Chapter 6 PBM in Surgical Settings
6.1 PBM in Cardiac Surgery
The transfusion rate in cardiac surgery is much higher than that in other surgical disciplines (Gombotz et al 2007, Maddox et al 2009, Bennett-Guerrero et al 2010, Likosky et al 2014, McQuilten et al 2014). For example, in the Austrian Benchmark Studies, on average more than 50 % of patients received transfusions even for uncomplicated coronary bypass operations, despite a decline in perioperative blood loss over the years (Gombotz et al 2014). Besides, there continues to be widespread variability in the consumption of allogeneic blood and allogeneic blood derivatives between different centers (Gombotz et al 2007, Maddox et al 2009, Bennett-Guerrero et al 2010, Gombotz et al 2014, Likosky et al 2014). The disease severity and the presence of concomitant diseases (a factor that is increasing in prevalence) have, of course, a prominent impact on the indication for transfusion and affect the disease course (Dixon et al 2013, Roubinian et al 2014a). The avoidance of perioperative anemia through the reduction of perioperative surgical blood loss does not only help to decrease the frequency of unnecessary allogeneic blood transfusions, or preempt them altogether, but it also enhances patient safety and improves the disease course (Bracey et al 1999, Oliver et al 2009, Howard-Quijano et al 2013, Goodnough et al 2014a, Willems et al 2014). The cardiac surgeon is therefore confronted with the particular challenges associated with a peri-operative multidisciplinary strategy, such as PBM, to improve outcome through the avoidance of surgical blood loss (Moskowitz et al 2010, Vivacqua et al 2011, Gombotz 2012, Dixon et al 2014, Frank et al 2014b).
This chapter presents a number of techniques and operative strategies based on the author’s own experience.
6.1.2 Preoperative Measures
The prevalence of anemia among patients undergoing cardiac surgery is as high as 50 % (Gombotz et al 2007, Van Mieghem et al 2011, David et al 2013, Gombotz et al 2014, Kim et al 2015a). In addition to preexisting conditions such as iron deficiency, possible causes include blood loss secondary to preoperative interventions such as coronary angiography, or simply frequent blood draws (Ereth et al 2000, Hung et al 2015). Despite the fact that even moderate preoperative anemia—when left untreated—leads to a two- to threefold rise in the transfusion rate and negatively affects the course of disease, it continues to go untreated in more than 90 % of patients (Gombotz et al 2007, Kulier et al 2007, Dunkelgrun et al 2008, Karkouti et al 2008a, De Santo et al 2009, Patel and Carson 2009, Weber et al 2009, Carrascal et al 2010, Gombotz 2011, Musallam et al 2011, Ranucci et al 2012, Gupta et al 2013, Gombotz et al 2014, Miceli et al 2014).
The preoperative diagnosis and treatment of existing anemia is of paramount importance for the subsequent course of disease (Gombotz 2011). It reduces the probability of allogeneic red blood cell (RBC) transfusion and improves the outcome. Therefore, patients undergoing cardiac surgery should—whenever permitted by the urgency of the operation—be referred as soon as possible to a preanesthesia clinic or similar institution (Sowade et al 1997, Goodnough and Shander 2012, Gombotz and Hofmann 2013). Ideally, such clinics will investigate and treat not only the anemia but also any other relevant concomitant diseases, including coagulation disorders, while making the necessary preparations for anesthesia.
Since it is very hard to predict the bleeding risk (Vuylsteke et al 2011, Gombotz and Knotzer 2013), it is crucial to take a detailed bleeding and coagulation history and to discontinue anticoagulants and platelet inhibitors in a timely fashion (Harder et al 2004, Nuttall et al 2006, Levi et al 2011, Tafur et al 2012, Emeklibas et al 2013). In special cases, required antiplatelet therapy can be provided by short-acting platelet inhibitors (Savonitto et al 2010). If the patient responds to the treatment of anemia, a hemoglobin rise of around 1 g/dL per week can be expected (Doodeman et al 2013).
The treatment of preoperative anemia can result in greater logistical efforts because of changes to the surgical schedule. However, the short-term use, or even a single dose, of erythropoietin a few days before surgery can significantly reduce the transfusion requirement (Yazicioglu et al 2001, Weltert et al 2010, Yoo et al 2011). Since erythropoietin gives rise to a relative iron deficiency, iron deficiency must be ruled out or treated before and during the course of therapy (Sowade et al 1997). A hematologist should be consulted in complex cases.
Preoperative autologous blood donation increases the risk of anemia, and it is time-consuming and expensive. It is therefore no longer used as a global measure (Gombotz et al 2000, Singbartl 2007).
