Personalized approach to define transfusion support to surgical patients

Instruction

Blood donation and transfusion practise have been drammatically affected by recent changes in the medical and public perception of risks (1.2) and benefits of blood transfusion. Consequently, the use of autologous blood, obtained using different techniques (3-5) has increased in most countries (6-8). Preoperative autologous blood donation (PABD) is an attractive way of obtaining autologous blood, because it is simple to perform, relatively economical and safe in most patients scheduled for elective surgery. Moreover, when correctly utilized, it significantly reduces the use of allogeneis blood. As a result, PABD programs have become increasingly more popular with patients and wiewed as a standard of care by physicians sharing the public’s concern about the risk of using allogeneic blood and anxious about legal liability (9,10).

However, expected benefits of PABD may be declining as stricter criteria for donor selection and more reliable laboratory assay for infectious disease markers contribute to increase the safety of allogeneic supply. Moreover, autologous blood is considered more costly than allogeneic blood due to the more labor-intensive donation processes (11,22).

Improving PABD cost-effectiveness will become increasingly more important as financial pressures on the health care system place great emphasis on the costs and priority of medical interventions. Thus every effort should be made to make the practise of autologous transfusion more efficient in order to lower the cost of autologous units.

PABD can be made more cost-effective by reducing the cost of collection, which is possible through a better organization of presurgical evaluation and scheduling, using single collection bags, simplifyng the patient’s visit, and donation process, especially in subsequent donations along with avoiding serological tests for infectious disease markers (13).

However, primary responsible for the higher cost of autologous blood and its variations according to procedure, results mainly from the units that are collected and discarded because not transfused. Thus PABD lowtransfusion riskekective surgery is inappropriate and should be avoided since it is costly, time consuming and can involve unnecessary health risks to patients during the donations procedure (14).

The first step is to identify procedures associated with low transfusion requirements. A reasonable and practical approach would be to base decisions on the need for PABD, on the maximum surgical blood order schedule (MSBOS) (15) for the procedure in the hospital where surgery is to be performed. When patients are candidated to an operation, prior to which a type and screen procedure is usually performed, they might be discouraged by predeposit autologous blood. Autologous blood collection should be limited surgical procedures in which the need for blood transfusion has already been clearly established. Howewer, even in procedures where PABD is appropriate, collection in excess of transfusion need, although considered inevitable to provide sufficient blood to meet the need of most patients, should be kept to a minimum. A widely utilized strategy to define the number of autologous blood units to be collected for each surgical procedure is the schedule of optimal preoperative collection of autologous blood (SOPCAB), as suggested by Axelrod et al (16), which takes into account the number of blood units (autologous and allogenic) tranfused to each patient throughtout the entire hospital stay for each surgical procedure. The number of units to be collected is determined by the physical capability of the patients, but ideally it is equal to the number of units of autologous blood that would guarantee at least 80-90% of patients completely avoiding exposure to allogenic blood.

In our Institute the use of these strategies has allowed the overall wastage of autologous blood to be kept below 15%, with a range from 6% to 15% according to the different surgical procedures.

Although valuable for the proper management of a PABD program, MSBOS and SOPCAB give no indication of the appropriateness of transfusion indication or of the transfusion need of a specific patient.

Algorythm to define the patient’s transfusion requirement

In order to optimize the PABD program we have defined a new and more personalized approach to the utilization of all the methods of obtaining autologous blood so as to offer to each single patient what has really proven to be effective in reaching the main goal of an autotrasfusion program, i.e. avoiding the use of allogeneic blood (17).

This new approach is aimed at defining the patient’s transfusion requirement, taking into account the two parameters on which it depends, i.e. the perioperative blood loss and the volume of blood loss tolerated by the patient before blood transfusion support is indicated. The perioperative blood loss can be calculated through a constantly updated analysis of the real blood loss of each patient undergoing a specific surgical operation performed by a specific surgical team. This can be obtained by performing a retrospective analysis of the patients operated during the last 6-12 months prospectively.

The surgical RCB loss in each patient is given by the circulating RCBs volume reduction from presurgery to a properly determined postoperative time, plus the volume of RBC transfused during that period.

