Artículo de Revisión

Daniel Rivera Tocancipá*, Antonio Pérez Ferrer**

* Anestesiólogo de trasplante. Epidemiólogo. Coordinador, Posgrado Anestesiología, Facultad de Medicina, Servicio de Anestesiología y Reanimación, Universidad Surcolombiana. Neiva, Colombia. Correspondencia: Calle 9 con Carrera. 14. Neiva, Huila. Correo electrónico: riverato@hotmail.com

** Anestesiólogo pediátrico y de trasplantes, Hospital Universitario La Paz. Madrid, España.

Recibido: noviembre 16 de 2010. Enviado para modificaciones: noviembre 18 de 2010. Aceptado: agosto 19 de 2011.

Introduction. Blood transfusions are tissue transplants with morbimortality and costs involved.

Methodology. A description of the strategies consistent with the current literature that offers a review of de last decade.

Results and Conclusions. We have to deal with elderly patients with comorbidities who will undergo complex procedures. Blood transfusions must be streamlined, thorugh the development of technical protocols, improving the patient’s condition, decreasing operative blood loss, recovering any blood losses and establishing an institutional program for autologous blood donation.

Blood transfusions must be streamlined due to the potential complications (1,2) including the reluctance of patients to accept the transfusion and the shortage of available blood (a situation that is becoming increasingly serious due to the decreasing numbers of young donors as the population pyramid becomes inverted), in addition to costs. In order to cope with such difficulties, the following strategies are suggested (3):

1. Raise the preoperative hemoglobin (Hb)

2. Reduce the transfusion threshold

3. Diminish surgical bleeding

4. Implementation of autologous blood transfusions

5. Dissemination of strategies

The purpose of this article is to restore and organize basic, simple and feasible clinical strategies to be adopted in most medical care facilities so as to “save” blood during the perioperative period and reduce both morbimortality and costs.

Raise the pre-op hemoglobin

The patient shouldn’t be anemic prior to surgery. Men are considered anemic if Hb <13 g/dl and <12 g/dl in women and these values must be determined (4) (Figure 1); most cases of anemia are iron-deficient (5) and can be managed with iron or erythropoietin supplementation prior to surgery. When the decision is to transfuse, the goal should be to increase the tissue oxygenation by increasing the transport medium (Hb) (6). Other types of anemia require hematological evaluation and blood tests should be performed 3 weeks prior to surgery.

Iron deficiency anemia (the most common type of anemia) is typically microcytic - hypochromic (7) and is caused by increased iron demand, iron losses or inadequate intake of the mineral. Iron deficiency anemia is diagnosed using the mean corpuscular volume (MCV) <100 fl, ferritin <12 mcg/L or Transferrin Sat. <15 %. Anemia due to a chronic disease (second cause) is typically hypoproliferative (8), such as in cancer, autoimmune diseases and chronic renal failure. Its origin is multifactorial: increased hepcidin synthesis, inhibition of the erythropoietin synthesis and the erythroid proliferation, and increased hematophagocytosis. The diagnosis is based on laboratory tests (Table 1).

Preoperative Management of Iron Deficient Anemia

Supplement with 50 to 100 mg/day of iron by mouth. The iron body deficit can be calculated in milligrams, according to Ganzoni’s formula (9):

Weight (kg) x (desired HB - actual Hb) x 2.4 + iron deposits

Over 35 kg: desired Hb: 15 gr/dl. Iron deposits: 500 mg.

Lees than 35 kg: desired Hb: 13 gr/dl. Iron deposits: 15 mg/kg.

Pregnancy and post-partum: desired Hb: 12 gr/dl.

