Gasless vNOTES vs traditional vNOTES for benign gynecological disease: a randomized controlled clinical trial

doi:10.21203/rs.3.rs-3987559/v1

Background: Gasless transvaginal natural orifice transluminal endoscopic surgery (G-vNOTES) can avoid complications related to pneumoperitoneum, but there is limited research on G-vNOTES. Here, we aimed to compare the hemodynamic profiles and outcomes of G-vNOTES with traditional vNOTES in the treatment of patients with benign gynecologic disease.

Methods: A total of 120 patients with benign gynecologic disease were randomly assigned to G-vNOTES (n=60) or traditional vNOTES (n=60). The primary outcome was vital sign at different time points. Secondary outcomes included conversion rate, surgical time, anesthesia time, the usage of anesthetics, estimated intraoperative blood loss, visual analogue scale (VAS) score for abdominal and shoulder pain and postoperative nausea and vomiting (PONV) at 2 and 24 hours, intraoperative and postoperative complications, time to first anal exhaust, eating, and getting out of bed after surgery, and length of postoperative hospital stay.

Results: There was no significant difference between the two groups at the baseline level. The results of the multi-level model indicate that the PetCO₂ of the G-vNOTE group is lower than that of the T-vNOTES group (p=0.024). The conversion rate in the G-vNOTES group was higher than that in the G-vNOTES group (16.95% vs 5.26%, p=0.046). No significant differences were observed in other areas.

Conclusions: The PetCO₂ in the G-vNOTES group was lower than that in the T-vNOTES group, which may be more beneficial for the treatment of patients with concomitant cardiovascular and pulmonary diseases. The surgical conversion rate of the G-vNOTES group is higher than that of the G-vNOTES group, which may be related to poor surgical field exposure in the G-vNOTES group, making it more suitable for experienced and confident surgeons.

transvaginal natural orifice transluminal endoscopic surgery (vNOTES)

gasless vNOTES

pneumoperitoneum

benign gynecological disease

Following the application of vNOTES for cholecystectomy, appendectomy and nephrectomy, vNOTES was first used for gynecologic surgery in 2012^[1]. Due to gynecologist's familiarity with the vaginal approach and the advantages of vNOTES in reducing postoperative pain, speeding up postoperative recovery and excellent cosmetic results, the number of gynecological vNOTES surgeries is increasing rapidly worldwide and its safety and feasibility have been demonstrated^[2–4]. Now, vNOTES has been used in gynecological surgery for ovarian cystectomy, myomectomy, adnexal surgery, hysterectomy, uterosacral ligament suspension, sacrocolgapexy, pelvic lymphadenectomy, retroperitoneal sentinel node resection for endometrial cancer, radical hysterectomy for cervical cancer, etc^[5–13]. The first step in conventional laparoscopic surgery is to establish a pneumoperitoneum to facilitate adequate working and observation space^[14]. CO₂ absorption leads to hypercapnia、acidosis、postoperative pain, and is also associated with various cardiopulmonary complications such as tachycardia, arrhythmias, and pulmonary oedema^[15]. Gasless laparoscopic surgery can avoid related problems, and it has a better performance in operation time and hospital stay. However, it also has the problem of higher conversion rate^[16]. Some researchers have explored the application of gasless vNOTES in gynecology^[17–19], including robot-assisted surgery, but there are few clinical trials comparing traditional vNOTES with gasless vNOTES. This prospective randomized controlled study aims to compare the hemodynamic profiles and perioperative indicators of patients with benign gynecologic disease between the two methods (T-vNOTES vs G-vNOTES). We hypothesize that compared with the T-vNOTES group, the G-vNOTES group will perform better in terms of intraoperative hemodynamics and postoperative pain while ensuring surgical safety.

