[Effect of landiolol hydrochloride for intraoperative tachycardia--multicenter questionnaire study].

BACKGROUND: The purpose of this study was to evaluate effects of landiolol hydrochloride, which is an ultra-short-acting beta-1 selective blocker, for intraoperative tachycardia and to establish practical methods of administration of the drug. METHODS: We retrospectively examined by multicenter questionnaires the effects and practical methods of administration of landiolol for 100 patients who showed tachycardia needing treatment during anesthesia. The techniques for anesthesia and administration of landiolol were entrusted to each anesthesiologist. RESULTS: One case was excluded because the dose of landiolol hydrochloride was uncertain. Fifty-nine patients received an intravenous bolus injection of landiolol, and continuous injection was performed in 34 patients. Six patients had both bolus and continuous injections. In the 99 patients, heart rate was significantly reduced to desired levels. The time required to reduce heart rate by more than 10% after injection was shorter in the bolus group than in the continuous group. Bolus injection, however, did not reduce blood pressure. Although low-dose continuous administration significantly reduced blood pressure, treatment for increasing blood pressure was not needed in any of the patients. CONCLUSIONS: Information obtained by the questionnaire suggests that bolus injection and/or low-dose continuous administration of landiolol, which are not described in the drug information documents, are effective and safe for treatment of tachycardia during anesthesia.

Differential pressor response to intravenous ephedrine during recovery from deliberate hypotension.

STUDY OBJECTIVE: To determine whether nitroglycerin or trimethaphan alters pressor response to intravenous (i.v.) ephedrine. DESIGN: Prospective, randomized study. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA physical status I female patients scheduled for mastectomy. INTERVENTIONS: Patients were assigned to one of six groups (n = 10 in each). Group 1: nitroglycerin + normal saline (NS) i.v., Group 2: nitroglycerin + ephedrine 0.1 mg/kg i.v., Group 3: nitroglycerin + ephedrine 0.15 mg/kg i.v., Group 4: trimethaphan + NS i.v., Group 5: trimethaphan + ephedrine 0.1 mg/kg i.v., and Group 6: trimethaphan + ephedrine 0.15 mg/kg i.v. MEASUREMENTS: Hemodynamic responses to ephedrine following withdrawal of vasodilators were observed for 15 minutes. MAIN RESULTS: Ephedrine increased heart rate and mean blood pressure. After ephedrine 0.1 mg/kg i.v., the maximum pressor response in the trimethaphan group was approximately twofold that of the nitroglycerin group (p = 0.038). CONCLUSIONS: Ephedrine restored BP more easily in those patients who had received trimethaphan compared with those who had received nitroglycerin for deliberate hypotension.

Role of prostaglandin receptor subtype EP1 in prostaglandin E2-induced nociceptive transmission in the rat spinal dorsal horn.

It has been indicated that prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the facilitated generation of nociception. This study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the nociceptive transmission, using behavioral and intracellular calcium ion concentration ([Ca2+]i) assays and in situ hybridization. Experiments were conducted on Sprague-Dawley rats. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated using von Frey filament. The effect of an intrathecally administered selective EP1 antagonist, 6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid (ONO-8711), on the intrathecal PGE2-induced hyperalgesia was examined. In [Ca2+]i assays, we measured [Ca2+]i in the dorsal horn of spinal cord slices and examined the effects of PGE2 and ONO-8711 perfusion on the [Ca2+]i changes. In situ hybridization using EP1 digoxigenin probe was performed on the slice sections of the lumbar spinal cord and bilateral L4 and L5 dorsal root ganglions (DRGs). Mechanical hyperalgesia was observed after intrathecal PGE2 administration. Intrathecal administration of ONO-8711 attenuated the PGE2-induced mechanical hyperalgesia in a dose- and time-dependent manner. Perfusion of ONO-8711 markedly suppressed PGE2-induced [Ca2+]i increment in laminae II-VI in dorsal horn of the spinal cord slice. Moreover, in situ hybridization revealed EP1 hybridization signals in the DRG neurons, but not in the spinal cord. The results of this study suggested that spinal PGE2 activates the EP1 receptors existing on the central terminals of primary afferents, subsequently increasing in [Ca2+]i in the spinal dorsal horn, which are involved in the mechanisms of spinal PGE2-induced nociceptive transmission.

[Pneumothorax during laparoscopic adrenal surgery: a case report].