If ferritin >50 ng/ml do not add stores

Each PRBC unit contributes with 200 mg of elemental iron

Parenteral iron may be administered if the chronic losses exceed the iron absorption, the oral treatment fails or whenever a fast correction is required; the contraindications for parenteral iron are hemochromatosis, hypersensitivity to the preparations, liver dysfunction, active infection and transferrin saturation >20 % or ferritin >400 ng/ml. (10)

There are several parenteral iron presentations. The saccharose type is the classic European type and the most popular. Dextrane, which is rarely used, requires a sensitivity test to determine anaphylactic reactions. Gluconate doesn’t require any tests but its low concentration limits replacement. Carboxymaltose is a more recent presentation and must be diluted and administered slowly. Around 200 mg of parenteral iron raises the Hb level by approximately 1 gr/dl; its effect begins at day 7. The usual dosing ranges from 100 mg per dose, up to 600 mg per week; however, each presentation should be reviewed individually to adjust the dose according to each particular situation (11).

Lower transfusi on thres hold

Numerous studies have shown that the transfusion threshold may be lowered to 7 gr/dl of Hb (12) (restrictive threshold), even in critical patients (13). A subgroup of “coronary” patients showed contradictory results and apparently tolerates the restrictive threshold if asymptomatic (14); the symptomatic coronary patients must have a hemoglobin level of 10-12 gr/dl (15). In contrast, a traditional “liberal” threshold (Hb = 10 gr/dl) increases mortality (16), raises costs (17) in addition to postoperative infections (18), including pediatric patients (19,20). You should keep in mind the ASA guidelines for transfusions (21). Having an SvO2 >70 % as an independent parameter may be useful and may even avoid the transfusion (22-24).

The “allowable blood loss” formula (ABL) estimates the tolerable blood loss before a transfusion is needed (25). The clinic of the patient always prevails, considering patients on a case-by-case basis (26).

ABL = (Actual Hematocrit - Threshold Hematocrit)/average Hematocrit x Volemia

Threshold Hematocrit: Minimum allowable hematocrit before making the decision to transfuse; this is a theoretical concept derived from reducing the actual hematocrit of the patient by 30 %, or by 20 % in stable cardiopulmonary pathology and even by 10 % in the critical patient; the end value should be less than 25 %.

Volemia (ml): Weight of the patient (kg) x 70. In pre-term babies, multiply by 110; for newborns and neonates, multiply by 90; in children x 80; in youngsters x 70; in elderly males x 65; and in elderly women x 60. The younger and stouter the patient, the higher the percentage of body water (volemia).

Strategies to reduce surgical bleeding

For study purposes the strategies are segmented; however, in a blood saving program, these strategies must be complementary to one another.

Pharmacological Strategies

Some drugs improve the thrombogenesis and others reduce the fibrinolysis. Overall, the evidence favors tranexamic acid on account of its safety, risk-benefit ratio and costs. The second choice options are aminocaproic acid, prothrombin complex and activated Factor VII, though the latter is questioned on the basis of its cost-benefit ratio (27). The adverse reactions override the benefits if not used in the right patient and according to the appropriate prescription; for instance, if the patient is at high risk of bleeding and of being transfused. A lot has been learned about the physiology of fluids (28,29) and the management of hemorrhagic shock (30) to enable an overview of the available drugs.

Recombinant Activated Factor VII: The conventional dose is 80 to 120 mcg/kg. For massive bleeding blunt trauma: 200 mcg/kg, followed by 100 mcg/kg after one and then three hours (31). Recombinant Activated Factor VII increases the number of thromboembolic events. In obstetric bleeding (32-34) and trauma (35) its use is “off-label”. Cost is the most important limiting factor. It is indicated for bleeding in hemophilic patients with inhibitor, in patients with acquired hemophilia, congenital Factor VII deficit and Glanzmann’s thrombasthenia; additionally, it provides a potential benefit in incoercible bleeding, as long as adequate conventional treatment is administered under the following conditions: Prior utilization of surgical approaches, embolization and use of blood products, hemoglobin >7 gr/dl, platelets >50,000 x L, fibrinogen >0.5 gr/L, arterial pH >7.20, temperature >32 °C and ionized calcium >0.08 mmol/L (36).