Trial design

This is a prospective, single-blind, single-center randomized controlled clinical trial conducted in Chengdu Women's and Children's Central Hospital, lasting from October 2022 to December 2023. Due to the pilot trial and statistical calculations, considering the dropout rate of 20%, we planned to include 60 patients in each group for a total of 120 patients. This study was approved by the Institutional Review Committee of Chengdu Women’s and Children’s Central Hospital on September 27, 2022 [IRB approved number: 2022(112)]. This trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 on 17/10/2022, and the registration number is No.ChiCTR2200064779. The protocol of this trial has been published in BMC Anesthesiology (DOI: 10.1186/s12871-023-02322-7) in 2023. The whole trial was carried out smoothly in accordance with the requirements of the RCT trial during the research process. and there was no methodological change. The results of this RCT were reported according to the CONSORT 2010 checklist of information.

Participants

The inclusion criteria were patients with benign gynecological diseases with a body mass index (BMI) of 18–25 kg/m², aged 18–60 years, who were to undergo vNOTES surgery under general anesthesia, ASA status I-III, and voluntary participation. Exclusion criteria were no sexual activity, pregnancy or lactation, surgery time greater than 3 hours, history of 2 or more abdominal surgeries, suspected infection or malignancy or rectovaginal endometriosis, participation in other clinical trials within 3 months. During the implementation of the trial, if the patient requests to withdraw from the trial, it can be terminated at any time.

Interventions

Both groups received the same anesthesia method. Anesthesia induction was performed using propofol (2 mg/kg), sulfentanyl (0.3 µg/kg) and cisatracurium (0.15 mg/kg). Adjust sevoflurane to maintain anesthesia and achieve the target bispectral index (BIS) between 40–60 during surgery. All surgeries are performed by gynecologists with more than 3 years of experience in vNOTES surgery. The patient took Trendelenburg position, and underwent surgical disinfection according to the standard of vaginal surgery. Urinary catheterization 10 minutes before surgery, and immediately remove the catheter after surgery. All patients receive prophylactic use of 24-hour antibiotics. Patients in the T-vNOTES group established pneumoperitoneum with carbon dioxide and maintained pneumoperitoneum pressure of 12–14 mmHg during surgery. Use conventional laparoscopic instruments to complete the surgery according to the conventional surgical procedure. For patients in the G-vNOTES group, a steel needle with a diameter of 1.2mm is used to puncture the abdominal wall horizontally 3-5cm below the navel(Fig. 1). The steel needle is then fixed to the steel needle grip above the abdominal wall to create a surgical operating space. The entire surgical process does not use carbon dioxide. Other surgical procedures are the same as T-vNOTES.

Outcomes

The primary outcomes were hemodynamic indicators such as blood pressure, heart rate (HR), airway pressure, tidal volume and PetCO₂ at different time points during surgery. Measured time includes pre-anesthesia (T0), at the time of endotracheal intubation (T1), 10 minutes after endotracheal intubation (T2), at the start of surgery (T3), 10 minutes after the start of surgery (T4), 10 minutes before the end of surgery (T5), at the end of surgery (T6), and at the time of tracheal extubation (T7). Secondary outcomes included time to surgery, time to anaesthesia, intraoperative blood loss, conversion rate, anesthetic consumption, VAS score of abdominal pain, VAS score of shoulder pain and VAS score of PONV at 2 and 24 hours postoperatively, postoperative and intraoperative complications, time to first anal exhaust, eating, and getting out of bed after surgery. Conversion rate is defined as the patient not receiving the surgical modality which they are assigned. It includes the transfer to transumbilical laparoscopic single-site surgery (LESS) or traditional multiport laparoscopic surgery or open surgery or pneumoperitoneal laparoscopy due to bleeding, pelvic adhesions, etc. And it also includes the surgeon who decides to take another surgical method after re-evaluating the patient's vaginal condition and the size or location of the lesion after anesthesia. In the protocol, it was mentioned that a secondary outcome measure was the administration of vasopressor drugs from the start of general anesthesia induction to 15 minutes after endotracheal intubation. However, during the trial, only one patient experienced this situation, so we removed this observation indicator.

