Waters, Jonathan h.
Transfusion of blood from one human to another was first proposed in 1818 by James Blundell. With this idea, he subsequently transfused 10 women suffering from postpartum hemorrhage.1 Without the knowledge of ABO typing, Blundell succeeded in saving five of these women.2 After Blundell’s innovation, allogeneic (human-to-human) transfusion became an accepted therapy; however, during this early era, it was dependent upon the skill of the treating physician and the availability of a donor. These two conditions were not always easy to achieve, especially in the rural setting. In 1874, in a setting without an available donor, William Highmore in observation of a woman exsanguinating from a postpartum hemorrhage thought that “the haemorrhagic blood of the woman, and defribrinated and warmed” might have provided the only opportunity for her survival.3 Thus, the concept of autotransfusion was conceived. Over the ensuing decades, blood was collected via “mopping, ladling, bulb suction and line suction….Citrate or hemodilution served as an anticoagulant and cheese cloth and fine gauze were used as a filter.”4
In 1900, Karl Landsteiner discovered the ABO blood types and, several years later, the Rh system. Because of the ease and convenience that banking of allogeneic blood provided, as well as a perceived safety, allogeneic transfusion became the dominant treatment for severe anemia. In the modern era, blood transfusion is now the most common medical therapy provided for hospitalized patients.5 During the early to mid 1980s the HIV epidemic gave clinicians the first impetus to think about other methods of providing for the blood needs of their patients. This led to resurgence in the use of autotransfusion or what is more commonly referred to as blood salvage.
The process of collecting autologous blood and its reinfusion has many synonyms including autotransfusion, blood salvage, and cell saving. Salvaged blood has been shown to have high concentrations of free hemoglobin, inflammatory mediators, and other cellular debris (Table 1). With these contaminants, many investigators recommend that the salvaged blood be washed before readministration.6 In the intraoperative setting, salvaged blood is generally washed. In the postoperative setting, where the volume of shed blood is relatively small, the blood is sometimes washed but is generally readministered in an unwashed state. Postoperative unwashed blood salvage is most commonly performed in orthopedic surgery where blood from a surgical drain is readministered. For this review, the intraoperative form of blood salvage will be the focus. If this technique is used appropriately, several blood volumes of red cells can be recovered and readministered.
Collection of Blood
The blood salvage system can be generally broken into a collection system and a processing system (Figure 1). There are four components that allow for the collection of shed surgical blood. They include a suction line and suction tip that is used in the surgical field; suction for removal of blood from the surgical site and delivery of the blood to a collection reservoir; an anticoagulant to prevent clotting; and the collection reservoir. Salvage of erythrocytes begins with aspiration of blood from the surgical wound. At the suction tip, shed cells are mixed with an anticoagulant. The cells are then stored in a collection reservoir to await processing.
For blood salvage systems to work it is necessary to deliver shed blood to a collection reservoir. This is done through negative pressure aspiration. How this suction pressure is applied changes the mechanical forces applied to the red cell. Shear forces occur any time a fluid moves in contact with a solid surface.7 Shear-induced hemolysis can be produced with high suction pressures. So, the lowest tolerable suction pressure should be applied when sucking blood from the surgical field. Negative pressure is typically regulated to 80–120 torr, which is adequate for most surgical procedures.8, 9 The vacuum level can be temporarily raised to clear the field in the event of massive blood loss, then reduced to a lower level.
Selection of the style of the suction tip and the method of use can also affect the degree of turbulence and red cell recovery rates (Figure 2). Entrainment of air causes formation and breakage of bubbles, causing cellular destruction. To minimize air entrainment, suction tips should be immersed in the shed blood during collection, and not dipped in and out. Whenever possible, shed blood should immediately be aspirated and not be allowed to pool in contact with the wound surface. Prolonging contact time exponentially activates the coagulation and inflammatory systems. Occasional irrigation of the wound with anticoagulant solution will help prevent loss of salvageable blood caused by clot formation.
Gauze pads that have been used to wipe blood away from the surgical field can be a rich source of salvaged red cells. It has been estimated that each 18” × 18” laparotomy sponge can contain up to 100 ml of red cells.10 These sponges should be soaked in a basin of saline and wrung out before their discard. This saline rinse solution can then be periodically suctioned into collection reservoir for return of the red cells. This practice has been reported to increase red cell retrieval rates by 28%.11 Many fear this practice because of cotton fibers possibly being entrained into the blood from the sponge or possible bacterial contamination being introduced into the system via the sponge. In unpublished data from the Cleveland Clinic, no cotton fibers were retrievable from rinse solutions. Discussion with the manufacturer of these sponges revealed that no fiber shedding results from a tight weave of the cotton fibers and a double-washing process. In addition, macroaggregate filtering at the collection reservoir should remove large particles such as cotton fibers.
