BACKGROUNDThe mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODSMedian effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTSFrom a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONSThree Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Anesthetics, Inhalation ; pharmacology ; Animals ; Chloroform ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; Enflurane ; pharmacology ; Female ; Halothane ; pharmacology ; Isoflurane ; analogs & derivatives ; pharmacology ; Male ; Methoxyflurane ; pharmacology ; Methyl Ethers ; pharmacology ; Trichloroethylene ; pharmacology

BACKGROUND: Sevoflurane and desflurane are widely used anesthetics and can be simulated in pharmacokinetic models. These models are related to steady state pharmacokinetics, As anesthetic elimination is a non-steady state process, we evaluated the elimination data of volatile anesthetics using a two-compartment model (bi-exponential function). 50, 80, and 90% context-sensitive decrement times were evaluated with this function. These times are related to awakening and cognitive function recovery. METHODS: Forty-eight healthy patients were enrolled for minimal surgery under general anesthesia. They were randomly anesthetized with either sevoflurane or desflurane. At the end of surgery, when the administration of the volatile anesthetics was discontinued, end-tidal concentrations (PE) were recorded for 15 minutes. We calculated and analyzed the fraction of anesthetic concentrations (PE/PE0) using a bi-exponential function (PE0: the last end-tidal concentration of anesthetics during anesthesia). RESULTS: A bi-exponential function was fit to the elimination data using non-linear mixed-effect modeling. It showed that the anesthetic duration had effects on the coefficients of early and late components and not on the log rate constants. The coefficient of late components increased and the coefficient of early components decreased with prolonged anesthetic duration. Irrespective to the type of anesthetics, prolonged anesthesia did not affect the context-sensitive half-life; however, a prolonged period of time was required to reach 80 and 90% decrement after prolonged anesthesia. CONCLUSIONS: Prolonged anesthetic duration slowed down the elimination of volatile anesthetics. It delayed awakeness and a return to normal cognitive function after anesthesia.
Anesthesia ; Anesthesia, General ; Anesthetics ; Humans ; Isoflurane ; Methyl Ethers

Halothane, isoflurane and desflurane are metabolized to hepatotoxic trifluoroacetyl proteins. But sevoflurane is metabolized to hexafluoroisopropanol. Hexafluoroisopropanol has a low binding affinity for liver protein and is therefore rapidly converted to glucuronidate that are excreted in the urine. Thus sevoflurane has been considered to have a very low potential for hepatotoxicity. We report a case of a 67 years old woman who developed acute hepatic dysfunction after sevoflurane anesthesia.
Anesthesia ; Female ; Halothane ; Humans ; Isoflurane ; Liver ; Methyl Ethers ; Propanols ; Proteins

No abstract available.
Anesthesia ; Dihydroergotamine ; Methyl Ethers

BACKGROUND:Rocuronium is widely used because of rapid onset and intermediate duration of action.The volatile anesthetics potentiate the effect of nondepolarizing muscle relaxants. This study was designed to compare effects of inhalational agents with that of propofol on the muscle relaxation of rocuronium. METHODS:One hundred and thirty-six patients were divided four groups, which were given sevoflurane, isoflurane, desflurane and propofol.Anesthesia was induced with propofol 2 mg/kg and fentanyl 100microg.A ulnar nerve was stimulated with supramaximal stimuli.Anesthesia was maintained with 1.25 MAC inhalational agents or propofol of 7 mg/kg/hr for twenty minutes.Rocuronium 0.1, 0.15 or 0.2 mg/kg was administered.The degree and onset time of maximal depression was recorded.A supplementary dose of rocuronium was given so that all patients received a cumulative dose of rocuronium 0.6 mg/kg. We measured 10% recovery time. RESULTS:The ED50 of rocuronium were 0.157 in the sevoflurane, 0.167 in the isoflurane, 0.169 in the desflurane, and 0.187 mg/kg in the propofol. The ED95 were 0.296 in the sevoflurane, 0.313 in the isoflurane, 0.325 in the desflurane, and 0.407 mg/kg in the propofol.The onset time to maximal depression was prolonged in inhalational agent groups which were administered rocuronium 0.2 mg/kg. The 10% recovery time was delayed in inhalational agent groups than in propofol group. CONCLUSIONS:The inhalational anesthetics had more potent muscle relaxation effect than propofol.We suggest that the dose of rocuronium for adequate muscle relaxation be adjusted according to anesthetics used.
Androstanols ; Anesthetics ; Depression ; Fentanyl ; Humans ; Isoflurane ; Methyl Ethers ; Muscle Relaxation ; Muscles ; Neuromuscular Blockade ; Propofol ; Ulnar Nerve