Randomisation

A researcher who did not participate in the trial and follow-up process generated a random number sequence using the random number method before the start of the trial. Odd numbers were assigned to the G-Vnotes group, and even numbers were assigned to the T-vNOTES group. After obtaining written informed consent from the patient, the grouping results are placed in an envelope and handed over to the surgeon to begin the surgery, ensuring that postoperative follow-up and statistical analysts are not aware of the grouping information.

Statistical methods

R studio 4.2.2 for Windows (Armonk, NY, United States) was used for statistical analysis. Qualitative data is described using n (%). The chi-square test and Fisher's exact probability method were used for inter group comparison. For data that follow a normal distribution, \(\overline{x}\pm s\) description is used, and t-test is used for inter group comparison; For quantitative data that do not conform to normal distribution, M(P₂₅,P₇₅) is used to describe, and rank-sum test is used for inter group comparison. This study repeated measurements of BIS, airway pressure, PetCO₂, tidal volume, heart rate, blood pressure, and SpO₂ at different time points during surgery. Considering the intra group correlation of repeated measurement data, a multi-level model was used for modeling. Among them, individuals are measured as 2 units horizontally, and each time point is measured as 1 unit horizontally. Taking PetCO2 as an example, the corresponding model can be expressed as:\({\text{PetCO}}{{\text{2}}_{ij}}={\beta _{00}}+{\beta _{01}}{\text{Treatmen}}{{\text{t}}_j}+{\beta _{10}}{t_{ij}}+{\beta _{11}}{\text{Treatmen}}{{\text{t}}_j}{t_{ij}}+\sum\nolimits_{1}^{m} {{\beta _m}} {x_j}_{m}+({\mu _{0j}}+{\mu _{1j}}{t_{ij}}+{e_{ij}})\). Among them, i represents level 1 unit (time); J represents level 2 units (individuals); Treatment represents T-vNOTES/G-vNOTES.

A total of 235 patients who planned to undergo vNOTES surgery were screened, including 9 refused to participate in this trial and 106 did not meet the inclusion criteria. Finally, 120 patients were included. 120 patients were randomly divided into T-vNOTES group (n=60) or G-vNOTES group (n=60) (Figure 2). One patient with T-vNOTES was excluded because the operation time reached 3 hours. Two patients in the T-vNOTES group were excluded due to loss during postoperative follow-up. One patient initially receiving T-vNOTES was converted to LESS due to severe pelvic adhesions. Two patients who initially received T-vNOTES did not undergo vNOTES and went directly to LESS because the decision of the surgeon after re-evaluating the vaginal condition after anesthesia. The conversion rate of the T-vNOTES group was 5.26%. In G-vNOTES group, one patient was excluded due to loss during postoperative follow-up. One patient was converted to T-vNOTES due to hemorrhage, one patient was converted to T-vNOTES due to severe pelvic adhesions, and 1 patient was injected with CO₂ into the abdominal cavity for pelvic exploration due to poor exposure of the surgical field after the operation. Because the surgeon re-evaluated the vaginal condition and condition after anesthesia, 3 patients were converted to T-vNOTES and 4 patients were transferred to LESS. The conversion rate of the G-vNOTES group was 16.95%. The conversion rate of G-vNOTES group was higher than that of T-vNOTES group(p=0.046).

Table 1 summarizes the baseline characteristics of the two groups. There were no statistically significant differences between two groups in terms of age, body mass index, number of vaginal births, number of abdominal surgeries, ASA grade and inverted bed angle. This trial included 60 cases of fallopian tube surgery, 34 cases of oophorocystectomy, 2 cases of adnexectomy, and 20 cases of hysterectomy (with or without adnexectomy). There was no statistically significant difference in the surgical composition between the two groups.

