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Clinical Investigations: SURGERY |

Use of Intraoperative Hetastarch Priming During Coronary Bypass* FREE TO VIEW

Charles C. Canver, MD, FCCP; Ronald D. Nichols, CCP
Author and Funding Information

*From the Division of Cardiothoracic Surgery (Dr. Canver), Albany Medical College, Albany, NY; and William S. Middleton Memorial Veterans Hospital (Mr. Nichols), Madison, WI.

Correspondence to: Charles C. Canver, MD, FCCP, Division of Cardiothoracic Surgery, Albany Medical College, 47 New Scotland Ave, Mail Code S5, Albany, NY; e-mail: CanverC@mail.amc.edu



Chest. 2000;118(6):1616-1620. doi:10.1378/chest.118.6.1616
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Background: The use of hetastarch during coronary bypass surgery has been limited due to its unresolved potential risk for hemorrhage. Therefore, the purpose of this study was to investigate the effects of using 6% hetastarch in priming cardiopulmonary bypass (CPB) circuitry on the need for blood product transfusions and outcome after coronary bypass.

Materials and methods: This nonrandomized retrospective study involved 887 patients who underwent isolated primary coronary artery bypass grafting. Based on the type of solution used in priming the CPB circuitry, patients were stratified into the following four different groups: group 1, crystalloid (500 mL; n = 211); group 2, 25% human albumin (50 mL; n = 217); group 3, 6% hetastarch (500 mL; n = 298); and group 4, 25% human albumin (50 mL) and 6% hetastarch (500 mL; n = 161). Patient characteristics and clinical variables were compared among the groups using the Kruskal-Wallis test. Patient survival estimates were compared using log-rank test.

Results: Demographic patient characteristics for all groups were similar (p > 0.05). Intraoperative and perioperative variables among groups were comparable (p > 0.05). The use of hetastarch as a part of prime solution in CPB circuitry did not alter the need for banked blood, platelets, or fresh frozen plasma transfusions (p > 0.05). The length of stay in the ICU or in the hospital was unaffected in all groups. The early (ie, 30-day) mortality rate was 1.4% in group 1, 1.8% in group 2, 1.0% in group 3, and 3.1% in group 4. Long-term survival among the groups was unaffected by the type of priming solution.

Conclusions: The use of hetastarch in priming CPB circuitry is devoid of any added hemorrhagic risk after coronary bypass, and the type of prime solution for CPB has no influence on the early or late survival rates of patients undergoing primary coronary bypass.

Figures in this Article

Coagulation abnormalities occur in all patients undergoing open-heart surgery with cardiopulmonary bypass (CPB). However, serious postoperative bleeding requiring surgical reexploration is uncommon (ie, only 2 to 3% of coronary bypass patients).1A major concern prevails within the cardiac surgical community regarding the use of hetastarch in coronary bypass patients because of its effects on the blood coagulation system. In fact, a 1997 report suggested avoiding the use of intraoperative hetastarch until the safe timing of its administration is clarified.2 In contrast, we have been using 6% hetastarch solution as a part of the priming solution for CPB for many years. Therefore, in this study, our purpose was to investigate the effects of hetastarch as a priming solution for CPB on the need for blood product transfusions and on the survival rate of patients undergoing isolated primary coronary bypass.

We reviewed the clinical records of 887 patients who underwent isolated primary coronary artery bypass grafting (CABG) between January 1987 and December 1995. We did not include patients who had undergone repeat CABG or patients who had undergone CABG incidental to heart valve repair or replacement, resection of a ventricular aneurysm, or other surgical procedures. No specific selection process was employed other than that patients simply were classified into the following four groups based on the type of prime solution used for CPB: group 1, crystalloid (500 mL; n = 211 patients); group 2, 25% human albumin (50 mL; n = 217 patients); group 3, 6% hetastarch (500 mL; n = 298 patients); and group 4, 25% human albumin (50 mL) and 6% hetastarch (500 mL; n = 161 patients). Since the cessation of aspirin and IV heparin administration preoperatively in patients with unstable angina was believed to be unsafe, the use of aspirin and/or IV heparin preoperatively was not considered in the analysis.

The decision to use a particular type of priming solution for CPB was arbitrarily made by a clinical perfusionist (RDN). Although the study was not blinded, the knowledge of which patient had what type of priming solution during a coronary bypass operation was unknown to the surgeon or to the cardiothoracic surgical fellow and surgical residents, who provided daily patient care and were responsible for ordering the postoperative transfusion of allogenic blood and blood products.