As blood is suctioned from the surgical field, an anticoagulant is mixed with the blood. The purpose of the anticoagulant is to prevent clot formation in the collection reservoir or processing system. Clotting of blood in the collection system will result in loss of otherwise recoverable blood as well as the need for system replacement when large clots obstruct blood flow through the system. Either citrate or heparin can be used for anticoagulation during blood salvage. Some controversy exists as to which anticoagulant is best.12, 13 Because of its low cost and ready availability, heparin is most commonly used. Added to a carrier such as normal saline at a dosage of 30,000 units/L of heparin, the solution is then titrated through the aspiration suction system at a rate of 15 ml per 100 ml of collected blood. Over administration of heparin during shed blood salvage is of no consequence in a cell-washing system. Adequate washout will remove all but a trace of heparin with less than 10 units residual remaining in the final blood product.
Citrate has also been used as an anticoagulant. The administration rate for citrate bearing anticoagulants (ACD, CPD, etc.) is also 15 ml per 100 ml of collected blood. On reinfusion, rapid liver metabolism makes citrate toxicity a difficult state to achieve. In compromised liver function, correction with small doses of calcium provides immediate and nontoxic reversal. At the Mayo Clinic in Rochester, Minnesota, 7500 units/L of heparin is mixed in a liter of the citrate solution. Use of this solution has been noted to eliminate the commonly observed protein deposits on the interior surface of the processing bowl.
The reservoir is the collection site for blood as it awaits processing. In general, three times the size of the processing bowl is the minimum amount of blood, which will be needed in the reservoir to fill the processing bowl. The reason for the three times multiplier is that the final product is concentrated into a range of 15–25 gm/dl hemoglobin levels, depending upon the type of machine used. As blood is lost from the patient, it typically ranges in concentration from the starting patient hemoglobin level of 13–15 gm/dl to the transfusion point of 7 gm/dl. As a result, there needs to be enough red cell mass shed to result in the final hemoglobin level of 15–20 gm/dl. In addition, some blood is destroyed during processing. Thus, approximately three times the bowl size is what is needed to process a complete bowl. Processing bowls typically range from 125 to 250 ml in volume, depending on the manufacturer.
The collection reservoirs are generally available with filter sizes ranging from 40–120 µ. When inadequate anticoagulation occurs and clot forms in the collection reservoir, red cells can be trapped in the clot. Smaller filter sizes tend to be more prone to trapping red cells. These red cells can be retrieved by mechanically agitating the reservoir while simultaneously infusing normal saline into the collection reservoir. This can be performed by using one of the suction lines, or infusing saline directly through ports on the top of the reservoir. These ports are available on some manufacturer’s reservoirs but not all. Surprisingly, large quantities of red cells can be retrieved through this mechanical agitation.
Blood Salvage Processing System
The working component of blood-washing devices has evolved over the years. This is the separation chamber which, in essence, is a centrifuge chamber. Regardless of bowl design, all washing systems process blood components using basic laws of physics.
Processing starts as blood is pumped from the collection reservoir. It enters the bowl through a central straw (Figure 3), exiting from the bottom of the bowl while the centrifuge is spinning. The speed at which blood can be moved into and out of the bowl is partially dependent on the physical characteristics of this straw.
As the blood enters the processing bowl, the bowl is spinning rapidly to generate centrifugal force. Separation of salvaged blood components depends on the balance between densities of the various constituents of blood (Table 2), the fluid flow rate, and the centrifugal forces applied in the processing bowl.
As the cell-separation bowl spins around a central vertical axis, centrifugal forces (G force) are generated radially around the central axis of rotation. The centrifugal force generated by a blood salvage processor is proportional to the rotation rate of the rotor (in rpm) and the distance between the rotor center and the walls of the bowl. The force applied to a particle changes depending on its mass. Because red cells are heavier than other blood components, they will sediment against the walls of the bowl with the smaller, lighter particles (plasma) sedimenting closer to the core of the bowl.
