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25 Blood Management intheLiver Transplant Patient
https://t.me/medicina_free
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40. Liang TB, Li DL, Liang L, etal. Intraoperative blood salvage dur­ing liver transplantation in patients with hepatocellular carcinoma: efciency of leukocyte depletion lters in the removal of tumor cells. Transplantation. 2008;85(6):863–9.
TP.0b013e3181671f2e
41. Muscari F, Suc B, Vigouroux D, etal. Blood salvage autotransfu­sion during transplantation for hepatocarcinoma: does it increase the risk of neoplastic recurrence? Transpl Int. 2005;18(11):1236–9.
https://doi.org/10.1111/j.1432-2277.2005.00207.x.
42. Massicotte L, Denault AY, Beaulieu D, Thibeault L, Hevesi Z, Nozza A, Lapointe RAR. Transfusion rate for 500 consecutive living donor liver transplantations: experience of one liver trans­plantation center. Transplantation. 2012;94(11):e66–7.
org/10.1097/TP.0b013e318274ab4a
43. Lisman T, Porte RJ.Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases. Res Pract Thromb Haemost. 2017;1(2):150–61. https://doi.org/10.1002/
rth2.12028
44. Chow JH, Lee K, Abuelkasem E, Udekwu OR, Tanaka KA. Coagulation management during liver transplantation: use of brinogen concentrate, recombinant activated factor vii, pro­thrombin complex concentrate, and antibrinolytics. Semin Cardiothorac Vasc Anesth. 2018;22(2):164–73.
org/10.1177/1089253217739689.
45. Toy P, Gajic O, Bacchetti P, etal. Transfusion-related acute lung injury: incidence and risk factors. Clin Trials Obs. 2012;119(7):1757–68.
https://doi.org/10.1182/blood-2011-08-370932.An.
46. Clifford L, Jia Q, Subramanian A, et al. Characterizing the epi­demiology of postoperative transfusion-related acute lung injury. Anesthesiology. 2015;122:12–20.
47. Benson AB, Austin GL, Berg M, et al. Transfusion-related acute lung injury in ICU patients admitted with gastrointestinal bleeding. Intensive Care Med. 2010;36(10):1710–7. https://doi.org/10.1007/
s00134-010-1954-x.
48. Smith NK, Kim S, Hill B, Goldberg A, DeMaria S, Zerillo J.Transfusion-Related Acute Lung Injury (TRALI) and Transfusion­Associated Circulatory Overload (TACO) in liver transplantation: a case report and focused review. Semin Cardiothorac Vasc Anesth. 2018;22(2). https://doi.org/10.1177/1089253217736298.
49. De Boer MT, Christensen MC, Asmussen M, et al. The impact of intraoperative transfusion of platelets and red blood cells on sur­vival after liver transplantation. Anesth Analg. 2008;106(1):32–44.
https://doi.org/10.1213/01.ane.0000289638.26666.ed.
50. Pereboom ITA, De Boer MT, Haagsma EB, Hendriks HGD, Lisman T, Porte RJ.Platelet transfusion during liver transplanta­tion is associated with increased postoperative mortality due to acute lung injury. Anesth Analg. 2009;108(4):1083–91. https://doi.
org/10.1213/ane.0b013e3181948a59.
51. Schiefer J, Lebherz-Eichinger D, Erdoes G, etal. Alterations of endo­thelial glycocalyx during orthotopic liver transplantation in patients with end-stage liver disease. Transplantation. 2015;99(10):2118–
23. https://doi.org/10.1097/TP.0000000000000680.
52. Spahn DR, Bouillon B, Cerny V, etal. Managment of bleeding and coagulopathy following major trauma: an updated European guide­line. Crit Care. 2013;17:R76.
53. Kozek-Langenecker S, Sørensen B, Hess JR, Spahn DR.Clinical effectiveness of fresh frozen plasma compared with brinogen con­centrate: a systematic review. Crit Care. 2011;15(5):R239. https://
doi.org/10.1186/cc10488.
54. Ghadimi K, Levy JH, Welsby IJ. Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting. Anesth Analg. 2016;122(5):1287–300. https://doi.org/10.1016/j.
physbeh.2017.03.040.
55. Sørensen B, Spahn DR, Innerhofer P, Spannagl M, Rossaint R.Clinical review: prothrombin complex concentrates– evaluation
.
.
https://doi.org/10.1097/
https://doi.
.
https://doi.
of safety and thrombogenicity. Crit Care. 2011;15(1):1–9.
doi.org/10.1186/cc9311
56. CSL Behring. [Package insert] Kcentra Prothrombin Complex Concentrate (Human). 2013.
57. Sarode R, Milling TJ, Refaai MA, etal. Efcacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma­controlled, phase IIIb study. Circulation. 2013;128(11):1234–43.
https://doi.org/10.1161/CIRCULATIONAHA.113.002283.
58. Majeed A, Eelde A, Ågren A, Schulman S, Holmström M.Thromboembolic safety and efcacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopa­thy. Thromb Res. 2012;129(2):146–51.
thromres.2011.07.024
59. Pereira D, Liotta E, Mahmoud AA.The use of Kcentra® in the reversal of coagulopathy of chronic liver disease. J Pharm Pract. 2018;31(1):120–5. https://doi.org/10.1177/0897190017696952.
60. Abuelkasem E, Hasan S, Mazzef MA, Planinsic RM, Sakai T, Tanaka KA.Reduced requirement for prothrombin complex con­centrate for the restoration of thrombin generation in plasma from liver transplant recipients. Anesth Analg. 2017;125(2):609–15.
https://doi.org/10.1213/ANE.0000000000002106.
61. Arshad F, Ickx B, Van Beem RT, etal. Prothrombin complex con­centrate in the reduction of blood loss during orthotopic liver trans­plantation: PROTON-trial. BMC Surg. 2013;13(1):1. https://doi.
org/10.1186/1471-2482-13-22.