Prothrombin Complex: Contains coagulation factors II, VII, IX y X. Some preparations include heparin and C-S protein complex. Indicated for coagulation factors deficiency, bleeding control with oral anticoagulants or in the case of vitamin K deficiency as well as prophylactic treatment intraoperative bleeding. Its use is contraindicated in cases of known allergies, in heparin thrombocytopenia, in new onset thromboembolic disease and high risk of DIC (37). Individualized INR dose: ≥5 administer 30 IU/kg, and <5 administer 15 IU/kg 1 ml/minute - Action after 10 minutes - Usually should be complemented with vitamin K (38).

Tranexamic Acid: Blocks fibrinolysis through reverse antagonism of the lysine receptor at the plasminogen - fibrin bond, hence preventing its transformation into plasmin. High doses block plasmin directly and are associated with seizures. Indicated for bleeding associated to hyperfibrinolysis (metrorrhagia, upper GI bleeding, dental bleeding) and surgical bleeding prophylaxis (cardiac surgery, major orthopedic surgery, liver transplantation). Suggested for major bleeding in trauma at a dose of 10-15 mg/kg, followed by a 1-5 mg/kg/h infusion until the bleeding is under control (39).

Epsilon-Aminocaproic Acid: Action and indications similar to tranexamic acid. Preserves platelet function by avoiding the degradation of the platelet glycoprotein 1b receptor. Dose: 100-150 mg/kg, followed by a 15 mg/kg/h infusion (40).

Desmopressin: Analogue of vasopressin, has a hemostatic effect through the induction and expression of the endothelial Von Willebrand Factor (VWF), activating Factor X. It can be helpful in bleeding episodes in Von Willebrand patients, in patients with hemophilia A and functional platelet defects. Intranasal dose of 150 ucg/kg up to 50 kg. In patients over 50 kg, administer 300 ucg/kg. Intravenous: 0.3 ucg/kg diluted in NSS, administered over 30 minutes. Subcutaneous: 0.3 ucg/kg (singe dose). Adverse effects include: tachycardia, flushing, headache and hyponatremia. Contraindications: atherosclerosis, venous thrombosis, thrombocytopenic purpura and Von Willebrand type 2B patients (41). Aprotinin is not discussed because the drug was removed from the market on the assumption that it raises mortality, as reported in a Canadian Trial in 2007 (42).

Anesthetic Strategies

Four key aspects are considered: First, controlled hypotension, meaning that the mean blood pressure (MBP) drops with no vital organ involvement but attenuating the pressure that drives bleeding in bloody beds. MBP may rise to 50 mmHg and in patients with cardiopulmonary or neurologic disease it should be <60 mmHg (43). Second: caution must be used with the administration of intravenous fluids; exceeding the level of fluids may result in dilutional coagulopathy (44); “colloids” may disrupt the platelet function. The recommendation is to keep the filling pressures low (45). Third, regional anesthesia decreases any blood losses against general anesthesia and should be preferred (46). And, Fourth, the patient’s position (47) with the surgical area above the heart decreases bleeding by reducing the hydrostatic pressure in the right atria; you must be watchful for the potential or air embolism in these cases. When the patient is in prone position, pillow rolls must be placed along both mid-clavicular lines in order to reduce intra-abdominal pressure and the pressure over the vena cava and hence limit the bleeding.

Surgical Strategies

Follow the Halstedian surgical principles (handle tissues gently, achieve meticulous hemostasis, dissect plane by plane and selective ligatures) to reduce blood loss (48). The electric scalpel and other options to dissect, cut and achieve clotting simultaneously (such as the electrocautery, argon laser and the ultrasound or radiofrequency scalpel, as well as endoscopic or video-assisted surgery) all reduce bleeding. Both the tourniquet for limb surgery and adrenalin for surgical incision should be used, except when contraindicated (49).

