What Are the Latest Advances in Esketamine's Clinical Applications?

Esketamine, a derivative of ketamine, has emerged as a promising adjunct in the perioperative management of elderly patients, offering benefits such as enhanced analgesia, improved hemodynamic stability, and potential reductions in postoperative complications. This article reviews its pharmacological properties, clinical applications, and implications for geriatric anaesthesia.

Last updated: 06 November 2023 (BST)

Key Takeaways

• Esketamine provides effective sedation and analgesia with minimal respiratory depression.
• It helps maintain hemodynamic stability in elderly patients during surgery.
• Esketamine may reduce postoperative pain and the need for opioids.
• This medication has potential antidepressant effects, addressing perioperative mood disorders.
• Research indicates its role in improving sleep quality and cognitive recovery post-surgery.

Introduction to Esketamine and Its Relevance

Population aging has resulted in a growing demand for geriatric medical care, particularly concerning surgical procedures. Elderly patients often present with multiple comorbidities and reduced physiological resilience, making them susceptible to a range of perioperative complications, including cardiovascular events and cognitive dysfunction. Consequently, there is a pressing need for anaesthetic protocols that enhance safety and outcomes in this demographic. Esketamine, first marketed in China in November 2019, has garnered attention due to its unique pharmacological profile. Unlike traditional intravenous sedatives, esketamine offers effective analgesia while exerting minimal effects on respiratory and circulatory functions. Its ability to stimulate sympathetic nerves can be particularly advantageous during anaesthesia induction, where maintaining hemodynamic stability is crucial.

Pharmacological Properties of Esketamine

Esketamine is the S-enantiomer of ketamine, possessing a higher affinity for N-methyl-D-aspartate receptors (NMDARs) compared to its counterpart, R-ketamine. This increased potency translates to enhanced sedative and analgesic effects, with fewer associated psychomimetic side effects. The multifaceted mechanism of action of esketamine also includes modulation of opioid receptors and various neurotransmitter systems, contributing to its efficacy in pain management and mood enhancement. Recent pharmacokinetic studies have shown that esketamine reaches peak plasma concentrations rapidly, with a shorter half-life compared to ketamine, making it suitable for procedural sedation in elderly patients who may have limited physiological reserves. Importantly, esketamine's metabolites exhibit pharmacological activity, further supporting its analgesic properties.

Effect of Esketamine on Perioperative Hemodynamics in Elderly Patients

Elderly patients often experience impaired peripheral perfusion and hypotension during anaesthesia induction, increasing the risk of adverse postoperative outcomes. Studies indicate that administering esketamine (0.2–0.5 mg/kg) as an adjunct to traditional sedatives like propofol can significantly improve hemodynamic stability. For instance, research by Tu et al. demonstrated that esketamine combined with propofol resulted in better cognitive recovery and fewer adverse effects in elderly patients undergoing surgery. Moreover, the sympathomimetic effects of esketamine can counteract the hypotensive effects commonly seen with other anaesthetic agents, making it a valuable addition to anaesthesia protocols for geriatric patients.

Effect of Esketamine on Intraoperative and Postoperative Analgesia in Elderly Patients

Postoperative pain remains a significant concern, particularly in the elderly, where inadequate pain control can exacerbate complications. Esketamine has shown promise as a non-opioid analgesic, reducing opioid consumption and associated side effects. A meta-analysis of multiple studies confirmed that intravenous esketamine significantly lowers pain scores and opioid requirements in the early postoperative period. In various surgical contexts, including gastrointestinal and orthopaedic procedures, esketamine has effectively reduced postoperative pain and improved recovery outcomes. For example, in a study involving total hip arthroplasty, patients receiving esketamine experienced lower pain ratings and reduced opioid use compared to those receiving conventional analgesics.

