Impact of Fluid Restriction Policy in Reducing the Use of Red Cells in Cardiac Surgery

• Sponsor: Larissa University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00600704
• Collaborator: (none)
• Enrollment: 192
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

The investigators' hypothesis is that restriction of circulating fluids in comparison to a liberal fluid administration policy would lead to a reduction of allogenic red blood cells exposure in patients undergoing cardiopulmonary bypass (CPB) for primary coronary artery bypass graft supported by reinfusion of washed shed blood from thoracic cavities.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Coronary Artery Bypass; Erythrocyte Transfusion	Procedure: Fluid Restriction Policy; Procedure: Free fluid infusion	N/A

Detailed Description

192 patients operated under equal conditions were assigned prospectively and randomly either for a restrictive protocol for intravenous fluid administration (group A, 100 patients) or not (group B, 92 patients). Transfusion guidelines were common for the two groups. The volumes of intravenous fluids, priming, "extra" volume on pump and cardioplegic solution and the volume of urine were recorded. Net erythrocyte volume loss was calculated. The number of the transfused PRC was analyzed as a continuous variable. "Transfusion" was analyzed as a categorical characteristic. Analysis employed Student's two-tailed t-test, t-paired test and chitest.

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Impact of Fluid Restriction Policy Added to Intra-Operative Cell Salvage in Reducing the Use of Red Cells in Cardiac Surgery
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: RESTRICTED FLUIDS Infusion of Hes 130/0.4 up to 500 ml until the beginning of Cardiopulmonary Bypass	Procedure: Fluid Restriction Policy; Infusion of Hes 130/0.4 up to 500 ml until the beginning of Cardiopulmonary bypass
Active Comparator: FREE FLUIDS Free fluid infusion unless Hb< 6g/dl(allogenic blood use), until the beginning of Cardiopulmonary bypass	Procedure: Free fluid infusion; Free fluid infusion unless Hb< 6g/dl(allogenic blood use), until the beginning of Cardiopulmonary bypass

Outcome Measures

Primary Outcome Measures

1. Mean Number of Packed Red Cells Units Transfused During Hospital Stay [20 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ejection fraction (EF) of left ventricle (LV) > 35%

• Preoperative serum Creatinine < 150 μmol/l

• Preoperative Haemoglobin > 10/dl

• Peripheral anastomosis scheduled =< 3

Exclusion Criteria:

• redo bypass-emergency operations

• prior coronal stenting

• active congestive heart failure

• documented Myocardial Infraction within the previous 6 weeks

• NYHA class > 3

• Carotid stenosis > 50%

• CVA

• INR > 1.5

• chronic obstructive pulmonary disease (COPD)

• Steroid therapy-chronic inflammatory process

• Use of aprotinin or tranexamic acid

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Larissa University Hospital	Larissa	Thesalia	Greece	41110

Sponsors and Collaborators

• Larissa University Hospital

Investigators

• Principal Investigator: ATHINA KLEITSAKI, Dr, Larissa University Hospital
• Study Director: GEORGE VRETZAKIS, M.D. PhD, Cardiac Anesthesia Unit, Department of Anesthesiology, University Hospital of Larissa, Greece
• Study Chair: KONSTANTINOS STAMOULIS, M.D., Cardiac Anesthesia Unit, Department of Anesthesiology, University Hospital of Larissa, Greece
• Study Chair: CHRISTOS DRAGOUMANIS, M.D. PhD, Cardiac Anesthesia Unit, Department of Anesthesiology, University Hospital of Larissa, Greece
• Study Chair: VASILIOS TASOUDIS, M.D., Cardiac Anesthesia Unit, Department of Anesthesiology, University Hospital of Larissa, Greece
• Study Chair: KATERINA KYRIAKAKI, M.D., Cardiac Anesthesia Unit, Department of Anesthesiology, University Hospital of Larissa, Greece
• Study Chair: DEMETRIOS MIKROULIS, M.D. PhD, Department of Cardiothoracic Surgery, University Hospital of Larissa, Greece
• Study Chair: ATHANASIOS GIANNOUKAS, MD MSc PhD, Department of Vascular Surgery, University Hospital of Larissa, Greece
• Study Chair: NIKOLAOS TSILIMINGAS, M.D. PhD, Department of Cardiothoracic Surgery, University Hospital of Larissa, Greece

Study Documents (Full-Text)

None provided.

More Information

Publications

• DeFoe GR, Ross CS, Olmstead EM, Surgenor SD, Fillinger MP, Groom RC, Forest RJ, Pieroni JW, Warren CS, Bogosian ME, Krumholz CF, Clark C, Clough RA, Weldner PW, Lahey SJ, Leavitt BJ, Marrin CA, Charlesworth DC, Marshall P, O'Connor GT. Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg. 2001 Mar;71(3):769-76.
• Dial S, Delabays E, Albert M, Gonzalez A, Camarda J, Law A, Menzies D. Hemodilution and surgical hemostasis contribute significantly to transfusion requirements in patients undergoing coronary artery bypass. J Thorac Cardiovasc Surg. 2005 Sep;130(3):654-61.
• Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed? J Thorac Cardiovasc Surg. 2003 Jun;125(6):1438-50.
• Karkouti K, Djaiani G, Borger MA, Beattie WS, Fedorko L, Wijeysundera D, Ivanov J, Karski J. Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg. 2005 Oct;80(4):1381-7.
• Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007 May;83(5 Suppl):S27-86. Review.
• Stover EP, Siegel LC, Parks R, Levin J, Body SC, Maddi R, D'Ambra MN, Mangano DT, Spiess BD. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology. 1998 Feb;88(2):327-33.

