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Samuel Merritt University

2023

Gail Crawford, DNPA, CRNA

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blood component therapy transfusion medicine anesthesia medical procedures

Summary

This document reviews blood component therapy, including the donation process, compatibility testing, indications for transfusion, and blood conservation techniques. It covers various blood products and their uses, like packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate. The document also details assessment and planning for elective surgeries, including pre-operative blood conservation strategies.

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Blood Component therapy Gail Crawford, DNPA, CRNA Samuel Merritt University Program of Nurse Anesthesia Principles of Anesthesia I Summer 2023 Recommended Readings • Barash, P. G., Cullen, B. F., Stoelting, R. K., Cahalan, M. K., Stock, M. C., Ortega, R. A., Holt, N. F. (2017). Clinical anesthesia...

Blood Component therapy Gail Crawford, DNPA, CRNA Samuel Merritt University Program of Nurse Anesthesia Principles of Anesthesia I Summer 2023 Recommended Readings • Barash, P. G., Cullen, B. F., Stoelting, R. K., Cahalan, M. K., Stock, M. C., Ortega, R. A., Holt, N. F. (2017). Clinical anesthesia. Philadelphia, PA: Wolters Kluwer. • Chapter: 17: Hemostasis and Transfusion Medicine • Gropper, M. A., & Miller, R. D. (2020). Millers anesthesia (9th ed.). Philadelphia, PA: Elsevier. • Chapter 49: Patient Blood Management: Transfusion Therapy • Elisha, John Nagelhout, S. Nurse Anesthesia. (2023) (7th Edition). Elsevier Health Sciences (US), • Chapter 22: Blood and Blood Component Therapy • Pardo, M. C., & Miller, R. D. (2018). Basics of anesthesia. Philadelphia: Elsevier. • Chapter 24: Blood Therapy Objectives • Describe the blood donation, components separation and storage process. • Review the ABO-Rh compatibility and the differences between type and screen versus cross typing. • Summarize the indication for blood components therapy and the expected increases in hematologic parameter. • Demonstrate understanding of the blood conservation techniques • Describe potential complications associated with blood components therapy • Summarize the ASA Transfusion guidelines Crystalloids Normal Saline Lactated Ringers Dextrose Plasmalyte Colloids Synthetic Colloids Albumin BLOOD Type and Screen • “Type” • Patient blood is mixed with commercial “Anti A” and “Anti B” serums. • Reaction to “Anti A” = type A, etc. • Reaction to Both = Type AB • Reaction to neither = Type O • “Screen” • Coombs test for Rhesus Factor (Rh) • Exposed to Anti-D antibodies • Donor blood cells mixed with intended recipient • Takes approximately 1 to 1.5 hour to complete • 1) Immediate Spin. • 2) Incubate for 1 hour. • 3) Check for antibodies • Major crossmatch: Plasma from recipient + • • Type and Cross RBC from donor (99.9% effective) Minor crossmatch: RBC from recipient + Plasma from donor • Rarely done because donors are prescreened for unexpected antibodies. Autocontrol: Recipient plasma + Recipient RBC = Checks processes • Identify incompatibility that was not evident on T&S Compatibility Testing • ABO-Rh typing – 99.8% accuracy • Antibody screening – 99.94% accuracy • Cross matching – 99.95% accuracy Ordering Blood • Order T&S • Usually requires 2 draws 5 min apart (Safety) • Order Crossmatch • How many units of pRBCs to crossmatch? • Indication (Hct < 7, Intra-op, Pre-op, Active bleeding….etc) • Takes time • 1 hour for T&C, + 1.5hours for Crossmatch • Rare antibodies? How long would it take to finish the crossmatch process? Blood Storage Citrate: Prevents Clotting • Stored at temperatures of 1° C to 6° C • Citrate-Phosphate-Dextrose (CPD) • 21 days shelf-life • Citrate-Phosphate-Dextrose-Adenine (CPDA) • • • • Citrate prevents clotting by binding to calcium Phosphate acts as a buffer Dextrose is an RBC source of energy allowing glycolysis and maintaining ATP Shelf-life 35 days • Other additives • • • • AS-1 (Adsol) contains adenine, glucose, mannitol and NaCl AS-3 (Nutricel) contains adenine, glucose, citrate, phosphate and NaCl AS-5 (Optisol) contains adenine, dextrose, mannitol, and NaCl Shelf life 42 days Phosphate: Buffer Dextrose: Energy Adenine: Resynthesis of ATP Biochemical Changes in Stored Blood Take-home points regarding stored blood • Acidosis and increase H+ levels • RBCs metabolize into glucose to lactate • Hydrogen ions accumulation • Ultimately lowering the plasma pH • Hyperkalemia • The storage temperature of 1°C to 6°C inhibits the sodium-potassium pump, resulting in a loss of potassium ion (K + ) from the cells into the plasma and a gain of intracellular sodium • Decrease 2,3-DPG levels • Left shift in the oxyhemoglobin dissociation curve When to Transfuse: ASA Transfusion Task Force 1.A close watch on assessment of blood loss during surgery and assessment of tissue perfusion should be maintained. 2.Transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dL, and is almost always indicated when it is less than 6 g/dL. 3.For intermediate hemoglobin concentrations (6-10 g/dL), justifying or requiring RBC transfusion should be based on the patient’s risk for complications of inadequate oxygenation. 4.Use of a single hemoglobin “trigger” for all patients and other approaches that fail to consider all important physiologic and surgical factors affecting oxygenation are not recommended. 5.When appropriate, preoperative autologous blood donation, intraoperative and postoperative blood recovery, acute normovolemic hemodilution, and measures to decrease blood loss (deliberate hypotension and pharmacologic agents) may be beneficial. 6.The indications for transfusion of autologous RBCs may be more liberal than for allogeneic RBCs because of the lower risks associated with autologous blood. AABB : American Association of Blood Banks Transfusion Recommendations 1. Restrictive transfusion strategy for hemoglobin (7–8 mg/dL) in hospitalized, stable patients. 2. Restrictive transfusion strategy for hemoglobin (≤8 mg/dL) in hospitalized patients with preexisting cardiovascular disease with symptoms. 3. No recommendation for liberal or restrictive transfusion threshold in stable hospitalized patients with acute coronary syndrome. 4. Transfusion decision should be influenced by symptoms in addition to hemoglobin concentration. From Carson JL, et al. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2012;157(1):49–58 Massive Transfusion Protocol • Hospital-based protocol for severe blood loss > 10 units PRBC in 24 hr, or 1 blood volume • • Streamlines release of large amounts of blood products in a short time • Initiated by Anesthesia Communication between surgeon, anesthesia, blood bank, laboratory, and support personnel • • Standardized transfusion ratios (determined by hospital) 1:1:1:1 = 1 PRBC: 1 FFP, 1Platelet, 1 Cryoprecipitate • • • (If using Jumbo FFP = 2:1:1:1) Or 2:2:1/1 (2 PRBC, 2 FFP or 1 jumbo FFP, 1 Platelet alternated with 1 Cryoprecipitate) • Goal is minimizing dilution of clotting factors, avoiding DIC • Consider calcium with every 4 units PRBC EMERGENCY! • Trauma • Hemorrhage • Severe anemia • Universal donor: Type O, Rh-negative • Universal recipient: Type AB, Rh-positive • Type O blood is typically transfused • Rh negative units are generally given to women below the age of 50 • Rh positive units are generally given to women over 50 and male patients • Transfusion of Rh positive to Rh negative patients will result in anti-D formation in 20-50% of patients • If must give Rh-positive to Rh-negative women, consider prophylaxis Rh immunization with RhoGAM 300 mcg IM x 1 This Photo by Unknown Author is licensed under CC BY-NC-ND BLOOD PRODUCTS This Photo by Unknown Author is licensed under CC BY-SA Packed Red Blood Cells 1 UNIT PRBC: ~ 300mL Hct ~60-70% •Ideal for •Anemia •Replacement of blood loss anemia •Increase O2 carrying capacity •NOT for volume replacement •Blood warmer: cold blood and ↑Hgb 1 gm/dL ↑ Hct by 3%. hypothermia => coagulopathy •Filter: 170-260 μm filter (clots and debris) This Photo by Unknown Author is licensed under CC BY-SA-NC • Separated from whole blood or can be collected by apheresis • Frozen within 6 hours (-18o C) • Thawed when needed for transfusion • Thawed in a water bath over 20-30 minutes • Once thawed must be transfused within 24 hours FRESH FROZEN PLASMA (FFP) FFP Indications: INR/PT/PTT > 1.5 times normal Reversal of Coumadin (INR > 2) Massive Transfusion Protocol Advanced liver disease Coagulopathy disorders (DIC) Vitamin K dependent Factor replacement (II, VII, IX, and X) ACEI associated angioedema. Dose: 10-15ml/kg Increases factors ~20% 1 U FFP: 200-250 mL Jumbo: 300-600mL Contains ALL coagulation factors except platelets •Risk of complications (contains antibodies) •Transfusion-related acute lung injury (TRALI) •Transfusion-related cardiac overload (TACO) •Allergic or anaphylactic reactions. PLATELETS • 2 types: • Pooled platelet concentrates (PC): removed from whole blood • 1 unit of PC contain approximately 5.5x10 10 (55B) in 45-65 ml plasma • A unit of pooled platelet is derived from 46 different donors. • Less expensive to prepare than single donor, BUT more exposure to multiple donors per dose • Apheresis or a single donor concentrates • A unit of apheresis platelets contain approximately 3x10 11 in 200 ml plasma • More expensive but the yield is higher • Only one donor is required per platelet transfusion This Photo by Unknown Author is licensed under CC BY-SA-NC PLATELETS cont. 1 apheresis = 3 x 1011 (300B) ↑ U ~30-60 K/ml • Indications: • Thrombocytopenia • < 50K (minor surgery) • < 100K (Major surgery) • Higher if active Bleeding • ASA or Plavix • DIC • Massive Transfusion Protocols • ABO matching not necessary, but is recommended 1 pooled Unit = 5.5x10 10 (55B) in 45-65 ml plasma • Storage: • Stored at room temperature (higher risk of infection) • Cold temperature induces clustering of von • Willebrand receptors on the platelet surface and morphological changes (loss of discoid morphology) Shelf life is approximately five days at room temperature due to the risk of bacterial infection. Cryoprecipitate • Subcomponent of Plasma. Precipitates when FFP thawed • Indications: • • • • • von Willebrand disease Fibrinogen < 150mg/dl DIC, MTP Hemophilia A Liver disease • 1 Pooled unit= 2G fibrinogen, ↑ fibrinogen by ~70 mg/dl • 45 minutes to defrost and thaw. • Must use within 6 hours of thawing Contains: Fibrinogen: Factor I Fibronectin vWF Factor VIII Factor XIII 1 donor = 5-20mL Avg dose: 5-10 units Pooled 1Pool – 50-200mL Cryoprecipitate ONE unit of Cryoprecipitate contains: Fibrinogen – >150 mg of fibrinogen (range: 150 to 250 mg) Factor VIII – >80 international units (range: 80 to 150 unit) Factor XIII – 50 to 75 units von Willebrand factor – 100 to 150 units Fibronectin is also present (although there is no dosage requirement, concentration is not measured) Fibronectin is important for clots adhesion (super glue) I ate 13 vanilla Wafers. (With Super Glue) ASSESSMENT AND PLANNING Optimize for Elective Surgery • Treat anemia • Iron deficiency IDA) • Optimize underlying conditions • Cardiovascular disease • Increased risk for organ ischemia • Bleeding disorders • Address anticoagulants • Bleeding vs clotting risk • Pre-op transfusions if indicated Oral • • • Improved symptoms of IDA 2-3 weeks 3-6 months for increased H/H results • Side effects of N/V/C, Dark stool, abdominal pain Iron Transfusions • • • • may require multiple doses Symptom improvement 1 week Improved H/H 2-3 weeks • Side effects: allergic reaction, hypotension/syncope, respiratory distress Pre-op Blood conservation • Recombinant erythropoietin • Treatment of anemia prior to surgery • ESRD patient, chemotherapy, knee and hip surgery • Jehovah’s witnesses • Usual dose is 300 IU/kg for 10 days prior to surgery or 600 IU/kg once weekly for three weeks prior to surgery • Increases risk of blood clots. Preoperative Autologous Donation Criteria Preoperative autologous blood donation • Patient can donate own blood ahead of time • Every 4-7 days, up to 72 hours before surgery • Stored for up to 6 weeks • Donor’s hemoglobin must > 11g/dL prior to donation Advantages: • Less risk for transfusion–related diseases • Less Antibody-related reactions Disadvantages: • Risk of bacterial contamination • Risk of clerical errors • Higher cost than allogenic blood • Blood can be wasted if not used • Risk of Peri-operative anemia • Increased rate of transfusion Exclusions: • Severe cardiopulmonary Disease (AS, MI, CAD, CVA) • Scheduled surgery for Aortic Stenosis • Unstable Angina • MI or CVA within 6 month • Active Seizure disorder • Cyanotic heart disease • Uncontrolled hypertension • Evidence of infection and risk of bacteremia ASSESSMENT Pre-Op • • • Informed Consent for blood transfusion History: • Prior transfusions • History complications • possible antibodies from prior transfusion • Bleeding disorders/clotting disorders • Anticoagulants (Reverse?) • Labs: • H/H, Platelets, PT/ PTT, INR, bleeding times • T&S, Crossmatch if indicated • Comorbidities Order Blood Intra – Operative Start 2nd IV if anticipate transfusion • • • • Arms tucked? Robotic case? Blood warmer if multiple units Hang NS/ Compatible solution • • Keep patient warm (cold = bleeding) Consider fibrinolytics (TXA) early • Blood Loss: • Evaluation of blood loss • Sponges • Canisters (minus irrigation) Monitoring of patient status: • • • Hemodynamics PVV, SVV, Vitals • I-Stat Post-Operative • Monitor blood loss • Continue to treat anemia • Maintain normothermia • Minimizes O2 consumption • Decreases risk for bleeding • Resume Anticoagulants ? Blood Conservation Techniques Surgeon: “Quick Case….Probably just needs a little sedation” Acute Normovolemic Hemodilution • Process: • Initiated before the start of significant blood loss • Whole blood from a patient is removed • Citrate is added as anticoagulant • Intravascular volume is replaced with either crystalloid (3:1 ratio) or Colloid (1:1 ratio) • Can be stored in the operating room for up to 8 hours or at 4°C for 24 hours • When major bleeding has stopped or clinically appropriate • The blood is then re-infused into the patient Acute Normovolemic Hemodilution • Indications? • Likelihood of transfusion exceeding 10% of blood volume • Bilateral hip replacements • Hepatic resection • Major vascular surgery • Cardiac surgery • Absence coronary, pulmonary, renal or liver disease • Absence of severe hypertension • Absence of infection and risk of bacteremia Cell Saver (Interoperative Blood Salvage) • Blood from the operating field is collected, processed and reinfused during surgery • May be acceptable for SOME Jehovah’s Witnesses • Indications? • Anticipated EBL>20% of the patient blood volume • Some sources say > 500mL anticipated EBL • Crossmatch compatibility is unobtainable • The procedure is likely to require more than one unit of pRBCs • Risks: • Electrolyte disturbances • Dilutional coagulopathy • DIC • Exclusions? • Cancer cases • Possible bowel/fecal contaminants • Sepsis Tranexamic Acid (TXA) • Synthetic lysine analogue that reversibly blocks lysine binding site on plasminogen (and plasmin), therefore blocking fibrin binding and degradation of clots • Dose 1 g over 10 minutes • Repeat every 8 hours. • Uses: • Surgeries high risk for bleeding • Ortho: Given prophylactically at start of joint replacements • Spine surgeries • OB • Oral dose available for heavy vaginal bleeding Complications Viral or Bacterial Infections Very Low risk Pre-screening questionnaire Donated blood IS screened for • Hep B: (1 in 220,000) • HIV (1 in 1.8M transmission) • Hep C (1 in 1.6M) • Human T-Lymphocytic Virus (HTLV) • (1 in 640,000) • West Nile (1in >1M) • Syphillis Miller and Pardo, p 417 NOT tested for: • Covid (Respiratory virus, not blood-born) • Malaria (No donation for 3 years after moving from high-risk countries, or 1 year after visiting, without s/sx disease) • Chigas, babesiosis (1st time donor screened) • Prion Diseases (Creutzfeld-Jacob disease): Donor