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Year : 2017  |  Volume : 10  |  Issue : 1  |  Page : 3-9

Effectiveness of minimal acute normovolemic hemodilution to minimize allogenic blood transfusion and re-exploration in elective adult coronary artery bypass graft surgery using colloid as a replacement solution

Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Web Publication3-Aug-2018

Correspondence Address:
Dina Salah
8595 El Reda and Nour Street, Mokattam, Cairo
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.238460

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Background and aim Various studies have questioned the efficacy of intraoperative acute normovolemic hemodilution (ANH) in reducing bleeding, the need for allogenic transfusion, and the incidence of re-exploration in cardiac surgery. The aim of the present study was to evaluate the effectiveness of the use of minimal ANH for blood transfusion requirements and re-opening in elective adult coronary artery bypass graft surgery using cardiopulmonary bypass.
Patients and methods This prospective, randomized controlled study was conducted on 100 consecutive adult patients who underwent elective coronary artery bypass graft. Patients were randomly divided into two equal groups: the ANH group (n=50) and the control group (n=50). In the ANH group, 5–8 ml/kg of autologous blood was withdrawn after administering anesthesia and before systemic heparinization. Simultaneously, colloid solution (6% hydroxyethyl starch 130/0.4; Voluven) was infused in a ratio of 1:1, and then the blood was re-infused after bypass. Hemodilation was not carried out for the control group.
Total amount of allogenic-packed red blood cell, fresh frozen plasma, platelet concentrate transfusion, and the number of patients undergoing re-opening because of excessive bleeding were calculated for the two groups.
Results A significant decrease was observed in the number of red blood cell units and fresh frozen plasma transfusion per patient in the ANH group compared with the control group. Conversely, chest tube output, representing postoperative bleeding and platelet count, did not differ between the two groups.
Conclusion In this study, the use of the minimal ANH technique reduced the consumption of allogenic red blood cells and fresh frozen plasma in adult cardiac surgery patients. However, this technique had no effect on postoperative bleeding, incidence of re-exploration, and platelet count.

Keywords: acute normovolemic hemodilution, bleeding, re-exploration

How to cite this article:
Shorbagy MS, Salah D. Effectiveness of minimal acute normovolemic hemodilution to minimize allogenic blood transfusion and re-exploration in elective adult coronary artery bypass graft surgery using colloid as a replacement solution. Ain-Shams J Anaesthesiol 2017;10:3-9

How to cite this URL:
Shorbagy MS, Salah D. Effectiveness of minimal acute normovolemic hemodilution to minimize allogenic blood transfusion and re-exploration in elective adult coronary artery bypass graft surgery using colloid as a replacement solution. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2023 Dec 3];10:3-9. Available from:

  Introduction Top

The hematologic management of the cardiac surgical patient entails a complex balance between extreme degrees of anticoagulation and the restoration of normal hemostasis after the procedure. These two contrasting processes must be managed carefully and modified with respect to preoperative disease state, duration of cardiac surgery, use of extracorporeal circulation, and the desired hemostatic outcome [1].

Skillful surgery combined with blood-saving methods and careful management of blood coagulation will help to reduce unnecessary blood loss and transfusion requirements. Excessive surgical bleeding causes hypovolemia and hemodynamic instability, anemia, and reduced oxygen delivery to tissues with a subsequent increase in postoperative morbidity and mortality [2].

The risks associated with the use of allogenic blood product transfusion include ABO/Rh incompatibility, sepsis, febrile reactions, immunosuppression, and viral transmission [3]. Coagulation dysfunction is common following cardiopulmonary bypass (CPB). Platelet dysfunction, decreased activity of clotting factors, insufficient inactivation of heparin, and vigorous fibrinolysis are the main causes of post-CPB nonsurgical bleeding [4].

Acute normovolemic hemodilution (ANH) before a major surgery is a relatively simple, cheap, and effective tool to avoid or reduce allogenic blood transfusions. The anesthesiologist, however, must be familiar with the practical aspects of ANH. In addition, knowledge of the physiologic compensatory mechanisms that occur during ANH and their limits is mandatory for the safe use of this blood-saving technique [4].

There are additional benefits of ANH that are not common to other autologous transfusion modalities. When the blood is kept in the same operating room, the chances of clerical error are eliminated. On the other hand, because blood collected by ANH is stored at room temperature and is usually returned to the patient within eight hours of collection, there is little deterioration of platelets or coagulation factors [5].