Intraoperative Hemostatic Agents

Various fibrin glue products, topical pro-coagulation techniques and hemostatic agents on the surgical field as a barrier method have questionable evidence and are costly. Good quality studies are required to systematically recommend these methods (50).

Strategies for Autologous Transfusion

Any patient with adequate preoperative Hb, and a higher risk of bleeding benefits from autologous blood transfusion (51). There are three options for autologous transfusion: Preoperative autologous donation (PAD); normovolemic intraoperative hemodilution (NIH); and blood recovery from the operative field (52). They all differ with regards to the technique used, the times and indications for each case. These should become part of the blood-saving strategies program; otherwise, their benefit shall be limited (53).

Preoperative Autologous Donation (PAD)

The patient previously donates blood and this blood is reserved for the surgical procedure; this limits the risk of allogeneic transfusion. With adequate stimulation (iron and erythropoietin) (54) any loss is compensated before surgery (55). The process begins 3 week prior to surgery; however, a faster option takes one week. Another option is to do an Normovolemic Induced Hemodilution (NIH) (42).

With the use of PAD the transmission of transfusion diseases decreases, as well as the erythrocyte alloimmunization, the need for allogeneic blood, adverse reactions and any transfusion risks; furthermore, it is compatible with patients presenting autoantibodies. The disadvantages are the risk of bacterial contamination, ABO incompatibility due to human error; the fact that it is more costly than allogeneic blood (non INH) and may result in blood loss if not transfused (56).

The above considerations may lead us to conclude that the indications for PAD are three: shortage of allogeneic blood (rare blood type groups or multiple allo/autoantibodies), surgery with a high risk of massive bleeding and the patient’s rejection of allogeneic blood.

Conditions for PAD

1. Surgery with a high probability of transfusion

2. Definite date for the surgery

3. Minimum one-week time in between each donation, and three days between the last donation and surgery.

4. Hb pre-donation level above 11 gr/dl

Contraindications for PAD

1. Serious or cyanotic heart disease

2. HIV infection or hepatitis C or B

3. Active bacterial infection

4. Unstable angina

5. Myocardial infarction or cerebrovascular accident in the past 6 months

6. Uncontrolled high blood pressure

How should the PAD be performed?

1. Explicit prescription by the anesthesiologist: Diagnosis, volume requested and date of surgery. The volume to be drawn must be a maximum of 13% of the volemia in adults and 10% in children (approximately 10.5 ml/K) (57).

2. Informed consent signed by the patient or his/her legal representative

3. Evaluation by the blood bank to rule out any contraindications

4. Blood extraction and testing as in a conventional blood donation. Draw up to 1 unit of PRBC per week with at least a 3-day interval between the last draw and the surgery.

5. Supplementary iron is controversial. If there is no contraindication, administer 100 mg per day orally. For special cases consider parenteral administration.

6. EPO is effective to rule any neoplasms and thromboembolic disease.

Abbreviated PAD Guide

Obtain a maximum of 1 unit of PRBC one week prior to surgery; the abbreviated PAD regime is started and iron supplementation when the probability of major bleeding is high. Normovolemic Intraoperative Hemodilution (NIH) can be considered an option.

Recombinant Human Erythropoietin (EPO )

The role of is to promote the production, differentiation and survival of erythrocytes and retards apoptosis. It also acts on the EPO cell-surface receptor (EPO-R) and hence increases the resistance to cell hypoxia by protecting the tissues against ischemia.

Apparently, EPO has an angiogenic effect, a half-life of 4-9 hours when ad ministered IV and 18-24 hours if administered subcutaneously.