The use of proton pump inhibitors to avoid gastrointestinal bleeding complications and to administer antibiotic prophylaxis is standard.
Patients undergoing elective surgery should be referred to the preanesthesia clinic as early as possible—ideally once the surgical indication has been established. Timely referral does not only enable the treatment of potential anemia but also the preoperative management of other risk factors.
6.1.3 Intraoperative Measures (Second Pillar of PBM)
The views presented here are subjective perceptions, based on the author’s own experiences; the methods have stood the test of time over several years of using a restrictive transfusion approach, including approaches in patients who declined transfusion. Experience has shown that it is rarely an isolated measure but rather the combination of various measures that leads to the desired outcome. Of the many ways to minimize blood loss, I would like to present the most important methods actually implemented in our department, which were also used for the 19 cardiac operations in Jehovah’s Witness patients described below.
▶ The sternum. The sternum plays a major role as a cause of continuous intraoperative bleeding because of its structure, with widely open red-bone-marrow sinusoids following sternotomy. In surgical terms, it should therefore be viewed as a parenchymatous organ. Although blood entering the surgical area can be collected, continuous aspiration with the cardiotomy suction device of the heart–lung machine causes hemolysis and leukocyte activation because the blood is exposed to air and the RBCs are mechanically destroyed by the roller pumps (Osborn et al 1962, El-Sabbagh et al 2013). During embryological development, the sternum forms from a paired ossification center, thus assuring the symmetrical perfusion of both sides of the body. Hence, precise midline sternotomy can reduce blood loss.
▶ Bone wax. Bone wax is commonly used in cardiac surgery to minimize blood loss. It is composed of a nonabsorbable mixture of 75 % white beeswax (cera alba), 15 % paraffin wax, and 10 % isopropyl palmitate as a softening agent. It does not have hemostatic activity; rather, its action derives from mechanical hemostasis. Once applied to the bone surface, bone wax is usually not resorbed (Sudmann et al 2006, Vestergaard et al 2010). Furthermore, bone wax acts as a physical barrier that inhibits osteoblasts from reaching the bone defect and thus impairs bone healing (Alberius et al 1987, Allison 1994, Vestergaard et al 2010). The use of bone wax is a major risk factor for the development of sternocutaneous fistulas (Steingrimsson et al 2009). Experimental studies have shown that when a bone defect is treated with bone wax, the number of bacteria needed to initiate an infection is reduced by a factor of 10,000 (Johnson and Fromm 1981, Nelson et al 1990, Gibbs et al 2004, Vestergaard et al 2010). Radiological bone healing assessed by a radiologist using computed tomography at 3 and 6 months postoperatively was significantly impaired in the bone wax group (Vestergaard et al 2014).
▶ Alternatives to bone wax. Given the drawbacks of conventional bone wax, we use a variety of commercially available local hemostatic products, including TachoSil (Takeda Austria) and SeraSeal (Wortham Laboratories). TachoSil is a sponge impregnated with a hemostatic agent based on equine collagen, human fibrinogen, and human thrombin. TachoSil has been used in cardiac surgery to seal graft anastomoses, bleeding from aortic sutures, bleeding from atrial sutures, etc. (Maisano et al 2009, Alizadeh Ghavidel et al 2014, Vida et al 2014). It is also suitable for immediate sealing of the sternum following sternotomy ( Fig. 6.1 ).
Another way to minimize bleeding from the sternum is to use SeraSeal, which is a liquid hemostatic agent containing agar and activated factors II, VII, IX, and X. SeraSeal is sprayed directly onto the bony surface of the sternum, where it forms a clot. Once the clot has formed, the surface should not be touched (e.g., with swabs) for a few minutes, until its structure has stabilized.
The traditional use of bone wax should be replaced by the use of modern local hemostatic products.
▶ Crucial point: harvesting the vein. The blood lost during vein harvesting for coronary artery bypass graft (CABG) surgery is taken up by the drapes and swabs and can normally not be retransfused (Markar et al 2010). A meticulous surgical technique is absolutely necessary to reduce this avoidable blood loss. We prefer the suturing of bleeding veins to the customary use of diathermy. The saphenous stumps are precisely ligated. Sternotomy and vein harvesting should be carried out as a collaborative effort. It is unfair to open the sternum as quickly as possible without allowing the assistant enough time to remove the leg vein. Enough time must be allowed especially under difficult circumstances, e.g., varicose veins, anatomical variations, or obesity ( Fig. 6.2 ).
Sternotomy and vein harvesting should be carried out as a collaborative effort.
