Effective dose of remimazolam co-administered with remifentanil to facilitate I-gel insertion without neuromuscular blocking agents: an up-and-down sequential allocation trial.

BACKGROUND: Remimazolam is a new anesthetic drug developed and is an ultra-short-acting agent with rapid onset and offset. The pharmacology of this drug seems to be ideal for short surgeries eligible for I-gel insertion. Therefore, this study aimed to determine the optimal bolus dose of remimazolam for I-gel insertion when co-administered with remifentanil without neuromuscular blocking agents (NMBAs). METHODS: Patients aged 19-65 years with American Society of Anesthesiologists physical status I or II scheduled for general anesthesia were enrolled. The first dose of remimazolam was 0.15 mg/kg and remifentanil was co-administered at an effect-site concentration (Ce) of 3.0 ng/mL. The dose of remimazolam for the following patient was decreased or increased by 0.05 mg/kg depending on the success or failure of I-gel insertion in the previous patient. RESULTS: The remimazolam bolus dose required for successful I-gel insertion in 50% of adult patients using modified Dixon's up-and-down method with remifentanil Ce 3.0 ng/mL and no NMBAs was 0.280 ± 0.048 mg/kg. Isotonic regression analysis showed that the 50% and 95% effective doses were 0.244 (83% confidence interval [CI] 0.213-0.313) mg/kg and 0.444 (95% CI 0.436-0.448) mg/kg, respectively. The mean time to loss of consciousness (Modified Observer's Assessment of Alertness/Sedation score < 2) was 52.2 s. Three patients (12.0%) showed a reduction in systolic blood pressure of more than 30% from baseline. CONCLUSIONS: Selecting the appropriate dose of remimazolam/remifentanil without NMBAs makes it feasible to insert the I-gel. TRIAL REGISTRATION: This study protocol was registered at http://cris.nih.go.kr (KCT0007801, 12th, October, 2022).

The Effect of Ramosetron on Remifentanil in Preventing Emergence Cough from Sevoflurane Anesthesia in Female Patients.

BACKGROUND: Remifentanil reduces cough during extubation. Ramosetron, a 5-HT3 receptor antagonist, is a potent antiemetic. Regarding the antitussive property of 5-HT receptor agonists, ramosetron can mediate the cough reflex by increasing the remifentanil requirement. This study evaluated the effect of ramosetron on the optimal effect-site concentration (Ce) of remifentanil for preventing emergence cough from sevoflurane anesthesia in female patients. METHODS: Forty-seven randomly selected female patients undergoing laparoscopic cholecystectomy received either ramosetron 0.3 mg (n = 23) or the same volume of normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce using target-controlled infusion in 50% of patients (EC50) and 95% of patients (EC95) were assessed using Dixon's up-and-down or isotonic regression method with a bootstrapping approach. RESULTS: Using Dixon's up-and-down method, the EC50 of remifentanil in the control group (1.33 ± 0.38 ng/mL) was comparable to that of ramosetron group (1.50 ± 0.69 ng/mL) (P = 0.615). Using isotonic regression analysis, the EC50 (83% confidence interval) did not differ between the two groups (1.17 [0.86-1.43] ng/mL and 1.13 [0.68-1.56] ng/mL in control and ramosetron groups). However, the EC95 (95% confidence interval) was significantly lower in the control group than in the ramosetron group (1.90 [1.45-1.96] ng/mL and 2.92 [2.35-2.97] ng/mL). CONCLUSION: Remifentanil Ce for preventing emergence cough was higher in the ramosetron group than in the control group. It may indicate the lowering effect of ramosetron on the antitussive activity of remifentanil.

Determination of the 95% effective dose of remimazolam to achieve loss of consciousness during anesthesia induction in different age groups.

BACKGROUND: Remimazolam is a new ultra short-acting benzodiazepine originally developed as an improved version of midazolam. Recent studies have demonstrated non-inferiority of remimazolam to propofol in general anesthesia. However, to date, few studies have investigated the induction bolus dose of remimazolam required to achieve general anesthesia. We aimed to determine the 95% effective dose (ED95) of remimazolam bolus required to achieve loss of consciousness (LOC) and the appropriate doses for different age groups. METHODS: Patients aged 20-79 years with the American Society of Anesthesiologists physical status of I or II were enrolled in this study. A total of 120 patients were included representing young, middle-aged, and elderly groups. Loss of eyelash reflex and verbal response after the administration of remimazolam was considered successful LOC. The ED95 of remimazolam was determined using a biased coin up-and-down design with sequential allocation and the isotonic regression method. RESULTS: The ED95 of remimazolam for induction of general anesthesia was 0.367 mg/kg (95% CI [0.277, 0.392]) in the young group, 0.369 mg/kg (95% CI [0.266, 0.394]) in the middle-aged group, and 0.249 mg/kg (95% CI [0.199, 0.288]) in the elderly group. During the study period, none of the patients required rescue medications for hypotension or bradycardia. CONCLUSIONS: This study investigated the ED95 of remimazolam bolus for anesthesia induction. The precise dosing of the ED95 can help maintain hemodynamic stability during the induction of anesthesia.

Age- and sex-dependence of five major elements in the development of human scalp hair.

BACKGROUND: Human scalp hair is composed of bio-synthesized protein that stores and excretes excess elements from the body. Thus, the concentration of major and trace elements in the hair may provide insight into both the physiology and health status of humans. Monitoring of health status by hair analysis is limited by the uncertainty surrounding natural changes in composition based on age and sex parameters. METHODS: A total of 322 hair samples from subjects aged 0-89 years were collected and analyzed to determine their sulfur, calcium, magnesium, zinc, and copper concentrations by inductively coupled plasma mass spectrometry. The age- and sex-dependence of the concentrations of these elements within scalp hair was evaluated. Age-dependence was analyzed by least squares fitting of the data from young people (up to 25 years old). Sex-dependence was evaluated by comparing the average element concentrations of males and females in each age groups. RESULTS: The concentration of mineral elements increased with age up to 25 years old. Calcium and magnesium contents were strongly affected by age, whereas the effects were weaker for zinc and copper. In participants over 20 years old, sex and the concentrations of calcium and magnesium were significantly associated. The concentrations of these elements were higher in most of the subgroups of adult women. The concentrations of sulfur, zinc, and copper were not significantly associated with age or sex. CONCLUSIONS: The concentrations of major inorganic elements in scalp hair showed an increasing trend up to 25 years of age, and a strong sex dependence of calcium and magnesium concentrations in the subjects older than 20 years. More research is needed to understand the physiology of calcium and magnesium excretion though scalp hair.