bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preemptive Intravenous Morphine-6-glucuronide Is Ineffective for Postoperative Pain Relief
Authors: Motamed Cyrus , Mazoit Xavier , Ghanouchi Khaldoun , Guirimand Frédéric , Abhay Kou , Lieutaud Thomas , Bensaid Saïd , Fernandez Christine , Duvaldestin Philippe 
Published: November 2003

Background
Morphine-6-glucuronide (M-6-G), a major metabolite of morphine, is reported to be more potent than morphine when administered intrathecally; however, its efficiency remains under debate when administered intravenously. This study was designed to assess the analgesic efficiency of intravenous M-6-G for the treatment of acute postoperative pain.

Methods
After informed consent was obtained, 37 adults (American Society of Anesthesiologists physical status I-II) who were scheduled for elective open knee surgery were enrolled in the study. General anesthesia was induced with thiopental, alfentanil, and vecuronium and was maintained with a mixture of nitrous oxide/isoflurane and bolus doses of alfentanil. At skin closure, patients were randomized into three groups: (1) morphine group (n = 13), which received morphine 0.15 mg/kg; (2) M-6-G group (n = 12), which received M-6-G 0.1 mg/kg; and (3) placebo group (n = 12), which received saline. At the time of extubation, plasma concentration of morphine and M-6-G was measured. Postoperative analgesic efficiency was assessed by the cumulative dose of morphine delivered by patient-controlled analgesia. Opioid-related side effects were also evaluated.

Results
No difference was noted in patient characteristics and opioid-related side effects. Morphine requirements (mean +/- SD) during the first 24 h in the M-6-G group (41+/-9 mg) and the placebo group (49+/-8 mg) were significantly greater (P<0.05) compared with the morphine group (29+/-8 mg).

Conclusion
A single intravenous bolus dose of M-6-G was found to be ineffective in the treatment of acute postoperative pain. This might be related to the low permeability of the blood-brain barrier for M-6-G.
Low-dose Clonidine and Neostigmine Prolong the Duration of Intrathecal Bupivacaine–Fentanyl for Labor Analgesia
Authors: Owen Medge D. , Özsaraç Özer , Şahin Şükran , Uçkunkaya Nesimi , Kaplan Nuray , Maǧunaci Ihsan 
Published: November 2003

Background
Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor.

Methods
Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed.

Results
Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P<0.001) or BFC (123+/-21 min; P<0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P<0.05 as compared with BFC).

Conclusions
The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated.
Bedside Assessment of Cerebral Blood Flow by Double-indicator Dilution Technique
Authors: Wietasch Götz J. K. , Mielck Frank , Scholz Martin , von Spiegel Tilman , Stephan Heidrun , Hoeft Andreas 
Published: November 2003

Background
Currently, quantitative measurement of global cerebral blood flow (CBF) at bedside is not widely performed. The aim of the present study was to evaluate a newly developed method for bedside measurement of CBF based on thermodilution in a clinical setting.

Methods
The investigation was performed in 14 anesthetized patients before coronary bypass surgery. CBF was altered by hypocapnia, normocapnia, and hypercapnia. CBF was measured simultaneously by the Kety-Schmidt inert-gas technique with argon and a newly developed transcerebral double-indicator dilution technique (TCID). For TCID, bolus injections of ice-cold indocyanine green were performed via a central venous line, and the resulting thermo-dye dilution curves were recorded simultaneously in the aorta and the jugular bulb using combined fiberoptic thermistor catheters. CBF was calculated from the mean transit times of the indicators through the brain.

Results
Both methods of measurement of CBF indicate a decrease during hypocapnia and an increase during hypercapnia, whereas cerebral metabolic rate remained unchanged. Bias between CBF(TCID) and CBFargon was -7.1+/-2.2 (SEM) ml x min(-1) x 100 g(-1); precision (+/- 2 x SD of differences) between methods was 26.6 ml x min(-1) x 100 g(-1).

Conclusions
In the clinical setting, TCID was feasible and less time-consuming than alternative methods. The authors conclude that TCID is an alternative method to measure global CBF at bedside and offers a new opportunity to monitor cerebral perfusion of patients.
Walking with Labor Epidural Analgesia
Authors: Cohen Sheila E. , Yeh Julie Y. , Riley Edward T. , Vogel Tracey M. 
Published: November 2003

Background
Regional analgesia techniques for labor that permit ambulation are popular among parturients. This study evaluated the influence of bupivacaine bolus concentration and a 3-ml 1.5% lidocaine-epinephrine test dose, on analgesic effectiveness and the ability to walk after block placement.

