Crystalloids or Colloids for Goal-directed Fluid Therapy With Closed-loop Assistance in Major Surgery

Phase IV, Multicentric, Prospective, Controlled, Randomized, Double Blind Study Comparing a Crystalloid to a Colloid Used in the Perioperatory Hemodynamic Optimisation With a 'Closed Loop' Automatic Filling System, on the Post-surgery Morbidity in Major Abdominal Surgery.

Study goal: This study will examine whether there is a significant difference in postoperative outcomes between GDFT using a colloid solution versus a crystalloid solution.

Hypothesis: Perioperative fluid optimization through the use of a closed-loop assistance with a balanced starch solution (volulyte®) will be associated with a decrease in postoperative complications compared to the same approach using a balanced crystalloid solution (Plasmalyte®).

Objective: To establish which kind of intravenous fluid used for goal directed therapy with closed-loop assistance will reduce the number of postoperative complications (evaluation made by the POMS score).

Study Overview

• Status: Completed
• Conditions: Surgery
• Intervention / Treatment: Drug: Volulyte; Drug: Plasmalyte

Detailed Description

Controversy still persists regarding the type of fluid to use in the operating room to avoid hypovolemia and any circulatory insufficiency. While crystalloids and colloid solutions are frequently used to optimize intravascular volume during surgery, crystalloid solutions require more volume for hemodynamic optimization which may result in higher volumes of fluid administration and potentially side effects. Compared with crystalloids, colloids have the advantages of remaining in the intravascular space longer, achieving faster circulatory stabilization, maintaining colloid osmotic pressure and increasing micro perfusion. However, colloids are more expensive and may have various side effects.

In addition to the effect of crystalloids and colloids on the patient, the amount of each fluid administered is also under debate. Goal-directed fluid therapy (GDFT) strategies based on cardiac output (CO) optimization have been shown to benefit moderate- to high-risk surgery patients and have recently been recommended by professional societies in the UK, in France, and in Europe. However, despite the growing evidence, these strategies are often not implemented in current practice. One of the reasons for this lack of implementation is that GDFT strategies, like any other complex clinical protocol, require significant provider attention and vigilance for consistent implementation and it is well known that even under study conditions protocol compliance rates are often not greater than 50% In another hand, one of the chief complicating factors in fluid administration studies is variation in provider administration practices, even when attempting to follow a protocol. Previous studies have used closed-loop (automated) systems to deliver fluid by a standardized protocol, removing variation between providers as one of the confounders of the study. Dr. Cannesson and Rinehart (UC Irvine, California, USA) have recently developed and used a closed-loop system for the provision of GDFT in clinical studies at UC Irvine and La Pitie hospital in France. The closed-loop system is beneficial because it involves the standardization of fluid management and all patients are treated equivalently. This system will thus provide consistent GDFT for all cases in the protocol and remove inter-provider variability as a confounder between groups.

Study goal: This study will examine whether there is a significant difference in postoperative outcomes between GDFT using a colloid solution versus a crystalloid solution.

Hypothesis: Perioperative fluid optimization through the use of a closed-loop assistance with a balanced starch solution (volulyte®) will be associated with a decrease in postoperative complications compared to the same approach using a balanced crystalloid solution (Plasmalyte®).

Objective: To establish which kind of intravenous fluid used for goal directed therapy with closed-loop assistance will reduce the number of postoperative complications (evaluation made by the POMS score).

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann
  • Brussels, Belgium, 1070
    • Erasme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (over the age of 18) undergoing elective major abdominal surgery that is expected to take longer than 3 hours and requiring a general anesthesia and a minimally invasive cardiac output monitoring (Vigileo/Flotrac)
• Patients who provide written informed consent

Exclusion Criteria:

