Effects of changing from sevoflurane to desflurane on the recovery profile after sevoflurane induction: a randomized controlled study.

PURPOSE: Desflurane has the lowest solubility of currently available volatile anesthetics and may allow for more rapid emergence and recovery compared with sevoflurane. Nevertheless, after volatile induction with sevoflurane, it has not been determined whether the use of desflurane provides faster emergence and recovery. The present study aimed to elucidate the effects of changing from sevoflurane to desflurane during the early part of anesthesia. METHODS: Fifty-two patients who were scheduled for vitreous surgery with general anesthesia were enrolled in this randomized controlled study. Anesthesia was induced with volatile induction consisting of 100% oxygen (6 L·min(-1)) and 5% sevoflurane. For anesthesia maintenance, patients were randomized to receive 1-2% sevoflurane or 3-6% desflurane. In the desflurane group, the anesthetic agent was changed from sevoflurane to desflurane within five minutes following endotracheal intubation. After surgery, we assessed the following endpoints: the times from discontinuing volatile anesthetics to eye opening, obeying the command to squeeze the investigator's hand, tracheal extubation, and orientation to the patients' full name, date, and place. RESULTS: Emergence and recovery were significantly faster in the desflurane group than in the sevoflurane group in times to mean (SD) eye opening [6.5 (2.9) vs 10.1(3.0) min, respectively; mean difference, 3.6 min; 95% confidence interval (CI), 1.9 to 5.3; P < 0.001], obeying commands [6.6 (2.7) vs 10.1 (3.1) min, respectively; mean difference, 3.5 min; 95% CI, 1.9 to 5.2; P < 0.001], and tracheal extubation [7.0 (2.5) vs 10.6 (3.0) min, respectively; mean difference, 3.6 min; 95% CI, 1.9 to 5.1; P < 0.001]. Similarly, the times from discontinuation of volatile anesthetics to orientation to the patients' full name, date, and place were significantly shorter in the desflurane group compared with the sevoflurane group. There were no significant differences between groups on a 100-mm visual analogue scale assessing postoperative nausea and vomiting, eye pain, and patient satisfaction regarding anesthesia. CONCLUSION: Changing the anesthetic agent from sevoflurane to desflurane after sevoflurane induction provides faster emergence and recovery compared with sevoflurane anesthesia. This study protocol was registered at http://www.umin.ac.jp/ctr/index.htm , (UMIN000009941).

Enhanced effects of isoflurane on the long QT syndrome 1-associated A341V mutant.

BACKGROUND: The impact of volatile anesthetics on patients with inherited long QT syndrome (LQTS) is not well understood. This is further complicated by the different genotypes underlying LQTS. No studies have reported on the direct effects of volatile anesthetics on specific LQTS-associated mutations. We investigated the effects of isoflurane on a common LQTS type 1 mutation, A341V, with an unusually severe phenotype. METHODS: Whole cell potassium currents (IKs) were recorded from HEK293 and HL-1 cells transiently expressing/coexpressing wild-type KCNQ1 (α-subunit), mutant KCNQ1, wild-type KCNE1 (ß-subunit), and fusion KCNQ1 + KCNE1. Current was monitored in the absence and presence of clinically relevant concentration of isoflurane (0.54 ± 0.05 mM, 1.14 vol %). Computer simulations determined the resulting impact on the cardiac action potential. RESULTS: Isoflurane had significantly greater inhibitory effect on A341V + KCNE1 (62.2 ± 3.4%, n = 8) than on wild-type KCNQ1 + KCNE1 (40.7 ± 4.5%; n = 9) in transfected HEK293 cells. Under heterozygous conditions, isoflurane inhibited A341V + KCNQ1 + KCNE1 by 65.2 ± 3.0% (n = 13) and wild-type KCNQ1 + KCNE1 (2:1 ratio) by 32.0 ± 4.5% (n = 11). A341V exerted a dominant negative effect on IKs. Similar differential effects of isoflurane were also observed in experiments using the cardiac HL-1 cells. Mutations of the neighboring F340 residue significantly attenuated the effects of isoflurane, and fusion proteins revealed the modulatory effect of KCNE1. Action potential simulations revealed a stimulation frequency-dependent effect of A341V. CONCLUSIONS: The LQTS-associated A341V mutation rendered the IKs channel more sensitive to the inhibitory effects of isoflurane compared to wild-type IKs in transfected cell lines; F340 is a key residue for anesthetic action.