questionnaire for risk. No hx of transmission • Bacteria: No donation if on antibiotics, fever, illness Acute or Delayed. Immune or NonImmune Reactions Acute, Immune-related: ABO incompatibility (Clerical error, faulty Type and Cross, or antibody reactions) Incidence: 1 ~ 80,000 transfusions, Fatal in~ 1:800,000 units Williamson, Snyder 2019) Recipient antibodies attaching to donor RBC antigens forming antigen-antibodies complex Transfused cells lysed by the patient antibodies, which activates immune response Non-Immune Related: • Acute Hemolytic Transfusion Reaction Thermal reactions, osmosis, or mechanical injury to transfused blood cells causing lysis Acute Hemolytic Transfusion Reactions Pathophysiology: • Allergens react with and IgE and IgG antibodies • Antibodies bind to mast cell and basophils => histamine release • S/s Anaphyllaxis • Other mediators (heparin, leukotrienes, cytokines and activating factors) • Activation of complement system • Intravascular RBC hemolysis • Renal failure due to Hgb precipitation in renal tubules • Shock • DIC Signs/Symptoms: Chills Fever Urticaria Chest/Flank pain Hypotension Tachycardia Hemoglobinuria Shock DIC Anesthetized: Urticaria Brochospasm Hypotension Tacycardia Shock DIC Management of Acute Hemolytic Reaction 1. Stop transfusion 2. IVF to maintain UOP, BP and CVP 3. Maintain UOP > 1.5ml/kg/H. May use diuretics such as mannitol. Consider alkalization of urine with bicarbonate to prevent precipitation of hematin in the kidneys 4. Treat bronchospasm with bronchodilators 5. Review records 6. Hemolysis check – visually check urine for signs of free hemoglobin (pink or red colored plasma) 7. Draw labs Immediately, 1. Direct antiglobulin test (DAT). (Shows presence of antibodies or complements bound to RBC) 1-4 hours, and 24 hours 2. Tryptase levels (shows mast cell granules = anaphylaxis) within 60 min 3. Histamine levels immediately (within 30 min) This Photo by Unknown Author is licensed under CC BY-SA-NC Delayed Hemolytic Reaction • Usually mild • 3 days to 3 weeks after transfusion • Prior exposure (Pregnancy, transfusion, needle stick) • Non-D antigens of the Rh system • Cause reaction when “see” antigen again • Self-limiting symptoms: • Mild fever, • Jaundice, • Hemoglobinuria. • Diagnosed by Coombs (antiglobulin) test Febrile Nonhemolytic Transfusion Reaction • Acute and nonhemolytic cause • Commonly caused by cytokines released by WBCs during storage • Most common complications of transfused blood products (0.03-2%) • Signs and symptoms: increased in temperature by 1 degree Celsius WITHOUT hemolysis, may have increased BP and HR • Effective treatments: Acetaminophen and diphenhydramine • Future transfusion? Consider leukocytes reduction • Prior to leukocytes reduction technique, the incidence of FNHTR was as high as 30% Transfusion-associated Graft versus Host Disease (TA-GVHD) • Rare condition (1.0%) and almost always fatal (90%)` • Antibody activation: • T Lymphocytes from Donor => immune response against the recipient's tissue \ • Skin, bone marrow, GI tract • Pancytopenia, and liver dysfunction • DIC • Usually seen in immunocompromised patient • Prevention: Consider radiation of the lymphocyte and leukocyte reduction blood products in immunocompromised patients Transfusion-related acute lung injury (TRALI) • Epidemiology: • Second leading cause of blood transfusion related • • complication Leukocyte reduction strategies have reduced risk in past 10 years Plasma containing products, all products are implicated but FFP is the most common cause Incidence • 0.04% (healthy) • 8% ICU Mortality 5-25% • Pathophysiology • Antibody-mediated • Leukocytes antibodies in donor blood react with antigens in recipient • Systemic inflammation => activates neutrophils and pulmonary endothelial cells • Platelet migration into alveolar spaces may play a role • Capillary leak and lung injury • Noncardiogenic, inflammatory pulmonary edema https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324877/ TRALI • Risks: • Inflammation pre-transfusion • Elevated Cytokines interleukin 6 (IL-6) , IL-8 , and C-reactive proteins • Treatments • Supportive care • Mortality rate of 25% in general population but 58% in ICU patient • Ventilator support as lung injury is often transient • Administration of diuretic may worsen symptoms • Intravascular volume depleted • IVF to treat hypotension • Oxygen level usually returns to pretransfusion level within 48-96 hours • CXR returns to normal within 96 hours Transfusion-Associated Circulatory Overload (TACO) • Pulmonary edema following blood transfusion • NOT immune mediated (unlike TRALI) • Most common cause of transfusion-related reaction • (1-4% of transfusions) • Highest cause of transfusion-related mortality • Pathophysiology: • High colloid osmotic pressure of blood • Pulmonary capillary pressure overwhelmed • Increased L atrial pressure and pulmonary capillary pressures • Diagnosis criteria: 3 or more symptoms within 6 hr post transfusion TACO : Clinical Manifestations Risk Factors History of CHF Renal insufficiency Chronic use of diuretics Rapid transfusion of blood products Positive fluid balance Clinical manifestations Dyspnea Hypoxemia Tachypnea Rales/Wheezing Hypertension (Distinguished from TRALI) Hypotension with heart failure Tachycardia Increase left atrial pressure Widened pulse pressure JVD Distention Treatment Stop or slow transfusion. Oxygen Intubation and ventilation Diuretics Cardiovascular support as needed Hypothermia • Rapid Infusion • Large volume • Unwarmed blood • Temp below 35o C • Hypothermia • Shivering • Cardiac irritability • Decreased medication clearance • Poor wound healing • Cardiac ischemia • Coagulopathies USE BLOOD WARMER if > 2 units Citrate Toxicity • Rapid transfusion of multiple units (MTP) • Stored blood has approximately 3g of citrate per 1 unit RBC • In healthy adult, liver metabolizes 3 g of citrate in 5 minutes • Cictrate => bicarb => metabolic alkalosis and respiratory acidosis • Citrate chelation of calcium (hypocalcemia) => hypotension, muscle weakness, tetany, arrhythmias, acquired coagulopathy and myocardial depression • Treatment • Calcium chloride 1 gm (central line or large PIV) • Calcium gluconate 3 grams What fluid to use? LR, Plasma-lyte, D5%, D5 ½ NS, D5 NS, NaCL? • • • • • • • • • Paresthesia Muscle Spasms Bradycardia Long QT Hypotension Cardiac arrest Bronchospasm Laryngospasm Seizures • Large volume of transfusions = low ionized calcium • Citrate in stored blood binds with calcium, precipitates from serum • • • • • Recommended solutions are 5% dextrose in 0.45 Nacl 5% dextrose in Nacl NaCl Plasmalyte • LR not recommended (Contains calcium) • What about with Cell-Saver??? References American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. 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;105:198–208. Barash, P. G., Cullen, B. F., Stoelting, R. K., Cahalan, M. K., Stock, M. C., Ortega, R. A., . . . Holt, N. F. (2017). Clinical anesthesia. Philadelphia, PA: Wolters Kluwer. • Chapter 17: Hemostasis and transfusion medicine Blood banking. (n.d.). Retrieved September 17, 2017, from https://library.med.utah.edu/WebPath/TUTORIAL/BLDBANK/BLDBANK.html Carson JL, et al. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2012;157(1):49–58 Keidan, L., Amir, G., Mandel, M., & Mishali, D. (2004). The metabolic effects of fresh versus old stored blood in the priming of cardiopulmonary bypass solution for pediatric patients. The Journal of Thoracic and Cardiovascular Surgery , 127(4), 949952. doi:10.1016/S0022-5223(03)013163 Roubinian N. TACO and TRALI: biology, risk factors, and prevention strategies. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):585-594. doi: 10.1182/asheducation-2018.1.585. Epub 2018 Dec 14. PMID: 30570487; PMCID: PMC6324877. Schwartz, A. J., Matjasko, M. J., & Otto, C. W. (2003). Refresher courses in anesthesiology: Intraoperative fluid management and choice of fluids (Vol. 31). Lippincott Williams & Wilkins.

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