Acute Preoperative Hemodilution in Cardiac Surgery: Volume Replacement a Hypertonic Saline-Hydroxyethyl Starch Solution Joachim

Boldt, MD, Dieter

Kling, MD, Burghard Friedhelm

Dapper,

Weidler,

MD, Bernfried

MD, and Gunter

Zickmann,

Hempelmann,

MD, Christoph

With

Herold,

MD

Preoperative hemodilution (HD) is a recommended practice in cardiac surgery that conserves blood and reduces the complications of homologous blood transfusion. In 45 patients undergoing myocardial revascularization, HD was performed preoperatively. Withdrawn volume (10 mL/kg) was replaced either by a new hypertonic saline (HS) solution prepared in hydroxyethyl starch (HES) (2,400 mOsm/L, HSHES group, n = 15) or by a standard low molecular weight hydroxyethyl starch solution (6% HES 2OOlO.5, HES group, n = 15) to maintain baseline PCWP (acute normovolemic hemodilution [ANH]). Fifteen comparable patients without HD served as controls. Significantly less HS-HES (210 t 20 mL) than HES 6% (890 2 90 mL) was necessary to sustain hemodynamics during HD. Stable cardiocirculatory conditions were obtained even after termination of bypass. Fluid balance during cardiopulmonary bypass as well as in

the postoperative period was significantly lower in HS-HEStreated patients. Wiih regard to hemodynamics, Cl increased most in the HS-HES group (+36%), whereas systemic vascular resistance was lower in these patients. Right ventricular ejection fraction increased only in HS-HES patients (+15%). However, sodium concentration as well as osmolarity increased after volume replacement with HS-HES, without exceeding normal values. None of the patients suffered from organ failure. Pulmonary gas exchange (PaO,) was less compromised in the HS-HES patients. There were no renal function differences between the groups. In conclusion, HS solution prepared in HES is an attractive alternative for blood substitution in cardiac patients undergoing acute hemodilution for blood conservation. Copyright o 199 1 b y W. B. Saundan Company

G

and pancuronium. Al1 patients were ventilated mechanically without positive end-expiratory pressure and with an F,O, of 0.5 (oxygeniair) until the end of the operation.

ROWING AWARENESS of the risk of transmitting viral diseases such as hepatitis and acquired immunodeficiency syndrome (AIDS) by transfusion of donor blood or blood products has resulted in more aggressive blood conservation efforts at many centers.‘.” Acute normovolemic hemodilution (ANH) is becoming an established technique for blood conservation during coronary artery surgery, because it is undeniable that the safest blood for transfusion is the patient’s own.4.5 However, the ideal solution for replacement of the withdrawn blood is stil1 considered controversial.6 The current tendency is to infuse colloid solutions rather than large amounts of Ringer’s solution for this putpose.‘.’ Recently, there has been a renewal of interest in hypertonic saline (HS) solutions as volume substitutes in patients with severe shock from hemorrhage or burns.‘” It has been termed “smal1-volume resuscitation” because this kind of solution improves hemodynamics in doses in which isotonic saline solution (0.9% NaCl) is ineffective. Solution concentrations investigated range from 450 to 2,400 mOsm/L. Because hemodynamic response to HS solutions appears to be transient,14-” the addition of a colloid results in more sustained hemodynamic effects.8.‘7.‘R The purpose of this study was to investigate the effects of a new HS solution prepared in hydroxyethyl starch (HES) for volume replacement in coronary artery surgety patients undergoing

ANH. MATERIALS

AND METHODS

Forty-five patients undergoing elective aortocoronary

bypass grafting were investigated after informed consent was obtained from each patient according to the protocol of the Human Ethics Committee of the hospital. Exclusion criteria were reduced myocardia1 function (left ventricular ejection fraction [LVEF] < 50%; left ventricular end-diastolic pressure [LVEDP] > 20 mm Hg), treatment with B-blocking agents, pulmonary capillary wedge pressure (PCWP) greater than 10 mm Hg, hemoglobin (Hgb) value below 13 gidL, and preoperative coagulation abnormalities. Induction and maintenance of anesthesia were standardized, and consisted of weight-related dosages of fentanyl, midazolam, Journal of Cardiotboracic and Vascularhesthesia,

