Citations

Background The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity). Method The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine. Results The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence. Conclusions Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.

Background Halothane and other volatile anesthetics relax airway smooth muscle in part by decreasing the amount of force produced for a particular intracellular calcium concentration (the Ca2+ sensitivity) during muscarinic receptor stimulation. In this study, ketamine, propofol, and midazolam were evaluated to determine whether the inhibitory effect of volatile anesthetics on this signal transduction pathway is a general property of other types of anesthetic drugs. Methods A beta-escin permeabilized canine tracheal smooth muscle preparation was used. Ketamine, propofol, and midazolam, in concentrations producing near-maximal relaxation in intact airway smooth muscle (200 microM, 270 microM, and 100 microM, respectively), were applied to permeabilized muscles stimulated with calcium in either the absence or the presence of muscarinic receptor stimulation provided by acetylcholine. The effect of halothane also was evaluated. Results Confirming previous studies, halothane (0.75 mM) decreased calcium sensitivity during muscarinic receptor stimulation. None of the intravenous anesthetics studied affected Ca2+ sensitivity, either in the absence or the presence of muscarinic receptor stimulation. Conclusions Intravenous anesthetics in high concentrations directly relax canine tracheal smooth muscle without affecting Ca2+ sensitivity. The inhibition of agonist-induced increases in Ca2+ sensitivity of canine tracheal smooth is not a common property of anesthetics, but is unique to volatile agents.

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.

AbstractSurgical treatment for adrenal disease may be withheld from elderly patients because of concern about prohibitive operative morbidity and mortality. To obtain objective data in our practice, we analyzed the results of adrenalectomy for patients aged 65 years and older. From 1984 to 1993 there were 85 patients (41 men, 44 women) with ages ranging from 65 to 84 years (median 69 years) who underwent adrenalectomy for Cushing syndrome (n= 19), pheochromocytoma (n= 16), adrenocortical carcinoma (n= 7), benign adenoma (n= 26), or primary hyperaldosteronism (n= 17) at our institution. Median follow‐up was 26 months (range 1 month to 9.1 years). A retrospective review with respect to preoperative risks and postoperative morbidity and mortality was performed utilizing the American Society of Anesthesiologists (ASA) physical status classification and the modified Goldman multifactorial cardiac risk scheme. Survival was estimated by the Kaplan‐Meier methods. Operative mortality was 7% (six patients). No patients with pheochromocytoma or primary hyperaldosteronism died during the postoperative period. Patients undergoing adrenalectomy for adrenocortical carcinoma had a significantly higher operative mortality (43%) (p= 0.006). Postoperative complications developed in 19 patients (22%), and there was a reoperation rate of 6% (5 patients). Nineteen percent of patients required postoperative intensive care admission and had a median stay of 2 days (range, 1–38 days). Median hospital stay was 7 days (range 3–47 days). Seventy‐three patients (86%) remained alive at study completion. Two‐ and five‐year survivals were 86% and 84%, respectively. Goldman class II or greater was an excellent predictor of increased morbidity (p= 0.032) and mortality (p= 0.036). With the exception of adrenocortical carcinoma, adrenal surgery for elderly patients can be performed with acceptable morbidity and mortality. The Goldman multifactorial cardiac risk scheme reliably predicts postoperative outcome in this elderly group of patients.