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Ann Thorac Surg 1997;63:78-83
© 1997 The Society of Thoracic Surgeons
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia
Accepted for publication July 23, 1996.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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Methods. Indices of postoperative hemostasis were analyzed in 189 consecutive patients undergoing coronary artery bypass grafting. Three groups were compared: one group (n = 68) received a mean of 796 mL of hetastarch only in the operating room (a few minutes after cessation of cardiopulmonary bypass), another group (n = 59) received a mean of 856 mL postoperatively only, and a third group (n = 62) received no hetastarch.
Results. Compared with the other two groups, those patients administered hetastarch intraoperatively exhibited significant reductions in hematocrit and platelet count, a significant prolongation in the prothrombin time, and significant increases in both blood loss and hemostatic drug requirement. Also identified were obvious trends toward a greater transfusion requirement and reexploration rate for bleeding in the latter group.
Conclusions. Hetastarch infusion just after weaning from cardiopulmonary bypass produces a clinically important impairment in post-cardiac surgical hemostasis. Intraoperative use of this agent during heart operations should be avoided until the safe timing of its administration is clarified.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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Mediastinal hemorrhage after cardiac operations remains an important problem of multifactorial etiology. A cluster of cases of excessive bleeding after cardiac operations was identified at our institution from August to November 1994. Contemporaneous with the bleeding outbreak period there existed a hospital-wide shortage of 5% albumin, mandating the preferential use of 6% hydroxyethyl starch (HES) for perioperative colloid replacement. Hydroxyethyl starch, commonly known as hetastarch, is a synthetic colloid derived from amylopectin that has colloidal properties similar to those of 5% albumin [1]. Hetastarch is a worthy substitute to albumin for perioperative volume expansion, as the former is much less expensive and in greater supply.
However, there remain concerns over the adverse effects of HES on coagulation [2, 3], especially with regard to its use in patients undergoing cardiopulmonary bypass (CPB), in whom effective hemostasis is already compromised by virtue of the deleterious effects of extracorporeal circulation [4]. Despite such concerns, appropriate doses of HES have an established safety record for postoperative volume expansion after cardiac operations [5–7] as well as for use in CPB prime solutions [8–10]. However, the safety of administering this agent in the operating room (OR), specifically during the period of time just after weaning from CPB, is not known. As such, this retrospective review was undertaken with two major objectives: (1) to evaluate the effects of intraoperative HES infusion shortly after termination of CPB on hemostasis following a cardiac operation and (2) to investigate the potential role of perioperative HES administration in the bleeding outbreak mentioned above.
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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All operations were performed by two surgeons (I.L.K. and C.G.T.) who employed similar techniques. In all cases the extracorporeal circuit was equipped with a centrifugal pump (Medtronic Biomedicus, Inc, Eden Prairie, MN) and a Bentley Univox membrane oxygenator (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, CA). The CPB prime solution consisted of 1,700 mL of Plasmalyte (Baxter Healthcare Corp, Deerfield, IL), 100 mL of 25% albumin, and 10,000 units of bovine heparin sodium. Before the institution of CPB, 300 units/kg of heparin was administered into the right atrium, with supplemental doses injected directly into the CPB circuit to maintain the activated clotting time (ACT) greater than 480 seconds. All patients were systemically cooled to a bladder temperature of 30°C. Electromechanical quiescence was maintained during the aortic cross-clamp period with cold blood cardioplegic solution. After termination of CPB, heparin was neutralized with 2 to 3 mg/kg of protamine sulfate to restore the ACT to baseline values.
Intraoperatively, packed red blood cells (PRBCs) were transfused as necessary to maintain a hematocrit of 20% or greater. Platelet concentrates, fresh frozen plasma, cryoprecipitate, and nonprotamine hemostatic agents (eg, desmopressin acetate, 
-aminocaproic acid) were administered for the subjective assessment of excessive diffuse oozing from mediastinal surfaces, a phenomenon that indicates the presence a generalized coagulopathy. Other than the ACT, no other coagulation indices were measured during the operation. After weaning from CPB, intravascular volume was enhanced as necessary by the anesthesiologist with intravenous boluses of 6% HES (Hespan; DuPont Pharmaceuticals, Wilmington, DE) or 5% albumin, depending upon the availability of these colloidal solutions. As mentioned above, HES was used as the predominant intraoperative volume expander from August to November 1994 as a result of near-depletion of our hospital's albumin supply. However, immediately before and after the outbreak period, albumin was the colloidal agent of choice. Aside from this difference in the type of colloid preferred for volume expansion, there were no other features that distinguished the outbreak period from the surrounding months.
Upon admission to the ICU, arterial blood samples were collected from each patient for determination of hematocrit, platelet count, prothrombin time, partial thromboplastin time, and ACT. Additional doses of protamine were administered early in the postoperative period for an abnormally prolonged ACT. It is the practice of our ICU staff to initiate an hourly record of mediastinal blood loss upon arrival of all post-cardiac surgical patients in the ICU by measuring the total volume of blood shed into the thoracostomy tubes each hour. This record is maintained until tube removal. However, in the current study we recorded mediastinal blood loss during only the first 8 postoperative hours to focus our analysis on the rate of bleeding in the early postoperative period.
