Gery Lamblin
email: gery.lamblin@chu-lyon.fr

M De Boisredon

L Picard

A Atallah

J Massardier

G Chene

E Nohuz

Fourth degree perineal tears: surgical repair technique in 10 steps

Keywords: fourth degree perineal tears, obstetrical anal sphincter injury (OASI), vaginal birth fourth degree perineal tears, obstetrical anal sphincter injury (OASIS), vaginal birth, anal sphincter, postpartum urinary retention

Obstetrical anal sphincter injury (OASIS) may lead to significant comorbidities, including anal incontinence, rectovaginal fistula, and pain. A correct repair is required to avoid improper healing, as a persistent defect in the external anal sphincter after delivery can increase the risk of complications and worsening of symptoms following subsequent vaginal deliveries. Herein is described the surgical repair technique for a fourth degree perineal tear. Regarding resident education, there are challenges associated with the proper training in OASIS repair. The procedure is illustrated by an instructive video article that standardizes the essential steps to make the technique ergonomic and easy to perform with step-by-step explanations.

Introduction

Obstetrical anal sphincter injury (OASIS) may lead to significant comorbidities, including anal incontinence, rectovaginal fistula, and pain. Proper repair is required to avoid the risk of complications and worsening of symptoms following subsequent vaginal deliveries. OASIS should be repaired by practitioners appropriately trained and comfortable with performing such repairs.

Case presentation

The case of a 25-year-old primiparous patient, at 39 weeks of amenorrhea, delivered vaginally spontaneously without episiotomy is presented. A fourth degree OASIS was diagnosed and the patient was transferred to the operating room.

Surgical technique

We present the surgical technique of a Fourth degree perineal tears repair in ten steps.

The surgical team should be familiar with the anal sphincter complex anatomy.

The internal anal sphincter is a 3 to 5 mm thick continuation of the rectal smooth muscle and is responsible for ensuring continence at rest. The Obstetrical Anal Sphincter Injuries international classification was used: the fourth degree represents an injury to the perineum involving the anal sphincter complex and anal epithelium.

The Step 1 consists in the proper installation of the patient and preparation of the surgical area

The surgical repair should be performed in an operating room, to ensure appropriate and optimal lighting, under neuraxial anesthesia, and should absolutely be performed by an experimented obstetrician. A Prophylactic antibiotics by cephalosporin second generation at the start of the repair should be administered.

The Step 2 consists in a proper physical examination, including vaginal and rectal examination

Before starting the repair, a proper physical examination of the vagina and rectum is required. The vaginal examination consists in an inspection of the perineum and distal posterior vagina, thorough tracking of the full extent of vaginal tears in order to allow the correct repair, plan by plan, of the anorectal mucosa, the internal anal sphincter, and the external anal sphincter. The ends of the external sphincter are first identified and grasped with 2 temporary sutures because they often retract.

The Step 3 consists in anal mucosa suture

The mucosal repair is carried out with a 3.0 absorbable synthetic monofilament suture.

Knots must absolutely be tied externally to the anal canal. The anal mucosa is very thin. The mucosal repair is gradually and slowly performed with a submucosal continuous suture, and stopped just at the anal margin limit, then knots are tied.

The Step 4 consists in a very careful rectal examination

This step ensures that the repair is adequate and allows the identification of any sutures connecting the vagina to the rectum.

The step 5 consists in the Internal Sphincter suture

This is a critical step. Indeed, the internal sphincter defect absolutely needs to be repaired to allow an improvement of anal continence. This step is performed with a 2.0 braided absorbable interrupted horizontal suture, as seen in the cartridge in the lower part, with "U"-shaped knots. The mattress suture must be regularly swabbed with polyvidione iode. Three knots are necessary in this case to suture the internal sphincter.

The Step 6 consists in the vaginal wall suture

The vaginal wall suture is initiated in order to get a better exposition and to decrease vaginal bleeding. A 2.0-braided absorbable continuous suture is used in the beginning with the vaginal superior angle. The running process is stopped just before the external sphincter suture step.

The Step 7 consists in the external anal sphincter suture

At first, the muscle ends previously grasped with the 2 temporary sutures must be tracked. Three knots are used to tighten properly the external sphincter and then knots are tied.

The Step 8 consists in continuing the suturing of the lower part of the vaginal wall.

The process is stopped just before the hymeneal remnants, as for a usual second degree perineal tear.

The Step 9 consists in suturing the hymeneal remnants and posterior perineum.

The step 10 consists in suturing vaginal muscles and perineal skin.

The perineal body and perineal muscles (bulbo cavernous and transverse perineal muscles) are reconstructed to release the tension on the anal sphincter.

Finally, the perineal skin is sutured with a 2.0 braided absorbable suture.

A final rectal examination is performed to ensure that the repair is adequate and to identify any sutures connecting the vagina to the rectum potentially made during the repair. After the surgical repair is done, the bladder is emptied by catheterization.

Postoperative care consists in:

Analgesia with nonsteroidal anti-inflammatory drugs (NSAIDS) and acetaminophen as first line analgesics, antibiotics for 2 days, and the use of postoperative laxatives.

Early pelvic floor physiotherapy and a follow-up with an obstetrician are planned 10 days after the repair.