The aim of the present study was to evaluate the effectiveness of the use of minimal ANH on blood transfusion requirements and re-opening in elective adult coronary artery bypass graft (CABG) surgery using CPB.

  Patients and methods Top

After obtaining approval from our university ethics committee and written informed consent from all patients, the study was conducted in Ain Shams University Hospitals (in the period from January 2014 to February 2015) on 100 patients with American Society of Anesthesiologists physical status II–III undergoing elective coronary bypass grafting using CPB.

Exclusion criteria were as follows: left main coronary artery stenosis, left ventricular ejection fraction less than 40%, unstable angina pectoris in combination with coronary artery disease and severe aortic stenosis, Euro score II of greater than 2%, pump time of greater than 2.5 h, history of hematological disorders, advanced chronic renal impairment (serum creatinine>2 mg/dl), active chronic hepatitis or cirrhosis, preoperative hematocrit less than 34%, and known allergy to colloid.

Preoperative preparations

All cardiovascular medications were continued till the morning of the surgery except angiotensin-converting enzyme inhibitors due to risk of perioperative hypotension.

Insulin or oral hypoglycemic medications were withheld on the morning of the surgery. All patients were premedicated with diazepam 5 mg orally on the night of the surgery and morphine 5 mg one hour before the surgery through intramuscular route.

Warfarin was stopped at least for 4 to 7 days or till international normalized ratio reached 1.2, aspirin for 3 days, and clopidogrel for 7 days.

Anesthetic techniques

Anesthetic techniques were standardized for all patients. Standard monitoring such as pulse oximetry, lead II and V5 of the ECG, automated segment trend analysis, end tidal capnography, and continuous measurement of central venous pressure, invasive blood pressure, nasopharyngeal temperature, and urine output were carried out. Serial blood gas analysis and serum electrolytes were also performed.

Smooth balanced anesthesia with fentanyl 2–5 μg/kg, propofol 1–2 mg/kg, pancuronium 0.1 mg/kg, and inhaled isoflurane 0.5 to 1% was administrated. Patients were mechanically ventilated to keep ETCO2 between 30 and 35 mmHg.

After heparinization (300 IU/kg), CPB including a membrane oxygenator and a circuit primed with a crystalloid solution was applied using nonpulsatile flow (2.2–2.5 l/min/m2) and hypothermia (28–30°C).

An α-stat control for acid–base management was applied and mean arterial pressure was targeted between 50 and 80 mmHg. At the end of CPB, protamine was administered to neutralize heparin (1:1 ratio); further doses of 50 mg were administered if activated clotting time was greater than the baseline value.

Operative techniques

All patients were operated upon in our hospital with standardized techniques. After median sternotomy, the left internal mammary artery was isolated through an extrapleural approach for left anterior descending artery graft.

The saphenous veins were used as routine grafts for other coronary anastomoses. Before closure of the chest, mediastinal and pleural drains were positioned and a low-grade suction was instituted.

ICU management

All patients were transferred to ICU and were intubated and mechanically ventilated till ready for extubation, when stable circulatory condition and no major bleeding were noted.

Blood conservation techniques

Patients were randomly divided into two equal groups by using a computer-generated random-number sequence: the ANH group (n=50 patients) and the control group (n=50 patients).

In ANH group, after induction of anesthesia before systemic heparinization and initiation of CPB, 5–8 ml/kg of whole blood was withdrawn through a large bore cannula (14 G) placed in the external jugular vein with gravity drainage.

At the same time, during withdrawal of autologous blood same volume of 6% hydroxyethyl starch (HES) 130/0.4 solution (Voluven; Fresenius Kabi Deutschland, GmbH, Germany) was infused in a large bore peripheral cannula. The collected blood was stored in citrate phosphate dextrose collection bags, kept on a rocking platform shaker, preserved at room temperature under sterile conditions, and labeled appropriately for patient identification.

Euvolemia was evaluated through standard monitoring (systemic arterial pressure, ECG, and central venous pressure).

All collected blood was returned to the patients before leaving the operation room.

Samples were taken from the central venous catheter for evaluation of hemoglobin (Hb), hematocrit, platelet count, prothrombin time (PT), and activated partial thromboplastin time (PTT), which were carried out at the following times: before induction of anesthesia (time 1), on arrival in ICU (time 2), 24 h after the arrival in ICU (time 3), 48 h after ICU admission (time 4), and at discharge from ICU (time 5).