62. Kirchner C, Dirkmann D, Treckmann JW, etal. Coagulation man­agement with factor concentrates in liver transplantation: a single­center experience. Transfusion. 2014;54(1):2760–8. https://doi.
org/10.1111/trf.12707.
63. Zamper RPC, Amorim TC, Queiroz VNF, et al. Association between viscoelastic tests-guided therapy with synthetic factor con­centrates and allogenic blood transfusion in liver transplantation: a before-after study. BMC Anesthesiol. 2018;18(1):1–12. https://doi.
org/10.1186/s12871-018-0664-8.
64. Yank V, Tuohy CV, Logan AC, et al. Systematic review: benets and harms of in-hospital use of recombinant factor VIIa for off­label indications. Ann Intern Med. 2011;154(8)529–40.
65. Levi M, Levy JH, Andersen HF, Truloff D.Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363(19):1791–800.
66. Hendriks HGD, Meijer K, De Wolf JTM, etal. Reduced transfu­sion requirements by recombinant factor VIIa in orthotopic liver transplantation. Transplantation. 2001;71(3):402–5. https://doi.
org/10.1097/00007890-200102150-00011.
67. Busani S, Semeraro G, Cantaroni C, Masetti M, Marietta M, Girardis M.Recombinant activated factor VII in critical bleeding after ortho­topic liver transplantation. Transplant Proc. 2008;40(6):1989–90.
https://doi.org/10.1016/j.transproceed.2008.05.021.
68. Planinsic RM, van der Meer J, Testa G, et al. Safety and efcacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transplant. 2005;11(8):895–900. https://doi.org/10.1002/lt.20458.
69. Lodge JPA, Jonas S, Jones RM, etal. Efcacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplanta­tion. Liver Transplant. 2005;11(8):973–9. https://doi.org/10.1002/
lt.20470.
70. Bosch J, Thabut D, Bendtsen F, etal. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a random­ized, double-blind trial. Gastroenterology. 2004;127(4):1123–30.
https://doi.org/10.1053/j.gastro.2004.07.015.
71. Lodge JPA, Jonas S, Oussoultzglou E, etal. Recombinant coag­ulation factor VIIa in major liver resection. Anesthesiology. 2005;102(4):269–75. https://doi.org/10.1097/01.
sa.0000172532.43755.3b.
.
https://doi.org/10.1016/j.
.
https://
268
https://t.me/medicina_free
D. Romano et al.
72. Pham HP, Hsu SX, Parker-Jones S, Samstein B, Diuguid D, Schwartz J.Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience. Vox Sang. 2014;106(1):75–82.
vox.12067
73. Scheffert JL, Taber DJ, Pilch NA, McGillicuddy JW, Baliga PK, Chavin KD.Timing of factor VIIa in liver transplantation impacts cost and clinical outcomes. Pharmacotherapy. 2013;33(5):483–8.
https://doi.org/10.1002/phar.1230.
74. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of aprotinin and llysine analogues in high risk cardiac surgery. N Engl J Med. 2008;358(22):2319–31. https://doi.org/10.1056/
NEJMoa1602001
75. Trzebicki J, Kosieradzki M, Flakiewicz E, etal. Detrimental effect of aprotinin ban on amount of blood loss during liver transplanta­tion: single-center experience. Transplant Proc. 2011;43(5):1725–
7.
.
.
https://doi.org/10.1016/j.transproceed.2011.01.182.
https://doi.org/10.1111/
76. Schoeld N, Sugavanam A, Thompson K, Mallet SV. No increase in blood transfusions during liver transplantation since the with­drawal of aprotinin. Liver Transplant. 2014;20:584–90. https://doi.
org/10.1002/lt.23839
77. Molenaar IQ, Warnaar N, Groen H, TenVergert EM, Slooff MJH, Porte RJ. Efcacy and safety of antibrinolytic drugs in liver transplantation: a systematic review and meta­analysis. Am J Transplant. 2007;7(1):185–94. https://doi.
org/10.1111/j.1600-6143.2006.01591.x
78. Badenoch A, Sharma A, Gower S, et al. The effectiveness and safety of tranexamic acid in orthotopic liver transplanta­tion clinical practice: a propensity score matched cohort study. Transplantation. 2017;101(7):1658–65.
TP.0000000000001682
.
.
https://doi.org/10.1097/
.
Liberal vs. Conservative
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Blood Strategies
LisaFarmer, DeepinderS.Mann, andDonaldS.Prough
26
Abbreviations
AABB American Association of Blood Banks ASA American Society of Anesthesiologists ATLS Advanced Trauma Life Support DO
Delivery oxygen
2
ECG Electrocardiogram ESA Erythropoietic-stimulating agents FDA Food and Drug Administration FOCUS Functional Outcomes in Cardiovascular patients
Undergoing Surgical Repair Hgb Hemoglobin ICP Intracranial pressure NISHOT Noninfectious serious hazards of transfusions O2 Oxygen PPH Postpartum hemorrhage RBC Red blood cell SCA Society of Cardiovascular Anesthesiologists STS Society of Thoracic Surgeons TAXI Transfusion and Anemia Expertise Initiative TBI Traumatic brain injury TIPS Transjugular intrahepatic portosystemic shunt TXA Tranexamic acid TITR Transfusion Indication Threshold Reduction TRACS Transfusion Requirements After Cardiac
Surgery TRiCS Transfusion Requirements in Cardiac Surgery VO2 Oxygen consumption
L. Farmer (*) · D. S. Mann · D. S. Prough Department of Anesthesiology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA e-mail: lrfarmer@utmb.edu; dsmann@utmb.edu;
dsprough@utmb.edu
Introduction
Historically, the standard approach to anemia in a hospital­ized patient was to treat liberally with allogenic blood trans­fusions to maintain a hemoglobin ([Hgb]) exceeding 10g/ dL, i.e., the customary transfusion trigger was 10g/dL.The safety of a more conservative approach was suggested by normovolemic hemodilution studies of the late 1990s which established that healthy, elderly, and stable cardiac patients compensated for severe anemia without increases in serum lactate, suggesting that tissue oxygenation remained ade­quate as long as intravascular volume was maintained [1]. Multiple studies report that allogenic blood transfusions are both risky to patients and costly to hospitals [2, 3]. In fact, mortality increases in a dose-dependent manner with each intraoperative red blood cell (RBC) unit transfused [4]. Thus, if outcomes are similar, a conservative strategy with a more restrictive transfusion trigger is recommended for most patient populations.
