bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Prostaglandin Receptor EP1in the Spinal Dorsal Horn in Carrageenan-induced Inflammatory Pain
Authors: Nakayama Yoshito , Omote Keiichi , Namiki Akiyoshi 
Published: November 2003

Background
Prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the generation of hyperalgesia caused by inflammation. The current study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the development and maintenance of inflammatory pain, using behavioral, microdialysis, and intracellular calcium ion concentration ([Ca2+]i) assays.

Methods
Inflammation was induced by an injection of carrageenan into the plantar surface of the rat hind paw. The effects of inflammation were evaluated at the time points of 3 h (early phase) and 15 h (late phase) after carrageenan injection. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated. The effect of an intrathecally administered selective EP1 antagonist, ONO-8711, on the carrageenan-induced hyperalgesia was examined. Using a spinal microdialysis method, PGE2 concentration in the spinal dorsal horn was measured. In [Ca2+]i assays, we measured [Ca2+]i in the spinal dorsal horn in transverse spinal slices and examined the effects of pretreatment with ONO-8711. Sensitivities of the changes in [Ca2+]i to PGE2 perfusion were also assessed.

Results
Mechanical hyperalgesia and paw edema were observed in both the early and late phases. The hyperalgesia was inhibited by intrathecal ONO-8711 in the late, but not early, phase. The concentration of PGE2 in the spinal dorsal horn increased in the late phase. The [Ca2+]i in the dorsal horn increased on the ipsilateral side to the inflammation in the late, but not early phase. This increase was suppressed by the pretreatment with ONO-8711. Magnitude of the increase in [Ca2+]i on the ipsilateral side in response to PGE2 perfusion was greater in the late phase than in the early phase.

Conclusion
The results suggested that activation of spinal EP1 receptors was crucial in the carrageenan-induced mechanical hyperalgesia in the late phase. It seems that some of the mechanisms underlying inflammation-induced plastic changes are mediated by time-dependent increase in PGE2 concentration, activation of EP1 receptors, and increase in [Ca2+]i in the spinal dorsal horn.
Gabapentin and Pregabalin Can Interact Synergistically with Naproxen to Produce Antihyperalgesia
Authors: Hurley Robert W. , Chatterjea Debika , Rose Feng Meihua , Taylor Charles P. , Hammond Donna L. 
Published: November 2003

Background
Gabapentin and pregabalin are anticonvulsants with antihyperalgesic effects in animal models of neuropathic and inflammatory nociception. This study characterized the manner in which gabapentin or pregabalin interacts with naproxen to suppress thermal hyperalgesia and inflammation in the carrageenan model of peripheral inflammation.

Methods
Gabapentin, pregabalin, naproxen, or a fixed-dose ratio of gabapentin + naproxen or pregabalin + naproxen was administered orally to rats after the induction of inflammation by intraplantar injection of lambda-carrageenan in one hind paw. Nociceptive thresholds were determined by the radiant heat paw-withdrawal test. Paw edema was measured by plethysmometry. Drug plasma concentrations were determined by a liquid chromatography-mass spectroscopy-mass spectroscopy method.

Results
Gabapentin, pregabalin, and naproxen alone reversed thermal hyperalgesia with ED50 values of 19.2, 6.0, and 0.5 mg/kg, respectively. Mixtures of gabapentin + naproxen in fixed-dose ratios of 50:1, 10:1, or 1:1 interacted synergistically to reverse carrageenan-induced thermal hyperalgesia. However, 1:50 gabapentin + naproxen produced only additive effects. No combination of gabapentin + naproxen decreased paw edema in a manner greater than additive. Plasma concentrations of gabapentin and naproxen were unaltered by the addition of the other drug. The mixture of 10:1 of pregabalin + naproxen interacted synergistically to reverse thermal hyperalgesia on the inflamed hind paw, whereas mixtures of 1:1 or 1:10 produced additive effects.