All patients were premedicated 1 h before the induction of anesthesia, using morphine sulfate (0.1 to 0.2 mg/kg) and diazepam (0.1 to 0.2 mg/kg). The induction and maintenance of anesthesia was standardized at our institution. The general anesthesia protocol was designed to allow early extubation and was mainly a combination of midazolam hydrochloride (0.1 to 0.2 mg/kg), fentanyl (8 to 10μ g/kg), and pancuronium bromide supplemented with isoflurane and nitrous oxide.

CPB was performed with a membrane oxygenator (Sarns Inc; Ann Arbor, MI) with a nonpulsatile flow between 1.5 and 2.4 L/min/m2. The heart-lung bypass machine circuit was primed with 2,200 mL crystalloid solution (Isolyte-S; McGaw, Inc; Irvine, CA), 100 mg lidocaine hydrochloride, and 1 mg phenylephrine hydrochloride. Fifty milliliters of human serum albumin or 500 mL 6% hetastarch solution (Hespan; DuPont, Inc; Wilmington, DE) was used as a replacement for the primer solution, as described for each group. Before CPB was initiated, anticoagulation was achieved by the administration of 300 IU/kg heparin sodium with the goal of achieving an activated clotting time of > 480 s. This level was maintained throughout the CPB procedure with administration of supplementary heparin as indicated by repeated determinations of the activated clotting time.

To conserve blood during coronary bypass surgery, we used intraoperative autologous blood sequestration.3 Autologous blood was withdrawn from the patient after heparinization and insertion of the cannulas. Initially, 500 to 800 mL primer solution was infused via an aortic cannula. On completion, the heart was allowed to pump the blood through the aortic cannula toward the heart-lung machine. This heparinized blood was channeled through the arterial tubing, avoiding the arterial filter, into the oxygenator. From the recirculation port, the blood was rapidly transferred into the cardiotomy reservoir. Once blood began to enter the reservoir, it was directed into a 1-L collection bag. Autologous blood sequestration continued until systemic hypotension occurred (systolic BP, < 80 mm Hg) or until two collection bags were completely full. If hypotension occurred, the blood volume removed was replaced with primer solution from the pump through the aortic cannula. Patients with a red cell volume (blood volume multiplied by preoperative hematocrit) < 1,500 mL and patients with a platelet count < 150,000/mL had no blood sequestered. In all but 51 patients, at least one internal thoracic artery graft was used with additional saphenous vein aortocoronary grafts. The left pleura was opened routinely. The ascending aorta was cross-clamped during the performance of the distal anastomosis, and myocardial protection consisted of cold blood cardioplegia and topical hypothermia with ice slush. The patients were rewarmed to a core temperature> 37°C. Suction (The Cell Saver; Haemonetics, Inc; Braintree, MA) was used throughout the operation, and surgical hemostasis was achieved before the administration of protamine sulfate. At the completion of extracorporeal circulation, anticoagulation was reversed with protamine sulfate to obtain an activated clotting time of < 125 s.

The blood remaining in the oxygenator and the tubing set was drained into blood collection bags and was retransfused gradually in the operating room. No cell separation or hemofiltration was undertaken. The leg wounds were closed as soon as possible before the reversal of anticoagulation, without drainage, and were wrapped with a compressive bandage. Before the closure of the sternum, mediastinal and pleural tubes were placed and connected to an underwater drainage apparatus with an autotransfusion reservoir (Deknatel, Inc; Fall River, MA). The shed mediastinal blood was retransfused in 4-h intervals in a closed system for up to 18 h postoperatively. After the normalization of temperature and coagulation parameters, reexploration of the mediastinum to manage bleeding was indicated when > 1,200 mL blood was lost within the first 3 h after the operation, and, thereafter, when > 200 mL/h was lost over 3 h. Banked packed RBCs were transfused postoperatively when the hematocrit level fell to< 25%. Patients received fresh frozen plasma (FFP) when prothrombin time or activated partial thromboplastin time were prolonged (ie, > 1.8 times normal values). Platelet transfusions (single-donor units or random, pooled concentrates) were given when the platelet count was < 40,000/mL. As a general principle, allogenic blood and blood derivatives were transfused only in patients showing clinical or laboratory evidence of active postoperative bleeding. In the initial hours after the operation, a mean systemic BP < 90 mm Hg was maintained using IV infusions of nitroglycerin or sodium nitroprusside.