As blood is pumped into the bowl, force of the pumping will be exerted on the contents of the bowl. Thus, two forces (pumping and centrifugal) will be applied to the bowl contents. Because the plasma and red cell stroma and other debris have less mass than the red cells, the centrifugal force applied to them is less. Thus, these lighter particles will preferentially exit the bowl. If blood is pumped at too fast a rate, or with too great a force, this pumping force will overcome the centrifugal force on the red cells, thus pushing the cells out of the top of the bowl and into the waste bag. Because the pumping force can overcome the centrifugal force when rapid pump speeds are chosen, the bowl needs to be observed carefully to guarantee that red cells are not being lost during massive blood loss where rapid pumping is chosen. Pumping of shed blood is continued until the packed red cells nearly fill the bowl and the advancing erythrocyte column reaches the midpoint of the upper bowl shoulder. By filling the bowl with compacted red cells, unwanted irrigation fluids and contaminated plasma are discharged from the bowl to a waste bag.
Concentrating red cells, while expressing irrigants and plasma, removes 70–90% of the soluble contaminants in salvaged blood. However, many contaminants are still retained. These contaminants can be further removed by washing. Washing takes place by changing the solution being pumped into the bowl from salvaged blood to a wash solution. This wash solution is generally 0.9% saline solution (normal saline) but one investigator has suggested that a more balanced isotonic solution such as Lactated Ringer’s solution may offer slight advantages when compared with normal saline.14, 15 This advantage relates to minimizing the chloride load, which would be administered to the patient after a saline wash.
The wash solution percolates through the red cell pack, with the wash solution carrying away lighter debris and irregular agglomerates into the wash bag. Such washing also progressively dilutes contaminated plasma between the cells reducing soluble contaminants. Washing is considered complete when the effluent line appears clear to the eye and a wash volume of at least three times the bowl volume has been used.
To empty the washed blood, the roller pump is reversed, and clean, packed red cells are aspirated from the bowl through the central straw into a primary reinfusion bag. Simultaneously, sterile air is drawn from the waste bag back into the bowl. Once the bowl is emptied of blood, another cycle may begin. It is important that the blood in the primary reinfusion bag be moved into a secondary bag before readministration. Air will accumulate in the primary reinfusion bag over time. If blood is administered directly from the primary reinfusion bag, the patient is placed at risk of air embolism. Through the use of a secondary bag, blood is moved out of the primary reinfusion bag, followed by air being “burped” out of the secondary bag back into the primary reinfusion bag. Under no circumstances should a pressure cuff be used on the primary reinfusion bag when blood is being directly reinfused into the patient.
Good practice also dictates the use of blood filters during transfusion. Although 170 µ blood filter sets are routinely part of a blood administration set, microaggregate filters of 40 µ are recommended by the machine manufacturers. In addition to a microaggregate filter, a leukocyte depletion filter may be used. A leukocyte depletion filter works through a different mechanism than does a microaggregate filter. A simple microaggregate filter is a screen filter and works much like a window screen. A leukocyte depletion filter works by binding DNA containing cellular material to a polyethylene filter material. These filters have been demonstrated to remove bacteria, cancer cells, or amniotic fluid contaminants, which can frequently contaminate salvaged blood.
Indications for Blood Salvage Use
In the past, the AABB (formerly known as the American Association of Blood Banks) has recommended the following general indications for blood salvage use: the anticipated blood loss should be 20% or more of the patient’s estimated blood volume; blood would ordinarily be crossmatched; more than 10% of patients undergoing the procedure would require transfusion; the mean transfusion for the procedure should exceed 1 unit.16 These recommendations are derived from the comparison of allogeneic blood costs to perceived blood salvage cost. Because these recommendations were developed, the cost of allogeneic blood has escalated although a better understanding has been gained of the costs associated with blood salvage. For this reason, implementation of blood salvage should be considered when much smaller amounts of blood loss are anticipated.
Accurately predicting the probability of sizeable blood loss and need for allogeneic transfusion is difficult. Because of this lack of predictability, implementation of blood salvage should start with a collection system that includes a reservoir, a suction line, and an anticoagulant. This simple collection system has been called a stand-by setup in anticipation of potential major blood loss. This collection or a stand-by setup costs comparably to the reagent costs for typing and crossing 2 units. Although a major paradigm shift, hospitals should consider implementation of a stand-by setup rather than the type and cross. In cases where the blood loss is certain, such as in a thoracoabdominal aneurysm repair, it is reasonable to bypass the stand-by setup and set up all components necessary to process blood. Before adopting this type of strategy, it is important to take into account whether one’s hospital’s strategy is to contract out the blood salvage service or provide it through an in-house service. It is beyond the scope of this article to address all the financial permutations of blood salvage services.