Conclusions
These data suggest that gabapentin + naproxen and pregabalin + naproxen can interact synergistically or additively to reverse thermal hyperalgesia associated with peripheral inflammation. Therefore, the use of gabapentin or pregabalin in low-dose combinations with naproxen may afford therapeutic advantages for clinical treatment of persistent inflammatory pain.
Major Complications of Regional Anesthesia in France
Authors: Auroy Yves , Benhamou Dan , Bargues Laurent , Ecoffey Claude , Falissard Bruno , Mercier Frédéric , Bouaziz Hervé , Samii Kamran 
Published: November 2003

Background
Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful.

Methods
All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants.

Results
The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used.

Conclusion
This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.
Antiemetic Prophylaxis for Office-based Surgery
Authors: Tang Jun , Chen Xiaoguang , White Paul F. , Wender Ronald H. , Ma Hong , Sloninsky Alexander , Naruse Robert , Kariger Robert , Webb Tom , Zaentz Alan 
Published: November 2003

Background
Office-based surgery has become increasingly popular because of its cost-saving potential. However, the occurrence of postoperative nausea and vomiting (PONV) can delay patient discharge. Prophylaxis using a combination of antiemetic drugs has been suggested as an effective strategy for minimizing PONV. The authors designed this randomized, double-blinded, placebo-controlled study to assess the efficacy of ondansetron and dolasetron when administered in combination with droperidol and dexamethasone for routine antiemetic prophylaxis against PONV in the office-based surgery setting.

Methods
Following institutional review board approval, 135 consenting outpatients with American Society of Anesthesiologists physical status I-III who were undergoing superficial surgical procedures lasting 20-40 min were randomly assigned to one of three antiemetic treatment groups. Propofol was administered for induction of anesthesia, followed by 2-4% desflurane with 67% nitrous oxide in oxygen. Desflurane was subsequently adjusted to maintain a clinically adequate depth of anesthesia with an electroencephalographic Bispectral Index value between 50 and 60. All patients received 0.625 mg intravenous droperidol and 4 mg intravenous dexamethasone after induction of anesthesia. The study medication, containing normal saline (control), 12.5 mg intravenous dolasetron, or 4 mg intravenous ondansetron, was administered prior to the end of surgery. All patients received local anesthetics at the incisional site and 30 mg intravenous ketolorac to minimize postoperative pain. Recovery profiles, incidence of PONV, requirement for rescue antiemetic drugs, complete response rates, and patient satisfaction were assessed.

Results
The recovery times to patient orientation, oral intake, ambulation, and actual discharge did not differ among the three groups. The incidence of PONV, nausea scores, and requirement for rescue antiemetics were also similar in all three groups during the 24-h study period. In addition, the complete response rates to the prophylactic antiemetics (96-98%) and percentages of very satisfied patients (93-98%) were equally high in all three groups. However, the antiemetic drug acquisition costs were US $2.50, $15.50, and $18.50 in the control, dolasetron, and ondansetron groups, respectively.

Conclusion
The addition of dolasetron (12.5 mg) or ondansetron (4 mg) failed to improve the antiemetic efficacy of droperidol (0.625 mg intravenous) and dexamethasone (4 mg intravenous) when they were used for routine prophylaxis in the office-based surgery setting.
Effects of EDTA- and Sulfite-containing Formulations of Propofol on Respiratory System Resistance after Tracheal Intubation in Smokers
Authors: Rieschke Petra , LaFleur Bonnie J , Janicki Piotr K. 
Published: November 2003

Background
The formulation of sulfite-containing propofol (SCP) has not been thoroughly investigated in patients with the extensive smoking history for the effects on the total respiratory system resistance after tracheal intubation. However adverse effects, including acute asthma and bronchospasm, have been reported with several other parenteral formulations of drugs containing sulfite as preservative. Therefore, the aim of this prospective randomized and double blind study was to investigate the effects of EDTA-containing propofol (ECP) and SCP on total respiratory system resistance (Rrs) in patients with the prolonged smoking history and undergoing propofol-based total intravenous anesthesia with tracheal intubation.