Methods
Using a randomized double-blind study design, epidural analgesia was initiated in 60 parturients undergoing labor as follows: Group TD/B.0625 received a 3-ml lidocaine-epinephrine test dose + 12 ml bupivacaine, 0.0625%; group TD/B.125 received a 3-ml test dose + 12 ml bupivacaine, 0.125%; group B.0625 received 15 ml bupivacaine, 0.0625% (no test dose); and group B.125 received 15 ml bupivacaine, 0.125% (no test dose). Initial boluses in all groups contained 10 microg sufentanil. Bupivacaine, 0.0625%, with 0.33 microg/ml sufentanil was infused throughout labor at 13.5-15 ml/h. Analgesia balance, proprioception, motor block, and patient ability to stand and walk were evaluated at various intervals.

Results
A bolus of 0.125% bupivacaine containing sufentanil, without a previous test dose, proved to be optimal with respect to analgesia and early ambulation. When a test dose was given before bupivacaine, 0.125%, fewer women walked within 1 h of block placement. Bupivacaine, 0.0625%, with sufentanil, with or without a test dose, provided inadequate analgesia, necessitating additional bupivacaine, which impaired the ability to walk. A high percentage of women in all groups (73-93%) walked at some stage during labor.

Conclusions
Omitting a lidocaine-epinephrine test dose and using 0.125% bupivacaine for the initial bolus should permit ambulation in the early postblock period for most parturients who elect this option.
The Pharmacodynamic Effect of a Remifentanil Bolus on Ventilatory Control
Authors: Babenco H. Daniel , Conard Pattilyn F. , Gross Jeffrey B. 
Published: November 2003

Background
In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously.

Methods
In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PET(CO2)) at approximately 46 or 56 mm Hg (alternate subjects). After 6 min of equilibration, subjects received 0.5 microg/kg remifentanil over 5 s, and minute ventilation (V(E)) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mm Hg). The V(E) data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (k(eo)), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration-response curve (gamma).

Results
The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l x min(-1) x mm Hg(-1) [-0.12 to 0.66] 2 min after remifentanil (P<0.001); within 5 min, it recovered to approximately 0.6 l x min(-1) x mm Hg(-1), and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mm Hg (VE50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P<0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of VE50 included k(eo) = 0.24 min(-1) (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and gamma = 1.74.

Conclusions
After administration of 0.5 microg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.
Comparison of Plasma Compartment versus Two Methods for Effect Compartment–controlled Target-controlled Infusion for Propofol
Authors: Struys Michel M. R. F. , De Smet Tom , Depoorter Birgit , Versichelen Linda F. M. , Mortier Eric P. , Dumortier Frank J. E. , Shafer Steven L. , Rolly Georges 
Published: November 2003

Background
Target-controlled infusion (TCI) systems can control the concentration in the plasma or at the site of drug effect. A TCI system that targets the effect site should be able to accurately predict the time course of drug effect. The authors tested this by comparing the performance of three control algorithms: plasmacontrol TCI versus two algorithms for effect-site control TCI.

Methods
One-hundred twenty healthy women patients received propofol via TCI for 12-min at a target concentration of 5.4 microg/ml. In all three groups, the plasma concentrations were computed using pharmacokinetics previously reported. In group I, the TCI device controlled the plasma concentration. In groups II and III, the TCI device controlled the effect-site concentration. In group II, the effect site was computed using a half-life for plasma effect-site equilibration (t1/2k(eo)) of 3.5 min. In group III, plasma effect-site equilibration rate constant (k(eo)) was computed to yield a time to peak effect of 1.6 min after bolus injection, yielding a t1/2keo of 34 s. the time course of propofol was measured using the bispectral index. Blood pressure, ventilation, and time of loss of consciousness were measured.

Results
The time course of propofol drug effect, as measured by the bispectral index, was best predicted in group III. Targeting the effect-site concentration shortened the time to loss of consciousness compared with the targeting plasma concentration without causing hypotension. The incidence of apnea was less in group III than in group II.

Conclusion
Effect compartment-controlled TCI can be safely applied in clinical practice. A biophase model combining the Marsh kinetics and a time to peak effect of 1.6 min accurately predicted the time course of propofol drug effect.
Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2· kg−1· min−1
Authors: Lieberman Jeremy A. , Weiskopf Richard B. , Kelley Scott D. , Feiner John , Noorani Mariam , Leung Jacqueline , Toy Pearl , Viele Maurene 
Published: November 2003

Background
The "critical" level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2.

Methods
With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a beta-adrenergic antagonist, esmolol.

