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Ann Thorac Surg 2011;91:740-749. doi:10.1016/j.athoracsur.2010.11.007
© 2011 The Society of Thoracic Surgeons
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Justin M. Schaffer
George J. Arnaoutakis
Eric S. Weiss
Nishant D. Patel
Ashish S. Shah
John V. Conte
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Right arrow Mechanical Circulatory Assistance

Original Articles: Adult Cardiac

Bleeding Complications and Blood Product Utilization With Left Ventricular Assist Device Implantation

Justin M. Schaffer, MSa, George J. Arnaoutakis, MDa, Jeremiah G. Allen, MDa, Eric S. Weiss, MDa, Nishant D. Patel, MDa, Stuart D. Russell, MDb, Ashish S. Shah, MDa, John V. Conte, MDa,*

a Department of Surgery, Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
b Department of Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Accepted for publication November 8, 2010.

Abbreviations and Acronyms APACHE II = Acute Physiology and Chronic Health Evaluation II; CF = continuous flow; DSC = delayed sternal closure; FFP = fresh frozen plasma; INTERMACS = Interagency Registry for Mechanically Assisted Circulatory Support; LVAD = left ventricular assist device; PF = pulsatile flow; pRBC = packed red blood cells; SHFM = Seattle Heart Failure Model

* Address correspondence to Dr Conte, Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Blalock 618, 600 N Wolfe St, Baltimore, MD 21287 (Email: jconte{at}csurg.jhmi.jhu.edu).

Presented at the Fifty-sixth Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 4–7, 2009.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Discussion
 References
 
Background: Bleeding complications are a major source of morbidity and reoperation after left ventricular assist device (LVAD) implantation, yet remain poorly characterized in patients receiving LVADs. We assessed bleeding complications in an institutional cohort of LVAD patients.

Methods: We reviewed patients who received continuous-flow (CF) LVADs at our institution (October 2004 to May 2009). Intraoperative and postoperative transfusion requirements (packed red blood cells, fresh frozen plasma, and platelets), chest tube output, and reoperation for bleeding complications were assessed. Univariate and multivariable Cox proportional hazard analysis assessed the impact of intraoperative bleeding on mortality. A subset of our patient population underwent delayed sternal closure as opposed to primary closure and an analysis of reoperation for bleeding was undertaken stratifying patients by approach to closure.

Results: Eighty-six CF LVADs were implanted over our study period. Patients had poor preoperative cardiac function and high preoperative risk indices. Patients receiving LVADs had high intraoperative (11.6 ± 7.5 units) and postoperative (15.6 [±12.6] units in the first week) blood product requirements, as well as significant chest tube output (5,880 [±4,480] milliliters in the first week). On multivariable analysis, intraoperative packed red blood cell transfusions were a significant predictor of mortality. Eleven (28%) patients undergoing primary sternal closure required reoperation for bleeding, while delayed sternal closure patients generally had resolution of bleeding prior to sternal closure. The incidence of gastrointestinal bleeding was 28% at one year.

Conclusions: On multivariable analysis, intraoperative packed red blood cell transfusions were a significant predictor of 30-day and one-year mortality, while chest tube output during the first postoperative 48 hours predicted 30-day but not one-year mortality.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Discussion
 References
 

Drs Russell and Conte disclose that they have financial relationships with Thoratec.

 

Bleeding complications are a major cause of morbidity and reoperation in left ventricular assist device (LVAD) patients. Analyses of first-generation pulsatile-flow (PF) LVADs identified intraoperative and early postoperative bleeding as common adverse events [1–3]. These data are replicated in second-generation continuous-flow (CF) devices: nearly one-third of CF patients in the 2007 HeartMate II (Thoratec Corporation, Pleasanton, CA) bridge to transplantation trial required reoperation for bleeding, while over 50% of patients required 2 or greater units of packed red blood cells (pRBC) within 30 days of LVAD placement [4]. Although the recent randomized controlled trial comparing HeartMate CF and PF devices suggests a reduced incidence of bleeding complications in CF patients, postoperative bleeding requiring either blood transfusion or reoperation remained a significant source of morbidity, occurring in 81% and 30% of the CF cohort, respectively [5].

