New transfusion strategies

New A. Gerson

T

Transfusion Greenburg,

Strategies

MD, PhD, Providence,

ransfusion therapy continues to be widely discussed throughout all of medicine but particularly in surgery, where great regional and local variation in blood and blood product use can be documented.’ Although the Sanguis study was conducted in Western Europe there is little reason to doubt similar results with respect to variation in transfusion practices would be obtained if examined in the United States. This well-documented variability in the use of blood and blood products, the timing of delivery, and the lack of really hard data on the benefits of transfusion therapy simply add to the transfusion decision confusion. It is therefore safe to say that universally accepted “transfusion triggers” are not recognized and their absence is likely the major driver of this difference in practice. More recently a number of other issues have also influenced red cell transfusion practice. Ranging from a greater appreciation of the risks of transfusion to regulatory directives, and from economics to practical logistic reality these “drivers” have created pressures sufficiently strong to create a general “transfusion avoidance” strategy among many surgeons. No blood product is without risk nor can one expect this to be the case in the near future. It is also clear that “avoidance” is a decision that could add risk for the patient.

Rhode /s/and

TABLE Estimated

Risks of Transfusion per Unit in the United States (1995)

Minor allergic reactions Bacterial infection (platelets) Viral hepatitis Hemolytic transfusion reaction HTL VI/II infection HIV infection Acute lung injury Anaphylactic shock Fatal hemolytic reaction Graft-vs-host disease lmmunosuppression HTLV = human oency virus. Source: Harvey

1:lOO 1:2,500 15,000 1 :6,000 1:200,000 1:420,000 1:500,000 1:500,000 1:600,000 Rare Unknown

T-ceil /eukemfa-lymphoma G. Kiein,

voking a “transfusion exposure.

UNDERLYING

wrus. H/V = human

fmmunodefi-

M.D.

avoidance

strategy”

to minimize

risk

PHYSIOLOGY

It is not clear that avoidance is a universally applicable therapeutic principle as the oxygen delivery physiology would dictate some limits, tempered by age, disease state, RISKS and ongoing pharmacologic intervention, to the relationThe major perceived risks of blood and blood product ship of cardiac output (flow) and oxygen carrying capacity transfusion are primarily related to transmission of infec(hemoglobin concentration). The essential need is, of tious diseases. Although these risks are actually decreasing course, to assure adequate delivery of oxygen to tissues, tissteadily as newer screening tests are introduced and better sue perfusion, to maintain aerobic metabolism, or reverse anti-viral processing and storage capabilities evolve, the an induced anaerobic metabolic state. The extent and rate risks of blood-related transmission of infectious disease conof blood loss influences both tissue perfusion and therefore tinues to be a problem’.’ A recent review by Klein estimates patient outcome.4 Outcome measures include not only mortransfusion risks per unit (Table).’ In recent years transfutality but also morbidity as might he related to acute tissue/ sion therapy has also been linked to some aspects of immune organ ischemia (eg, myocardial infarction, CVA/stroke, suppression with significant adverse consequences relative acute renal inilure) or even rate of recovery to activities of to postoperative infectious complications or tumor recurdaily living or rehabilitation. rence: decreased survival in patients with breast or colon Oxygen delivery physiology - perhaps a more contemcancer.’ Finally, it must be recognized that a blood banking poraneous way of defining the presence of anemia - is “system” is in large part dependent on human input for becoming more sophisticated as an ever-increasing appredecisions and processing and thus subject to human error. ciation of this vital physiologic system develops.5 By dissecIn the case of fatal transfusion reactions - basically transtion of the oxygen delivery system intO its components it is fusion of incompatible blood - “clerical error” continues possible to select targets for specific intervention. The analto be the primary etiology. Taken together, awareness of ysis creates a continuum of options for interventions, which these risks has sensitized the surgical community and forced can broadly he taken as “transfusion strategies.” a consideration of alternatives to transfusion, frequently inOxygen delivery to tissues is determined, broadly, by cardiac output - governed by preload, contractility and afterload - and hemoglobin concentration. In roughly a Am J Surg. 1997;173:49-52. From the Department of Surgery, The Miriam Hospital, Provilinear relationship, a 50% decrease in hemoglobin concendence, Rhode Island. tration requires a doubling of cardiac output to effect the Requests for reprints should be addressed to A. Gerson Greensame oxygen delivery. Increases in cardiac output by pharburg, MD, PhD, The Miriam Hospital, 164 Summit Avenue, Provmacologic intervention, while avoiding transfusion of red idence, Rhode Island 02906. .. .. 1 cells, is an excellent Hurststrategy assummg there is the necQ 1997 by Excerpta All rights reserved.

