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Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery
Journal Pre-proof Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery Chetan Pasrija, MD, Mehrdad Ghoreishi, MD, Glenn Whitman, MD, Niv Ad, MD, Diane E. Alejo, BA, Sari D. Holmes, PhD, Stefano Schena, MD, Rawn Salenger, MD, Michael A. Mazzeffi, MD, Clifford E. Fonner, BA, Bradley Taylor, MD, MPH, on behalf of the Investigators for the Maryland Cardiac Surgery Quality Initiative PII:
S0003-4975(19)31895-8
DOI:
https://doi.org/10.1016/j.athoracsur.2019.10.076
Reference:
ATS 33322
To appear in:
The Annals of Thoracic Surgery
Received Date: 4 February 2019 Revised Date:
23 August 2019
Accepted Date: 1 October 2019
Please cite this article as: Pasrija C, Ghoreishi M, Whitman G, Ad N, Alejo DE, Holmes SD, Schena S, Salenger R, Mazzeffi MA, Fonner CE, Taylor B, on behalf of the Investigators for the Maryland Cardiac Surgery Quality Initiative, Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery, The Annals of Thoracic Surgery (2020), doi: https://doi.org/10.1016/j.athoracsur.2019.10.076. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery Running Head: Transfusion or Reop for Bleeding
Chetan Pasrija, MD1, Mehrdad Ghoreishi, MD1, Glenn Whitman, MD2, Niv Ad, MD1, Diane E Alejo, BA2, Sari D. Holmes, PhD1, Stefano Schena, MD2, Rawn Salenger, MD1, Michael A Mazzeffi, MD4, Clifford E Fonner, BA3, Bradley Taylor, MD, MPH1; on behalf of the Investigators for the Maryland Cardiac Surgery Quality Initiative
1
University of Maryland School of Medicine, Division of Cardiac Surgery. Baltimore, MD
2
The Johns Hopkins Medical Institutions, Division of Cardiac Surgery. Baltimore, MD
3
Maryland Cardiac Surgery Quality Initiative. Baltimore, MD
4
University of Maryland School of Medicine, Department of Anesthesiology. Baltimore, MD Oral Presentation at the Society of Thoracic Surgeons 55th Annual Meeting
Word Count: 4329 Address for Correspondence: Chetan Pasrija, MD University of Maryland, Division of Cardiac Surgery 110 S Paca St, 7th Floor Baltimore, MD 21201 Email: [email protected]
Abstract Background: Several studies have established morbidity associated with bleeding after cardiac surgery. While reoperation has been implicated as the marker for this morbidity, there remains limited understanding regarding relative morbidities of reoperation and substantial transfusion. Methods. The Society of Thoracic Surgeons (STS) Maryland adult cardiac surgery database (7/20119/2018) was reviewed (N=23,240). Substantial transfusion was defined as requiring greater than the reoperation group median red blood cells (RBC; 5 units) and non-RBCs (4 units). Patients were stratified into 4 subgroups: Group 1, no reoperation without substantial transfusion (n=22,365); Group 2, reoperation without substantial transfusion (n=351); Group 3, no reoperation with substantial transfusion (n=350); and Group 4, reoperation with substantial transfusion (n=167). Operative morbidity and mortality were compared. Results. Reoperation patients were older with a higher STS predicted risk of mortality(1.8% vs. 1.2%, P<0.001). Multivariable analysis demonstrated that Group 4 (reoperation with substantial transfusion) increased the odds of renal failure (OR=7.36, P<0.001), stroke (OR=3.24, P=0.002), and operative mortality (OR=8.68, P<0.001) compared with Group 1 (neither reoperation or substantial transfusion). Both Group 2 (reoperation alone) and Group 3 (substantial transfusion alone) increased the odds of mortality and renal failure compared to Group 1. However, Group 3 had greater risk for renal failure (OR=3.48, P<0.001) and mortality (OR=2.91, P<0.001) than Group 2. Conclusions. While reoperation for bleeding is associated with morbidity after cardiac surgery, substantial transfusion without reoperation appears to increase morbidity compared to a limitedtransfusion reoperative approach. Better timing for reoperation and guided transfusion approaches may mitigate morbidity compared to substantial transfusion alone. Word Count: 250