In addition to intraoperative and early postoperative bleeding, late bleeding complications are also common adverse events in LVAD patients [2, 4]. Different devices have different anticoagulation requirements; the HeartMate II CF device requires anticoagulation to an international normalized ratio (INR) between 1.5 and 2.5 plus an antiplatelet agent, while the HeartMate I PF device only requires antiplatelet therapy [4–7]. As well, an early series of patients implanted with the CF Jarvik 2000 [Jarvik Heart Inc, Manhattan, NY] found that several patients developed chronic gastrointestinal bleeding secondary to arteriovenous malformation, data corroborated by subsequent studies suggesting increased incidence of gastrointestinal bleeding in HeartMate II CF patients compared with PF patients [8, 9]. The prevalent theory explaining this increase in gastrointestinal bleeding is that the shear stress of the CF LVAD results in proteolysis of high molecular weight multimers of von Willebrand's factor leading to angiodysplasia and increased bleeding [10, 11].

With second-generation CF devices having largely replaced first-generation PF devices, it is important to characterize the magnitude of adverse events related to bleeding in these newer generation devices. Therefore, we examined our institutional LVAD experience to determine the incidence of bleeding complications and product utilization in second-generation CF devices.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Discussion
 References
 
Study Design
We conducted a retrospective review of patients who underwent CF LVAD implantation at our institution (October 2004 to May 2009) after Institutional Review Board approval. We excluded all non-HeartMate (Thoratec Corp, Pleasanton, CA) LVADs, and patients whose pumps were implanted through thoracotomy.

Relevant baseline, operative, and postoperative data were collected. Preoperative risk scores including the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Seattle Heart Failure Model (SHFM) risk scores, as well as the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile were calculated for all patients [12–17]. Because the Leitz-Miller and Columbia risk scores did not predict mortality in our cohort, they were not employed in this analysis [18–20].

Primary endpoints included units of total blood products transfused, chest tube output, and bleeding complications requiring reoperation. In addition, the incidences of reoperation for bleeding, gastrointestinal bleeding, and anemia requiring blood transfusion were analyzed secondarily.

Statistical Analysis
Univariate and multivariable Cox proportional hazards regression analyses assessed the impact of intraoperative transfusions on the risk of 30-day and 1-year mortality. A multivariable model was constructed using seven variables: the INTERMACS, APACHE II, and SHFM preoperative risk scores as well as year of operation, chest tube output in the first 48 hours postoperatively, duration of cardiopulmonary bypass, and intraoperative pRBC transfusions. Censoring occurred for individuals who underwent device explant or did not have a bleeding complication by the end of the time point examined (administratively censored). Incidences were calculated using Kaplan-Meier survival analyses and are compared with a log-rank test.

Ordinal cut points of intraoperative pRBCs transfused were identified, and patients were stratified into high (≥5 units) and low (<5 units) transfusion groups. These thresholds were based on visual inspection of linear breaks in the risk of mortality along the continuum of blood products transfused in our cohort. The distribution of intraoperative transfusion requirements was plotted by histogram, and patients were stratified into groups based on the cut point that best fit the population. A Kaplan-Meier estimate of survival comparing the groups was performed up to one year of device support to ensure adequate follow-up. Survival curves were compared using the log-rank test.

Box plots are shown for blood product transfusions and chest tube output. The center line of the box plot represents the median value, the outer edges represent the 75th and 25th percentiles, and the distal lines represent the 95th and 5th percentiles, respectively. Outliers are not shown for graph legibility.

Means are presented with standard deviations, medians with interquartile ranges, and hazard ratios with 95% confidence intervals. For all analyses, a p value less than 0.05 was considered significant. Analyses were conducted using Stata software (version 9.2SE; StataCorp LP, College Station, TX).

Preoperative Anticoagulation
Over 90% of the cohort received a device on a nonemergent basis, allowing for management of preoperative medications prior to operation. Aspirin doses were typically held on the day of operation, while both clopidogrel and warfarin were held 5 to 7 days prior to operation. Patients withdrawn from warfarin therapy preoperatively were bridged using a heparin drip or enoxaparin.

