Effect of low-dose esketamine on postoperative quality of recovery in total laparoscopic hysterectomy: a randomized controlled trial.

We enrolled a total of 118 women who underwent gynecological surgery and total hysterectomy, 4 who had surgery cancelled for special reasons before the start of surgery and 8 who changed surgical modality during surgery were excluded, and 106 patients completed the study—53 in group P and 53 in group S. Figure  1 shows the flowchart of the study. There was no statistically significant difference between group P and group S at baseline (Table  1 ). Fig. 1 Flow diagram of the study Table 1 Patient’s characteristics of demographic data Group P ( n  = 53) Group S ( n  = 53) P Age (y) 46.2 ± 10.7 47.6 ± 8.5 0.448 BMI (kg/m 2 ) 24.5 ± 2.8 24.6 ± 3.3 0.916 Operation history 21 (40%) 26 (49%) 0.328 ASA physical status (I/II) 0.353 I 39 (74%) 43 (81%) II 14 (26%) 10 (19%) Menopause or not [ n ( % )] 0.632 Nonmenopause 43 (81%) 41 (77%) Menopause 10 (19%) 12 (23%) Education (primary/middle/high/university) 0.673 Primary 24 (45%) 28 (53%) Middle 15 (28%) 11 (21%) High 11 (21%) 9 (17%) University 3 (6%) 5 (9%) Pathological features Uterine fibroid/cervical intraepithelial neoplasia/adenomyosis 0.917 Uterine fibroid 30 (57%) 32 (60%) Cervical intraepithelial neoplasia 16 (30%) 15 (28%) Adenomyosis 7 (13%) 6 (11%) Preoperative Hb (mg/dl) 126.1 ± 15.1 124.9 ± 19.7 0.732 Preoperative NLR 2.2 ± 0.8 2.1 ± 0.7 0.505 Preoperative CRP (× 10 9 /L) 1.3 (1.0, 1.7) 1.4 (1.1, 1.9) 0.212 ASA , American Society of Anesthesiologists; Hb , hemoglobin; NLR , neutrophil-to-lymphocyte ratio; CRP , C-reactive protein. Data are presented as mean ± SDs, numbers (%), or medians (interquartile range) Flow diagram of the study Patient’s characteristics of demographic data Pathological features Uterine fibroid/cervical intraepithelial neoplasia/adenomyosis ASA , American Society of Anesthesiologists; Hb , hemoglobin; NLR , neutrophil-to-lymphocyte ratio; CRP , C-reactive protein. Data are presented as mean ± SDs, numbers (%), or medians (interquartile range) The generalized estimation equation (GEE) shows that the interaction does not occur at an intermediate time within the group (Wald χ 2  = 6.409, P  = 0.268). No significant differences were found in the QoR-40 scores between groups P and S at the seven different time points ( P  > 0.05). The QoR-40 score of the two groups at six postoperative time points was lower than the baseline value ( P  < 0.05, Fig.  2 ). Fig. 2 The scores of QoR-40 Group P, saline group; group S, esketamine group. The median values are shown as solid lines within the boxes of the 25th and 75th percentile values. Whiskers represent maximum and minimum values. #Compared with baseline within group, P  < 0.05 The scores of QoR-40 Group P, saline group; group S, esketamine group. The median values are shown as solid lines within the boxes of the 25th and 75th percentile values. Whiskers represent maximum and minimum values. #Compared with baseline within group, P  < 0.05 The intraoperative HR was analyzed at different time points. There was a significant interaction effect of time with group ( F  = 3.374, P  < 0.05); in contrast to the control group, the HR of the experimental group was significantly greater at T1, T3, T4, and T5 ( P  = 0.005, P  = 0.023, P  = 0.014, P  = 0.010, Fig.  3 ). Similarly, analysis of the two groups’ intraoperative MBP showed a significant interaction effect of time with group ( F  = 3.141, P  < 0.05); in contrast with the control group, the experimental group had an upper MBP at T3 ( P  < 0.001, Fig.  3 ). Fig. 3 Intraoperative hemodynamic outcomes Group P, saline group; group S, esketamine group. Data are presented as the mean ± SD. *Compared with baseline within group, P  < 0.05 Intraoperative hemodynamic outcomes Group P, saline group; group S, esketamine group. Data are presented as the mean ± SD. *Compared with baseline within group, P  < 0.05 In contrast to those in the control group, the experimental group had significantly reduced refentanil consumption ( P  < 0.05), lower phenylephrine usage and hypotension ( P  = 0.05, P  < 0.001), a lower postoperative NLR ( P  < 0.05), a shorter extubation time and PACU residence time ( P  < 0.001), and a lower NRS score after extubation ( P   0.05, Table S1 ). The control group had a greater 24-h PSQI score than did the experimental group ( P   0.05, Table  3 ). The postoperative 8-h and 48-h NRS scores in the experimental group were inferior to those in the control group ( P  < 0.05, Table  3 ). Table 2 Perioperative data between the two groups Group P ( n  = 53) Group S ( n  = 53) P Consumption of remifentanil (mg) 2.3 ± 0.9 1.6 ± 0.6  < 0.001 Phenylephrine 27 (51%) 13 (25%) 0.005 Number of episodes of hypotension 2 (2, 5) 1 (0, 3)  < 0.001 Extubation time (min) 15.7 ± 5.7 10.8 ± 4.5  < 0.001 PACU dwell time (min) 36.5 ± 8.8 26.2 ± 7.6  < 0.001 NRS score 10 min after extubation 3 (2, 4) 2 (1, 3) 0.006 Postoperative NLR 8.1 (5.2, 10.4) 4.9 (4.1, 7.5) 0.003 NLR neutrophil-to-lymphocyte ratio. Data are presented as mean ± SDs, numbers (%), or medians (interquartile range) Perioperative data between the two groups NLR neutrophil-to-lymphocyte ratio. Data are presented as mean ± SDs, numbers (%), or medians (interquartile range) Table 3 PSQI, HAMD, and NRS scores compared at multiple points in time Group Pre 8h 24h 48h 72h 7d 30d PSQI P 4.2±2.5 - 17.9±2.4 # - 5.3±2.2 4.3±1.9 3.9±2.0 S 3.8±1.9 - 16.8±2.4 * # - 4.8±2.1 4.0±2.0 4.0±1.9 HAMD P 9.6±3.0 - - - 9.3±2.9 9.1±2.7 10.0±3.0 S 10.0±2.8 - - - 9.0±1.8 9.8±1.6 9.8±2.6 NRS P 0(0-0) 5(5-6) # 3(2,4.5) # 2(1,3) # 1(1,2) # 1(0,1) # 0(0-0) S 0(0-0) 4(3,5.5)* # 2(2,4) # 1(1,2)* # 1(0,1) # 0(0,1) # 0(0-0) PSQI, Pittsburgh Sleep Quality Index; HAMD, Hamilton Depression Scale NRS, Numerical Rating Scale; Pre, preoperative baseline; Data are presented as Mean ± SDs or medians (interquartile range). *Compared with group P, P < 0.05; # Compared with baseline, P < 0.05. PSQI, HAMD, and NRS scores compared at multiple points in time PSQI, Pittsburgh Sleep Quality Index; HAMD, Hamilton Depression Scale NRS, Numerical Rating Scale; Pre, preoperative baseline; Data are presented as Mean ± SDs or medians (interquartile range). *Compared with group P, P < 0.05; # Compared with baseline, P < 0.05. The multiple linear regression results shown in Table S2 were the QoR-40 scores of group P and group S at 72 h postoperatively. Through univariate linear regression analysis, we learned that several factors, such as educational attainment, preoperative NLR, preoperative HAMD, and preoperative CRP ( P  < 0.1), correlated with the quality of recovery. However, according to multiple linear regression analysis, education was positively correlated with quality of recovery ( P  < 0.05).