BACKGROUND:Rocuronium is widely used because of rapid onset and intermediate duration of action.The volatile anesthetics potentiate the effect of nondepolarizing muscle relaxants. This study was designed to compare effects of inhalational agents with that of propofol on the muscle relaxation of rocuronium. METHODS:One hundred and thirty-six patients were divided four groups, which were given sevoflurane, isoflurane, desflurane and propofol.Anesthesia was induced with propofol 2 mg/kg and fentanyl 100microg.A ulnar nerve was stimulated with supramaximal stimuli.Anesthesia was maintained with 1.25 MAC inhalational agents or propofol of 7 mg/kg/hr for twenty minutes.Rocuronium 0.1, 0.15 or 0.2 mg/kg was administered.The degree and onset time of maximal depression was recorded.A supplementary dose of rocuronium was given so that all patients received a cumulative dose of rocuronium 0.6 mg/kg. We measured 10% recovery time. RESULTS:The ED50 of rocuronium were 0.157 in the sevoflurane, 0.167 in the isoflurane, 0.169 in the desflurane, and 0.187 mg/kg in the propofol. The ED95 were 0.296 in the sevoflurane, 0.313 in the isoflurane, 0.325 in the desflurane, and 0.407 mg/kg in the propofol.The onset time to maximal depression was prolonged in inhalational agent groups which were administered rocuronium 0.2 mg/kg. The 10% recovery time was delayed in inhalational agent groups than in propofol group. CONCLUSIONS:The inhalational anesthetics had more potent muscle relaxation effect than propofol.We suggest that the dose of rocuronium for adequate muscle relaxation be adjusted according to anesthetics used.
Androstanols ; Anesthetics ; Depression ; Fentanyl ; Humans ; Isoflurane ; Methyl Ethers ; Muscle Relaxation ; Muscles ; Neuromuscular Blockade ; Propofol ; Ulnar Nerve

BACKGROUND: Various maneuvers are commonly used to achieve the ideal operative field necessary for successful endoscopic sinus surgery (ESS). There are a few contradictory reports on this subject and the consensus is that propofol anesthesia results in a better or similar surgical field and less or similar amount of bleeding than volatile anesthesia. The aim of this study was to compare the surgical field in patients in whom intravenous anesthesia is used as opposed to balanced general anesthesia. METHODS: Sixty patients undergoing ESS were randomly assigned into three groups, each of which used a different type of anesthesia: propofol/remifentanil (PRO/REM) group, sevoflurane/remifentanil (SEV/REM) group, and desflurane/remifentanil (DES/REM) group. We aimed to maintain the intraoperative mean blood pressure (MBP) at 65 mmHg and the heartrate (HR) at about 75 beats per minute. The quality of visibility of the surgical field was graded, using a validated scoring system, 60 minutes after the start of the operation. RESULTS: All groups had a similar MBP and mean HR at 60 minutes after the operation started. There was no significant differences among the three groups for surgical grade score (P = 0.83). CONCLUSIONS: In this comparative study of three anesthetic combinations (PRO/REM, SEV/REM, and DES/REM) in patients undergoing ESS with controlled BP and HR, we did not observe any significant differences in the surgical grade scores.
Anesthesia ; Anesthesia, Intravenous ; Blood Pressure ; Consensus ; Hemorrhage ; Humans ; Isoflurane ; Methyl Ethers ; Piperidines ; Propofol ; Sinusitis

BACKGROUND: Wake-up tests may be necessary during surgery for kypho-scoliosis to ensure that spinal function remains intact. It is difficult to predict the time when patients can respond to a verbal command. We evaluated the effectiveness of the bispectral index (BIS) and its relation to patients' levels of consciousness in wake-up tests during desflurane and sevoflurane anesthesia. METHODS: Eighteen patients each were enrolled in the desflurane and sevoflurane groups for spinal correction surgery. We measured BIS values, blood pressure, heart rate, and consciousness state and time, at the points when patients responded during the wake-up test. RESULTS: The BIS values when patients made fists upon a verbal command (T3) were 86.7 +/- 7.5 for desflurane and 90.3 +/- 5.4 for sevoflurane. Patients in the desflurane group had significantly shorter wake up delays than those in the sevoflurane group (6.9 +/- 1.8 min vs. 11.8 +/- 3.6 min). However, there was no difference between the groups in the time between the response to a verbal command and the time when a patient moved their toes in response to verbal commands. No recall of the wake-up tests occurred in either group. CONCLUSIONS: The values obtained using the BIS index could to some extent predict the time of a patient's and would be informative during desflurane and sevoflurane anesthesia. Moreover, desflurane permitted faster responses to verbal commands than sevoflurane, and allowed the wake-up test to be performed sooner.
Anesthesia ; Blood Pressure ; Consciousness ; Dietary Sucrose ; Heart Rate ; Humans ; Isoflurane ; Methyl Ethers ; Toes

