The use of intraoperative cell salvage for cesarean delivery has historically been controversial. In 1818, James Blundell first attempted a cell salvage transfusion by using saline to wash the bloody swabs of patients with postpartum hemorrhage.1 Although the technology and safety of cell salvage have markedly improved over the past 2 centuries, concerns of causing an iatrogenic amniotic fluid embolism or inducing maternal alloimmunization have prevented cell salvage from becoming a common method of blood conservation in parturients for whom cell salvage might otherwise be indicated for postpartum hemorrhage.
The incidence of postpartum hemorrhage in the United States increased by 26% between 1994 and 2006, primarily because of an increase in uterine atony.2 Approximately 10% of women diagnosed with uterine atony require transfusion.2 Although there have been significant improvements in reducing the infectious risk of allogeneic blood transfusions over the past several decades,3 patients and providers still have concerns about the safety of transfusions.4 Furthermore, the refusal of certain patients to accept blood products and ongoing shortages in the blood supply have led to increased interest in strategies to avoid allogeneic transfusion, such as the use of cell salvage.4 Medical advancements, such as the use of Rho (D) immune globulin (RhoGAM) for the prevention of maternal alloimmunization, and changes in the understanding of the pathophysiology in amniotic fluid embolism have resulted in the increased acceptability of cell salvage in obstetrics.
The purpose of this article was to review the risks and efficacy of cell salvage in the obstetric population.
OVERVIEW OF CELL SALVAGE TECHNIQUE
Cell salvage in the obstetric population is comparable to the technique used in the general population with 2 important exceptions. It is a common practice to use a separate suction source and to waste blood and amniotic fluid collected before the delivery of the placenta.5 The addition of leukocyte depletion filters to the cell salvage circuit is also advised.6 Leukocyte depletion filters have been shown to satisfactorily reduce levels of contaminants, such as lamellar bodies, phospholipids, squamous fetal cells, and amniotic fluid–derived tissue factor. The latter 2 have been implicated in the pathogenesis of amniotic fluid embolism.5–9 Waters et al.5 compared contaminants in maternal venous blood and postwash, postfiltration cell–salvaged blood (Table 1). Except for a slightly higher concentration of fetal hemoglobin in the cell-salvaged blood, the levels of contaminants were lower or no different in the salvaged than maternal venous blood. Amniotic fluid–derived tissue factor, which is a potent initiator of coagulation and has been implicated as a possible mechanism for the disseminated intravascular coagulation seen in amniotic fluid embolism, is completely removed by modern cell salvage equipment and processing.5,10
GENERAL RISKS OF CELL SALVAGE
To date, there have been 7 peer-reviewed studies that collectively included >299 obstetric patients who have received cell-salvaged autologous blood. None of these studies has reported serious complications (Table 2).9,11–17 The potential risks of cell salvage in the obstetric population parallel the risks in the general population. Dilutional coagulopathy from transfusion of large volumes of salvaged blood is rare, with only a single case report of an obstetric patient who had received >2 L of salvaged blood.18 Bacterial contamination of cell salvage units is surprisingly common, but there have been no reported cases of sepsis or infection attributable to autologous transfusion of salvaged blood.7,12,19 There are several cases in the literature describing hypotension after the administration of salvaged blood administered through a leukocyte depletion filter.20–23 In several cases, there was a temporal association between the administration of salvaged blood and subsequent hypotension and the rapid resolution with cessation of the transfusion. Disruption of leukocytes is presumed to cause a release of cytokines, leading to hypotension.21 The U.S. Food and Drug Administration recommends that the transfusion be immediately discontinued if there is a precipitous decrease in arterial blood pressure during the administration of filtered salvaged blood.a Because there is limited evidence to suggest that leukocyte depletion filters are harmful, clinicians should continue to use these filters in the obstetric setting. Technical errors with the cell salvage equipment are rare. Hemolysis related to the use of an improper wash solution has been reported in 2 nonobstetric cases, one of which progressed to disseminated intravascular coagulation. There is one reported case of apparent heparin toxicity from inadequate washing that resolved with protamine.19 It is recommended that a trained technician manage the cell salvage circuit, and a standardized inspection of every salvage unit be performed before reinfusion.24
RISKS OF CELL SALVAGE UNIQUE TO OBSTETRICS
Historically, maternal alloimmunization was a major concern of cell salvage use. Cell salvage machines are unable to discriminate between maternal and fetal erythrocytes. The latter make up an estimated 1.5% of recovered erythrocytes when cell salvage is used during cesarean delivery.8,19 The Rh antigen is the primary concern because ABO antigens in the fetus are not well-developed. Rho (D) immune globulin (RhoGAM) is administered for the prevention of maternal alloimmunization, and the Kleihauer-Betke test is used to quantify exposure and calculate the appropriate dose necessary for Rh-negative mothers after an autologous transfusion. Studies have found that required doses of RhoGAM rarely exceeded 2500 IU after autologous transfusions. In comparison, it is the standard practice to administer 500 IU to Rh-negative mothers after delivery.19,25
Amniotic fluid embolism is a peripartum syndrome of rapid-onset dyspnea, hypoxemia, and cardiac collapse, with a mortality rate as high as 60% in developed nations.26 Amniotic fluid embolism occurs with an estimated incidence of 1 in 13,000 parturients in the United States.27 Fetal squamous cells, previously thought to be pathognomonic for amniotic fluid embolism, are found at relatively high levels in salvaged blood. This raised concerns that reinfusion may induce iatrogenic amniotic fluid embolism.28 However, amniotic fluid embolism is no longer thought to be due to embolization of fetal squamous cells but instead to be an anaphylactoid syndrome caused by an unknown fetal antigen.26 Several studies have found that fetal squamous cells are present in the blood of healthy parturients at the time of placental separation at levels comparable to those in salvaged blood.5,6 In 2000, a patient was reported to experience an amniotic fluid embolism after transfusion of salvaged blood.29 The case, reported in a Letter to the Editor, was a Jehovah Witness who presented at 30 weeks’ gestation with intrauterine growth restriction, preeclampsia complicated by HELLP (hemolysis-elevated liver enzymes-low platelet count) syndrome, and severe preoperative anemia. No leukocyte depletion filter was used. The diagnosis of amniotic fluid embolism was reached as a diagnosis of exclusion and not supported by pathologic examination. A response letter questioned the diagnosis and called for appropriate peer review before accepting the diagnosis of amniotic fluid embolism.30 Hundreds of other cases have reported the use of cell salvage in obstetrics, and to date, no definitive case of iatrogenic amniotic fluid embolism has been reported.