This study was a prospective, single-blind, randomized controlled trial. Ethical approval (XYFY2022-KL067-01) was achieved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Chairperson Tie Xu) on 16 April 2022. The study was registered in the Chinese Clinical Trial Registry before subject enrolment (ChiCTR2100049857). After obtaining ethical approval and obtaining written informed consent from all patients, we recruited 118 women who underwent laparoscopic total hysterectomy under general anesthesia from April 2022 to July 2022. The inclusion criteria were as follows: body mass index < 32, age between 25 and 65 years, and American Society of Anesthesiologists (ASA) physical status I to II. Patients with severe cardiopulmonary dysfunction, an allergy to narcotics, diabetes mellitus, moderate to severe hypertension, severe liver and kidney dysfunction, and anemia ( Hb  < 9.0 mg/dL) were excluded. Intraoperative changes in surgical modalities, postoperative transfer to the ICU, alcoholism, or long-term use of sedative-hypnotic drugs were exclusion criteria as well. All participants were randomly allocated to normal saline (group P) or esketamine (group S) using a tool at www.randomization.com . The randomization was revealed to the researchers when opening an opaque envelope after entering the operating room. Patients were recruited and followed up; data analysts were unaware of the grouping. Patients were taken to the operating room, where routine monitoring, including electrocardiography (ECG), pulse oxygen saturation, and upper-limb mean blood pressure measurements, was established. After intravenous access was achieved, a crystalloid solution was started. All patients received preoxygenation. Anesthesia index (Ai, Pearlcare Anesthesia Depth Monitor, ConView YY-105, Zhejiang Yiyang Medical Technology Co., Ltd.) was recorded to monitor the depth of anesthesia over a range from 0 to 100. The lower the value, the deeper the anesthesia. For patients in group P, a bolus of 0.9% saline (20 ml) was given as placebo, followed by 2 mg/kg propofol, 0.3 µg/kg sufentanil, 0.6 mg/kg rocuronium, and 0.3 mg/kg midazolam. The patients in group S received 0.25 mg/kg esketamine, 2 mg/kg propofol, 0.3 µg/kg sufentanil, 0.6 mg/kg rocuronium, and 0.3 mg/kg midazolam. For anesthesia maintenance, all patients received propofol at a dose of 3–6 mg/kg/h and remifentanil 0.1–0.3 µg/kg/min after intubation. By adjusting the infusion rate of propofol, the Ai values of the two groups were titrated between 40 and 60 (the recommended value). The nasopharyngeal temperature was monitored with a body temperature probe. Intraoperative inspiratory oxygen flow rate was set to 2 l/min, respiratory rate (RR) to 10–15 times/min, and tidal volume (Vt) to 8–10 ml/kg to maintain PetCO 2 between 28 and 35. After the pneumoperitoneum was established, the intra-abdominal pressure was kept between 9 and 13 mmHg. Intraoperative MBP fluctuations were maintained between 30% above and below baseline with ephedrine (3 mg each time), phenylephrine (40 µg each time), and urapidil (5 mg each time). A total of 0.5-mg atropine was used when the HR was < 40 times/min. A total of 0.075-mg palonosetron and 30 mg of ketorolac tromethamine were given to all patients 30 min before the end of the procedure. All intravenous drugs were stopped at the end of the skin suturing. After the procedure, all patients were transferred to a PACU for monitoring and extubation. One milligram of neostigmine and 0.5 mg of atropine were administered to antagonize neuromuscular blockade in patients without contraindications. During the PACU, patients will have their Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) scores, length of PACU stay, and NRS scores. The presence of adverse reactions such as chills, nausea, and vomiting was recorded. Rescue analgesia on the ward consisted of intramuscular injection of 50 mg of bucinnazine. We measured baseline scores of the Quality of Recovery-40 (QoR-40) questionnaire, the Numerical Rating Scale (NRS), and the Pittsburgh Sleep Quality Index (PSQI) before surgery and at 8 h, 24 h, 48 h, and 72 h, 7 days, and 30 days after surgery. Hamilton Depression Scale (HAMD) scores were evaluated preoperatively and at 72 h, 7 days, and 30 days after surgery (the data for 7 days and 30 days were collected via telephone). Mean blood pressure and heart rate were recorded before induction (T0), and 3 min (T1), 5 min (T2), 10 min (T3), and 30 min (T4) after intubation, at the complete end of surgery (T5) and after leaving the PACU (T6). We also recorded preoperative and postoperative nasopharyngeal temperature, time of extubation, PACU stay time, duration of anesthesia, number of episodes of hypotension (MBP less than 30% of the baseline), amount of blood loss, vasoactive drug dosage, preoperative and postoperative neutrophil–lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP) and hemoglobin (Hb) values, the 10-min NRS score after extubation, postoperative adverse effects, and hospital stay. The Quality of Recovery-40 questionnaire has a total score of 200 points and includes 40 questions in 5 categories: each question is scored from 1 to 5, and higher scores indicate higher quality of recovery. The PSQI was used to score 21 out of the 7 areas, with higher scores indicating worse sleep quality. The NRS is represented by 11 numbers from 0 to 10, and patients use 11 numbers from 0 to 10 to describe the intensity of pain; the higher the number is, the more severe the pain. The sample size was calculated based on the work of Lee W. K. et al., [ 13 ] with the QoR-40 score as the primary outcome. There, the QoR-40 score averaged 174 after intravenous anesthesia, with a standard deviation of 17. Assuming that 10 points would improve recovery quality by 15%, 80% power, 5% bilateral significance, and a dropout rate of 20%, 59 patients per arm were required in our trial. PASS 15.0 (software, NCSS, LLC, Kaysville, USA) was used for the estimation. Data normality was assessed by the Shapiro‒Wilk test. The Levene test was used to verify the homogeneity of variance. Normally distributed data are expressed as the mean and standard deviation (SD). Student’s t -test was used for intergroup comparisons. The data collected at multiple points in time were analyzed using repeated-measures analysis of variance (ANOVA). Postoperative scores were compared with baseline values within the group, and the Bonferroni correction was applied for multiple post hoc comparisons. Nonnormally distributed data are represented as medians (interquartile ranges), and comparisons between groups were assessed by the Mann‒Whiney U -test. Nonnormally distributed data collected at multiple points in time, such as the QoR-40 score, were analyzed using the generalized estimated equation (GEE). Categorical variables are described as numbers (%) and were analyzed using the chi-square test. Multiple linear regression analyses were applied for QoR-40 scores 72 h after surgery. A variance inflation factor (VIF) > 10 was considered to indicate statistically significant multicollinearity among the variables. Age, BMI, education, preoperative NLR, preoperative CRP, preoperative Hb, NRS, PSQI, and HAMD were included as independent variables in the univariate linear regression. Univariate linear regression identified factors with P  < 0.1 that were included in the subsequent multivariate linear regression. A P -value less than 0.05 was considered to indicate statistical significance. All the statistical analyses were conducted using SPSS 26.0 (SPSS, Inc., Chicago, IL, USA).

In patients undergoing total laparoscopic hysterectomy, one single injection of low-dose esketamine at anesthesia induction did not affect QoR-40 scores. However, esketamine stabilized intraoperative hemodynamics, decreased intraoperative opioid requirements, and shortened postoperative extubation. It reduced the PACU stay and alleviated postoperative inflammatory response and pain. Use of esketamine was not associated with additional adverse effects.