Reducing unnecessary blood transfusions through appli­cation of appropriate restrictive transfusion strategies has become the standard of care [5]. Numerous randomized con­trolled trials have shown that restrictive transfusion triggers are safe for most hemodynamically stable, nonbleeding patients [6]. Over the last 20 years, transfusion guidelines from multiple international societies, including the Society of Cardiovascular Anesthesiologists (SCA) and the Society of Thoracic Surgeons (STS), recommend restrictive transfu­sion strategies with a [Hgb] threshold of 7g/dL in asymp­tomatic patients [6–10]. A higher [Hgb] threshold of 8g/dL is suggested for postoperative patients, hospitalized patients with preexisting cardiovascular disease, and symptomatic patients with chest pain, congestive heart failure, orthostatic hypotension, or tachycardia unresponsive to uid resuscita­tion [1]. For patients with acute coronary syndrome, recom­mendations differ, although most guidelines support a restrictive transfusion trigger between 7g/dL and 9g/dL [8,
10–12].
© Springer Nature Switzerland AG 2021 C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
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It is important to note that guidelines from most societies target hemodynamically stable patients without signicant ongoing bleeding [6]. There is not enough evidence to support either restrictive or liberal transfusion strategies in unstable patients or in patients with active bleeding, although patients with active gastrointestinal bleeding and those with hemorrhagic shock have been studied most extensively [13]. Patients with hemorrhagic shock should be transfused empirically with RBCs, plasma, and platelets in xed ratios until life-threatening bleeding is controlled.
As frontline administrators of blood products, anesthesi­ologists are thought to be involved in almost half of the decisions to transfuse the 21 million blood components used annually [14]. The American Society of Anesthesiologists (ASA) generally support restrictive transfusion practices, dened as a [Hgb] threshold of less than 8g/dL, and report that the decision to transfuse should be based on a patient’s generalized risk of developing complications from inadequate tissue oxygenation as opposed to a single [Hgb] trigger [15, 16]. Since initial guidelines were published in 1996, the ASA has agreed that transfusions are rarely indicated when [Hgb] is greater than 10g/dL and is usually indicated when [Hgb] <6g/dL [17]. Unfortunately, the ASA and other international societies are unable to give clear [Hgb] thresholds for patients at risk for tissue hypoxia and end-organ dysfunction in the acute care setting [18].
Anemia is common, affecting 20–40% of surgical patients and is a strong predictor of perioperative transfusions [19]. Perioperative anemia is an independent predictor of worsened patient outcomes, including increased length of hospital and ICU stay, and is associated with increased risk of postoperative complications and mortality [3, 20]. The combination of perioperative anemia and intraoperative blood transfusions further increases morbidity and mortality. It is unclear which factors cause the risks of acute anemia to exceed the risks associated with allogenic blood transfusions, especially for high-risk patients with ongoing blood loss. The challenge is to differentiate patients who will benet from conservative transfusion strategies from those that will be compromised by them, and thus not benet from the procedure.
Under normal physiologic conditions, systemic oxygen (O
) delivery (DO2) exceeds O2 consumption (VO2) in a 5:1
2
ratio creating a positive O2 reserve [18, 21]. In anemic patients, compensatory mechanisms allow for increased car­diac output, right shifting of the oxyhemoglobin dissociation curve, and altered regional blood ow to increase O2 extrac­tion and maintain tissue DO2 [3]. Surgical stressors and anes­thetic medications lead to multiple factors that disrupt normal
supply-demand, which inuence patients’ tolerance to
O
2
and compensation for anemia. For example, hypoventilatory hypoxia, common perioperatively, compromises DO2 at the same time that surgical trauma and pain increases VO2.
Anesthetic drugs can reduce cardiac contractility and cause widespread vasodilation, limiting the patient’s ability to increase DO2 via increased cardiac output and altered regional blood ow. Hypotension, intravascular volume changes, and increased catecholamines, all of which are common perioperatively, further limit blood ow to vital organs. Clinicians must incorporate available indicators of DO2 into the decision to transfuse [22].
Traditional neurologic, cardiovascular, and respiratory features of tissue hypoxia are masked during general anes­thesia. Unstable vital signs can result from anesthetic side effects or surgical manipulation, making it difcult to deter­mine the primary driver of changes in heart rate, blood pres­sure, and electrocardiogram. Furthermore, inadequate tissue perfusion is possible despite normal blood pressure and heart rate [23]. Hypovolemia can result from ongoing periopera­tive losses or from relative changes in systemic vasodilation associated with anesthesia. Tissue hypoxia secondary to hypovolemia is readily reversed by restoration of intravascu­lar volume. Assessing the heart rate, blood pressure, urinary output, and laboratory response to uid challenges provide partial information. Intermittent boluses of vasopressors can temporize severe hypotension during ongoing volume resus­citation, but careful evaluation of intravascular volume is necessary to assure end-organ perfusion is maintained.