Partial restoration of the long QT syndrome associated KCNQ1 A341V mutant by the KCNE1 ß-subunit.

BACKGROUND: The A341V mutation in the pore-forming KCNQ1 subunit of the slowly activating delayed-rectifier potassium current (IKs) underlies a common form of the long QT syndrome, and is associated with an unusually severe phenotype. However, there is controversy regarding the underlying mechanism responsible for the clinically observed phenotype. We investigated the biophysical characteristics of A341V in a cardiac environment by utilizing a cardiac cell line, and in particular the impact of the KCNE1 ß-subunit. METHODS: Whole-cell current were recorded from transiently transfected HL-1 cells, a cardiac cell line. Mutant KCNQ1 and KCNE1 were constructed by site-directed mutagenesis. RESULTS: The A341V mutant resulted in a non-functional channel when expressed alone. When co-expressed with wild type KCNE1, A341V produced a slowly activating current, with a smaller current density, slower rates of activation, and a depolarized shift in its activation curve compared to the wild type KCNQ1+KCNE1. Confocal microscopy confirmed the surface expression of GFP-tagged A341V, suggesting a functionally defective protein. A T58A mutation in KCNE1 abolished functional restoration of A341V. Under heterozygous conditions, the expression of A341V+KCNQ1+KCNE1 reduced but did not abolish the electrophysiological changes observed in A341V+KCNE1. A dominant negative effect of A341V was also observed. Action potential simulations revealed that the A341V mutation is arrhythmogenic. CONCLUSIONS: The KCNE1 ß-subunit partially rescued the non-functional A341V mutant, with electrophysiological properties distinct from the wild type IKs. GENERAL SIGNIFICANCE: The severity of the A341V phenotype may be due to a combination of a significant suppression of the IKs with altered biophysical characteristics.

Efficacy of intrathecal morphine with epidural ropivacaine infusion for postcesarean analgesia.

STUDY OBJECTIVE: To evaluate the analgesia following cesarean delivery and the frequency of side effects of intrathecal morphine when combined with a continuous epidural infusion. DESIGN: Randomized, double-blinded study. SETTING: University hospital. PATIENTS: 76 ASA physical status I and II term parturients undergoing cesarean delivery with combined spinal-epidural anesthesia. INTERVENTIONS: Patients were randomized to one of three groups to receive 0, 50, or 100 microg (Group 0, Group 50, and Group 100, respectively) intrathecal morphine in addition to 8 mg of hyperbaric bupivacaine. Each patient received a continuous epidural infusion of 0.2% ropivacaine at the rate of 6 mL/hr. MEASUREMENTS: 24-hour visual analog pain scores (VAPS), number of patients who requested rescue analgesics, frequency of requests for rescue analgesics per patient, and time interval before the first request for rescue analgesics were recorded. Frequency of pruritus and postoperative nausea and vomiting (PONV) were also recorded. MAIN RESULTS: Group 50 and Group 100 patients exhibited lower VAPS and longer time intervals before the first request for rescue analgesics, and they requested rescue analgesics less frequently than Group 0 patients. The frequency of pruritus was significantly higher in Group 100 than Group 0. The groups did not differ with regard to PONV. CONCLUSIONS: 50 microg and 100 microg of intrathecal morphine improve analgesia when combined with a continuous epidural infusion of 0.2% ropivacaine (6 mL/hr) after cesarean delivery. 50 microg of intrathecal morphine is associated with a low frequency of side effects such as pruritus and PONV.