Effect of Esketamine on Postoperative Depression in Elderly Patients

Perioperative depression is prevalent among elderly patients and can hinder recovery. Esketamine's rapid antidepressant effects have been investigated as a potential intervention for postoperative mood disorders. Studies indicate that esketamine administration may lead to lower levels of pro-inflammatory cytokines associated with depressive symptoms, thereby enhancing recovery and quality of life post-surgery. Furthermore, research suggests that esketamine can elevate levels of brain-derived neurotrophic factor (BDNF) and serotonin, both of which are implicated in mood regulation. This positions esketamine as a dual-action agent that can address both pain and mood disturbances in perioperative care.

Effect of Esketamine on Postoperative Sleep Disturbance in Elderly Patients

Postoperative sleep disturbances are common in elderly patients and can adversely affect recovery. Esketamine may play a role in mitigating these disturbances due to its unique effects on sleep architecture. Animal studies have shown that esketamine can enhance slow-wave sleep, which is crucial for recovery. Clinical investigations have begun to evaluate esketamine's impact on sleep quality in postoperative settings. Preliminary results indicate that esketamine may improve sleep outcomes, particularly following thoracic surgery, highlighting its potential as an adjunct in managing postoperative sleep disorders.

Effects of Esketamine on Perioperative Neurocognitive Dysfunction in Elderly Patients

Cognitive dysfunction after surgery is a significant concern for elderly patients, manifesting as postoperative delirium or cognitive decline. While esketamine's psychoactive properties raise concerns about potential cognitive impairment, emerging evidence suggests it may have neuroprotective effects. Studies have indicated that esketamine could reduce the incidence of postoperative delirium and promote cognitive recovery, although results have been mixed. Further investigation is necessary to understand the optimal dosing and timing of esketamine to maximise its protective effects on cognitive function during the perioperative period.

Adverse Events

While generally well tolerated, esketamine can produce side effects, including transient hypertension, neuropsychiatric symptoms such as agitation and hallucinations, and gastrointestinal disturbances. The potential for elevated blood pressure necessitates careful monitoring, particularly in elderly patients with pre-existing cardiovascular issues. Optimising dosing strategies—such as using lower doses for elderly patients—can help mitigate these risks. Future research should focus on establishing clear guidelines for the safe use of esketamine in this vulnerable population.

Summary and Future Directions

Esketamine is rapidly becoming an integral part of the anaesthetic management of elderly patients, recognised for its ability to improve analgesia, hemodynamic stability, and even mood and cognitive outcomes. However, the optimal dosing strategies and long-term effects of esketamine require further exploration. Future studies are essential to validate the findings surrounding esketamine's benefits and to develop comprehensive protocols for its use across various surgical settings. As the geriatric population continues to grow, the need for effective and safe anaesthetic strategies will only increase, making research in this area crucial.

FAQs

What is esketamine and how is it used in elderly patients?

Esketamine is a derivative of ketamine used for sedation and analgesia. In elderly patients, it helps maintain hemodynamic stability and reduces opioid requirements during and after surgery.

What are the benefits of using esketamine in perioperative care?

Esketamine provides effective pain relief, enhances mood, improves sleep quality, and may reduce the risk of postoperative complications such as delirium and cognitive dysfunction.

Are there any side effects associated with esketamine?

Common side effects include transient increases in blood pressure, neuropsychiatric symptoms like agitation, and gastrointestinal issues. Monitoring is essential, especially in elderly patients.

How does esketamine compare to traditional anaesthetics?

Esketamine has a unique profile that allows for effective analgesia with fewer respiratory depressant effects compared to traditional anaesthetics, making it safer for elderly patients.

What is the future of esketamine in geriatric anaesthesia?

Future research will focus on optimising dosing strategies and exploring esketamine's long-term effects, with the goal of enhancing postoperative recovery in the elderly population.

As the landscape of geriatric anaesthesia evolves, esketamine's role will likely expand, highlighting the importance of ongoing research to ensure the best outcomes for elderly patients. #GeriatricCare #Anaesthesia #Esketamine