Rehabilitation occurs when the patient returns to a relatively normal state through gradual recovery of physical function and psychology to achieve independent living and a relatively happy state [ 13 , 16 , 17 ]. Compared with laboratory tests, patient perceptions of a disease are also very important in the clinic, and female patients are more sensitive. Simple uterine fibroids or cervical precancerous lesions are often removed via minimally invasive surgery. This study revealed that low-dose esketamine did not improve the overall quality of recovery after laparoscopic total hysterectomy, but low-dose esketamine could reduce the incidence of intraoperative hypotension, maintain intraoperative hemodynamic stability, and shorten extubation time and PACU stay. Additionally, it reduced short-term postoperative pain levels and postoperative inflammation. Esketamine improved sleep quality, which is conducive to postoperative recovery. The use of low-dose esketamine did not cause psychoactive or other unwanted medical effects. The QoR-40 scale assesses the quality of recovery through five different dimensions, namely, physical comfort, life independence, emotional state, psychological support, and pain, and is currently the most widely used recovery quality measurement scale at home in China and abroad [ 18 ]. The QoR-40 scale is a full-text scale that requires certain reading and comprehension skills, and linear regression analysis also found that education level was correlated with recovery quality. Our study showed that although the total QoR-40 score at 7 days after surgery was significantly lower than that before surgery, there was no clear difference in the effect of low-dose esketamine versus placebo on recovery after total hysterectomy. Emerging evidence suggests that esketamine’s impact on early postoperative recovery quality is contingent upon dosing regimens and surgical contexts. Zhang et al. [ 19 ] demonstrated significantly improved QoR-40 scores on postoperative day 1 with intraoperative infusion of 0.5 mg/kg/h esketamine in laparoscopic bariatric surgery patients. This finding aligns with Gao et al.’s report of enhanced 24-h recovery metrics following a 0.2 mg/kg bolus plus 0.2 mg/kg/h continuous infusion during modified radical mastectomy. [ 20 ] Notably, Zhu et al. further established dose-dependent efficacy, where 4 μg/kg/h maintenance dosing (after 0.5 mg/kg loading) provided optimal recovery benefits on POD1 and POD3 in the same surgical cohort [ 21 ]. Conversely, contradictory outcomes emerged in abdominal procedures. Moro et al. observed no significant QoR-40 improvement with either a 0.2 mg/kg or 0.4 mg/kg ketamine bolus in laparoscopic cholecystectomy patients. [ 22 ] Similarly, Zhao et al. reported null effects on POD1 global recovery despite utilizing a 0.5 mg/kg bolus followed by a 0.25 mg/kg/h infusion throughout breast cancer surgery. [ 23 ] Collectively, these divergent results highlight the critical interplay between esketamine administration protocols (bolus dose, infusion rate, duration) and procedure-specific factors (particularly surgical stress magnitude and patient phenotypes) in determining recovery outcomes. During laparoscopic gynecological surgery, factors such as endotracheal intubation, CO 2 pneumoperitoneum, and painful stimuli predispose patients to elevated levels of catecholamines and vasopressin in the postoperative period, the former of which further activates the renin–angiotensin–aldosterone system and increases the risk of hemodynamic complications. Esketamine can inhibit the uptake of epinephrine, thereby increasing the level of circulating epinephrine, which can contribute to stable hemodynamics [ 7 , 24 ]. Our results showed that intraoperative hemodynamics in group S were more stable, and that the incidence of hypotension was less than in group P. Similar to our findings, Tu and coworkers’ study showed that anesthesia induction with propofol plus esketamine was more beneficial for stabilizing the hemodynamics of geriatric surgical patients than use of propofol alone [ 25 ]. Our study revealed that the wake time was much shorter in group S than in group P. Yang’s research also suggested that esketamine can shorten the wake-up time and reduce the incidence of hypotension in older patients [ 26 ]. This may be related to the fact that esketamine reverses the inhibitory effect of general anesthetics on the activity of glutamatergic neurons in the paraventricular nucleus of the thalamus (PVT) [ 27 ]. Propofol was used in this study, and PVT glutamatergic neurons play an important role in the transition of consciousness during propofol anesthesia [ 28 ]. The sedative and analgesic effects of esketamine may be due to the positive and negative regulation of the cholinergic and aminergic systems, respectively [ 7 , 29 ]. Remifentanil consumption in the experimental group (group S) was significantly reduced. In addition to playing a role in analgesia, esketamine