ANZCTR - Registration

Registration number

ACTRN12612000022864

Ethics application status

Approved

Date submitted

30/12/2011

Date registered

6/01/2012

Date last updated

8/02/2016

Type of registration

Prospectively registered

Titles & IDs

Public title

Plasmalyte and Hartmann’s solution for cardiopulmonary pump prime during cardiopulmonary bypass

Scientific title

Effect of Plasmalyte and Hartmann’s solution as cardiopulmonary pump prime on acidosis, strong-ion-difference and unmeasured ions during cardiopulmonary bypass

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1126-7371

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cardiopulmonary bypass

Cardiac surgery

Condition category

Condition code

Cardiovascular

Coronary heart disease

Anaesthesiology

Anaesthetics

Surgery

Surgical techniques

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Plasmalyte 148 Intravenous Fluid Solution

Plasma-lyte 148 (pH 7.4) is a replacement electrolyte commonly used as a crystalloid priming solution for cardiopulmonary bypass prime. In addition, the presence of bicarbonate precursors (acetate and gluconate) produces a metabolic alkalinising effect that helps counteract metabolic acidosis of patients undergoing cardiopulomary bypass. It is an isontonic solution and compatible with blood or blood components.

The electrolyte composition of Plasmalyte is as follows:

3 mEq of magnesium = 3 mmol/L.
140 Eq of sodium ion = 140 mmol/L.
98 mEq of chloride ion = 98 mmol/L.
27 mEq of acetate = 27 mmol/L.
23 mEq of gluconate = 23 mmol/L.
5 mEq of potassium ion = 5 mmol/L.

For this clinical trial Plasmalyte will be used an a one off intervention only for the duration of cardiopulmonary bypass.

Cardiopulmonary bypass will be performed using a membrane oxygenator (Sorin Monolyth; Biomedica, Mirandola, Italy). The pump rate will be set at 2.4 l.m-2.min-1 and body temperature will be kept at 32 to 34 Degrees.

Plasmalyte will be infused as the cardiopulmonary bypass prime fluid prime fluid together with a standard cardioplegia solution minimising differentiating effects of exogenous ions given by this route.

Prime volume to be administered:
A crystalloid prime volume of 1500mL Plasmalyte will be used in this study representing 30-35% of the patient’s blood volume. Generally, the volume of prime required is either based on a standard empirically derived volume greater than a minimum safe priming volume, or is guided by the patient’s weight or body surface area. In practice the minimum volume required is that which fills both the venous and arterial limbs of the circuit and maintains adequate reserve volume in the venous reservoir to ensure that air is not entrained into the arterial side of the circuit during initiation of CPB. This volume is determined by both the calibre and length of the tubing connecting the patient to the CPB machine and by the design and therefore capacity of the venous reservoir and oxygenator. The volume of the prime in relation to the patient’s pre-CPB haematocrit determines the initial haematocrit achieved after the initiation of CPB. In adults, priming volumes are commonly in the range of 1400-1800mL, typically representing 30-35% of the patient’s blood volume.

Additional fluid boluses of Plasmalyte solution will be administered to any patient if volume supplementation is required.

Intervention code [1]

Other interventions

Comparator / control treatment

Hartmanns Intravenous Fluid Solution

Hartmanns solution is a replacement electrolyte commonly used as a crystalloid priming solution for cardiopulmonary bypass prime. In addition, the presence of bicarbonate precursors (lactate) helps counteract metabolic acidosis of patients undergoing cardiopulomary bypass.

The electrolyte composition of Hartmanns solution is as follows:

One litre of Hartmann's solution contains:

131 mEq of sodium ion = 131 mmol/L.
111 mEq of chloride ion = 111 mmol/L.
29 mEq of lactate = 29 mmol/L.
5 mEq of potassium ion = 5 mmol/L.
4 mEq of calcium ion = 2 mmol/L .