Results
Reduction of hemoglobin from 12.5+/-0.8 g/dl to 4.8+/-0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0+/-2.9 to 9.9+/-20 ml O2 x kg(-1) x min(-1); all P<0.001). Oxygen consumption (VO2; 3.0+/-0.5 to 3.4+/-0.6 ml O2 x kg(-1) x min(-1); P<0.05) and plasma lactate concentration (0.50+/-0.10 to 0.62+/-0.16 mM; P<0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3+/-1.4 ml O2 x kg(-1) x min(-1); all P<0.01 vs. before esmolol). VO2 (3.2+/-0.6 ml O2 x kg(-1) x min(-1); P>0.05) and plasma lactate (0.66+/-0.14 mM; P>0.05) did not change further. No value of plasma lactate exceeded the normal range.

Conclusions
A decrease in DO2 to 7.3+/-1.4 ml O2 x kg(-1) min(-1) in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value.
Comparison of Intravenous or Epidural Patient-controlled Analgesia in the Elderly after Major Abdominal Surgery
Authors: Mann Claude , Pouzeratte Yvan , Boccara Gilles , Peccoux Christophe , Vergne Christine , Brunat Georges , Domergue Jacques , Millat Bertrand , Colson Pascal 
Published: November 2003

Background
Patient-controlled analgesia (PCA) with intravenous morphine and patient-controlled epidural analgesia (PCEA), using an opioid either alone or in combination with a local anesthetic, are two major advances in the management of pain after major surgery. However, these techniques have been evaluated poorly in elderly people. This prospective, randomized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient.

Methods
Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned randomly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA, using a mixture of 0.125% bupivacaine and sufentanil (PCEA group), or general anesthesia followed by PCA with intravenous morphine (PCA group). Pain intensity was tested three times daily using a visual analog scale. Postoperative evaluation included mental status, cardiorespiratory and gastrointestinal functions, and patient satisfaction scores.

Results
Pain relief was better at rest (P = 0.001) and after coughing (P = 0.002) in the PCEA group during the 5 postoperative days. Satisfaction scores were better in the PCEA group. Although incidence of delirium was comparable in the PCA and PCEA groups (24% vs. 26%, respectively), mental status was improved on the fourth and fifth postoperative days in the PCEA group. The PCEA group recovered bowel function more quickly than did the PCA group. Cardiopulmonary complications were similar in the two groups.

Conclusion
After major abdominal surgery in the elderly patient, patient-controlled analgesia, regardless of the route (epidural or parenteral), is effective. The epidural route using local anesthetics and an opioid provides better pain relief and improves mental status and bowel activity.
Bupivacaine Inhibits Acylcarnitine Exchange in Cardiac Mitochondria
Authors: Weinberg Guy L. , Palmer June W. , VadeBoncouer Timothy R. , Zuechner Mikko B. , Edelman Guy , Hoppel Charles L. 
Published: November 2003

Background
The authors previously reported that secondary carnitine deficiency may sensitize the heart to bupivacaine-induced arrhythmias. In this study, the authors tested whether bupivacaine inhibits carnitine metabolism in cardiac mitochondria.

Methods
Rat cardiac interfibrillar mitochondria were prepared using a differential centrifugation technique. Rates of adenosine diphosphate-stimulated (state III) and adenosine diphosphate-limited (state IV) oxygen consumption were measured using a Clark electrode, using lipid or nonlipid substrates with varying concentrations of a local anesthetic.

Results
State III respiration supported by the nonlipid substrate pyruvate (plus malate) is minimally affected by bupivacaine concentrations up to 2 mM. Lower concentrations of bupivacaine inhibited respiration when the available substrates were palmitoylcarnitine or acetylcarnitine; bupivacaine concentration causing 50% reduction in respiration (IC50 +/- SD) was 0.78+/-0.17 mM and 0.37+/-0.03 mM for palmitoylcarnitine and acetylcarnitine, respectively. Respiration was equally inhibited by bupivacaine when the substrates were palmitoylcarnitine alone, or palmitoyl-CoA plus carnitine. Bupivacaine (IC50 = 0.26+/-0.06 mM) and etidocaine (IC50 = 0.30+/-0.12 mM) inhibit carnitine-stimulated pyruvate oxidation similarly, whereas the lidocaine IC50 is greater by a factor of roughly 5, (IC50 = 1.4+/-0.26 mM), and ropivacaine is intermediate, IC50 = 0.5+/-0.28 mM.