can also be used to reduce and prevent opioid-induced hyperalgesia and to combat opioid-induced respiratory depression. Activation of N-methyl-D-aspartate (NMDA) receptors, one of the two subunits of NMDA, subunit 2B (NR2B), is thought to be the main mechanism that promotes responses to sensory stimuli and leads to hyperalgesia from remifentanil [ 9 ]. It has been shown that low-dose esketamine used for perioperative analgesia prevents nociceptive hypersensitivity and thus improves the quality of analgesia [ 30 ]. However, other studies have found that low-dose esketamine did not significantly reduce pain scores [ 8 , 31 , 32 ]. In this study, we found that NRS scores were significantly lower in the experimental group at 8 or 48 h after extubation, but there was no significant difference in pain scores between the two groups after 48 h [ 33 ]. This suggests that a single subanesthetic dose of esketamine may only affect short-term postoperative pain scores. This finding is consistent with the results of a study by Wang et al., [ 8 ] which did not find that a single injection of 0.25 mg/kg of esketamine increased the incidence of adverse events, hence affirming the safety of the experimental dosage [ 34 ], [ 35 ], [ 36 ]. However, the QoR-40 scores were consistently similar between the groups, possibly because the QoR-40 scale focused more on pain frequency and because the NRS scores tended to indicate pain severity. The inflammatory response after surgery has a great impact on clinical recovery and postoperative complications [ 37 ]. NLR and hs-CRP have been widely used clinically as inexpensive and readily available indicators for assessing the severity of the systemic inflammatory response [ 38 , 39 ]. In this study, the postoperative fever rate was similar between the two groups, but the postoperative NLR in the S group was significantly lower than that in the P group, indicating that esketamine may have a strong anti-inflammatory effect. Depression is related to abnormalities in glutamatergic synaptic transmission, leading to the loss of synaptic plasticity in mood and emotional circuits [ 40 , 41 ]. Esketamine demonstrates rapid antidepressant effects in the postoperative setting through inhibition of glutamatergic receptors. This is evidenced by Zhao et al.’s findings of reduced Hospital Anxiety and Depression Scale (HADS) scores in breast cancer patients receiving low-dose esketamine [ 23 ] and further corroborated by Gan et al.’s report of decreased depressive symptom incidence at 1-month post-thoracoscopic lung cancer surgery with perioperative administration. [ 42 ] Similar to our findings, the study by Yang et al. found that the effect of low-dose esketamine (≤ 0.25 mg/kg) through IV injection during surgery did not affect the incidence of postpartum depression significantly. [ 43 ] Our findings showed that low-dose esketamine did not affect Hamilton Depression Scale (HAMD) scores in patients undergoing total hysterectomy, which may be closely related to the lower dose of a single injection. Limitations of this study are as follows: This was a single-center, small-sample trial. In addition to the primary outcome indicators, the reliability of the conclusions may be limited by the sample size. Moreover, because of the lack of data on intraoperative hemodynamics and postoperative acute pain indices, additional patients still need to be included to achieve statistical efficacy. In particular, when interpreting the results of multiple regression analyses, more cautious telephone follow-up should be used on the 7th and 30th days after surgery, which may bias the accuracy of the assessment results after discharge, unlike the scale collected during hospitalization. The learning effect generated by multiple measurements of the QoR-40 was not analyzed or corrected. The QoR-40 is a full-text scale that requires some reading and comprehension skills, which may necessitate further research on the relationship between the scale’s scores and the subjects’ educational level. This was a single-center, small-sample trial. In addition to the primary outcome indicators, the reliability of the conclusions may be limited by the sample size. Moreover, because of the lack of data on intraoperative hemodynamics and postoperative acute pain indices, additional patients still need to be included to achieve statistical efficacy. In particular, when interpreting the results of multiple regression analyses, more cautious telephone follow-up should be used on the 7th and 30th days after surgery, which may bias the accuracy of the assessment results after discharge, unlike the scale collected during hospitalization. The learning effect generated by multiple measurements of the QoR-40 was not analyzed or corrected. The QoR-40 is a full-text scale that requires some reading and comprehension skills, which may necessitate further research on the relationship between the scale’s scores and the subjects’ educational level.