Grouping

Preoperatively, the patients were subdivided into three groups according to an open, random sequence: (1) acute hemodilution (HD) was performed within 20 minutes after induction of anesthesia; withdrawn volume was 10 mL/kg and bloed was replaced by a new HS solution prepared in a HES solution (72 g/L NaCI, 60 g/L HES; osmolarity, 2,400 mOsm/L) in order to maintain baseline PCWP (HS-HES patients, n = 15); (2) HD was performed withdrawing 10 mIJkg of autologous blood; a low-molecular weight HES solution (6% HES 200/0.5 - 9.0 g/L NaCl; osmolarity, 309 mOsm/L) was used in order to maintain baseline PCWP (HES patients, n = 15); and (3) HD was not performed (control patients, n = 15). HD was always started after induction of anesthesia during a hemodynamic steady state; after HD was completed, the operation was started. A dose of 300 U/kg of heparin was administered to achieve anticoagulation, and cardiopulmonary bypass (CPB) was performed with membrane oxygenators (Sorin 41; Sorin, Turino, Italy). The circuit was primed with 1,000 mL of Ringer’s solution, 1,000 mL of 5% dextrose, and 250 mL of 5% albumin. A flow of 2.4 Liminim” was maintained throughout CPB; a single atria1 cannulation technique was used, and a “partial” bypass at almost normothermia (recta1 temperature > 33.O”C)was performed. For myocardial preservation, Bretschneider’s cardioplegic solution was infused. Twenty minutes after the start of CPB, the perfusate was concentrated by a cell saver (CS IV; Haemonetics, Munich, Germany). When necessary, Ringer’s solution was added to maintain circuit volume, and packed red cells were given when Hgb value fel1 below 7 g/dL. After termination of CPB the blood remaining in the

From the Departments of Anesthesiology and Intensive Care Medicine and Cardiovascular Swgety, Justas-Liehig University, Giessen, Germany. Address reprint requests to Joachim Boldt, MD, Department of Anesthesiology and Intensive Care Medicine, Klinikstr 29, JusrusLiebig Univers@ Giessen, 0-6300 Giessen, Gemany. Copyright 0 1991 by W.B. Saunders Company 1053-077019110501-0005$03.00/0

Vol 5, NO 1 (February), 1991:

pp 23-28

23

24

BOLDT ET AL

Table 1. Data from Cardiopulmonary

Bypass and Postoperative

HS.HES

Care

HES 6%

Control

Weight (kg)

75.8 + 5.5

77.3 f 8.0

73.6 z? 9.0

LVEF (%)

64.3 2 3.3

66.1 ? 9.1

68.9 + 7.0

LVEDP (mm Hg)

12.4 -c 2.5

16.6 + 4.4

14.9 z? 7.8

Amount of replaced volume (mL)

210 * 20s

890 + 90

CPB (min)

70.6 + 12.3

62.9 r 13.1

66.1 2 12.5

Ischemia (min)

43.9 + 6.6

41.1 r 6.1

40.9 + 7.2

0.017 + 0.01t

0.103 ;L 0.09*

0.169 + 0.11

Operation day

210 2 130

400 2 300

500?

First postoperative day

470 I 200

600 + 350

580 2 220

1,640 i: 420

1,870 r 700

Fluid balance during CPB (mL/kg/min) Blood loss (mL)

110

Volume (mL) Crystalloids First postoperative day

1,270 + 290*

Donor blood (patientdunits)

o/o

o/o

212

*Different from control group. tDifferent from control and HES patients.

extracorporeal oxygenation equipment was prepared by the CS and retransfused together with the autologous blood from hemodilution until the end of the operation. Hemodynamic monitoring consisted of measuring heart rate (HR), mean arterial pressure (MAP), pulmonary arterial pressure (PAP), PCWP, cardiac output (CO; thermodilution technique), right atria1 pressure (RAP), right ventricular (RV) systolic pressure (RVPsyst), and right ventricular end-diastolic pressure (RVEDP); derived parameters (cardiac index [CI], systemic vascular resistance [SVR]) were calculated. The pulmonary artery catheter was specifically designed to measure RV variables. Determination of RV ejection fraction (RVEF), right ventricular endsystolic volume (RVESV), and right ventricular end-diastolic volume (RVEDV) was made possible by a microprocessor (REF-1, Edwards Laboratory, Santa Ana, CA). Details of this monitoring instrument have been reported elsewhere,‘920 and accuracy as wel1 as validity have been demonstrated in comparison to standard techniques for assessing RV function (echocardiography, angiography, nuclear imaging techniques).” In addition to hemodynamic parameters, various laboratory values, PaO,, (Hgb), osmolarity (blood and urine), and plasma viscosity were measured from arterial blood samples. Free water clearance (CH,O) was calculated in order to estimate renal function. Blood loss (suction, drainage), volume administration (Ringer’s solution to maintain PCWP >5 mm Hg), and use of blood (to maintain Hgb value > 9 g/dL) were documented until the

