Differential effects of remimazolam and propofol on heart rate variability during anesthesia induction

“3 mg/kg being commonly used (Doi et al., 2020; Dai et al., 2021; Liu et al., 2021; Tang et al., 2021; Hari et al., 2022; Hasegawa et al., 2022; Shi et al., 2022) have not been addressed.”

“…not used to assess sedation depth because the application of bispectral monitoring in remimazolam sedation and anaesthesia is still controversial, 49,50 but a good correlation has been determined between the plasma concentration of remimazolam and MOAA/S score, 17 so we adopted this easy-to-use…”

“Sedation studies in adults comparing hemodynamic responses between remimazolam and propofol suggest that only remimazolam preserves the balance between sympathetic and parasympathetic activity during induction [24].”

“Comparing the hemodynamic response to propofol and remimazolam during induction in adults, only remimazolam was determined to balance the sympathetic and parasympathetic response [20].”

“However, other studies indicate that remimazolam has a lower incidence of intraoperative hypotension compared to propofol (8, 9).”

“17 As sedation deepened, the parasympathetic dominance of propofol became apparent.”

“However, it remains unclear whether remimazolam increases sympathetic activity or maintains a balance between sympathetic and parasympathetic activities [26].”

“Remimazolam decreased autonomic nervous activity during anesthesia induction too (Hasegawa et al., 2022).”

“8 However, the mechanism by which remimazolam preserves haemodynamics, including cardiac contractility, remains unclear.”

“This can be attributed to the dominant parasympathetic effect of propofol and the dominant sympathetic effect of midazolam during sedation [18,19].”

“However, no significant difference was observed in SBP and HR between the two groups in this study, which might be since general anesthesia with remimazolam can maintain the balance between sympathetic and parasympathetic nerve activities (Hasegawa et al., 2022) without affecting the cardiac output and evident cardiac…”

“One study had suggested that the administration of remimazolam and propofol had lowered autonomic nerve activity judging by hemodynamic measurements and heart rate variability before and after anesthesia.(33) In patients undergoing cervical conization, bradycardia is a common concern because of the vagal reflex.”

“Based on literature reports and the expert consensus on sedation/anesthesia for the treatment of digestive endoscopy in China [6,11,12], we set the Ramsay sedation score between 5 and 6, BIS between 50 and 70, and RR between 10 and 18 breaths.”

“Thirty patients were recruited in Hasegawa’s study, which reported pulse changes with remimazolam [14].”

“[24] reported that remimazolam showed a lower variability of heart rate during the induction of anesthesia, preserving the balance of sympathetic and parasympathetic activities, while propofol modulated it to sympathetic dominance.”

“This could be due to the modulating effect of remimazolam on the autonomic nervous system, making it more sympathetically innervated and thus stimulating sympathetic arousal, resulting in a slight increase in heart rate, but the duration is short [20].”

“Remimazolam decreased LF and HF but maintained the LF/HF ratio [23].”

“42 Additionally, HRV serves as a monitoring and diagnostic indicator for driver fatigue in the field of vehicle driving.”

“21 This indicates that the hemodynamics of remimazolam are more stable, which is more conducive to reducing surgical stress, maintaining perfusion of transplanted renal blood flow and promoting the recovery of transplanted kidney function.”

“Focusing on the difference between MAP before and after the induction of anesthesia, remimazolam anesthesia results in significantly fewer reductions in MAP over a significantly narrower range than propofol anesthesia [9, 28].”

“32 In contrast, remimazolam appears to preserve hemodynamic stability through sympathetic activation, a characteristic shared with other benzodiazepines, which mitigates its potential depressant effects on cardiovascular function.”

“…has been shown to reduce overall autonomic nerve activity without disturbing the balance between sympathetic and parasympathetic nerve activity during the induction of general anesthesia [8]; however, its impact on autonomic nerve activity associated with surgical stimulation remains unknown.”

“19 22 Thus, we conducted this study to investigate whether remimazolam, compared to conventional propofol intravenous anesthesia, can reduce the incidence of TCR during the PBC procedure.”

“Propofol has been shown to decrease HF across two studies, although it is unclear whether it has an effect on LF: one study concludes that it increases LF [102], while another does not find an effect [103].”

“Remimazolam reportedly preserves the balance between sympathetic and parasympathetic activities more effectively than propofol [29].”

“In the peri-operative setting, practitioners should consider utilising appropriate remimazolam doses as premedication to effectively mitigate the occurrence of hypotension and bradycardia.”

“This observation aligns with the findings of previous studies involving patients without obesity receiving remimazolam infusion, where changes in blood pressure and heart rate were maintained within 20% of the baseline values during anesthesia induction [25,26].”

“It has less impact on autonomic nervous activity [22] and is expected to be safer for use in patients with cardiovascular complications [23, 24].”

“During the induction period, after propofol was administered, most patients presented with a transient increase in HR followed by a decrease, a phenomenon reported in the literature to be due to the predominance of sympathetic innervation by propofol [25].”

“It typically suppresses parasympathetic activity and variably inhibits sympathetic tone, 8– 11 reflected in HRV indices, including reduced high-frequency power and elevated low-to-high frequency ratio (LHR), indicating altered sympathovagal balance.”

“Hasegawa et al. [6] investigated autonomic nervous system function through heart rate variability analysis and reported that remi-mazolam preserved the balance between sympathetic and parasympathetic activities.”

“Hasegawa et al 30 discovered through a randomized controlled trial that compared with propofol, remimazolam can maintain the balance of sympathetic and parasympathetic nerves and keep hemodynamic stability.”

“There were no significant differences observed between Group R and Group P in terms of the postoperative NRS score (2[0, 4] vs. 2[2, 4], P = 0.413) and the sufentanil usage of PCIA (39[31–52] vs. 43 [28– 52 ], µg, P = 0.”

“Unlike propofol, which blunts autonomic reflexes and induces bradycardia, remimazolam preserves baroreflex sensitivity, allowing for physiological heart rate compensation to maintain cardiac output [23].”

“To date, no studies have examined the effects of remima - zolam on autonomic function during anesthesia induction in patients with advanced cardiac pathology; prior work comparing remimazolam and propofol using HRV during induction has largely focused on relatively healthy populations [10].”

“…frequency power, which reflects both sympathetic and parasympathetic activities before and after anesthesia, was less in the remimazolam group than in the propofol group, and propofol broke the balance of sympathetic and parasympathetic activities and modulated it to a sympathetic dominance [10].”

“[7] HRV has been implicated as a predictor of cardiovascular mortality and AIS prognosis, [8‑10] with abnormalities in HRV parameters associated with poststroke complications, stroke severity, and functional outcomes.”