Table 1. The patients’ characteristics

Characteristics		G-vNOTES (n=59)	T-vNOTES (n=57)	Statistics	P
Number of vaginal deliveries (times)	None	36(61.02)	41(71.93)	—	0.241*
	1	19(32.20)	11(19.30)
	2	4(6.78)	5(8.77)
Number of abdominal surgeries (times)	None	37(62.71)	31(54.39)	χ²=0.83	0.363
Number of abdominal surgeries (times)	1	22(37.29)	26(45.61)
Age (year) (̅x±s)		36.46±10.04	34.67±8.64	t=1.03	0.306
BMI (kg/m²) (̅x±s)		21.84±2.04	21.69±2.29	t=0.37	0.711
ASA classification	I	39(62.96)	36(60.38)	χ²=0.08	0.783
ASA classification	II	20(37.04)	21(39.62)
Operating table tilt angle (°)(Median [lQR])		29.00(20.00,30.00)	30.00(20.00,30.00)	Z=0.28	0.780#
Complications	Hypertension	4(6.78)	1(1.75)	χ²=0.77	0.382
	Hepatitis B	2(3.39)	6(10.53)	χ²=1.32	0.250
	Pulmonary tuberculosis	1(1.69)	0(0.00)	—	1.000*
	Diabetes	1(1.69)	0(0.00)	—	1.000*

Note: “*” use Fisher's exact probability method; “#” use rank sum test.

Table 2 summarizes the main outcomes of this study. This experiment adopted per-protocol analysis. We analyzed the main outcomes after excluding lost follow-up cases, a case excluded due to surgery time reaching 3 hours, and transferred cases (G-vNOTES group n=49, T-vNOTES group n=54). The estimation results of the null model showed that the (Intraclass Correlation Coefficient, ICC) of HR, systolic blood pressure (SBP), SpO_2, diastolic blood pressure (DBP), airway pressure, PetCO₂, and tidal volume were 21.68%, 4.80%, 0.32%, 0.10%, 40.36%, 30.66%, and 40.61%. In terms of HR, airway pressure, PetCO₂, and tidal volume, 21.68%, 40.36%, 30.66%, and 40.61% of the variation came from repeated measurements of the same individual at different time points, indicating the existence of a two-level structure in the data. The estimation results of the multi-level model show that there is no statistically significant difference between the T-vNOTES group and the G-vNOTES group in terms of HR, DBP SBP, SpO₂, BIS and tidal volume, but the PetCO₂ in the G-vNOTES group was lower than that in the T-vNOTES group(p=0.024). Separately, the PetCO₂ levels in the G-vNOTES group were lower than those in the T-vNOTES group 10 minutes before the end of surgery (p<0.001) and at the end of surgery (p=0.023) (Figure 3). The airway pressure in the G-vNOTES group was lower than that in the T-vNOTES group at 10 minutes after the start of surgery (p=0.009) and 10 minutes before the end of surgery (p=0.039) (Figure 4).

