Leukocyte Reduction with Arterial Line Filters

Pulmonary Dysfunction is a Costly Complication of CPB Surgery

Taylor et al 1 reported pulmonary failure as an expensive complication of open heart surgery leading to added patient charges that exceeded $28,000 per episode. The frequency of occurrence of pulmonary dysfunction has been reported to vary from 5 to 15%.2,4

While actual costs of managing patient morbidity are not well known, patient charges appear to be a reasonable approximation of costs. Using basic assumptions about costs and charges, it is possible to develop some appreciation of hospital costs to manage this complication as shown in the accompanying table.

Table 1. Estimated Cost of Managing Pulmonary Failure following CPB

Frequency of
Occurrence2,4
   
Cost per
Occurrence
   
Cost per 1,000
patients
undergoing CPB
 5%
 5%
 5%
$  8,400
$14,000
$22,500
$   420,000
$   700,000
$1,125,000
10%
10%
10%
$  8,400
$14,000
$22,500
$1,400,000
$1,400,000
$2,250,000
15%
15%
15%
$ 8,400
$14,000
$22,500
$1,260,000
$1,400,000
$2,250,000


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Leukocytes Mediate Pulmonary Dysfunction

There are considerable data pointing to leukocytes as the mediator of this morbidity. Cardiopulmonary bypass causes complement and, in turn, neutrophil activation.5 Activated neutrophils, when presented to the lungs upon pulmonary reperfusion, leads to oxidant and proteolytic enzyme-mediated parenchymal cell destruction.6,7 Typically, leukocyte levels fall (leukopenia) during the initial period of CPB and then rebound (leukocytosis) at the end of bypass reflecting the development of the inflammatory process and mobilization of damaging leukocytes.8,9

Figure 1. Leukocytes during CPB adapted from Gu8

Therefore, activated neutrophils are important in the cause of pulmonary dysfunction which, in its extreme form, may present as respiratory failure. This, in turn, could result in costly protracted ventilator time and increased length of stay in the hospital.


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Leukocyte Reducing Arterial Line Filters Selectively Remove Noxious Agents

Two recent studies support the view that the Pall leukoreducing filters (LeukoGuard®) selectively reduce activated neutrophils.10,11 These filters do not appreciably alter lymphocytes or platelets.12

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Leukocyte Reducing Arterial Line Filters Improve Pulmonary Function

A number of studies have accumulated to suggest that leukocyte reduction during CPB attenuates reperfusion injury to the pulmonary vasculature. Some show either suggestive or clear clinical benefit. The following table summarizes the salient features of these clinical studies.

Summary of Clinical Efficiency Leukoreduction During CPB

Clinical Outcome   Other Observations   Reference

• decrease in time to extubation
(13.3 vs 9.2 hrs P<0.05) compared with controls
 
• significant reduction in WBCs at 4 hrs post-bypass (LG= 11.5 vs Control=13.9 [x103 cells/ul]) and in both groups these values were higher than pre-op levels
 
Palanzo et al, 199312
• decrease in per patient charges averaging $2,892  

• no further reduction in platelets compared with control filters

• increase in PaO2 at FiO2=1 early post-op (412 vs 348 mm Hg P<0.05)

  Prospective, randomized; N=36


• decrease in time to extubation
(15.2 vs 11.0 hrs P<0.05)

• decreased hospital length of stay by 1.4 days (from 9.6 vs 8.2 days
P<0.05)

• decrease in per patient charges averaging $1,942


• significant reduction in WBCs immediately post-bypass (LG= 11.8 vs Control=13.4 [x103 cells/ul]) and in both groups these values were higher than pre-op levels

Palanzo & Manley, 199413 Retrospective, matched controls; N=240

• improvement in intrapulmonary shunt fraction at 1 and 4 hrs post bypass (aggregate means of 24 vs 19% (P<0.05)
 
• significant reduction in WBCs at 4 hrs post-bypass (LG= 9.9 vs Control=12.2 [x103 cells/ul]) and in both groups these values were higher than pre-op levels
 
Johnson et al, 199514 Prospective, randomized; N=16/group

• cost-effective reduction in the requirement for supplementary nasal oxygen upon hospital discharge
 
• a significantly greater proportion of older patients had oxygen saturation values above 90% upon discharge when leukoreduction was employed during CPB
 
Coleman &
Demastrie, 199415 Prospective, randomized; N=188 total


• Reduced hospital LOS among low risk (predicted mortality <5%) patients by 1.4 days (from 6.8 to 5.4 days)

• Reduced per patient charges by $2-6,000

 
• Total Leukocyte Reduction employed leukocyte and reducing filters for allogeneic transfusions, arterial blood cardioplegia lines as well as intraoperatively salvaged blood
 
Gott et al, 199716 Prospective, randomized; N=100/group


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Leukocyte Reducing Effect Characterized

The Pall LeukoGuard® filter for use in the arterial line has been shown to significantly reduce circulating levels of neutrophils. Recently Silvay et al 17 characterized the neutrophil counts of patients undergoing CPB either with a conventional arterial line filter or a leukoreducing arterial line filter. These data illustrate the transient neutropenia occurring in both groups of patients followed by a rebound neutrophilia. The overall burden of neutrophils circulating are lower in the leukocyte reduced group compared with controls. The colored lines depict the rise in neutrophils that might be expected with longer pump runs (as in the data of Palanzo et al 13) where it may be seen that patients are not left neutropenic early in the post bypass period.