Intraoperative Transfusion Strategies
When choosing between conservative and liberal transfusion strategies, it is important to consider the clinical context including both surgical type and patient comorbidities. In 2016, Hovaguiman and Myles [18] performed a meta­analysis on 31 randomized controlled trials in which they grouped patients into ve context-specic strata. In patients with cardiovascular disease undergoing cardiac or vascular procedures and in elderly patients undergoing orthopedic procedures, application of restrictive transfusion strategies resulted in increased “inadequate O2 supply” events and/or mortality. Application of restrictive transfusion triggers in acute care, medical-surgical patients and in younger patients with subarachnoid bleeding or traumatic brain injury showed similar outcomes to the liberal transfusion group. This sug­gests an approach to perioperative transfusions that “one size may not t all” [24]. More research is needed to identify which high-risk patients will do better with a less conserva­tive approach.
During anesthesia a primary goal is to maintain adequate tissue perfusion and DO physiologic parameters other than [Hgb]. Clinicians should strive to reduce O2 demand and optimize heart rate, rhythm, contractility, preload, and afterload before deciding to trans­fuse except in the case of hemorrhagic shock [25].
. DO2 is dependent on multiple
2
26 Liberal vs. Conservative Blood Strategies
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Intravascular decits should be treated with crystalloid administration and anesthesia-related vasodilation with vasopressors. The decision to transfuse must be based on multiple factors including the potential for or actual ongoing bleeding, intravascular volume status, signs of organ isch­emia, and the adequacy of cardiopulmonary reserve [15]. Each of these factors is challenging to measure, requires astute clinical judgment to interpret, and is more subjective than an arbitrary [Hgb]. Integration of patient data through vigilance and meticulous monitoring is key in determining when transfusions are necessary during surgery.
Estimating blood loss is a critical step in transfusion deci­sions but better techniques are necessary to improve accu­racy with its measure. Multiple reports show that estimation of blood loss is difcult, frequently inaccurate, and inconsis­tent among nurses, surgeons, and anesthesiologists [26, 27]. The rate, magnitude, and potential for ongoing bleeding must also be considered. The denition of massive hemor­rhage varies but generally includes one of the following cri­teria: need for >10 units of red blood cells, loss of ≥one blood volume in 24hours, loss of ≥50% of blood volume in 3hours, or blood loss ≥150mL/min.
The Advanced Trauma Life Support (ATLS) identies four classes of hemorrhage based on estimated blood loss, as shown in Table 26.1 [28, 29]. Class I hemorrhage involves loss of 15% of blood volume and results in minimal hemodynamic changes. Class II involves loss of 15–30% of blood volume and results in tachycardia without a change in systolic blood pressure. It is important to note that pulse pressure will begin to narrow with loss of 15–30% of blood volume as diastolic blood pressure increases to maintain tissue perfusion [28]. Increased diastolic blood pressure and a base decit of −2 to −6mEq/L may be the rst marker of ongoing blood loss and ensuing metabolic acidosis [29]. Class II hemorrhage is usually effectively corrected with uid administration although transfusion maybe indicated if the patient has preexisting
Table 26.1 Advanced trauma life support classes of hemorrhage
[29, 30]
Class I Class II Class III Class IV
Blood loss %<15 15–30 30–40 >40
Pulse rate <100 100–120 120–140 >140 Blood pressure Pulse pressure Urinary output (ml/ hr) Base decit (mEq/L) Blood products needed
No change No
Normal to increased >30 20–30 5–15 Minimal
0 to −2 −2 to −6 −6 to −10 −10 or less
Unlikely Possible Ye s Activate massive
change Decreased Decreased Decreased
Decreased Greatly
decreased
transfusion protocol
anemia or cardiovascular disease. Class III hemorrhage involves loss of 30–40% of blood volume resulting in signicant tachycardia (HR 120–140bpm), hypotension, base decit of −6 to −10mEq/L, and oliguria. Blood loss of >40% of estimated blood volume denes Class IV hemorrhage and results in marked tachycardia (HR >140), severe hypotension, base decit greater than −10mEq/L, and anuria. Immediate transfusion of blood and blood products is indicated for Class III or IV hemorrhage to restore intravascular volume, maintain DO2, and prevent development of coagulopathy [29].
Estimating intravascular blood volume is challenging due to inaccuracies of intraoperative blood loss measurements, intercompartmental uid shifts, and the dilutional effects of crystalloid administration [17]. Meticulous monitoring for vital organ perfusion and clinical indications of tissue hypoxia is key in assessing the intravascular volume status of surgical patients. Preoperative evaluation of volume status with careful attention to conditions associated with increased volume losses, diuretic use, and duration of preoperative fasting is important in pre-surgical patients. The blood pressure and heart rate response to anesthesia induction, blood loss, and uid administration are common metrics used to estimate volume status. Urinary output of at least
0.5 mL/kg/h is a sign of adequate intravascular volume and adequate renal perfusion. Non-invasive cardiac output monitors and assessment of cardiac chamber size with echocardiography provide a more objective measure of uid responsiveness. Invasive pressure measures such as stroke volume or pulse pressure variation or trends in central venous pressure or pulmonary arterial occlusion pressure should be used as needed to respond to the dynamic volume changes associated with surgery and anesthesia [23].
Hypovolemia is associated with labile blood pressure dur­ing anesthesia and exaggerated changes in [Hgb] with uid administration. After transfusion and without ongoing blood loss, euvolemic adults should have a 1g/dL rise in [Hgb] for every unit of RBCs given. Of note, 10ml/kg of RBCs will produce similar effects in children. Hypovolemic patients will have larger than expected increases in [Hgb] with each unit of RBCs transfused and conversely will have greater dilution of [Hgb] with uid administration.
The critical [Hgb] required for each patient varies inversely with cardiovascular reserve [30]. Clinicians must consider a patient’s comorbidities, response to uid adminis­tration, and need for vasoactive medications to determine cardiopulmonary reserve. Transfusion is usually not neces­sary when a patient is able to compensate for acute anemia without signs of tissue hypoxia. High-risk patients with low cardiopulmonary reserve do not tolerate the combination of acute anemia and impaired compensatory response. The increase in cardiac output and heart rate required to compen­sate for anemia in these patients cause increased myocardial O
demands.