Discussion

Obstetrical anal sphincter injuries (OASIS) are obstetrical lesions of the anal sphincter corresponding to third and fourth degree tears according to the WHO-RCOG Classification [START_REF]World Health Organization classification of diseases (ICD)[END_REF].

OASIS may cause many functional consequences, such as perineal pain, acute retention of urine, dyschesia, and abscess in the short term, and fistulas, dyspareunia, neuropathy, and anal incontinence in the long term [START_REF] Sideris | Risk of obstetric anal sphincter injuries (OASIS) and anal incontinence: A meta analysis[END_REF]. Active or passive gas and/or stool incontinence affects on average 39% of patients after OASIS [START_REF] Sideris | Risk of obstetric anal sphincter injuries (OASIS) and anal incontinence: A meta analysis[END_REF][START_REF] Ekstein-Badichi | Temporal trends in the incidence of and associations between the risk factors for obstetrical anal sphincter injuries[END_REF]. These injuries can have a significant impact on women as they impair their quality of life and are responsible for a significant financial and psychological burden on patients [START_REF] Chiu | Risks and Associations of Third-and Fourth-Degree Lacerations: An Urban Single Center Experience[END_REF]. Furthermore, in terms of resident education, there are challenges associated with proper training in OASIS repair. This article is part of this perspective of facilitating teaching of the proper repair technique of obstetric perineal lesion [START_REF] Hickman | Accurate diagnosis and repair of obstetric anal sphincter injuries: why and how[END_REF].

It is necessary to make a very acute assessment of perineal and rectal lesion postdelivery. The study by Fernando et al. conducted by the RCOG has found that 33% of obstetricians consider a third degree injury as a second degree injury, and 22% of residents consider a third degree injury as a second degree injury [START_REF] Fernando | Management of obstetric anal sphincter injury: a systematic review & national practice survey[END_REF][START_REF] Andrews | Occult anal sphincter injuries-myth or reality?[END_REF]. Careful examination by a vaginal touch and a rectal touch is essential after childbirth [START_REF] Ekstein-Badichi | Temporal trends in the incidence of and associations between the risk factors for obstetrical anal sphincter injuries[END_REF][START_REF] Chiu | Risks and Associations of Third-and Fourth-Degree Lacerations: An Urban Single Center Experience[END_REF].

The means of prevention are mainly represented by the control of the descent of the fetal head allowing a reduction of 50% to 70% of OASIS [START_REF] Marty | Déchirures périnéales obstétricales et épisiotomie : aspects techniques. RPC prévention et protection périnéale en obstétrique CNGOF[END_REF]. Perineal support by host sponge or perineal massage seem to be interesting to limit the expulsion efforts during the expulsion phase [START_REF] Seidenari | Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management[END_REF]. Mediolateral or lateral episiotomy (60° angle) decreases the risk of OASIS during an instrumental delivery compared to a midline episiotomy or no episiotomy [START_REF] Schreiber | The role of mediolateral episiotomy during vacuum assisted vaginal delivery with soft cup devices[END_REF].

Vacuum-assisted vaginal extraction presents less risk of OASIS lesion than forceps;

it is advisable to remove forceps before the expulsion phase [START_REF] Schreiber | The role of mediolateral episiotomy during vacuum assisted vaginal delivery with soft cup devices[END_REF].

A few studies have compared different suture types used for external and internal sphincter repair. Suture should be absorbable or quickly absorbable. Studies comparing polyglactin 2-0 (Vicryl) to polydioxanone 3-0 (PDS) have found no difference in terms of morbidity at 6 weeks post-delivery [START_REF]Prevention and Management of Obstetric Lacerations at Vaginal Delivery[END_REF].

There is currently no comparative study that could help define the best repair technique to use for anal mucosa repair. The repair of the anal mucosa can be performed either using interrupted sutures of polyglactin 3-0 or using monofilament running suture with polydioxanone 3-0. It is advisable to avoid "X"-shaped knots, as they are most ischemic and ineffective regarding healing [START_REF] Hickman | Accurate diagnosis and repair of obstetric anal sphincter injuries: why and how[END_REF][START_REF] Lindqvist | A modified surgical approach to women with obstetric anal sphincter tears by separate suturing of external and internal anal sphincter. A modified approach to obstetric anal sphincter injury[END_REF][START_REF] Viannay | Management and consequences of obstetrical anal sphincter injuries: Review[END_REF]. The recent good clinical practices of the CNGOF (Collègue national des gynécologues et obstétriciens français, French college of gynecologists and obstetricians) is in accordance with these recommendations [START_REF] Marty | Déchirures périnéales obstétricales et épisiotomie : aspects techniques. RPC prévention et protection périnéale en obstétrique CNGOF[END_REF].

Internal sphincter repair has been shown to be essential to improve anal continence [START_REF] Ekstein-Badichi | Temporal trends in the incidence of and associations between the risk factors for obstetrical anal sphincter injuries[END_REF][START_REF] Viannay | Management and consequences of obstetrical anal sphincter injuries: Review[END_REF]. The external sphincter can be sutured using the end-to-end technique or the overlap technique, neither of these techniques is preferred over the other. The studies assessing either of both techniques are heterogeneous, include a small number of patients, and poorly assess the quality of life regarding incontinence and patient satisfaction; it is therefore unclear whether one of these techniques is preferable compared to the other regarding the long-term outcome [START_REF] Hickman | Accurate diagnosis and repair of obstetric anal sphincter injuries: why and how[END_REF][START_REF] Fernando | Management of obstetric anal sphincter injury: a systematic review & national practice survey[END_REF]. The end-toend technique allows the use of Metzenbaum scissors to dissect the ends of the external sphincter. The overlap technique requires more dissection and mobilization of the sphincter ends, along the ischioannal fossa.