first postoperative day. The use of volume was decided by an anesthesiologist who was not involved in the study. Measurements were performed (1) after induction of anesthesia during hemodynamic steady state; (2) after HD had been completed (before onset of operation; (3) 20 minutes after the end of HD; (4) 40 minutes after the end of HD (before start of CPB, chest open); (5) 20 minutes after the start of CPB; (6) 5 minutes after termination of CPB (chest open); (7) 45 minutes after termination of CPB (at the end of operation); (8) 5 hours after termination of CPB (laboratory values only); and (9) at the first postoperative day (laboratory values only). Al1 parameters are expressed as mean values (X) and standard deviation (SD). One- and two-factorial analyses of variante were used for statistical interpretation. A relationship between two parameters was tested with the help of the analysis of covariance; P values 320 mOsm/L). Plasma viscosity decreased in both HD groups, but did not change after bypass. Analysis of covariance showed no correlation between changes in viscosity and changes in SVR. Free water clearance (CH,O) was always within the normal range (Table 4). Pulmonary gas exchange (PaO,) was significantly less compromised after bypass in the HS-HES patients (- 10%) compared with HES (- 19%) and control groups (-37%). None of the patients suffered sequelae attributable to the study.

ment that significantly less HS-HES than standard HES was able to maintain hemodynamics. Results from other author? indicate that a relatively smal1 volume of high osmotic saline solution was sufficient to permanently reverse the conditions of severe shock in dogs and to produce permanent survival. Velasco et al” demonstrated that 4 4.5

4.0

3.5

3.0

2.5 H -

HS-HES HES

(n =15)

1

2.0

50

45-

45

40-

40

35DISCUSSION

The major question studied was of HS solution prepared in HES cardiovascular function in acutely artery patients without detrimental

whether smal1 volumes could sustain normal hemodiluted coronary effects. The data docu-

before after LHD-I

20 40 min CP6 Lafter HDJ

10 45 min Lafter CWSJ

Fig 1. Changes in Cl and RVEF in the three groupe. *Different from control group; ?? *dlfierent from control and HES patients.

BOLDT ET AL

i H M -

betere after 20 min LHDA

CPB

HS-HES (n.15) HES bl=151 control (n=15)

5 min 45 min 5 hrs 1. p.o. L after CPB J day

lasting effects of the HS-HES solution in this study are in agreement with studies from others using HS prepared in dextran.l*~” However, because dextran might be associated with an alteration in coagulation, it is not recommended for volume therapy in cardiac surgery patients. In studies examining ANH, the end-point of volume replacement may be taken as blood pressure, fìlling pressures (RAP and PCWP), or clinical judgment. Maintcnance of baseline PCWP was used to determine the amount of replaced volume in this study. In addition to standard hemodynamic monitoring, a thermodilution technique was used for assessing RVEDV, RVESV, and RVEF. Both RVEDV and RVESV had the largest increases in the HS-HES patients, indicating pronounced volume expansion with this solution. RAP and PCWP did not show these effects. Martyn et al”’ showed that RVEDV measured by the thermodilution technique is a useful clinical tool for assessment of preload. RVEF was increased only in the HS-HES patients, resulting either from an increase in preload, a decrease in RV afterload due to a decrease in pulmonary impedance, or direct effects on the myocardium. The beneficial effects of concentrated solutions on myocardial blood flow help to explain their value in cardiac resuscitation.” Others have reported positive inotropic effects by direct action on the myocardial cells.22~” Administration of the new HS-HES solution resulted in a

Fig 2. Changes in SVR and plasma viscosity in the three groups. *Different from control group; **different from control and HES patients.

mL/kg of hypertonic solution (2,400 mOsm/L), which was equivalent to 10% of the shed blood, was effective to rapidly restore pressure in severely hemorrhagic shock animals. In studies from Smith et al,” approximately 4 mL/kg of HS solution increased plasma volume 10 to 12 mL/kg. Clinically, HS solutions from 540 to 2,400 mOsm/L have been used to improve cardiovascular function and tissue perfusion in a variety of situations.2’-26 Shackford et al” used HS solutions (514 mOsm/L) for volume replacement in patients undergoing elective major aortic reconstruction and demonstrated a significantly reduced volume requirement during the early postoperative period. This is in accordance with the present results using a more concentrated HS solution in patients undergoing cardiac surgery. Water transferred from the interstitial to the intravascular compartment might be responsible for these volume-expanding effects. Intagliettaz stated that HS solutions provide an effective mechanism for deswelling tissues. Red cel1 volume did not change in the present study, indicating no adverse effects of HS solution on cellular elements of the blood. The cardiocirculatory effects of the new HS-HES were not transitory. Stable hemodynamics were found in the beginning of CPB and after termination of bypass, whereas the hemodynamic effects of other hypertonic solutions have been reported to be only transitoTy.‘4.‘5 The addition of a colloid to the hypertonic sodium chloride solution resulted in a more sustained hemodynamic response.” The long-

150

145

-

HS-HES

(n = 15)

320

300

280

befriDa>ter

20 min

CPB

5 min 45 min 5 hrs L after CPB0

1 p.o. day

Fig 3. Changes in sodium concentration (Na) and ormolarity in the three groups. *Different from control group; **different from control and HES patients.