BACKGROUND: In the Korean National Health Insurance Corporation (KNHIC), payment for inhaled anesthetics are made according to the simulated dose and not the consumed dose. We compare the consumption of inhaled anesthetics according to fresh gas flow (FGF) and anesthetic circuits to compare the consumption of anesthetics and the guidelines for KNHIC payments. METHODS: 161 patients were randomized into six groups who received isoflurane using a closed circuit (group I-C), a semi-closed circuit with FGF 3 L/min (group I-3), or 4 L/min (group I-4), as for the sevoflurane group (group S-C, S-3, and S-4). Mean arterial pressure (MAP) and heart rate (HR) were maintained within +/- 20% of baseline. Minimum alveolar concentration (MAC) and consumption of inhaled anesthetics were recorded by a new anesthetic machine. RESULTS: There were no significant differences among the groups for MAP, HR, and MAC. During anesthesia maintenance, the mean consumption per 15 minutes of inhaled anesthetics was significantly lower in group I-C (1.0 +/- 0.3 ml) than in group I-3 (3.5 +/- 0.7 ml) and than group I-4 (4.9 +/- 0.9 ml) and similar to the sevoflurane groups (group S-C [1.3 +/- 0.4 ml] vs group S-3 [5.3 +/- 1.0 ml] vs group S-4 [6.9 +/- 1.3 ml], respectively; P < 0.05). CONCLUSIONS: In sevoflurane groups, inhaled anesthetics were consumed more than in isoflurane groups. The KNHIC payment guidelines were close to the actual consumption of inhaled anesthetics under using a semi-closed circuit with FGF 3 L/min in sevoflurane and FGF 4 L/min in isoflurane.
Anesthesia ; Anesthetics ; Arterial Pressure ; Heart Rate ; Humans ; Insurance, Health ; Isoflurane ; Methyl Ethers ; National Health Programs

BACKGROUND: Core temperature decreases rapidly after the induction of general anesthesia, because the heat is redistributed to peripheral tissues. Thermoregulatory responses of volatile anesthetics have been tested, but their effects have not been directly compared. Therefore, we evaluated the thermoregulatory responses to sevoflurane, desflurane, and isoflurane. METHODS: Sixty healthy patients scheduled for laparoscopic myomectomy or radical hysterectomy were allocated into three groups; Group S (sevoflurane, n = 20), Group D (desflurane, n = 20), and Group I (isoflurane, n = 20). Anesthesia was maintained with 1 minimum alveolar concentration (MAC) of sevoflurane, desflurane, and isoflurane in a 50/50 mixture of N2O/O2. Patients were maintained in a normovolemic and normocapnic state. The core temperature and forearm minus fingertip skin-temperature gradient (an index of peripheral vasoconstriction) were monitored after the induction of general anesthesia. RESULTS: Each of the seven patients given sevoflurane, desflurane, and isoflurane vasoconstricted at a core temperature of 35.3 +/- 0.5degrees C, 33.6 +/- 0.4degrees C, and 35.2 +/- 0.4degrees C, respectively. The vasoconstriction threshold was the lowest in patients anesthetized with desflurane. The core temperature gradient (Ti-Tf) was significantly higher in patients that were anesthetized with desflurane than in those that were anesthetized with sevoflurane or isoflurane. The core temperature of desflurane was significantly lower than that of sevoflurane or isoflurane 15 minutes after the induction of anesthesia until 180 minutes of anesthesia. CONCLUSIONS: These results indicate that the core temperature is maintained at a higher level in patients that have been anesthetized with sevoflurane or isoflurane than in those that have been anesthetized with desflurane.
Anesthesia ; Anesthesia, General ; Anesthetics ; Forearm ; Hot Temperature ; Humans ; Hysterectomy ; Isoflurane ; Laparoscopy ; Methyl Ethers ; Vasoconstriction