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ORIGINAL ARTICLE |
Division of Cardiothoracic Anaesthesia
1 Division of Cardiothoracic Surgery, Heart and Lung Centre, Hospital Universiti Kebangsaan Malaysia Kuala Lumpur, Malaysia
Joanna Ooi Su Min, MMed(Anaes) Tel: +603 91455555 Ext 5852 Fax: +603 91737826 Email: joanna{at}ppukm.ukm.my, Department of Anaesthesiology & Intensive Care, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
ABSTRACT
The aim of this study was to compare 6% hydroxyethyl starch 130/0.4 with 4% succinylated gelatin for priming the cardiopulmonary bypass circuit and as volume replacement in patients undergoing coronary artery bypass, in terms of postoperative bleeding, blood transfusion requirements, renal function, and outcome after surgery. Forty-five patients received 6% hydroxyethyl starch 130/0.4 (Voluven) and another 45 were given 4% succinylated gelatin (Gelofusine) as the priming solution for the cardiopulmonary bypass circuit as well as for volume replacement. Postoperative bleeding was quantified from the hourly chest drainage in the first 4 h and at 24 h postoperatively. The baseline characteristics of both groups were similar. In the hydroxyethyl starch group, the total amount of colloid used was 1.9 ± 1.0 L, while the gelatin group had 2.0 ± 0.7 L. There was no significant difference in hourly chest drainage between groups. Blood transfusion requirements, estimated glomerular filtration rate, extubation time, intensive care unit and hospital stay were similar in both groups. It was concluded that 6% hydroxyethyl starch 130/0.4 is a safe alternative colloid for priming the cardiopulmonary bypass circuit and volume replacement in patients undergoing coronary artery bypass surgery.
Key Words: Cardiopulmonary Bypass • Coronary Artery Bypass • HES 130/0.4 [Voluven] • succinylated gelatin [Gelofusine]
INTRODUCTION
Controversy regarding the most suitable colloid for use as a plasma volume expander in cardiac surgery is unresolved despite many ongoing studies. Although there have been improvements in technology, cardio-pulmonary bypass (CPB) is still associated with adverse effects on coagulation and multiple organ dysfunction.1 Therefore, colloids chosen for priming the CPB circuit and volume replacement must not interfere with the coagulation system or any other body system, and incur minimal risk of adverse reactions. Gelatins are poly-dispersed polypeptides produced by degradation of bovine collagen. Gelatin-based colloids have been used as they are free of adverse effects on hemostasis, cross matching, and renal function, and there is no limit to their use.2 Hydroxyethyl starch (HES) is a derivative of amylopectin, the highly branched polysaccharide component of waxy maize, which closely resembles glycogen. With large volumes of HES infused perioperatively, inhibitory effects on hemostasis, most notably on von Willebrand factor, have been reported. These effects are most pronounced with large and highly substituted HES molecules, such as hetastarch which has an average molecular weight of 450,000 daltons and a degree of substitution of 0.7 (HES 450/0.7). However, a new HES specification, HES 130/0.4, offers a better pharmacokinetic and pharmacodynamic profile and can be used safely up to 50 mL · kg–1 per day.3–5 It has been suggested that correcting hypovolemia with HES is associated with increased risk of acute renal failure, and interest has recently focused on the influence of HES solutions on renal function.6 The aim of this study was to compare the effects of using 6% HES 130/0.4 vs. 4% succinylated gelatin for priming the CPB circuit and volume replacement on postoperative bleeding, blood transfusion requirements, renal function, and outcome of coronary artery bypass surgery.
PATIENTS AND METHODS
This was a prospective, randomized, single-blind controlled study involving 90 patients aged 40–75 years undergoing elective coronary artery bypass grafting. The study was approved by the hospital’s ethical committee, and written informed consent was obtained from all patients. Exclusion criteria were: repeat coronary artery bypass; congestive heart failure; recent antiplatelet therapy (<7 days); coagulopathy; renal dysfunction, defined as serum creatinine >106 µmol · kg–1 (males) and >80 µmol · kg–1 (females); liver dysfunction (serum aspartate aminotransferase >40 U · L–1, alanine aminotransferase >40 U · L–1); history of pancreatitis; and known hypersensitivity to HES. The patients were randomized to receive either 6% HES 130/0.4 (Voluven; Fresenius Kabi, Bad Homburg, Germany) or 4% succinylated gelatin (Gelofusine; B Braun, Melsungen, Germany) together with 0.5 g · kg–1 mannitol to a total of 1,600 mL as the priming solution for the CPB circuit.
Anesthesia was induced with fentanyl 10 µg · kg–1, midazolam 3 mg, and rocuronium 0.6 mg · kg–1 and maintained with sevoflurane to achieve a minimal anesthetic concentration of 1.0. Intravenous tranexamic acid 2 g was given after induction. All patients received Ringer’s lactate solution via a peripheral line administered by the anesthesiologist for maintenance and intraoperative replacement throughout the surgery. Before establishing CPB, intravenous heparin 300 U· kg–1 was given to achieve an activated clotting time >400 s. During CPB, the patients were cooled to 30°C–33°C using alpha-stat acid-base gas management. When necessary, either HES or gelatin solution was added to the pump by the perfusionist to maintain the filling volume. Packed red blood cells (PRBC) were given if the hematocrit fell below 25%. Cold blood cardioplegia was used in all cases. On terminating CPB, coagulation was reverted to the baseline value with protamine sulphate. Postoperatively, the patients were transferred to the cardiac intensive care unit (ICU) and mechanically ventilated. Volume replacement with either 6% HES 130/0.4 (n = 45) or 4% succinylated gelatin (n = 45) was used to maintain central venous pressure at 10–14 mm Hg. Chest tube drainage was recorded hourly up to 24 h, and bleeding needing reexploration was defined as chest tube drainage >200 mL · h–1 for 2 consecutive hours. PRBC were transfused when the hemoglobin level was <9 g · dL–1. Fresh frozen plasma, platelet concentrates, and cryoprecipitate were transfused when there was bleeding postoperatively in the presence of abnormal coagulation values (international normalized ratio>1.5, activated prothrombin time>60 s, platelet count <100 x 109 · L–1), or suspected platelet dysfunction or a clotting factor deficiency. The primary outcome variables included postoperative blood loss (measured hourly for the 1st 4 h and at 24 h in ICU), transfusion of PRBC, blood products, and total volume of colloids infused per treatment group intraoperatively and in the 1st 24 h postoperatively (in ICU) were recorded. Other data included duration of mechanical ventilation, complications related to colloid usage, ICU and hospital stay, and renal function based on estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula: 175 x (serum creatinine) –1.154 x (age) – 0.203 x (0.742 if female).