The postoperative hematocrit was maintained greater than 25% with transfusions of PRBCs, whereas blood products (eg, platelet concentrates, fresh frozen plasma, and cryoprecipitate) were used as necessary to control abnormally high rates of postsurgical blood loss. Similarly, nonprotamine hemostatic drugs such as desmopressin acetate, -aminocaproic acid, and vitamin K were administered for excessive blood drainage from the thoracostomy tubes irrespective of laboratory values. In the current review we recorded the total postoperative PRBC and blood product transfusion requirement of each patient during the first 24 hours after arrival in the ICU. In addition, a record was maintained of the number of patients requiring infusion of hemostatic agents as well as reexploration for mediastinal bleeding during the same 24-hour time interval.
All measured variables including certain demographic data, all hematologic parameters, mediastinal blood loss, and postoperative transfusion requirements are reported as the mean ± standard error of the mean and were analyzed for between-group differences by analysis of variance. All other parameters, such as the number of patients receiving hemostatic agents or undergoing reexploration for bleeding, are reported as the fraction or percentage of the total number of patients in each group; these data were analyzed by the 
2 test. A linear regression analysis was performed on the HIO group to determine whether the total dose of HES administered intraoperatively (mg/kg) correlated with the rate of postoperative blood loss. A p value of less than 0.05 was considered significant for all analyses.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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Preoperative Patient Data |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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indicates, the three groups were similar with regard to preoperative weight, age, the number of patients having undergone previous cardiac operations, and the number of patients who received aspirin within 10 days of coronary artery bypass grafting. In addition, there were no differences among the groups in terms of preoperative hematologic parameters (Table 2).
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Operative Data |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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). This difference may be explained on the basis of a reluctance by the OR and ICU staff to infuse HES into patients who had been exposed to longer periods of extracorporeal circulation. There were no between-group differences with regard to the number of patients undergoing concomitant cardiac surgical procedures or receiving hemostatic drugs intraoperatively, nor was there a significant difference in the average number of distal coronary anastomoses performed. However, there did appear to be a trend toward a higher intraoperative PRBC and blood product transfusion requirement in the NH group, which is perhaps related to the longer duration of time spent on CPB in this group.
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Parameters of Postoperative Hemostasis |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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, patients who received HES in the OR (HIO group) exhibited a significantly lower postoperative hematocrit and platelet count, as well as a significantly prolonged prothrombin time, compared with the HPO and NH groups. However, the partial thromboplastin time was similar among the three groups. Commensurate with these derangements in hematologic indices, patients in the HIO group sustained significantly higher rates of chest tube drainage over the first 2, 4, and 8 postoperative hours. As Figure 1 indicates, the dose of HES (mg/kg) infused intraoperatively directly correlated with the rate of mediastinal blood loss during the first 8 postoperative hours (r = 0.37; p = 0.002). As outlined in Table 4, the number of patients in the HIO group requiring administration of hemostatic agents to control brisk chest tube drainage was significantly higher than that of the NH group. Although the result was not quite statistically significant, the HIO group exhibited a clear trend toward a greater need for postoperative PRBC and blood product transfusions, as well as a tendency toward a higher rate of reexploration for unrelenting mediastinal hemorrhage. Among the 5 patients in the HIO group undergoing reexploration, 3 were found to lack a discrete anatomic bleeding site and were thus thought to have a generalized coagulopathy.
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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The reasons for the derangements in hemostasis produced by intraoperative HES infusion cannot be explained by this review. However, there appears to be a critical timing factor related to exposure of the blood elements to HES during the first few minutes after cessation of CPB, a time when fibrinolytic activity is at a maximum and platelet function is at a nadir.
In the present study the mean dose of HES administered either intraoperatively or postoperatively (
800 mL for each group) is well within the range purported by other investigators to be safe for post–cardiac surgical use in the ICU [5–7]. In agreement with these previous investigators, we have confirmed that the administration of HES to postoperative CABG patients in the ICU does not impair hemostasis. Kirklin and associates [6] have previously shown that when the total HES volume infused postoperatively is within the suggested dosage range, the mean dose does not correlate with an increased rate of blood loss. However, our analysis reveals a direct correlation between HES dose administered in the OR and the rate of mediastinal bleeding, suggesting that there may not be a truly safe dose of this agent for intraoperative use during cardiac operations.
A potential criticism of this study may involve the issue of selection bias. One could argue that because all individuals in the HIO group received an infusion of colloid intraoperatively as opposed to less than half of patients in the other two groups, patients in this former group were bleeding excessively in the OR and were thus manifesting signs of volume depletion, necessitating colloid infusion intraoperatively to maintain intravascular volume. Using this line of reasoning, one might argue that such patients were suffering from a hemostatic defect before they ever received HES in the OR. However, if this were true we would expect those patients to have received more PRBCs, blood products, and hemostatic agents intraoperatively. Clearly, our data do not support this contention.
A limitation of the present investigation involves its retrospective nature. As is true of any retrospective analysis, our study is limited by factors beyond our control that might confound interpretation of the data. However, the between-group differences identified in this study were both multiple and highly statistically significant, thus lending considerable support to our claim that intraoperative HES administration increases the propensity for postoperative bleeding. Nevertheless, a controlled, prospective, randomized study would be the ideal method to evaluate the safety of HES administration during cardiac operations.
In summary, the current study indicates that administration of 6% HES in the OR-within only a few minutes after termination of CPB-produces a clinically relevant impairment in hemostasis after coronary artery bypass grafting. Intraoperative use of this colloid for bolus expansion of the intravascular space should be avoided until more specific guidelines are established regarding the safe timing of its administration during cardiac operations.
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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References |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsPreoperative Patient DataOperative DataParameters of Postoperative...CommentReferences |
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