Intraoperative Anticoagulation and Monitoring
Cardiopulmonary bypass was performed using a centrifugal pump, nonheparin-coated polyvinylchloride tubing, and polycarbonate connectors. In patients with a preoperative hematocrit greater than 30%, retrograde autologous priming and vacuum-assisted venous drainage were employed to achieve an intended bypass hematocrit between 24% and 30%. Autologous blood removed intraoperatively, as well as blood scavenged by cell saver (employed in all cases), were reinfused at the discretion of the anesthesiologists and perfusionists and were not included in our analysis. Surgicel (Johnson & Johnson Medical Inc, Arlington, TX) and gelfoam thrombin (Baxter, Hayward, CA) were employed for topical hemostasis at the surgeon's discretion. Of note, all patients receiving a CF device had the LVAD outflow cannula wrapped with a Gore-Tex (Gore Medical, Newark, DE) soft tissue patch.

Anticoagulation during bypass was accomplished using heparin in >90% of our cohort (others received either argatroban or bivalirudin due to suspected heparin-induced thrombocytopenia). Baseline activated clotting times (ACT) were drawn after skin incision, and a 300 units/kilogram dose of heparin was administered prior to cannulation, with another 10,000 units of heparin in the pump. Heparin was redosed based on serial ACT measurements to maintain an ACT greater than 480 seconds. Heparin was neutralized with protamine at a fixed dose of 1.3 mg of protamine for each 100 units of heparin. A repeat ACT was obtained after heparin reversal, with additional protamine administered if full reversal was not achieved.

Aprotinin was our antifibrinolytic of choice until its suspension by the Food and Drug Administration on November 5, 2007, with greater than 90% of patients receiving aprotinin prior to its removal from the market. Patients not receiving aprotinin received {varepsilon}-aminocaproic acid, which has replaced aprotinin as our institution's antifibrinolytic. Aprotinin was dosed in a weight-adjusted manner, with a 3.5 mg/kg intravenous bolus, 70 mg in the pump prime, and a 1 mg · kg–1 · hour–1 continuous infusion. The {varepsilon}-aminocaproic acid was dosed at 5 g prior to heparinization, 5 g in the pump prime, and infused at 1 g/hour during surgery.

Postoperative Anticoagulation
Patients receiving a CF device required long-term antiplatelet therapy as well as warfarin anticoagulation to achieve an INR between 1.5 and 2.5 [6, 7]. Therapy was initiated after delayed sternal closure (DSC) and resolution of active bleeding. Patients with hemostasis but without chest closure were maintained on intravenous heparin until definitive chest closure.

Transfusion Protocol
During active bleeding patients received blood product transfusions per the clinical judgment of the surgeon or ICU attending with goals of the following: hemoglobin 8 to 10 mg/dL, venous oxygen saturation greater than 60%, INR 1 to 1.4, and platelets greater than 100,000/µL unless heparin-induced thrombocytopenia or other hematologic problems are identified. In the absence of active bleeding, pRBCs were transfused if hemoglobin was less than 8 mg/dL, fresh frozen plasma was transfused for suspected coagulopathy, and platelets were transfused for counts less than 100,000/µL in the perioperative period and later for counts less than 50,000/µL unless heparin-induced thrombocytopenia or other hematologic problems were identified.

Delayed Sternal Closure
To avoid the need for resternotomy for active bleeding, tamponade, or poor hemodynamics in the early perioperative period, in June 2007 we adopted the practice of DSC. This approach involves approximating the skin and applying a sterile occlusive dressing with a nonapproximated sternum after LVAD implantation. A planned return to the operating room for chest exploration and presumptive sternal closure is typically performed within 48 hours. If bleeding and hemodynamics do not permit closure, patients remain with a nonapproximated sternum until appropriate for closure. We now await normalization of thromboelastograph curves prior to chest closure.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Discussion
 References
 
Baseline Characteristics and Preoperative Risk Scores
During the study period 86 patients received a CF device. Baseline characteristics are shown in Table 1. The high clinical acuity in this series is illustrated by the low preoperative cardiac index and high prevalence of preoperative cardiogenic shock, as well as low INTERMACS, high APACHE II, and high SHFM risk scores.


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  		Table 1 Baseline Characteristics and Preoperative Risk Scores (n = 86)
 
Operative Variables
Continuous-flow patients spent an average of 84 minutes on cardiopulmonary bypass, with a total operative (skin-to-skin) time of just over 5 hours (Table 2). Over 60% of the population received aprotinin for antifibrinolysis, and 46 (53%) patients underwent our technique of DSC. An average of 11.6 units of product were administered intraoperatively, including 5.1 units of pRBCs, 5.1 units of fresh frozen plasma, and 1.4 units of platelets transfused.


