Management of intraoperative fluid balance and blood conservation in adult cardiac surgery

Management of intraoperative fluid balance and blood conservation in adult cardiac surgery Eleftheriadis S, Stamoulis K, Ieropoulos Ch, Flossos A The reduction of homologous blood transfusions remains an important goal. The actual blood loss and the positive fluid balance during cardiac operations involving CPB result in a fall in the haematocrit and represent major risk factors for blood transfusions. Methods and techniques which lead to a decrease of haemodilution are important when aiming at fewer transfusions in such operations. Considering volume load as modifiable, a number of efforts have been made to reduce the resulting positive fluid balance under CPB. The minimization of the prime volume with or without the use of hyperoncotic solutions is crucial in the attenuation of haemodilution. The beneficial effect of minimized circuits on inflammation and haemodilution and the retrograde autologous priming of the cardiopulmonary bypass circuit have a positive result in a reduce need for allogeneic blood. Autologous blood cell salvage and intraoperative autotransfusion decreases requirements for homologous blood. Experience in these techniques increases their effectiveness and reduces their possible dangers. A multimodal approach and change in physician transfusion practices is deemed necessary for reducing homologous blood transfusion during cardiac operations. The reduction of blood transfusions is considered to be an important and relevant goal as described in numerous reviews [1]. Minimizing transfusion has become desirable for all patients. Behavioral and simple interventions appear to be effective in changing physician transfusion practices and reducing blood utilization [2]. Cardiac surgery has been identified as a major consumer of donor blood products. In a recently published report by the Society of Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists[3], a number of variables were identified as important indicators of risk for transfusion: advanced age, low preoperative red blood cell volume (preoperative anaemia or small body size), preoperative antiplatelet or antithrombotic drugs, complex procedures or emergency operations, and noncardiac patient comorbidities. In the same report, careful review revealed a number of interventions that were likely to reduce blood transfusion, including limitation of antithrombotic drugs, use of drugs that increase preoperative blood volume (eg, erythropoietin) or decrease post-operative bleeding (eg, antifibrinolytics), selective use of off-pump coronary artery bypass graft surgery, use of autologous predonation and normovolemic haemodilution, and routine use of a cell-saving devices. Existing guidelines underline the significance of a 1 Cardiac Anaesthesia Unit, University Hospital of Alexandroupolis, Greece 2 Cardiac Anaesthesia Unit, University Hospital of Larissa, Greece The Greek E-Journal of Perioperative Medicine 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal ©2009 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2009 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος 31 multimodal approach to blood conservation, with the high-risk patients receiving all available peri-operative interventions under appropriate institution-specific transfusion algorithms [3,4]. Nevertheless and despite its worldwide approval, the application of conservation or alternative therapies for transfusion has been slow[5,6]. It seems that in order to change practices, appropriately designed clinical trials are still needed to determine the relative effectiveness of different interventions [2]. During cardiac operations under CPB, the combination of two factors, namely the actual blood loss and the positive fluid balance associated with CPB, result in a fall in haematocrit and the consequent transfusion of allogeneic blood. The importance of clinical evaluation to avoid unnecessary transfusion has been highlighted[7]. This review focuses on the intraoperative methods and techniques available to the anesthesiologist for blood sparing during cardiac operations. The reader can seek elsewhere for blood saving techniques and alternatives to blood transfusion which can be applied throughout the peri-operative period and in a wide spectrum of surgeries. Haemodilution in cardiac operations with extracorporeal circulation The application of CPB alone leads to an acute dilutional anaemia, impacting insignificantly on the number of circulating erythrocytes. The administration of fluids during the pre-bypass period has an additive effect. The inevitable dilution of the red blood cell mass, occurring on initiation of CPB, becomes a primary determinant of transfusion practices, as clinically, the actual value of the haemoglobin concentration or the haematocrit significantly affect