Methods
40 patients scheduled for general anesthesia were enrolled into the study. Anesthesia was induced with either 2 mg/kg ECP, or 2 mg/kg SCP followed by vecuronium (0.1 mg/kg) to ensure complete neuromuscular relaxation for the time of the study. Maintenance anesthesia was continued with propofol infusion at 0.15 mg/kg/min for the first 15 min after intubation. Total respiratory system resistance (Rrs), was measured continuously for 10 min postintubation.

Results
The analysis of repeated Rrs measurements taken every minute for 10 min postintubation revealed trend consisting of higher Rrs in the SCP group when compared to the ECP group. The statistical analysis of the data performed using repeated measures analysis of covariance demonstrated statistically significant effect (P < 0.05) of the treatment group factor (SCP vs. ECP) and the time factor (time after intubation) on the postintubation Rrs.

Conclusion
The total respiratory system resistance measured repeatedly for 10 min after tracheal intubation in patients with smoking history is significantly elevated after induction with SCP than after induction with ECP. The preservative used for propofol formulation may alter the effects of propofol on the total respiratory system resistance in smokers.
Antifibrinolytic Therapy and Perioperative Blood Loss in Cancer Patients Undergoing Major Orthopedic Surgery
Authors: Amar David , Grant Florence M. , Zhang Hao , Boland Patrick J. , Leung Denis H. , Healey John A. 
Published: November 2003

Background
Aprotinin has been reported to reduce blood loss and transfusion requirements in patients having major orthopedic operations. Data on whether epsilon amino-caproic acid (EACA) is effective in this population are sparse.

Methods
Sixty-nine adults with malignancy scheduled for either pelvic, extremity or spine surgery during general anesthesia entered this randomized, double-blind, placebo-controlled trial, and received either intravenous aprotinin (n = 23), bolus of 2 x 10(6) kallikrein inactivator units (KIU), followed by an infusion of 5 x 10(5) KIU/h, or EACA (n = 22), bolus of 150 mg/kg, followed by a 15 mg/kg/h infusion or saline placebo (n = 24) during surgery. Our goal was to determine whether prophylactic EACA or aprotinin therapy would reduce perioperative blood loss (intraoperative + first 48h) >30% when compared to placebo.

Results
The mean age of the study population was 52 +/- 17 yr. The groups did not differ in age, duration of surgery, perioperative blood loss or number of packed erythrocyte units transfused. When compared to the placebo group, the two treated groups had a significantly lower D-Dimer level immediately after surgery, P < 0.01.

Conclusions
Under the conditions of this study, we were unable to find a clinical benefit to using aprotinin or EACA to reduce perioperative blood loss or transfusion requirements during major orthopedic surgery in cancer patients.
Phonomyography as a Novel Method to Determine Neuromuscular Blockade at the Laryngeal Adductor Muscles
Authors: Hemmerling Thomas M. , Babin Denis , Donati François 
Published: November 2003

Background
Neuromuscular blockade at the laryngeal adductor muscles may be measured using the cuff of a endotracheal tube placed between the vocal cords. Phonomyography is an alternative method of neuromuscular monitoring. In this study, phonomyography is applied to determine blockade at the larynx and compared with the cuff pressure method.

Methods
After the authors obtained approval from the ethics committee and informed consent, 28 patients were entered in the study. After induction of anesthesia, a endotracheal tube was inserted. Its cuff was placed in the trachea in routine fashion (n = 14) or between the vocal cords (n = 14). In all patients, a small condenser microphone was placed in the vestibular fold, just lateral to the tube, next to the laryngeal adductor muscles. The recurrent laryngeal nerve was stimulated supramaximally with single twitch stimulation (0.1 Hz) for onset, and train-of-four stimulation every 12 s during offset of neuromuscular blockade was produced by 0.1 mg/kg mivacurium. Onset and recovery of neuromuscular blockade measured by the two methods were compared using the test (P < 0.05), and a Bland-Altman test was performed to define agreement between the two methods. Onset and recovery of neuromuscular blockade measured by phonomyography with the cuff placed between the vocal cords or in the trachea were compared using the test (P < 0.05).

