Cardiovascular Surgery: Recent Studies

Reference:
Gott JP, Cooper WA, Schmidt FE Jr, Brown WM III, Wright CE, Merlino JD, Fortenbery JD, Clark WS, Guyton RA: Modifying risk for extracorporeal circulation: trial of four anti-inflammatory strategies. Ann Thor Surg 1998; 66 (3) 747-754.

Brief Summary:
In a prospective, randomized trial, three anti-inflammatory interventions were compared to a standard of surgical practice (which included the use of corticosteroids) in 400 patients undergoing cardiopulmonary bypass surgery. The alternative interventions comprised either use of the serine protease inhibitor, aprotinin, heparin-bonded circuits, or a program of treatment designed to reduce the burden of leukocytes presented to the patient from a variety of filters using leukocyte reduction filtration technology (Pall Corporation), termed Total Leukocyte Control (TLC).

The TLC program included:

• Leukocyte reduction of all allogeneic transfusion products (including packed red cells, platelets and fresh frozen plasma)
• Reduction of systemic circulating leukocytes with a filter in the arterial line of the bypass circuit
• Reduction of the blood in the blood cardioplegia line
• Reduction of all salvaged blood

The patient groups were stratified based upon an assessment of pre-operative risk scores. The primary end-points, which were length of stay in the hospital and patient charges, were tabulated as a surrogate marker of costs.

Only two of the three interventions displayed statistically significant differences when compared to conventional practice. The vast majority of patients studied, more than 70%, were stratified as a low-risk population. These patients, when provided with TLC treatment, demonstrated a significant reduction in length of hospital stay (mean reduction of 1.4 days/19%). TLC was also associated with a reduction in charges averaging $6,000 per patient. Among patients in the high-risk group (comprising 8% of the total patient population), significant benefit was provided using aprotinin in conjunction with surgery. No other comparison revealed statistically significant differences.

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Dr. J. P. Gott
Section of Cardiothoracic Surgery
The Emory Clinic, Inc.
550 Peachtree Street, NE
Suite 7700
Atlanta, GA 30365

A reprint of this article may also be obtained by contacting Dr. Jerry Ortolano at (800) 645-6532 ext. 4053 or by faxing your request to (516) 484-3683. Please provide your return address and indicate reorder code E-Gott98. To order a reprint of this article online, click here.

Reference:
van de Watering L, Hermans J, Houbiers JGA, van den Broek PJ, Bouter H, Boer F, Harvey MS, Huysman H, Brand A: Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery. Circulation 97:562-568, 1998.

Brief Summary:
This prospective randomized trial examines the effect of leukocyte-reducing banked blood (accomplished either pre-storage or at the bedside using filters) upon complications among relatively high-risk open-heart surgery patients. Approximately one third of the 914 total study patients were distributed across the following treatment groups:

1. The control group was a group of patients transfused with the standard preparation of buffy coat poor packed cells (PC) containing an average leukocyte count of 0.8 x 10⁹ cells/unit.
   
   
2. Pre-storage leukoreduced patients were transfused with freshly filtered (FF) and stored packed cells (leukocyte reduced) with residual white cells averaging 1.2 x 10⁶ cells/unit (counted by Nageotte hemocytometry).
   
   
3. Bedside leukoreduced patients were transfused with stored packed cells which were then filtered at the point of use (SF= bedside leukocyte reduction) with residual white cells averaging 1.1 x 10 ⁶ cells/unit. The primary endpoints reported in this publication were infectious complications.
   
   
4. Mortality was one of several secondary endpoints as were length of stay in the hospital and ICU. A separate follow-up paper will address alloimmunization.

Distinguishing Features of the Study:

1. Packed (red blood) cells (PC) used at this institution is one in which the buffy coat is removed as part of the preparation of the packed cell unit. Buffy coat reduced blood has a leukocyte burden that is about three times lower than that found in packed cell preparations commonly used in the United States.
   
   
2. Patients were high-risk cardiac patients with nearly 95% requiring transfusions, overall mortality 4.9% and the average length of hospital stay was 10.2 days.
   
   
3. Patients were followed for 60 days post-op and the rate of infectious complications overall approached 20%.
   
   
4. Of all transfused patients 59% received three or more units of blood.

Results:

Infectious complication rates were significantly (P=0.04) reduced among the subset of patients receiving three or more transfusions. Infectious complication rates among controls were 31.4% and reduced by 8.9% with complication rates averaging 22.5% among the combined (pre-storage plus bedside) leukoreduced group (calculated from data in Table 4, p. 567).