Based on previous data showing that the standard deviation for 24-h postoperative blood loss indicated by chest tube drainage was 350 mL, we estimated that a minimum sample size of 82 patients (41 per group) was sufficient to detect a 250-mL difference in chest tube drainage between groups (with 90% power at 0.05 significance level). With a presumed 10% dropout, we included a total of 90 patients. Data were analyzed using SPSS version 11 software (SPSS, Inc., Chicago, IL, USA). The results are presented as % or mean ± standard deviation. The paired Student’s t test was used for analyses. A p value <0.05 was taken as significant.
RESULTS
All 90 patients recruited completed the study. Patient demographics, baseline characteristics and intraoperative findings were comparable in both groups (Tables 1
and 2). Patients in the HES group received 1,942.3 ± 1,046.1 mL (27.7 mL · kg–1) of the solution, while those in the gelatin group received 1,973.3 ± 728.8 mL (29.5 mL · kg–1) intraoperatively and in the 1st 24 h postoperatively in ICU (Table 3). No patient had chest tube drainage >200 mL · h–1 for 2 consecutive hours, and postoperative blood loss in the 1st 24 h was comparable in both groups. The number of patients who received at least one unit of PRBC or blood products was also not significantly different between groups, although a larger proportion of patients in the gelatin group required fresh frozen plasma (Table 3). Coagulation variables measured postoperatively on postoperative day 1 compared with baseline values were also similar in both groups, as shown in Table 4. The mean baseline eGFR was similar in both groups. The eGFR values were noted to deteriorate temporarily on day 1, 2, and 4 postoperatively, but were improved 4 weeks later in both groups (Table 5, Figure 1). None of the patients in this study required any form of renal replacement therapy during the postoperative period. The mean duration of postoperative ventilation, length of ICU and hospital stay were similar in both groups. No patient required re-exploration due to bleeding. There were no adverse effects related to the use of colloids, and no mortality (Table 6).
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This study has shown that 6% HES 130/0.4 as the priming solution for CPB as well as volume replacement for CABG is comparable to 4% gelatin when used up to 30 mL · kg–1 because it did not significantly increase postoperative blood loss or allogenic transfusion. In fact, a smaller proportion of patients in the HES group required fresh frozen plasma transfusion postoperatively compared to the gelatin group. This finding contrasts with several studies showing that starch solutions have a negative effect on coagulation.7–9 Niemi and colleagues10 compared the use of 15 mL · kg–1 of 4% succinylated gelatin solution, 6% HES 200/0.5, and 4% albumin solutions on hemostasis after cardiac surgery and concluded that the greatest impairment of coagulation was seen with HES. However, the newer starch formulation of 6% HES 130/0.4 has been shown to be safe and comparable to gelatin-based colloids in cardiac surgery.11,12 Using thromboelastography, Haisch and colleagues1 compared HES 130/0.4 with a gelatin-based fluid in cardiac surgical patients and found that different activators and inhibitors showed typical changes seen in cardiac surgery, without identifying any fluid-specific effects. They also found that postoperative blood loss was similar in both groups, and concluded that volume replacement with the new HES preparation was as safe as gelatin-based therapy with regard to coagulation in cardiac surgical patients.1
Renal failure is one of the most serious complications after cardiac surgery, and there is concern about the influence of HES on kidney function, whereas gelatin has no such adverse effects. We calculated perioperative eGFR and found a similar temporary deterioration in both groups on postoperative days 1–4, which subsequently normalized at 4 weeks. We excluded patients with preexisting renal dysfunction (based on elevated serum creatinine levels) as development of renal dysfunction is one of the major concerns with the use of HES. In a prospective randomized clinical trial involving 60 patients aged >80 years undergoing cardiac surgery with CPB, Boldt and colleagues6 compared the effects of 4% succinylated gelatin and 6% HES 130/0.4 on renal function and inflammatory response. They concluded that the gelatin-based volume replacement strategy showed a greater inflammatory response with more endothelial injury and short-term impaired kidney integrity than 6% HES 130/0.4; however, there was no difference in renal function between the 2 groups 60 days after discharge from hospital.
We observed no adverse reactions in either group, but the sample size was too small to address this issue. Another limitation of this study is that we were unable to reliably blind the investigators to the use of the 2 colloids, due to technical reasons. Measurements of coagulation in these patients could have been performed more objectively, for example, using thromboelastography. Nevertheless, it was concluded that 6% HES 130/0.4 is a safe alternative colloid for priming the CPB circuit and volume substitution in patients undergoing CABG.
REFERENCES
Asian Cardiovasc Thorac Ann 2009;
17:368-372
© 2009 by SAGE Publications
DOI: 10.1177/0218492309338101
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