There are many types of cases where blood salvage might be indicated. The most common setting is in cardiac surgery.17 The types of cases should be individualized by the institution and the surgeon performing the procedure. The patients starting hematocrit, sex, age, and body weight can all influence the risk of receiving blood products.18 Table 3 lists many of the surgical procedures that should be considered for implementation of blood salvage.
Contraindications to Blood Salvage
The list of contraindications to blood salvage is extensive (Table 4); however, most contraindications are relative rather than absolute, which means that little data exist to support the danger of these proposed contraindications. When a decision is being made to not use blood salvage, it needs to be considered in light of the known risks associated with the alternative therapy, which is allogeneic blood.
Relative contraindications to blood salvage encompass a wide range of materials that, if incorporated into the salvaged blood product, could potentially injure the patient upon readministration. Definite contraindications would include anything that results in red cell lysis. This would include sterile water, hydrogen peroxide, and alcohol. If blood is washed with these solutions or a hypotonic solution is aspirated into a collection reservoir, it would result in red cell hemolysis. In the presence of these contaminants, lysed cells will be washed out if the blood is adequately washed but it is best to avoid incorporation into the blood salvage system. If the blood is administered without adequate washing, it could result in renal insufficiency and failure, decreases in hematocrit, elevations in serum lactate dehydrogenase level, increases in total serum bilirubin concentration, disseminated intravascular coagulation, and, potentially, death.19, 20
Many contraindications to blood salvage are not as definitive as those just described. This would include blood aspirated from contaminated or septic wounds, obstetrics, and malignancy.
The impact of blood salvage processing on blood that has been bacterially contaminated was first investigated by Boudreaux,21 who inoculated expired units of blood with bacteria and found that washing was capable of reducing contamination to 5–23% of the starting contamination. In a similar study, Waters et al.22 found an approximately 99% reduction in bacterial contamination when the combination of cell washing and a leukocyte depletion filtration was performed. In the same article, a dose–response curve was generated, which showed that a 99% reduction of a starting load of bacteria of 107 still left 105 bacteria. This level of contamination was identified to occur in surgical procedures where gross fecal contamination of the blood was observed. Thus, differentiating between gross contamination and possible or unobserved contamination is important.
It is important to keep in mind that during the course of most operations, a bacteremia is present related to the surgical trauma. Broad-spectrum antibiotics are routinely used to manage this routine bacteremia. Several studies have suggested that these drugs add additional safety when contaminated salvaged blood is readministered.23, 24
Dzik and Sherburne,25 in a review of the controversies surrounding blood salvage, pointed out that allogeneic transfusion leads to an increase in infection rate and that when faced with bacterial contamination of salvaged blood, a clinical decision needs to be made as to which therapy offers the least risk to the patient. Known risk exists with allogeneic blood, yet only theoretical risk is associated with salvaged blood. Until data is generated supporting the theoretical risk of salvaged in these circumstances, it seems reasonable to avoid the known risk of allogeneic blood through the use of blood salvage.
One of the leading causes of death during childbirth is hemorrhage, so the use of blood salvage would naturally be attractive26, 27 When applying blood salvage during the peripartum period, shed blood can be contaminated with bacteria, amniotic fluid, and fetal blood. Amniotic fluid contamination is feared because of the theoretical potential to create an iatrogenic amniotic fluid embolus. Unfortunately, amniotic fluid embolus rarely occurs (1:8000–1:30,000 deliveries), making definitive study impossible. Thus, we are left to look at surrogate markers, which might be associated with the syndrome. Waters et al.28 demonstrated that leukocyte depletion filters along with cell washing will remove fetal squamous cells to an extent comparable to the concentration of these cells in a maternal blood sample after placental separation. From this study it was concluded that the combination of blood salvage washing and filtration produces a blood product comparable to circulating maternal blood with the exception of the fetal hemoglobin contamination. Support for the use of blood salvage in obstetric hemorrhage now encompasses 390 reported cases where blood contaminated with amniotic fluid has been washed and readministered without filtration.29–31
The last area of controversy is blood salvage in cancer surgery. Administration of tumor-laden blood from blood salvage would also seem to be contradictory to a good patient outcome; however, during tumor surgery, hematogenous dissemination of cancer cells is common.32–34 In fact, it has been demonstrated that a high percentage of patients presenting for cancer surgery have circulating tumor cells but this presence does not seem to correlate with patient survival.35 It has been estimated that of these circulating tumor cells, only 0.01–0.000001% have the potential to form metastatic lesions.36 So, the importance of administration of tumor cells via blood salvage blood must be questioned.
