Determinants of postoperative complications in high-risk noncardiac surgery patients optimized with hemodynamic treatment strategies: A post-hoc analysis of a randomized multicenter clinical trial.

STUDY OBJECTIVE: This post-hoc analysis of a randomized controlled trial was undertaken to establish the determinants of postoperative complications and acute kidney injury in high-risk noncardiac surgery patients supported with hemodynamic treatment strategies. DESIGN: We conducted a post-hoc analysis of patients enrolled in the OPtimization Hemodynamic Individualized by the respiratory QUotiEnt (OPHIQUE) trial. SETTING: Operating rooms in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. PATIENTS: We enrolled 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia. INTERVENTIONS: All patients were treated according to hemodynamic treatment strategies which included cardiac output optimization by titration of fluid challenge and targeted systolic blood pressure to remain within ±10% of the reference value. MEASUREMENTS: We assessed the association between pre-operative and intra-operative exposure of interest with a composite primary outcome of major complications or death within seven days following surgery using a multivariable logistic regression model. We also assessed the association between these exposures of interest and acute kidney injury. MAIN RESULTS: The data of 341 patients were analyzed. In multivariate analysis, the factors independently associated with the primary outcome were age (OR = 1.04 (1.01-1.06), P = 0.002), preoperative hemoglobin concentration (OR = 0.85 (0.75-0.96), P = 0.012), non-vascular surgery (OR = 0.30 (0.17-0.53), P < 0.0001), and intraoperative surgical complications (OR = 2.08 (1.02-4.24), P = 0.046). The factors independently associated with postoperative acute kidney injury were age (OR = 1.04 (1.01-1.08), P = 0.008), preoperative creatinine concentration (OR = 1.01 (1.00-1.01), P = 0.049), non-vascular surgery (OR = 0.36 (0.20-0.66), P = 0.001), and intraoperative surgical complications (OR = 3.36 (1.50-7.55), P = 0.031). CONCLUSIONS: Surgical complications, a lower preoperative hemoglobin concentration, age, and vascular surgery were associated with postoperative complications in a high-risk noncardiac surgery population supported with hemodynamic treatment strategies.

Respiratory Exchange Ratio guided management in high-risk noncardiac surgery: The OPHIQUE multicentre randomised controlled trial.

BACKGROUND: There is a need to develop non-invasive markers to identify the occurrence of anaerobic metabolism in high-risk surgery. Our objective was to demonstrate that a goal-directed therapy algorithm incorporating the respiratory exchange ratio (ratio between CO2 production and O2 consumption) can reduce postoperative complications. METHODS: We conducted a randomized, multicenter, controlled clinical trial in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia were enrolled. The control group was treated according to current hemodynamic guidelines. The interventional group was treated according to an algorithm based on the measurement of the respiratory exchange ratio. The primary outcome was a composite of major complications or death within seven days of surgery. The secondary outcomes were the length of hospital stay, 30-day mortality, and the total intraoperative volume of fluids administered. RESULTS: The primary outcome occurred for 78 patients (45.6%) in the interventional group and 83 patients (48.8%) in the control group (relative risk: 0.93, 95% confidence interval [CI]: 0.75-1.17; p = 0.55). There were no clinically relevant differences between the two groups for secondary outcomes. CONCLUSIONS: In high-risk surgery, a goal-directed therapy algorithm integrating the measurement of the respiratory-exchange ratio did not reduce a composite outcome of major postoperative complications or death within seven days after surgery compared to routine care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03852147.

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial.

OBJECTIVE: To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery. DESIGN: Multicentre, randomised, double blind, placebo controlled trial. SETTING: 11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019. PARTICIPANTS: 926 adults scheduled for elective colorectal surgery. INTERVENTION: Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery. RESULTS: Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%). CONCLUSION: Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618720.

Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial.

OBJECTIVE: To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. DESIGN: Phase III, randomised, double blind, placebo controlled trial. SETTING: 34 centres in France, December 2017 to March 2019. PARTICIPANTS: 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. INTERVENTIONS: Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. MAIN OUTCOMES MEASURES: The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). RESULTS: Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). CONCLUSIONS: Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT03218553.

Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study).

BACKGROUND: Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study's objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing  procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. METHODS: The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 µg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. DISCUSSION: The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. TRIAL REGISTRATION: ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.

Individualized hemodynamic optimization guided by indirect measurement of the respiratory exchange ratio in major surgery: study protocol for a randomized controlled trial (the OPHIQUE study).

BACKGROUND: Observational studies have suggested that a high respiratory exchange ratio (RER) is associated with the occurrence of postoperative complications. The study's primary objective is to demonstrate that the incidence of postoperative complications is lower in an interventional group (patients monitored using a hemodynamic algorithm that incorporates the RER) than in a control group (treated according to standard practice). METHODS: We shall perform a prospective, multicenter, randomized, open-label, superiority trial of consecutive patients undergoing major noncardiac surgery (i.e., abdominal, vascular, and orthopedic surgery). The control group will be treated according to the current guidelines on standard hemodynamic care. The interventional group will be treated according to an algorithm based on the RER. The primary outcome will be the occurrence of at least one complication in the 7 days following surgery. The secondary outcomes will be the length of hospital stay, the total number of complications per patient, the 30-day mortality, the total intraoperative volume of fluids administered, and the Sequential [sepsis-related] Organ Failure Assessment (SOFA) score and laboratory data measured on postoperative days 1, 2, and 7. A total of 350 patients will be included. DISCUSSION: In the operating theater, the RER is potentially a continuously available, easy-to-read, indirect marker of tissue hypoperfusion and postoperative complications. If the RER does predict the occurrence of tissue hypoperfusion, it will help the physician to provide personalized hemodynamic management and limit the side effects associated with excessive hemodynamic optimization (volume overload, vasoconstriction, etc.). TRIAL REGISTRATION: ClinicalTrials.gov NCT03852147 . Registered on February 25, 2019.

Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial.

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.