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Transfusions may be necessary before laboratory mea­surements of [Hgb] during acute intraoperative bleeding. During acute blood loss, [Hgb] will be normal or mislead­ingly high unless substantial volumes of asanguineous uids have been administered, making [Hgb] a less accurate trigger for transfusion. To guide transfusions, the clinician must continuously assess the operative eld, hemodynamic response to volume administration, and laboratory values. Meticulous monitoring for signs of tissue hypoxia, such as unstable vital signs, ECG changes, echocardiographic wall motion abnormalities, cerebral oximetry, new onset of oligu­ria, metabolic acidosis, elevated base excess, or increased serum lactate, is key to optimize end-organ perfusion. The best intraoperative monitoring technique and optimal physi­ologic metrics and biomarkers needed to establish individual transfusion thresholds have not been identied in adult or pediatric patients [15, 25].
Comprehensive Conservative Strategies
Conservative transfusion strategies are preferred if tissue perfusion and DO2 can be maintained. This is only possible with a more comprehensive approach to anemia and periop­erative bleeding. After implementing broad-based restrictive transfusion strategies, multiple institutions have reported a signicant decrease in blood utilization and have shown sim­ilar to improved outcomes for patients in restrictive transfu­sion groups compared to those in liberal groups [31–34].
Careful preoperative assessment is necessary to identify potential for organ ischemia and risk factors for bleeding [15, 19]. Cardiopulmonary reserve should be optimized to improve tolerance to acute anemia and anesthesia. Whenever possible, anticoagulant and antiplatelet drugs should be stopped early enough to allow their effects to dissipate. If identied early, preoperative anemia is a modiable risk, but effective management requires screening 4–8weeks preop­eratively to allow time to regenerate RBC mass. Treatment of preoperative anemia should be considered for all high-risk patients undergoing major elective procedures, especially if the procedure is associated with a >10% likelihood of need­ing a blood transfusion [13, 35].
Intraoperatively, every attempt should be made to mini­mize blood loss and improve the patient’s tolerance to ane­mia, such that restrictive transfusion triggers can be utilized and transfusions avoided. Goal-directed uid therapy and appropriate use of inotropic and vasoactive drugs is impor­tant to assure adequate DO2 during surgery. Meticulous attention to hemostasis is the job of both the surgeon and the anesthesiologist. Surgical technique and appropriate use of hemostatic agents are key determinants of perioperative blood loss [19]. ASA practice guidelines for perioperative blood management recommend using multimodal protocols
and algorithms to decrease bleeding whenever possible [15]. Aggressively treating hypothermia, acidosis, and hypocalce­mia is critical to facilitate clot formation; otherwise this triad creates a vicious cycle, prolonging surgery and increasing blood loss. Additional techniques to minimize blood loss may include maintaining the blood pressure at the lowest safe level, lowering of central venous pressure, and careful positioning [19].
Prophylactic use of cell saver and antibrinolytics for patients at risk for excessive bleeding is advocated. Hemostasis requires adequate presence of coagulation factors, platelets, and brinogen to produce a stable clot. Use of point-of-care testing such as viscoelastic monitoring to guide fresh frozen plasma, platelets, cryoprecipitate, factor concentrates, and antibrinolytic drugs is recommended and has been shown to signicantly reduce transfusion requirements [15].
Application of conservative transfusion strategies are also advocated in the postoperative period. Use of iron to treat postoperative iron deciency will improve the patient’s toler­ance to anemia, as symptoms frequently resolve prior to regeneration of RBC mass once iron stores have been replaced [5]. Post-operative blood loss can be signicantly reduced by minimizing laboratory tests and using low­volume collection tubes. A comprehensive approach to ane­mia and meticulous control of blood loss are required to minimize transfusion and improve patient outcomes.
The remainder of this chapter will focus on outcomes of liberal versus conservative transfusion strategies in specic high-risk patient populations.
Transfusion Strategies inCardiac Surgery
Cardiac surgery is frequently associated with signicant blood loss, and patients undergoing cardiac surgery have limited cardiopulmonary reserve due to common high-risk co morbidities. The STS Adult Cardiac Surgery Database notes that 50% of patients undergoing cardiac procedures receive blood transfusions [12]. The 2010 Transfusion Requirements After Cardiac Surgery (TRACS) study found that transfusions were an independent risk factor for morbid­ity and mortality in this patient population [36]. These nd­ing are supported by several other retrospective studies and systematic reviews. For example, patients undergoing coro­nary artery bypass grafting experienced an increase risk of death and pneumonia after high amounts of RBC transfu­sions [37, 38]. Of course, during acute hemorrhage associ­ated with cardiac surgery, RBC transfusions can be lifesaving by providing increased O microcirculation [39].
TRACS documented the safety of restrictive transfusion strategies after cardiopulmonary bypass, showing no differ­ence in the 30-day mortality between patients transfused to a
-carrying capacity and improved
2
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restrictive goal ([Hgb] >8 g/dL, hematocrit >24%) versus liberal ([Hgb] >10 g/dL, hematocrit >30%). In 2015, the safety of restrictive strategies in cardiac surgery was ques­tioned when the Transfusion Indication Threshold Reduction (TITRe2) clinical trial reported a signicantly increased 90-day mortality in the restrictive group compared to the lib­eral group [40]. In 2017 the Transfusion Requirements in Cardiac Surgery III (TRiCS III) trial concluded that for patients at moderate to high risk of death, application of a restrictive strategy ([Hgb] threshold <7.5 g/dL) was non­inferior to a liberal strategy for outcomes including death and major disability (myocardial infarction, stroke, or new­onset renal failure with dialysis). These outcomes were achieved with less blood being transfused [41]. The current international consensus on evidence-based patient blood management strongly recommend a restrictive transfusion trigger of [Hgb] <7.5g/dL for patients undergoing cardiac surgery [13].