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  		Table 2 Intraoperative and Postoperative Variables
 
Postoperative Blood Product Utilization and Chest Tube Output
Box plots of intraoperative and postoperative blood product transfusions over the first week of device support are shown in Figure 1. Patients required an average of 12.6 units of blood product transfusions over 48 hours and 15.6 units over the first week after their operation (Table 2). A box plot of chest tube output over the first postoperative week is shown in Figure 2. An average chest tube output of 3 liters in the first postoperative 48 hours, and nearly 6 liters by the end of the first postoperative week was observed in our cohort.


Figure 1
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  		Fig 1. Box plot of daily product transfusion requirements for the first postoperative week according to (A) total products, (B) packed red blood cells, (C) fresh frozen plasma, and (D) platelets. (POD = postoperative day.)

 

Figure 2
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  		Fig 2. Box plot of daily chest tube output for the first postoperative week. (POD = postoperative day.)

 
Delayed Sternal Closure and Reoperation for Bleeding
Twenty (23%) patients underwent reoperation for bleeding, with 17 (20%) of patients requiring reoperation for bleeding after sternal closure (Table 2). The breakdown of patients undergoing DSC is depicted in Figure 3. Forty-six (53%) patients underwent DSC, of whom 2 (4%) expired prior to chest closure. On average, patients undergoing DSC were closed on postoperative day 2 (±1.9). Of the 46 patients undergoing DSC, 4 (9%) developed active bleeding and 3 (7%) acquired hematoma causing tamponade physiology and required operative intervention prior to definitive chest closure. Among DSC patients, 6 (13%) required reoperation for bleeding or hematoma causing tamponade physiology after initial closure. Of the six patients requiring reoperation after DSC, two had active bleeding, one had hematoma causing tamponade physiology, and three had no signs of active bleeding prior to their initial sternal closure. Meanwhile, of the 40 patients undergoing primary sternal closure, 11 (28%) underwent reoperation for bleeding. Blood products transfused in the operating suite during a delayed sternal closure or reoperation for bleeding were tallied in the "postoperative blood product transfused" variables shown in Table 2 and Figure 1.


Figure 3
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  		Fig 3. Breakdown of our CF patient population by closure approach (primary closure vs delayed sternal closure), with delineation of subsequent bleeding complications.

 
Operative Bleeding and Mortality: Univariate and Multivariable Analysis
On univariate Cox proportional hazards analysis, operative pRBCs transfused, operative fresh frozen plasma transfused, operative platelets transfused, duration of cardiopulmonary bypass, year of implantation, as well as all three risk scores (INTERMACS, APACHE II, and SHFM) predicted overall mortality (Table 3). Similarly, these same variables predicted 30-day mortality on univariate analysis, except for year of implantation which did not achieve significance (p = 0.07). Notably, DSC did not predict either 30-day or overall mortality on univariate analysis, and thus was not included on multivariable analysis. On multivariable analysis only operative pRBCs transfused remained a significant predictor of both 30-day and cumulative mortality after risk adjustment, with an increase in risk of 14% and 9%, respectively (Table 3). Chest tube output in the first postoperative 48 hours predicted 30-day mortality (an increased risk of 16% for every extra liter of chest tube output) but not overall mortality in our multivariable models.


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  		Table 3 Univariate and Multivariable Cox Proportional Hazard Analysis of 30-Day and Overall Mortality
 
Operative Bleeding and Mortality: Kaplan-Meier Survival Analysis
The distribution of total transfused intraoperative pRBCs along with a Kaplan-Meier survival curve stratified by units of operative blood products is shown in Figure 4. The incidence of mortality in patients receiving less than 5, 5 or greater units of operative pRBCs was significantly different (19% vs 41% at 1 year, p < 0.001 by log-rank).


Figure 4
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  		Fig 4. (A) Histogram of operative pRBCs transfused. (grey column = < 5 units pRBC transfused [p = 49]; black column = ≥ 5 units pRBC transfused [n = 37]). (B) Kaplan-Meier survival curve by strata of intraoperative blood transfusion requirements groups. (— = < 5 units pRBC transfused; --- = ≥ 5 units pRBC transfused; p > 0.001, by log-rank test.)

