Reduced-exposure neuromuscular blockade strategies for total laparoscopic hysterectomy within an ERAS pathway: a randomized controlled trial.

As shown in the CONSORT flow diagram (Fig.  1 ), 152 patients were assessed for eligibility. Seventeen were excluded before randomization, including 13 who did not meet the inclusion criteria, one who declined participation, and three with anticipated difficult airway. The remaining 135 patients were randomized equally into the NM, MI, and MIC groups (45 patients each). After randomization, five patients (two in the MI group and three in the MIC group) were excluded from the analysis because intraoperative pathological examination revealed malignant disease requiring a change in the surgical procedure. Consequently, 130 patients (NM = 45, MI = 43, MIC = 42) were included in the final analysis. Fig. 1 CONSORT flow diagram of participant recruitment and study allocation. The diagram illustrates the screening, inclusion, and exclusion process. A total of 152 candidates were assessed, with 130 patients completing the final analysis across the three study groups: NM (no muscle relaxant), MI (muscle relaxant induction), and MIC (muscle relaxant induction and maintenance) CONSORT flow diagram of participant recruitment and study allocation. The diagram illustrates the screening, inclusion, and exclusion process. A total of 152 candidates were assessed, with 130 patients completing the final analysis across the three study groups: NM (no muscle relaxant), MI (muscle relaxant induction), and MIC (muscle relaxant induction and maintenance) Baseline characteristics and intraoperative variables are summarized in Table  3 . Baseline P values were provided for descriptive reporting using the statistical rules specified above and were not used to assess randomization balance. Table 3 Baseline characteristics and intraoperative variables of the analyzed cohort Characteristic NM ( n  = 45) MI ( n  = 43) MIC ( n  = 42) P value Baseline characteristics  Age, years 50.00 [47.00, 56.00] 52.00 [45.50, 57.00] 49.50 [43.25, 56.75] 0.732  Weight, kg 62.56 ± 7.82 63.56 ± 7.42 61.14 ± 5.25 0.210  Height, cm 160.36 ± 7.31 160.60 ± 7.60 161.88 ± 5.21 0.461  BMI, kg/m² 23.62 [21.63, 26.45] 24.88 [22.94, 26.70] 23.09 [22.03, 24.88] 0.066 ASA physical status, n (%) 0.700  1 28 (62.2) 27 (62.8) 23 (54.8)  2 17 (37.8) 16 (37.2) 19 (45.2) Diagnosis, n (%) 0.990  Abnormal uterine bleeding 2 (4.4) 1 (2.3) 2 (4.8)  Adenomyosis 10 (22.2) 11 (25.6) 10 (23.8)  CIN 4 (8.9) 3 (7.0) 4 (9.5)  Endometrial hyperplasia 2 (4.4) 2 (4.7) 1 (2.4)  Multiple uterine fibroids 16 (35.6) 11 (25.6) 13 (31.0)  Uterine fibroids 11 (24.4) 15 (34.9) 12 (28.6) Mallampati class, n (%) 0.917  1 19 (42.2) 20 (46.5) 19 (45.2)  2 26 (57.8) 23 (53.5) 23 (54.8) Intraoperative surgical and anesthetic exposure  Surgery duration, min 90.00 [73.00, 104.00] 91.00 [80.00, 103.50] 87.00 [75.50, 106.75] 0.676  Anesthesia duration, min 113.00 [98.00, 126.00] 115.00 [109.00, 134.00] 113.00 [97.00, 136.00] 0.497  Blood loss, mL 20.00 [10.00, 40.00] 20.00 [20.00, 40.00] 20.00 [10.00, 37.50] 0.697  Fluid intake, mL 1200.00 [1000.00, 1300.00] 1200.00 [1000.00, 1400.00] 1100.00 [925.00, 1200.00] 0.167  Urine output, mL 300.00 [200.00, 400.00] 300.00 [200.00, 400.00] 300.00 [200.00, 475.00] 0.740  Propofol total dose, mg 588.24 [522.10, 679.17] 604.80 [549.61, 704.93] 586.21 [478.17, 686.92] 0.444  Remifentanil total dose, mg 3.09 [2.68, 3.65] 3.19 [2.84, 3.74] 3.05 [2.42, 3.65] 0.462 Values are mean ± SD, median [IQR], or n (%). P values for baseline variables were provided for descriptive reporting only and were not used to infer randomization balance. Continuous variables were compared using Welch ANOVA or the Kruskal-Wallis test according to distribution and variance structure; categorical variables were compared using Pearson chi-square tests or Fisher-Freeman-Halton exact tests with Monte Carlo simulation for sparse r x c tables. ASA American Society of Anesthesiologists, BMI body mass index, CIN cervical intraepithelial neoplasia, SD standard deviation, IQR interquartile range Baseline characteristics and intraoperative variables of the analyzed cohort Values are mean ± SD, median [IQR], or n (%). P values for baseline