Figure 2. Neutrophils during bypass adapted from Silvay et al, 1997.17


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The LeukoGuard® AL Offers Flexibility and Potentially Enhances Clinical Value

The LeukoGuard® filter is a novel technological advancement. The LeukoGuard AL, not only affords uninterrupted filtration protection but may be used to employ leukocyte reduction strategically, toward the end of the bypass period, when neutrophilia predominates and coincides with pulmonary reperfusion. Any incidence of high line pressures associated with the use of the Pall LeukoGuard® filter may require the use of the filter bypass line. In order to ensure uninterrupted use, the latest version of LeukoGuard® (the LGAL) provides a filtration system complete with two filters; a conventional air-eliminating and microaggregate-reducing arterial line filter positioned proximal to a leukoreducing filter in one convenient package.

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Summary Of Evidence

  • Respiratory dysfunction accompanies CPB and, in its most severe form, manifests as respiratory failure.1,4
  • Neutrophil-mediated reperfusion injury can contribute to costly pulmonary dysfunction following CPB.5,6
  • Leukocyte reduction in the arterial line has been shown to improve outcome and decrease patient charges by reducing pulmonary dysfunction.12,16

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    References

    1. Taylor GJ, Mikell FL, Moses HW, et al: Determinants of hospital charges for coronary artery bypass surgery: the economic consequences of postoperative complications. Am J Cardiol 1990;65:309-313.
    2. Shapira N, Zabatino SM, Ahmed S, et al: Determinants of pulmonary function in patients undergoing coronary bypass operations. Ann Thor Surg 1990; 50:268-273
    3. Maggart M, Stewart S: The mechanisms and management of non-cardiogenic pulmonary edema following cardiopulmonary bypass. Ann Thorac Surg 1987; 43:231-236.
    4. Hedlund K: Pulmonary complications following cardiopulmonary bypass. Am Acad Cardiovasc Perfusion Newsletter, Fall, 1994; pp. 6-7.
    5. Kirklin JK: Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg 1991; 51:529-531.
    6. Allen S: The role of leucocytes in the systemic inflammatory response and the potential impact of leucocyte depletion. Cardiovasc Eng 1997; 2:34-54.
    7. Bulkley GB. Reactive oxygen metabolites and reperfusion injury: aberrant triggering of reticuloendothelial function. Lancet 1994; 344: 934-936.
    8. Gu YJ: Inhibition of the inflammatory response initiated during cardiopulmonary bypass [PhD Thesis]. Groningen, The Netherlands: University Hospital, 1992.
    9. Quiroga MM, Miyagishima R, Haendschen LC, et al: The effect of body temperature on leukocyte kinetics during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1985; 90: 91-96.
    10. Thurlow PJ, Doolan L, Sharp R, et al: Studies of the effect of Pall leukocyte filters LG6 and AV6 on an in-vitro simulated extracorporeal circulatory system. Perfusion 1995; 10:291-300.
    11. Hurst T, Johnson D, Cujec B, et al: Depletion of activated neutrophils by a filter during cardiac valve surgery. Can J Anaesth 1997; 44:131-139.
    12. Palanzo DA, Manley NJ, Montesano RM, et al: Clinical evaluation of the LeukoGuard (LG-6) arterial line filter for routine open-heart surgery. Perfusion 1993; 8:489-496.
    13. Palanzo DA, Manley NJ. Cost effectiveness of using a leuko-depleting arterial line filter. Proc Amer Acad Cardiovasc Perfusion 1994; 15:124-127.
    14. Johnson D, Thomson D, Mycyk T, Burnbridge B, Mayers I. Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest 1995; 107: 1253-1259.
    15. Coleman SM, Demastrie L. Leukocyte depletion reduces postoperative oxygen requirements. Ann Thorac Surg 1994; 58:1567-8.
    16. Gott JP, Cooper W, Schmidt F, et al: Documentation of risk neutralization for extracorporeal circulation in four limbed, 400 patient, risk stratified, prospective, randomized trial. Presented at the Southern Thoracic Surgical Association meeting, Nov 7, 1997; Naples, FL.
    17. Silvay G, Ammar T, VelaCantos L: Preservation of platelet reactivity with leukocyte reduction. Anesthesiology (1997) 87:A66.

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