Table2. A summary of the main outcomes

Characteristics		G-vNOTES (n=49)	T-vNOTES (n=54)	statistic	p
T0	HR (bpm)(̅x±s)	77.58±10.57	77.85±14.64	t=0.10	0.918
	SBP (mmHg)(̅x±s)	119.94±14.77	114.68±13.10	t=1.90	0.061
	DBP (mmHg)(̅x±s)	75.29±8.55	71.47±8.77	t=2.21	0.029
	SpO₂ (%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-0.03	0.978#
T1	Airway pressure (cmH₂O)(Median [lQR])	11.00(10.00,12.00)	12.00(11.00,14.00)	Z=-1.45	0.147#
	PetCO₂ (mmHg)(̅x±s)	33.03±4.36	32.30±4.44	t=0.73	0.466
	Tidal volume (mL)(Median [lQR])	374.00(344.00,400.00)	371.00(311.00,436.00)	Z=0.74	0.461#
	HR (bpm)(̅x±s)	76.04±13.72	74.07±11.15	t=0.80	0.427
	SBP (mmHg)(Median [lQR])	106.00(99.00,118.50)	107.50(99.00,112.00)	Z=0.14	0.887#
	DBP (mmHg)(Median [lQR])	67.50(62.00,74.00)	67.50(58.00,74.00)	Z=1.28	0.199#
	SpO₂ (%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-0.83	0.408#
T2	Airway pressure (cmH₂O)(Median [lQR])	12.00(11.00,13.00)	12.00(11.00,13.00)	Z=-0.56	0.577#
	PetCO₂ (mmHg)(̅x±s)	32.78±3.09	33.41±3.94	t=0.90	0.370
	Tidal volume (mL)(Median [lQR])	386.49±45.46	393.39±61.54	t=0.64	0.522
	HR (bpm)(̅x±s)	64.78±9.81	64.04±10.14	t=0.37	0.709
	SBP (mmHg)(Median [lQR])	97.00(91.00,102.00)	97.00(91.00,104.00)	Z=-0.53	0.599#
	DBP (mmHg)(̅x±s)	58.24±9.61	57.59±9.53	t=0.35	0.730
	SpO₂ (%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-0.95	0.340#
T3	Airway pressure (cmH₂O)(Median [lQR])	12.00(11.00,13.00)	12.00(11.00,14.00)	Z=-0.35	0.724#
	PetCO₂ (mmHg)(̅x±s)	32.67±3.02	33.54±3.46	t=1.34	0.182
	Tidal volume (mL)(Median [lQR])	386.00(358.00,414.00)	398.00(349.00,420.00)	Z=0.23	0.817#
	HR (bpm)(̅x±s)	63.31±10.48	64.22±11.31	t=0.43	0.672
	SBP (mmHg)(Median [lQR])	96.00(91.00,103.00)	96.00(91.00,105.00)	Z=-0.13	0.894#
	DBP (mmHg)(Median [lQR])	58.00(54.00,63.00)	55.00(49.00,66.00)	Z=1.17	0.240#
	SpO₂ (%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-1.11	0.269#
T4	Airway pressure (cmH₂O)(̅x±s)	13.27±2.62	14.79±3.15	t=2.65	0.009
	PetCO₂ (mmHg)(̅x±s)	33.29±2.75	34.11±3.52	t=1.32	0.190
	Tidal volume (mL)(̅x±s)	378.20±41.80	378.70±53.91	t=0.05	0.958
	HR (bpm)(̅x±s)	61.16±8.96	63.17±9.11	t=1.12	0.264
	SBP (mmHg)(Median [lQR])	99.00(94.00,105.00)	100.00(96.00,106.00)	Z=-0.62	0.532#
	DBP (mmHg)(̅x±s)	61.10±8.37	64.22±11.15	t=1.59	0.114
	SpO₂(%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-1.48	0.138#
T5	Airway pressure (cmH₂O)(Median [lQR])	14.00(12.00,15.00)	15.00(13.00,18.00)	Z=-2.05	0.039#
	PetCO₂ (mmHg)(Median [lQR])	35.00(33.00,36.00)	37.00(35.00,39.00)	Z=-3.87	<0.001#
	Tidal volume (mL)(̅x±s)	378.69±38.29	391.74±46.14	t=1.55	0.124
	HR (bpm)(Median [lQR])	63.00(59.00,70.00)	65.50(58.00,73.00)	Z=-1.15	0.248#
	SBP (mmHg)(Median [lQR])	98.00(95.00,107.00)	97.00(94.00,106.00)	Z=0.28	0.780#
	DBP (mmHg)(Median [lQR])	62.00(54.00,69.00)	61.00(53.00,66.00)	Z=0.58	0.561#
	SpO₂(%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-1.26	0.208#
T6	Airway pressure (cmH₂O)(Median [lQR])	14.00(12.00,15.00)	14.00(12.00,16.00)	Z=-0.55	0.581#
	PetCO₂ (mmHg)(̅x±s)	34.29±3.12	35.67±2.97	t=2.30	0.023
	Tidal volume (mL)(̅x±s)	371.10±42.03	384.65±52.80	t=1.43	0.156
	HR (bpm)(̅x±s)	63.06±8.27	66.78±11.01	t=1.92	0.058
	SBP (mmHg)(̅x±s)	101.45±9.67	100.04±9.30	t=0.75	0.452
	DBP (mmHg)(̅x±s)	61.00(53.00,69.00)	58.50(51.00,67.00)	Z=0.94	0.348#
	SpO₂(%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-0.45	0.649#
T7	Airway pressure (cmH₂O)(̅x±s)	10.56±5.95	11.76±6.37	t=0.58	0.565
	PetCO₂ (mmHg)(̅x±s)	37.18±4.40	39.00±6.62	t=1.09	0.281
	Tidal volume (mL)(Median [lQR])	300.00(284.00,380.00)	310.00(281.00,394.00)	Z=-0.54	0.591#
	HR (bpm)(̅x±s)	83.49±12.89	87.51±13.72	t=1.52	0.131
	SBP (mmHg)(̅x±s)	113.69±11.00	114.04±13.40	t=0.14	0.888
	DBP (mmHg)(̅x±s)	73.14±10.34	71.02±11.06	t=1.00	0.318
	SpO₂(%)(Median [lQR])	100.00(100.00,100.00)	100.00(100.00,100.00)	Z=-1.43	0.153#
T8	HR (bpm)(̅x±s)	86.04±7.88	85.40±6.51	t=0.41	0.682
	SBP (mmHg)(Median [lQR])	84.48±10.53	85.61±13.38	t=0.46	0.643
	DBP (mmHg)(̅x±s)	117.00(112.00,123.00)	116.00(109.00,124.00)	Z=0.86	0.390#
	SpO₂ (%)(Median [lQR])	76.00±8.89	73.76±11.52	t=1.08	0.282