[Hgb] is not the only indication for blood transfusion in this population. All cardiac surgery patients are at risk for both tissue hypoxia from anemia and worsened outcomes secondary to blood transfusions. Current STS and SCA guidelines for patients with [Hgb] between 7 and 10 g/dL undergoing cardiac surgery recommend transfusion in patients with “critical noncardiac end-organ ischemia,” active blood loss, or clinical indication of tissue hypoxia [7]. Low mixed venous O echocardiographic evidence of myocardial ischemia is dened as an indication of tissue hypoxia.
Treatment of preoperative anemia can be challenging in cardiac surgery patients due to the urgency of the procedure and US Food and Drug Administration (FDA) restrictions against use of erythropoietic-stimulating agents (ESAs) in cardiac and vascular surgery [31]. Implementing a variety of other conservative strategies including meticulous surgical hemostasis, use of antibrinolytic agents, thromboelasto­graphic guided coagulation algorithms, postoperative use of intravenous iron, and application of restrictive transfusion thresholds result in decreased number of transfusions, less kidney injury, shorter length of hospital stays, and lower costs [31].
saturation or electrocardiographic or
2
Transfusion Strategies inOrthopedic Surgery
Although a [Hgb] threshold of 7g/dL appears safe for most asymptomatic orthopedic patients, the current American Association of Blood Banks (AABB) guidelines for RBC transfusions recommend a restrictive [Hgb] trigger of 8g/dL for this population [6, 32]. Hip fracture patients represent a vulnerable orthopedic population as most are elderly and have cardiovascular disease or other comorbidities associated with
decreased cardiovascular reserve. In 2011, the Functional Outcomes in Cardiovascular patients Undergoing Surgical repair (FOCUS) trial assessed hip fracture patients who were over 50years of age and had a history of either cardiovascular disease, diabetes, peripheral vascular disease, or smoking. Restrictive strategies were found non-inferior to liberal strate­gies regarding 30-and-60 day mortality and morbidity [42]. The current international consensus on evidence- based patient blood management concludes that high-risk hip fracture patients who are treated with restrictive transfusion triggers have similar critical outcomes to patients transfused liberally [13]. Another benet of restrictive strategies in this population is that 42% fewer patients receive transfusions in the restric­tive transfusion group ([Hgb] trigger <8g/dL) compared to the liberal threshold groups [13]. Symptomatic anemia, dened as chest pain, congestive heart failure, tachycardia, or hypoten­sion unresponsive to uid, should be used as criteria for trans­fusion even when [Hgb] >8g/dL [32, 42].
A variety of conservative transfusion strategies have been studied in orthopedic surgery. Use of tranexamic acid in hip and knee arthroplasty is instrumental at reducing overall blood loss and transfusion requirements, especially if given prior to tourniquet deation [15]. Identication and effective management of preoperative anemia is advocated for elec­tive major orthopedic procedures [13]. Anesthetic techniques such as maintenance of normothermia and controlled hypo­tension can decrease blood loss. Regional anesthesia, espe­cially in major joint surgery, can signicantly reduce perioperative blood loss [43]. Reducing perioperative blood loss in total knee arthroplasty has additional benets, such as decreased intra-articular hemorrhage, limb swelling, postop­erative pain, and increased range of motion leading to improved rehabilitation and patient satisfaction [44].
Transfusion Strategies inthePediatric Population
Pediatric anemia is common, occurring in up to 75% of criti­cally ill children, resulting in almost half of PICU patients receiving a blood transfusion if admitted for more than 48hours [45]. The risks of anemia and transfusions differ in pediatric patients. Children appear to tolerate anemia better than adult populations as they typically do not have ow lim­iting lesions that jeopardize DO2 to vital organs. However, noninfectious serious hazards of transfusions (NISHOT), in particular transfusion-associated lung injury and transfusion­associated circulatory overload, are much more prevalent in critically ill children for unclear reasons [25]. In fact, RBC transfusion is an independent risk factor for mortality in crit­ically ill children [46].
In critically ill, hemodynamically stable children, a restrictive transfusion strategy is non-inferior to a liberal
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transfusion strategy and reduces exposure to blood products, making restrictive strategies preferred during periods of hemodynamic stability [25]. The 2007 Transfusion Requirements in the Pediatric Intensive Care Unit (TRIPICU) study was a multicenter, randomized controlled trial that compared restrictive ([Hgb] ≤ 7 g/dL) to liberal ([Hgb] ≤ 9.5 g/dL) transfusion thresholds in critically ill children. TRIPICU reported similar rates of multi-organ dys­function in both groups, although restrictive practices reduced transfusion frequency by half [47]. A study of acute pediatric burn patients found that a restrictive transfusion group ([Hgb] <7g/dL) had signicantly lower mortality than a liberal transfusion group ([Hgb] <10g/dL) [48].
Despite the benets of reduced RBC transfusions in chil­dren, pediatric intensivists have been slow to adopt restric­tive practices [25]. There is limited evidence to guide transfusion decisions in critically ill hemodynamically unstable patients, dened as mean arterial pressure greater than 2 standard deviations below normal mean for age or an increase in cardiovascular support (vasoactive drugs or u­ids) over the last 2hours [47]. Likewise, there is lack of evi­dence to guide transfusion strategies for critically ill children undergoing surgical procedures, especially for medically fragile patients with complicated physiology [45].