variables were provided for descriptive reporting only and were not used to infer randomization balance. Continuous variables were compared using Welch ANOVA or the Kruskal-Wallis test according to distribution and variance structure; categorical variables were compared using Pearson chi-square tests or Fisher-Freeman-Halton exact tests with Monte Carlo simulation for sparse r x c tables. ASA American Society of Anesthesiologists, BMI body mass index, CIN cervical intraepithelial neoplasia, SD standard deviation, IQR interquartile range Intraoperative characteristics are also summarized in Table  3 . The duration of surgery and anesthesia, anesthetic drug consumption, estimated blood loss, intraoperative fluid administration, and urine output did not differ significantly among the three groups. The Narcotrend index remained within the target range (40–60) throughout anesthesia, with no statistically significant between-group differences at scheduled time points (Fig.  2 ). Fig. 2 Primary intubation endpoint and supportive airway outcomes. Panel A shows Cooper intubation-grade distribution; Panel B shows clinically acceptable intubation proportions with exact binomial 95% CIs; Panel C shows Cormack-Lehane grades. Cooper grades of excellent or good were classified as clinically acceptable. Panel C is a supportive airway summary; the prespecified primary acceptable-intubation comparison is shown in Panel B Primary intubation endpoint and supportive airway outcomes. Panel A shows Cooper intubation-grade distribution; Panel B shows clinically acceptable intubation proportions with exact binomial 95% CIs; Panel C shows Cormack-Lehane grades. Cooper grades of excellent or good were classified as clinically acceptable. Panel C is a supportive airway summary; the prespecified primary acceptable-intubation comparison is shown in Panel B The primary endpoint was the proportion of patients achieving clinically acceptable intubating conditions, defined as excellent or good according to the Cooper score (Table  4 ; Fig.  3 ). Successful tracheal intubation was achieved in all patients. Clinically acceptable intubating conditions were observed in 43/45 patients (95.6%; 95% CI, 84.9%-99.5%) in the NM group, 43/43 patients (100.0%; 95% CI, 91.8%-100.0%) in the MI group, and 42/42 patients (100.0%; 95% CI, 91.6%-100.0%) in the MIC group, with no statistically significant between-group differences observed (exact P  = 0.328). Two patients in the NM group were graded as “Fair,” and no patient was graded as “Poor.” No statistically significant between-group differences were observed in Cormack-Lehane grades ( P  = 0.865), with most patients classified as Grade I or II. No patient required rescue neuromuscular blockade to facilitate tracheal intubation. Table 4 Primary intubation endpoint and supportive airway and surgical workspace outcomes Outcome NM ( n  = 45) MI ( n  = 43) MIC ( n  = 42) P value Successful tracheal intubation, n (%) 45 (100.0) 43 (100.0) 42 (100.0) - Cooper intubation condition, n (%) 0.477  Excellent 33 (73.3) 34 (79.1) 32 (76.2)  Good 10 (22.2) 9 (20.9) 10 (23.8)  Fair 2 (4.4) 0 (0.0) 0 (0.0)  Poor 0 (0.0) 0 (0.0) 0 (0.0) Clinically acceptable intubating conditions, n (%) [95% CI] 43 (95.6) [84.9–99.5] 43 (100.0) [91.8–100.0] 42 (100.0) [91.6–100.0] 0.328 Rescue NMBA during intubation, n (%) 0 (0.0) 0 (0.0) 0 (0.0) -  C-L grade, n (%) 0.865  Grade I 27 (60.0) 28 (65.1) 26 (61.9)  Grade II 17 (37.8) 14 (32.6) 16 (38.1)  Grade III 1 (2.2) 1 (2.3) 0 (0.0) Surgical workspace score 4.53 ± 0.43 4.62 ± 0.34 4.58 ± 0.27 0.505 Surgical workspace score  ≧ 4, n (%) 43 (95.6) 42 (97.7) 42 (100.0) Values are mean ± SD or n (%). Cooper grades of excellent or good were classified as clinically acceptable intubating conditions. Exact binomial 95% confidence intervals are shown for the primary endpoint proportions. P values are shown for prespecified or supportive group comparisons; ‘-’ indicates all-zero events or no formal hypothesis test. C-L Cormack-Lehane, NMBA neuromuscular blocking agent Primary intubation endpoint and supportive airway and surgical workspace outcomes Values are mean ± SD or n (%). Cooper grades of excellent or good were classified as clinically acceptable intubating