 
Long-Term Bleeding: Gastrointestinal Bleeding
The incidence of gastrointestinal bleeding (defined as bleeding with an identifiable gastrointestinal source by esophagogastroduodenoscopy, colonoscopy, or tagged red blood cell scan) was high in our cohort, with 28% of patients developing a gastrointestinal bleed at one year (Fig 5). The majority of gastrointestinal bleeding in our cohort occurred within the first 6 months postoperatively. All CF patients were anticoagulated with warfarin (goal INR 1.5 to 2.5), with an average INR at 30 days and 6 months postoperatively of 2.08 (±0.57) and 2.21 (±0.69), respectively.


Figure 5
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  		Fig 5. Kaplan-Meier estimate of freedom from gastrointestinal bleeding.

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Discussion
 References
 
In this study we review bleeding complications in a single institutional cohort of 86 CF LVAD patients. Though previous studies have implicated bleeding complications as significant sources of morbidity and reoperation in LVAD patients, a focused analysis of blood products transfused, chest tube output, and reoperation for bleeding has not been performed [1–7]. Moreover, these data indicate a direct relationship between intraoperative pRBC transfusion requirement and one-year Kaplan-Meier mortality. This relationship persisted after risk adjustment using multivariable analysis. There is growing evidence to support the adverse effect of pRBC transfusions with respect to infection rates and length of stay, as well as early and long-term outcomes in cardiac surgery patients [21–23].

Population Characteristics
The severity of our cohort is illustrated by their low ejection fractions and cardiac indices, near uniform classification as New York Heart Association class IV, and high preoperative risk assessed by the APACHE II, INTERMACS, and SHFM scores. This cohort of CF patients represents a recent era of device support, with lower preoperative risk as assessed by the APACHE II, INTERMACS, and SHFM scores compared with our PF cohort [24]. This likely reflects the more recent practice of early establishment of mechanical circulatory support.

Operative Bleeding and Mortality
There was an absolute decrease in Kaplan-Meier one-year survival of 22% when comparing patients who received less than 5, and 5 and greater units. Some of this difference in mortality can be attributed to the acuity of the patient at the time of operation as well as the difficulty of the operation. However, that intraoperative pRBC transfusions persisted as an independent contributor to the risk of 30-day and cumulative mortality after adjustment for three preoperative risk indices and duration of cardiopulmonary bypass supports an independent effect of pRBC transfusion on mortality. Certainly a 13% increase in 30-day and 9% increase in overall mortality per unit transfused on multivariable analysis is clinically significant. Although operative pRBC transfusions are in part a surrogate of operative difficulty, they remained significant despite adjustment for another surrogate of operative difficulty, cardiopulmonary bypass time. These data add to the growing body of literature suggesting an independent effect of intraoperative pRBC transfusions alone on mortality.

Delayed Sternal Closure and Reoperation for Bleeding
Although patients undergoing DSC required fewer reoperations for bleeding after sternal closure compared with patients closed primarily, it should be noted that 7 (15%) of DSC patients had either active bleeding or tamponade at the time of initial closure. However, only 6 (13%) of DSC patients required reoperation for bleeding after their delayed closure, which is in contrast to the 11 (28%) patients with primary chest closure who required reexploration for bleeding. These results suggest that the practice of DSC may be a useful strategy in LVAD patients at high risk for bleeding.

Late Bleeding
The incidence of gastrointestinal bleeding was consistent with recent reports of late bleeding in CF patients (28% at one year compared with approximately 25% at one year reported by Crow and colleagues [9]). As mentioned by Crow and colleagues, this incidence is far above the 5.7% events per patient year suggested by Levine and colleagues [25] for patients receiving anticoagulation. Further investigation is needed to corroborate the acquired von Willebrand's disease theory and to better characterize the observed incidence of late bleeding in CF LVAD patients.

Prior Work
Definitions of bleeding complications in LVAD patients vary widely in the literature, and little has been reported regarding intraoperative and postoperative transfusion requirements [1–4]. A study using Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure patients reports that PF patients received 8.1 units of pRBCs; however, it does not indicate the timing of the transfusions [2]. Only 8% of our CF patients avoided receiving pRBC in the postoperative period, compared with 19% of CF patients in the recent destination therapy trial [5]. The 31% and 30% of patients requiring reoperation for bleeding in the HeartMate II bridge to transplant and destination therapy trials were similar to our primary closure cohort, of whom 28% underwent reoperation for bleeding [4, 5]. It is impractical to attempt to compare our DSC cohort with other published data regarding reoperation for bleeding.