Reoperation for bleeding is an uncommon but morbid event after cardiac surgery. Recent studies have demonstrated that it is necessary in 2 to 6% of patients, and is associated with 3 to 7-fold increase in operative mortality (1-4). Due to this substantial increase in mortality, the Society of Thoracic Surgeons (STS) has deemed surgical re-exploration to be a critical adult cardiac surgery performance measure, in line with stroke, deep sternal wound infection, postoperative renal failure, and prolonged intubation (5). In order to reduce the incidence of surgical re-exploration, bleeding after cardiac surgery may be treated medically with blood product transfusions, reserving reoperation for refractory cases. However, the morbidity of allogeneic blood product transfusions have been well-established, with an increased risk of transfusion-related acute lung injury, infection, and renal failure, among other morbidities (6-9). Since these appear to correlate with the quantity of products transfused, patients receiving a considerable amount of blood products for bleeding are at the highest risk of these complications (10). The impact of substantial transfusion for bleeding compared to an early, guided reoperative approach without substantial blood transfusion is currently poorly understood. We hypothesized that bleeding after cardiac surgery treated either medically with substantial blood transfusions alone, or surgically but after administration of considerable blood products, would increase morbidity and mortality compared to a guided reoperative approach prior to the administration of substantial blood products. Patients and Methods Study Population The STS statewide database for Maryland was reviewed between July 1, 2011 and September 30, 2018 for patients who underwent adult cardiac surgery including isolated coronary artery bypass grafting (CABG), isolated mitral valve repair/replacement, isolated aortic valve repair/replacement, or a combination of the above operations. Patients were included in the cohort for this study if their procedure was eligible for STS predicted risk scoring and data on reoperation for bleeding were available. There were 23,240 eligible patients, including 518 patients with reoperation for bleeding. Patients were then stratified into 4 groups based on reoperation for bleeding and substantial transfusion. The substantial transfusion cohort was defined based on the median amount of red blood cell (RBC) units and non-RBC
units transfused in the reoperation for bleeding group of patients. Consequently, greater than 5 units of RBC and greater than 4 units of non-RBC products transfused postoperatively was defined as substantial transfusion. The 4 study groups included: 1) patients without reoperation for bleeding and without substantial transfusion (Group 1; -Reop/-Blood); 2) patients with reoperation for bleeding without substantial transfusion (Group 2; +Reop/-Blood); 3) patients without reoperation for bleeding and with substantial transfusion (Group 3; -Reop/+Blood); 4) patients who required reoperation for bleeding and substantial transfusion (Group 4; +Reop/+Blood). Outcomes The primary outcome for this study was STS-defined 30-day mortality. Secondary outcome measures were also STS-defined and included: renal failure (3× increase in serum creatinine from baseline or rise in creatinine to >4 mg/dL with a minimum increase of 0.5 mg/dL, or new need for hemodialysis), stroke, short length of stay (LOS; discharged alive and within 5 days of surgery), prolonged LOS (>14 days), and readmission within 30 days. Statistical Analysis All analyses were conducted with SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY) and the alpha level was set at P < 0.05, two-tailed. Continuous variables are presented as median (interquartile range [IQR]) and categorical variables are presented as frequency (percent). Some variables had missing values and in those cases percentages are presented out of the total valid sample size. Patient and surgical characteristics were compared between the 4 study groups using the Kruskal-Wallis test with Bonferroni correction for continuous variables and Chi-square tests for categorical variables. Group contrast comparisons for categorical variables with significant overall group differences were conducted using univariate logistic regression analyses with Group 1 as the reference. Multivariable logistic regression was conducted to examine the impact of the 4 study groups on STS-defined outcome measures after adjustment for age, gender, race, outcome-specific STS predicted risk score, status (elective vs nonelective), preoperative hematocrit, type of procedure (isolated CABG, isolated AV, isolated MV,