The 2018 Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) brought together international, multidisciplinary experts to address different types of critically ill children, including those with non­hemorrhagic and hemorrhagic shock, non-life-threatening bleeding, and traumatic brain injury [25]. Consensus of >80% was reached for each recommendation, including the
need to consider the overall clinical context (symptoms, signs, physiologic markers, laboratory results) and the risks, benets, and alternatives when deciding to transfuse. The use of physiologic-based metrics and biomarkers of DO2 are recommended, but the experts could not give guidance on thresholds or priorities of these measures to inform transfusion decisions. More research is needed to identify biomarkers and/or physiologic measures that suggest intolerance to anemia and indicate a patient-specic likelihood of transfusion benet.
Figure 26.1 represents an RBC transfusion clinical deci­sion support tree that summarizes the TAXI recommenda­tions for critically ill children [25]. [Hgb] should be measured before transfusion unless a patient has life-threatening bleed­ing. Transfusion is recommended for [Hgb] <5 g/dL and should be considered if [Hgb] is between 5 and 7g/dL in general or during periods of non-life-threatening bleeding. For acute brain injury patients, transfusion should be consid­ered for [Hgb] between 7 and 10g/dL. Due to inadequate evidence, TAXI could not recommend for or against the use of brain O
monitoring to guide transfusion decisions. During
2
non-hemorrhagic shock, all strategies to augment DO2 and decrease O2 demands should be considered before transfu­sion. TAXI recommended not transfusing patients who are hemodynamically stable with a [Hgb] >7 g/dL. The post transfusion goal should be to relieve the indication for trans­fusion as opposed to achievement of a certain [Hgb]. During hemorrhagic shock, empiric ratios of RBCs, plasma, and platelets should be given until bleeding is controlled as chil­dren with life-threatening hemorrhage have >50% mortality [45].
Fig. 26.1 Pediatric critical care
Transfusion and Anemia Expertise Initiative (TAXI). Red Blood Cell (RBC) Transfusion Clinical Decision Tree. Transfusion and Anemia Expertise Initiative (TAXI) RBC transfusion decision tree for critically ill children. ACS acute chest syndrome, ECMO extracorporeal membrane oxygenation, Hb hemoglobin, HbS Hb S, PARDS pediatric acute respiratory distress syndrome, VAD ventricular assist device. (With permission from Valentine etal. [25])
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Transfusion Strategies intheObstetric Population
Maternal anemia is common and is associated with increased premature delivery and worsened child morality [49]. Multiple physiologic changes occur during pregnancy to assure adequate DO2 to the parturient and developing fetus. These include increased maternal 2, 3-diphosphoglycerate, plasma volume, red cells, and cardiac output. Dilutional anemia develops as the increase in plasma volume exceeds that of red cell mass. Oral iron and folic acid supplementation, both of which are part of routine antenatal care, help the parturient tolerate anemia and avoid the associated adverse outcomes.
Physiologic changes provide a compensatory reserve that allows the parturient to tolerate the acute blood loss com­monly associated with delivery [50]. Post-delivery changes of increased peripheral resistance and hemoconcentration help maintain blood pressure and further reduce the need for transfusion [50]. Despite this compensatory reserve, approx­imately 1% of women receive a blood transfusion after spon­taneous vaginal delivery and 5–6% after instrumental deliveries or cesarean sections [51]. Pregnancy, especially when accompanied by preeclampsia, is associated with increased risk of transfusion reactions [52].
There is considerable variability in transfusion guidelines among international obstetric societies, likely due to the lack of clear evidence specic for obstetric patients regarding safety of conservative transfusion strategies. Most societies recommend transfusing based on the degree of blood loss even though there are well-known inaccuracies in peripartum blood loss measurements especially at higher volumes [49]. Hancock etal. [53] found that improved accuracy of blood loss measurement did not result in earlier identication of postpartum hemorrhage (PPH). Clinicians must assess vital signs and severity of bleeding to determine when transfusion is indicated. A high suspicion for PPH as well as a standardized approach to patients at risk for hemorrhage is needed. These may include preemptive blood ordering, emergency release of blood products, and massive transfusion protocols.
PPH is a leading cause of maternal death after child­birth. At term, uterine blood ow is approximately 5 liters per minute, which can result in a high rate of blood loss. Clinicians must maintain a high index of suspicion for PPH in order to recognize and treat it quickly. A 2017 Cochrane review of the efcacy of antibrinolytic drugs for treating primary PPH found that intravenous tranexamic acid (TXA) reduces risk of maternal death from bleeding if given early, ideally 1–3hours after childbirth, although it did not reduce the risk of serious bleeding or need for blood transfusion. The use of TXA was not associated with increased risk of thromboembolic events in this population [54].
Strategies to reduce unnecessary transfusions in the obstetric population include treatment of preoperative anemia, decreasing iatrogenic blood loss, optimization of
hemostasis, and establishment of transfusion thresholds [49]. Anemia and iron deciency, common in the postpartum period, are associated with decreased exercise tolerance, impaired lactation, reduced cognitive performance, emotional instability, and depression all of which can inter­fere with maternal baby bonding. Treatment with iron may protect against these negative effects [49]. Adequate brino- gen necessary to optimize hemostasis during obstetric hem­orrhage varies between 100 and 200mg/dL depending on the obstetric society guideline [49]. Additional research focused on context-specic indicators of volume status and tissue O2 delivery in obstetric patients, especially as it applies to maternal hemorrhage, is needed to determine the safety of restrictive versus liberal transfusion practices in the obstetric population.
Transfusion Strategies inGI Bleeding
Upper gastrointestinal bleeding is a very common cause of acute blood loss and therefore a very common cause for transfusion. For patients who are not experiencing massive exsanguination, a [Hgb] transfusion trigger <7g/dL has been shown to be superior to a liberal threshold <9g/dL. A key trial from 2013 found most patients in the restrictive group had lower 45-day mortality, fewer rebleeding events, fewer cardiac complications, and shorter hospital stays compared to a liberal group. Importantly, patients with Child-Pugh class C cirrhosis did not see the mortality benet [55]. Currently, for bleeding varices, the American Association for the Study of Liver Disease recommends transfusing when [Hgb] approaches 7g/dL with a goal of maintaining between 7 and 9g/dL [56]. Additional strategies to reduce bleeding and keep patients above transfusion triggers include early use of vasoactive drugs (e.g., octreotide or vasopressin), early esophagogastroduodenectomy, and the use of transjugular intrahepatic portosystemic shunt (TIPS) in selected patients [57].