Limitations
Our study is limited by its retrospective nature and small sample size. Our institutional cohort may not be widely generalizable given the lack of standardized LVAD implantation criteria. Additionally, our study is limited by the novelty of CF LVADs, and consequently, the lack of long-term follow-up for these patients. Our analysis did not stratify patients by therapeutic intent, as therapeutic intent was not a significant covariate for any of our mortality or bleeding endpoints.

Conclusions
This study examines the incidence of bleeding complications in a single institutional cohort of CF LVAD patients. Despite improvements in device design and increased ease of implantation, patients receiving CF devices still experience significant morbidity related to bleeding. Intraoperative pRBC transfusions have a significant impact on 30-day and overall mortality, which persisted after risk adjustment.


   Discussion
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
References
 
DR CURTIS G. TRIBBLE (Gainesville, FL): This is a nice review about an important subject, and a subject actually that is increasing in importance as more left ventricular assist devices are used and as ventricular assist devices improve. However, obviously this study is limited by a comparison of very different devices in very different eras, and even different patients, I believe. As I read through your paper, the patients had been selected at a less sick time for the HeartMate II implantations.

I think there are some lessons. It does certainly seem like the HeartMate II is a better device for most patients. There are some exceptions to that, I suppose, people that can't have anticoagulation, et cetera. It sounds like the current selection process for who is going to get a device is better now than it used to be. I was intrigued by the fact that there seemed to be no increased risk of GI [gastrointestinal] bleeding. I think that has been something that people have been talking about in these continuous-flow devices. So it is nice to see that at least in your series it doesn't look like that is so true. And I am pretty sure blood transfusions are bad. That has been a theme not just of your talk.

There are still some unknowns, and as we get through this we will ask Dr Conte to comment on this, but I think there is still a question of whether it is better to leave the chest open or not. There is some controversy about that. A lot of people do that, a lot of other people don't. And another thing that I think is unknown is do the HeartMate IIs really need triple anticoagulation with all three drugs? Maybe they don't and maybe that would even make the bleeding issues less, and I don't think that is known. I know you didn't address that.

But I have two questions for you, Justin, and then we will ask Dr Conte to comment, I think he is here, somewhere back there, about the leaving the chest open.

The first, I saw in your several slides that I reviewed and I saw you presented today again that it seems like you did a pretty careful analysis to try to sort out if the blood transfusions were really the source of the increased mortality in the long run, but it seems like they were so closely tied to the earlier era and the earlier devices that I just want to ask you, as you thought through this do you really think that that was as independent a predictor of mortality as your slides suggested? It sure seemed to me like there are an awful lot of other variables in that equation and it would be hard to sort them out. So that is one question.

And the only other one I have got for you; in your review, even though this wasn't the focus of it, given that you left these HeartMate II patients' chests open for a day or two or three or however long it took to get things to settle down, did you see in your review of those patients any hint of an increase in infection? We worry so much about infection in placing these devices, they have got a cord that comes out of their side, et cetera, et cetera, and I don't believe you mentioned that in your talk or in your paper, but you might remember whether there was or wasn't.

MR SCHAFFER: Thank you very much, Dr Tribble, for those kind comments. In terms of your first question, our opinion is that blood products transfused are a marker of operative risk, and that they do, independently, predict mortality. Evidence supporting this claim comes from our multivariable analysis presented earlier, where we included measures of preoperative risk as well as device type and year of implantation. So if we go back to our slide of that multivariable analysis assessing both 30-day and overall mortality, we see that independent of the era effect, preoperative risk, and device type, blood products transfused still significantly predicted mortality. Now, as mentioned previously, a number of factors play into the amount of blood products transfused, including operative complexity, and in our analysis we were unable to tease out which factors contributing to transfused blood products were most significant. Nonetheless, our, albeit limited, analysis appears to show that complexity of the operation as assessed by operative blood products transfused has a big effect on long-term mortality.

As for your second question regarding delayed sternal closure, we do have a subset of patients in the cohort we presented today that did undergo delayed sternal closure. I believe it is a total of 57 patients of the 133 presented. We looked at rates of reoperation for bleeding in those patients after initial sternal closure. In other words, once those patients are taken back to the operating room and have their chests closed we then analyzed rates of reoperations for bleeding. What we found is that patients who underwent delayed sternal closure had a lower incidence of reoperation for bleeding.