A 55-year-old female patient was scheduled for laparoscopic adrenal surgery. In the operating room, anesthesia was induced with propofol and maintained with nitrous oxide/sevoflurane and epidural anesthesia. The operation was completed uneventfully. After tracheal extubation, Spo2 decreased suddenly from 98 to 92% and chest auscultation revealed weaker breathing sound on the left side. Left pneumothorax and pneumomediastinum were noticed on a chest X-ray. The pneumothorax in this case was thought to have been caused by passage of insufflation gas through the retroperitoneum to the mediastinum and thoracic cavity or by a minor injury of diaphragm. Although pneumothorax complication in laparoscopic surgery is rare, the frequency of its occurrence in laparoscopic adrenal surgery appears to be higher than other laparoscopic operations and may be due to the organ's location in the retroperitoneum near the diaphragm. Attention should be paid to the possibility of pneumothorax occurring during laparoscopic adrenal surgery even if there is no apparent surgical injury.

Role of prostaglandin receptor EP1 in the spinal dorsal horn in carrageenan-induced inflammatory pain.

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.

The effects of intrathecal administration of an antagonist for prostaglandin E receptor subtype EP(1) on mechanical and thermal hyperalgesia in a rat model of postoperative pain.

UNLABELLED: Despite substantial advances in understanding acute pain mechanisms and in the treatment of pain, postoperative pain, especially mechanically evoked pain (incident pain), is generally not effectively treated. Tissue injury and inflammation increase the release of prostaglandin E(2) in the spinal cord, contributing to the development of hyperalgesia. We designed the present study to determine whether the intrathecal administration of an antagonist for prostaglandin E(2) receptor subtype EP(1), ONO-8711, has an analgesic effect on incision-induced mechanical and thermal hyperalgesia. A 1-cm longitudinal skin incision was made in the plantar aspect of the rat foot. The withdrawal threshold to mechanical stimulation and the withdrawal latency to thermal stimulation applied adjacent to the wound of the hindpaw were investigated. Both mechanical and thermal hyperalgesia were observed at 2 h and 24 h after the incision had been made. ONO-8711 (50, 80, 100 micro g) or saline was administered intrathecally. ONO-8711 significantly increased the withdrawal thresholds to mechanical stimulation, but not to thermal stimulation, in a dose- and time-dependent manner. We conclude that EP(1) receptor-mediated sensitization of the spinal dorsal horn may contribute to the generation of mechanical, but not thermal, hyperalgesia and that an EP(1) receptor antagonist administered intrathecally is a potential analgesic for postoperative pain, especially mechanically evoked pain (incident pain). IMPLICATIONS: We examined the effects of an intrathecally administered selective EP(1) receptor antagonist on mechanical and thermal hyperalgesia in a postoperative pain model. The intrathecal EP(1) receptor antagonist inhibited the mechanical, but not thermal, hyperalgesia, indicating the potential for an EP(1) receptor antagonist to be used as an analgesic for postoperative pain, especially incident pain.

Effects of a novel selective agonist for prostaglandin receptor subtype EP4 on hyperalgesia and inflammation in monoarthritic model.

BACKGROUND: Cytokines have crucial role in the development and maintenance of inflammation and pain in arthritis. Activation of prostaglandin receptor subtype EP(4) suppresses cytokine production in immune cells. The purpose of this study was to evaluate whether a novel EP(4) agonist would be able to suppress thermal and mechanical hyperalgesia and paw swelling in acute and chronic phases in rat monoarthritic model. METHODS: Monoarthritis was induced by an injection of complete Freund's adjuvant (CFA) intracapsularly into the tibiotarsal joint of the rats. Withdrawal latencies to thermal stimulation on the hind paw, withdrawal thresholds to mechanical stimulation, paw volume, and ankle diameter were measured 24 h and 4 weeks after the CFA injection. A novel selective EP(4) receptor agonist, ONO-AE1-329 (10, 25, or 50 microg) or saline was administered intracapsularly into the joint. RESULTS: Withdrawal latencies and withdrawal thresholds were significantly (P < 0.05) shortened and decreased, respectively, on the arthritic side but not on the contralateral side 24 h and 4 weeks after the CFA injection. In addition, significant (P < 0.05) increases in paw volume and ankle diameter on the arthritic side were observed. Intracapsularly administered ONO-AE1-329 showed significant (P < 0.05) inhibition of thermal and mechanical hyperalgesia and significant (P < 0.05) decrease in paw volume and ankle diameter in a dose-dependent manner at 24 h and 4 weeks after CFA. CONCLUSION: Intracapsular administration of EP(4) receptor agonist effectively inhibited mechanical and thermal hyperalgesia and inflammatory reactions in acute and chronic monoarthritis. An EP(4) agonist would be a potential strategy for inflammatory pain in arthritis.