Forty patients who met the eligibility criteria were enrolled to the study between November 2021 and February 2022, and randomly assigned to either the remimazolam or propofol group. All patients completed the protocol and were included in the primary endpoint analysis. Two patients in the propofol group were excluded from CO and SV analyses due to lack of esCCO data (Fig. 1).
Characteristics of patients in the groups are listed in Table 1. All patients in the two groups achieved loss of consciousness with the dose of anesthetics specified in the protocol.
Table 1
Demographic and clinical characteristics of patients
Characteristics | Remimazolam (n = 20) | Propofol (n = 20) |
Age, years | 67 (10) | 62 (10) |
Sex, male/female | 6/14 | 4/16 |
ASA-PS, 1/2 | 5/15 | 4/16 |
Height, cm | 157.8 (5.7) | 157.5 (6.0) |
Body weight, kg | 59.2 (8.9) | 57.1 (9.4) |
BMI | 23.7 (2.6) | 23.1 (3.7) |
Hypertension, ± | 11/9 | 7/13 |
Antihypertensive drug, ± | 11/9 | 6/14 |
Values are mean (standard deviation, SD) or the number of patients. |
n, number; ASA-PS, American Society of Anesthesiologists physical status; BMI, body mass index. |
MAP tended to decrease after induction in both the groups, without significant differences between the groups (-41.1 [16.4] mmHg and − 42.8 [10.8] mmHg in remimazolam and propofol group, respectively; mean difference: 1.7 mmHg [95% CI: -8.2 to 4.9]; p = 0.613). Further, HR, CO, and SV tended to decrease after induction of anesthesia in both the groups, without significant differences between the groups (HR: -9.6 [6.6] bpm and − 13.8 [9.9] bpm, p = 0.129; CO: -18.4 [10.8]% and − 24.6 [12.2]%, p = 0.101; SV: -12.7 [8.4]% and − 10.1 [5.7]%, p = 0.262; in the remimazolam and propofol groups, respectively) (Table 2).
Table 2
Hemodynamic changes after induction
Characteristics | Remimazolam (n = 20) | Propofol (n = 20) | Mean difference (95% CI) | p |
MAP changes, mmHg | -41.1 (9.6) | -42.8 (10.8) | -1.7 (-8.2 to 4.9) | 0.613 |
HR changes, bpm | -9.6 (6.6) | -13.8 (9.9) | 4.2 (-1.3 to 9.6) | 0.129 |
CO changes, % | -18.4 (10.8) | -24.5 (12.2) | 6.2 (-1.7 to 13.7) | 0.101 |
SV changes, % | -12.7 (8.4) | -10.1 (5.7) | -2.6 (-7.2 to 2.0) | 0.262 |
Values are the mean (standard deviation, SD). |
n, number; CI, confidence interval; MAP, mean arterial pressure; HR, heart rate; bpm, beats per minute; CO, cardiac output; SV, stroke volume. |
The remimazolam group had a significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; mean difference: 1.8 min [95% CI: 0.8 to 2.6] p < 0.001). The time until loss of consciousness had no significant effect on MAP and SV decline (MAP: F[1, 37] = 0.311, p = 0.580; SV: F[1, 36] = 2.49, p = 0.123), without significant differences between the groups despite adjusting the time until loss of consciousness (MAP: F[1, 37] = 0.535, p = 0.469; SV: F[1, 36] = 3.43, p = 0.072). The time until loss of consciousness significantly affected HR and CO decline after induction of anesthesia (HR: F[1, 37] = 5.00, p = 0.031; CO: F[1, 36] = 9.17, p = 0.005), and the degree of decline increased proportional to time until loss of consciousness. However, changes in HR and CO were not significantly different between the groups despite adjusting time until loss of consciousness (HR: F[1, 37] = 0.011, p = 0.916, CO: F[1, 36] = 0.05, p = 0.824). According to ANCOVA, the time until loss of consciousness and anesthesia group were not significantly associated for all variables (Table 3, Fig. 2).
Table 3
Effects of anesthetic group allocation and time until loss of consciousness on hemodynamic changes after induction of anesthesia
Characteristics | Estimate | Std. error | 95% CI | p value |
MAP changes, mmHg | | | | |
Intercept | -42.3 | 3.1 | -48.7 to -35.9 | < 0.001 |
Anesthetic group | -2.8 | 3.9 | -10.9 to 5.1 | 0.469 |
Times until LoC | 0.7 | 1.3 | -1.8 to 3.3 | 0.580 |
HR changes, mmHg | | | | |
Intercept | -5.9 | 2.4 | -10.8 to -0.9 | 0.021 |
Anesthetic group | -0.3 | 3.1 | -6.5 to 5.9 | 0.916 |
Times until LoC | -2.1 | 1.0 | -4.2 to 0.2 | 0.031 |
CO changes, % | | | | |
Intercept | -11.7 | 3.2 | -18.2 to -5.3 | < 0.001 |
Anesthetic group | 0.9 | 4.1 | -7.4 to 9.2 | 0.82 |
Times until LoC | -3.9 | 1.3 | -6.5 to -1.3 | 0.005 |
SV changes, % | | | | |
Intercept | -10.4 | 2.2 | -14.8 to -6.0 | < 0.001 |
Anesthetic group | 5.1 | 2.8 | -0.5 to 10.7 | 0.072 |
Times until LoC | -1.4 | 0.9 | -3.2 to 0.4 | 0.123 |
Std, standard; CI, confidence interval; LoC, loss of consciousness; MAP, mean arterial pressure; HR, heart rate; CO, cardiac output; SV, stroke volume. |
The remimazolam group tended to have a lower frequency of hypotension (MAP < 65 mmHg over 2.5 min) than propofol group (7 cases [35%] and 11 cases [55%], respectively, p = 0.341). Ephedrine was used when hypotension persisted for > 2.5 min; its administration successfully treated postoperative complications related to hypotension, such as myocardial and kidney injuries, in all patients.