Citations

Background Volatile anesthetics relax airway smooth muscle (ASM) by altering intracellular Ca2+ concentration ([Ca2+]i). The authors hypothesized that relaxation is produced by decreasing sarcoplasmic reticulum Ca2+ content via increased Ca2+ "leak" through both inositol trisphosphate (IP3) and ryanodine receptor channels. Methods Enzymatically dissociated porcine ASM cells were exposed to acetylcholine in the presence or absence of 2 minimum alveolar concentration (MAC) halothane, and IP3 levels were measured using radioimmunoreceptor assay. Other cells were loaded with the Ca2+ indicator fluo-3 and imaged using real-time confocal microscopy. Results Halothane increased IP3 concentrations in the presence and absence of acetylcholine. Inhibition of phospholipase C blunted the IP3 response to halothane. Exposure to 2 MAC halothane induced a transient [Ca2+]i response, suggesting depletion of sarcoplasmic reticulum Ca2+. Exposure to 20 microM Xestospongin D, a cell-permeant IP3 receptor antagonist, resulted in a 45+/-13% decrease in the [Ca2+]i response to halothane compared with halothane exposure alone. In permeabilized cells, Xestospongin D or 0.5 mg/ml heparin decreased the [Ca2+]i response to halothane by 65+/-13% and 68+/-22%, respectively, compared with halothane alone. In both intact and permeabilized cells, 20 microM ryanodine blunted the [Ca2+]i response to halothane by 32+/-13% and 39+/-21%, respectively, compared with halothane alone. Simultaneous exposure to Xestospongin D and ryanodine completely inhibited the [Ca2+]i response to halothane. Conclusions The authors conclude that halothane reduces sarcoplasmic reticulum Ca2+ content in ASM cells via increased Ca2+ leak through both IP3 receptor and ryanodine receptor channels. Effects on IP3 receptor channels are both direct and indirect via elevation of IP3 levels.

Background The goal of this project was to study the frequency and natural history of perioperative lower extremity neuropathies. Methods A prospective evaluation of lower extremity neuropathies in 991 adult patients undergoing general anesthetics and surgical procedures while positioned in lithotomy was performed. Patients were assessed with use of a standard questionnaire and neurologic examination before surgery, daily during hospital stay in the first week after surgery, and by phone if discharged before 1 postoperative week. Patients in whom lower extremity neuropathies developed were observed for 6 months. Results Lower extremity neuropathies developed in 15 patients (1.5%; 95% confidence interval, 0.8-2.5%). Unilateral or bilateral nerves were affected in patients as follows: obturator (five patients), lateral femoral cutaneous (four patients), sciatic (three patients), and peroneal (three patients). Paresthesia occurred in 14 of 15 patients, and 4 patients had burning or aching pain. No patient had weakness. Symptoms were noted within 4 h of completion of the anesthetic in all 15 patients. These symptoms resolved within 6 months in 14 of 15 patients. Prolonged positioning in a lithotomy position, especially for more than 2 h, was a major risk factor for this complication (P = 0.006). Conclusions In this surgical population, lower extremity neuropathies were infrequent complications that were noted very soon after surgery and anesthesia. None resulted in prolonged disability. The longer patients were positioned in lithotomy positions, the greater the chance of development of a neuropathy. These findings suggest that a reduction of duration of time in lithotomy positions may reduce the risk of lower extremity neuropathies.