• ClinicalTrials.gov Identifier: NCT00600704
• Other Study ID Numbers: LUH 1975 AK; POL 1969 TT
• First Posted: Jan 25, 2008
• Last Update Posted: Jun 7, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Allogenic Blood Use; Total Blood Loss; Reinfusion of Washed Shed Blood
• Additional relevant MeSH terms: Coronary Artery Disease

Study Results

Participant Flow

Recruitment Details	This prospective study was conducted in our University Hospital over a 20-month period, after approval from the Institution Ethics committee, and written informed consent was obtained from all patients before entering the study. All the participants were patients of the Cardio-Thoracic Clinic of our Hospital.
Pre-assignment Detail	Exclusion criteria were emergency or re-do operations, operations starting after 18.00, administration of tissue plasminogen activator (TPA) or other thrombolytic medications, pre-existing hematologic disease or coagulation abnormality, advanced cirrhosis, renal failure, preoperative blood product transfusion, combined cardiac and carotid surgery.

Arm/Group Title	RESTRICTED FLUIDS	FREE FLUIDS
Arm/Group Description	Infusion of Hes 130/0.4 up to 500 ml	Free fluid infusion unless Hb< 6g/dl(allogenic blood use)
Period Title: Overall Study
STARTED	100	92
COMPLETED	100	92
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	RESTRICTED FLUIDS	FREE FLUIDS	Total
Arm/Group Description	Infusion of Hes 130/0.4 up to 500 ml	Free fluid infusion unless Hb< 6g/dl(allogenic blood use)	Total of all reporting groups
Overall Participants	100	92	192
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	100 100%	92 100%	192 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (7.9)	65.5 (8.3)	65.77 (8.1)
Sex: Female, Male (Count of Participants)
Female	17 17%	16 17.4%	33 17.2%
Male	83 83%	76 82.6%	159 82.8%
Region of Enrollment (participants) [Number]
Greece	100 100%	92 100%	192 100%

Outcome Measures

1. Primary Outcome

Title	Mean Number of Packed Red Cells Units Transfused During Hospital Stay
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

Patients between ages 18-85 undergoing elective cardiac surgery under cardiopulmonary bypass

Arm/Group Title	RESTRICTED FLUIDS	FREE FLUIDS
Arm/Group Description	Infusion of Hes 130/0.4 up to 500 ml	Free fluid infusion unless Hb< 6g/dl(allogenic blood use)
Measure Participants	100	92
Measure PRC Units	113	176
Mean (95% Confidence Interval) [packed red cells units]	1.13	1.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RESTRICTED FLUIDS, FREE FLUIDS
	Comments	Sample size calculation was based on a two-sided alpha error of .05 and 80% power. After applying the protocol in two equal groups of 10 patients, the analysis showed that the study requires 60 patients per group. However, we decided to enroll up to 100 patients per group to allow for patient attrition or missing data, and also in order to look for differences with regards to transfusion between patient subgroups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.379
	Confidence Interval	(2-Sided) 95%; 0.189 to 0.569
	Parameter Dispersion	Type: Standard Deviation; Value: 0.096
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RESTRICTED FLUIDS, FREE FLUIDS
	Comments	Null hypothesis :restrictive fluid protocol does not have any effect concerning the mean number of PRC units transfused.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.797
	Confidence Interval	(2-Sided) 95%; 0.465 to 1.129
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.168
	Estimation Comments	The mean difference between groups B and A is adjusted for age, gender, BMI and preoperative HCT, while BSA, weight, height, postoperative HCT were not included in the final model to avoid collinearity.

Adverse Events

Arm/Group Title	RESTRICTED FLUIDS		FREE FLUIDS
Arm/Group Description	Infusion of Hes 130/0.4 up to 500 ml		Free fluid infusion unless Hb< 6g/dl(allogenic blood use)
All Cause Mortality
	RESTRICTED FLUIDS		FREE FLUIDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	RESTRICTED FLUIDS		FREE FLUIDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/100 (20%)		18/92 (19.6%)
Cardiac disorders
myocardial infraction	5/100 (5%)	5	4/92 (4.3%)	4
persistent significant arrythmia	8/100 (8%)	8	6/92 (6.5%)	6
Congenital, familial and genetic disorders
low output syndrome	6/100 (6%)	6	7/92 (7.6%)	7
Nervous system disorders
persistent neurological dysfunction	1/100 (1%)	1	0/92 (0%)	0
Vascular disorders
lower extremity ischemia	0/100 (0%)	0	1/92 (1.1%)	1
Other (Not Including Serious) Adverse Events
	RESTRICTED FLUIDS		FREE FLUIDS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/100 (2%)		2/92 (2.2%)
Renal and urinary disorders
renal failure	1/1 (100%)	1	1/1 (100%)	1
Surgical and medical procedures
reoperation for bleeding	1/1 (100%)	1	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.