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Inc.

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Llmin Figure 1. Changes in oxygen delivery (DO4 with changes in hemoglobin (Hb) concentration and oxygen saturation (SaO,). Note the effect of decreased SaO, on the need to increase cardiac output (CO) to maintain normal global DO,. Correction of SaO, will measurably decrease CO.

essary cardiovascular reserve to reach the end point without inflicting further ischemia or other damage on the myocardium. Measurement of global oxygen delivery, while desirable, is not always possible. In controlled situations (eg, ICU, OR) with invasive monitoring it is possible to obtain a value for global oxygen delivery as well as global oxygen utilization, or consumption. The ratio of oxygen consumption to oxygen delivery is the oxygen extraction ratio (OER). The OER becomes a factor and variable for determining whether a transfusion is indicated on the basis of data and information, and is not an empiric decision. Two other concepts are important. There is an apparent flow-dependent relationship between global oxygen consumption and oxygen delivery. A “critical oxygen delivery point” - more likely a small range of values - can be identified if one constructs the consumption delivery relationship. The interesting aspect of this critical oxygen delivery point, between 8 and 10 mL oxygen/kg per minute, is its correspondence to an OER of about 35-40%, an increase in lactate (indicating anaerobic metabolism), and a maximum left ventricular efficiency.5 Thus, it is possible to define a point where a transfusion, addition of red cells, is indicated. However, it requires data gathering, invasive monitoring, and analysis to make that specific determination. A reasonable approach in the arena where invasive monitoring is available, an appropriate strategy is: identify a physiologic basis for a transfusion indication (Figures 1 and 2).

TRANSFUSION

ALTERNATIVES

Most transfusions are given without the physiologic data to support the decision. Strategies and decisions are generally empirically based, often predicated on past experience. If the objective is to minimize exposure to allogeneic red cell transfusion, modern alternatives have been devised and can apply to routine patient care in most areas of sur50

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gery (eg, orthopedics, vascular, urology, gynecology, cardiac, and general). In considering new strategies, the separation of situation by emergency and elective timing is appropriate as the number of useful options is greater in the elective scenario if only because of the longer available time frame.

EMERGENCY STRATEGIES

ALTERNATIVE

Minimizing blood loss with good surgical technique has the net effect of conserving red cells and could result in a decreased need for allogeneic transfusion. Autologous transfusions in the emergency trauma situation could be a logistic problem. Small volume resuscitation (eg, crystalloid, colloid, crystalloid/colloid, hypertonic saline, hypertonic hyperoncotic solutions) have the beneficial effect of decreasing ongoing blood loss by maintaining perfusion without normalizing blood pressure. In essence, this is a “blood conservation technique.” Broad experience with this approach is necessary to appreciate its application and to assure a physician comfort zone with the technique. This may be a reasonable concept for “scoop and run” systems but could be unyielding in the face of delayed transport for primary intervention. Resuscitation under these conditions is aimed at maintaining tissue perfusion with minimal volumes. If blood loss is assumed to be greater than 25% of the estimated blood volume the addition of an oxygen carrier appears necessary. The difficulty with this as a firm decision point is the inability to correlate vital signs and other simple chemical measures with blood volume, an elusive entity not easily measured even in controlled situations. Universal donor, O-negative, or type-specific red cell transfusions are effective alternatives and appear to be equally safe in the emergency situation6 In emergency nontrauma or acute blood loss surgical interventions where prior or ongoing blood loss is not a factor, JANUARY

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/ NEW

High

Flow-dependent O1 cixwumption

I / ,

TRANSFUSION

STRATEGIESIGREENBURG

Flowindependent OS ccn~umption

I I

OER High

Lactic acid High

! NOfMl rang.3

Global

Figure 2. Schematic representation by oxygen extraction ratio (OER) independent of DO,.

DO,

of the relationship of oxygen delivery (DO,), and lactic acid levels. Metabolism appears

the use of perioperative hemodilution can be considered to attain the objective of allogeneic transfusion avoidance. This has not been widely reported in a clinical series but is logical in concept. Additionally, in some emergency surgery, absent the presence of infection, stool, or malignant cells, intraoperative and postoperative cell salvage techniques are useful. Key to the success of cell salvage is the use of devices that wash and concentrate red cells prior to reinfusion.

