bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Ketamine and Its Enantiomers on the Morphine- or Dexmedetomidine-induced Antinociception after Intrathecal Administration in Rats
Authors: Joó Gabriella , Horvath Gyöngyi , Klimscha Walter , Kekesi Gabriella , Dobos Ildiko , Szikszay Margit , Benedek György 
Published: November 2003

Background
The spinal administration of some N-methyl-d-aspartate receptor antagonists results in antinociception and potentiates the effects of opioids and alpha2-adrenoceptor agonists, but ketamine and its enantiomers have not been examined. The present study investigated the interactions of racemic ketamine, R(-)-ketamine and S(+)-ketamine with morphine and with dexmedetomidine.

Methods
Intrathecal catheters were implanted into male Wistar rats. Three days later, the acute nociceptive sensitivity was assessed using the tail-flick test. Analgesic latencies were converted to the percentage maximum possible effect. The dose that yielded 50% of the maximum possible effect (ED50) and dose-response and time-course curves were determined for the ketamines (30-300 microg), morphine (0.1-3.0 microg), dexmedetomidine (0.3-10.0 microg), and mixtures of two doses of ketamines (30 or 100 microg) with different doses of morphine or dexmedetomidine for fixed-dose analysis.

Results
Neither racemic ketamine nor its enantiomers alone had a significant effect on the tail-flick test, with the exception of the highest dose of racemic ketamine, which caused motor impairment. Morphine and dexmedetomidine each produced dose-dependent antinociception, with ED50 of 1.7 microg (95% confidence interval: 1.04-2.32) and 4. 85 microg (3.96-5.79), respectively. A low dose (30 microg) of racemic ketamine or its enantiomers did not influence the ED50 of morphine significantly. Coadministration of 100 microg racemic ketamine or S(+)-ketamine, but not R(-)-ketamine, significantly enhanced and prolonged the antinociceptive effect of morphine. Both doses of racemic ketamine or its isomers significantly decreased the ED50 value for dexmedetomidine, although the higher dose of racemic or S(+)-ketamine had the highest potency. One-hundred micrograms of racemic ketamine or S(+)-ketamine also prolonged the effects of dexmedetomidine.

Conclusions
These data indicate that racemic ketamine and S(+)-ketamine, but not R(-)-ketamine, exhibit similar effectiveness in potentiating the antinociceptive effects of both morphine and dexmedetomidine.
Intraoperative Cerebral Arterial Embolization during Total Hip Arthroplasty
Authors: Edmonds Chris R. , Barbut Denise , Hager David , Sharrock Nigel E. 
Published: November 2003

Background
Fat embolism to the pulmonary circulation is known to occur during total hip arthroplasty, especially during insertion of a cemented femoral component. Fat and air bubbles may enter the systemic circulation via a patent foramen ovale or through pulmonary circulation.

Methods
To determine whether microemboli to the brain were occurring during total hip arthroplasty, 23 patients underwent transcranial Doppler assessment of emboli to the middle cerebral artery during total hip arthroplasty. Surgery was performed with the patient in the lateral decubitus position so that the probe recorded from the nondependent side.

Results
Successful recordings were made in 20 patients, in 8 of 20 patients there were embolic signals, which ranging from 1 to 200. In all eight patients, signals were recorded during impaction of a cemented component or after relocation of the hip. Only one patient showed evidence of emboli with impaction of the acetabulum component. In two patients there were 150 and 200 embolic signals: in both mild respiratory symptoms developed. One patient became overtly agitated during a flurry of emboli.

Conclusion
Cerebral microemboli can occur during total hip arthroplasty. Whether this contributes to changes in postoperative cognitive function is unknown.
Omission of Nitrous Oxide from a Propofol-based Anesthetic Does Not Affect the Recovery of Women Undergoing Outpatient Gynecologic Surgery
Authors: Arellano Ramiro J. , Pole Meena L. , Rafuse Sara E. , Fletcher Mary , Saad Yousri G. , Friedlander Mark , Norris Andrew , Chung Frances F. T. 
Published: November 2003

Background
Although nitrous oxide (N2O) is used commonly during anesthesia, clinically relevant advantages-disadvantages of using this agent are not well established in the ambulatory setting. This study in women undergoing ambulatory gynecologic surgery compares outcomes in patients administered total intravenous anesthesia with propofol versus the propofol plus N2O. The primary outcome was the time to home readiness. Secondary outcomes included the incidence of postanesthetic adverse events.

Methods
Women presenting for elective ambulatory termination of pregnancy or gynecologic laparoscopy were induced with an intravenous sleep dose of propofol and fentanyl. After induction, subjects were randomly allocated to maintenance anesthesia with propofol alone or propofol plus 65% N2O. Patients were assessed by a blinded observer in the postanesthetic care unit at 20-min intervals to determine home readiness. Postoperative pain and nausea were measured with visual analog scales. Postoperative analgesics and antiemetics were recorded. The incidence of adverse events occurring after hospital discharge was assessed by a telephone interview 24 h postoperatively.