conditions. Exact binomial 95% confidence intervals are shown for the primary endpoint proportions. P values are shown for prespecified or supportive group comparisons; ‘-’ indicates all-zero events or no formal hypothesis test. C-L Cormack-Lehane, NMBA neuromuscular blocking agent Fig. 3 Perioperative hemodynamic and anesthetic depth trends. Mean arterial pressure (MAP), heart rate (HR), and Narcotrend index were summarized from baseline through recovery. Points represent group means and error bars represent standard errors (SEs). T0 baseline, T1 induction, T2 intubation, T3 incision, T4 pneumoperitoneum, T5 30 min intraoperative, T6 1 h intraoperative, T7 end of surgery, T8 extubation, and T9 recovery. The shared time axis includes T9 for recovery; Narcotrend values were available through T8 only. Induction-period hypotension was defined as MAP <60 mmHg at T1 or T2 and occurred in 12/45 NM patients, 9/43 MI patients, and 7/42 MIC patients ( P = 0.522) Perioperative hemodynamic and anesthetic depth trends. Mean arterial pressure (MAP), heart rate (HR), and Narcotrend index were summarized from baseline through recovery. Points represent group means and error bars represent standard errors (SEs). T0 baseline, T1 induction, T2 intubation, T3 incision, T4 pneumoperitoneum, T5 30 min intraoperative, T6 1 h intraoperative, T7 end of surgery, T8 extubation, and T9 recovery. The shared time axis includes T9 for recovery; Narcotrend values were available through T8 only. Induction-period hypotension was defined as MAP <60 mmHg at T1 or T2 and occurred in 12/45 NM patients, 9/43 MI patients, and 7/42 MIC patients ( P = 0.522) Mean surgical workspace scores were 4.53 ± 0.43, 4.62 ± 0.34, and 4.58 ± 0.27 in the NM, MI, and MIC groups, respectively, with no significant difference among groups ( P  = 0.505). Mean arterial pressure remained similar among groups throughout the perioperative period (Fig.  2 ). Heart rate differed at extubation (T8), with higher values observed in the NM group than in the MI and MIC groups ( P  < 0.05). Induction-period MAP < 60 mmHg at T1 or T2 occurred in 12/45 NM patients, 9/43 MI patients, and 7/42 MIC patients ( P  = 0.522). No chest-wall rigidity, difficult mask ventilation, failed intubation, or rescue NMBA administration for intubation difficulty occurred in any group. Extubation times were similar across groups (Table  5 ; P  = 0.664). Table 5 Perioperative recovery, intubation safety, and adverse events among the three groups Outcome NM ( n  = 45) MI ( n  = 43) MIC ( n  = 42) P value Extubation time, min 9.00 [7.00, 12.00] 8.00 [7.00, 11.00] 9.00 [7.00, 11.00] 0.664 Body movement, n (%) 2 (4.4) 0 (0.0) 0 (0.0) 0.328 Additional NMBA beyond assigned protocol after intubation, n (%) 4 (8.9) 3 (7.0) 2 (4.8) 0.909 Lowest scheduled MAP during induction/intubation, mmHg 64 [60, 68] 64 [60, 71] 64 [62, 68] 0.665 Induction-period MAP < 60 mmHg at T1/T2, n (%) 12 (26.7) 9 (20.9) 7 (16.7) 0.522 Scheduled induction-intubation bradycardia, n (%) 4 (8.9) 3 (7.0) 1 (2.4) 0.533 Chest-wall rigidity, n (%) 0 (0.0) 0 (0.0) 0 (0.0) - Difficult mask ventilation, n (%) 0 (0.0) 0 (0.0) 0 (0.0) - Failed intubation, n (%) 0 (0.0) 0 (0.0) 0 (0.0) - PACU stay, min 51 [43–67] 48 [33–80] 59 [56–87] 0.117 Hospital stay, days 8 [7–10] 8 [7–10] 8 [7–9] 0.879 Serious complications, n (%) 0 (0.0) 0 (0.0) 0 (0.0) - Any recorded postoperative AE, n (%) 4 (8.9) 6 (14.0) 8 (19.0) 0.397 Nausea and vomiting, n (%) 4 (8.9) 5 (11.6) 8 (19.0) 0.395 Shoulder pain, n (%) 0 (0.0) 1 (2.3) 0 (0.0) 0.654 Other adverse events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) - Values are median [IQR] or n (%). The lowest scheduled MAP was compared using the Kruskal-Wallis test, and scheduled bradycardia was compared using the Fisher-Freeman-Halton exact test. Other P values are shown when formal group comparisons were performed; ‘-’ indicates all-zero events or no formal test. Induction-period hypotension was defined as MAP < 60 mmHg at T1 induction or T2 intubation. Scheduled bradycardia was defined as HR < 50 beats/min at T1 or T2; treatment-requiring bradycardia and vasopressor drug/dose were not retained as structured treatment fields. Patient-level rescue analgesic drug, dose, and timing; quantitative