It is possible to delay the repair for 8 to 12 hours in order to wait for an experimented obstetrician to be available with no difference in the incontinence scores at 6 and 12 months [START_REF] Lewicky-Gaupp | Early Secondary Repair of Obstetric Anal Sphincter Injury Breakdown: Contemporary Surgical Techniques and Experiences From a Peripartum Subspecialty Clinic[END_REF]. A detailed account of the extent of the lesions, method of repair, and equipment used is recommended.

As latest studies have demonstrated, the administration of a prophylactic single dose intravenous antibiotics at the beginning of the repair (2nd generation cephalosporin) allows to prevent perineal wound complications and morbidity [START_REF] Fernando | Methods of repair for obstetric anal sphincter injury. Cochrane Pregnancy and Childbirth Group, éditeur[END_REF][START_REF] Buppasiri | Antibioticprophylaxis for third-and fourth-degree perineal tear during vaginal birth. Cochrane Pregnancy and Childbirth Group, éditeur[END_REF]. In addition, early administration of NSAIDS decreases perianal pain [START_REF] Seidenari | Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management[END_REF][START_REF] Hedayati | Rectal analgesia for pain from perineal trauma following childbirth. Cochrane Pregnancy and Childbirth Group, éditeur[END_REF].

Patients with OASIS and epidural anesthesia are at elevated risk for postpartum urinary retention [START_REF] Mulder | Delivery-related risk factors for covert postpartum urinary retention after vaginal delivery[END_REF][START_REF] Lamblin | Identification of risk factors for postpartum urinary retention following vaginal deliveries: A retrospective case-control study[END_REF]. Epidural analgesia is also considered a risk factor for postpartum urinary retention as it directly affects the sensitivity and contractility of the bladder.

Several authors have proposed a systematic indwelling catheterization for a minimum of 12 hours post-partum [START_REF] Seidenari | Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management[END_REF][START_REF] Mulder | Delivery-related risk factors for covert postpartum urinary retention after vaginal delivery[END_REF]. Taking into consideration the augmented risk of urinary infections, some author have proposed to empty the bladder by catheterization at the end of the repair and implement a systematic bladder scanning protocol to ensure proper bladder emptying [START_REF] Lamblin | Identification of risk factors for postpartum urinary retention following vaginal deliveries: A retrospective case-control study[END_REF]. The use of laxatives allows for quicker and less painful bowel motions and an earlier discharge from hospital, but has not been associated with a significant difference in the scores of continence or anal manometry and endoanal ultrasound at 3 months post-partum [START_REF] Seidenari | Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management[END_REF][START_REF] Mahony | Randomized, Clinical Trial of Bowel Confinement vs. Laxative Use After Primary Repair of a Third-Degree Obstetric Anal Sphincter Tear[END_REF].

Conclusion

Obstetrical anal sphincter injuries (OASIS) diagnosed properly and repaired in good conditions can lead to a good functional outcome. All women after delivery should be carefully examined for perineal or vaginal tears with systematic rectal examination to avoid missing OASIS.

In order to reduce the rate of unknown sphincter lesions, it is essential to improve the skills of the teams in charge of delivery, as well as midwife, residents, and experimented obstetricians.

The authors declare no conflict of interest


MD Sachiko Matsuzaki
email: smatsuzaki@chu-clermontferrand.fr

PhD Martine Bonnin

MD Aurelie Fournet-Fayard

MD Jean-Etienne Bazin

MD, PhD Revaz Botchorishvili

Effects of Low Intraperitoneal Pressure on Quality of Postoperative Recovery after Laparoscopic Surgery for Genital Prolapse in Elderly Patients Aged 75 Years or Older

Keywords: length of hospital stay after surgery, pneumoperitoneum, Quality of Recovery-40

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTERVENTIONS

Laparoscopic promontofixation for the treatment of genital prolapse was performed using low IPP and warmed, humidified CO2 gas . When a promontory could not be easily identified, laparoscopic pectopexy was alternatively performed.

MEASUREMENTS

The primary outcome was the QoR-40 (Quality of Recovery-40) score at 24 hours postoperatively. Secondary outcomes were postoperative pain using a 100-mm visual analogue scale (VAS) and length of hospital stay after surgery (LHSS).