combination procedure), length of surgery, and intraoperative units of blood. The STS risk score for morbidity/mortality was used for the analysis of readmission within 30 days since there is no specific STS predicted risk for readmission. Secondary analyses compared patients with early (≤24 hours) and late (>24 hours) timing of reoperation for bleeding on outcome measures using Chi-square or Fisher’s Exact tests. Results Overall Patient Characteristics In this sample, most patients did not require a reoperation for bleeding (n = 22,722; 98%). The incidence of reoperation for bleeding was 2% (n = 518). There was heterogeneity across hospitals in the state regarding incidence of reoperation for bleeding, but no center had an incidence greater than 3% (Figure 1). Those who required reoperation for bleeding were older, more likely to be dialysis-dependent, and have congestive heart failure. Moreover, these patients were less likely to have diabetes or dyslipidemia (Table 1). Patients who required reoperation for bleeding were more likely to have had a valve procedure, either isolated or in combination, and less likely to have undergone an isolated CABG (Table 1). For the 4 study group analyses, most patients were categorized into Group 1 (-Reop/-Blood, n = 22,365) with 351 patients in Group 2 (+Reop/-Blood), 350 patients in Group 3 (-Reop/+Blood), and 167 patients in Group 4 (+Reop/+Blood). There were 7 patients who were missing postoperative blood product transfusion data and could not be stratified into the 4 study groups, but none had a reoperation for bleeding. Preoperative patient and surgical characteristics were different between Group 1 and the other groups. Specifically, Group 1 was younger, less likely to be dialysis-dependent and in congestive heart failure, and more likely to have diabetes and elective status (Table 2). Group 1 was also more likely to have isolated CABG and less likely to have a combination surgical procedure than the other 3 groups. Median units of postoperative blood products transfused was 0 (0–1) in Group 1, which was significantly less than Group 2 (5 [2–8], P < 0.001), Group 3 (16 [12–23], P < 0.001), and Group 4 (20 [14–28], P < 0.001). Median postoperative RBC units was 0 (0–1) in Group 1, which was significantly less than Group 2 (3 [1–4], P < 0.001), Group 3 (7 [5–10], P < 0.001), and Group 4 (8 [6–12], P < 0.001). Median
postoperative non-RBC units was 0 (0–0) in Group 1, which was significantly less than Group 2 (2 [0–4], P < 0.001), Group 3 (8 [6–13], P < 0.001), and Group 4 (11 [6–16], P < 0.001). Differences in postoperative blood products transfused were also significantly different between Groups 2 and 3 (P < 0.001), as well as Groups 2 and 4 (P < 0.001). Impact of Both Reoperation and Transfusion The incidence of mortality within 30 days was 1.5% in Group 1 (n = 329), 6% in Group 2 (n = 21), 20% in Group 3 (n = 70), and 19% in Group 4 (n = 31). After multivariable adjustment, patients with reoperation for bleeding plus substantial transfusion (Group 4) had significantly greater risk for renal failure (OR = 7.36, P < 0.001), stroke (OR = 3.24, P = 0.002), prolonged LOS (OR = 6.08, P < 0.001), readmission within 30 days (OR = 1.65, P = 0.036), and mortality within 30 days (OR = 8.68, P < 0.001) compared with Group 1 (Figure 2). Group 4 also had reduced odds of short LOS (OR = 0.19, P < 0.001). There were no significant differences in outcomes between Group 3 and Group 4 (Figure 3) indicating that patients with substantial transfusion alone had similar outcomes to those with substantial transfusion who also underwent a reoperation for bleeding. Impact of Transfusion in Reoperation Patients Within all patients who required reoperation for bleeding, the impact of transfusion was examined by comparing those with (Group 4) and without substantial transfusion (Group 2). After multivariable adjustment, Group 4 had greater risk for renal failure (OR = 2.19, P = 0.026), prolonged LOS (OR = 2.41, P < 0.001), and mortality within 30 days (OR = 2.81, P = 0.002) compared with Group 2 (Figure 4). Transfusion Alone vs Reoperation Alone In multivariable analysis, the reoperation for bleeding alone (Group 2) and substantial transfusion alone (Group 3) groups had increased risk of mortality (Group 2: OR = 3.09, P < 0.001; Group 3: OR = 8.97, P < 0.001), renal failure (Group 2: OR = 3.37, P < 0.001; Group 3: OR = 11.71, P < 0.001), and prolonged LOS (Group 2: OR = 2.52, P < 0.001; Group 3: OR = 6.71, P < 0.001) compared with Group 1. Both Group 2 and Group 3 also had reduced odds for short LOS compared with Group 1 (Group 2: OR = 0.34, P < 0.001; Group 3: OR = 0.18, P < 0.001). However, when comparing the two groups, Group 3 was
