Lowering the transfusion trigger

Lowering the “transfusion trigger” means accepting lower hemoglobin/hematocrit levels for treatment without blood transfusion. The “10/30” (hemoglobin/hematocrit) transfusion trigger employed for decades to dictate blood transfusion practices was based on a study in dogs by Adams and Lundy in 1942 and has been demonstrated to be invalid in humans. Lowering the transfusion trigger from 10 g/dL to 7 g/dL in critically ill patients in intensive care reduced red cell unit transfusions by 54% and improved clinical outcomes.4,10

The Association of Anaesthetists of Great Britain and Ireland affirms that “a haemoglobin concentration of 8–10 g.dL⁻¹ is a safe level even for those patients with significant cardiorespiratory disease” (2008, http://www.aagbi.org/). The current guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists24 suggests a transfusion trigger of hemoglobin less than 7 g/dL. However, patients have survived with hemoglobin below 3 g/dL, and so currently there is no universal transfusion trigger (Spence, 2004, www.orthosupersite.com).

Optimizing the hematocrit

Optimizing the hematocrit increases the tolerable blood loss or the margin of safety in the event of blood loss. Iron therapy is at the center of current efforts in this regard, with or without erythropoiesis-stimulating agents (ESAs), even in the absence of absolute iron deficiency4,25:

1. Oral iron therapy is the modality of choice for eligible patients. Ferrous sulfate, gluconate, or fumarate may be used to administer ideally 200–220 mg of elemental iron per day. Adjuncts to be given daily include vitamin C, 500 mg; vitamin B₁₂, 150 µg; folic acid, 5 mg; multivitamins; and nutritional support.2,25 The author avoids folic acid in malignant disease.26

2. Parenteral iron therapy corrects anemia more rapidly and may be used alone or in conjunction with ESAs. Iron dextran is the classical preparation, but less allergenic preparations are favored when available, such as iron sucrose (preferred) and iron gluconate.25 Dose in mg can be weight × [normal Hb − actual Hb] × 0.24 + 500 (where Hb  =  hemoglobin concentration in g/L),25 or [normal Hb − actual Hb] × 200 + 500 (where Hb is in g/dL).2

   Iron dextran is diluted in normal saline at a ratio of 5 mL (250 mg):100 mL saline and administered intravenously initially at 20 drops/min for 5 minutes, then 60 drops/min if no side effects occur. The total dose may be given at once to a maximum of 20 mg/kg body weight over 4–6 hours or in divided doses on alternate days (preferably).2,25 The author found that administering 100 mg hydrocortisone intravenous (i.v.) 15 minutes before iron dextran and diluting 5 mL (250mg) of iron dextran in 250–500 mL of normal saline successfully averts allergic reactions, even in a patient who previously reacted when those measures were not taken.26

3. Erythropoietin alfa, which has been in use for blood conservation in oncology since 1989, was approved for perisurgical use in the United States in 1996. Beta preparations are also available. In general surgery 100–150 U/kg subcutaneous (s.c.) for 6 doses (e.g., twice weekly for 3 weeks) is recommended.2 In oncology 150 U/kg s.c. 3 times weekly or 40,000 U s.c. weekly is the recommended starting dose.27 Darbopoietin alfa is a long-acting ESA that can be administered s.c. weekly (2.25 µg/kg) or every 3 weeks (500 µg). Intravenous iron is recommended in conjunction with ESAs as it potentiates the response and averts functional iron deficiency.2,28

   ESAs stimulate RBC production by up to 4 times the basal marrow rate. Reticulocyte count increases by day 3, and hemoglobin typically increases at 1 g/dL every 4–7 days.28 Use of ESAs is not recommended when the hemoglobin is above 12 g/dL in oncology.27

Optimizing the hemoglobin with the appropriate medication is indicated in virtually all surgical patients, in elective and emergency cases, and for treatment and prophylaxis of anemia.2 Interventions in this regard do not start working slowly after 21 days, as some may imagine; they start working immediately and build up over time.25,28 Provided the main pathology is properly treated, the patient's improvement with bloodless care is sometimes dramatic, compared with patients who are transfused.

Minimizing blood loss

Efforts towards minimizing blood loss in the surgical patient start from the first contact and span through the entire perioperative period.

1. Good history, physical examination, and laboratory investigations are essential even in emergencies, taking note of the following among others:

   1. History of bleeding disorders

   2. Anticoagulant therapy

   3. Site of external hemorrhage (to be promptly arrested)

   4. Estimate of blood loss

   5. Full blood count

   6. Clotting profile (if indicated)

2. Pharmacological agents that can reduce hemorrhage include the following2:

   1. Vitamin K, 10 mg (2.5–50 mg) per os (p.o.), intramuscular (i.m.), s.c., i.v.

   2. Tranexamic acid, between 1.5 g 3 times per day and 1 g 6 times per day for 5–7 days, first i.v. then p.o. (for prophylaxis, 1 g p.o. preoperative).

   3. Aprotinin, 500,000 KIU i.v., then 150,000 KIU/h in infusion (low-dose regimen for noncardiac surgery); or 2,000,000 KIU i.v., then 2,000,000 KIU in cardiopulmonary bypass (CPB) prime, then 500,000 KIU in infusion for duration of surgery (Hammersmith high-dose regimen for cardiac surgery).

