foot and closed. During postoperative days 1 and 2 the antihyperalgesic effects induced by intrathecal MPV-2426, clonidine, and dexmedetomidine were determined by assessing the hind limb withdrawal threshold to calibrated von Frey hairs applied to the skin of the hind paw adjacent to the wound.

Results

MPV-2426 administered into the lumbar spinal cord produced a dose-dependent (0.3-10 microg) attenuation of the mechanical hyperalgesia, and this antihyperalgesic effect was completely reversed by yohimbine (1 mg/kg, subcutaneous), an alpha2-adrenoceptor antagonist. Dexmedetomidine (1-3 microg) produced an equipotent antihyperalgesic effect, whereas the effect of clonidine (1-10 microg) was markedly weaker. MPV-2426 (10 microg in 20 microl) administered adjacent to the wound did not produce any effect. Preoperative treatment with an antihyperalgesic dose of MPV-2426 did not prevent the development of hyperalgesia.

Conclusions

Intrathecal MPV-2426 dose-dependently attenuates postoperative hyperalgesia to mechanical stimulation because of an action on alpha2 adrenoceptors. Its antihyperalgesic action is as effective as that produced by dexmedetomidine and is considerably stronger than that produced by clonidine. However, preoperative treatment with MPV-2426 does not prevent the development of postoperative hyperalgesia.
Halothane and Isoflurane Augment Depolarization-induced Cytosolic CA2+Transients and Attenuate Carbachol-stimulated CA2+Transients
Authors: Xu Fang , Zhang Jin , Recio-Pinto Esperanza , Blanck Thomas J. J.
Published: November 2003

Background

Neuronal excitability is in part determined by Ca2+ availability that is controlled by regulatory mechanisms of cytosolic Ca2+ ([Ca2+]cyt). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca2+ concentration ([Ca2+]cyt) in response to K+ and carbachol stimulation were investigated.

Methods

Volatile anesthetic (0.05-1 mm) action on stimulated [Ca2+]cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mm) was used to depolarize and activate Ca2+ entry through voltage-dependent calcium channels; 1 mm carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP3)-dependent intracellular Ca2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca2+ stores.

Results

Halothane and isoflurane in clinically relevant concentrations enhanced the K+-evoked [Ca2+]cyt transient whether intracellular Ca2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca2+]cyt transient when the intracellular Ca2+ stores were full but had no effect when the Ca2+ stores were partially depleted by KCl stimulation.

Conclusions

Volatile anesthetics acted on sites that differently affect the K+- and carbachol-evoked [Ca2+]cyt transients. These data suggest the involvement of an intracellular Ca2+ translocation from the caffeine-sensitive Ca2+ store to the inositol triphosphate-sensitive Ca2+ store that was altered by halothane and isoflurane.
Isoflurane Alters the Recirculatory Pharmacokinetics of Physiologic Markers
Authors: Avram Michael J. , Krejcie Tom C. , Niemann Claus U. , Enders-Klein Cheri , Shanks Colin A. , Henthorn Thomas K.
Published: November 2003

Background

Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution.

Methods

The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition.

Results

Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered.

Conclusions

The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.
Pentobarbital, but not Propofol, Suppresses Vasopressin-stimulated Heat Shock Protein 27 Induction in Aortic Smooth Muscle Cells
Authors: Kozawa Osamu , Tanabe Kumiko , Matsuno Hiroyuki , Niwa Masayuki , Yamamoto Takuji , Akamatsu Shigeru , Kato Kanefusa , Dohi Shuji , Uematsu Toshihiko
Published: November 2003

Background

Although it is known that systemic blood pressure decreases after the administration of pentobarbital or propofol, the mechanisms underlying the cardiovascular effects of these anesthetics are still poorly understood. The authors previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low-molecular-weight HSP, by a protein kinase C-dependent manner in aortic smooth muscle A10 cells. It is recognized that HSP27 may act as a chaperone like high-molecular-weight HSPs such as HSP70. HSP27 is reportedly associated with agonist-induced contraction of vascular smooth muscle cells. The authors examined the effects of pentobarbital and propofol on the vasopressin-stimulated HSP27 induction in A10 cells.

Methods

Cultured A10 cells were pretreated with pentobarbital or propofol and then stimulated by vasopressin or 12-o-tetradecanoylphorbol 13-acetate (TPA). The effect of vasopressin on HSP70 was evaluated by Western blot analysis and compared with its effect on HSP27. The concentrations of HSP27 were determined by a specific immunoassay. The effect of pentobarbital on the expression levels of mRNA for HSP27 by vasopressin was evaluated by Northern blot analysis.

Results

Vasopressin induced HSP27 but had little effect on HSP70. At concentrations used clinically, pentobarbital inhibited the accumulation of HSP27 by vasopressin or TPA. Pentobarbital reduced the levels of mRNA for HSP27 induced by vasopressin. In contrast, propofol affected neither the vasopressin- nor TPA-induced HSP27 accumulation.