Arterial blood samples were obtained before the start of intraoperative autologous blood sequestration for determination of activated clotting time and hematocrit. At the end of the operation (30 min after the termination of CPB), a blood sample was sent for determination of hematocrit, platelet count, prothrombin time, and partial thromboplastin time. Activated clotting time was measured in the operating room, and additional protamine sulfate was administered when necessary. The blood scavenged by the intraoperative autologous blood sequestration technique was infused gradually during sternal closure. The remaining pump circuit contents also were retransfused in the operating room, in most cases, prior to the patient’s transfer to the ICU.

The following patient variables were abstracted from the patient records: age, body surface area, RBC volume, hematocrit, platelet count, perfusion time, cross-clamping time, number of anastomoses, ejection fraction, prebypass hematocrit, preoperative creatinine level, length of ICU stay, and length of hospital stay. Patient variables were expressed as the mean ± SEM. All analyses were performed with computer software (SAS; SAS Institute; Cary, NC). Patient characteristics and clinical variables were compared among the groups using the Kruskal-Wallis test. Fisher’s Exact Test was used to compare the percentage of patients in whom an internal thoracic artery graft was used. Patient survival estimates were obtained using the methods of Kaplan and Meier and were compared using a log-rank test. Statistical significance was assumed when at p < 0.05.

The study population consisted of 881 men and 6 women. In all groups, demographic characteristics of the patient population were similar (p > 0.05; Table 1 ). Intraoperative and perioperative variables were also comparable for all groups (Table 2 ). Due to the inherent constraints within the Veterans Administration hospital system, the lengths of ICU and hospital stays for patients in both groups were longer than current nonveteran patients at other institutions. The significant differences in perfusion and ischemia time between the two groups were due to the differences in operative conduct by different surgeons.

The amount of blood and blood products transfused during the hospitalization varied among the four groups (Table 3 ). The use of hetastarch as a part of the priming solution for CPB did not alter the need for banked blood, platelets, or FFP transfusions (p > 0.05).

None of the patients sustained sequelae attributable to the use of hetastarch priming for extracorporeal circulation. The overall rate of reexploration requiring sternotomy to manage postoperative hemorrhaging was 1.3% (12 of 887 patients) and was comparable among all groups (Table 2). The early (30-day) mortality rate was 1.4% in group 1, 1.8% in group 2, 1.0% in group 3, and 3.1% in group 4. The overall long-term survival rate after coronary bypass was unaffected by the type of priming solution used during CPB (Fig 1 ).

Blood transfusions, once believed to be relatively safe, are now considered to be potentially dangerous due to their potential risk of transmitting incurable infectious diseases such as HIV. Cardiac surgical procedures requiring extracorporeal circulation continue to consume a large proportion of the limited donor blood supply. Therefore, many strategies have been explored in the last 2 decades to reduce the need for blood and blood product transfusions both during and after CPB. All these modalities have their advantages and disadvantages, and incur expenses to some degree.

Hydroxyethyl starch (hetastarch) is a term used to describe a synthetic class of molecules that are similar to glycogen.4 Hetastarch was produced as the result of an effort to find a colloid with minimal reactions. Clinical studies of human serum albumin have supported its use as an effective volume expander in many disease states58; however, guidelines for albumin use still tend to be controversial, often reflect product cost, and may be unrelated to scientific data. The major complication of albumin use over the past 2 decades has been its suggested deleterious effect on pulmonary function.910 The loudest complaints about albumin use center around its high cost. Pulmonary edema has not been a problem caused by hetastarch; indeed, some authors believe that the use of hetastarch may have a role in preventing pulmonary edema.7 The cost of hetastarch, although more than crystalloid, is less than that of albumin.

The development of coagulopathy is controversial when using hetastarch. Although it may alter coagulation profiles, hetastarch itself has not been associated with clinical bleeding.7,1112 Extracorporeal circulation alone causes considerable hematologic derangements, including thrombocytopenia and platelet dysfunction.13Acquired quantitative and qualitative platelet defects secondary to extracorporeal circulation are primarily due to the activation and release of alpha granules.14 The consumption of coagulation factors and increased fibrinolysis also contribute to excessive post-CABG hemorrhaging. These hematologic derangements are probably enhanced by the prolonged exposure of platelets to surfaces of the tubing and to mechanical forces of the heart-lung bypass machine. Our study demonstrates no evidence of deleterious hematologic effects secondary to the intraoperative use of hetastarch solution as a priming solution during the coronary bypass operation.