   4. Epsilon aminocaproic acid, 0.1 g/kg i.v. over 30–60 minutes, then 8–24 g/d or 1 g every 4 hours. When bleeding stops, 1 g every 6 hours. The same dosage can be given p.o.

   5. Desmopressin (1-deamino-8-D-arginine vasopressin or DDAVP), 0.3 µg/kg i.v. or s.c., 2 times perioperative, second dose 6–8 hours after the first; or 2 intranasal “standard puffs” totaling 300 µg for home use (e.g., menorrhagia), repeated as necessary after 8–12 hours.

   6. Recombinant factor VIIa, 90 µg/kg i.v.; repeat dose every 2–3 hours or as needed.

   7. Somatostatin

   8. Vasopressin

3. Noninvasive monitoring such as pulse oximetry, whenever possible, minimizes blood loss.

4. Restriction of diagnostic phlebotomies reduces blood wastage. Microsampling is a recent technique that drastically reduces the volume of blood needed for tests, with obvious benefit in blood conservation.

5. Intraoperative strategies that could be employed to reduce blood loss include the following:

   1. Normothermia averts coagulopathy due to hypothermia1,2,29 and may be achieved by (1) maintaining room temperature above 27°C, (2) using thermal suits or blankets, and (3) warming intravenous infusions.

   2. Acute normovolemic hemodilution involves withdrawal of some of the patient's blood in theatre prior to incision and replacement with colloids and/or crystalloids, so that intraoperatively the patient loses dilute blood with less effect on the total red cell mass. The withdrawn blood is kept within view in theater and is reinfused at the end of surgery.

      Up to 4 units may be withdrawn safely using the formula V  =  [Baseline HCT − Target HCT] / Average HCT × EBV, where V  =  volume, HCT  =  hematocrit, and EBV  =  estimated blood volume (Loubser, 2009, http://wiki.noblood.org/Acute_Normovolemic_Hemodilution).

   3. Regional anesthesia results in less intraoperative blood loss than general anesthesia through mechanisms not yet fully elucidated.2

   4. Positioning of patients to minimize blood loss is guided by two principles2: (1) elevate the operation site above the right atrium (e.g., Trendelenburg for prostatectomy, reverse Trendelenburg for thyroidectomy), and (2) avoid compression of venous drainage (e.g., tilting patient in supine position slightly to the left to avoid compression of inferior vena cava in abdominal surgery).

   5. Meticulous hemostasis and good operative technique can save up to 1 or more units of blood.1 Use of diathermy and topical adhesives like fibrin glue and Surgicel (Johnson & Johnson, Somerville, New Jersey) limits blood loss, as does judicious use of tourniquet. Argon beam coagulator and Cavitron Ultrasonic Surgical Aspirator are blood-conserving innovations in hemostasis and dissection, respectively.1,2,30

   6. Cell salvage and autotransfusion can be performed effectively by techniques ranging from simple manual scooping of blood from a wound, filtration, and then reinfusion, to use of sophisticated computerized cell salvage machines that return washed blood into the patient.

   7. Other techniques like controlled hypotension and hypothermia may be used cautiously in selected patients.2,4

Optimizing tissue oxygenation

Allogeneic blood transfusion has been shown not to improve tissue oxygenation.19–21 However, tissue oxygenation can be improved by other methods that avoid blood transfusion by considering the equation for oxygen delivery31: DO₂  =  CO × CaO₂  =  CO × {(Hb × SaO₂ × 1.39) +(PaO₂ × 0.003)}, where DO₂  =  oxygen delivery, CO  =  cardiac output, CaO₂  =  arterial O₂ content, Hb  =  hemoglobin concentration, SaO₂  =  fraction of hemoglobin saturated with O₂, and PaO₂  =  partial pressure of O₂ dissolved in arterial blood). Thus, even when Hb is low, DO₂ can be improved by improving the CO and CaO₂ (SaO₂ and PaO₂).

1. Volume replacement with crystalloids (e.g., normal saline and Ringer's lactate) or colloids (e.g., Hetastarch, Hemacel, Dextran, and Isoplasma) reduces blood viscosity and improves cardiac output. The crystalloid requirement is 3 times blood volume lost, while colloid requirement is equivalent volume lost.

2. Oxygen therapy increases SaO₂ and PaO₂. Intraoperative hyperoxic ventilation not only improves tissue oxygenation but also can augment acute normovolemic hemodilution and avert allogeneic blood transfusion.2,4 Hyperbaric oxygen is rarely needed but may be used when indicated and available.2,4

3. Minimizing oxygen consumption may be achieved through appropriate interventions, such as adequate analgesia, treatment of sepsis, and mechanical ventilation (to reduce the work of breathing).

4. Causes of tissue hypoxia should be treated promptly (e.g., pneumonia and bronchial asthma).

5. Inotropic and vasoactive agents may be used in extreme cases to improve cardiac output.

6. Artificial oxygen carriers are still largely experimental. They include Perfluorocarbon emulsions and modified hemoglobin-based solutions. They have been used successfully in augmented acute normovolemic hemodilution.2,4