found to have greater risk for renal failure (OR = 3.48, P < 0.001), prolonged LOS (OR = 2.66, P < 0.001), and mortality within 30 days (OR = 2.91, P < 0.001), as well as reduced odds for short LOS (OR = 0.53, P = 0.009; Figure 5) compared with Group 2. Optimal Reoperation Timing The timing of reoperation for bleeding was early (≤24 hours) in 86% of patients (n = 445) and these patients had lower incidence of renal failure (7% vs 21%, P < 0.001), prolonged LOS (18% vs 51%, P < 0.001), and mortality within 30 days (8% vs 22%, P < 0.001) and greater incidence of short LOS (21% vs 3%, P < 0.001) compared to late reoperation for bleeding. Comment This study provides further evidence that reoperation for bleeding after cardiac surgery is highly morbid. However, these data also suggest that medically treated bleeding, with extensive blood product transfusion and without reoperation, increases morbidity and mortality compared to a guided reoperative approach prior to the administration of numerous blood products. Late reoperation, greater than 24 hours after operation, appears to be particularly morbid, with a 14% increase in 30-day mortality. The impact of reoperation after cardiac surgery has been well-studied over the past two decades. Vivacqua et al. demonstrated that the risk of morbidity and mortality increases with the number of RBCs transfused, but reoperation for bleeding heightened the risk of morbidity and mortality for any number of transfused RBCs (11). In a large single center review, Ruel and colleagues found that the observed-toexpected mortality ratio increased from 0.7 in patients who were not re-explored, and 1.8 in those who were re-explored (2). This group also found that reoperation and intraoperative blood product transfusion independently contributed to perioperative mortality. The present study, similar to the above studies, also demonstrates that bleeding and reoperation after cardiac surgery are morbid. However, in previous analyses, direct comparisons of the morbidity associated with medically treated bleeding utilizing substantial blood transfusions, reoperation without substantial transfusion, and reoperation with substantial transfusion have been limited (12, 13). This study suggests that, among patients with
postoperative bleeding, an early, guided approach to reoperation may mitigate morbidity compared to an observational strategy associated with considerable blood transfusion. Given the morbidity and mortality associated with reoperation for bleeding, the STS has established surgical re-exploration as an important measure of hospital and surgeon quality (5). While these data support the notion that reoperation is a morbid event, this quality measure may dissuade surgeons from returning to the operating room early and expeditiously. Instead, surgeons may opt to transfuse this cohort of patients until the bleeding subsides, reserving reoperation for patients who continue to bleed despite significant transfusion. This study suggests that, within the cohort of bleeding patients after cardiac surgery, early, guided reoperation may, in fact, be the desired strategy to limit morbidity. On the other hand, substantial transfusion appears to be the more morbid treatment strategy. While future studies are needed to confirm and expand upon these findings, these data suggest that substantial transfusion after cardiac surgery should be added as a quality measure, in conjunction or potentially even in place of surgical re-exploration. While individual center thresholds vary, centers included in this study support the findings of this study: guided, early reoperation prior to the administration of numerous blood products may mitigate morbidity associated with bleeding after cardiac surgery. The etiology underlying the morbidity of substantial transfusions is likely multifactorial, including the impact of allogeneic blood product transfusion and hemodynamic effects of a large volume of clotted blood within the mediastinum. Several studies have established the negative impact of allogeneic blood product transfusion, and in particular, massive transfusion. Massive transfusion increases the odds of transfusion-related acute lung injury by 450%, with increased mechanical ventilation time and end-organ failure (14). Moreover, given that each RBC unit can contain approximately one million donor leukocytes, massive transfusion leads to immune dysfunction leading to infection and sepsis (15). Outside of the impact of blood product transfusion, large volume clotted blood within the mediastinum can have subtle hemodynamic effects leading to low cardiac output and high venous pressure, also resulting in endorgan dysfunction and ultimately, mortality. Still, this study is unable to evaluate mechanisms of
