Restrictive Versus Liberal Fluid Therapy in Major Abdominal Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 3,000
- 试验地点
- 2
- 主要终点
- Disability-free Survival
研究概览
简要总结
The optimal fluid regimen, haemodynamic (or other) targets and fluid choice (colloid or crystalloid) for patients undergoing major surgery are based on rationales that are not supported by strong evidence. Practices vary substantially, guidelines are vague, small trials and meta-analyses are contradictory. The strongest and most consistent evidence, and biological plausibility because of tissue edema, supports a restrictive fluid strategy. But other evidence supports goal-directed therapy, requiring additional IV fluid. There is no good evidence that use and choice of colloids improves outcome. RELIEF will study the effects of fluid restriction, and the possible effect-modification of goal-directed therapy and colloids. The first will be randomly assigned; the latter will be measured covariates dictated by local practices and beliefs.
Study Hypotheses A restrictive fluid regimen for adults undergoing major abdominal surgery leads to reduced complications and improved disability-free survival when compared with a liberal fluid regimen.
Secondary hypothesis: The effects of fluid restriction are similar whether or not goal-directed therapy is used (assessed as a statistical test of interaction). A restrictive fluid regimen will reduce a composite of 30-day septic complications and mortality.
详细描述
The investigators have completed a pilot study of 82 subjects to test the feasibility of the trial (2011), and are currently doing a cost-effectiveness substudy (2012-13)
- AIM OF THE TRIAL To investigate the effectiveness of fluid restriction (vs. liberal), and the possible effect-modification of goal-directed therapy (eg. oesophageal Doppler, Flotrac®). The first will be randomly assigned; the latter will be measured covariates according to local practices and beliefs.
The optimal fluid regimen and haemodynamic (or other) targets for patients undergoing major surgery are based on rationales that are not supported by strong evidence. Practices vary substantially; guidelines are vague, small trials and meta-analyses are contradictory. The strongest and most consistent evidence, and biological plausability regarding tissue oedema, supports a restrictive fluid strategy. There is less (and more contradictory) evidence supporting goal-directed therapy using a flow-directed device and/or dopexamine, and use and choice of colloids. A large, definitive clinical trial evaluating perioperative fluid replacement in major surgery is required.
Study Hypotheses A restrictive fluid regimen for adults undergoing major abdominal surgery leads to reduced complications and improved disability-free survival when compared with a liberal fluid regimen.
Secondary hypotheses: The effects of fluid restriction are similar whether or not goal-directed therapy is used (assessed as a statistical test of interaction). A restrictive fluid regimen will reduce a composite of 30-day septic complications and mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (≥18 years) undergoing elective major surgery and providing informed consent
- •All types of open or lap-assisted abdominal or pelvic surgery with an expected duration of at least 2 hours, and an expected hospital stay of at least 3 days (for example, oesophagectomy, gastrectomy, pancreatectomy, colectomy, aortic or aorto-femoral vascular surgery, nephrectomy, cystectomy, open prostatectomy, radical hysterectomy, and abdominal incisional hernia repair)
- •At increased risk of postoperative complications, defined as at least one of the following criteria:
- •age ≥70 years
- •known or documented history of coronary artery disease
- •known or documented history of heart failure
- •diabetes currently treated with an oral hypoglycaemic agent and/or insulin
- •preoperative serum creatinine >200 µmol/L (>2.8 mg/dl)
- •morbid obesity (BMI ≥35 kg/m²)
- •preoperative serum albumin <30 g/L
- •anaerobic threshold (if done) <12 mL/kg/min
- •or two or more of the following risk factors:
- •ASA 3 or 4
- •chronic respiratory disease
- •obesity (BMI 30-35 kg/m²)
- •aortic or peripheral vascular disease
- •preoperative haemoglobin <100 g/L
- •preoperative serum creatinine 150-199 µmol/L (>1.7 mg/dl)
- •anaerobic threshold (if done) 12-14 mL/kg/min
排除标准
- •Urgent or time-critical surgery
- •ASA physical status 5 - such patients are not expected to survive with or without surgery, and their underlying illness is expected to have an overwhelming effect on outcome (irrespective of fluid therapy)
- •Chronic renal failure requiring dialysis
- •Pulmonary or cardiac surgery - different pathophysiology, and thoracic surgery typically have strict fluid restrictions
- •Liver resection - most units have strict fluid/CVP limits in place and won't allow randomisation
- •Minor or intermediate surgery, such as laparoscopic cholecystectomy, transurethral resection of the prostate, inguinal hernia repair, splenectomy, closure of colostomy - each of these are typically "minor" surgery with minimal IV fluid requirements, generally low rates of complications and mostly very good survival.
结局指标
主要结局
Disability-free Survival
时间窗: 1 year postoperative
Disability-free survival up to 1 year: survival and freedom from disability. The latter is defined as a persistent (≥6 months) reduction in health status as measured by a 12-item version (12-60 points) of World Health Organisation Disability Assessment Schedule score (WHODAS) of 24 points, reflecting a disability level of at least 25% and being the threshold point between "disabled" and "not disabled" as per WHO guidelines. Disability will be assessed by the participant, but if unable then we will use the proxy's report. The date of onset of new disability will be recorded. Further details are provided in the Procedures Manual and the Statistical Analysis Plan.
次要结局
- Death(90 days, then up to 12 months after surgery)
- Composite Septic Outcome or Death(30 days postoperative)
- Sepsis(30 days postoperative)
- Pneumonia(30 Days postoperative)
- Surgical Site Infection(30 days postoperative)
- Total Duration of Time Spend in the ICU or HDU (in Days)(30 day postoperative)
- Acute Kidney Injury(30 days postoperative)
- Pulmonary Oedema(30 days postoperative)
- Hospital Stay(30 days postoperative)
- Quality of Recovery(days 3)
- Anastomotic Leak(30 days postoperative)
- C-reactive Protein(Day 3 postoperative)
- mmol/L(24 hours post surgery)
- Total ICU Stay and Unplanned ICU Admission to ICU(30 days postoperative)