During surgery, serial blood arterial analysis was performed to determine Hb, hematocrit, electrolytes, and blood gases.

Transfusion guidelines were as follows. Packed red blood cells (PRBCs) were transfused during CPB if Hb value was less than 7 g/dl and hematocrit value less than 25%. In addition, PRBCs were transfused after bypass and throughout the hospitalization period if Hb value became less than 9 g/dl and hematocrit less than 27%.

Fresh frozen plasma (FFP) was infused after protamine administration if prothrombin time value was 1.5 times the baseline in presence of active bleeding given as 15 ml/kg.

Platelet concentrate was transfused if platelet count was less than 50 000/mm3 in presence of active bleeding and given as 1 U/10 kg body weight.

Surgical re-exploration: Quantitative chest tube drainage criteria for reoperation were as follows: >500 ml/h>800 ml during 2 successive hours, >900 ml during 3 successive hours, or total bleeding>1200 ml after 5 h.

Sample size calculation

Sample size calculation was based on a power of 80% in detecting a 40% reduction in the requirement of red blood cell transfusion when the significance level is α is equal to 0.05 with two-sided testing and previous unpublished experience showing normally distributed data. With equal allocation ratio, it was estimated that each group would include 45 patients. Allowing for a 10% drop-out, we included 50 patients in each group.

Statistical analysis

Data were collected, revised, coded, and entered to the statistical package for social science, version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. USA). The qualitative data were expressed as number and percentages and compared using the χ2-test or Fisher’s exact test as appropriate, whereas the quantitative data were expressed as mean and SDs and compared using the independent t-test. The confidence interval was set to 95%, and thus the P-value was considered significant at the level of less than 0.05.

  Results Top

The current study was performed on 100 adult patients of different ages and of either sex undergoing elective CABG surgery. They were divided into two equal groups. In the first group (50 patients) we used minimal ANH after induction of anesthesia and before systemic heparinization and the second group (50 patients) was the control group.

The patients’ characteristics in both groups did not differ significantly (as P>0.05) ([Table 1]).
Table 1 Patients’ characteristics

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In addition, Hb level, hematocrit, platelet count, and coagulation tests before surgery in patients in the two groups were not significantly different ([Table 2]).
Table 2 Baseline hematological data

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The two groups matched as regards intraoperative data, use of internal mammary artery, average number of distal anastomoses, cross clamp time, CPB time, and duration of the operation ([Table 3]).
Table 3 Intraoperative data

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Hb and hematocrit decreased significantly in the ANH group at times 4 and 5 compared with time 1. In the control group, Hb and hematocrit decreased significantly at times 3, 4, and 5 compared with time 1. Hb and hematocrit were significantly lower at time 2 and significantly higher at time 3 in the ANH group compared with the control group ([Table 4]).
Table 4 Perioperative hematological data for hemoglobin and hematocrit

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Platelet count showed significant decrease in the ANH group at times 3, 4, and 5 compared with time 1, and showed significant decrease in the control group at times 2, 3, 4, and 5 compared with time 1, whereas it showed no significant difference between the two groups. PT was significantly prolonged at times 2 and 3 compared with time 1 in the two groups, but it showed no significant difference between the two groups. Activated PTT showed neither significant difference compared with time 1 in the two groups nor between the two groups ([Table 5]).
Table 5 Perioperative hematological data for platelet count, PT, and PTT

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The number of patients who received PRBC and FFP was significantly higher in the control group than in the ANH group. There were no significant differences between the two groups regarding transfusion of platelets, chest tube drainage volume, and number of patients re-explored ([Table 6]).
Table 6 Perioperative allogenic blood transfusion and postoperative data

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  Discussion Top

Our results demonstrated that minimal (10% of patient’s blood) ANH before the on-pump CABG reduced the need for red blood cell and FFP transfused with minimal effects on the coagulation profile.

Intraoperative withdrawal of a part of circulating blood volume and substitution with crystalloid and/or colloid solution to obtain fresh whole blood to transfuse after the end of surgery was proposed in the 1960s [6]. In patients with a normal or high initial Hb levels who are undergoing cardiac surgery, decreased blood viscosity associated with the induced anemia may have cardioprotective effects [7],[8]. At the microcirculatory level, improvement in blood fluidity results in an increased red blood cell velocity in the capillaries and an enhanced flow motion. Both mechanisms allow for a better spatial and temporal distribution of red cells within the capillary network, leading to a more homogenous delivery of oxygen to the tissues [9], and also to redistribution of blood flow to areas of high oxygen demand, like the brain and the myocardium, at the expense of other organs with lower metabolic needs, such as the kidney, the gastrointestinal tract, and the liver, producing a better matching of oxygen delivery to tissue oxygen demand [10].