Among all patients, mortality was significantly reduced from 7.9% in controls down to 3.5% and 3.6% among patients who received prestorage or bedside leukoreduced blood, respectively (Table 5, p. 567). The benefit was evident among those sustaining non-cardiac mortality where values fell from 3.3% down to 0.3% with leukoreduction.

The authors conclude that: "Leukocyte reduction by filtration results in a significant reduction in postoperative mortality that can only partially be explained by the higher incidence of postoperative infections in the PC [control] group."

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Dr. A. Brand
Blood Bank Leidsenhage
Albinusdreef 2, Bldg 1, E4-67
PO Box 2184
2301 CD Leiden, Netherlands
E-mail: mailto:%20lvdwat@stad.dsl.nl

Reference:
Komai H, Naito Y, Fujiwara K, Takagaki Y, Noguchi Y, Nishimura Y: The protective effect of a leukocyte removal filter on the lung in open-heart surgery for ventricular septal defect. Perfusion 13:27-34, 1998.

Brief Summary:
This prospective, randomized clinical study of patients undergoing cardiopulmonary bypass for ventricular septal defect repair comprised a group with an average age of 22.5 months. Since blood is often added to, or the major constituent of, the circuit prime for these patients, all blood transfused or used to prime the circuit was leukoreduced by filtration (Pall RC100 or Pall RC400) in the treated group.Control patients received the same amount of blood without leukocyte reduction filtration.

The study served to test the hypothesis that leukocytes found in banked blood may exacerbate the whole body inflammatory response by compromising patient recovery and leukocyte reduction may reduce this effect. Previous work by these authors has demonstrated that among patients spanning a wide range of ages and cardiac abnormalities requiring surgical repair, those receiving leukoreduced banked blood showed improvement in pulmonary function with corresponding reductions in the markers of activated neutrophils. The current study was designed to examine similar effects in a more homogenous patient population where variability would be expected to be far lower and beneficial clinical effects more readily discernable. Respiratory index was measured before and immediately after bypass, shortly after surgery and again at 3 and 6 hours postoperatively Control patients showed a transient but significant rise in the respiratory index immediately after bypass compared with patients receiving leukoreduced blood. The difference in respiratory index between groups of patients disappeared at all postoperative times studied.

Interestingly, while extubation times tended to be shorter for the leukoreduced group (15.8 vs 23 hrs) the difference did not achieve a level of statistical significance but clinically important length of stay in the ICU was significantly reduced (from 4.1 down to 3.0 days) in the group receiving leukoreduced blood.

The authors conclude: "We elucidated the protective effect of a leukocyte removal filter on a patient's lung function after open heart surgery. Although this method alone is not enough to prevent all lung dysfunction, it is a safe and simple technique which is ready to use for young children with congenital heart disease."

Reprint Availability
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Dr. H. Komai
Department of Thoracic and Cardiovascular Surgery
Wakayama Medical College
27. 7-bancho
Wakayama 640, Japan

A reprint of this article may also be obtained by contacting Dr. Jerry Ortolano at (800) 645-6532 ext. 4053 or by faxing your request to (516) 484-3683. Please provide your return address and indicate reorder code E-Komai98. To order a reprint of this article online, click here.

Reference:
Webb DP, Altenbern CP, Tritt C, Downey FX, Minkel D: Pulmonary implications of filtering various mediators of morbidity found in salvaged blood. Journal of Extra-Corporeal Technology 1998: 30:108-114.

Brief Summary:
Ten open-heart surgery patients reinfused with approximately 750 ml of lipid- and leuko-reduced intra-operatively salvaged, concentrated and washed blood were compared with five, otherwise similarly treated, control patients in whom salvaged blood was filtered only for the removal of micro-aggregates. Lung function, as determined by measurement of the pulmonary shunt fraction, was assessed 40 minutes following pulmonary vascular reperfusion consequent to bypass surgery and about 20 minutes prior to initiating reinfusion of salvaged blood. Pulmonary shunt fraction was measured again about 35 minutes following reinfusion of salvaged blood.

