NCT03537989

Brief Summary

This is a protocol for a trial carried out from 1999 to 2002. At that time, surgical patients received a large volume of intravenous saline during operations on the colon or the rectum, often so much fluid that their bodyweight increased by 4-6 kilograms. We hypothesized; that a restricted fluid regimen could prevent the development of cardiopulmonary complications and improve wound healing including the healing of an anastomosis of the gut. We designed a clinical randomized assessor blinded multi-center trial comparing a restricted fluid regimen to a standard fluid regimen, the difference being the volume of saline administered to the patients. Patients undergoing surgery on the colon or the rectum were included after informed oral and written consent. The restricted regimen aimed at zero-fluid balance with allowance for a body weight increase of 1 kg. The standard regimen was a bit "dryer" than the actual standard; our patients in the standard group received saline causing a body weight increase of only 3-4 kg. The fluid therapy started at midnight the day of operation, went on through the operation and continued on the wards until discharge. The patients were encouraged to eat and drink as much and as soon as possible after the operation. The primary outcome was the number of patients who died or suffered a complication measured within 30 days of surgery. We looked at all complications, but especially heart and lung complications and complications related to the healing of wounds and anastomosis. The patients was examined in the outpatient clinic after 30 days, and in addition, blinded assessors were reviewing the medical files for registration of postoperative complications. The results are published in The Annals of Surgery 2003; 238(5)641-48. The restricted regimen nearly halved the number of patients with complications, and heart and lung complications were almost eliminated. Other investigators confirmed the results, and a more restricted approach to fluid therapy to surgical patients has been implemented worldwide.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
172

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 1999

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 1999

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2001

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2001

Completed
16.7 years until next milestone

First Submitted

Initial submission to the registry

May 11, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

May 25, 2018

Completed
Last Updated

October 5, 2018

Status Verified

October 1, 2018

Enrollment Period

1.8 years

First QC Date

May 11, 2018

Last Update Submit

October 3, 2018

Conditions

Colorectal SurgeryPostoperative Complications

Keywords

fluid therapyRestricted fluid therapysaline

Outcome Measures

Primary Outcomes (1)

  • Postoperative complications and mortality

    The complications was defined by protocol.

    After 30 days of follow-up

Secondary Outcomes (2)

  • Cardiopulmonary complications

    After 30 days of follow-up

  • Complications related to tissue healing

    After 30 days of follow-up

Other Outcomes (1)

  • Hospital stay

    after 30 days of follow-up

Study Arms (2)

Restricted group

EXPERIMENTAL

Oral fluid to 2 h before surgery. Intra-operatively: Glucose 5% (500 ml - volume drunk during fast); HAES 6% for blood loss volume to volume; IV-medicine in saline 0.9% for anesthesia and antibiotics. Blood products after current rules. Postoperatively: 1000 ml glucose containing fluid in the recovery room. Free oral intake of fluid and food as well as enteral feeding by tube 500 ml. In the wards: Enteral feeding by tube 1000 ml postoperative day 1-3. Free fluid and food by mouth. If less than 1500 ml fluid pr. mouth supplement with VI-fluid. Pathological fluid loss (high output stoma, aspirate, vomit etc.) - replace with IV-fluid. Goal: zero fluid balance with up to 1-kilogram body weight increase. Urine \< 0.5 ml/kg/h: supplement with fluid. MAP \< 60 and hypovolemia: treat with fluid.

Drug: Saline

Standard group

ACTIVE COMPARATOR

Oral fluid to 2 h before surgery. Intra-operatively: Saline 500 ml for fasting; 500 ml HAES 6% for the epidural, Saline for the third space: 7 ml/kg/h first hour, 5 ml/kg/h 2.-3. Hour, 3 ml/kg/h subsequent hours. 1000-1500 ml Saline replaced lost blood up to 500 ml, additional HAES 6% for additional blood loss; IV-medicine in saline. Postoperatively: 1000-2000 ml isotonic fluid in the recovery room. Free oral fluid and food as well as enteral feeding by tube 500 ml. In the wards: Enteral feeding by tube 1000 ml postoperative day 1-3. Free fluid and food by mouth. Supplemental iv-fluid according to department rules. Pathological fluid loss (high output stoma, aspirate, vomit etc.) - replace with IV-fluid. Urine \< 0.5 ml/kg/h: supplement with fluid. MAP \< 60 and hypovolemia: treat with fluid.