the decision to transfuse[8,9]. Nevertheless, recommendations for transfusion, often referred to as the “transfusion triggers”, are not supported by high-level evidence[2,10]. In case of iatrogenic haemodilution, the value of a specific haemoglobin or haematocrit level as the indicator for transfusion becomes less appropriate. But as accurate estimates of blood loss and intravascular blood volume are difficult or impossible, other measurements may be needed. These measurements include whole body oxygencarrying capacity, oxygen consumption, oxygen extraction ratios, and oxygen delivery. In many reports, female sex and low body surface area have been recognized, among others, as independent predictors of erythrocyte transfusion in cardiac surgery patients[11-14]. When compared to a male population with normal somatometric values, blood loss and initiation of CPB are both expected to affect haemoglobin concentration to a greater degree in the above group of patients. These observations underline the significance of the degree of haemodilution on the amount of blood product usage. One of the most important factors in achieving blood conservation in cardiac surgery is the acceptance of haemodilution[15]. During cardiopulmonary bypass, oxygenation and systemic perfusion are provided under conditions of heparinization, haemodilution and reduced blood viscosity, nonpulsatile blood flow and hypothermia. This situation creates a number of physiological consequences that affect systemic physiology and blood formed elements[16]. Adequate oxygen delivery to tissues may be well maintained with haematocrit well below normal baseline levels. Past studies showed that haemoglobin values of 5.0 g/dL under dilution provide adequate oxygen delivery during CPB [17,18] and a study performed in patients immediately after CPB showed no change in myocardial lactate extraction or production even with elective haemodilution to the same haemoglobin level[19]. In practice, these observations create feelings of reassurance and shift the so-called “trigger value” towards a lower haematocrit. At the same time it leaves greater scope for subjectivity, when a decision to transfuse must be taken. This seems to be of greater importance for female and low body surface area patients, as they are more prone to haemodilution. Under these circumstances, clinicians have to estimate the degree of anaemia that is tolerated by the patient with measurements other than the change of haemoglobin or haematocrit values. Lack of these measurements leads to adoption of “triggers” and may explain to a degree the higher inciThe Greek E-Journal of Perioperative Medicine 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal ©2009 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2009 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος 32 dence of blood product usage in easily haemodiluted patients. Considering volume load as modifiable, a number of efforts have been made to reduce the resulting positive fluid balance during surgical procedures under CPB. These studies focused on the minimization of the prime volume with or without the use of hyperoncotic solutions, the retrograde autologous priming of the cardiopulmonary bypass circuit, the application of cell salvage techniques, and the use of mechanical support by filters for plasma concentration. Reduction in prime volume Low prime volume is crucial in the attenuation of haemodilution. As prime volume stands at the core of this well recognized problem of cardiac surgery, numerous efforts have been made to minimize the circuit. Conventional circuits need volumes of more than 1.400ml for the pump and oxygenator, while newer integrated circuits combine centrifugal pump and oxygenator thus reducing the necessary volume to 450ml. It is needless to say that techniques such as retrograde autologous priming and hyperoncotic prime (see below for details) aim to reduce both prime and “extra” volume on pump. In one retrospective study of 970 patients undergoing elective CABG a significant reduction in red blood cell transfusion rates was found with minimized circuits (MC) compared to conventional circuits[20]. Another group of researchers published two prospective studies including surgeries of valve replacement and reported at least a 50% reduction in transfusion rates with the use of minimized circuits[21,22]. Cardiac surgery for Jehovah's Witness patients is a challenge as they not only reject homologous transfusion but also blood that has been separated from their own circulatory system i.e. autologous transfusion. This challenge is greater for paediatric patients. In one report, open-heart surgery was performed in three Jehovah's Witness infants with a body weight between 3.1 and 4.5kg without transfusion of blood components. This was achieved by using a low-volume CPB circuit (priming volume of 200mL), designed