Note: “#” uses rank sum test.

Table 3 summarises the other outcomes. There is no statistically significant difference between the G-vNOTES group and the T-vNOTES group in terms of surgical time, anesthesia time, intraoperative blood loss, anesthesia consumption, VAS and PONV scores at 2 and 24 hours post surgery, postoperative and intraoperative complications, time to first anal exhaust, eating, and getting out of bed after surgery.

Table3. A summary of the other outcomes

Characteristics	G-vNOTES (n=49)	T-vNOTES (n=54)	statistic	p
Operative time (min)(Median [lQR])	65.00(50.00,81.00)	64.00(55.00,85.00)	Z=-0.41	0.679#
Blood loss (mL)(Median [lQR])	20.00(20.00,50.00)	20.00(20.00,30.00)	Z=0.28	0.781#
Anesthesia time (min)(̅x±s)	93.35±26.61	97.50±31.07	t=0.72	0.470
Dosage of sufentanil use (ug)(Median [lQR])	17.50(15.60,19.00)	18.00(16.50,20.00)	Z=-1.45	0.147#
Shuna usage (mg)(Median [lQR])	8.40(8.00,9.50)	9.00(7.50,10.00)	Z=-1.16	0.248#
M-hydroxylammonia usage (mg)(Median [lQR])	0.00(0.00,0.00)	0.00(0.00,0.00)	Z=1.10	0.272#
CPR on the first postoperative day (mg/L)(Median [lQR])	7.10(5.20,10.10)	7.40(6.10,11.60)	Z=-0.31	0.757#
Intraoperative complications	0	0	—	—
Postoperative complications	1(2.04)	1(1.85)	—	1.000*
Abdominal pain 2 hours postoperatively(Median [lQR])	1.00(0.00,3.00)	2.00(0.00,4.00)	Z=-1.21	0.226#
Shoulder pain 2 hours postoperatively (Median [lQR])	0.00(0.00,0.00)	0.00(0.00,0.00)	Z=-1.23	0.218#
PONV 2 hours postoperatively (Median [lQR])	0.00(0.00,0.00)	0.00(0.00,0.00)	Z=-0.72	0.472#
Abdominal pain 24 hours postoperatively(Median [lQR])	0.00(0.00,1.00)	0.00(0.00,2.00)	Z=-0.74	0.459#
Shoulder pain 24 hours postoperatively(Median [lQR])	0.00(0.00,0.00)	0.00(0.00,0.00)	Z=0.33	0.741#
PONV 24 hours postoperatively (Median [lQR])	0.00(0.00,0.00)	0.00(0.00,0.00)	Z=1.82	0.068#
First postoperative anal exhaust time (Median [lQR])	9.00(7.00,15.00)	13.00(8.00,17.00)	Z=-1.51	0.130#
First postoperative eating time (Median [lQR])	10.00(7.00,18.00)	14.50(9.00,18.00)	Z=-1.44	0.149#
First time getting out of bed after surgery(Median [lQR])	7.00(5.00,18.00)	8.00(6.00,18.00)	Z=-0.59	0.555#
Postoperative hospitalization days(Median [lQR])	3.00(2.00,3.00)	3.00(2.00,3.00)	Z=0.94	0.348#