morbidity associated with transfusion compared to reoperation, and additional studies are needed to better understand these differences. Numerous definitions have been proposed for significant transfusion associated with bleeding after cardiac surgery, ranging from any transfusion of a non-RBC blood product to greater than 10 RBC and 10 non-RBC transfusions for massive bleeding (16-18). In an effort to standardize definitions for bleeding, the Bleeding Academic Research Consortium (BARC) established evidence-based bleeding classifications (19). CABG-related bleeding was considered any perioperative intracranial hemorrhage, reoperation, transfusion greater than 5 units within 48 hours, or chest tube output greater than 2L within 24 hours. However, given the limitations of this retrospective database analysis, we were unable to quantify chest tube output or define transfusion within pre-specified time periods. We, therefore, utilized the median number of RBCs and non-RBC blood products within the cohort of patients who were reexplored as the threshold for substantial transfusion. This definition has potential limitations for generalizability. For instance, there may be bleeding patients after cardiac surgery who were not included in the substantial transfusion cohort but still benefit from an early reoperation. Still, we controlled for known factors associated with blood transfusion, such as preoperative hemoglobin, and excluded patients at high risk for needing substantial blood transfusions outside of acute postoperative bleeding, such as those on mechanical circulatory support. Prospective studies are needed to evaluate exact bleeding cutoffs, where the morbidity of continued transfusion is greater than that of surgical re-exploration. At several of our institutions, patients at high-risk for considerable bleeding are monitored in the operating room after skin closure for 30 to 60 minutes. While thresholds to re-explore vary, this strategy allows for early re-exploration prior to the administration of a substantial amount of blood products. Limitations This study is a retrospective cohort analysis with the associated limitations. While we performed a multivariable analysis to control for differences in patients, those who required a reoperation or numerous blood transfusions may have unaccounted morbidities that contributed to their bad outcome. There may also be residual confounding between the specific groups, as patients within Group 3 may have had
unaccounted reasons for not undergoing a reoperation. Given the limitations of a database analysis, we are unable to evaluate granular data such as chest tube output prior to reoperation. While this study suggests that reoperation and/or substantial transfusion after cardiac surgery increases morbidity and mortality, we are unable to definitively establish a causal relationship between reoperation, transfusion, and morbidity. Importantly, bleeding after cardiac surgery is a multifactorial problem, with several contributing factors. This study suggests that timing of reoperation and the administration of numerous blood transfusions are morbid, but given its retrospective nature, does not account for intrinsic patient coagulopathy, hemostasis management techniques, or use of anti-fibrinolytics. Future, prospective studies are needed to establish a protocol-driven, guided reoperative approach, where morbidity is minimized by surgical re-exploration or limited blood transfusion, when appropriate. A standardized protocol for assessment and treatment of bleeding will be necessary to account for surgical-team and patient differences. Conclusion While reoperation for bleeding is associated with morbidity after cardiac surgery, substantial transfusion without reoperation appears to increase morbidity compared to a limited-transfusion reoperative approach. Early, guided reoperation approaches may mitigate the adverse impact and thus, morbidity, of substantial transfusion. Studies standardizing timing and indications for reoperation are needed to optimize outcomes for patients with postoperative bleeding.
