Trial Outcomes & Findings for REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery: RELIEF Study (NCT NCT01424150)

NCT ID: NCT01424150

Last Updated: 2026-01-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 3000 participants
• Primary outcome timeframe: 1 year postoperative
• Results posted on: 2026-01-20

Participant Flow

Participant milestones

Measure	Liberal At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Overall Study STARTED	1501	1499
Overall Study COMPLETED	1493	1490
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.	Total n=2983 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 13 • n=1493 Participants	66 years STANDARD_DEVIATION 13 • n=1490 Participants	66 years STANDARD_DEVIATION 13 • n=2983 Participants
Sex: Female, Male Female	710 Participants n=1493 Participants	719 Participants n=1490 Participants	1429 Participants n=2983 Participants
Sex: Female, Male Male	783 Participants n=1493 Participants	771 Participants n=1490 Participants	1554 Participants n=2983 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Australia	841 participants n=1493 Participants	836 participants n=1490 Participants	1677 participants n=2983 Participants
Region of Enrollment Canada	247 participants n=1493 Participants	250 participants n=1490 Participants	497 participants n=2983 Participants
Region of Enrollment United Kingdom	134 participants n=1493 Participants	141 participants n=1490 Participants	275 participants n=2983 Participants
Region of Enrollment Hong Kong	116 participants n=1493 Participants	111 participants n=1490 Participants	227 participants n=2983 Participants
Region of Enrollment United States	75 participants n=1493 Participants	74 participants n=1490 Participants	149 participants n=2983 Participants
Region of Enrollment New Zealand	48 participants n=1493 Participants	46 participants n=1490 Participants	94 participants n=2983 Participants
Region of Enrollment Italy	32 participants n=1493 Participants	32 participants n=1490 Participants	64 participants n=2983 Participants
American Society Anesthesiologists (ASA) Physical Status ASA 1	21 Participants n=1493 Participants	25 Participants n=1490 Participants	46 Participants n=2983 Participants
American Society Anesthesiologists (ASA) Physical Status ASA 2	540 Participants n=1493 Participants	542 Participants n=1490 Participants	1082 Participants n=2983 Participants
American Society Anesthesiologists (ASA) Physical Status ASA 3	868 Participants n=1493 Participants	849 Participants n=1490 Participants	1717 Participants n=2983 Participants
American Society Anesthesiologists (ASA) Physical Status ASA 4	64 Participants n=1493 Participants	74 Participants n=1490 Participants	138 Participants n=2983 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Disability-free Survival	165 Participants	172 Participants

SECONDARY outcome

Timeframe: 90 days, then up to 12 months after surgery

deceased within 12 months

Outcome measures

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Death	96 Participants	95 Participants

SECONDARY outcome

Timeframe: 30 days postoperative

composite of 1 or more of:sepsis, surgical site infection, anastomotic leak, death and pneumonia

Outcome measures

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Composite Septic Outcome or Death	295 Participants	323 Participants

SECONDARY outcome

Timeframe: 30 days postoperative

using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria, two or more features of the systematic inflammatory response syndrome (SIRS) plus evidence of a source or site of infection (can be positive blood culture or purulence from any site)

Outcome measures

Measure	Liberal n=1487 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1481 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Sepsis	129 Participants	157 Participants

SECONDARY outcome

Timeframe: 30 days postoperative

using CDC criteria (http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf):

Outcome measures

Measure	Liberal n=1481 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1487 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Surgical Site Infection	245 Participants	202 Participants

SECONDARY outcome

Timeframe: 30 Days postoperative

The presence of new and/or progressive pulmonary infiltrates on chest radiograph plus two or more of the following:

1. Fever ≥ 38.5°C or postoperative hypothermia <36°C

2. Leukocytosis ≥ 12,000 WBC/mm3 or leukopenia < 4,000 WBC/mm3

3. Purulent sputum and/or

4. New onset or worsening cough or dyspnoea.

Outcome measures

Measure	Liberal n=1481 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1487 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Pneumonia	54 Participants	57 Participants

SECONDARY outcome

Timeframe: 30 days postoperative

according to The Kidney Disease: Improving Global Outcomes (KDIGO) group criteria, but not urine output - for Stage 2 or worse AKI defined as at least 2-fold increase in creatinine, or estimated GFR decrease >50%.(73) We also plan to report renal replacement therapy up to 90 days after surgery. Because a restrictive IV fluid regimen may artificially elevate serum creatinine due to a smaller dilutional effect from less IV fluids, we therefore calculated adjusted creatinine by first estimating the volume of distribution for creatinine as equal to total body water (assumed to be 60% of body weight, expressed in mL).