Note: “*” use Fisher's exact probability method; “#” use rank sum test.

One patient in the T-vNOTES group underwent debridement and suturing on the 5th day after surgery due to vaginal incision infection, and the wound recovered well. One patient in the G-vNOTES group was complicated with postoperative acute pelvic inflammation and was discharged after 14 days of antibiotic treatment. No other postoperative complications were observed.

In this study, we compared the surgical treatment of benign gynecological diseases using traditional pneumoperitoneum vNOTES and gasless vNOTES. According to our review of the literature, there is no similar RCT trial. We found that the G-vNOTES group had lower airway pressure and PetCO₂. In previous studies, some cardiopulmonary changes (increased peak airway pressure, decreased cardiac output, pulmonary compliance) occurred during pneumoperitoneum, which is consistent with the results of our trial^[20].

Conventional vNOTES uses CO₂ to form an artificial pneumoperitoneum to provide a field of view for the operation. Increased intra-abdominal pressure, compression of abdominal organs, increased blood volume flowing back to the heart, and increased central venous pressure (CVP). High CVP is associated with poor microcirculatory flow perfusion^[21]. CO₂ pneumoperitoneum causes the rising of diaphragm, increasement of intrathoracic pressure and ventricular afterload. Animal models have shown that during intra-abdominal injection of CO_2, pulmonary artery pressure increases to two times the baseline level^[22]. Patients with coronary artery disease, chronic hypertension, and other conditions are extremely sensitive to changes in left ventricular afterload^[23]. CO₂ pneumoperitoneum can also slow blood flow, increase blood viscosity, and cause microtears in the vascular endothelium, which promotes the formation of venous thrombosis^[24]. On the other hand, CO₂ pneumoperitoneum causes hypercapnia, acidosis, and a 20% decrease in stroke volume at normal blood volume, and this more pronounced with moderate blood loss^[25].

A systematic review suggested that there was moderate to strong evidence to support a similar safety profile in low intra-abdominal pressure during laparoscopic surgery compared with conventional abdominal pressure laparoscopic surgery, with lower pain scores, lower rates of mild postoperative complications, lower rates of PONV, and shorter hospital stays^[26]. We did not find similar results in this trial, and we suspect that it may be related to the shorter operation time in this trial. Although there was no statistically significant difference in PONV at 24 hours postoperatively(p = 0.068), it was seen that the G-vnotes group appeared to have some advantages which might be related to the lower amount of anesthetic consumed. The first postoperative exhaust median time in the G-vNOTES group was 9 (IQR7,15) hours verses 13 (IQR8,17) hours in the T-vNOTES group (p = 0.13). The first postoperative meal median time was 10 (IQR7,18) hours, and 14.5 (IQR9,18) hours in the T-vNOTES group (p = 0.149). G-vNOTES seems to be more conducive to rapid postoperative recovery.

Many studies on vNOTES have mentioned the advantages of vNOTES in avoiding abdominal incisions and their complications^[27–29]. In our trial, there was one postoperative infection complication in each group, and both recovered well after anti-inflammatory therapy, but this means that the incision healing and infection prevention of the vNOTES procedure deserve more attention.