In our setting we decided to consider the patient’s RBC mass 5 days after surgery as a postoperative reference as at that time he is normovolemic, postoperative bleeding has stopped and blood transfusion is a rare event. The patient’s circulating RCB volume can be calculated using appropriate formulas that take into account patient height, weight and hematocrit.

The volume of allogeneic RBCs transfused can be easily defined as each unit contains around 200 ml of RBCs; the volume of RBCs present in autologous blood units can be easily calculated knowing the volume of blood collected and donor/patient hematocrit value at the time of collection. Similarly, for perioperative salvaged blood the volume of RBCs transfused can be calculated taking into account the volume of washed RBCs transfused and the average hematocrit of salvaged blood after the washing cycle.

Once the total RBC loss of about 40-50 patients is determined the value to assign the predicted surgical RBC loss for each procedure, subdivided for each surgical team can be mean, median or the appropriately selected percentile value of the distribution. In our setting we decided to consider the value corresponding to the 80^th centile of the distribution as the expected blood loss.

The formulas to calculate perisurgical RBC loss and an example of their application are reported in Table I.

The volume of blood loss that can be tolerated by each patient depends on the baseline circulating RBC mass

(which in turn depends on baseline hct and body mass) and the circulating RBC mass that gives an Hct value compatible with the clinical and cardiocirculatory condition of the patients. Patients who are young and in good general condition can safely tolerate a low Hct/Hb value (21-24% oh Hct) while those who are elderly or suffer from cardiovascular or respiratory diseases, affecting oxygen delivery to the tissues, have be maintained at higher Hct/Hb value (27-30% of Hct).

Once the patient’s baseline hematocrit and minimal acceptable Hct value are determined the volume of tolerated RBC loss can be established according to the formula reported in Table II.

The difference between the predicted blood loss and the tolerated blood loss is the transfusion requirement of the patient expressed in ml of pure RBCs (Tab.III).

When a negative figure is obtained it means that the patient can tolerate the loss of larger volume of blood than is expected to be induced by the procedure the patient is undergoing. In this case PABD is not indicated and the patient is discouraged from predepositing blood. In such cases the "Type and screen" procedure will be adopted to protect the patient from unexpected high surgical blood loss, perioperative blood salvage with the "stand-by procedures" is carried out. This procedure consists of mounting the aspiration set and reservoir at the beginning of the operation, and proceeding to the washing cycle only when the volume of the blood, collected in the reservoir is considered clinically useful by the anesthesiologist.

When a positive figure is obtained, the figure represents the transfusion need expressed in ml of RBCs. In this case the safest, and possibily the most cost-effective transfusion strategy, has to be defined to obtain the predicted volume of RBCs necessary to cover the transfusion requirement of the patient. The first step considered is the possibility of reducing the surgical blood loss utilizing pharmacological agents or sealants when indicated.

Other options are:

I Option: transfusion of allogenis blood 180-200 mL of RBCs/unit)

II Option: autotrasfusion techniques currently available (PABD, ANH, Perioperative salvage)

III Option: rHuEPO to increment baseline Hct values or to increase the volume of predeposited RBCs

IV Option: blood substitutes in addition to the use of autologous blood and/or rHuEPO

The choice of transfusion strategy depends on the type of surgery; time to surgery, applicability of the specific autotransfusion techniques; general clinical status of the patient (hematological, cardiopulmonary), consideration of cost/effectiveness.

To help make the choice of the best strategy to be used to fulfill the transfusion need expressed in volume of RBCs, we tried to define the net gain expressed in ml of RBCs that each transfusion strategy can provide.

If the only possibility is the transfusion of allogeneic blood, the number of units to be assigned to the patient to cover transfusion need is easily calculated, a red unit (whole blood or RCB concentrate) contains between 180 ml and 220 ml of RBCs.

If the autotrasfusion techniques currently available are feasible then it is necessary to know in terms of volume of RBCs produced or conserved what each of different techniques can provide.

Autologous blood donation (ABD)

The volume of blood that a patient can predeposit during the period before surgery is a function of the total baseline circulating volume of red blood cells (which in turn depends on the initial Hct and body mass) and the rate of recovery of RBCs collected at each donation, depending on the degree of stimulation of erythropoiesis during the interval between donations. If we fail to give the patient enough time to compensate for red cells collected through the normal (physiologic) erytropoiesis mechanisms, predonation offers very little advantage, because in this case it only reduces intraoperative red cell loss through the slight hemodilution, induced by the blood donation.