MAIN RESULTS

Introduction

The chance of a woman experiencing a prolapse increases with age [START_REF] Olsen | Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence[END_REF]. The lifetime risk of undergoing a single operation for prolapse or incontinence by age 80 is 11.1% [START_REF] Olsen | Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence[END_REF]. A recent study demonstrated that the population undergoing surgery is aging at a faster rate than the general population [START_REF] Søreide | Surgery for an ageing population[END_REF]. By 2030, it is estimated that one-fifth of patients ≥75 years will undergo surgery each year in England [START_REF] Søreide | Surgery for an ageing population[END_REF]. Therefore, the number of very elderly patients (age ≥75 years) who require surgery for genital prolapse is also expected to rise [START_REF] Olsen | Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence[END_REF][START_REF] Søreide | Surgery for an ageing population[END_REF]. The elderly are often excluded from clinical trials [START_REF] Søreide | Surgery for an ageing population[END_REF][START_REF] Cherubini | The persistent exclusion of older patients from ongoing clinical trials regarding heart failure[END_REF], particularly surgical trials [START_REF] Søreide | Surgery for an ageing population[END_REF]. Therefore, the best available evidence frequently does not apply to the elderly patient [START_REF] Søreide | Surgery for an ageing population[END_REF][START_REF] Cherubini | The persistent exclusion of older patients from ongoing clinical trials regarding heart failure[END_REF].

Our previous randomized 2x2 factorial trial controlled trial (RCT) showed that low intraperitoneal pressure (IPP) (8 mmHg) and warmed, humidified carbon dioxide (CO2) gas independently decreased postoperative pain in patients <75 years old who underwent laparoscopic surgery for genital prolapse [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. In the present prospective study, we attempted to evaluate benefits and harms of low IPP and warmed, humidified CO2 gas in very elderly patients (age ≥75 years) who underwent laparoscopic surgery for genital prolapse.

Materials and Methods

Methods

The study was designed as a prospective, single-center, observational trial. Anesthetic management was performed by staff anesthesiologists and anesthesiology residents or nurse anesthetists under their supervision. Standard ASA anesthetic monitors were placed in the operating room. All patients received the same general technique, as we previously reported [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. After induction of anesthesia, all patients received forced-air warming blanket, which was maintained until the end of the operation. Intraoperative core temperatures were recorded at 15-minute intervals by a probe inserted into the distal esophagus throughout surgery. Paracetamol (1g) and ketoprofene (50mg) were injected 30-minutes before the end of the operation to prevent postoperative pain.

Consecutive patients age

All operations were performed by the same surgeon (RB) with the assistance of a gynecological surgical resident. Insufflation of CO2 gas was performed using a Storz electronic endoflator (KARL STORZ SE & Co. KG, Tuttlingen, Germany). All patients received warm (37 °C), humidified (98% relative humidity) CO2 insufflation gas delivered by the Fisher & Paykel MR860 Laparoscopic Humidification System (HumiGard, Fisher & Paykel Healthcare, Auckland, New Zealand) [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. When the IPP reached 15 mmHg, four trocars were inserted. Then, the IPP was immediately decreased to 6 mmHg, at which it was maintained for the duration of surgery. We used 6 mmHg instead of 8 mmHg for low IPP in the present study, according to the European Association for Endoscopic Surgery clinical practice guideline on pneumoperitoneum for laparoscopic surgery, which recommends using the lowest IPP possible that allows adequate exposure of the operative field rather than using a routine pressure [START_REF] Neudecker | The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery[END_REF]. For all patients, 5 mL ropivacaine hydrochloride solution (2 mg/mL) were infiltrated around the trocar wounds before incisions [START_REF] Olsen | Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence[END_REF]. In addition, 20 mL ropivacaine solution (2 mg/mL) were infused under the right hemidiaphragm just after insertion of the four trocars [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF].

We have been systematically performing infusion of ropivacaine solution under the right hemidiaphragm for over 10 years [START_REF] Chou | Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council[END_REF]. During this time, we have had no or few complaints about shoulder pain after laparoscopic surgery [START_REF] Olsen | Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence[END_REF]. Laparoscopic promontofixation with or without (for patients who have already undergone hysterectomy) sub-total hysterectomy using the same surgical technique as we previously described [START_REF] Rivoire | Complete laparoscopic treatment of genital prolapse with meshes including vaginal promontofixation and anterior repair: a series of 138 patients[END_REF]. When a promontory as well as surrounding blood vessels and/or nerves could not be very easily identified, laparoscopic pectopexy (the iliopectineal ligament on both sides is used for the mesh fixation) [START_REF] Noé | Laparoscopic pectopexy: a prospective, randomized, comparative clinical trial of standard laparoscopic sacral colpocervicopexy with the new laparoscopic pectopexy-postoperative results and intermediate-term followup in a pilot study[END_REF] was alternatively performed to avoid potential surgical complications such as blood vessels and/or nerves injuries. A RCT showed that both surgical techniques are equally effective in treatment for genital prolapse [START_REF] Noé | Laparoscopic pectopexy: a prospective, randomized, comparative clinical trial of standard laparoscopic sacral colpocervicopexy with the new laparoscopic pectopexy-postoperative results and intermediate-term followup in a pilot study[END_REF]. We did not attempt to increase IPP prior to making the decision to proceed to pectopexy, because we know from our experiences that increased IPP does not enable us to identify a promontory and surrounding vessels and nerves more easily [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF].