With this understanding, the use of leukocyte depletion filters is advocated for removal of tumor cells during cancer surgery. These filters have been used for filtration of malignancy in blood salvage for urologic surgery,37, 38 pulmonary surgery,39 and in a variety of cell lines that were used to contaminate discarded blood.40, 41 These studies have all concluded that leukocyte depletion filters were highly effective at removing tumor cell contamination.
Blood salvage during tumor surgery has been studied in hepatic resection for malignancy and urologic oncology.42–44 In these uncontrolled studies, actual outcome was compared with expected outcome. No increases in metastasis or death were seen, thus suggesting that diffuse cancer metastasis does not occur after blood salvage use. In these studies, the use of leukocyte depletion filters was not mentioned.
To date, two studies have been performed evaluating the use of blood salvage in controlled trials. One study was prospective whereas the other was retrospective.45, 46 In both these studies, patients undergoing radical retropubic prostatectomy were compared with preoperative autologous donation. Both studies demonstrated that outcome was equivalent. Again, this would suggest that massive metastasis does not occur because of the use of blood salvage.
Complications of Blood Salvage
The process of blood salvage is associated with few complications. Air embolism is a concern if the primary reinfusion bag of the blood salvage circuit is directly connected to the patient’s vascular access.47 This complication can be prevented by simply transferring the blood into a secondary reinfusion bag, as was previously discussed. When using a leukocyte depletion filter, the filter should be given to the anesthesiologist for use. These filters should be changed after every 500 ml of blood. A blood pressure bag pressurized to 300 mm Hg should be applied to the blood salvage unit to move the red cells through the leukocyte depletion filter. Pressures greater than 300 mm Hg will pressurize contaminants through the filter. If the autotransfusionist places the filter between the holding bag and the transfer bag, it will not be possible to remove the air in the unit.
Blood salvaged during removal of pheochromocytomas has been shown to cause hypertension in patients after reinfusion,48 because extensive washing does not completely eliminate epinephrine and norepinephrine. Likewise, oxymetazoline (Afrin, Merck & Co., Inc., Whitehouse Station, NJ) nasal spray, which is sometimes used during ear, nose, and throat surgery, may remain in salvaged blood in high enough concentrations after washing; therefore, hypertension and tachycardia may ensue after readministration.
Some authors have attributed a dilutional coagulopathy to blood salvage. Blood lost during a surgical procedure contains all components of blood. Processing of the blood will only return red cells without the coagulation factors and platelets. The coagulation factors and platelets will be removed with the processing so that upon readministration, the remaining coagulation factors and platelets will be diluted. However, this effect is not different than what would occur with transfusion of allogeneic red blood cells, which also contain no coagulation factors nor platelets.
Blood Salvage Efficiency
Mathematical modeling of blood salvage has revealed that small changes in red cell processing efficiency can make large differences in the maximum allowable blood loss that a patient can sustain before allogeneic transfusion therapy.49 These models suggest that a 70 kg patient with a starting hematocrit of 45% can sustain a blood loss of 9,600 ml if a transfusion guideline of 21% is used and blood salvage captures 60% of lost red blood cells. The sustainable blood loss rises to 13,750 ml if 70% red cell recovery is achieved. This small change in red cell recovery with a large change in the ability of a patient to avoid a blood transfusion highlights the importance of optimizing the blood salvage system.
Rheologic characteristics of a patient’s red cell membrane may make them more or less prone to hemolysis during blood salvage. More hemolysis means fewer red cells to return to the patient. Red cells from premenopausal women appear to have less susceptibility to mechanical forces than do red cells from men or postmenopausal women. Additionally, the rheology of the red cells may change depending on the fluid environment in which they are suspended. The osmotic fragility of erythrocytes can be affected by pH, temperature, and the electrolyte and colloid composition of the suspending medium.50–53 Further work needs to be performed in vitro on factors that alter red cells’ tolerance of the mechanical forces exerted upon them during blood salvage processing.
Recent findings would suggest that every effort should be made to minimize transfusion of allogeneic blood. The most efficacious way of doing so is through the use of blood salvage systems. These systems allow for the collection and return of multiple blood volumes of red blood cells. Better understanding of how to maximize the collection and return of red blood cells is warranted.
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red blood cells; surgery; cell saving; cell salvage