This prospective, randomized clinical trial (RCT) was conducted at the Department of General and Visceral Surgery of Sisters of Charity Hospital Linz (Linz, Austria), a high-volume tertiary care center with experience in advanced laparoscopic surgery. The aim of this study was to compare AirSeal® to a standard CO2 insufflator for surgical outcomes in patients who underwent laparoscopic procedures in visceral surgery. The study protocol was approved by the ethical committee of the Hospital of the Sisters of Charity in Linz, a member of the independent Ethics Committee (IEC) of Austria (Study number: 28/12 AirSeal® Trial) and all patients gave written informed consent for participation. The study was conducted in accordance with principles of the Declaration of Helsinki and guidelines for Good Clinical Practice . The study was registered on ClinicalTrials.gov with inscription number NCT01740011. Consecutive patients scheduled to undergo laparoscopic surgery at our department were recruited between January 2013 and January 2014. Results are presented according to the CONSORT statement (Supplemental Digital Content 1, https://links.lww.com/SLA/B352) . The study protocol has been published previously .
Consecutive patients scheduled for elective laparoscopic cholecystectomy, colorectal surgery (sigmoid resection) and hernia repair (unilateral/bilateral inguinal hernias or ventral abdominal wall hernias), aged over 18 years, were included in the study. Clinical evaluation and pre-randomization assessment were completed for every patient including the review of eligibility criteria, a signed and dated informed consent, inquiry of relevant past medical history and anesthesiologic preoperative assessment, including American Society of Anesthesiologists (ASA) class. In case of conversion to open surgery, participants were excluded from per-protocol analysis. Exclusion criteria were as follows: previous extensive abdominal surgery, e.g., previous laparotomy with major organ resection; previous urgent/emergency abdominal surgical intervention, immunological disfunction, severe chronic hepatic, renal, pulmonary, or cardiac disease; pregnancy and lactation; and patient’s refusal to participate.
Patients undergoing elective laparoscopic cholecystectomy, colorectal surgery or hernia repair were randomized 1:1 to either laparoscopic surgery with an AirSeal® CO2 pressure insufflator (group A) or with a standard CO2 pressure insufflator (group S). Randomization was stratified according to type of operation (cholecystectomy, sigmoid resection, hernia-inguinal unilateral/bilateral or ventral hernia). Patients were randomized using a web-based, central randomization and registration system (www.randomizer.at) upon induction of anesthesia in the preoperative area.
All patients were operated in one center by three surgeons, with experience in advanced laparoscopic surgery. A pilot study had previously been carried out with 86 patients in each group for the prior ranking primary endpoint (time of surgery). In this retrospective evaluation, operative time was significantly longer in standard CO2 pressure insufflator group compared to AirSeal® CO2 pressure insufflator group (68 ± 15 vs. 58 ± 15 min (mean ± SD), p = 0.026) in patients undergoing laparoscopic cholecystectomy. All procedures were performed under general anesthesia, and the surgical technique and perioperative care were performed in the following manner. In all patients, access was achieved using four working ports (trocars) for cholecystectomy, as well as sigmoid resection and three working ports for the herniotomy procedure. The use of surgical instruments was standardized and did not differ within the operation groups. Pneumoperitoneum was created using a Veress needle inserted through a small skin incision in the umbilical region. Reverse Trendelenburg position with both arms secured to the sides was used after the induction of pneumoperitoneum in cholecystectomy and Trendelenburg position in inguinal hernia and sigmoid resection procedures. Operative details for laparoscopic ventral hernia repair and transabdominal pre-peritoneal (TAPP) repair have been described previously [15, 16]. Pneumoperitoneum was created using the AirSeal® system CO2 pressure insufflator (Surgiquest Inc., Milford, USA insufflator) (group A) or with a standard CO2 pressure insufflator (Olympus America Inc. UHI-3, Center Valley, PA, US) (group S) with a CO2 flow rate of 2 L/min. Having created a 12 mmHg pneumoperitoneum, the surgeons proceeded to insert trocars. The AirSeal® consists of three devices: Intelligent Flow System (IFS), the AirSeal® trocar, and the AirSeal® Mode Evacuation (ASM-Evac) Tri-lumen Filter Tube Set. The AirSeal® valve-free trocar includes CO2 nozzles that act as pressure gas barriers and preserve the set intra-abdominal pressure, in contrast to the trapdoor valves of conventional trocars. The ASM-Evac Tri-lumen Filter consists of one lumen for CO2 influx, one lumen for CO2 outflux to the IFS, and a third lumen for concurrent uninterrupted pressure assessment. Once the fixed pressure is reached, the CO2 flow is spontaneously reduced to 3 L/min, while preserving the fixed pressure. In group A, a 5 mm AirSeal® access port was used instead of a standard 5 mm port. Through the trial, laparoscopic equipment manufactured by Storz GmbH, Tuttlingen Germany, was employed. At the end of the surgery, the trocars were opened to release intra-abdominal CO2 and the abdomen was compressed by the surgeon’s hands to evacuate the residual gas. No local anesthetic was used in any patient.