Conclusions
Bupivacaine inhibits mitochondrial state III respiration when acylcarnitines are the available substrate. The substrate specificity of this effect rules out bupivacaine inhibition of carnitine palmitoyl transferases I and II, carnitine acetyltransferase, and fatty acid beta-oxidation. The authors hypothesize that differential inhibition of carnitine-stimulated pyruvate oxidation by various local anesthetics supports the clinical relevance of inhibition of carnitine-acylcarnitine translocase by local anesthetics with a cardiotoxic profile.
Changes in Intravascular Volume during Acute Normovolemic Hemodilution and Intraoperative Retransfusion in Patients with Radical Hysterectomy
Authors: Rehm Markus , Orth Victoria , Kreimeier Uwe , Thiel Manfred , Haller Mathias , Brechtelsbauer Heinz , Finsterer Udilo 
Published: November 2003

Background
Changes in blood volume during acute normovolemic hemodilution (ANH) and their consequences for the perioperative period have not been investigated sufficiently.

Methods
In 15 patients undergoing radical hysterectomy, preoperative ANH to a hematocrit of 24% was performed using 5% albumin solution. Intraoperatively, saline 0.9% solution was used for volume substitution, and intraoperative retransfusion was started at a hematocrit of 20%. Plasma volume (indocyanine green dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labeling erythrocytes with fluorescein) was determined before and after ANH and postoperatively.

Results
Mean normal plasma volumes (1,514 +/- 143 ml/m2) and reduced red cell volumes (707 +/- 79 ml/m2) were measured preoperatively. Blood (1,150 +/- 196 ml) was removed and replaced with 1,333 +/- 204 ml of colloid. Blood volume before and after ANH was equal and amounted to 3,740 ml. Intraoperatively, plasma volume did not increase until retransfusion despite infusing 3,389 +/- 1,021 ml of crystalloid (corrected for urine output) to compensate for an estimated surgical blood loss of 727 +/- 726 mi. Postoperatively, after retransfusion of all autologous blood, blood volume was 255 +/- 424 ml higher than preoperatively before ANH. Despite mean calculated blood loss of 1,256 +/- 892 ml, only one patient received allogeneic blood.

Conclusions
During ANH, normovolemia was exactly maintained. After surgical blood loss of 1,256 +/- 892 ml, crystalloid and colloid supplies of 5,752 +/- 1,462 ml and 1,667 +/- 548 ml, respectively, and complete intraoperative retransfusions of autologous blood in every patient, mean blood volume was 250 ml higher than preoperatively before ANH.
Effect of Ambient Temperature on Human Pain and Temperature Perception
Authors: Strigo Irina A. , Carli Franco , Bushnell M. Catherine 
Published: November 2003

Background
Animal studies show reduced nociceptive responses to noxious heat stimuli and increases in endogenous beta-endorphin levels in cold environments, suggesting that human pain perception may be dependent on ambient temperature. However, studies of changes in local skin temperature on human pain perception have yielded variable results. This study examines the effect of both warm and cool ambient temperature on the perception of noxious and innocuous mechanical and thermal stimuli.

Methods
Ten subjects (7 men and 3 women, aged 20-23 yr) used visual analog scales to rate the stimulus intensity, pain intensity, and unpleasantness of thermal (0-50 degrees C) and mechanical (1.2-28.9 g) stimuli applied on the volar forearm with a 1-cm2 contact thermode and von Frey filaments, respectively. Mean skin temperatures were measured throughout the experiment by infrared pyrometer. Each subject was tested in ambient temperatures of 15 degrees C (cool), 25 degrees C (neutral), and 35 degrees C (warm) on separate days, after a 30-min acclimation to the environment. Studies began in the morning after an 8-h fast.

Results
Mean skin temperature was altered by ambient temperature (cool room: 30.1 degrees C; neutral room: 33.4 degrees C; warm room: 34.5 degrees C; P < 0.0001). Ambient temperature affected both heat (44-50 degrees C) and cold (25-0 degrees C) perception (P < 0.01). Stimulus intensity ratings tended to be lower in the cool than in the neutral environment (P < 0.07) but were not different between the neutral and warm environments. Unpleasantness ratings revealed that cold stimuli were more unpleasant than hot stimuli in the cool room and that noxious heat stimuli were more unpleasant in a warm environment. Environmental temperature did not alter ratings of warm (37 and 40 degrees C) or mechanical stimuli.

Conclusions
These results indicate that, in humans, a decrease in skin temperature following exposure to cool environments reduces thermal pain. Suppression of Adelta primary afferent cold fiber activity has been shown to increase cold pain produced by skin cooling. Our current findings may represent the reverse phenomenon, i.e., a reduction in thermal nociceptive transmission by the activation of Adelta cutaneous cold fibers.