All patients were treated according to our standardised postoperative pain management as we previously reported [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. After arrival of patients in the postanesthesia care unit (PACU), they were asked to rate intensity of their pain at rest using a 100-mm visual analogue scale (VAS) every 20 minutes. When the VAS pain score was >30 of 100 (clinically relevant moderate to severe pain), patients received an IV bolus of 2 to 3 mg morphine, and then 1 to 2 mg IV every 10 minutes to achieve a VAS pain score ≤30 of 100 (no or mild pain). After arrival of patients in the ward, they were asked to rate intensity of their pain at rest using a VAS, every 4 hours for the first 24 hours postoperatively, and then 3 times daily until discharge. The patients received intravenous paracetamol (1g) and ketoprofene (50 mg) every 6 hours for the first 24 hours postoperatively.

The quality of postoperative functional recovery was evaluated using the Quality of Recovery-40 questionnaire (QoR-40) [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF][START_REF] Myles | Validity and reliability of a postoperative quality of recovery score: the QoR-40[END_REF]. The QoR-40 the quality of postoperative recovery through five dimensions (emotional state, physical comfort, psychological support, physical independence, and pain) [START_REF] Myles | Validity and reliability of a postoperative quality of recovery score: the QoR-40[END_REF]. This tool has been confirmed as the most suitable one for perioperative clinical studies [START_REF] Herrera | A systematic review of postoperative recovery outcomes measurements after ambulatory surgery[END_REF].

The day before surgery (between 7:00 and 8:00 pm), patients were asked to complete QoR-40 questionnaire as a measure of baseline score. The QoR-40 was then administered three times, 24 hours and 48 hours postoperatively. Surgical complications were categorized according to the Clavien-Dindo classification [START_REF] Dindo | Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey[END_REF].

The quality of the surgical conditions (the operative technical difficulty, working space, visibility, and pain experienced by the surgeon during surgery) was rated by the operating surgeon at the end of surgery using a 100-mm VAS [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF].

Statistical analysis

Statistical analysis was performed using the STATA program version 13.1 (StataCorp, College Station, TX, USA). The power calculation of the present trial was based on our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF].

VAS pain scores were categorized as either ≤30 of 100 or >30 of 100, providing a binary variable, as previously reported [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF][START_REF] Bodian | The visual analog scale for pain: clinical significance in postoperative patients[END_REF]. Comparisons of the global QoR-40 scores and the dimensions of the QoR-40 questionnaire between the day before surgery (baseline) and at 24 hours were made using Wilcoxon's matched pairs test. To identify factors that influence the length of hospital stay after surgery (LHSS), the first set of analyses compared the characteristics of patients in the two length of stay groups (<48 hours versus <72 hours).

Continuous variables were compared between groups using either the unpaired t-test, if found to be normally distributed, or the Mann-Whitney test or one-way analysis of variance (ANOVA) otherwise. Categorical variables were compared between groups using Fisher's exact test. The second stage examined the joint association between patient factors and LHSS in a multivariable analysis. As there were only two different lengths of stay (<48 hours versus <72 hours), the analysis was performed using logistic regression. Due to the relatively small sample size, only variables showing some association with LHSS from the initial analyses (p<.1) were included in this stage of the analysis. A backwards selection procedure was used to retain only the statistically significant variables in the final model. This involved omitting non-significant variables, one at a time, until only significant variables remain.

Statistical significance was accepted at the .05 level.

Results

A total of 32 consecutive patients age ≥75 years underwent surgical treatment for genital prolapse by the same surgeon (RB) during the study period. Among them, 2 patients declined participation in completing the QoR-40 questionnaire. The present analysis therefore included 30 patients. Patient and surgical characteristics are presented in Table 1.

A total of 27 patients underwent laparoscopic promontofixation and the remaining 3 patients underwent pectopexy. A total of 6 patients had previously undergone total hysterectomy. The surgery could be performed with 6 mmHg and the IPP was maintained for the duration of surgery in all the patients.

Quality of Recovery-40 score

Results are shown in Table 2. For the global QoR-40 score and for the four dimensions of the QoR-40, "emotional state," "physical comfort," "psychological support," and "pain," no differences were observed between the basal score (the day before surgery, between 7:00 and 8:00 pm) and at 24 hours (Table 2). The score for the "physical independence" dimension was significantly lower at 24 hours than the basal score (Table 2).

For further evaluation of the effects of a low IPP in elderly patients, we compared the present results with those of our previous RCT in elderly patients age ≥65 years [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF] (Supplementary Table 1). In our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF], we included only patients who underwent laparoscopic sub-total hysterectomy with promontofixation. Thus, we performed a subgroup analysis of patients underwent the same surgical procedure (n=21) for comparison (Supplementary Table 1). The operating time was significantly longer in our previous RCT compared with those of the present study (Supplementary Table 1). The results of the QoR40 scores (Supplementary Table 2) in these patients (n=21) were nearly identical to those in the full cohort of patients (Table 2). In the low IPP group (8 mmHg, n=17) of our previous RCT study [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF], the scores for the two dimensions of the QoR-40, "physical comfort," and "physical independence," were significantly lower at 24 hours than the basal score (Supplementary Table 2). In the standard IPP group (12 mmHg, n=20) of our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF], the scores for the global QoR-40, and for the three dimensions of the QoR-40, "physical comfort," "physical independence," and "pain," were significantly lower at 24 hours than the basal score (Supplementary Table 2).