Results
A total of 740 patients received propofol alone, and 750 patients received propofol plus N2O. Mean home readiness times were not significantly different between treatment groups. There were no significant differences between groups in pain scores, nausea scores, analgesia administration, or antiemetic administration before discharge. There were no significant differences in the frequency of adverse events for 24 h after discharge from hospital.

Conclusions
Omission of N2O from a propofol-based anesthetic for ambulatory gynecologic surgery does not affect time to home readiness or the incidence of postoperative adverse events up to 24 h after discharge from hospital. (Key words: Awareness; outpatient surgery; total intravenous anesthesia.)
Preanesthetic Train-of-four Fade Predicts the Atracurium Requirement of Myasthenia Gravis Patients
Authors: Mann Ruth , Blobner Manfred , Jelen-Esselborn Sabine , Busley Raimund , Werner Christian 
Published: November 2003

Background
The most sensitive diagnostic criterion of myasthenia gravis is a decrement in the muscular response to repetitive stimulation. The authors hypothesized that myasthenia gravis patients who show a train-of-four ratio (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to nondepolarizing neuromuscular blocking agents compared with myasthenia gravis patients with preanesthetic T4/T1 > or = 0.9.

Methods
After institutional review board approval was obtained, 20 electrophysiologically documented myasthenia gravis patients were studied. Current pyridostigmine therapy was continued until the morning of surgery. Before induction of anesthesia, neuromuscular transmission was recorded from the hypothenar muscles using electromyography with train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio, patients were assigned to the "normal" group (T4/T1 > or = 0.9) or the "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms.

Results
In 14 patients, preanesthetic T4/T1 was > or = 0.9 (normal), whereas 6 patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients were extubated within 30 min after surgery. Postoperative pyridostigmine infusion did not differ significantly between groups.

Conclusions
The requirement for atracurium is significantly reduced in myasthenia gravis patients with a T4/T1 ratio < 0.9 before anesthesia. This study indicates that routine neuromuscular monitoring in myasthenia gravis patients should be extended into the preinduction period to identify patients who require less atracurium.
Endotoxin Desensitization of Human Mononuclear Cells after Cardiopulmonary Bypass
Authors: Grundmann Ulrich , Rensing Hauke , Adams Hans-Anton , Falk Sabine , Wendler Olaf , Ebinger Nicole , Bauer Michael 
Published: November 2003

Background
The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide.

Methods
Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-alpha release were studied.

Results
Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0-6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-alpha response in vitro, their addition post-treatment failed to restore the monocytic TNF-alpha response.

Conclusions
Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.
Arterial to End-tidal Carbon Dioxide Pressure Difference during Laparoscopic Surgery in Pregnancy
Authors: Bhavani-Shankar Kodali , Steinbrook Richard A. , Brooks David C. , Datta Sanjay 
Published: November 2003

Background
There is controversy about whether capnography is adequate to monitor pulmonary ventilation to reduce the risk of significant respiratory acidosis in pregnant patients undergoing laparoscopic surgery. In this prospective study, changes in arterial to end-tidal carbon dioxide pressure difference (PaCO2--PetCO2), induced by carbon dioxide pneumoperitoneum, were determined in pregnant patients undergoing laparoscopic cholecystectomy.

Methods
Eight pregnant women underwent general anesthesia at 17-30 weeks of gestation. Carbon dioxide pnueumoperitoneum was initiated after obtaining arterial blood for gas analysis. Pulmonary ventilation was adjusted to maintain PetCO2 around 32 mmHg during the procedure. Arterial blood gas analysis was performed during insufflation, after the termination of insufflation, after extubation, and in the postoperative period.

Results
The mean +/- SD for PaCO2--PetCO2 was 2.4 +/- 1.5 before carbon dioxide pneumoperitoneum, 2.6 +/- 1.2 during, and 1.9 +/- 1.4 mmHg after termination of pneumoperitoneum. PaCO2 and pH during pneumoperitoneum were 35 +/- 1.7 mmHg and 7.41 +/- 0.02, respectively. There were no significant differences in either mean PaCO2--PetCO2 or PaCO2 and pH during various phases of laparoscopy.

Conclusions
Capnography is adequate to guide ventilation during laparoscopic surgery in pregnant patients. Respiratory acidosis did not occur when PetCO2 was maintained at 32 mmHg during carbon dioxide pneumoperitoneum.
Acute Opioid Tolerance
Authors: Guignard Bruno , Bossard Anne Elisabeth , Coste Carole , Sessler Daniel I. , Lebrault Claude , Alfonsi Pascal , Fletcher Dominique , Chauvin Marcel 
Published: November 2003

Background
Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement.

Methods
Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 microg. kg-1. min-1 and desflurane titrated to autonomic responses (desflurane group). All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients-who were also blinded to group assignment-controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h.