Conclusions

These results suggest that pentobarbital suppresses the vasopressin-stimulated HSP27 induction in vascular smooth muscle cells. This inhibitory effect is probably exerted at a point downstream from protein kinase C.
Pulsus Alternans during General Anesthesia with Halothane
Authors: Saghaei Mahmood , Mortazavian Mojtaba
Published: November 2003

Background

Pulsus alternans is a classic type of abnormal pulse. It can be defined as a regular alternation of pulse amplitude in which runs of weak and strong beats follow each other alternatively without any change in cycle length. It may be a sign of severe decompensated congestive heart failure. The authors infrequently encountered some cases of pulsus alternans during halothane anesthesia with spontaneous respiration in otherwise normal subjects in association with high levels of end-tidal carbon dioxide. This study was conducted to determine if there is any relation between this phenomena and hypercapnia.

Methods

One hundred twenty patients undergoing elective lower extremity surgery were selected. Halothane was used for maintenance of anesthesia, and the patients were allowed to breath spontaneously. The occurrence of pulsus alternans was determined by plethysmographic display of pulse wave and then confirmed by palpation of the radial artery.

Results

Ten patients (8.3%) developed pulsus alternans together with elevated levels of end-tidal carbon dioxide (57 +/- 4 mmHg vs. 41 +/- 4 mmHg in patients without pulsus alternans [mean +/- SD]). The pulsus alternans disappeared after switching to controlled ventilation and 15-20% reduction in end-tidal carbon dioxide. During the period of pulsus alternans, vital signs and electrocardiography remained within normal limits.

Conclusions

There may be some relation between occurrence of pulsus alternans and hypercapnia during halothane anesthesia. Pulsus alternans occurs in a small fraction of spontaneously breathing, halothane-anesthetized patients. Although hypercapnia is clearly a factor, the mechanism of this phenomenon is unknown.
Differences in Cardiovascular Response to Airway Stimulation at Different Sites and Blockade of the Responses by Lidocaine
Authors: Hamaya Yoshihiro , Dohi Shuji
Published: November 2003

Background

Mechanical stimulation of the airways elicits abrupt cardiovascular responses (CVR) in anesthetized humans. We examined a potential difference in such responses by comparing changes in heart rate (HR) and arterial blood pressure (AP) responses to mechanical stimulation of three different parts of the airways, as well as the effects of localized airway anesthesia with lidocaine on these responses.

Methods

After induction of general anesthesia, the larynx under laryngeal mask insertion (L, n = 20), the trachea-carina under tracheal intubation (T, n = 20), or the bronchus under bronchial intubation (B, N = 20) of each patient was mechanically stimulated in a similar manner. The same stimulation was repeated in 15 patients in each group after 5 ml of 4% lidocaine had been sprayed onto the part of the airway being stimulated. To test the systemic effect, intravenous lidocaine 1 mg/kg was given to five patients in each group, followed by the same airway stimulation. Consequent changes in HR and AP were continuously recorded and analyzed.

Results

Significant increases in HR and AP in response to airway tactile stimulation differed in magnitude according to the stimulated sites (L > T > or = B). These responses were completely blocked by topical application of lidocaine and partially blocked by intravenous lidocaine.

Conclusions

We found that CVRs to tactile stimulation differ in their magnitude at three different sites within the airways, and localized anesthesia with lidocaine can abolish these responses in humans. The inhibition of lidocaine could be mainly due to direct blockade of the mechanoreceptors of the airways and partly to its systemic effect.
Anesthesiologist Direction and Patient Outcomes
Authors: Silber Jeffrey H. , Kennedy Sean K. , Even-Shoshan Orit , Chen Wei , Koziol Laurie F. , Showan Ann M. , Longnecker David E.
Published: November 2003

Background

Anesthesia services for surgical procedures may or may not be personally performed or medically directed by anesthesiologists. This study compares the outcomes of surgical patients whose anesthesia care was personally performed or medically directed by an anesthesiologist with the outcomes of patients whose anesthesia care was not personally performed or medically directed by an anesthesiologist.

Methods

Cases were defined as being either "directed" or "undirected," depending on the type of involvement of the anesthesiologist, as determined by Health Care Financing Administration billing records. Outcome rates were adjusted to account for severity of disease and other provider characteristics using logistic regression models that included 64 patient and 42 procedure covariates, plus an additional 11 hospital characteristics often associated with quality of care. Medicare claims records were analyzed for all elderly patients in Pennsylvania who underwent general surgical or orthopedic procedures between 1991-1994. The study involved 194,430 directed and 23,010 undirected patients among 245 hospitals. Outcomes studied included death rate within 30 days of admission, in-hospital complication rate, and the failure-to-rescue rate (defined as the rate of death after complications).

Results

Adjusted odds ratios for death and failure-to-rescue were greater when care was not directed by anesthesiologists (odds ratio for death = 1.08, P < 0.04; odds ratio for failure-to-rescue = 1.10, P < 0.01), whereas complications were not increased (odds ratio for complication = 1.00, P < 0.79). This corresponds to 2.5 excess deaths/1,000 patients and 6.9 excess failures-to-rescue (deaths) per 1,000 patients with complications.

Conclusions

Both 30-day mortality rate and mortality rate after complications (failure-to-rescue) were lower when anesthesiologists directed anesthesia care. These results suggest that surgical outcomes in Medicare patients are associated with anesthesiologist direction, and may provide insight regarding potential approaches for improving surgical outcomes. (Key words: Anesthesiologists; anesthesia care team; quality of care; mortality; failure-to-rescue; complication; Medicare; general surgery; orthopedics.)