Geriatrics
In the general geriatric population, the prevalence of anemia may be as high as 25%. The elderly are the most common group to receive transfusions for anemia treatment. There is some evidence that the presence of anemia, independent of other comorbidities, can be a risk factor for the development of dementia and rapid cognitive decline [58]. The mechanism for this is unknown. Chronic hypoxia and systemic effects from micronutrient deciency are two possible explanations for this association [59]. Other researchers have not found a link between anemia and delirium [60]. Currently, it is unknown whether simply being a geriatric patient necessitates either liberal or conservative transfusion thresholds.
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Neurologic Injury
For many acute neurological injuries, patients presenting with anemia is an independent and signicant predictor of poor outcomes [61, 62]. Adequate O2 delivery is key during the early phases of brain injury. However, during these events normal brain auto-regulation is suspected to be altered. For many common injuries (including acute stroke, intracerebral hemorrhage, and subarachnoid hemorrhage), several studies have found harm or no benet to liberal transfusion goals compared to restrictive [61, 63–66].
Traumatic brain injury (TBI) is the most common cause of death in the rst half of life, and many survivors are left with permanent impairment. More than 1/3 of patients with TBIs are transfused. Extra-cerebral injuries are the most common precipitator of transfusion. Not only is auto­regulation affected, but there is also concern that even mild anemia may cause vasodilation and thereby increase intra­cranial pressure in these patients [67].
Many trials have included small numbers of TBI patients; however, there is not enough information for a clear consen­sus whether liberal or restrictive transfusions strategies are superior. A clinician survey found most medical providers felt a threshold between 7 and 8g/dL was best for acute brain injury in general. When it came to TBIs, however, there were nearly an equal number of responders in all groups between 7 and 10g/dL [68]. There is also disagreement if those pre­senting with high ICPs might have different thresholds. A multicenter, randomized controlled trial (HEMOTION trial) may shed light on this area in the future (results expected in
2021) [69].
Patients who develop intracerebral hemorrhage while treated with antiplatelet drugs can have worse outcomes compared to patients with normal platelet function. The role of platelet transfusion has been investigated in this population. In a recent trial, platelet transfusion was associated with greater disability at 3 months than in those who did not receive platelets [70]. This study excluded patients with platelet counts <100,000/L, and there was a relatively low rate of acute strokes in the trial. The role of platelet function tests to selectively choose who might benet from transfusion is ongoing [71]. Some experts suggest avoiding platelet administration unless a surgical intervention is planned regardless of what antiplatelet agent the patient has taken [72].
References
1. Auron M, Duran Castillo MY, Kumar A.Parsimonious blood use
and lower transfusion triggers: what is the evidence? Cleve Clin J Med. 2017;84(1):43–51. Epub 2017/01/14.
2. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H,
Spahn DR.Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010;50(4):753–65. Epub 2009/12/17.
3. Shander A, Javidroozi M, Ozawa S, Hare GM.What is really dan­gerous: Anaemia or transfusion? Br J Anaesth. 2011;107(Suppl
1):i41–59. Epub 2011/12/22.
4. Johnson DJ, Scott AV, Barodka VM, Park S, Wasey JO, Ness PM, et al. Morbidity and mortality after high-dose transfusion. Anesthesiology. 2016;124(2):387–95. Epub 2015/11/17.
5. Shander A, Bracey AW Jr, Goodnough LT, Gross I, Hassan NE, Ozawa S, et al. Patient blood management as standard of care. Anesth Analg. 2016;123(4):1051–3. Epub 2016/09/20.
6. Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, etal. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316(19):2025–
35. Epub 2016/10/13.
7. Society of Thoracic Surgeons Blood Conservation Guideline Task F, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, et al. 2011 Update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944–82. Epub 2011/03/01.
8. Retter A, Wyncoll D, Pearse R, Carson D, McKechnie S, Stanworth S, et al. Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. Br J Haematol. 2013;160(4):445–64. Epub 2013/01/03.
9. Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37(12):3124–57. Epub 2009/09/24.
10. National Blood Authority. Patient blood management guidelines: module 3 – medical: quick reference guide. Canberra, Australia: National Blood Authority, 2012. https://www.blood.gov.au/system/
les/documents/20180426-Module3-QRG.pdf.
11. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coro­nary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(23):2999–3054. Epub 2011/08/30.
12. Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(11):770–9. Epub 2013/12/04.
13. Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, et al. Patient blood management: recommenda­tions from the 2018 Frankfurt consensus conference. JAMA. 2019;321(10):983–97. Epub 2019/03/13.
14. Wanderer JP, Rathmell JP.Perioperative transfusion: a complicated story. Anesthesiology. 2015;122(1):A23. Epub 2015/01/23.
15. American Society of Anesthesiologists Task Force on Perioperative Blood M.Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management*. Anesthesiology. 2015;122(2):241–75. Epub 2014/12/30.
16. Practice guidelines for perioperative blood transfusion and adju­vant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology. 2006;105(1):198–208.
17. Practice Guidelines for blood component therapy: a report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology. 1996;84(3):732–47. Epub 1996/03/01.
18. Hovaguimian F, Myles PS. Restrictive versus liberal transfu­sion strategy in the perioperative and acute care settings: a context- specic systematic review and meta-analysis of random­ized controlled trials. Anesthesiology. 2016;125(1):46–61. Epub 2016/05/12.
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