Evaluation of the early use of norepinephrine in major abdominal surgery on medical and surgical postoperative complications: study protocol for a randomised controlled trial (EPON STUDY).

BACKGROUND: Post-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH. METHODS AND ANALYSIS: The EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien-Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month. ETHICS AND DISSEMINATION: Ethical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05276596.

Assessment of fluid unresponsiveness guided by lung ultrasound in abdominal surgery: a prospective cohort study.

A fluid challenge can generate an infraclinical interstitial syndrome that may be detected by the appearance of B-lines by lung ultrasound. Our objective was to evaluate the appearance of B-lines as a diagnostic marker of preload unresponsiveness and postoperative complications in the operating theater. We conducted a prospective, bicentric, observational study. Adult patients undergoing abdominal surgery were included. Stroke volume (SV) was determined before and after a fluid challenge with 250 mL crystalloids (Delta-SV) using esophageal Doppler monitoring. Responders were defined by an increase of Delta-SV > 10% after fluid challenge. B-lines were collected at four bilateral predefined zones (right and left anterior and lateral). Delta-B-line was defined as the number of newly appearing B-lines after a fluid challenge. Postoperative pulmonary complications were prospectively recorded according to European guidelines. In total, 197 patients were analyzed. After a first fluid challenge, 67% of patients were responders and 33% were non-responders. Delta-B-line was significantly higher in non-responders than responders [4 (2-7) vs 1 (0-3), p < 0.0001]. Delta-B-line was able to diagnose fluid non-responders with an area under the curve of 0.74 (95% CI 0.67-0.80, p < 0.0001). The best threshold was two B-lines with a sensitivity of 80% and a specificity of 57%. The final Delta-B-line could predict postoperative pulmonary complications with an area under the curve of 0.74 (95% CI 0.67-0.80, p = 0.0004). Delta-B-line of two or more detected in four lung ultrasound zones can be considered to be a marker of preload unresponsiveness after a fluid challenge in abdominal surgery.The objectives and procedures of the study were registered at Clinicaltrials.gov (NCT03502460; Principal investigator: Stéphane BAR, date of registration: April 18, 2018).