To evaluate the effects of additional surgical procedures (Burch colposuspension [Burch] or tension-free vaginal tape procedure [TVT]), we compared the QoR40 scores between patients with (n=18) versus without (n=12) additional surgical procedures (Supplementary Table 3). The operating time was significantly longer in patients with additional surgical procedures (Supplementary Table 3). There was no significant difference in the QoR40 scores between patients with versus without additional surgical procedures (Supplementary Table 4)

VAS pain score

No patients had a VAS pain score >30 the day before surgery. No patients had postoperative shoulder pain. In the PACU, 7 (23%) patients had VAS pain scores >30. Upon arrival in the ward, 4 patients (13%) had VAS pain scores >30. No patient had VAS pain scores >30 at 12 hours or later (Supplementary Table 5).

Intraoperative core temperature

Results are shown in Table 1. We observed that 15 of 30 (50.0%) patients were already hypothermic just before starting the surgical procedure. Of these, 10 patients remained hypothermic at the end of surgery. A total of 15 patients (50.0%) were hypothermic at the end of surgery.

Intraoperative and postoperative complications

analysis (Table 4). The results of the multivariable analysis showed that both OR exit time and QoR-40 score at baseline were associated with LHSS (Table 4). After adjusting for these two variables, no additional effects of either operating time or QoR-40 score at 24 hours were observed, both of which showed some association with LHSS in the initial analyses. OR exit time was again associated with an increased chance of a LHSS >48 hours. The odds of a LHSS >48 hours were more than 8 times higher in those with an afternoon discharge from the OR compared with those with a morning discharge (Table 4). Higher baseline QoR-40 scores were associated with a lower chance of a LHSS >48 hours (Table 4). A one-unit increase in this score was associated with a 20% reduction in the odds of a LHSS >48 hours (Table 4).

Discussion

The present study showed the feasibility, safety, and clinical benefits of use of a low IPP in very elderly patients who undergo laparoscopic surgery for genital prolapse, in agreement with the results of our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. Laparoscopic surgery confers several benefits, including decreased postoperative pain, shorter LHSS, and a more rapid return to regular daily activities [START_REF] Bates | Laparoscopic surgery in the elderly: a review of the literature[END_REF][START_REF] Manceau | Comparative outcomes of rectal cancer surgery between elderly and non-elderly patients: a systematic review[END_REF]. However, previous clinical trials for laparoscopic surgery have included few very elderly patients age ≥75 years [START_REF] Schiphorst | Representation of the elderly in trials of laparoscopic surgery for colorectal cancer[END_REF][START_REF] Weber | CM. Age-dependent changes in temperature regulation -a mini review[END_REF], who may benefit the most from laparoscopic surgery [START_REF] Bates | Laparoscopic surgery in the elderly: a review of the literature[END_REF][START_REF] Manceau | Comparative outcomes of rectal cancer surgery between elderly and non-elderly patients: a systematic review[END_REF]. The present clinical trial could provide useful information for very elderly population who require surgical treatment for genital prolapse.

Several limitations of the present study should be considered, and thus, the present findings may not be generalized. First, the present study included only a small number of patients and the same surgeon performed all procedures. Second, there were no agematched controls. Because our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF] has already showed that a low IPP could result in better clinical outcomes, it was not ethically possible to include age-matched elderly patients who undergo laparoscopic surgery under a standard IPP (12mmHg). However, compared with those of our previous RCT in elderly patients age ≥65 years, the present findings suggested that the use of a low IPP could result in better quality of postoperative recovery in elderly patients. Third, there may be biases associated with the heterogeneity of the present study population. However, we found no significant differences in the QoR 40 scores between patients with versus without additional surgical procedures. In a subgroup analysis of patients who underwent laparoscopic sub-total hysterectomy with promontofixation, results of the QoR40 scores were nearly identical to those in the full cohort of patients. Furthermore, the objective of the present study was not to identify factors that influence LHSS; thus, we did not calculate the required number of patients for this. A large, prospective, multicenter study is required to confirm the external validity of the present results.

Aging is associated with impaired thermoregulatory function [START_REF] Blatteis | Age-dependent changes in temperature regulation -a mini review[END_REF][START_REF] Baquero | Perioperative care in older adults[END_REF][START_REF] Jin | Minimizing perioperative adverse events in the elderly[END_REF]; thus, elderly people are at greater risk of perioperative hypothermia [START_REF] Blatteis | Age-dependent changes in temperature regulation -a mini review[END_REF][START_REF] Baquero | Perioperative care in older adults[END_REF][START_REF] Jin | Minimizing perioperative adverse events in the elderly[END_REF]. The present study showed no significant effect of warmed CO2 gas on the prevention of intraoperative hypothermia, also consistent with our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. Studies have suggested that extending systemic warming into the preoperative period could be more beneficial than limiting it to surgery alone [START_REF] Wong | Randomized clinical trial of perioperative systemic warming in major elective abdominal surgery[END_REF][START_REF] Lau | Effect of preoperative warming on intraoperative hypothermia: a randomized-controlled trial[END_REF][START_REF] Becerra | Prospective observational study of the effectiveness of prewarming on perioperative hypothermia in surgical patients submitted to spinal anesthesia[END_REF]. Further studies are required to investigate whether the preoperative plus intraoperative systemic warming could be more effective for prevention of hypothermia in elderly patients.