Finally, as for your third question regarding infectious complications, we actually performed an analysis of these complications comparing first-generation and second-generation devices at the ISHLT [International Society for Heart and Lung Transplantation] in 2007, and found a significant reduction in overall sepsis, as well as driveline infections and pocket infections in second-generation continuous-flow device patients. To put it bluntly, in our cohort infectious complications of all varieties were significantly reduced in the second-generation devices. How delayed sternal closure plays into this is certainly up for debate. I can tell you that a higher percentage of our second-generation devices underwent delayed sternal closure, and yet we still saw a lower incidence of infectious complications in those patients. But we have not specifically assessed the effect of delayed sternal closure on infectious complications using a multivariable analysis. That's a great idea for another paper, though.

DR TRIBBLE: I would just like to ask John to comment. I think a lot of people might be interested in your strategy for how you handle that delayed sternal closure. Specifically, do you use VAC [vacuum assisted closure] sponges, do you pack them with Gelfoam and thrombin, do you explore them every day whether you are ready to close them or not? In other words, I think this sort of thing is very well worked out in the trauma literature for open abdomens, maybe not so well worked out when we have got a device, et cetera, et cetera. I thought it would be interesting to hear just a few comments from you about that.

DR CONTE: Thank you for the kind comments, and Justin did a great job. He flew in here last night from his general surgery interview at the University of Michigan. I know Rich Prager is here, and you can't have him, Rich. (Laughter).

What we have evolved into doing wasn't our idea. Bud Frazier was the one who got us doing this, and he said as you get older you don't want to take patients back in the middle of the night, so he started packing patients, and when I started to get a little grayer I happened to agree with him. So we just simply will go and close the skin. I think a lot of the bleeding we have in these VAD [ventricular assist device] patients are from hepatic congestion and coagulopathy. We and our hematologists, and we have a hematologist who follows every one of our VAD patients, really don't have a good handle on why these people bleed. We like to say it is because of liver dysfunction, but in fact if you go and look at your standard liver function test, if you go and look at vitamin K stores, if you go and look at many of the traditional coagulation parameters that we look at, they are not that bad and they are easily correctable, but yet the patient still bleeds 400 cc's an hour. And so we basically just stopped putting holes in the sternum with our sternal wires and we just closed the skin. We don't pack them with anything in particular, although we are going to be participating in a study where we pack people with antifibrinolytic laparotomy sponges with the idea that the local fibrinolysis may be adding to the coagulopathy. But, quite simply, we just close the skin with a running or an interrupted stitch, put an occlusive dressing on top, and that is it. We either take them back the next day when we have documented that their bleeding has resolved or we will take them back the next available day. So if we have a busy day the next day, I won't rush to take them back to the operating room. And since we have adopted that policy we have had zero infections, and, in fact, we have begun to adopt this policy for our difficult standard cardiac surgery cases. We don't waste time in the operating room giving rounds and rounds of products. We close them, we take them to the ICU [intensive care unit], and we bring them back, and we really have not had a problem.

I think the key in all of this is closing the skin. That is the same barrier to infection we would have regardless of the type of operation. So if you close the skin, you shouldn't have any higher incidence of infection, at least in the mediastinum, as you do otherwise. So it is very simple, wasn't our idea, but it seems to work.

DR CHARLES KLODELL (Gainesville, FL): Congratulations on an outstanding presentation. Since this really does, as Dr Tribble alluded to, represent two different eras in VADs, I wonder if you could comment on the differences very quickly of preoperative optimization in these patients. Did you use more TEGs [thromboelastograms], did you use more PFA-100s [platelet function analyzer], did you augment the red cells pharmacologically, and also were there different intraoperative fibrinolytic strategies utilized?

MR SCHAFFER: I can't specifically comment on most of what you asked. I have not performed that analysis, unfortunately. But I can tell you in terms of our more rudimentary assessment preoperative risk, it had no effect.

DR CONTE: There was very little difference in the strategy. We put balloons in people who have central venous pressures above 20 whenever we can; however, that hasn't been optimized as much as we could have, and there were more patients in the nonpulsatile group that used aprotinin. We did use that very frequently. We don't anymore. The interesting thing is it didn't seem to make a difference, it really didn't. In this population or in our other population of horrible redo patients that we thought we needed aprotinin for, it turns out we haven't increased our blood utilization at all.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Discussion
 References
 

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