Enhancing anaesthetic care for the elderly

As the elderly population continues to grow, safety considerations in this demographic undergoing general anaesthesia are paramount given their increased susceptibility to perioperative complications. Although widely used, propofol has been associated with adverse events such as hypotension, bradycardia, respiratory depression and delayed emergence. Remimazolam, with its shorter duration of action and titratable effects, may offer a safer anaesthetic option with a reduced risk of prolonged sedation and haemodynamic instability. A recent meta-analysis, coupled with trial sequential analysis, comparing remimazolam with propofol in individuals over 60 years old, provides new insights into this field of research.1 The review, which included 11 randomised controlled trials (RCTs; n = 947 patients) suggested that compared with propofol, remimazolam was associated with lower incidences of postinduction and intraoperative hypotension and bradycardia.1 Remimazolam was also associated with a higher heart rate, longer time to loss of consciousness, higher bispectral index and a lower incidence of injection pain. Interestingly, there were no differences in the mean arterial blood pressure, emergence time, extubation time or incidence of emergence agitation between propofol and remimazolam. The trial sequential analysis demonstrated that the required information size was achieved for hypotension. It adds to recent similar meta-analyses and confirms previous evidence that remimazolam is associated with less hypotension compared with midazolam and propofol both during procedural sedation and general anaesthesia in both young and old patient populations.2–4 Unfortunately, the selected cut-off age of 60 years was relatively low, and the meta-analysis failed to distinguish between patients with or without serious comorbidities. However, given the increased susceptibility of elderly patients to haemodynamic fluctuations and the risks associated with hemodynamic instability in a potentially frail population, maintaining stable blood pressure and heart rate during anaesthesia is crucial. However, using hypotension as an outcome measure to choose between propofol and remimazolam for anaesthesia in the elderly has several limitations. Hypotension, defined simply as low blood pressure, is a nonspecific outcome measure that may be influenced by various factors beyond the choice of anaesthetic agent. Elderly patients often have preexisting conditions such as cardiovascular disease, dehydration, bleeding, anaemia, or autonomic dysfunction, which can predispose them to hypotension irrespective of the anaesthetic used. Therefore, attributing hypotension solely to the anaesthetic agent may not accurately reflect its causal role. Although hypotension is a clinically relevant event that requires prompt management, its occurrence alone may not necessarily correlate with adverse outcomes. The severity and duration of hypotensive episodes, as well as their impact on patient outcomes such as organ perfusion and postoperative morbidity, need to be considered as well. Simply counting hypotensive events without evaluating their clinical significance may provide a skewed representation of the safety profile of the anaesthetic agents. Remember, most anaesthetics used in clinical practice cause hypotension, particularly in the elderly. However, this may suggest that remimazolam could be safer than propofol for older and more fragile patients, particularly those who struggle with tolerating hypotension. Future RCTs will provide further clarity on this matter. Variability in the definition and threshold for hypotension across studies also poses challenges in interpreting and comparing results. Differences in monitoring techniques, such as invasive arterial blood pressure monitoring versus noninvasive methods, may further confound the interpretation of hypotension as an outcome measure. Interestingly, mean arterial blood pressure was similar between propofol and remimazolam groups in the meta-analysis by Pereira et al.1 Although minimising hypotension is an important clinical goal, it is just one aspect of anaesthesia management in elderly patients. Other outcomes, such as recovery time, postoperative cognitive function and incidence of respiratory complications, may be equally or more clinically relevant. Importantly, in this meta-analysis, recovery characteristics were similar between propofol and remimazolam. Although the current evidence to some extent supports the potential benefits of remimazolam in elderly patients undergoing general anaesthesia, further research is warranted. Additionally, it is worth mentioning that remimazolam can be used safely in this population, and that it might have a role in procedural sedation by nonanaesthetists as well, which is not the case for propofol in certain countries. Moreover, remimazolam's pharmacokinetics are largely unaffected by renal and hepatic disease, which are much more prevalent in the elderly population. Prospective studies should focus on elucidating optimal dosing regimens, intraoperative monitoring protocols and long-term outcomes, including postoperative cognitive function and mortality rates. The doses of propofol administered in the studies analysed were relatively high compared with those of remimazolam. Consequently, it is plausible that the propofol and remimazolam doses utilised in these studies were not equivalent in potency. This supposition gains further credence from the observation that the time taken to achieve loss of consciousness was longer, and the bispectral index was higher among patients administered remimazolam. Assessing the overall incidence and severity of adverse events, including cardiovascular events, respiratory events, allergic reactions, and drug-related complications and neurocognitive outcomes, is essential for evaluating the safety profiles of remimazolam and propofol in elderly patients. Ultimately, the most important outcome measure regarding remimazolam and propofol in the elderly should align with clinical priorities, patient preferences and healthcare objectives (including economics), emphasizing a comprehensive approach that considers multiple, clinically relevant endpoints to inform evidence-based anaesthesia decision-making and optimize perioperative care outcomes. A more comprehensive approach considering multiple, clinically relevant outcomes is necessary to provide a nuanced understanding of the comparative efficacy and safety of these two drugs. Although both agents have demonstrated comparable efficacy in achieving adequate sedation levels for procedural success, the economic implications cannot be overstated. Propofol, owing to its decades-long tenure in clinical practice and availability in generic formulations, often carries a lower price tag, rendering it a financially appealing option for healthcare facilities. Conversely, remimazolam, being a newer entrant, may come with a higher upfront cost, potentially posing challenges in resource-constrained healthcare systems. The economic analysis must be juxtaposed with considerations of safety and side effects. The capacity of remimazolam to mitigate adverse events and expedite recovery could translate into long-term cost savings by reducing postoperative complications and hospital length of stay or increasing turnover in busy units. The authors of this meta-analysis acknowledge its limitations. Variability in study methodologies, patient populations, dosing and outcome measures may introduce biases and confounders into the analysis. Additionally, long-term outcomes and rare adverse events are not adequately captured within the scope of short-term clinical trials. Moving forward, clinicians and healthcare policymakers must carefully weigh these factors to optimise anaesthesia protocols and ensure the best possible outcomes for elderly patients while managing healthcare costs responsibly. Undoubtedly, new sedatives and anaesthetic agents such as remimazolam have a role to play in modern, patient-centred sedation and anaesthesia. Finding the correct role and niche is the challenge of the upcoming years.