Results
Mean onset, maximum effect, and time to reach 25% and 75% of control twitch response for phonomyography cuff pressure method were 145 s (SD, 25) 156 s (SD, 33), 89% (SD, 4) 91% (SD, 4), 9 min (SD, 4) 10 min (SD, 3), and 27 min (SD, 4) 29 min (SD, 4), respectively, without being significantly different. Mean bias was -2%, with limits of agreement of -20 and +18% for all signals (cuff method minus phonomyography). There was no significant difference in onset and offset of neuromuscular blockade measured using phonomyography with the cuff placed between the vocal cords or in the trachea.

Conclusions
Both methods can be used interchangeably to determine neuromuscular blockade of the laryngeal adductor muscles. Phonomyography allows measurement of laryngeal blockade with the endotracheal tube in the normal position.
Isoflurane Alters Energy Substrate Metabolism to Preserve Mechanical Function in Isolated Rat Hearts following Prolonged No-Flow Hypothermic Storage
Authors: Finegan Barry A. , Gandhi Manoj , Cohen Matthew R. , Legatt Donald , Clanachan Alexander S. 
Published: November 2003

Background
Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined.

Methods
Isolated working rat hearts were subjected to cardioplegic arrest with St. Thomas' II solution, hypothermic no-flow storage for 8 h, and subsequent aerobic reperfusion. The consequences of isoflurane treatment were assessed during the following conditions: (1) isoflurane exposure before and during storage; (2) brief isoflurane exposure during early nonworking poststorage reperfusion; and (3) isoflurane preconditioning before storage. The selective mitochondrial and sarcolemmal K(atp) channel antagonists, 5-hydroxydecanoate and HMR 1098, respectively, were used to assess the role of K(atp) channel activation on glycogen consumption during storage in isoflurane-preconditioned hearts.

Results
Isoflurane enhanced recovery of mechanical function if present before and during storage. Isoflurane preconditioning was also protective. Isoflurane reduced glycogen consumption during storage under the aforementioned circumstances. Storage of isoflurane-preconditioned hearts in the presence of 5-hydroxydecanoate prevented the reduction in glycogen consumption during storage and abolished the beneficial effect of isoflurane preconditioning on recovery of mechanical function.

Conclusions
Isoflurane provides additive protection of hearts subject to cardioplegic arrest and prolonged hypothermic no-flow storage and favorably alters energy substrate metabolism by modulating glycolysis during ischemia. The effects of isoflurane preconditioning on glycolysis during hypothermic no-flow storage appears to be associated with activation of mitochondrial K(atp) channels.
Preconditioning with Sevoflurane Reduces Changes in Nicotinamide Adenine Dinucleotide during Ischemia–Reperfusion in Isolated Hearts
Authors: Riess Matthias L. , Novalija Enis , Camara Amadou K. S. , Eells Janis T. , Chen Qun , Stowe David F. 
Published: November 2003

Background
Ischemia causes an imbalance in mitochondrial metabolism and accumulation of nicotinamide adenine dinucleotide (NADH). We showed that anesthetic preconditioning (APC), like ischemic preconditioning, improved mitochondrial NADH energy balance during ischemia and improved function and reduced infarct size on reperfusion. Opening adenosine triphosphate-sensitive potassium (K(atp)) channels may be involved in triggering APC. The authors tested if effects of APC on NADH concentrations before, during, and after ischemia are reversible by 5-hydroxydecanoate (5-HD), a putative mitochondrial K channel blocker.

Methods
Nicotinamide adenine dinucleotide fluorescence was measured in 60 guinea pig Langendorff-prepared hearts assigned into five groups: (1) no treatment before ischemia; (2) APC by exposure to 1.3 mm sevoflurane for 15 min; (3) 200 microm 5-HD from 5 min before to 15 min after sevoflurane exposure; (4) 35 min 5-HD alone; and (5) no treatment and no ischemia. Sevoflurane was washed out for 30 min, and 5-HD for 15 min, before 30-min ischemia and 120-min reperfusion.

Results
Nicotinamide adenine dinucleotide was reversibly increased during sevoflurane exposure before ischemia, and the increase and rate of decline in NADH during ischemia were reduced after APC. 5-HD abolished these changes in NADH. On reperfusion, function was improved and infarct size reduced after APC compared with other groups.

