Median effective dose of remifentanil for awake laryngoscopy and intubation

Background Awake intubation requires an anesthetic management that provides sufficient patient safety and comfort, adequate intubating conditions, and stable hemodynamics. In this prospective clinical study, our aim was to determine the median effective dose （ED50） of remifentanil in combination with midazolam and airway topical anesthesia for awake laryngoscopy and intubation. Methods Thirty-six female adult patients, scheduled for elective plastic surgery under general anesthesia requiring orotracheal intubation were included in this study. Ten minutes after intravenous administration of midazolam 0.1 mg/kg, patients were assigned to receive remifentanil in bolus, followed by a continuous infusion. The bolus dose and infusion rate of remifentanil were adjusted by a modified Dixon＇s up-and-down method. Patient＇s reaction score at laryngoscopy and an Observer＇s Assessment of Alertness/Sedation Scale （OAA/S） were used to determine whether the remifentanil dosage regimen was accepted. During laryngoscopy, 2% lidocaine was sprayed into the airway to provide the topical anesthesia. ED50 of remifentanil was calculated by the modified Dixon up-and-down method, and the probit analysis was then used to confirm the results obtained from the modified Dixon＇s up-and-down method. In the patients who were scored as ＂accept＂, patient＇s OAA/S and reactJon scores at dJfferent observed points, JntubatJng conditJon score and patient＇s tolerance to the endotracheal tube after intubation were evaluated and recorded. Blood pressure and heart rate at different measuring points were also noted. Results ED50 of remifentanil for awake laryngoscopy and intubation obtained by the modified Dixon＇s up-and-down method was （0.62±0.02） μg/kg. Using probit analysis, ED50 and ED95 of remifentanil were 0.63 μg/kg （95% CI, 0.54-0.70） and 0.83 μg/kg （95% CI, 0.73-2.59）, respectively. Nineteen patients who were scored as ＂accept＂ had an OAA/S of 〉15 and tolerated well laryngoscopy without significant discomfort or gagging. The mean intubating condition score was 1.8±0.8. The endotracheal tube was well tolerated. During awake laryngoscopy and intubation, blood pressure and heart rate were also kept stable. The postoperative follow up showed that no patient recalled discomfort and pain for airway manipulation. Conclusions When combined with midazolam 0.1 mg/kg and airway topical anesthesia, ED50 of remifentanil for successful awake laryngoscopy and Jntubation is 0.62 μg/kg in bolus followed by continuous infusJon of 0.062 μg·kg·min^-1. This sedation and analgesia regimen can provide patient safety and comfort, ensure adequate intubating conditions, maintain hemodynamic stability, and prevent negative recall of the airway procedure.

Development of three Drosophila melanogaster strains with different sensitivity to volatile anesthetics

Background The 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. Methods Median effective doses （ED50） 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 （$1）. So did median ones of percentile 48-52 for breeding median offspring （M1）, resistant ones of percentile 91-95 for breeding resistant offspring （R1）. Process was repeated through 31 generations, in the 37th generation, S37, M37 and R37 were used to determine ED5o for enflurane, isoflurane, sevoflurane, desfiurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED50 values were correlated with minimum alveolar concentration （MAC） values in human. Results From 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, ED50 values in three strains correlated directly with MAC values in human. Conclusions Three Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED50 are directly correlated with MAC in human for eight volatile anesthetics.

Selective breeding of mice strains with different sensitivity to isoflurane

Background The mechanisms of action of volatile anesthetics are still unknown. Recently, the use of genetics as a means to investigate anesthetic action has increased in scale. However, only limited forward genetic approach studies were performed in mammals, especially with volatile anesthetics as the selection agent. In the present study, a selective breeding process was designed to produce strains of mice with different sensitivity to isoflurane. Methods One hundred and sixty male and female virgin outbred ICR/CD-1 mice at 65-70 days of age were selected as original generation, and the median effective dose （ED50） of inhaled isoflurane were measured by probit analysis with the loss of righting reflex as the endpoint of anesthesia. The most sensitive males and females were selected and mated one another randomly, as with the most resistant males and females. Thus two branches of mice （sensitive and resistant to isoflurane） were created and allowed to produce the next generation. At 65-70 days of age, screening experiment was performed in offspring, by selecting the most sensitive mice in sensitive branch and the most resistant mice in resistant branch. Selected males and females within each branch were mated one another randomly to produce the following generation. The same procedure was performed in the offspring. The process of screening and breeding was repeated for 8 generations, and then strains were conserved by mating the offspring one another randomly within each branch for 3 generations. Each pair of mice was allowed to produce the second litters as a backup, and isoflurane EDs0 was measured in mice from the second litters. Results Isoflurane righting reflex ED5os （95% confidence limit （CL）） in original mice were 0.65% （0.58%-0.72%） in females and 0.63% （0.56%-0.69%） in males. After the 4th generation, isoflurane ED50S in resistant branch were significantly higher than those in sensitive branch （P 〈0.05）, for both in females and males. In the 11th generation, isoflurane ED50 in the two branches differed by 32% in females and 36% in males. Conclusions After 8 generations of selective breeding and 3 generations of strain conservation, two strains of mice with high and low sensitivity to isoflurane were developed. The separation of inhaled anesthetic requirement in parents could be transferred to the offspring in mice.