• Patients under 18 years of age
• Patients not undergoing surgery, requiring anesthesia, or cardiac output monitoring
• Patients with arrhythmia and/or atrial fibrillation
• Patients who are allergic to HES
• Patients with renal insufficiency (serum creatinine of >2 mg/ml) or hepatic dysfunction (liver enzymes >1.5)
• Patients who has coagulation disorders (please define: values higher than 1.5x normal values
• Patients without the capacity to give written informed consent or refusal of consent
• Patients included in another protocol within a period of 3 months or Participating in another randomised trial
• Pregnancy at time of enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Volulyte; A baseline crystalloid infusion (plasmalyte®) will be set by the attending physician at 3 cc/kg/hr (standard patient care) for each of the randomized groups. The patient will receive fluid management via a closed loop (automated) system that will use an infusion pump (Q-Core) and a controller (a computer run index and algorithm developed by Sironis) to standardize the way fluids are administered intra-operatively and eliminate variation between clinical providers. The liquid perfused will be bolus amounts of volulyte.	Drug: Volulyte
Active Comparator: Plasma-Lyte; A baseline crystalloid infusion (plasmalyte®) will be set by the attending physician at 3 cc/kg/hr (standard patient care) for each of the randomized groups. The patient will receive fluid management via a closed loop (automated) system that will use an infusion pump (Q-Core) and a controller (a computer run index and algorithm developed by Sironis) to standardize the way fluids are administered intra-operatively and eliminate variation between clinical providers. The liquid perfused will be bolus amounts of plasma-lyte.	Drug: Plasmalyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
POMS score	Difference between the 2 groups in postoperative morbidity identified with the Post-Operative Morbidity Survey (POMS score) on postoperative days 2.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	Difference in 30-day post-operative mortality between the 2 groups	30 days
Length of hospitalisation	Difference in duration of hospital length of stay as well as ICU length of stay.	every day up to 90 days after hospitalisation
Quantity of fluid administered during surgery	Fluid balance during surgery	24 hours
Transfusion rate	Differences of transfusion rate between the two groups, in ml	8 days
Hypotension incidence	Incidence of hypotension (defined as total case time spent with 20% drop from baseline preoperative blood pressure).	8 days
Need of vasopressors	Difference in the need and quantity of vasopressors between the two groups	24 hours
Mean case cardiac index (L /BSA)	Mean case cardiac index (L /BSA), Mean case cardiac stroke volume index (mL/ BSA).	24 hours
Whodas scale	Enrolled patients will be contacted by phone and their quality of life assessed by the Whodas scale	6 months after surgery
Whodas scale	Enrolled patients will be contacted by phone and their quality of life assessed by the Whodas scale	1 year after surgery
Pruritus apparition	Enrolled patients will be contacted by phone 6 months after surgery and any pruritus apparition will be recorded	6 months after surgery
Pruritus apparition	Enrolled patients will be contacted by phone 1 year after surgery and any pruritus apparition will be recorded	1 year after surgery
Renal function - urea level	Urea levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	6 months after surgery
Renal function - urea level	Urea levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	1 year after surgery
Renal function - creatinine level	Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	6 months after surgery
Renal function - creatinine level	Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	1 year after surgery
Renal function - Estimated glomerular filtration rate (eGFR)	Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	6 months after surgery
Renal function - Estimated glomerular filtration rate (eGFR)	Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments.	1 year after surgery

Collaborators and Investigators

• Sponsor: Brugmann University Hospital
• Investigators: Principal Investigator: Amélie Delaporte, MD, CHU Brugmann; Principal Investigator: Alexandre Joosten, MD, Erasme; Principal Investigator: Philippe Van der Linden, MD, Pr, CHU Brugmann; Principal Investigator: Brigitte Ickx, Md, Pr, Erasme

Publications and helpful links

General Publications

• Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH, Elkjaer JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Soe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjaeldgaard AL, Fabritius ML, Mondrup F, Pott FC, Moller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012 Jul 12;367(2):124-34. doi: 10.1056/NEJMoa1204242. Epub 2012 Jun 27. Erratum In: N Engl J Med. 2012 Aug 2;367(5):481.
• Feldheiser A, Pavlova V, Bonomo T, Jones A, Fotopoulou C, Sehouli J, Wernecke KD, Spies C. Balanced crystalloid compared with balanced colloid solution using a goal-directed haemodynamic algorithm. Br J Anaesth. 2013 Feb;110(2):231-40. doi: 10.1093/bja/aes377. Epub 2012 Oct 30.
• Silva JM Jr, de Oliveira AM, Nogueira FA, Vianna PM, Pereira Filho MC, Dias LF, Maia VP, Neucamp Cde S, Amendola CP, Carmona MJ, Malbouisson LM. The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study. Crit Care. 2013 Dec 10;17(6):R288. doi: 10.1186/cc13151.
• Cannesson M. Arterial pressure variation and goal-directed fluid therapy. J Cardiothorac Vasc Anesth. 2010 Jun;24(3):487-97. doi: 10.1053/j.jvca.2009.10.008. No abstract available.
• Ramsingh DS, Sanghvi C, Gamboa J, Cannesson M, Applegate RL 2nd. Outcome impact of goal directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized controlled trial. J Clin Monit Comput. 2013 Jun;27(3):249-57. doi: 10.1007/s10877-012-9422-5. Epub 2012 Dec 22.
• Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, Grocott MP, Ahern A, Griggs K, Scott R, Hinds C, Rowan K; OPTIMISE Study Group. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA. 2014 Jun 4;311(21):2181-90. doi: 10.1001/jama.2014.5305. Erratum In: JAMA. 2014 Oct 8;312(14):1473.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2015
• Primary Completion (Actual): December 21, 2017
• Study Completion (Actual): December 21, 2017

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: laparotomy; abdominal surgery; close loop; plasma-Lyte; volulyte
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: CHUB-fluides

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No