Outcome measures

Measure	Liberal n=1439 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1443 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Acute Kidney Injury	72 Participants	124 Participants

SECONDARY outcome

Timeframe: 30 days postoperative

respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema

Outcome measures

Measure	Liberal n=1487 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1481 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Pulmonary Oedema	32 Participants	20 Participants

SECONDARY outcome

Timeframe: 30 day postoperative

including initial ICU admission and readmission times up to 30 days post operatively

Outcome measures

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Total Duration of Time Spend in the ICU or HDU (in Days)	1.8 days Interval 1.0 to 3.1	1.4 days Interval 0.9 to 2.9

SECONDARY outcome

Timeframe: 30 days postoperative

from the start (date, time) of surgery until actual hospital discharge

Outcome measures

Measure	Liberal n=1493 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Hospital Stay	5.6 days Interval 3.6 to 10.5	6.4 days Interval 3.6 to 10.6

SECONDARY outcome

Timeframe: days 3

15-item Quality of Recovery Score. The score is a patient reported outcome measure to score the individuals recovery following anaesthesia and surgery. Minimum value is 0 and maximum value is 150. The score of 150 is good. The higher the score the better

Outcome measures

Measure	Liberal n=1418 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1420 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Quality of Recovery	107 score on a scale Interval 90.0 to 122.0	106 score on a scale Interval 89.0 to 121.0

SECONDARY outcome

Timeframe: 30 days postoperative

A defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- an extra luminal compartments.

Outcome measures

Measure	Liberal n=1487 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1481 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Anastomotic Leak	35 Participants	49 Participants

SECONDARY outcome

Timeframe: Day 3 postoperative

plasma C-reactive protein (CRP, using site-specific assay) concentration on Day 3

Outcome measures

Measure	Liberal n=1073 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1068 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
C-reactive Protein	133 mg/L Interval 80.0 to 200.0	136 mg/L Interval 82.0 to 198.0

SECONDARY outcome

Timeframe: 24 hours post surgery

peak serum lactate within 24 hours of surgery

Outcome measures

Measure	Liberal n=436 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=404 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
mmol/L	1.6 mmol/L Interval 1.1 to 2.4	1.6 mmol/L Interval 1.1 to 2.4

SECONDARY outcome

Timeframe: 30 days postoperative

additive, including initial ICU admission and readmission times up to Day 30

Outcome measures

Measure	Liberal n=473 Participants At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=485 Participants Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Total ICU Stay and Unplanned ICU Admission to ICU	1.4 days Interval 0.9 to 2.9	1.8 days Interval 1.0 to 3.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 years

We plan several substudies (to be funded from other sources), each of which will have a separate protocol and authorship plan (using an expanded list of contributors). Additional blood tests and other investigations will be done at selected hospitals according to local interest and expertise.

1. Cost-effectiveness, to include hospital stay and complications as we have done previously

2. Hyperchloraemic acidosis (to measure strong ion difference, Cl-, lactate, albumin …)

3. Pulmonary oedema and acute lung injury (to measure FiO2/PaO2 ratio, CT/CXR-confirmed atelectasis …)

4. Perioperative oliguria and acute kidney injury 5. Obesity and perioperative risk 6. BNP and risk prediction 7. Goal directed therapy - decision analysis 8. Perioperative diabetes and HbA1C 9. CKD follow-up

Outcome measures

Outcome data not reported

Adverse Events

Liberal

Serious events: 295 serious events

Other events: 78 other events

Deaths: 96 deaths

Restrictive

Serious events: 323 serious events

Other events: 79 other events

Deaths: 95 deaths

Serious adverse events

Measure	Liberal n=1493 participants at risk At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 participants at risk Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Infections and infestations Surgical site infection	19.8% 295/1493 • Number of events 295 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	21.7% 323/1490 • Number of events 323 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up
Infections and infestations Sepsis	8.6% 129/1493 • Number of events 129 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	10.5% 157/1490 • Number of events 157 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up
Infections and infestations Anastomotic leak	2.3% 35/1493 • Number of events 35 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	3.3% 49/1490 • Number of events 49 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up
Respiratory, thoracic and mediastinal disorders Pneumonia	3.8% 57/1493 • Number of events 57 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	3.6% 54/1490 • Number of events 54 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up

Other adverse events

Measure	Liberal n=1493 participants at risk At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data. Liberal fluid therapy: Liberal protocol group is designed to provide approximately 6.0L per day.	Restrictive n=1490 participants at risk Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device \[see below\]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia. Restrictive fluid therapy: Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Cardiac disorders Cardiovascular	5.2% 78/1493 • Number of events 78 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	5.3% 79/1490 • Number of events 79 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up
Blood and lymphatic system disorders Thrombolism	1.5% 23/1493 • Number of events 23 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up	2.1% 31/1490 • Number of events 31 • Adverse events were collected at 30 days following surgery Please note that the patients reviewed for adverse events are the patients that completed the 30 day follow up data collection. There fore as per the Figure one according to follow up

Additional Information

Professor Paul Myles

Alfred Health

Phone: 61 3 9076 3176

Email: p.myles@alfred.org.au

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place