It has been experimentally defined that to obtain a net gain of volume of 200 ml of new RBCs through autologous blood donation the patient needs at least 15 days after donation, and when 3 units of blood are collected in 10-15 days and surgery is scheduled 25/30 days after the firste phlebotomy, 250-350 ml of new RBC production can be obtained (17).

Acute normovolemic hemodilution (ANH)

ANH consist of the withdrawal of an established volume of blood and the simultaneous infusion of crystalloid or colloids to maintain normovolemia. The blood is diluted and consequently the net RBC loss during the operation is reduced. The techniques is effective when the baseline Hct is drastically reduced and the intraoperative loss is significant (18,19).

Taking into account that the amount of RCBs saved with ANH is equivalent to the volume of blood lost multiplied by the difference between the baseline Hct and Hct at the end of the hemodilution process (target, Hct), it can be calculated that to conserve 1 unit of blood (180-200 ml of RBCs) in patients with expected surgical blood ranging from 1000 ml to 1500 ml of blood, ANH should reduce the preoperative Hct by 14-20% points. This requires the collection of a very large volume of blood (4-6 units) which involves safety concern in a relevant number of patients scheduled for elective surgery.

Perioperative salvage

Thi techniques gives in any case a net gain in RBCs since it recovers a product that otherwise would have been lost and is proportional to the intraoperative and postoperative blood loss.

It can be calculated, howewer, that the amount of RBCs conserved using this technique varies according to the rapidity of hemorrhage, the willingness of the surgeon to use the aspirator rather than gauzes, the aspiration pressure, and avoiding the formation of bubbles during aspiration, nevertheless it does not exceed the 30-50% of blood lost during the operation.

It has been calculate in our setting that the change of conserving more than of 1 unit of blood varies from 8% to 78% according to the operation. For this reason we use a "Stand-by strategy" which consits of mounting the aspiration set and reservoir in all those surgical operations where transfusion is indicated and proceeding to the washing cycle only when enough blood has been collected in the reservoir.

Rate of rHuEPO in blood conservation

It has been clearly demonstrated that rHuEPO (20) induces an accelerated rate of RBC production. In our setting different rHuEPO dose regiments have been adopted, but 150-300 IU/Kg given intravenously or 100 IU/Kg given subcutaneously (with an IV bolus of 200 Iu/Kg at the first visit) togheter with a proper iron support, (to compensate for iron extracted with the collection of autologous units and the increase of Hb concentration), produced a mean increase of 1g/dl of hemoglobin for each week of treatment (Fig. 1) (21).

Thi biological effect may be utilized for increasing baseline Hct values to increase the tolerated blood or to accelerated the recovery of the red blood cells collected in the autologous blood donation program.

Utilization of blood substitutes

The use of oxygen carrying products (Fluorocarbon based or modified hemoglobin) in association with autotrasfusion techniques and/or rHuEPO could optimize the autotransfusion program to further decrease the need for allogeneic transfusion (22.23).

The ideal application for oxigen carryng products with their documented limitations (brief intravascular half-life and dose-limiting side effects) is to use them during surgical procedures to compensate anemia due to either intentional blood removal (autologous predonation and/or isovolemic hemodilution) or unintentional surgical or traumatica blood loss. The repleacement of blood lost during or immediatly after surgery with the oxygen-carrying products can allow the surgeon to operate safely at a lower hct level, thereby minimizing the use of blood. Autologous blood, obtained through predonation and/or isovolemic hemodilution or perioperative salvage can be transfused at the end of the operation when the surgeon has obtained a satisfactory homeostasis.

It has been calculated in our hospital that 59% of the blood received by the patient during hospitalization is transfused the day of surgery (24).

The use of blood substitutes, ideally equivalent to 2-3 units of allogeneic blood, could help in conserving part of the blood that is currently transfused during the operation.

Conclusions

The availability of all these strategies of blood conservation and their judicious application could help to give patients the best treatment at the lowest cost, since the decision to use one or the other method is based on the clinical characteristic of the patient and on logistic and organizational considerations.