Outcomes and definitions
The primary endpoints were operative time, defined as the time from skin incision to closure of wound in minutes, and postoperative shoulder pain assessed by VAS (visual analogue pain scale). After surgery, patients were observed and interviewed for 2-day duration of shoulder pain evaluation by nurses. Postoperative pain was assessed in a double-blinded manner. Neither the patient, nor the assessor of shoulder pain, nor the postoperative caregivers were aware of the technique to which the patient was randomized. The 11-point VAS was used for assessment of the severity of shoulder pain (0 = none, 10 = severe) and scores were obtained at 1, 6, 12, 24 and 48 h after operation. All patients received standardized postoperative pain management. Anesthesia was terminated following extubation. Patients were closely monitored in the post-anesthetic care unit and then transferred to the surgical ward. A bolus of morphine sulfate (0.1 mg/kg) was administered intravenously (i.v.) after the operation. During postoperative period, all patients received 1 g Paracetamol and 1 g Metamizol i.v. every 6 h until 24 h postoperatively. Then pain was managed using oral Paracetamol and Metamizol on demand.
The secondary outcomes were length of hospital stay (days) and surgical side effects, including subcutaneous emphysema evaluation. Complications were graded according to the Clavien–Dindo classification .
For statistical analysis, both a per-protocol (PP) and an intention-to-treat (ITT) analysis were used. It was defined that the PP analysis takes precedence in the evaluation of efficacy. There were no missing values for the two primary endpoints, hence the foreseen replacement procedure not coming into effect.
The randomized study had a confirmatory status (two parallel groups: AirSeal® CO2 pressure insufflation vs. standard CO2 pressure insufflation). A superiority approach was used. The following primary endpoints were defined (ranking in brackets): (1) duration of surgery [min] and (2) shoulder pain one day after surgery [VAS]. The type I error of one-sided 2.5% was maintained by a gatekeeping approach.
A sample size estimation based on pilot data for the prior ranking primary endpoint (time of surgery) resulted in a demand of at least 86 valid cases for efficacy in each group, group A (mean ± standard deviation): 74.8 ± 41.3 min and group S: 93.5 ± 41.3 min (one-sided type I error = 2.5%, type II error = 20%). Continuous variables are reported as medians and quartiles (in brackets). Categorical variables are expressed as counts and percentages (in brackets).
Metric variables and variables measured on ordinal scales were compared between the two groups by the exact Mann–Whitney U test, categorical variables by either the Fisher’s exact test or the exact chi-square test. Subgroup comparisons of time of surgery were performed by a non-parametric analysis of variance (Kruskal–Wallis one-way analysis of variance followed by Nemenyi's multiple comparisons).
Statistical analysis was performed using the open-source R statistical software package, version 3.0.1. The detailed sample size estimation and hypothesis have been published previously in our study protocol .