Drug: Saline

Interventions

SalineDRUG

To reduce the volume of saline administered during surgery of the colon and the rectum

Also known as: NaCl 0.9%
Restricted groupStandard group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients scheduled for planned surgery on the colon or the rectum
  • ASA group 1-3

You may not qualify if:

  • Patients unable to give informed consent (mental disorders, dementia, language problems)
  • Patients with:
  • Diabetes mellitus
  • Renal insufficiency
  • Disseminated cancers or secondary cancers
  • Inflammatory bowel disease
  • Diseases hindering epidural analgesia
  • Alcohol consumption more than 35 drinks pr. Week
  • Pregnant and lactating woman.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (10)

  • Lowell JA, Schifferdecker C, Driscoll DF, Benotti PN, Bistrian BR. Postoperative fluid overload: not a benign problem. Crit Care Med. 1990 Jul;18(7):728-33. doi: 10.1097/00003246-199007000-00010.

    PMID: 2364713BACKGROUND

  • Beier-Holgersen R, Boesby S. Influence of postoperative enteral nutrition on postsurgical infections. Gut. 1996 Dec;39(6):833-5. doi: 10.1136/gut.39.6.833.

    PMID: 9038665BACKGROUND

  • Nielsen OM, Engell HC. Increased glomerular filtration rate in patients after reconstructive surgery on the abdominal aorta. Br J Surg. 1986 Jan;73(1):34-7. doi: 10.1002/bjs.1800730113.

    PMID: 3947870BACKGROUND

  • Rasmussen LA, Rosenberg J, Crawford ME, Kehlet H. [Perioperative fluid therapy. A quality control study]. Ugeskr Laeger. 1996 Sep 16;158(38):5286-90. Danish.

    PMID: 8966776BACKGROUND

  • Vamvakas EC, Carven JH, Hibberd PL. Blood transfusion and infection after colorectal cancer surgery. Transfusion. 1996 Nov-Dec;36(11-12):1000-8. doi: 10.1046/j.1537-2995.1996.36111297091746.x.

    PMID: 8937412BACKGROUND

  • Cosnett JE. The origins of intravenous fluid therapy. Lancet. 1989 Apr 8;1(8641):768-71. doi: 10.1016/s0140-6736(89)92583-x. No abstract available.

    PMID: 2564573BACKGROUND

  • Vermeulen LC Jr, Ratko TA, Erstad BL, Brecher ME, Matuszewski KA. A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. Arch Intern Med. 1995 Feb 27;155(4):373-9. doi: 10.1001/archinte.155.4.373.

    PMID: 7848020BACKGROUND

  • Weinstein PD, Doerfler ME. Systemic complications of fluid resuscitation. Crit Care Clin. 1992 Apr;8(2):439-48.

    PMID: 1568149BACKGROUND

  • Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, Rasmussen MS, Lanng C, Wallin L, Iversen LH, Gramkow CS, Okholm M, Blemmer T, Svendsen PE, Rottensten HH, Thage B, Riis J, Jeppesen IS, Teilum D, Christensen AM, Graungaard B, Pott F; Danish Study Group on Perioperative Fluid Therapy. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003 Nov;238(5):641-8. doi: 10.1097/01.sla.0000094387.50865.23.

    PMID: 14578723RESULT

  • Brandstrup B, Beier-Holgersen R, Iversen LH, Starup CB, Wentzel LN, Lindorff-Larsen K, Petersen TC, Tonnesen H. The Influence of Perioperative Fluid Therapy on N-terminal-pro-brain Natriuretic Peptide and the Association With Heart and Lung Complications in Patients Undergoing Colorectal Surgery: Secondary Results of a Clinical Randomized Assessor-blinded Multicenter Trial. Ann Surg. 2020 Dec;272(6):941-949. doi: 10.1097/SLA.0000000000003724.

    PMID: 31850996DERIVED

MeSH Terms

Conditions

Postoperative Complications

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Birgitte Brandstrup, PhD

    Holbaek Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Surgeon, Clinical Associate Professor, PhD

Study Record Dates

First Submitted

May 11, 2018

First Posted

May 25, 2018

Study Start

November 1, 1999

Primary Completion

August 31, 2001

Study Completion

August 31, 2001

Last Updated

October 5, 2018

Record last verified: 2018-10