to decrease the degree of haemodilution [23]. In cardiac surgery, CPB and circuits are considered to provoke systemic inflammatory response by complement activation and preinflammatory cytokine release[24]. Existing data support that minimized circuits reduce inflammatory reaction, activation of coagulation and fibrinolysis[25]. The beneficial effect of these circuits on inflammation and haemodilution seems to have a positive result on the number of transfusions, leading to less use of allogeneic blood[26,27]. On the other hand, a randomized control study of 204 patients undergoing CABG found no decrease in transfusion requirements with the use of a minimized circuit[28]. The authors stated that the possible transfusion benefits from minimized circuits must be balanced against possible risks including air embolism, and lack of cardiotomy suction associated with this technology. Currently, a number of circuits are commercially available and this technology is spreading quickly as more and more team members (anaesthesiologists, perfusionists and surgeons) are trained. Nevertheless, the impact of these circuits on transfusion, inflammatory response and outcome must be further investigated. Finally, the use of low prime and minimized extracorporeal bypass circuits to reduce the fall in haematocrit during CPB is classified in the report by the Society of Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists as Class IIb level of evidence, i.e. that their use is not unreasonable for blood conservation[3]. Hyperoncotic cardiopulmonary bypass prime Haemodilution and the consequent fall in colloid osmotic pressure (COP) with the initiation of CPB, was shown to play a key role in the development of post pump organ dysfunction. As COP falls, the microvascular blood pressure is less responsive, causing imbalance of microvascular net filtration and reduction in the removal of interstitial fluid by the lymphatics, thus leading to oedema formation. Rise in extravascular lung water (EVLW) and myocardial The Greek E-Journal of Perioperative Medicine 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal ©2009 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2009 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος 33 oedema contribute to cardiopulmonary dysfunction[29-31]. The disorder has a problematic course in ICU and bad outcome. Although there has been much discussion over the last 30 years of the optimal priming composition for the CPB circuit in order to avoid or at least to ameliorate post-pump organ dysfunction, the subject is still controversial. No beneficial effects regarding clinical parameters and outcome could be demonstrated in the majority of studies using colloidal prime compositions[32-34]. Reasons for this may be that the COP of the hyperoncotic priming solutions used was still less than physiological in many studies, and that the cardioplegia used was crystalloid. Currently in many centres, blood cardioplegic solution is drained from the reservoir (blood cardioplegia), and, if hyperoncotic priming is agreed, the fall of COP may be avoided. An improved clinical performance score and a reduced post-operative hospital stay for patients treated with a colloidal CPB prime were demonstrated in only one study[35]. Although cardioplegia was with crystalloid, the study was able to demonstrate a significant increase of COP before its administration. In a later study with hydroexylstarch (HES) versus crystalloid, the fall in COP, the degree of positive fluid balance, and weight gain were significantly less in the HES group[33]. There was also an improvement in haemodynamic parameters and in functional respiratory variables such as AaDO2 and Qs/Qt. As the number of the patients was small however and in good clinical condition, the study was unable to show an improved outcome. Despite the improved intra-operative fluid balance, there was no change in haemoglobin and haematocrit values 2 and 4 hours post-operatively. Furthermore, there was a trend towards increased calculated blood lost in the HES group. Unfortunately, the study does not provide information about the intra-operative course of these parameters or about the perioperative blood transfusions. Presently, it cannot be concluded that hyperoncotic priming solutions and attenuation of fall of colloid osmotic pressure show any beneficial effect on blood product usage in cardiac surgery. Retrograde Autologous Priming (RAP) of the cardiopulmonary bypass circuit RAP of the CPB circuit is a blood conservation method developed to limit the degree of haemodilution occurring during extracorporeal circulation. This concept was first described in 1960 [36] and revived in the late 1990s[37]. The technique involves the replacement of the crystalloid prime with the patient’s own blood. After arterial and venous cannulae are inserted, the crystalloid prime is