Hydroxyethyl Starch, Perioperative Volume Replacement
Conditions
Brief summary
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
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, sodium acetate Ringer will be replaced. In addition, patients will have a background infusion of sodium acetate Ringer's solution at 4 ml/kg/h to satisfy the maintenance fluid requirements during surgery.
DRUGSodium 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 sodium acetate, the maintenance fluid requirement during surgery.
Sponsors
Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Specifically, everyone except anesthesia clinicians will be blinded to treatment. Anesthesia clinicians who are not blinded will conduct treatment and record intraoperative conditions. Outcome assessors responsible for postoperative follow-up are blinded to patient randomization; Statistical analysis performed independently by the designated blinded statistician. Emergency unblinding will only be done by an investigator and/or dedicated authorized personnel (e.g., the Pharmacovigilance Department of the Sponsor).
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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: 1. Age ≥65 years; 2. History of peripheral arterial disease; 3. History of coronary artery disease; 4. History of stroke or transient ischemic attack; 5. Diabetes requiring medication; 6. Current smoking or 15-pack-year history of smoking tobacco; 7. Body mass index ≥30 kg/m2; 8. 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; 9. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum change in serum Cystatin-C based estimated glomerular filtration rate (eGFR) from baseline through initial 3 postoperative hospital days | Baseline and postoperative 1/2/3 day | The decrease in cystatin-C-based eGFR from preoperatively to the minimum value recorded during the initial three postoperative hospital days. Increases in postoperative eGFR will be considered a reduction of 0 for analysis purposes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cystatin-C based eGFR on postoperative 1 month | Postoperative 1 month | The absolute value of cystatin-C based eGFR on postoperative 1 month. |
| Cystatin-C based eGFR on postoperative 3 months | Postoperative 3 months | The absolute value of cystatin-C based eGFR on postoperative 3 months. |
| Postoperative major adverse cardiovascular events composite | Postoperative 30 days | Major adverse cardiovascular events are a composite of all-cause mortality or one or more of the following cardiovascular complications occurring within 30 days after surgery: myocardial injury after non-cardiac surgery (MINS), non-fatal cardiac arrest, stroke, ventricular arrhythmia requiring treatment. |
| The length of hospitalization | Postoperative 3 month | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Generalized average real variability of mean arterial pressure | Perioperative | — |
| Time to first defecation | Postoperative 30 days | — |
| Time to tolerance of oral liquid diet | Postoperative 30 days | — |
| the incidence of acute kidney injury based on available serum creatine | Postoperative 7 days | — |
| Hospital re-admission within 30 days | Postoperative 30 days | — |
| The rate of unscheduled transferring to intensive care unit (ICU) | Postoperative 30 days | — |
| Postoperative gastrointestinal complications | Postoperative 30 days | Postoperative gastrointestinal complications occurring by day 30 after surgery (defined as the need for surgical reoperation): anastomotic leakage, leakage of the rectum, intestinal obstruction, peritonitis, necrosis of stoma, et, at. which need reoperation or endoscopic drainage. |
| The incidence of renal replacement therapy within 90 days after surgery | Postoperative 3 month | — |
| Average cardiac index | Perioperative | — |
| Responses to boluses of each fluid | Perioperative | The average difference between the cardiac index measured before a bolus is given and of the cardiac index measured 30 after the beginning of each bolus. |
| Total fluid volume | Perioperative and the subsequent first 24 postoperative hours | Total fluid volume (sodium Acetate Ringer and 6% hydroxyethyl starch 130/0.4) given during anesthesia and the subsequent first 24 postoperative hours. |
Countries
China
Contacts
Primary ContactE Wang, M.D., Ph.D.
Outcome results
None listed