Benign uterine lesions such as uterine fibroids and adenomyosis can cause abnormal uterine bleeding, pain, or intra-abdominal hypertension in women, which in turn affects the normal life of patients and is a common disease of the female reproductive system [ 1 ].In the USA, hysterectomy is the most common gynecological procedure after cesarean Sect [ 2 ]. In the treatment of gynecological diseases, laparoscopic hysterectomy has become an indispensable surgical method that has many advantages, such as thorough abdominal exploration, small wound scars, and early resumption of daily life and work, and patients are more likely to accept this type of surgery [ 3 ]. Despite these advantages of minimally invasive surgery, surgical incisions, carbon dioxide pneumoperitoneum peculiar to laparoscopic surgery, a long duration of the operation, and the need for a higher dose of remifentanil may induce hyperalgesia and increase pain and restlessness during recovery [ 4 , 5 ]. Studies have shown that patients treated with laparoscopic gynecological surgery have an 80% chance of experiencing pain after surgery [ 6 ]. Improving the comfort and quality of postoperative patients is therefore a necessity. Racemic ketamine has been globally approved and routinely used in clinical anesthesia for decades, and its pharmacological properties, dosage regimen, and safety have been relatively well established in clinical practice. Dextrorotatory esketamine, the stereoisomer of racemic ketamine, has pharmacological effects similar to those of the racemate. The affinity of esketamine for NMDA receptors is approximately four times greater than that of levorotatory arketamine. Esketamine shows analgesic effects that are approximately 2 times greater than those of racemic ketamine and 3–4 times of arketamine. Esketamine also exerts greater hypnotic and anesthetic effects, which are approximately two times greater than those of racemic ketamine [ 7 ]. Previous studies have shown that esketamine can provide good sedative analgesia [ 8 ], reduce hyperalgesia [ 9 ], increase the effects of local anesthetic blockades [ 10 ], and provide rapid antidepressant effects [ 11 , 12 ]. As a result, esketamine has received increasing attention as a potential drug to promote postoperative recovery. However, a potential problem with esketamine may be its psychomimetic effects, such as visual disturbances, dizziness, or nausea, which may impair patient satisfaction. Nevertheless, as with all ketamines, esketamine’s side effects are dose dependent [ 13 ]. A recent meta-analysis showed that perioperative dosing of esketamine from 0.2 to 0.6 mg/kg has a favorable safety profile and improves the quality of patients’ postoperative recovery [ 14 ]. However, the optimal dose and duration of esketamine use to improve the quality of postoperative recovery in different surgical settings are still being explored. The primary objective of this study was to assess whether low-dose esketamine can improve the quality of recovery in patients undergoing total laparoscopic hysterectomy via the QoR-40 questionnaire [ 15 ]. Since esketamine is not yet approved in clinical anesthesia, the results of this study will provide important preliminary evidence for expanding the potential clinical use of this drug.

Supplementary Material 1: Table S1. Perioperative data with no statistical difference. Table S2. Multiple linear regression analysis for QoR-40 score (72 h). Supplementary Material 1: Table S1. Perioperative data with no statistical difference. Table S2. Multiple linear regression analysis for QoR-40 score (72 h).