For this clinical trial Hartmanns Solution will be used an a one off intervention only for the duration of cardiopulmonary bypass.

Cardiopulmonary bypass will be performed using a membrane oxygenator (Sorin Monolyth; Biomedica, Mirandola, Italy). The pump rate will be set at 2.4 l.m-2.min-1 and body temperature will be kept at 32 to 34 Degrees.

Hartmanns solution will be infused as the cardiopulmonary bypass prime fluid prime fluid together with a standard cardioplegia solution minimising differentiating effects of exogenous ions given by this route.

Prime volume to be administered:
A crystalloid prime volume of 1500mL Hartmanns solution will be used in this study representing 30-35% of the patient’s blood volume. Generally, the volume of prime required is either based on a standard empirically derived volume greater than a minimum safe priming volume, or is guided by the patient’s weight or body surface area. In practice the minimum volume required is that which fills both the venous and arterial limbs of the circuit and maintains adequate reserve volume in the venous reservoir to ensure that air is not entrained into the arterial side of the circuit during initiation of CPB. This volume is determined by both the calibre and length of the tubing connecting the patient to the CPB machine and by the design and therefore capacity of the venous reservoir and oxygenator. The volume of the prime in relation to the patient’s pre-CPB haematocrit determines the initial haematocrit achieved after the initiation of CPB. In adults, priming volumes are commonly in the range of 1400-1800mL, typically representing 30-35% of the patient’s blood volume.

Additional fluid boluses of Hartmanns solution will be administered to any patient if volume supplementation is required.

Control group

Active

Outcomes

Primary outcome [1]

Standard base deficit

Timepoint [1]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [1]

Strong-ion-difference. This is a quantitative physicochemical analysis using Stewart's quantitative equation: The formula used: measured SID, mEq/l =[Na+]+[K+]+[Mg2+]+Ca2+]-[Cl-]-[lactate]

Timepoint [1]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [2]

Serum albumin. The anion concentrations for albumin will be calculated using Figge's formulae: albumin anions, mEq/l =[albumin] X (0.123 X pH-0.631)

Timepoint [2]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [3]

Serum phosphate. The anion concentrations for phosphate will be calculated using Figge's formulae:

phosphate anions, mEq/l =[phosphate] X (0.309 X pH-0.469)

Timepoint [3]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [4]

Serum creatinine

Timepoint [4]

Blood sampling was performed at 2 time points:
1. T1: baseline immediately prior to CPB
2. T2 On rewarming, just prior to separation from CPB

Secondary outcome [5]

Peak urine neutrophil gelatinase-associated lipocalin (NGAL)

Timepoint [5]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [6]

Peak serum neutrophil gelatinase-associated lipocalin (NGAL)

Timepoint [6]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [7]

Serum Cystatin C

Timepoint [7]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [8]

Serum acetate

Timepoint [8]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [9]

Serum gluconate

Timepoint [9]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [10]

Serum lactate

Timepoint [10]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [11]

Cardiac troponin

Timepoint [11]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Secondary outcome [12]

Interleukin-6

Timepoint [12]

Blood sampling was performed at 5 time points:
1. T1: baseline immediately prior to CPB
2. T2: Five minutes after achieving full flows on CPB, prior to placement of aortic cross clamp
3. T3: Fifteen minutes after achieving full flows on CPB
4. T4: Thirty minutes after achieving full flows on CPB
5. T5: On rewarming, just prior to separation from CPB

Eligibility

Key inclusion criteria

1. Adult patient (age > 18years)
2. Elective CABG or valve surgery
3. Requirements for cardiopulmonary bypass

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. Decline to participate
2. Pregnancy
3. Abnormal pre-operative venous plasma bicarbonate concentration (< 22 mmol/L or > 27 mmol/L)
4. Hypercapnoeic respiratory failure
5. Chronic renal impairment (creatinine > 150 micromol/L)
6. Known diabetes mellitus or HbA1c > 10% (elevated blood acetate concentrations have been reported in patients with type 2 diabetes mellitus)
7. Chronic liver disease
8. Anaemia (haemoglobin level <10 g/dL)
9. Morbid obesity (BMI > 35kg/m2)
10. Known allergic reaction to study solutions