6.1.4 Cell Salvage, Cardiotomy Suction, Minimally Invasive Extracorporeal Circulation Technologies, Swabs
▶ Cell salvage. Extensive use of a cell salvage device is imperative in blood-sparing cardiac surgery (Vonk et al 2013). After all, it ensures that fully functional RBCs are retransfused. However, if the volume of salvaged blood is large, the coagulation potential can be reduced because of the loss of plasma coagulation factors (Rollins et al 2012).
▶ Cardiotomy suction. The action of the roller pumps and the aspiration process due to cardiotomy suction can cause hemolysis and leukocyte activation because of the mechanical destruction of RBCs and the exposure of blood to air (Osborn et al 1962, Lau et al 2007, El-Sabbagh et al 2013). Timely and meticulous surgical hemostasis is absolutely necessary to interrupt the vicious circle of continuous bleeding and continuous aspiration from the sternum and the cannulation sites. These drawbacks can be reduced by setting the flow rate on the cardiotomy suction device to “low” and avoiding “excessive suctioning” (Svitek et al 2010). Make sure that the assistant or the instrument nurse does not confuse the cell salvage or cardiotomy suction device with the normal operating-room suction device (nonretransfusable). This could lead to the unintentional loss of large quantities of blood! Such mistakes are not uncommon when new members of the team are not thoroughly briefed at the start of the operation as regards the use of the three different suction systems. The best approach in our opinion is to use the handpiece of the operating-room (nonretransfusable) suction device only when required.
▶ Minimally invasive extracorporeal circulation technology. The use of minimally invasive extracorporeal circulation technology (MiECT) for CABG operations significantly reduces blood loss because of the centrifugal pumps (less hemolysis), smaller priming volumes, and autologous priming (less hemodilution), and decreases the risk of systemic inflammatory response syndrome thanks to the reduction of blood–polymer contact (Kofidis et al 2008, Anastasiadis et al 2013, Baikoussis et al 2014). The disadvantages resulting from MiECT as a closed system are the absence of a cardiotomy suction device and, in rare cases, restriction of the cardiopulmonary bypass (CPB) flow during heart luxation.
▶ Swabs. Frequent use of swabs results in extensive blood loss from the surgical area, especially if large numbers of blood-soaked swabs are discarded. We try to minimize the number of swabs used, an approach that has led to the “single-swab method.” After its use, this single, blood-soaked swab is rinsed in saline, carefully squeezed out into a bowl by the instrumentation nurse, and reused by the surgeon. The recovered blood is later processed with the cell salvage device.
▶ Disastrous bleeding. We distinguish between expected bleeding (e.g., bleeding from the sternum or from cannulation sites) and disastrous bleeding (e.g., tearing of vital sutures and ligatures at the aortic and atrial cannulation sites as well as bleeding from major blood vessels) (Dyke et al 2014). Surgical redundancy is increased by repeat suturing of these vital sites because it minimizes the risk of failure of both sutures.
6.1.5 Postoperative Measures
Any increased bleeding tendency should be treated immediately at the end of the operation. Hypotensive circulatory situations can mask postoperative secondary bleeding and should be avoided. The body temperature should postoperatively be restored as soon as possible, and blood draws for laboratory diagnostic purposes should be limited to the absolute minimum. The use of point-of-care coagulation diagnostic tests has advantages over determination of the activated clotting time (Petricevic et al 2014). Their validity is on a par with that of conventional laboratory tests. However, they have only limited power to diagnose the underlying coagulation disorder (Pekelharing et al 2014, Welsh et al 2014). Nonetheless, point-of-care tests confer advantages such as rapid test results and therefore timely treatment intervention. Only weak evidence is available to support the repeated demand for a widespread use of fibrinogen—like all blood derivatives, this should only be administered when indicated (Warmuth et al 2012, Bilecen et al 2013, Wikkelso et al 2013, Lunde et al 2014). Conversely, the peri-operative administration of tranexamic acid reduces blood loss, but—in rare cases—it is associated with the onset of generalized cramps (Dietrich et al 2008, Koster et al 2013).
If, despite all these measures, there is heavy postoperative bleeding, extensive rethoracotomy must be performed as soon as possible—definitely before the onset of coagulation disorders (Vivacqua et al 2011). Postoperative bleeding is not uncommon in cardiac surgery and is difficult to classify (Dyke et al 2014). Therefore, the indication for rethoracotomy must be tailored to the individual patient. Blood lost from the chest drains can be collected, for example, by the closed Drentech Emotrans system (Redax), and directly retransfused to the patient using a special connecting line to the cell salvage device. This does not only reduce the transfusion requirement, but it also helps to preserve the oxygen transport capacity, and ultimately improves the outcome (Axford et al 1994, Schmidt et al 1995, Dalrymple-Hay et al 1999).