ELECTIVE

ALTERNATIVES/STRATEGIES

In this group of patients the broadest range of autologous options is possible. Because the procedures are elective the ability to use autologous predeposit alone or in combination with perioperative hemodilution becomes reality. Moreover, when combined with intraoperative cell salvage this combination of techniques - variations on autologous transfusion - is very powerful and could be used to advantage in an allogeneic transfusion avoidance program. At issue really is the product and the form of RBCs used, not necessarily the delivery technique or the system. By designing a strategy to use autologous red cells whenever possible the reliance on allogeneic red cells and their variations (eg, washed, irradiated, leukocyte free) is minimized with a decreased transfusion risk. Autologous predeposit has had its greatest impact in elective orthopedic surgery, especially total joint replacements. It is considered an expensive technique and argued against with cost/benefit ratios not favorable.‘-’ As surgical techniques have generally improved - an often unrecognized and under appreciated transfusion avoidance strategy minimizing blood loss, the overall requirement for transfusion after joint replacement has decreased significantly. Coupled with a better appreciation of oxygen delivery physiology and patient-associated risk factors for ischemia of not transfusing, tolerating a lower hemoglobin/hematocrit THE

AMERICAN

oxygen consumption appropriately aerobic

(VO,), and tissue perfusion reflected and adequate when global VO, is

level, it appears reasonable to use perioperative hemodilution. To obtain 2-3 units of RBCs for these cases immediately preoperatively generally equals or exceeds the actual blood loss based on maximum blood order schedules. This strategy, applicable to many similar elective surgical procedures in many areas of surgical endeavor, avoids both the allogeneic exposure and the risk associated with an autologous predeposit program while optimizing the benefits of autologous transfusion. Indeed, in this situation the autologous units are actually fresh whole blood, perhaps the “ideal replacement” for elective surgery; whole blood is certainly not generally available by any other means. This strategy is deemed reasonable and has been shown to be effective in orthopedics and urologic surgery as a means of decreasing or eliminating ‘-l’ allogeneic RBC transfusion. In the future, the use of an oxygen carrier (hemoglobin solution or perfluorocarbon-based red cell substitute) may be the diluent of choice for perioperative hemodilution. Providing both volume and oxygen carrying capacity, the risk of ischemic injury to specific target organs would be minimized and the patient afforded an extra degree of safety in an already effective allogeneic transfusion avoidance technique.”

SUMMARY The Xew transfusion strategies” are designed to minimize exposure to allogeneic transfusion while maximizing the use of autologous red cells. While not always possible in all clinical situations, this approach appears to be the current transfusion strategy paradigm. Physician and patient concerns about the risk of transfusion therapy are driving these strategies. When combined with management of the elements of cardiopulmonary physiology responsible for cardiac output and tissue perfusion, the autologous techniques of hemodilution, cell salvage, and predeposit are reasonable JOURNAL

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strategies for achieving the desired goals of allogeneic transfusion avoidance. Of the 11 policies and interventions proposed by the Blood Management Conference’ several need to be iterated as underpinnings for these strategies. They include: 1. assessing transfusion needs on a patient case basis; 2. transfusions are to be given and effect-benefit assessed before proceeding with additional transfusion; 3. limited exposure to allogeneic blood if possible; 4. minimize perioperative blood loss ranging from surgical technique to decreasing laboratory assessments; and 5. maximize oxygen delivery physiology as a first step in improving basic oxygen delivery.

REFERENCES 1. Sirchia G, Giovanetti AM, McClelland DBL, et al, &. Safe B Good Use of Blood in Surgery (Sanguis) Luxembourg: The European Commission, 1994. 2. Klein HG. Allogeneic transfusion risks m the surgical patient. AmJ Surg. 1995;17O(suppl 6A):21-26. 3. Schreider GB, Busch Ml’, Kleinman SH, et al. The risk of transfusion: transmitted viral infection. NEJM. 1996;334:1685-90.

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4. Carson, J.L. Morbidity risk assessment in the surgically anemic patient. AmJ Surg. 1995;17O(suppl 6A):32-36. 5. Greenburg, A.G. A physiologic basis for red blood cell transfusion decisions. Am J Surg. 1995;17O(suppl 6A):44-48. 6. Spence, R.K. for the Blood Management Practice Guidelines Conference. Surgical red blood cell transfusion practice policies. Am J Surg. 1995;17O(suppl 6A):3-15. 7. AuBuchon, J.P. Cost-effectivenw
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