LHSS after surgery can be influenced by many different factors, including medical and social factors [START_REF] Lim | Factors causing delay in discharge of elderly patients in an acute care hospital[END_REF][START_REF] Kelly | Factors predicting hospital length-ofstay and readmission after colorectal resection: a population-based study of elective and emergency admissions[END_REF][START_REF] Tan | Shorter duration of femoral-popliteal bypass is associated with decreased surgical site infection and shorter hospital length of stay[END_REF][START_REF] Dickinson | Factors influencing length of stay after surgery for benign foregut disease[END_REF][START_REF] Toh | Factors associated with prolonged length of stay in older patients[END_REF][START_REF] Ko-Iam | Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy[END_REF][START_REF] Agrawal | Characteristics associated with prolonged length of stay after hysterectomy for benign gynecologic conditions[END_REF][START_REF] Stethen | Factors Influencing Length of Stay after Elective Bowel Resection within an Enhanced Recovery Protocol[END_REF][START_REF] Aarts | Adoption of enhanced recovery after surgery (ERAS) strategies for colorectal surgery at academic teaching hospitals and impact on total length of hospital stay[END_REF][START_REF] Chong | Influencing factors on postoperative hospital stay after laparoscopic cholecystectomy[END_REF]. The presence of comorbidity has been a well-known risk factor [START_REF] Ko-Iam | Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy[END_REF][START_REF] Agrawal | Characteristics associated with prolonged length of stay after hysterectomy for benign gynecologic conditions[END_REF][START_REF] Stethen | Factors Influencing Length of Stay after Elective Bowel Resection within an Enhanced Recovery Protocol[END_REF]. In the present study, no patients had ASA III-IV. Because genital prolapse is not a life-threatening disease, only selected elderly patients who are in relatively good condition might be referred to our hospital for surgical treatment. In the present study as well as in our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF], all patients were informed of expected discharge on postoperative day 3.

Social reasons requiring a longer hospital stay are more common in elderly patients [START_REF] Lim | Factors causing delay in discharge of elderly patients in an acute care hospital[END_REF][START_REF] Kelly | Factors predicting hospital length-ofstay and readmission after colorectal resection: a population-based study of elective and emergency admissions[END_REF][START_REF] Dickinson | Factors influencing length of stay after surgery for benign foregut disease[END_REF][START_REF] Toh | Factors associated with prolonged length of stay in older patients[END_REF][START_REF] Aarts | Adoption of enhanced recovery after surgery (ERAS) strategies for colorectal surgery at academic teaching hospitals and impact on total length of hospital stay[END_REF]. Furthermore, studies have shown that older age can influence LHSS after surgery [START_REF] Dickinson | Factors influencing length of stay after surgery for benign foregut disease[END_REF][START_REF] Aarts | Adoption of enhanced recovery after surgery (ERAS) strategies for colorectal surgery at academic teaching hospitals and impact on total length of hospital stay[END_REF][START_REF] Chong | Influencing factors on postoperative hospital stay after laparoscopic cholecystectomy[END_REF]. Nevertheless, in the present study, 77.3% (22 of 30) patients were discharged within 48 hours after surgery, whereas among elderly patients age ≥65 years of our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF], only 25.0% (5 of 20) patients in the 12-mmHg group and 23.5 % (4 of 17) in the 8 mmHg group were discharged within 48 hours (Supplementary Table 1).

Shortening LHSS after surgery benefits patients who prefer to be at home [START_REF] Admi | From research to reality: minimizing the effects of hospitalization on older adults[END_REF]. Furthermore, in two 10-year age groups (68-77 years and 78-87 years), better functional outcomes were associated with short admissions [START_REF] Van Vliet | Decreasing Hospital Length of Stay: Effects on Daily Functioning in Older Adults[END_REF]. Finally, shortening LHSS benefits the healthcare system in terms of cost and resource utilization [START_REF] Fine | Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia[END_REF][START_REF] Taheri | Length of stay has minimal impact on the cost of hospital admission[END_REF]. Hospital health care resource utilization and costs are disproportionately incurred within the first 3 days of hospitalization [START_REF] Fine | Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia[END_REF][START_REF] Taheri | Length of stay has minimal impact on the cost of hospital admission[END_REF]. It is therefore clinically important for both elderly patients and the healthcare system to identify factors influencing LHSS. In the present study population, the odds of a LHSS >48 hours were more than 8 times higher in patients with an afternoon discharge from the OR compared with those with a morning discharge. Furthermore, we observed approximately a 40-minute decrease both operation time and CO2 pneumoperitoneum in the present t study compared to those in our previous RCT [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF]. Previous studies suggested operation time [START_REF] Dickinson | Factors influencing length of stay after surgery for benign foregut disease[END_REF][START_REF] Chong | Influencing factors on postoperative hospital stay after laparoscopic cholecystectomy[END_REF][START_REF] Scheer | Laparoscopic colon surgery: does operative time matter?[END_REF][START_REF] Hansen | Reduced length of stay and hospitalization costs among inpatient hysterectomy patients with postoperative pain management including IV versus oral acetaminophen[END_REF] and postoperative pain [START_REF] Ko-Iam | Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy[END_REF][START_REF] Hansen | Reduced length of stay and hospitalization costs among inpatient hysterectomy patients with postoperative pain management including IV versus oral acetaminophen[END_REF][START_REF] Butz | Postoperative Pain and Length of Stay Lowered by Use of Exparel in Immediate, Implant-Based Breast Reconstruction[END_REF] as factors that influence LHSS. Thus, at least three modifiable factors exist at an institutional and/or individual surgeon levelpostoperative pain, operative time, and OR exit time-that may potentially influence LHSS in very elderly patients after laparoscopic surgical treatment for genital prolapse. To reduce postoperative pain, a lower IPP [START_REF] Matsuzaki | Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial[END_REF][START_REF] Ko-Iam | Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy[END_REF][START_REF] Radosa | Impact of different intraoperative CO2 pressure levels (8 and 15 mmHg) during laparoscopic hysterectomy performed due to benign uterine pathologies on postoperative pain and arterial pCO2 : a prospective randomised controlled clinical trial[END_REF]] could be used. To reduce operative time, improving surgeon efficiency is required: at an institutional level by improving coordination of the surgical team and limiting unnecessary delays [START_REF] Harders | Improving operating room efficiency through process redesign[END_REF][START_REF] Lee | Design and impact of an intraoperative pathway: a new operating room model for team-based practice[END_REF][START_REF] Wolf | The efficacy of medical team training: improved team performance and decreased operating room delays: a detailed analysis of 4863 cases[END_REF][START_REF] Russ | Measuring safety and efficiency in the operating room: development and validation of a metric for evaluating task execution in the operating room[END_REF][START_REF] Phieffer | Improving Operating Room Efficiency: First Case On-Time Start Project[END_REF]. At the individual surgeon level, this could be achieved by improving technical skill and operative efficiency [START_REF] Hu | Postgame analysis: using video-based coaching for continuous professional development[END_REF][START_REF] Hull | The impact of nontechnical skills on technical performance in surgery: a systematic review[END_REF].