In short treatment courses like those used in PAD and NIH, virtually no side effects, with the exception of a potential increase in deep venous thrombosis in patients with no anti-thrombotic prophylaxis (58). On the contrary, its chronic administration is associated with adverse effects such as high blood pressure, headache, thrombocytosis, flue-like symptoms, AV fistula thrombosis, erythrocyte aplasia, hyperpotassemia and skin reactions. EPO is contraindicated in uncontrolled high blood pressure, coronary heart disease, peripheral arteriopathy, in patients with a history of myocardial infarction, CVA, red blood cells aplasia and absence of thromboprophylaxis (59).

In adults, the Hb level should be 10-12 gr/dl and in children 9,5-11 gr/dl; higher levels predispose to heart morbidity and increase overall mortality. EPO is not approved for pediatric patients as part of PAD.

EPO is a useful blood-saving strategy if the patient is anemic and important blood loss is expected (<1 liter), because it reduces the need for blood transfusions, especially in orthopedics. A reticulocyte response is observed on day three and increased Hb after one week.

How should EPO be used?

1. P P AD: 600 IU/K twice weekly, associated with iron, during the three weeks prior to surgery.

2. N N o PAD, conventional regime: 600 IU/K on day 21, 14 and 7 prior to surgery and the day of the operation.

3. Short regime: 300 IU/K per day for 10 days prior to surgery, on the day of surgery and up to the fourth day post-op.

Normovolemic Intraoperative Hemodilution (NIH)

Blood is drawn form the patient during the induction of anesthesia; it is replaced with crystalloids or colloids to dilute the patient’s red blood cells so that less erythrocyte mass will be lost during bleeding (60). Once the bleeding peak is over, the erythrocyte-rich blood extracted is re-infused. Be cautious with the quantity and the rate of blood extraction (61).

The blood drawn must never leave the OR and can be used within the next six hours and must be refrigerated (in the OR, never in the blood bank) for up to 24 hours for the post-op. The advantages of NIH are similar to the advantages of PAD; furthermore, the blood does not undergo any “storage injury”, there is less hypothermia as compared to transfusing bank blood, the platelet function is preserved if re-infused within 6 hours, the loss or erythrocytes during surgery decreases (because of lower hematocrit), blood rheology improves because of hemodilution and is simpler an cheaper as compared to PAD (62).

How to do the NIH?

1. Check the indications and contraindications

2. Basic intraoperative monitoring

3. Catheterization of a large peripheral vein

4. Through a second puncture extract the blood volume (BV) = (Hctoi - Hctof)/ average Hctof x Volemia (63). The Hctof is the individualized minimal allowable hematocrit and the recommendation is <25 %, or >70 % of the initial hematocrit.

5. Replace 3 ml of crystalloids per ml of extracted blood (3:1). When needed, restrict water intake, replace each ml extracted with 1 ml of colloid (1:1).

6. Store the extracted blood in bank bags in the OR.

7. Proceed to transfuse the autologous blood when the surgical bleeding has been controlled and with guaranteed hemostasis.

The indication, contraindications and the conditions for NIH are similar to those established for PAD.

Blood Recovery in the Operative Field

There are “blood cells saver devices” (64) for recovering, via aspiration, any operative bleeding and then a machine heparinizes, filters, centrifuges, washes and concentrates the erythrocytes in order to achieve blood cells concentrates suspended in normal saline solution with a hematocrit between 50 % and 70 % for re-infusion into the patient. These devices have been by Schaff (65) back in 1978 (65) but are beyond the scope of this review and therefore should be looked up in other articles (66).

Education and dissemination of strategies

Management commitment and interdisciplinary collaboration are required to disseminate, implement and evaluate the strategies and provide feedback. The Transfusions Committee is expected to lead the process by providing staff training, workshops and simulations similar to those offered by the AHA in the area of cardio-cerebral-pulmonary resuscitation (67). A weekly follow-up shloud be implemented, analyzing the successes and all blood transfusions to determine how relevant and adjusted to the protocols they were. A poorly articulated Program will not accomplish the goal but in contrast, will increase the number of complications and raise costs as a result of isolated actions.

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