27

HYPERTONIC VOLUME REPLACEMENT

Table 4. Changes in Hemoglobin, Pulmonary Gas Exchange, Red Cel1 Volume, and Ree Water Clearanw

Parameter Hgb (g/dL)

PaOJF,O, (mm Hg)

(kmJ)

20 Min

5 Min

After HD

CPB

After CPB

11.0 +- 1.0*

8.7 2 0.9

10.0 k 1.1

11.4 t 0.9*

8.1 ? 0.8

9.8 ? 0.7

12.0 I 0.7’

13.1 -+ 0.7

12.9 + 1.0

8.8 k 0.8

9.8 k 0.8

10.8 + 0.9

11.3 2 1.1

11.0 + 1.1

380 i 80

423 +I. 72

419 + 54

280 + 90

410 + 110t

380 + EO*

355 f 88

509 k 70

380 f 77

408 k 88

409+88

300 + 110

350 + 112

333 k 98*

318 -+ 78

511 2 100

355 f 89

380 + 57

390 2 80

277 i 87

334 k 115

249 + 88

278 2 42

487278

HS-HES

13.8 2 1.1

ll.8

+ 0.8’

HES

13.4 2 1.0

11.2 2 0.8”

Control

13.5 * 1.0

HS-HES HES

45 Min After CPB

12.8?

l.O*

5 Hrs After CPB

Fint PostoperativeDay

13.4 + l.O*

12.2 * 0.9

12.4 r 1.2

12.5 + 1.1

HS-HES

89.2 + 3.3

89.9 f 3.5

89.7 k 3.5

90.3 + 3.3

90.5 ‘- 3.1

90.2 f 2.9

90.3 1+ 3.3

90.8 k 2.8

HES

89.9 i 3.1

90.4 2 3.3

90.4 + 3.0

90.5 2 3.2

90.3 i 3.4

90.0 -c 2.8

90.0 + 2.7

89.8 + 2.5

91.0 i 3.1

91.1 5 3.0

91.2 + 3.7

91.4 + 3.0

91.3 ? 3.9

91.2 2 3.2

91.3 + 3.9

Control CH, 0 (mL)

40 Min

HD

Baseline

Control KV

Ah.3

Group

91.5 + 3.9

HS.-HES

-

-89

+ 33

-97

+ 40

-112

+ 35

-132

+ 50

-81

2 22

-115

i 55

HES

-

-100

2 29

-98

+ 42

-122

+ 58

-107

+ 33

-89

? 34

-133

+ 80

-108

+ 39

-120

+ 88

-128

2 59

-119

+r 54

-78

k 33

-110

-t 51

Control

-

NOTE. All data given as mean + SD. *Different from control group. tDifferent from control and HES patients.

decrease in SVR. Read et al” suggested that the decrease in peripheral resistance cannot be attributed to changes in viscosity from hemodilution. They demonstrated similiar results with either hypertonic saline or glucose. In the present study, no wrrelation was found between the decrease in SVR and change in viscosity, indicating direct vasodilating properties of the solution. One aspect of volume therapy is the establishment of normal tissue flow, particularly in cardiac surgery using extracorporeal circulation. Permanently underperfused capillaries during bypass, as wel1 as contact of blood with foreign materials, may lead to a release of various mediators and activation of deleterious cascades resulting in a deterioration of the patient’s microcirculation.H A decrease in viscosity seems to be of advantage in this situation. Others have demonstrated improved organ perfusion using microsphere technique when HS solution was used for volume replacement.” In this study, PaO, after bypass was less impaired in the HS-HES patients than in the control group because of a less pronounced fluid balance during CPB or an improvement in pulmonary microcirculation. Renal function was unchanged in this group of patients as detected by measure-

ment of free water clearance, which is thought to be a sensitive predictor of renal failure in patients undergoing cardiac surgery. The benefits of HS-HES solution must be weighed against the potential hazards of this technique, ie, increases in patients’ sodium concentration and osmolarity. Hypernatremia and hyperosmolarity can result in cerebral dysfunction such as disorientation, confusion, and seizures. Although sodium concentration was higher in the HS-HES patients than in the other two groups, it was within the normal range during the entire investigation period. Osmolarity showed a significant differente in both groups only immediately after hemodilution; however, it never reached critical values (maximum value, 320 mOsm/L). Moreover, values of 350 mOsm/L have been reported in patients without ill effects.j’ In summary, the new HS solution prepared in HES can be recommended for volume replacement in certain situations, eg, in coronary artery patients undergoing acute hemodilution for blood conservation. Its major positive effects resulted from a significant reduction in fluid needs during and after termination of cardiopulmonary bypass.

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