Effects of Esketamine on Oxygenation and Quality of Recovery in Patients Undergoing Thoracoscopic Surgery

Objective：To investigate the effects of esketamine on oxygenation during one-lung ventilation (OLV) and the quality of recovery in patients undergoing thoracoscopic surgery . This study aims to systematically evaluate the clinical efficacy of esketamine and explore its potential advantages in thoracoscopic procedures. The findings are expected to provide new insights into optimizing lung protection strategies during OLV, thereby enhancing perioperative management and improving outcomes for patients undergoing thoracoscopic surgery.

Method：A total of 126 patients undergoing elective thoracoscopic surgery under general anesthesia were randomly divided into three groups: normal saline group (Group C), dexmedetomidine group (Group D), and esketamine group (Group E),with 42 patients in each group.In Group C,an equal volume of normal saline was continuously infused. In Group D,a loading dose of dexmedetomidine (1 μg/kg) was administered 10 min before induction of anesthesia, followed by a continuous infusion at a rate of 0.4 μg·kg-1·h-1 until 30 minutes before the end of the surgery. In Group E, 0.2mg/kg esketamine was infused intravenously before the induction of anesthesia for 10 min, and then maintained at 0.15 mg·kg-1·h-1 until 30 minutes before the end of the surgery. The primary outcome measures of this study were the oxygenation index (OI) at the following time points: before one-lung ventilation (OLV) (T1), 30 minutes after OLV initiation (T2), and 60 minutes after OLV initiation (T3). The secondary outcome measures included: (1)The duration of OLV, blood loss, fluid infusion volume, the dosages of propofol, remifentanil and vasoactive drugs(ephedrine and atropine) were recorded in each group.(2)Heart rate (HR) and mean arterial pressure (MAP) were recorded at the following time points: upon entering the operating room (T0), before OLV (T1), 30 minutes after OLV initiation (T2), 60 minutes after OLV initiation (T3), before extubation (T4), and 5 minutes after extubation (T5).(3)Blood gas anlaysis parameters,airway plateau pressure,tidal volume and positive end-expiratory pressure were recorded from T1 to T3，and dynamic lung compliance and intrapulmonary shunt fraction were calculated.(4) White blood cell counts, neutrophil percentage,and C-reactive protein (CRP) levels were recorded preoperatively and 24 hours postoperatively.(5)Postoperative pain was evaluated using the visual analogue score (VAS) at 2, 6, 12, and 24 hours after surgery, and the number of patients requiring rescue analgesia in each group was recorded. The occurrence of postoperative adverse reactions and postoperative pulmonary complications (PCCs) within one week after surgery were recorded. The postoperative quality of recovery was evaluated using the QOR-15 scale at 24 and 48 hours after surgery,and the postoperative hospital stay was recorded.

