Safety and Efficacy of Perioperative Volume Replacement with Volulyte 6% in Moderate-to-high Cardiovascular Risk Patients Having Major Abdominal Surgery

Official title

Safety and Efficacy of Perioperative Volume Replacement with Volulyte 6% in Moderate-to-high Cardiovascular Risk Patients Having Major Abdominal Surgery: a Parallel-group, Double-blind Randomized Trial

Overview

The investigators propose a multicenter randomized trial to test the renal safety of 6% hydroxyethyl starch (HES) 130/0.4 combined with sodium acetate Ringer's crystalloid solution in moderate-to-high cardiovascular risk patients having major abdominal surgery. The reference group will only be given sodium acetate Ringer's crystalloid.

Detailed description

The investigators propose a multicenter randomized trial to test the renal safety of 6% hydroxyethyl starch (HES) 130/0.4 combined with sodium acetate Ringer's crystalloid solution in moderate-to-high cardiovascular risk patients having major abdominal surgery. The reference group will only be given sodium acetate Ringer's crystalloid.

The investigators will test the primary hypothesis that the maximum decrease in serum Cystatin-C-based estimated glomerular filtration rate (eGFR) from preoperatively through the initial 3 postoperative hospital days is non-inferior in patients who are randomized to a goal-directed combination of HES and crystalloid volume replacement versus goal-directed crystalloid alone.

Secondarily, the investigators will determine the long-term renal safety (cystatin C-based eGFR on postoperative 1 and 3 months) of HES and its effect on major adverse cardiovascular events and the length of hospitalization. Exploratory outcomes will include intraoperative hemodynamic indices, postoperative gastrointestinal indicators, the rate of unscheduled transferring to intensive care unit, the incidence of hospital re-admission within 30 days, the incidence of renal replacement therapy within 90 days after surgery, and the incidence of acute kidney injury based on serum creatine within 7 days.

Interventions

• Drug Hydroxyethyl starch 130/0.4
  Individualized goal-directed administration of 6% Hydroxyethyl starch (HES) 130/0.4: After the induction of anesthesia, 200 ml trial fluid will be infused over 20 min. If stroke volume (SV) increases \>10%, another 200 ml fluid will be given. After that, the use of trial fluid will be determined by the patients' Stroke Volume Variation (SVV). If the SVV exceeds 12%, 200 ml trial fluid will be given over 20 min; this will be repeated until SVV \<12%. If the use of HES exceeds 30 ml/kg, sodi
• Drug Sodium acetate Ringer
  Individualized goal-directed administration of crystalloid alone: After the induction of anesthesia, 200 ml trial fluid will be infused over 20 min. If stroke volume (SV) increases \>10%, another 200 ml fluid will be given. After that, the use of trial fluid will be determined by the patients' Stroke Volume Variation (SVV). If the SVV exceeds 12%, 200 ml trial fluid will be given over 20 min; this will be repeated until SVV \<12%. In addition, patients will have a background infusion of s

Primary outcome measures

• Maximum change in serum Cystatin-C based estimated glomerular filtration rate (eGFR) from baseline through initial 3 postoperative hospital days [Time frame: Baseline and postoperative 1/2/3 day]

Secondary outcome measures (4)

• Cystatin-C based eGFR on postoperative 1 month [Time frame: Postoperative 1 month]
• Cystatin-C based eGFR on postoperative 3 months [Time frame: Postoperative 3 months]
• Postoperative major adverse cardiovascular events composite [Time frame: Postoperative 30 days]
• The length of hospitalization [Time frame: Postoperative 3 month]

Eligibility criteria

Inclusion criteria

• Are at least 45 years old;
• Scheduled for elective open or laparoscopic gastrointestinal surgery expected to last ≥2 hours;
• Having general anesthesia;
• Expected to require at least overnight hospitalization;
• Subject to at least one of the following risk factors:

• Age ≥65 years;
• History of peripheral arterial disease;
• History of coronary artery disease;
• History of stroke or transient ischemic attack;
• Diabetes requiring medication;
• Current smoking or 15-pack-year history of smoking tobacco;
• Body mass index ≥30 kg/m2;
• Preoperative high-sensitivity troponin T ≥14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay), or 25% of the 99% percentile for other assays - all within 6 months;
• B-type natriuretic protein (BNP) ≥80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) ≥200 ng/L within six months.