References 1.
Ranucci M, Bozzetti G, Ditta A, Cotza M, Carboni G, Ballotta A. Surgical reexploration after
cardiac operations: Why a worse outcome? Ann Thorac Surg 2008;86(5):1557-1562. 2.
Ruel M, Chan V, Boodhwani M et al. How detrimental is reexploration for bleeding after cardiac
surgery? J Thorac Cardiovasc Surg 2017;154(3):927-935. 3.
Mehta RH, Sheng S, O'Brien SM et al. Reoperation for bleeding in patients undergoing coronary
artery bypass surgery: Incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes 2009;2(6):583-590. 4.
Karthik S, Grayson AD, McCarron EE, Pullan DM, Desmond MJ. Reexploration for bleeding
after coronary artery bypass surgery: Risk factors, outcomes, and the effect of time delay. Ann Thorac Surg 2004;78(2):527-534; discussion 534. 5.
Shahian DM, O'Brien SM, Filardo G et al. The Society of Thoracic Surgeons 2008 cardiac
surgery risk models: Part 1--coronary artery bypass grafting surgery. Ann Thorac Surg 2009;88(1 Suppl):S2-22. 6.
Koch CG, Li L, Duncan AI et al. Morbidity and mortality risk associated with red blood cell and
blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34(6):16081616. 7.
Scott BH, Seifert FC, Grimson R. Blood transfusion is associated with increased resource
utilisation, morbidity and mortality in cardiac surgery. Ann Card Anaesth 2008;11(1):15-19. 8.
Vamvakas EC, Blajchman MA. Transfusion-related mortality: The ongoing risks of allogeneic
blood transfusion and the available strategies for their prevention. Blood 2009;113(15):3406-3417. 9.
Popovsky MA. Pulmonary consequences of transfusion: Trali and taco. Transfus Apher Sci
2006;34(3):243-244. 10.
Sihler KC, Napolitano LM. Complications of massive transfusion. Chest 2010;137(1):209-220.
11.
Vivacqua A, Koch CG, Yousuf AM et al. Morbidity of bleeding after cardiac surgery: Is it blood
transfusion, reoperation for bleeding, or both? Ann Thorac Surg 2011;91(6):1780-1790.
12.
Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a
risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg 1996;111(5):10371046. 13.
Dacey LJ, Munoz JJ, Baribeau YR et al. Reexploration for hemorrhage following coronary artery
bypass grafting: Incidence and risk factors. Northern New England cardiovascular disease study group. Arch Surg 1998;133(4):442-447. 14.
Toy P, Gajic O, Bacchetti P et al. Transfusion-related acute lung injury: Incidence and risk
factors. Blood 2012;119(7):1757-1767. 15.
Leal-Noval SR, Rincon-Ferrari MD, Garcia-Curiel A et al. Transfusion of blood components and
postoperative infection in patients undergoing cardiac surgery. Chest 2001;119(5):1461-1468. 16.
Dyke C, Aronson S, Dietrich W et al. Universal definition of perioperative bleeding in adult
cardiac surgery. J Thorac Cardiovasc Surg 2014;147(5):1458-1463 e1451. 17.
Vuylsteke A, Pagel C, Gerrard C et al. The papworth bleeding risk score: A stratification scheme
for identifying cardiac surgery patients at risk of excessive early postoperative bleeding. Eur J Cardiothorac Surg 2011;39(6):924-930. 18.
Ranucci M, Baryshnikova E, Castelvecchio S, Pelissero G, Surgical, Clinical Outcome Research
G. Major bleeding, transfusions, and anemia: The deadly triad of cardiac surgery. Ann Thorac Surg 2013;96(2):478-485. 19.