In case of postoperative bleeding, extensive rethoracotomy must be performed as soon as possible—definitely before the onset of coagulation disorders.
Based on the current data, the routine postoperative administration of iron and erythropoietin cannot be recommended and must be investigated in future studies (Madi-Jebara et al 2004).
6.1.6 Cardiac Operations in Jehovah’s Witnesses
The religiously motivated refusal of blood transfusions by Jehovah’s Witnesses constitutes an ethical challenge. However, surgical operations can be performed for Jehovah’s Witnesses while utilizing all three pillars of PBM with comparable risk or even a better outcome (Gombotz et al 1985, Gombotz et al 1989, Stein et al 1991, Sparling et al 1996, Rosengart et al 1997, Gohel et al 2005, Stamou et al 2006, Casati et al 2007, Berend and Levi 2009, Emmert et al 2011).
Between 2008 and 2014, 46 operations—19 of which were cardiac surgery procedures—were carried out for Jehovah’s Witness patients at the First Surgical Department for Cardiovascular and Thoracic Surgery at Linz General Hospital in Austria ( Table 6.1 ). These operations were performed by two surgeons. No patient received a transfusion. Three patients would have accepted a transfusion if based on a vital indication, whereas the remainder categorically refused transfusions. Rethoracotomy was not needed in any of these patients and no patient died ( Table 6.2 ).
As can be seen from Fig. 6.3 , the hematocrit did not drop below 20 % in any of the 19 patients.
The cardiac surgeon is confronted with the particular challenges associated with a perioperative multidisciplinary strategy, such as PBM, to improve outcome through the avoidance of surgical blood loss (second pillar of PBM). Of the various blood-sparing methods available, those acquired through many years of surgical experience have been presented here. Experience has shown that it is rarely an isolated measure but rather a combination of various measures that contributes to the desired outcome. Using this approach, we were able to successfully perform 19 cardiac surgery operations (between 2008 and 2014) for Jehovah’s Witness patients without RBC transfusions. Clinical evidence shows that the use of appropriate blood conservation measures for patients who do not accept transfusions results in similar or better outcomes, compared with transfused patients (Pattakos et al 2012, Frank et al 2014b). We therefore believe that “every patient should be treated as a Jehovah’s Witness.”
6.2 PBM in Pediatric Cardiac Surgery
Although many of the measures that are cornerstones of a modern PBM strategy in adults have to be modified to be applicable in children undergoing cardiac surgery, the underlying principles stay the same: optimization of the RBC mass, minimization of blood loss and bleeding, and utilization of the physiological tolerance to anemia. However, because of different time frames, measures especially focusing on the preoperative period are largely hampered. Many of the surgical procedures in pediatric cardiac surgery have to be performed in the first few days or weeks of life and, as a consequence, prolonged preparation of the patient is impossible. However, unnecessary transfusions can be avoided even in these patients if several arrangements are undertaken.
6.2.2 Risks of Anemia and Transfusion in Children with Congenital Heart Disease
In the last few years, it has been demonstrated convincingly in adult as well as in pediatric cardiac patients that anemia is associated with a higher risk of mortality (Kammache et al 2012). In both populations, anemia (not only extreme anemia but also moderate anemia) is an independent driver of undesirable outcomes (Musallam et al 2011). The most obvious solution for this problem seems to be transfusion, which is the only way to immediately increase the amount of RBCs. Although the application of blood products is safer than ever before, both transfusion-transmitted infections and noninfectious serious hazards of transfusion can occur, limiting the positive effects of the administration of allogeneic blood products. Taking recently published studies into account, it has to be stated that RBC transfusion does not only increase the morbidity but also the mortality because of a conflicting risk–benefit ratio (Pattakos et al 2012). Therefore, alternative approaches are also desirable in this patient group.
6.2.3 Optimization of the RBC Mass
In many cases, congenital heart disease has to be treated by surgery within the first days of life to reduce mortality (Donofrio et al 2014). This tight time frame reduces the options to optimize the RBC mass preoperatively. However, anemia is not rare in pediatric patients undergoing cardiac surgery. Depending on the population studied, a pre-operative hemoglobin concentration as low as 11.8 g/dL is common in pediatric patients (Mulaj et al 2014). Unfortunately, preoperative anemia is also one of the most important drivers of intraand postoperative RBC transfusion in these patients (Mulaj et al 2014). However, the measures that have been demonstrated to be effective in adults lack good evidence in this patient population.
In children undergoing open heart surgery, preoperative anemia is one of the most important drivers for RBC transfusion and is associated with increased morbidity and mortality.