Unlike preoperative autologous donation (PAD), ANH may be performed on the day of surgery in the operation room. The minimal preoperative preparation required minimizes patient inconvenience and makes ANH suitable for both emergency and elective procedures.

Furthermore, ANH units are collected and stored at the patient’s bedside reducing the administrative costs associated with the collection, storage, and testing of PAD units. If proven effective, ANH could provide a cost-effective alternative to PAD for the provision of autologous blood.

In our study, using colloid as a replacement solution decreased allogenic blood exposure in patients undergoing on-pump CABG. The current study is the first one to evaluate the effects of minimal ANH on allogenic blood requirements in patients with CABG using Voluven, which is a HES derived from waxy maize amylopectin, a branched polysaccharide closely resembling glycogen, by cleavage and hydroxyethylation. The extent of hydroxyethylation (degree of substitution) and its pattern determine the degradation of HES by serum (α)-amylase, and therefore account for the pharmacological differences between various HES specifications [11]. It has an average molecular weight of 130 000 Da and a degree of substitution of 0.4 (HES 130/0.4). In-vitro and in-vivo coagulation seem to be less compromised by Voluven than by other HES specifications [12],[13],[14]. Voluven may not be associated with the typical undesired effects of higher substituted and higher molecular weight HES types − for example, plasma accumulation, impairment of coagulation, and tissue storage. This was reflected in our study as the effects on postoperative chest tube drainage and incidence of re-exploration were similar in the two groups. There was little deterioration of platelets and coagulation factors because the collected blood was stored at room temperature and returned to the patients within 6–8 h of collection.

In ANH, the choice of a diluting fluid can be either a crystalloid or colloid. The crystalloids are recommended in a 3:1 ratio to avoid a volume deficit. The colloids have a primary advantage of intravascular retention so the amount to be infused can be approximately equal to the amount of blood removed.

Colloids may be a better alternative than crystalloids in coronary artery disease patients receiving β-blockers because little replacement is required with colloids and there is no acute overload on the ventricles or dilutional anemia with three-time crystalloid replacement, which may lead to myocardial ischemia and hemodynamic instability [15].

Jalali et al. [16] studied 100 patients who were candidates for CABG following ANH to determine the effect of crystalloid on coagulation values. The number of patients using PRBC or FFP transfusion was significantly higher in the control group (74 vs. 58%); moreover, PT and PTT were significantly higher in the control group than in the ANH group.

Kaplan et al. [17] in a study on 100 patients concluded that the amount of blood needed to be transfused in the group taking autologous blood was 18% less than that in the control group. Furthermore, Mahoori et al. [5] studied the efficacy of minimal ANH (10% of patient’s blood volume) using a gelatin solution in avoiding homologous blood transfusion in 100 patients scheduled for CABG with CPB. Percentage of patients in whom allogenic red blood cells were transfused was 44% in the ANH group compared with 76% in the control group (P<0.01).

In contrast, Zisman et al. [4] concluded that autologous blood transfusion of 15% estimated blood volume did not affect post-CPB coagulation, nor did it decrease blood loss or homologous blood product transfusion in the early postoperative period.

  Conclusion Top

For patients undergoing elective CABG surgery, minimal ANH technique using 6% HES 130/0.4 (Voluven) reduces the need of allogenic red blood cells and plasma transfusion, has no effect on the platelet count, and no impact on postoperative bleeding and the incidence of re-exploration.

Conflicts of interest

There is no conflict of interest.

  References Top

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Arya VK, Nagdeve NG, Kumar A, Thingnam SK, Dhaliwal RS. Comparison of hemodynamic changes after acute normovolemic hemodilution using Ringer’s lactate versus 5% albumin in patients on beta-blockers undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2006;20:812–818.  Back to cited text no. 15
Jalali A, Naseri MH, Chalian M, Dolatabadi HL. Acute normovolaemic haemodilution with crystalloids in coronary artery bypass graft surgery: a preliminary survey of haemostatic markers. Acta Cardiol 2008;63:335–339.  Back to cited text no. 16
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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