Results demonstrate:

• Despite having the salvaged blood initially pass through a cardiotomy reservoir containing a 20 um screen filter, the subsequent centrifugation, saline washing and concentration of cellular elements resulted in large particles (approximating 1 mm in size) in the transfer bag where this blood product was destined for reinfusion. This observation emphasizes the importance of using at least a filter capable of removing particulate debris.
• Reinfusion of filtered salvaged blood can effectively increase the circulating mass of red cells thereby justifying the practice of intra-operatively salvaging blood intended to reduce the requirement for allogeneic transfused blood products.
• Concentrated and washed salvaged blood contains concentrations of white blood cells that approximate or exceed levels found in the circulation of cardiac patients and fat globules, normally undetectable in pre-operatively collected blood samples, show an average concentration of 3,000 globules per milliliter. Moreover, the pulmonary shunt fraction is reduced by approximately 25% over the time period of reinfusion in patients receiving lipid/leuko-reduced salvaged blood. In contrast, the recovery of lung function appears compromised in control patients receiving only the benefit of micro-aggregate removal filtration.

The authors state… "These results suggest that lipid/leukoreducing salvaged blood improves postoperative lung function and is efficacious."

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Charles P. Altenbern, BS, CCP
Milwaukee School of Engineering
EECS/Perfusion Department
Milwaukee, WI 53202-3109

Reference:
Allen BS, Shaikh R, Ilbawi MN, Kronon M, Bolling KS, Halldorsson AO, Feinberg H: Detrimental effects of cardiopulmonary bypass in cyanotic infants: preventing the reoxygenation injury. Ann Thor Surg 64: 1381-1388,1997.

Brief Summary:
This study was undertaken to determine the potential for hypoxia/reoxygenation injury to occur in chronically hypoxic neonates undergoing bypass and to elucidate the effect of either slow onset reoxygenation and/or leukocyte reduction filtration technology to blunt the injury. The response measure employed was an assessment of anti-oxidant reserve capacity of biopsied heart muscle as a surrogate marker of the potential for injury to this tissue.

The results suggest that infants manifesting chronic hypoxia with exposure to bypass surgery are at risk for myocardial hypoxia/reoxygenation injury. This injury may be blunted by initiating bypass at low oxygen partial pressures and slowly increasing the levels of oxygen as the case proceeds. Using leukocyte reducing filters for blood added to the circuit as well as during the bypass procedure provides substantially more oxidation reserve capacity than does reducing oxygen alone. The combination, however, provides the best protection to the heart of the cyanotic infant.

The authors conclude by saying: "In summary, our study findings support those of previous investigations and show that cyanotic infants are predisposed to generation of large quantities of oxygen free radicals in response to the initiation of cardiopulmonary bypass [references]. However, oxygen free radical production can be limited by decreasing the oxygen concentration of the bypass circuit or, more effectively, by leukocyte filtration."

Reprint Availability
Most medical libraries in institutions where open-heart surgery is performed or, Pall Medical at 800 645 6532 ext 4053 att: Dr. Jerry Ortolano (request re-order code 'E-BALLEN') or,

Address correspondence to:

Dr. Bradley S. Allen
Division of Cardiothoracic Surgery
University of Illinois at Chicago
840 S. Wood Street
417 CSB (M/C 958)
Chicago, IL 60612

A reprint of this article may also be obtained by contacting Dr. Jerry Ortolano at (800) 645-6532 ext. 4053 or by faxing your request to (516) 484-3683. Please provide your return address and indicate reorder code E-BALLEN. To order a reprint of this article online, click here.

Reference:
Suzuki I, Ogoshi N, Chiba M, Komatsu T, Moizumi Y: Clinical evaluation of a leukocyte-depleting blood cardioplegia filter (BC1B) for elective open-heart surgery. Perfusion 13:205-210,1998.

Brief Summary:
In a prospective, randomized clinical study, it has been shown that the patient's own leukocytes, presented to the heart muscle during blood cardioplegia delivery, lead to heart muscle damage that can be prevented with a leukocyte-reducing blood cardioplegia filter.