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/02/2012

Actual

1/02/2012

Date of last participant enrolment

Anticipated

Actual

23/08/2012

Date of last data collection

Anticipated

Actual

Sample size

Target

50

Accrual to date

Final

50

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Austin Hospital

Country [1]

Australia

Primary sponsor type

Hospital

Name

Austin Hospital

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Research Ethics Unit

Ethics committee address [1]

Austin Health Research Ethics Unit
Henry Buck Building
Austin Hopsital
Studley Road
Heidelberg, 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/08/2011

Approval date [1]

27/10/2011

Ethics approval number [1]

H2011/04377

Summary

Brief summary

Changes in acid-base balance, particularly metabolic acidosis are common in cardiac surgery with cardiopulmonary bypass. The mechanisms for such metabolic acidosis however, remain controversial, but previous research strongly suggests that the metabolic acidosis is iatrogenic in nature and that its extent and duration varies according to the priming solution of the
cardiopulmonary bypass circuit. The priming solution has been implicated as one of the potential causes of the disturbances of pH associated with the development of metabolic acidosis on initiation of cardiac bypass. This acidosis is in part caused by hyperchloraemia and is more likely to occur with normal saline, which has a higher chloride load than the more balanced physiological solutions such as Plasmalyte or Hartmanns solutions. 

Attempts to prevent metabolic acidosis have entailed alterations to circuit prime fluids, including partial replacement of chloride by rapidly metabolised anions such as L-lactate, acetate and gluconate or else by bicarbonate.
Study rationale: There are no published studies comparing Hartmann’s solution (contains anions lactate and chloride) and Plasmalyte (contains anions acetate, gluconate & chloride) as prime solutions for cardiopulmonary bypass. 

Both these crystalloid fluids are commonly used priming solutions for the cardiopulmonary bypass circuit. It is therefore not known if one solution has more beneficial effects on cardiopulmonary associated acidosis, strong-ion
difference and unmeasured ions.

Study design & hypothesis: We will conduct a single centre randomised controlled blinded study to test the hypothesis that when used as cardiopulmonary pump prime solution during cardiopulmonary bypass Plasmalyte solution will have a more favourable effect on metabolic acidosis than Hartmann’s solution.

Primary endpoint: Standard base deficit on rewarming, just prior to separation from cardiopulmonary bypass

Secondary endpoints: Strong-ion-difference; Total weak 
acids; Net-unmeasured-ions including lactate, acetate, gluconate; Serum creatinine; Renal biomarkers including: serum and urine NGAL, cystatin C; Pro-inflammatory effects using Interleukin-6; Cardiotoxic biomarkers using cardiac troponin.

Inclusion criteria: Adult patients (age > 18years) undergoing elective Cardiac Artery Bypass Grafting (CABG) or valve surgery requiring cardiopulmonary bypass.

No of participants: 50

Recruiting Hospital: Austin Hospital

Clinical significance: A finding that Plasmalyte solution has more favourable effects than Hartmanns solution on cardiac bypass associated acidosis, strong-ion difference, and
inflammation may influence the fluid chosen for prime solution in patients undergoing cardiopulmonary bypass.

Trial website

Nil

Public notes

Contacts

Principal investigator

Name

A/Prof Laurence Weinberg

Address

Department of Anaesthesia, Austin Hospital, Heidelberg, 3084, Victoria

Country

Australia

Phone

+61394965000

Email

[email protected]

Contact person for public queries

Name

Dr Laurence Weinberg

Address

Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Email

[email protected]

Contact person for scientific queries

Name

Dr Laurence Weinberg

Address

Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria

Country

Australia

Phone

+61 3 94965000

Email

[email protected]

Trial Review

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