TOF/PTC values; minimum PACU SpO₂; PACU hypoxemia; reintubation; and pneumonia were not retained as analyzable fields. AE adverse event, HR heart rate, MAP mean arterial pressure, NMBA neuromuscular blocking agent, PACU post-anesthesia care unit, PONV postoperative nausea and vomiting Perioperative recovery, intubation safety, and adverse events among the three groups Values are median [IQR] or n (%). The lowest scheduled MAP was compared using the Kruskal-Wallis test, and scheduled bradycardia was compared using the Fisher-Freeman-Halton exact test. Other P values are shown when formal group comparisons were performed; ‘-’ indicates all-zero events or no formal test. Induction-period hypotension was defined as MAP < 60 mmHg at T1 induction or T2 intubation. Scheduled bradycardia was defined as HR < 50 beats/min at T1 or T2; treatment-requiring bradycardia and vasopressor drug/dose were not retained as structured treatment fields. Patient-level rescue analgesic drug, dose, and timing; quantitative TOF/PTC values; minimum PACU SpO₂; PACU hypoxemia; reintubation; and pneumonia were not retained as analyzable fields. AE adverse event, HR heart rate, MAP mean arterial pressure, NMBA neuromuscular blocking agent, PACU post-anesthesia care unit, PONV postoperative nausea and vomiting Exploratory postoperative VAS scores and inflammatory biomarker trajectories are shown in Fig.  4 . VAS scores differed at 2 h and 4 h after surgery, with higher scores observed in the MIC group than in the NM and MI groups ( P  < 0.05); no statistically significant differences were observed thereafter. Serum IL-6 and TNF-alpha concentrations were similar before surgery. Immediately after surgery, IL-6 concentrations were higher in the MIC group than in the NM and MI groups ( P  = 0.011). A between-group difference was also observed for TNF-alpha at the immediate postoperative time point ( P  = 0.004), with the highest mean value in the MI group rather than a consistent dose-response pattern across NMBA exposure. Because patient-level rescue analgesic drug, dose, and timing were not retained as structured analyzable fields, these pain and biomarker findings should be interpreted as exploratory associations rather than causal effects. No statistically significant between-group differences were observed in body movement, additional muscle relaxant use after intubation, PACU stay, hospital stay, or recorded adverse events (Table  5 ). Recorded adverse events consisted mainly of postoperative nausea and vomiting (NM 4/45, MI 5/43, MIC 8/42) and one patient with shoulder pain in the MI group. Fig. 4 Exploratory postoperative pain and inflammatory biomarker trajectories. Panel A shows VAS pain scores at 2, 4, 8, 12, and 24 h postoperatively as medians with IQRs. Panel B shows IL-6 and TNF-alpha concentrations (pg/mL) preoperatively, immediately after operation, and 24 h postoperatively as means with standard errors (SEs). * indicates an exploratory overall between-group difference with P  < 0.05 at the scheduled time point. Bonferroni adjustment was applied to post hoc pairwise comparisons after a significant overall test; no additional multiplicity adjustment was applied across exploratory outcomes and time points. These biomarker comparisons were not linked to prespecified clinical inflammatory outcomes. Patient-level rescue analgesic drug, dose, and timing were not retained as structured analyzable fields. Exploratory postoperative pain and inflammatory biomarker trajectories. Panel A shows VAS pain scores at 2, 4, 8, 12, and 24 h postoperatively as medians with IQRs. Panel B shows IL-6 and TNF-alpha concentrations (pg/mL) preoperatively, immediately after operation, and 24 h postoperatively as means with standard errors (SEs). * indicates an exploratory overall between-group difference with P  < 0.05 at the scheduled time point. Bonferroni adjustment was applied to post hoc pairwise comparisons after a significant overall test; no additional multiplicity adjustment was applied across exploratory outcomes and time points. These biomarker comparisons were not linked to prespecified clinical inflammatory outcomes. Patient-level rescue analgesic drug, dose, and timing were not retained as structured analyzable fields.