Forty patients undergoing routine cardiopulmonary bypass were studied. Half the group had a leukocyte reducing filter positioned between the oxygenator and the cardioplegia pump while the remaining patients served as controls with no filtration employed. Leukocyte levels were reduced initially from about 2,300 cells/µl down to 300, averaging 99.5, 98.1 and 94.7% efficiency of white cell reduction for 1, 2 and 3 liters, respectively, of blood cardioplegia passing through the filter. The cardiac enzyme, CPK-MB [creatine phosphokinase myocardial band], and cardiac protein, troponin-T, measured in arterial blood are markers of heart muscle damage and both were shown to be significantly reduced in the group of patients receiving filtered blood cardioplegia.

The authors conclude: "Leucocyte activation and the resulting tissue damage immediately after re-perfusion following aortic declamp is one of the major problems associated with blood cardioplegia. In the present study we used a filter (Pall BC1B) which eliminates microemboli and leukocytes from blood cardioplegia solutions in the blood cardioplegia circuit in one group, and compared the outcome (safety and efficacy) with that obtained in another group where the filter was not used. No filter-related adverse effects or complications were observed, indicating that it is safe."

They also state: "In the present study, both TnT [troponin-T] and CPK-MB [creatine phosphokinase myocardial band] levels at 1, 3, 6, 12, 24 and 48 h after aortic declamp were significantly lower in group 1 than in group 2, indicating that myocardial injury can be minimized by using the BC1B filter."

Reprint Availability
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I. Suzuki
Department of Clinical Engineering
Sendai Medical Centre
5-22-1 Turugaya Miyaginoku
Sendai 983, Japan

A reprint of this article may also be obtained by contacting Dr. Jerry Ortolano at (800) 645-6532 ext. 4053 or by faxing your request to (516) 484-3683. Please provide your return address and indicate reorder code E-Suzuki98. To order a reprint of this article online, click here.

Reference:
Heggie AJ, Corder JS, Crichton PR, Hesford JW, Bingham H, Jeffries S: Clinical evaluation of the new Pall leucocyte-depleting blood cardioplegia filter (BC1). Perfusion :17-25,1998.

Brief Summary:
14 patients undergoing routine cardiopulmonary bypass surgery had a Pall LeukoGuard^® BC (product code BC1B) filter positioned between the oxygenator and the blood cardioplegia pump. Blood sample ports were positioned within the circuit to allow for near simultaneous sampling of blood just proximal and distal to the filter with samples taken at intervals of approximately 400 mL of blood passing through the filter up to a final volume of 5.3 liters.

The data shows efficiency of leukocyte reduction falls as a function of increasing volume with cumulative reduction of leukocytes in excess of 70% over the entire volume studied. Initial leukocyte reduction was very high (98.4%) at the first 400 mL but fell off nearly linearly to 60% at 2.8-3.2L of blood. The filter did not retain platelets nor red cells and the resistance to flow, measured using pressure transducers positioned both up and downstream of the filter, showed a pressure drop of about 11mm Hg.

The authors summarize by stating; "In our experience, the leukocyte-depleting filter for blood cardioplegia (Pall, BC1B) removed few platelets or red blood cells and had no adverse effect on the study subjects. The filter was also easy to prime and operate, and there were no cases of occlusion experienced during this study. In conclusion, we found the leukocyte-depleting blood cardioplegia filter to be a safe and efficient device. Blood cardioplegia is increasingly employed to combat post surgical morbidity experienced in the older and sicker surgical population, and leukocyte depletion has been shown to be a practical option in this system."

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A. Heggie
Department of Clinical Perfusion
Wythenshawe Hospital
Clay Lane, Southmoor Rd., Wythenshawe
Manchester M23 9LT, UK

A reprint of this article may also be obtained by contacting Dr. Jerry Ortolano at (800) 645-6532 ext. 4053 or by faxing your request to (516) 484-3683. Please provide your return address and indicate reorder code E-Heggie98. To order a reprint of this article online, click here.

Reference:
Halldorsson AO, Kronon M, Allen BS, Rahman S, Wang T, Layland M, Sidle D: Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation. Ann Thorac Surg 1998; 66:877-885.