Background：According to the cancer statistics report released by the American Cancer Society in 2024, about one in five people will develop cancer in lifetime, and about one in nine men and one in twelve women will die of cancer. Lung cancer is the most commonly occurring cancer worldwide (accounting for 1.4% of all new cases) and is also the leading cause of cancer death (accounting for 18.7% of total cancer deaths), nearly twice second leading cause of cancer death.At present, surgery is the preferred treatment for early-stage lung cancer, and timely and effective surgical treatment can effectively reduce risk of tumor recurrence and metastasis, and improve the survival rate of patients.With the continuous development of modern medical technology, the surgical approach for lung cancer has evolved from traditional open thoracotomy to video-assisted thor surgery (VATS). As a minimally invasive surgery, VATS has many advantages, such as small incision, rapid postoperative recovery, and fewer postoperative. VATS usually requires the use of a double-lumen endobronchial tube (DLT) or a bronchial blocker to perform one-lung (OLV) on the nonoperative side. OLV is a ventilation technique that separates the ventilation pathways of both sides at the level of the carina. The is to collapse the surgical side of the lung and protect the nonoperative side of the lung from contamination, while also facilitating the exposure of the surgical field and reducing the of surgical complications.However,during OLV, the atelectatic lung, although not ventilated, still has blood flow through it, and this blood is not oxygenated, in a mismatch in the ventilation/perfusion ratio (VA/Q), leading to an increase in intrapulmonary shunting and a decrease in oxygenation, which in leads to hypoxemia.Secondly, thoracic surgery is generally performed in the lateral position, and due to the influence of gravity, the patient's ventilation and blood flow distribution uneven, with the shunt fraction reaching as high as 40-50%.Hypoxia and ischemic injury as well as cellular damage can be caused by insufficient ventilation. During the process of restoring blood supply, will also aggravate cellular damage, cause pathological and physiological changes in the lung, trigger ischemia-reperfusion injury, hypoxemia, and then acute inflammatory response oxidative stress response, causing acute injury to a variety of organs. In recent years, with the implementation of lung-protective ventilation strategy, the application and popularization fiberoptic bronchoscopy and video double-lumen bronchial intubation, the incidence of hypoxemia has decreased, but the incidence in thoracic is still 10% to 25%.Strategies to improve hypoxemia include pharmacological reduction of intrapulmonary shunt, improvement of ventilation-perfusion mismatch, and improvement of strategies . The strategy of ventilating the surgical lung is not conducive to the collapse of the surgical lung during thoracoscopy, affecting the exposure of the field. At present, the use of pharmacological intervention is a new idea in the study of improving hypoxemia during OLV of thoracoscopy.

Esketamine, as a new type of intravenous anesthetic, is a high-affinity N-methyl-D-aspartate (NA) receptor non-competitive inhibitor. As the S-enantiomer of ketamine, it has a similar mechanism of action to ketamine, but with a higher for the NMDA receptor and a potency twice that of ketamine. Therefore, compared with traditional ketamine, a smaller dose can achieve the desired anesthetic effect while reducing the incidence of psychotropic side effects. Its effects can produce analgesia, sedation, anti-inflammation, anti-depression, mild respiratory depression and mild circulatory excitation.Esketamine can directly act on the airway smooth muscle, dilate the bronchi and relax the airway through voltage-dependent L-type calcium, effectively relieve bronchospasm, reduce airway resistance, improve lung compliance, and improve ventilation and gas exchange function.Meanwhile, esketamine can inhibit the release of inflammatory cells stimulated by oxygen free radicals, reduce the secretion of various cytokines such as TNFα, IL-6 and IL-8 by white blood cells, inhibit the expression of adhesion factors on the surface of neutrophils and the activity of induc nitric oxide synthase, and promote the secretion of anti-inflammatory cytokines, which can play a multi-level antagonistic role in inflammation.Many studies have suggested that esmolol may be a potential drug intervention to improve perioperative oxygenation.

Dexmedetomidine is a highly selective α2-adrenergic receptor agonist, which mainly produces sedative, analgesic,-anxiety, and sympatholytic effects by acting on the central nervous system, peripheral nervous system, and other organ tissues.Recent studies have shown that dexmedetomidine can reduce the inflammatory response and oxidative stress of thoracic surgery by reducing the levels of plasma,-6, IL-8, TNF-α, and lipid peroxidation in patients, improve the expression of aquaporin in lung tissue of thoracic, increase the concentration of nitric oxide in the blood, dilate the pulmonary vessels on the ventilated side, and effectively reduce intrapulmonary shunting and oxygenation.In addition, dexmedetomidine can directly enhance HPV by targeting α2B receptors in vascular smooth muscle and inducing vasoconstriction in the nonventilated lung, improving the intraoperative oxygenation index, reducing dead space ventilation, improving the dynamic compliance of the lung, and reducing the incidence of postoperative, playing an important role in lung protection.

Based on the above research on esmolol, this study will explore the effects of esmolol on patients' oxygenation and intrapul shunting during single-lung ventilation in thoracoscopy surgery on the basis of previous research, and further clarify the advantages of esmolol in thoracoscopy surgery and provide new clinical basis for optimizing the lung protection strategy during single-lung ventilation in thoracoscopy surgery patients.