This study was designed as a single-center, prospective, randomized, patient-, surgeon-, postoperative assessor-, and statistician-blinded, parallel-group controlled trial to evaluate different neuromuscular blockade (NMB) strategies within an Enhanced Recovery After Surgery (ERAS) framework. The study was conducted at the Gansu Provincial Maternity and Child Care Hospital between September 2022 and September 2023. The study protocol was developed before patient enrollment and received approval from the Gansu Provincial Maternity and Child Care Hospital Ethics Committee (approval no. 2022 GSFY Ethics Review 31, approved on September 8, 2022). Because prospective clinical trial registration was not routinely implemented at our institution when the study was initiated, the trial was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2400080065) after study completion. Written informed consent was obtained from all participants before enrollment, and all study procedures complied with the Declaration of Helsinki. The trial is reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement. The study population consisted of female patients scheduled for elective total laparoscopic hysterectomy under general anesthesia. Candidates were eligible for inclusion if they were aged between 40 and 65 years, presented with benign uterine conditions such as uterine fibroids or adenomyosis, and were classified as American Society of Anesthesiologists (ASA) physical status I or II. Exclusion criteria encompassed a history of intestinal obstruction or peptic ulcer, known allergies to nonsteroidal anti-inflammatory drugs or anesthetic agents, and a preoperative assessment indicating a potentially difficult airway, defined by a Mallampati score ≥ III or a thyromental distance of less than 6 cm. Participants were withdrawn from the analysis if intraoperative findings necessitated a modification of the surgical scope, such as conversion to laparotomy or a histological diagnosis of malignancy, or if they encountered severe adverse reactions during the intervention. Participants were randomly assigned in a 1:1:1 ratio to the no muscle relaxant (NM), muscle relaxant induction only (MI), or muscle relaxant induction plus maintenance (MIC) groups using a randomization sequence generated in SPSS version 26.0. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes. The randomization sequence was generated and stored by an investigator who was not involved in patient recruitment, anesthesia management, postoperative assessment, or statistical analysis. An independent anesthetic nurse prepared the study medications in identical, uniformly labeled syringes according to the allocation sequence. Patients, anesthesiologists, surgeons, postoperative evaluators, and statisticians remained blinded to treatment allocation throughout the study. Emergency unblinding was permitted only when necessary for patient safety. All patients were managed according to a standardized ERAS protocol, including preoperative fasting, carbohydrate loading, and multimodal preemptive analgesia with oral acetaminophen and ibuprofen. Standard intraoperative monitoring was applied, with anesthetic depth guided by the Narcotrend Index (Narcotrend-Compact, MT MonitorTechnik GmbH & Co. KG, Germany). General anesthesia was induced and maintained using manually controlled total intravenous anesthesia (TIVA). Propofol (25 mg/kg/h) and remifentanil (1 µg/kg/min) were continuously infused for 5 min during induction until cumulative doses of propofol (2.5 mg/kg) and remifentanil (5 µg/kg) had been administered, after which tracheal intubation was performed. Anesthesia was subsequently maintained with propofol (4–6 mg/kg/h) and remifentanil (0.4–0.5 µg/kg/min), with the depth of anesthesia adjusted to maintain a Narcotrend index between 40 and 60. In the NM group, a matching saline infusion was administered as placebo during both induction and maintenance. The MI group received rocuronium (0.6 mg/kg) during induction followed by a matching saline infusion, whereas the MIC group received rocuronium (0.6 mg/kg) for induction followed by continuous infusion at 0.2 mg/kg/h, which was discontinued approximately 30 min before the anticipated completion of surgery. Mechanical ventilation was standardized using a tidal volume of 6–8 mL/kg, a respiratory rate of 10–15 breaths/min, a positive end-expiratory pressure of 0–5 cmH₂O, and an inspired oxygen fraction of 0.5. Respiratory rate was adjusted to maintain end-tidal carbon dioxide between 35 and 45 mmHg. All procedures were performed in the lithotomy position with a steep Trendelenburg position (approximately 30°) and a pneumoperitoneum pressure of 12 mmHg. Lactated Ringer’s solution was administered at 8–10 mL/kg/h throughout the procedure. Rescue rocuronium (0.2 mg/kg) was administered if chest-wall rigidity, inadequate intubating conditions, unacceptable surgical conditions, or ventilation difficulties occurred, and all additional NMBA use was recorded. Ephedrine or atropine was administered as required to treat intraoperative hypotension or bradycardia. At the completion of surgery, propofol and remifentanil were discontinued. Patients in the MI and MIC groups received neostigmine (0.02 mg/kg) and atropine (0.01 mg/kg) for neuromuscular blockade reversal, whereas patients in the NM group received a matching volume of normal saline. All patients received intravenous sufentanil (0.25 µg/kg) together with incision-site infiltration using 10 mL of 0.75% ropivacaine. No perioperative corticosteroids or intraperitoneal local anesthetics were administered. Patients were extubated after meeting standardized extubation criteria and transferred to the PACU. Postoperative care followed a standardized ERAS pathway, and multimodal analgesia consisted of oral acetaminophen (500 mg every 6 h) and ibuprofen (600 mg every 12 h) for the first 3 postoperative days. Because patient-level rescue analgesic drug, dose, and timing were not retained as structured analyzable fields in the verified dataset, postoperative pain and inflammatory biomarker outcomes were interpreted as exploratory. Endotracheal intubation was performed by experienced attending anesthesiologists using direct laryngoscopy. Sniffing position was applied in all patients, and external laryngeal manipulation was permitted when clinically required. No alternative intubation devices were routinely used. The laryngoscopic view was evaluated using the Cormack–Lehane grading system [ 19 ], and intubating conditions were assessed using the Cooper intubation score [ 20 ] (Table  1 ). Intubating conditions rated as excellent or good were considered clinically acceptable. The operating surgeon, who remained blinded to treatment allocation, independently assessed the laparoscopic surgical workspace every 30 min after establishment of pneumoperitoneum using a validated five-point surgical rating scale [ 21 ] (Table  2 ). If surgical conditions worsened or ventilation difficulties arose, a rescue dose of rocuronium (0.2 mg/kg) was administered and recorded. Table 1 Cooper scoring system for intubating conditions Score Jaw relaxation Vocal cords Response to intubation 0 Poor (impossible) Closed Severe coughing or bucking 1 Minimal (difficult) Closing Mild coughing 2 Moderate (fair) Moving Slight diaphragmatic movement 3 Good (easy) Open None Total score classification Excellent: 8–9; Good: 6–7; Fair: 3–5; Poor: 0–2 The Cooper score is the sum of jaw relaxation, vocal cord position, and response to intubation scores (range, 0–9). Excellent or good intubating conditions were classified as clinically acceptable in this study Cooper scoring system for intubating conditions The Cooper score is the sum of jaw relaxation, vocal cord position, and response to intubation scores (range, 0–9). Excellent or good intubating conditions were classified as clinically acceptable in this study Table 2 Five-point surgical rating scale for laparoscopic surgical workspace Scale score Description 1 (Extremely poor) Unable to complete surgery without interventions 2 (Poor) Several minor adjustments were needed to complete surgery, such as changes in patient or surgeon position 3 (Acceptable) Surgery could be completed after a few minor adjustments 4 (Good) The surgical workspace was good, with some interference but no need for adjustment 5 (Optimal) The surgical workspace was optimal and the procedure could be completed without interference Interventions included increasing neuromuscular blockade depth and/or adjusting pneumoperitoneum. In the scale description, few interventions indicate 1–2 minor adjustments and several interventions indicate more than 2 adjustments Five-point surgical rating scale for laparoscopic surgical workspace Interventions included increasing neuromuscular blockade depth and/or adjusting pneumoperitoneum. In the scale description, few interventions indicate 1–2 minor adjustments and several interventions indicate more than 2 adjustments Demographic and perioperative data, including age, body mass index, ASA physical status, diagnosis, anesthetic drug consumption, duration of anesthesia and surgery, intraoperative fluid administration, urine output, estimated blood loss, and hospital stay, were recorded. Heart rate, mean arterial pressure, and Narcotrend index were documented at ten predefined time points (T0–T9): before anesthesia (T0), during induction (T1), at tracheal intubation (T2), at skin incision (T3), establishment of pneumoperitoneum (T4), 30 min after pneumoperitoneum (T5), 1 h after pneumoperitoneum (T6), at the end of surgery (T7), at extubation (T8), and upon recovery from anesthesia (T9). The primary endpoint was the proportion of patients achieving clinically acceptable intubating conditions, defined as excellent or good Cooper grades. Secondary endpoints included Cormack-Lehane grade, intraoperative surgical rating score, intraoperative body movement, rescue rocuronium administration, extubation time, duration of PACU stay, blood glucose concentrations, perioperative complications, adverse events, and postoperative hospital stay. Postoperative VAS scores and serum IL-6 and TNF-alpha concentrations were analyzed as exploratory recovery-related outcomes. Extubation time was defined as the interval between discontinuation of anesthetic agents and removal of the endotracheal tube. Postoperative pain was evaluated using a 10-point visual analogue scale (VAS) at 2, 4, 8, 12, and 24 h after surgery. Venous blood samples were collected before induction, immediately after surgery, and 24 h postoperatively. Serum IL-6 and TNF-α concentrations were measured using enzyme-linked immunosorbent assay (ELISA) and were analyzed as exploratory biomarkers of the perioperative inflammatory response. The sample size was based on the primary endpoint, defined as the proportion of patients achieving clinically acceptable intubating conditions (excellent or good Cooper grades). Effect-size assumptions were derived from the randomized study by Schlaich et al. [ 22 ], which compared propofol–remifentanil intubation with and without rocuronium. Clinically acceptable intubating conditions occurred in 96.7% of patients receiving rocuronium and 60.0% of those without neuromuscular blockade. Using these proportions, a two-sided α level of 0.0167 (Bonferroni-adjusted for three pairwise comparisons), 80% power, and a 1:1 allocation ratio, at least 25 patients were required per group. Allowing for approximately 20% attrition, the target sample size was increased to 32 patients per group. We therefore enrolled 45 patients in each group. The Cochrane review by Lundstrøm et al. [ 23 ] was used as supportive evidence because it demonstrated clinically important differences in difficult intubation between patients receiving and not receiving neuromuscular blocking agents. Statistical analyses were performed using SPSS version 26.0 and R version 4.6.0 for exact and Monte Carlo tests. Continuous variables were expressed as mean ± standard deviation or median [interquartile range], depending on the distribution assessed using the Shapiro-Wilk test and visual inspection. Three-group comparisons used one-way analysis of variance for approximately normally distributed variables with acceptable variance homogeneity, Welch analysis of variance for approximately normal variables with unequal variances, and the Kruskal-Wallis test for non-normal variables. Categorical variables were compared using Pearson chi-square tests or Fisher’s exact tests; for sparse r × c tables, Fisher-Freeman-Halton exact tests with Monte Carlo simulation were used. Repeated measurements were analyzed using generalized estimating equations incorporating treatment group, time, and the group-by-time interaction. When an overall between-group difference was significant, post hoc pairwise comparisons were performed with Bonferroni adjustment. All statistical tests were two-sided, and P  < 0.05 was considered statistically significant.