Conclusion
Anesthetic preconditioning was evidenced by improved mitochondrial bioenergetics as assessed from NADH concentrations during ischemia and by attenuated reperfusion injury. Reversal of APC by bracketing sevoflurane exposure with 5-HD suggests that APC is triggered by mitochondrial K channel opening or, alternatively, by attenuated mitochondrial respiration without direct involvement of mitochondrial K channel opening.
Antinociceptive Effect of Low-Dose Intrathecal Neostigmine Combined with Intrathecal Morphine following Gynecologic Surgery
Authors: Almeida Raquel A. , Lauretti Gabriela R. , Mattos Anita L. 
Published: November 2003

Background
The purpose of this study was to determine whether combination of 1-5 microg intrathecal neostigmine would enhance analgesia from a fixed intrathecal dose of morphine.

Methods
A total of 60 patients undergoing gynecologic surgery were randomized to one of five groups. Patients received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline, 100 microg morphine, or 1-5 microg neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 microg neostigmine group received spinal morphine and 1 microg neostigmine. The morphine + 2.5 microg neostigmine group received spinal morphine and 2.5 microg neostigmine. Finally, the morphine + 5 microg neostigmine group received spinal morphine and 5 microg neostigmine.

Results
The groups were demographically similar. The time to first rescue analgesic (minutes) was longer for all patients who received intrathecal morphine combined with 1-5 microg neostigmine (median, 6 h) compared with the control group (median, 3 h) (P < 0.02). The morphine group (P < 0.05) and the groups that received the combination of 100 microg intrathecal morphine combined with neostigmine (P < 0.005) required less rescue analgesics in 24 h compared with the control group. The incidence of perioperative adverse effects was similar among groups (P > 0.05).

Conclusions
The addition of 1-5 microg spinal neostigmine to 100 microg morphine doubled the duration to first rescue analgesic in the population studied and decreased the analgesic consumption in 24 h, without increasing the incidence of adverse effects. The data suggest that low-dose spinal neostigmine may improve morphine analgesia.
High Spinal Anesthesia for Cardiac Surgery
Authors: Lee Trevor W. R. , Grocott Hilary P. , Schwinn Debra , Jacobsohn Eric 
Published: November 2003

Background
This double-blind, randomized, controlled trial examined the effect of high-dose intrathecal bupivacaine in combination with general anesthesia on atrial beta-adrenergic receptor function, the stress response, and hemodynamics during coronary artery bypass graft surgery.

Methods
Thirty-eight patients were randomized to either control (n = 19) or intrathecal bupivacaine (ITB) groups (n = 19). Patients in the ITB group received 37.5 mg intrathecal hyperbaric bupivacaine before induction of general anesthesia. Control patients received an injection of local anesthetic into the skin and subcutaneous tissues (sham spinal). Comparisons were made between groups with respect to atrial receptor desensitization and down-regulation, in addition to circulating catecholamines and hemodynamics.

Results
In patients with cardiopulmonary bypass (CPB) times in excess of 1 h, the ITB group had significantly less atrial beta-receptor dysfunction, as measured by maximal isproteronol, 50% maximal isoproterenol, sodium fluoride-stimulated activity, and zinterol stimulation assays of adenylyl cyclase activity (P < or = 0.02) and beta-adrenergic receptor density (P = 0.02). Serum epinephrine, norepinephrine, and cortisol concentrations were significantly lower in the ITB group, independent of CPB times (P < 0.0001, P < 0.001, and P < 0.05, respectively). ITB patients had a higher cardiac index and a lower pulmonary vascular resistance index in the post-CPB time period (P < 0.01 and P < 0.05, respectively). In the pre-CPB period, mean arterial pressure and systemic vascular resistance index were significantly lower in the ITB group.

Conclusions
High-dose intrathecal bupivacaine, when combined with general anesthesia, resulted in less beta-receptor dysfunction and a lower stress response during coronary artery bypass graft surgery.