slowly drained into a recirculation bag. Up to 1L of the circuit volume can be displaced by the patient’s own blood immediately before the onset of CPB [37]. A 1000-mL blood transfer bag is connected to the venous line. Transfer is performed in three basic steps. First, crystalloid is displaced from the arterial line. Blood is allowed to flow by pressure gradients from the aorta and through the arterial line and filter, displacing crystalloid prime into the blood transfer bag. Next, the crystalloid in the venous reservoir and oxygenator is similarly displaced using pressure gradients from the aorta. Finally, the entire prime from the venous line is displaced into the bag at the onset of CPB. Approximately 300 mL of volume in the CPB circuit is replaced during each of these steps. The entire RAP process is completed in 5–8 min. Sequestered prime in the blood transfer bag can be reinfused after processing via a cell saver system. This technique maintains colloid osmotic pressure and reduces extravascular lung water compared with standard priming techniques. Caution needs to be taken if the displaced crystalloid is collected and excluded from the circuit with a vacuum assisted venous drainage system. On at least one occasion, this resulted in massive systemic air embolism through a patent foramen ovale, and vacuum-assisted venous drainage should not be used in such cases for retrograde autologous priming[3]. Haemodynamic instability is not rare and can develop when blood is drained from the patient into the arterial and venous lines. Transient hypotension occurring during the period until the pump reaches an adequate flow for organ perfusion, may be treated with phenylephrine bolus or infusion and crystalloids. Crystalloid The Greek E-Journal of Perioperative Medicine 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal Ελληνικό Περιοδικό Περιεγχειρητικής Ιατρικής 2009; 7:30-40 (ISSN 1109-6888) www.anesthesia.gr/ejournal ©2009 Society of Anesthesiology and Intensive Medicine of Northern Greece ©2009 Εταιρεία Αναισθησιολογίας και Εντατικής Ιατρικής Βορείου Ελλάδος 34 administration reduces the RAP effect. If these measures are unsuccessful, the RAP process must be terminated. In general, the technique induces hypovolemia in the system patientcircuit and the perfusionist must be cautious so that organ perfusion is not adversely affected. Usually, perfusionists are introduced to the RAP technique during a training period. A number of studies have demonstrated clinical efficacy of RAP in reducing the number of patients transfused or in decreasing total blood product usage[37-39]. However in a recent study, only a minimal reduction in PRC use was observed when RAP was routinely applied as a blood conservation modality[40]. The study included 257 patients in the RAP group and 288 in the non RAP group. Forty-four percent of patients in the RAP group received packed red cells versus 51% of patients in the non RAP group and patients with a larger initial red cell mass appeared to derive a greater benefit from this technique. The results of this study are limited by its retrospective character. In a later analysis, the same group of investigators found a decrease in the incidence of post-operative cardiac arrest in the RAP group and no evidence of any increase in other adverse events, suggesting that RAP is a safe technique[41]. Other investigators observed no effect of RAP on post-operative or total transfusion requirements[42,43], but on one occasion, they concluded that by reducing crystalloid fluid administration and fall of COP during CPB, RAP reduced post-pump EVLW accumulation and weight gain[43]. These clinical trials were limited by the small randomized sample sizes (1057 patients in the RAP group) and by the exclusion of patients at highest risk for perioperative transfusion. To determine the effect of different prime volumes on the typically observed post-operative hyperdynamic response, patients under CPB with large prime volume (2.350ml) versus small (1.400ml) were studied[44]. In the small prime group, COP was higher and associated with decreased degrees of positive fluid balance and an attenuated hyperdynamic response. With the on-bypass haematocrit aimed at 22% to 23%, autologous blood was predonated by 16 patients in the small prime group but by none in the large prime group. The authors concluded that reduction in blood bank products can be obtained with small prime volumes. In two other randomized trials, retrograde autologous priming caused a significant reduction in the frequency of allogeneic blood transfusion compared with usual practice[45,46]. Finally, retrograde autologous priming of the CPB circuit is classified in the report by the Society of Thoracic Surgeons and the Society of Cardiovascular Anaesthesiologists as Class IIb level of evidence, i.e. not unreasonable for blood conservation[3].