In this study, among selected patients undergoing elective total laparoscopic hysterectomy within an ERAS pathway, reduced NMBA exposure was not associated with differences in clinically acceptable intubating conditions, surgical workspace quality, or early recovery outcomes. These findings suggest that reducing NMBA exposure may be feasible under carefully standardized anesthetic conditions, although interpretation should remain limited to the studied population. Further prospective studies incorporating quantitative neuromuscular monitoring are warranted to validate these findings.

This randomized trial evaluated three neuromuscular blockade strategies during elective total laparoscopic hysterectomy within an ERAS pathway [ 1 – 3 ]. The primary finding was that clinically acceptable intubating conditions were achieved in most patients in all three groups, and successful tracheal intubation was achieved in every analyzed patient. This finding should be interpreted alongside prior propofol-remifentanil intubation literature, which indicates that intubation without an NMBA can be feasible in selected patients, while randomized and systematic-review evidence still shows that NMBAs generally improve intubating conditions or reduce difficult or unacceptable intubation [ 22 , 23 ]. Surgical workspace scores, interpreted in the context of prior workspace-rating and pelvic-laparoscopy literature [ 16 – 18 , 21 , 24 ], as well as Cormack-Lehane grades, extubation time, PACU stay, and hospital stay, did not differ significantly between groups. These findings support the feasibility of reduced NMBA exposure under the specific anesthetic protocol evaluated in this trial. They should not be interpreted as evidence that the strategies meet a prespecified margin of clinical similarity because the study was not designed or analyzed for that purpose. The airway findings should be interpreted within the details of the anesthetic protocol. Tracheal intubation was performed by experienced attending anesthesiologists using direct laryngoscopy after a standardized induction with propofol and high-dose remifentanil, a pharmacologic approach previously studied for tracheal intubation without muscle relaxants in selected adult patients and supported by evidence on anesthetic effects on upper-airway integrity [ 22 , 25 – 28 ]. No chest-wall rigidity, glottic closure, difficult mask ventilation, failed intubation, or rescue NMBA administration before intubation were observed. Induction-period hypotension, defined from scheduled MAP values below 60 mmHg at T1 or T2, also did not differ significantly among groups. Nevertheless, the use of remifentanil 5 ug/kg is higher than routine doses in many practices and requires careful patient selection, airway expertise, hemodynamic monitoring, and an explicit rescue plan because high-dose remifentanil can modify hemodynamic responses to intubation and has been associated with opioid-induced chest-wall rigidity depending on the administration conditions [ 29 , 30 ]. These results therefore apply most directly to relatively healthy ASA I-II patients without anticipated difficult airway. The surgical workspace findings support the interpretation that abdominal working conditions in selected pelvic laparoscopic procedures are influenced by multiple factors, including anesthetic depth, analgesia, pneumoperitoneum pressure, and patient positioning, rather than by neuromuscular blockade alone [ 16 – 18 , 21 , 24 ]. In this trial, all procedures were performed in lithotomy with approximately 30 degrees of Trendelenburg position and 12 mmHg pneumoperitoneum, and Narcotrend-guided TIVA was used to maintain a consistent hypnotic depth. Whether similar findings apply to other surgical procedures or different patient populations remains unclear and requires further investigation. Postoperative VAS scores and inflammatory biomarkers were interpreted as exploratory outcomes. Higher early VAS scores at 2 and 4 h and higher immediate postoperative IL-6 concentrations were observed in the MIC group; a between-group difference in TNF-alpha was observed at the same time point, with the highest immediate postoperative mean value in the MI group. The clinical meaning and mechanism of these differences remain uncertain. Pain scores and cytokine concentrations may be influenced by surgical manipulation, pneumoperitoneum, tissue traction, opioid exposure, reversal agents, local anesthetic technique, and rescue analgesia, and perioperative cytokine changes are nonspecific markers of surgical stress rather than direct evidence of NMBA-related inflammatory activation [ 18 , 31 – 35 ]. Because patient-level rescue analgesic drug, dose, and timing were not retained as structured analyzable fields, these findings cannot be attributed causally to the NMB strategy. Several limitations should be considered when interpreting these findings. First, quantitative neuromuscular monitoring, including TOF ratio, acceleromyography, electromyography, or PTC, was not performed, despite contemporary guidance emphasizing quantitative monitoring and appropriate antagonism to reduce residual neuromuscular blockade. Therefore, the study cannot confirm recovery to TOF ratio ≥ 0.9, estimate the incidence