EFFICACY AND INDICATIONS
Suggested indications for usage of cell salvage commonly cited in the literature are listed in Table 3.1,11,12,19,31 With the use of these indications, multiple large studies have found rates of autologous transfusion ranging from 36% to 100%, with 6% to 97% of these patients completely avoiding allogeneic transfusions.9 For very high-risk patients, such as those undergoing a planned cesarean hysterectomy for placenta accreta, a 75% rate of autologous transfusion was observed.11 Eighty-seven percent of these patients successfully avoided allogeneic transfusions. The high variability in the percentage of patients receiving autologous transfusions and avoiding allogeneic transfusions can be partially explained by the risk of postpartum hemorrhage because patients with low-volume blood loss did not have sufficient salvaged material to allow processing.1,9,12,31 As patient selection is refined and familiarity with the technique grows, it is reasonable to expect that the proportion of patients successfully avoiding allogeneic transfusions will increase.
An argument against the use of cell salvage has been that the need for transfusion during cesarean delivery is unusual.32 The Association of Anesthetists of Great Britain and Ireland, Royal College of Anesthetists, and the American Association of Blood Banks all recommend consideration of cell salvage when the expected blood loss is >1 L or 20% of the patient’s estimated blood volume, cross-match compatible blood is unobtainable, the patient is unwilling to accept allogeneic blood, >10% of patients undergoing the procedure require transfusion, or the mean transfusion requirement for the planned procedure exceeds 1 unit of blood.1,19,33,34 It is important to note that these recommendations are not tailored to the obstetric population. The American College of Obstetricians and Gynecologists currently endorses consideration of cell salvage for postpartum hemorrhage, and the American Society of Anesthesiologists recommends consideration of cell salvage in cases of postpartum hemorrhage when banked blood is not available or when the patient refuses banked blood.35,36
ECONOMIC CONSIDERATIONS OF CELL SALVAGE AS A STRATEGY FOR BLOOD CONSERVATION IN OBSTETRICS
A recent single-institution economic analysis found that the use of cell salvage is not cost-effective for routine cesarean deliveries but is cost-effective in patients with predictably high rates of hemorrhage and transfusion.37 The authors found that only high-risk cases such as severe maternal anemia or abnormal placentation had transfusion rates that justified cell salvage (54% and 75% of patients required transfusion, respectively). A 2007 cost analysis of intraoperative cell salvage suggested that “standby use” be considered to improve cost-effectiveness.38 Standby use consists of only a basic setup (suction and reservoir) to which the additional (and expensive) system components can be added if sufficient blood loss is collected to allow processing. The authors determined that the average cost of a unit of allogeneic packed red blood cells was $200 compared with $89.46 for a salvaged autologous unit.38 Both studies cited significant initial and fixed-cost expenses for cell salvage, which may be too substantial to allow for use at institutions with small case volumes. In addition, the generalizability of these conclusions may be limited because the cost analyses from these studies are dependent on factors that vary greatly across institutions.
Cell salvage has an acceptable safety profile and should be considered when treating patients at high risk for obstetric hemorrhage and transfusion. Cell salvage collection should start after delivery of the placenta. Leukocyte depletion filters should be added to the cell salvage circuit to improve safety. In Rh-negative mothers, the appropriate dose of RhoGAM should be administered after performance of the Kleihauer-Betke assay. Further trials investigating cell salvage as a means to reduce allogeneic transfusions should be considered.
Name: Haley Goucher, MD.
Contribution: This author helped write the manuscript.
Attestation: Haley Goucher approved the final manuscript.
Name: Cynthia A. Wong, MD.
Contribution: This author helped write the manuscript.
Attestation: Cynthia A. Wong approved the final manuscript.
Name: Samir K. Patel, MD.
Contribution: This author helped write the manuscript.
Attestation: Samir K. Patel approved the final manuscript.
Name: Paloma Toledo, MD, MPH.
Contribution: This author helped write the manuscript.
Attestation: Paloma Toledo approved the final manuscript.
The authors acknowledge Jennifer H. Kim, MD, for her assistance with this project.
Dr. Cynthia A. Wong is the Section Editor for Obstetric Anesthesiology for the Journal. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. Wong was not involved in any way with the editorial process or decision.
a Hypotension and Bedside Leukocyte Reduction Filters. Available at: http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062284.htm. Accessed February 17, 2015.
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