According to our definition of the conversion rate (not performed as planned) prior to the start of the trial, the conversion rate was 5.26% in the T-vNOTES group and 16.95% in the G-vNOTES group. Most transfers are caused by reassessment by surgeons after anesthesia, which is more pronounced in the G-VNOTES group (3.51% vs 11.86%), and mostly occur in relatively inexperienced doctors. The transfer in this situation did not cause additional harm to the patient. If this factor is excluded, the rate of T-vNOTES group and G-vNOTES group conversion due to factors such as adhesion or bleeding are 1.75% and 5.08%. It can be seen that sufficient and accurate preoperative evaluation is crucial. One patient in the G-vNOTES group was transferred to pneumoperitoneal laparoscopic exploration at the end of the operation, and the other patient switched to traditional vNOTES due to intraoperative bleeding, which showed that the surgical field exposure in the G-vNOTES group was worse than that in the T-vNOTES group. Taking G-vNOTES is a matter of caution for less experienced physicians or patients with a higher risk of bleeding. For patients suspected of severe pelvic adhesions, caution should be exercised in any form of vNOTES.

This trial has some limitations. Firstly, due to cost constraints and inadequate outcome measures, this trial did not measure the patient's blood pH, blood carbonate content, pulmonary artery pressure, cardiac stroke volume and other indicators, so the hemodynamic monitoring is not perfect, and more monitoring tools are needed to address this aspect. Secondly, this trial included a variety of surgical methods for benign gynecological diseases, including ovarian cystectomy, salpingectomy, hysterectomy, and various surgical procedures. Although it was verified that there was no statistical difference in the proportion of surgical composition between the two groups, it may still lead to errors. Thirdly, this trial was not performed by the same surgeon. Although each surgeon had more than 3 years of experience in vNOTES, we observed during the implementation of the trial that the exposure of G-vNOTES did not affect experienced surgeons, but had a certain impact on those who were relatively less experienced. Fourthly, the conversion rate of this trial is relatively high, which is closely related to insufficient preoperative evaluation, which cannot fully reflect the safety of the surgery. Finally, this trial was a single-center trial with a total of 120 cases, which was statistically significant, but still needed to be validated by a larger sample.

The PetCO₂ and airway pressure in the G-vNOTES group were lower than those in the T-vNOTES group, which may be more beneficial for the treatment of patients with concomitant cardiovascular and pulmonary diseases. G-vNOTES has a better trend in PONV, postoperative first exhaust time, and postoperative first meal time, but the conversion rate is higher. Due to its relatively poor visual field exposure, it is more suitable for experienced and confident surgeons. There was no significant difference between the two groups in terms of surgical time, estimated intraoperative blood loss, anesthetic usage, postoperative pain score, postoperative length of hospital stay, and first postoperative time of getting out of bed.

Due to the nature of this study, participants in this study do not consent to the public sharing of their data and therefore do not mention the original data in the supplementary notes, but may apply to the investigator for use through reasonable reasons.

Funding

None.

Author Contribution

Yanjun Wang, Kai Liu, and Zhaolin Gong contributed equally to this study as co-first authors. Qinghua Huang, Qianqian Zhang, Dan Feng, Jiaojiao Chen, Ang Mao, Xia Yu, and Lin Zhang all participated in the implementation of this trial. Yonghong Lin, Li He, and Yu Cui, as the corresponding authors, jointly guided the design and implementation of this trial. All authors reviewed the manuscript.

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No competing interests reported.

Gasless vNOTES vs traditional vNOTES for benign gynecological disease: a randomized controlled clinical trial

Status:

Version 1

Abstract

Figures

Introduction

Methods

Trial design

Participants

Interventions

Outcomes

Randomisation

Statistical methods

Results

Discussion

Conclusions

Declarations

Author Contribution

References

Additional Declarations

Status:

Version 1