Because of conflicting reports about the effects of hetastarch on blood coagulation, its routine use is not widely accepted within the cardiac surgical community. In the past, Cope and associates2 suggested that the intraoperative administration of hetastarch substitutes produces a clinically significant hemostatic defect. While their study was limited in drawing conclusive evidence, they questioned the safety of intraoperative hetastarch use during coronary bypass. In contrast, our findings clearly show that intraoperative hetastarch use as a priming solution does not have any untoward effect on the need for banked blood, platelets, or FFP transfusions. However, it is necessary to reiterate that patients in this analysis were male veterans with normal left ventricular function, and the results of the study also pertain primarily to men. The conclusions of this study may not be completely applicable to women or to those individuals undergoing cardiac operations other than primary CABG.

With recognition of the nonblinded, retrospective nature of this study, our experience demonstrates that the use of intraoperative hetastarch at a dose of 500 mL does not increase the need for blood, FFP, or platelets in a large cohort of male patients undergoing CABG. The safety of intraoperative hetastarch use needs to be further investigated in a prospective, randomized, controlled trial.

Abbreviations: CABG = coronary artery bypass grafting; CPB = cardiopulmonary bypass; FFP = fresh frozen plasma

Table Graphic Jump Location
Table 1. Characteristics of Patient Population**
** 

Values given as mean ± SEM unless otherwise indicated.

Table Graphic Jump Location
Table 2. Operative and Perioperative Parameters**
** 

Values given as mean ± SEM unless otherwise indicated. ITA = internal thoracic artery.

Table Graphic Jump Location
Table 3. Blood and Blood Product Transfusion Requirements During Hospitalization**
** 

Values given as mean ± SEM. PRBC = packed RBCs.

Figure Jump LinkFigure 1. Comparison of types of priming solutions used for CPB with the survival rate of coronary bypass patients.Grahic Jump Location

We are grateful for the statistical assistance of Glen Leverson, PhD, and for the assistance of Kimberly O’Brien in the preparation of the manuscript.

Harker, LA (1986) Bleeding after cardiopulmonary bypass.N Engl J Med314,1446-1448. [CrossRef] [PubMed]
 
Cope, JT, Banks, D, Mauney, MC, et al Intraoperative hetastarch infusion impairs hemostasis after cardiac operations.Ann Thorac Surg1997;63,78-82. [CrossRef] [PubMed]
 
Canver, CC, Kroncke, GM, Nichols, RD, et al The effects of intraoperative autologous whole blood sequestration on the need for transfusion of allogenic blood and blood products in coronary bypass operations.J Cardiovasc Surg1995;36,423-428
 
Griffel, MI, Kaufner, BS Pharmacology of colloids and crystalloids.Crit Care Clin1992;8,235-253
 
Boutros, AR, Ruess, R, Olson, L, et al Comparison of hemodynamic, pulmonary, and renal effects of use of three types of fluid after major surgical procedures on the abdominal aorta.Crit Care Med1979;7,9-13. [CrossRef] [PubMed]
 
Hauser, CJ, Shoemaker, WC, Turpin, I, et al Oxygen transport responses to colloids and crystalloids in critically ill surgical patients.Surg Gynecol Obstet1980;150,811-816. [PubMed]
 
Rackow, EC, Falk, JL, Fein, IA, et al Fluid resuscitation in circulatory shock: A comparison of the cardiorespiratory effects albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock.Crit Care Med1983;11,839-850. [CrossRef] [PubMed]
 
Velanovich, V Crystalloid versus colloid resuscitation: a meta-analysis of mortality.Surgery1989;105,65-71. [PubMed]
 
Karanko, MS, Klossner, JA, Laaksonen, VO Restoration of volume by crystalloid versus colloid after coronary artery bypass: hemodynamics, lung water, oxygenation, and outcome.Crit Care Med1987;15,559-566. [CrossRef] [PubMed]
 
Weaver, DW, Ledgerwood, AM, Lucas, CE, et al Pulmonary effects of albumin resuscitation for severe hypovolemic shock.Arch Surg1978;113,387-392. [CrossRef] [PubMed]
 