Exclusion criteria

• Participate in conflicting studies;
• Are designated American Society of Anesthesiologists physical status 4;
• Are pregnant and/or breastfeeding;
• Have hypoproteinemia (serum albumin <30 g/L) or were given preoperative intravenous colloids, including albumin;
• Have recent intracranial or cerebral hemorrhage;
• Have preoperative acute kidney injury or chronic renal insufficiency (Serum Creatine ≥140 µmol/L for men, Serum Creatine≥120 µmol/L for women and/or oliguria/anuria) or renal replacement therapy;
• Have severe hepatic impairment (Alanine Transaminase (ALT) and/or Aspartate Aminotransferase (AST) more than two times the upper limit of normal);
• Are in congestive heart failure or have pulmonary edema;
• Are critically ill or septic;
• Have electrolyte disorders such as hypernatremia, hyperchloremia, hyperkalemia, or severe alkalosis;
• Are fluid overloaded or dehydrated;
• Have clinically meaningful coagulation or bleeding disorders;
• Had a solid organ transplant;
• Have a current serious burn injury;
• Have a mental illness that precludes adequate consent or cooperation with the proposed trial;
• Have known hypersensitivity or contraindication to Volulyte 6% or any sodium acetate Ringer solution component.

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

Double blind

Primary purpose

Treatment

Study locations

China · 6 centers

• The First Affiliated Hospital of Zhengzhou University; — Zhengzhou
• Xiangya Hospital of Central South University — Changsha
• The First Hospital of China Medical University — Shenyang
• Shandong Provincial Qianfoshan Hospital — Jinan
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi&#39;an
• Chaoyang Hospital of Capital Medical University — Beijing

Publications

• Reiterer C, Kabon B, Taschner A, Zotti O, Kurz A, Fleischmann E. A comparison of intraoperative goal-directed intravenous administration of crystalloid versus colloid solutions on the postoperative maximum N-terminal pro brain natriuretic peptide in patients undergoing moderate- to high-risk noncardiac surgery. BMC Anesthesiol. 2020 Aug 4;20(1):192. doi: 10.1186/s12871-020-01104-9. PMID 32753064
• Yates DR, Davies SJ, Milner HE, Wilson RJ. Crystalloid or colloid for goal-directed fluid therapy in colorectal surgery. Br J Anaesth. 2014 Feb;112(2):281-9. doi: 10.1093/bja/aet307. Epub 2013 Sep 20. PMID 24056586
• Futier E, Garot M, Godet T, Biais M, Verzilli D, Ouattara A, Huet O, Lescot T, Lebuffe G, Dewitte A, Cadic A, Restoux A, Asehnoune K, Paugam-Burtz C, Cuvillon P, Faucher M, Vaisse C, El Amine Y, Beloeil H, Leone M, Noll E, Piriou V, Lasocki S, Bazin JE, Pereira B, Jaber S; FLASH Trial Group; Lasocki S, Huet O, Cadic A, Jacob C, Paugam-Burtz C, Restoux A, Ouattara A, Feitita I, Deloge E, Defaye M, PMID 31961418
• Kabon B, Sessler DI, Kurz A; Crystalloid-Colloid Study Team. Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity: A Randomized Trial. Anesthesiology. 2019 May;130(5):728-744. doi: 10.1097/ALN.0000000000002601. PMID 30882476
• Joosten A, Delaporte A, Ickx B, Touihri K, Stany I, Barvais L, Van Obbergh L, Loi P, Rinehart J, Cannesson M, Van der Linden P. Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a Closed-loop System: A Randomized, Double-blinded, Controlled Trial in Major Abdominal Surgery. Anesthesiology. 2018 Jan;128(1):55-66. doi: 10.1097/ALN.0000000000001936. PMID 29068831
• Reiterer C, Kabon B, Halvorson S, Sessler DI, Mascha EJ, Kurz A; Crystalloid-Colloid Research Group. Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery. Anesthesiology. 2022 Jan 1;136(1):127-137. doi: 10.1097/ALN.0000000000004040. PMID 34724045
• Calvo-Vecino JM, Ripolles-Melchor J, Mythen MG, Casans-Frances R, Balik A, Artacho JP, Martinez-Hurtado E, Serrano Romero A, Fernandez Perez C, Asuero de Lis S; FEDORA Trial Investigators Group. Effect of goal-directed haemodynamic therapy on postoperative complications in low-moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial). Br J Anaesth. 2018 Apr;120(4):7 PMID 29576114
• Ruetzler K, Khanna AK, Sessler DI. Myocardial Injury After Noncardiac Surgery: Preoperative, Intraoperative, and Postoperative Aspects, Implications, and Directions. Anesth Analg. 2020 Jul;131(1):173-186. doi: 10.1213/ANE.0000000000004567. PMID 31880630

Identifiers

NCT: NCT06663254 · XiangyaHMZKHES · 2024060725

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