of postoperative residual neuromuscular blockade, or determine whether subclinical residual blockade contributed to postoperative outcomes. Second, rNMB and structured postoperative respiratory outcomes were not prespecified study endpoints. Patient-level data on minimum PACU SpO 2 , hypoxemia, and postoperative pneumonia were also not retained as analyzable variables. Accordingly, the present findings should not be interpreted as evidence regarding respiratory safety or the prevention of postoperative residual neuromuscular blockade. Additional limitations relate to contemporary clinical practice and trial transparency. Neuromuscular blockade reversal in the MI and MIC groups used neostigmine-atropine, whereas sugammadex was not included in the protocol; the results may therefore not fully apply to institutions where sugammadex and quantitative neuromuscular monitoring are routinely used, particularly given contemporary guideline recommendations and outcome data comparing sugammadex with neostigmine for rocuronium reversal [ 9 – 11 ]. The trial was registered after completion of the study period, although project approval, ethics approval, and written informed consent preceded enrollment; delayed registration limits external verification of the prespecified outcome hierarchy and statistical analysis plan. Finally, the findings should be interpreted within the context of the study population and may not be generalizable to other patient populations.

Laparoscopic hysterectomy (LH) has become one of the standard surgical approaches for benign uterine diseases, such as symptomatic leiomyomas and adenomyosis, because it is associated with less intraoperative blood loss, shorter hospital stays, and faster postoperative recovery than open surgery. With the widespread adoption of Enhanced Recovery After Surgery (ERAS) protocols, perioperative management has increasingly focused on reducing surgical stress and promoting early functional recovery through evidence-based multidisciplinary care [ 1 ]. Within this framework, optimizing anesthetic management remains an important component of improving perioperative outcomes in minimally invasive gynecologic surgery [ 2 , 3 ]. Among these considerations, the appropriate use of neuromuscular blockade (NMB) during laparoscopic procedures remains a subject of clinical debate. Traditionally, neuromuscular blocking agents (NMBAs) have been routinely administered during laparoscopic surgery to improve abdominal wall relaxation and facilitate surgical exposure [ 4 ]. However, their use is also associated with postoperative residual neuromuscular blockade (rNMB), particularly when recovery is incomplete or reversal is inadequate. Although the incidence of rNMB has declined with advances in monitoring and reversal strategies, it remains a clinically relevant concern because it has been linked to delayed recovery and postoperative respiratory complications [ 4 – 11 ]. Consequently, reducing unnecessary exposure to NMBAs has attracted increasing attention, especially in the context of ERAS. At the same time, completely avoiding NMBAs is not without controversy. Large observational studies have suggested that omitting muscle relaxants may be associated with more difficult tracheal intubation [ 12 ]. In contrast, several studies have shown that satisfactory intubating conditions and acceptable surgical exposure can still be achieved without routine neuromuscular blockade when anesthesia is carefully optimized using propofol and remifentanil [ 13 , 14 ]. However, these findings have not been consistent across different surgical settings, and their applicability to laparoscopic hysterectomy remains uncertain. In gynecologic laparoscopy, interest in minimizing neuromuscular blockade has grown. Previous studies have reported that acceptable surgical conditions may be maintained without continuous neuromuscular blockade by combining adequate anesthetic depth with appropriate patient positioning [ 14 – 18 ]. Such strategies may reduce the need for pharmacological reversal and potentially simplify perioperative management within ERAS pathways. Nevertheless, whether continuous neuromuscular blockade is truly necessary for routine laparoscopic hysterectomy remains an important clinical question [ 14 – 18 ]. Despite growing interest in reduced-exposure NMB strategies, high-quality randomized evidence in patients undergoing laparoscopic hysterectomy remains limited. Most previous studies have compared different depths of neuromuscular blockade rather than evaluating complete avoidance of muscle relaxants together with perioperative recovery outcomes. Therefore, we conducted a prospective, randomized, blinded trial comparing three anesthetic strategies: no muscle relaxant, induction-only muscle relaxant, and continuous neuromuscular blockade. The primary objective was to compare clinically acceptable intubating conditions across these three strategies, with surgical workspace and recovery variables assessed as secondary or exploratory outcomes. Postoperative pain and inflammatory biomarkers were assessed to provide exploratory observations related to perioperative recovery in laparoscopic hysterectomy.

Supplementary Material 1. Supplementary Material 1.