Brief Summary:
Ten pigs were studied with half undergoing single lung transplantation in the customary fashion following 24 hours of cold storage of the harvested donor organ.The remaining animals were provided with controlled reperfusion of the transplanted lung for just 10 minutes prior to final suturing and systemic reperfusion.The significant variables adjusted for the controlled reperfusion were:

• Pulmonary artery perfusion pressure (20 - 30 mm Hg)
• Composition of the reperfusate (with pH buffered using tromethamine, intra-cellular calcium flux modified with citrate and magnesium, osmotic pressure regulated with dextrose, substrates for energy production provided with glutamate and aspartate and adequate perfusion facilitated with the vasodilator, nitroglycerine)
• Leukocyte reduced blood (using Pall LeukoGuard^® BC filters)

Just 4 hours after surgery, 60% of the control animals expired and the treated animals showed indices of lung function vastly improved compared to controls. Indices of lung function compared at comparable post-transplantation times included arterial oxygenation, pulmonary vascular resistance, lung compliance and lung edema. Improvement correlated with a decreased burden of leukocytes as reflected by lower levels of neutrophil-derived myeloperoxidase activity in the lung tissue samples of animals in the treated group compared to controls.

The authors conclude... "Because this model mimics the clinical situation and uses techniques that are currently available, these findings suggest surgeons should begin to use this modality in patients undergoing lung transplantation."

Reprint Availability:
Most medical libraries in institutions where open-heart surgery is performed or address correspondence to:

Dr. Bradley S. Allen
Division of Cardiothoracic Surgery
University of Illinois at Chicago
840 S. Wood Street
417 CSB (M/C 958)
Chicago, IL 60612

Reference:
Ji Zhang, Jamieson WRE, Sadeghi H, Gillespie K, Marier JR, Mickelson H, McGibbon R: Strategies of myocardial protection for operation in chronic model of cyanotic heart disease. Ann Thorac Surg 1998;66:1507-13.

Brief Summary:
Neonatal and pediatric open-heart surgery is often conducted to repair congenital malformations that leave babies hypoxic from birth up to the time of treatment. Surgical repair results in a precipitous rise in blood oxygen levels presented to all tissues of the body as soon as cardiopulmonary bypass is initiated. Evidence suggests that such a precipitous rise in oxygen tension in the blood can result in a so-called "hypoxia/re-oxygenation" injury that is mediated by either platelet-activating factor (PAF) or leukocytes or both.

This study employs a pig model of chronic cyanotic heart disease and examines the effect of either an antagonist of PAF or the use of leukoreducing filters used during the bypass procedure to reduce the injury to the heart and lungs. Twenty five young pigs were surgically rendered hypoxic and maintained for 5 – 7 weeks prior to bypass surgery. Hypoxia, defined as cyanosis characterized by an oxygen saturation of less than or equal to 85%, was allowed to develop by creating a connection between the pulmonary artery and the left atrium causing a right-to-left shunt.

Following the cyanotic period, all but 7 animals were followed after reparative bypass surgery (these 7 were excluded for a variety of technical reasons) leaving 5 – 7 animals in each of 3 treatment groups:

• Control reparative surgery (involving reversing the surgical manipulation that created the hypoxic state)
• Reparative surgery in the presence of a platelet factor antagonist during bypass
• Reparative surgery in which a leukocyte reducing filter (Pall LeukoGuard-6^® filter) was used during the cardiopulmonary bypass procedure.

Four of 7 animals in the control group died as a consequence of low cardiac output syndrome or ventricular arrhythmias or a combination of the two. In contrast, mortality was significantly reduced with either PAF antagonist or leukocyte reduction treatments. Inotrope requirements were significantly reduced in PAF antagonist and the leukocyte filter groups compared to controls suggesting these treatments reduce hypoxia/re-oxygenation injury. The performance of the heart as reflected by measurements of end-diastolic elastance (Emax) and stroke volume pre-load curves showed that only the leukoreducing filter treatment resulted in improved heart function.

The authors conclude…"Both leukocyte-depleting filters and platelet activating factor antagonism provided myocardial protection, and the filters afforded superior postoperative myocardial contractility."

Reprint Availability:
Most medical libraries in institutions where open-heart surgery is performed or address correspondence to:

Dr. Jamieson
Department of Surgery
University of British Columbia
910 West 10th Ave.; Room 3100
Vancouver, BC, Canada V5Z 4E3

• Use of Leukocytes Depleting Arterial Line Filter During Deep Hypothermic Cardiopulmonary Bypass and Circulatory Arrest: Correlation with Pulmonary Function
• Reduced Neutrophil Infiltration Protects Against Delayed Lung Reperfusion Injury Following Transplantation
• Strategies For Myocardial Protection for Surgical Correction of Chronic Congenital Cyanotic Heart Disease

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