Results
The mean remifentanil infusion rate was 0.3 +/- 0.2 microg. kg-1. min-1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg (25-75% interquartile range, 19-59; P < 0.01).

Conclusions
Relatively large-dose intraoperative remifentanil increased postoperative pain and morphine consumption. These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia.
Subarachnoid Meperidine (Pethidine) Causes Significant Nausea and Vomiting during Labor
Authors: Booth John V. , Lindsay David R. , Olufolabi Adeyemi J. , El-Moalem Habib E. , Penning Donald H. , Reynolds James D. 
Published: November 2003

Background
The combined spinal-epidural (CSE) technique using bupivicaine-fentanyl has become an established method of pain control during parturition. One limitation is the relatively short duration of effective analgesia produced by bupivicaine-fentanyl. In contrast, subarachnoid meperidine has been shown to provide a long duration of anesthesia in nonobstetric patients. Therefore, the authors tested the hypothesis that subarachnoid meperidine produces a significant increase in the duration of analgesia compared with bupivicaine-fentanyl.

Methods
Based on a power analysis of preliminary data, the authors intended to recruit 90 patients for the study, randomized to three groups: 2.5 mg bupivicaine-25 microg fentanyl, 15 mg meperidine, or 25 mg meperidine. However, after enrolling 34 patients, the study was discontinued because of a significant increase in nausea or vomiting in the study patients.

Results
Nausea or vomiting was substantially increased in both meperidine groups compared with the bupivicaine-fentanyl group: 16 with nausea or vomiting in the meperidine groups (n = 21), compared with 1 in the bupivicaine-fentanyl group (n = 11), P = 0.0011. The mean duration of analgesia provided by 25 mg meperidine was 126 +/- 51 min, compared with 98 +/- 29 min for bupivicaine-fentanyl and 90 +/- 67 min for 15 mg meperidine. These data were not significant (P = 0.27).

Conclusions
Although intrathecal meperidine could potentially prolong subarachnoid analgesia during labor, its use was associated with a significant incidence of nausea or vomiting. These data do not support the use of subarachnoid meperidine in doses of 15 or 25 mg for labor analgesia.
Propofol Selectively Attenuates Endothelium-dependent Pulmonary Vasodilation in Chronically Instrumented Dogs
Authors: Kondo Uruo , Kim Si-Oh , Murray Paul A. 
Published: November 2003

Background
The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state.

Methods
Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators.

Results
Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation.

Conclusion
These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.
Effects of Propofol on Hippocampal Synaptic Transmission in Behaving Rats
Authors: Tanner Kylie M. , Obasi Chinyere , Herrick Ian A. , Leung L. Stan 
Published: November 2003

Background
The action of propofol has been studied in vitro and in vivo, but the effects of intravenously administered propofol on synaptic transmission in freely behaving rats have not been studied before.

Methods
Rats were implanted with recording electrodes in the dentate gyrus and with stimulation electrodes in the medial perforant path (MPP). Paired pulses at different interpulse intervals (IPIs) were delivered to the MPP, and average evoked potentials were recorded in the dentate gyrus before and after a bolus of propofol (10 or 20 mg/kg administered intravenously) or control vehicle was injected via femoral vein cannula. Because of the layered structure of the hippocampus, population excitatory postsynaptic potentials and population spikes could be distinguished and analyzed.

Results
Propofol has no significant effect on the population excitatory postsynaptic potentials or population spike evoked by a single MPP stimulus pulse. However, paired-pulse inhibition of the dentate population spikes was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the population spike was most prominent when tail pinch response was lost (deep and moderate anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired-pulse facilitation of population spikes was observed during moderate anesthesia in most rats.

Conclusions
In freely behaving rats, intravenous propofol enhanced paired-pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric acid A receptor-mediated inhibition. Propofol also increased paired-pulse facilitation at 200 ms IPI through an unknown mechanism, which may contribute to the neuroexcitatory effect of propofol.
Effect of Pretreatment with Intrathecal Excitatory Amino Acid Receptor Antagonists on the Development of Pain Behavior Caused by Plantar Incision
Authors: Pogatzki Esther M. , Zahn Peter K. , Brennan Timothy J. 
Published: November 2003

Background
Drugs that block spinal excitatory amino acid receptor activation may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the present study, we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors (mGluRs) on the development of pain behavior after plantar incision.

Methods
Rats with lumbar intrathecal catheters were anesthetized with halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response frequencies to a blunt mechanical stimulus applied directly to the wound were measured before incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days.

Results
Preincision treatments with antagonists against the NMDA (MK-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development of mechanical hyperalgesia caused by incision. Preincision treatment with the non-NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on postoperative day 1 compared with the vehicle group; response frequencies were reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an additional group, postincision treatment with NBQX was similar to preincision treatment.

Conclusion
Spinal NMDA and mGluR antagonists may not be useful for preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain behaviors, but a preventive effect using preincision treatment was not apparent.