▶ Iron supplementation and erythropoietin. Furthermore, the Food and Drug Administration and the European Medicines Agency have placed severe restrictions on the use of many intravenous iron and erythropoietin preparations. This situation is not different to the use of other drugs in a pediatric patient population; however, only a limited number of studies exist that show the utility of these drugs in the environment of pediatric cardiac surgery. As a consequence, no general recommendation can be given to use these drugs in this situation.
However, the complete, general avoidance of iron and erythropoietin might exclude a potent strategy to adequately prepare pediatric patients. Anemia from iron deficiency is one of the most common alimentary deficits in children. Oral treatment with iron preparations may take months to correct the anemia. Modern intravenous iron preparations seem to be a safe alternative when a rapid reversal of iron deficiency anemia is necessary. The peak response following intravenous iron administration occurs in approximately 10 days. Modern iron preparations, such as ferrous gluconate and iron sucrose, are safer than the old ones, especially iron dextran, which may cause anaphylactic reactions in susceptible individuals. Low levels of iron and erythropoietin provide a rationale for the use of intravenous iron or erythropoietin in children. A recent randomized clinical trial (RCT) demonstrated that the combined treatment of high-dose erythropoietin (300 U/kg per day intravenously or 700 U/kg three times per week subcutaneously), iron (1.5 mg/kg per day intravenously or 9 mg/kg per day orally), folate (100 mg/kg per day orally), and vitamin E and B12 during the first weeks of life significantly reduced the transfusion need of infants with an extremely low birth weight (Haiden et al 2006).
To date, it is not known whether the short-term preparation of children with iron or erythropoietin in the cardiac surgery setting is effective in reducing the number of transfusions or in improving survival rates. Comparable studies in adults provide strong evidence that the application of iron or erythropoietin even some days before or after surgery might reduce the number of allogeneic RBC transfusions needed (Muñoz et al 2014b).
6.2.4 Minimization of Perioperative Blood Loss
Although most modern strategies to reduce peri-operative blood loss have been developed in adult patients, some of the underlying ideas are also applicable to the pediatric patient population.
▶ Cardiopulmonary bypass support. Most patients who undergo surgery for congenital heart defects require CPB support. The CPB circuit is usually primed with a mixture of fluids to prevent abrupt intravascular volume depletion caused by the elongation of the circulatory pathway. In addition, it is often necessary to mix RBC components with the priming fluid to prevent excessive hemodilution. In adult cardiac surgery, a relatively small-volume RBC transfusion will suffice to maintain adequate levels of hematocrit during CPB. However, in neonates and infants, the volume of the total priming fluid may represent 200 % to 300 % of their total blood volume. Consequently, the RBC volume that is initially mixed with the priming fluid frequently exceeds 50 % of the total blood volume. However, it is possible to reduce the priming volume considerably by so-called mini-volume priming methods. Among other things, oxygenators and hemofilters with small priming volumes, vertically aligned pump heads, vacuum-driven venous drainage, and small venous-circuit-tubing diameters might help to reduce the amount of allogeneic blood necessary to prepare the CPB circuit (Chang et al 2014b). In many centers, priming of the CPB circuit is additionally performed with fresh frozen plasma (FFP). However, the prophylactic use of FFP in the priming solution does not have obvious clinical benefits in pediatric patients undergoing cardiac surgery (Miao et al 2015).
Minimizing the priming volume is one of the key measures in pediatric cardiac surgery.
▶ Coagulation management. As in adult cardiac surgery, intraoperative blood loss in pediatric surgery does not only depend on the surgical technique but also on the sophisticated management of coagulation. Timely correction of the coagulation potency during surgery is effective in avoiding unnecessary perioperative bleeding, and it is known for adult cardiac surgery that special emphasis on the perioperative management of coagulation can reduce the number of necessary RBC transfusions. However, there is considerable variation in transfusion practice with respect to the threshold for FFP transfusion (Karam et al 2014), and it has to be stated that FFP transfusions are often prescribed for nonbleeding critically ill children.
▶ Iatrogenic anemia. Despite the fact that laboratory blood tests are essential for the monitoring and management of infants and children after heart surgery, excessive blood tests can lead to iatrogenic anemia and subsequent RBC transfusion. This is especially true in pediatric cardiac surgery patients, where the circulating blood volume is small and blood sampling is convenient because of indwelling catheters in most postoperative patients. Therefore, one very effective measure to reduce perioperative blood loss is to restrict postoperative laboratory tests as much as possible. Such an approach can effectively reduce the postoperative occurrence of anemia and thereby the transfusion of RBCs (Delgado-Corcoran et al 2014).