Achievement of a morning discharge from the OR is accomplished by a shorter operation time and by scheduling the procedure as the first case in the morning [START_REF] Phieffer | Improving Operating Room Efficiency: First Case On-Time Start Project[END_REF]. Because the number of very elderly patients who require surgical treatment is expected to rise [START_REF] Søreide | Surgery for an ageing population[END_REF], improving the operating schedule and OR efficiency are worthy of careful consideration for both patients and healthcare systems.

  ≥75 years who underwent laparoscopic surgery for genital prolapse by the same surgeon (RB) were recruited at CHU Clermont-Ferrand from October 2016 through December 2019. Informed written consent was obtained from each patient prior to surgery. The study protocol was approved on 29 th September 2016 by the IRB (00008526) of the Committee for Protection of Persons in Biomedical Research (CPP SE VI) of the Auvergne (France) (2016 / CE 57) and registered on ClinicalTrials.gov (NCT03095716).

Table 1 . Baseline Characteristics

 1

	Variable	6 mmHg warmed, humidified CO2 gas (n=30)
	Age, mean (SD), y	80.4 (3.5)
	Hight, mean (SD), cm	156.7 (19.4)
	Body weight, Mean (SD), kg	59.3 (12.7)
	Body mass index, mean (SD)	23.4 (3.7)
	ASA status, No. (%) ASA 1	4 (13.3)
	ASA 2	26 (86.7)
	ACCI	3.6 (0.50)
	Basal QoR 40, median [IQR]	191 [185, 197]
	Additional surgical procedure, No. (%)

Acknowledgements

We are most grateful to all the patients who participated in the present study. We also thank all the staff in the Department of Gynecology and operating room, CHU Clermont-Ferrand. This study was supported in part by KARL STORZ SE & Co. KG (Tuttlingen, Germany).

This study was supported in part by KARL STORZ SE & Co. KG (Tuttlingen, Germany).

The data that support the findings of the study are available from the corresponding author (SM), on reasonable request.

One patient who had previously undergone laparoscopic total hysterectomy following radiation therapy and chemotherapy due to uterine adenocarcinoma experienced an intraoperative complication (bladder perforation). This was not related to low IPP, but rather due to postsurgical and/or radiation-related adhesion. The patient was discharged on postoperative day 2 with an indwelling urinary catheter after an uneventful postoperative recovery. No patients experienced postoperative complications. No patients required readmission.

Quality of surgical conditions

Scores rated by the surgeon for operative technical difficulty and working space for dissection and suturing, surgical field visibility, pain experienced by the surgeon, are shown in Supplementary Table 6.

Factors influencing length of hospital stay after surgery

LHSS was <48 hours in 22 patients (73.3%) and <72 hours in 8 patients (26.7%). The results of analyses comparing the characteristics of patients with a LHSS <48 hours versus those >48 hours are summarized in Table 3. Only operating room (OR) exit time significantly differed between patients with a LHSS <48 hours versus those >48 hours (Table 3). The majority (n=7, 88%) of patients with a LHSS >48 hours were discharged from the OR in the afternoon, whilst only one third of those (n=7, 32%) with a LHSS <48 hours were discharged in the afternoon (Table 3). In addition to this significant factor, some evidence suggested that operating time and QoR-40 scores at both baseline and 24 hours varied between the two discharge time groups (Table 3). However, the results for all these variables did not quite reach statistical significance.

Next, we examined the joint association between select factors and LHSS. A