Effect of Subanesthetic Dose of Esketamine on Sleep Quality in Patients with Breast Cancer After Chemotherapy

In 2020, breast cancer became the most common cancer worldwide. Treatment methods for breast cancer include surgery, chemotherapy, and endocrine therapy, with surgery remaining the primary treatment option. The emergence of neoadjuvant chemotherapy has expanded the indications for breast cancer surgery, providing surgical opportunities for patients with late-stage clinical staging and a strong desire for breast preservation. Neoadjuvant chemotherapy has the effects of reducing tumor size, lowering clinical staging, assessing the tumor's sensitivity to chemotherapy drugs, and inhibiting tumor cell proliferation. However, chemotherapy, while treating the disease, also causes numerous adverse reactions that directly or indirectly lead to sleep disturbances in patients.

Sleep disturbances reduce cognitive function, immune function, and quality of life in breast cancer chemotherapy patients, with an incidence of sleep disturbances during chemotherapy reaching 80%. These patients, when undergoing surgery, are highly prone to postoperative sleep disturbances (Postoperative Sleep Disturbance, PSD) due to factors such as preoperative sleep disturbances, fear and anxiety about surgery, inflammatory responses, and pain. This negatively impacts their recovery process.

PSD refers to changes in sleep structure and quality in the early postoperative period. It is a clinical syndrome characterized by disturbances in the sleep-wake rhythm following surgery, leading to abnormal sleep quality or sleep behavior, usually manifesting as reduced rapid eye movement (REM) sleep, prolonged wakefulness, and fragmented sleep. There is no unified standard for the duration of PSD, as it varies according to disease type, surgical procedure, and individual differences. Generally, it occurs within a short time after surgery, such as 1-3 days postoperatively. PSD significantly affects the postoperative circadian rhythm, pain levels, inflammatory responses, cognitive function, and cardiovascular outcomes, leading to prolonged recovery time. Clinically, both pharmacological and non-pharmacological interventions are used, with pharmacological treatments primarily involving benzodiazepines, which increase sleep duration and reduce sleep latency. Studying short-term sleep disturbances helps identify and reduce postoperative complications, such as delirium, infections, and cardiovascular events, thus accelerating recovery, improving patient safety, and promoting multidisciplinary collaboration. However, there is limited research on the preventive improvement of sleep quality.

Esketamine, a non-competitive N-methyl-D-aspartate receptor (NMDA) antagonist, is the right-handed isomer of ketamine. It shares a similar pharmacological mechanism with ketamine, but its potency is higher. The most important effect of esketamine is its ability to inhibit the NMDA receptor-mediated glutamate entry into the GABA nervous system, causing excitability changes in the cortex and limbic system, ultimately leading to loss of consciousness. Sub-anesthetic doses of esketamine (0.5 mg/kg, 40-minute intravenous infusion) have been shown to produce rapid and sustained antidepressant effects in patients with treatment-resistant major depressive disorder (MDD).

Additionally, intravenous administration of esketamine at 0.2-0.4 mg/kg (single infusion over 40 minutes) has demonstrated rapid and potent antidepressant effects in the treatment of refractory depression. Apart from its antidepressant effects, esketamine has been proven to improve sleep disturbances in patients with MDD and sleep issues, suggesting that esketamine has potential as a treatment for sleep disorders. Some studies indicate that the antidepressant effect of esketamine is related to the neurobiological structure of wakefulness, sleep, and circadian rhythms. Animal studies also suggest that esketamine can modulate the NF-κB signaling pathway and oxidative stress, inhibiting the release of downstream inflammatory factors, thereby reducing surgical-induced inflammatory damage and playing an anti-anxiety, antidepressant role to improve postoperative recovery quality. However, it remains unclear whether continuous low-dose infusion of esketamine during surgery can reduce the incidence of PSD. This study aims to investigate the impact of continuous infusion of esketamine during surgery on postoperative sleep quality in patients undergoing modified radical mastectomy for breast cancer.