PRO STRESS Trial: Proactive Low-Dose Norepinephrine to Reduce Intraoperative Fluid Administration in Patients at High-Risk for Postoperative Pulmonary Complications Undergoing Laparoscopic Abdominal Surgery

Official title

Proactive Low-Dose Norepinephrine to Reduce Intraoperative Fluid Administration in Patients at High-Risk for Postoperative Pulmonary Complications Undergoing Laparoscopic Abdominal Surgery: A Randomized Controlled Trial

Overview

Intraoperative hypotension is commonly treated with fluid administration; however, excessive fluid therapy may contribute to postoperative pulmonary complications. This randomized double-blind controlled trial evaluates whether proactive administration of fixed low-dose norepinephrine reduces intraoperative crystalloid administration while maintaining hemodynamic stability in high-risk patients undergoing laparoscopic abdominal surgery. One hundred and thirty patients will be randomized to receive either norepinephrine infusion (0.03 µg/kg/min) or placebo from induction until skin closure within a protocolized hemodynamic strategy guided by mean arterial pressure and pulse pressure variation.

Interventions

• Drug Norepinephrine
  Continuous norepinephrine infusion administered at a fixed dose of 0.03 µg/kg/min from induction of anesthesia until skin closure.
• Other Placebo
  Equivalent volume normal saline infusion administered from induction of anesthesia until skin closure at the same infusion rate as the active intervention to maintain blinding within a protocolized hemodynamic management strategy.

Primary outcome measures

• Total intraoperative crystalloid administration [Time frame: From induction of anesthesia until skin closure (intraoperative period)]

Secondary outcome measures (10)

• Number of Participants with Postoperative Pulmonary Complications [Time frame: Within seven postoperative days]
• Number of Participants With Acute Kidney Injury [Time frame: Within seven postoperative days]
• Lactate Levels [Time frame: After induction of anesthesia, at the end of surgery, and 24 hours postoperatively]
• Urine Output [Time frame: From induction of anesthesia until skin closure (Intraoperative period)]
• Intraoperative Blood Loss [Time frame: From surgical incision until skin closure (Intraoperative period)]
• Duration of Rescue Norepinephrine Requirement [Time frame: From induction of anesthesia until skin closure (Intraoperative period)]
• Duration of Intraoperative Hypotension [Time frame: From induction of anesthesia until skin closure (Intraoperative period)]
• Number of Participants Admitted to the Intensive Care Unit [Time frame: Within seven postoperative days]
• Duration of Postoperative Hospital Stay [Time frame: Within seven postoperative days]
• Number of Participants With Postoperative Surgical Complications [Time frame: Within seven postoperative days]

Eligibility criteria

Inclusion criteria

• Adult patients aged 18 years or older.
• American Society of Anesthesiologists (ASA) physical status I-III.
• Scheduled for elective laparoscopic major abdominal surgery under general anesthesia with an expected duration greater than 2 hours.
• Patients with ARISCAT score ≥ 45 indicating high risk for postoperative pulmonary complications.

Exclusion criteria

• Known hypersensitivity to norepinephrine.
• Severe left ventricular dysfunction with ejection fraction < 35%.
• Significant cardiac arrhythmia.
• Uncontrolled hypertension defined as systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.
• End-stage renal disease.
• Requirement for vasopressor support before induction of anesthesia.
• Emergency surgery.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Suez Canal University Hospitals — Ismailia

Publications

• Persichini R, Lai C, Teboul JL, Adda I, Guerin L, Monnet X. Venous return and mean systemic filling pressure: physiology and clinical applications. Crit Care. 2022 May 24;26(1):150. doi: 10.1186/s13054-022-04024-x. PMID 35610620
• Felippe VA, Codeceira R, Irigaray M, Sckaff M, Wegner B, Nascimento T, Darcy C, Dutra L, Santiago B, Buchmann J, Lessa MA. Non-invasive goal-directed fluid therapy with the pleth variability index (PVI): a systematic review and meta-analysis. J Clin Monit Comput. 2025 Oct;39(5):917-927. doi: 10.1007/s10877-025-01334-7. Epub 2025 Aug 8. PMID 40778974
• Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11. PMID 26162676
• Canet J, Gallart L, Gomar C, Paluzie G, Valles J, Castillo J, Sabate S, Mazo V, Briones Z, Sanchis J; ARISCAT Group. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 2010 Dec;113(6):1338-50. doi: 10.1097/ALN.0b013e3181fc6e0a. PMID 21045639
• Cannesson M, Le Manach Y, Hofer CK, Goarin JP, Lehot JJ, Vallet B, Tavernier B. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach. Anesthesiology. 2011 Aug;115(2):231-41. doi: 10.1097/ALN.0b013e318225b80a. PMID 21705869
• Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, Christophi C, Leslie K, McGuinness S, Parke R, Serpell J, Chan MTV, Painter T, McCluskey S, Minto G, Wallace S; Australian and New Zealand College of Anaesthetists Clinical Trials Network and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. PMID 29742967

Identifiers

NCT: NCT07627360 · 6476# · 6476#

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