Moggio, RA, Rha, CC, Somberg, ED, et al Hemodynamic comparison of albumin and hydroxyethyl starch in postoperative cardiac surgery patients.Crit Care Med1983;11,943-945. [CrossRef] [PubMed]
 
Shatney, CH, Deepika, K, Militello, PR, et al Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock.Arch Surg1983;118,804-809. [CrossRef] [PubMed]
 
Holloway, DS, Summaria, L, Sandesara, J, et al Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients.Thromb Haemost1988;59,62-67. [PubMed]
 
Mezzano, D, Aranda, E, Urzua, J, et al Changes in platelet B-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptamine, ATP, and ADP during and after surgery with extracorporeal circulation in man.Am J Hematol1986;22,133-142. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Comparison of types of priming solutions used for CPB with the survival rate of coronary bypass patients.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Characteristics of Patient Population**
** 

Values given as mean ± SEM unless otherwise indicated.

Table Graphic Jump Location
Table 2. Operative and Perioperative Parameters**
** 

Values given as mean ± SEM unless otherwise indicated. ITA = internal thoracic artery.

Table Graphic Jump Location
Table 3. Blood and Blood Product Transfusion Requirements During Hospitalization**
** 

Values given as mean ± SEM. PRBC = packed RBCs.

References

Harker, LA (1986) Bleeding after cardiopulmonary bypass.N Engl J Med314,1446-1448. [CrossRef] [PubMed]
 
Cope, JT, Banks, D, Mauney, MC, et al Intraoperative hetastarch infusion impairs hemostasis after cardiac operations.Ann Thorac Surg1997;63,78-82. [CrossRef] [PubMed]
 
Canver, CC, Kroncke, GM, Nichols, RD, et al The effects of intraoperative autologous whole blood sequestration on the need for transfusion of allogenic blood and blood products in coronary bypass operations.J Cardiovasc Surg1995;36,423-428
 
Griffel, MI, Kaufner, BS Pharmacology of colloids and crystalloids.Crit Care Clin1992;8,235-253
 
Boutros, AR, Ruess, R, Olson, L, et al Comparison of hemodynamic, pulmonary, and renal effects of use of three types of fluid after major surgical procedures on the abdominal aorta.Crit Care Med1979;7,9-13. [CrossRef] [PubMed]
 
Hauser, CJ, Shoemaker, WC, Turpin, I, et al Oxygen transport responses to colloids and crystalloids in critically ill surgical patients.Surg Gynecol Obstet1980;150,811-816. [PubMed]
 
Rackow, EC, Falk, JL, Fein, IA, et al Fluid resuscitation in circulatory shock: A comparison of the cardiorespiratory effects albumin, hetastarch, and saline solutions in patients with hypovolemic and septic shock.Crit Care Med1983;11,839-850. [CrossRef] [PubMed]
 
Velanovich, V Crystalloid versus colloid resuscitation: a meta-analysis of mortality.Surgery1989;105,65-71. [PubMed]
 
Karanko, MS, Klossner, JA, Laaksonen, VO Restoration of volume by crystalloid versus colloid after coronary artery bypass: hemodynamics, lung water, oxygenation, and outcome.Crit Care Med1987;15,559-566. [CrossRef] [PubMed]
 
Weaver, DW, Ledgerwood, AM, Lucas, CE, et al Pulmonary effects of albumin resuscitation for severe hypovolemic shock.Arch Surg1978;113,387-392. [CrossRef] [PubMed]
 
Moggio, RA, Rha, CC, Somberg, ED, et al Hemodynamic comparison of albumin and hydroxyethyl starch in postoperative cardiac surgery patients.Crit Care Med1983;11,943-945. [CrossRef] [PubMed]
 
Shatney, CH, Deepika, K, Militello, PR, et al Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock.Arch Surg1983;118,804-809. [CrossRef] [PubMed]
 
Holloway, DS, Summaria, L, Sandesara, J, et al Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients.Thromb Haemost1988;59,62-67. [PubMed]
 
Mezzano, D, Aranda, E, Urzua, J, et al Changes in platelet B-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptamine, ATP, and ADP during and after surgery with extracorporeal circulation in man.Am J Hematol1986;22,133-142. [CrossRef] [PubMed]
 
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