Mehran R, Rao SV, Bhatt DL et al. Standardized bleeding definitions for cardiovascular clinical
trials: A consensus report from the bleeding academic research consortium. Circulation 2011;123(23):2736-2747.
TABLE 1. Patient and surgical characteristics by reoperation for bleeding
No Reoperation for Bleeding (n = 22,722)
Reoperation for Bleeding (n = 518)
P value
Age (years)
66 (58–73)
68 (60–76)
<0.001
Female
6694 (30)
145 (28)
0.468
Caucasian
17016 (76)
386 (76)5
0.867
28.9 (25.5–33.2)
28.3 (24.9–31.6)
<0.001
Diabetes
9648 (43)
186 (36)
0.003
Dyslipidemia
18404 (81)
402 (78)
0.045
Hypertension
18919 (83)
439 (85)
0.399
Creatinine level (mg/dL)
1 (0.8–1.2)
1 (0.9–1.3)
<0.001
Liver disease
825 (4)
28 (5)
0.033
Dialysis
677 (3)
24 (5)
0.030
Chronic pulmonary disease
4210 (19)
95 (18)
0.896
Cerebrovascular disease
3784 (17)
97 (19)
0.207
Congestive heart failure
5962 (26)
168 (33)
0.001
Acute myocardial infarction
5175 (23)
104 (20)
0.159
1.2 (0.6–2.5)
1.8 (0.9–4.1)
<0.001
10211 (45)
229 (44)
0.739
Isolated CABG
15709 (69)
284 (55)
<0.001
Isolated AV
2847 (13)
83 (16)
0.018
Isolated MV
1883 (8)
57 (11)
0.027
Combination
2283 (10)
94 (18)
<0.001
Intraoperative blood units
0 (0–2)
1 (0–5)
<0.001
Postoperative length of stay (days)
6 (4–8)
8 (6-14)
<0.001
Body mass index (kg/m2)
STS predicted risk of mortality (%) Elective Surgery type
AV, aortic valve; CABG, coronary artery bypass graft; MV, mitral valve; STS, Society of Thoracic Surgeons
TABLE 2. Patient and surgical characteristics by four study groups Neither (n=22,365) 66 (58–73)
Reoperation Only (n=351) 67 (59–75)
Blood Only (n=350) 69 (61–77)
Both (n=167) 71 (64–77)
6596 (30)
93 (27)
98 (28)
52 (31)
16747 (76)
265 (76)
265 (76)
121 (74)
29 (26–33)
29 (26–32)
27 (24–31)
27 (24–30)
Diabetes *^
9526 (43)
128 (37)
121 (35)
58 (35)
Dyslipidemia
18129 (81)
272 (78)
270 (77)
130 (78)
18619 (83)
294 (84)
296 (85)
145 (87)
1.0 (0.8–1.2)
1.0 (0.9–1.3)
1.1 (0.9–1.5)
1.1 (0.9–1.3)
800 (4)
21 (6)
25 (7)
7 (4)
650 (3)
14 (4)
26 (7)
10 (6)
Chronic pulmonary disease
4137 (19)
62 (18)
71 (21)
33 (20)
Cerebrovascular disease
3712 (17)
63 (18)
72 (21)
34 (21)
5815 (26)
109 (31)
147 (43)
59 (36)
5097 (23)
66 (19)
78 (22)
38 (23)
1.2 (0.6–2.5)
1.6 (0.9–3.5)
2.8 (1.2–6.9)
2.3 (1.1–5.3)
10078 (45)
168 (48)
130 (37)
61 (37)
Isolated CABG *^+
15515 (69)
194 (55)
189 (54)
90 (54)
Isolated AV
2802 (13)
60 (17)
43 (12)
23 (14)
1848 (8)
35 (10)
35 (10)
22 (13)
2200 (10)
62 (18)
83 (24)
32 (19)
0 (0–2)
1 (0–4)
4 (1–8)
2 (0–6)
Age (years) *^+ Female Caucasian +
Body mass index (kg/m2) ^ +
Hypertension +
Creatinine level (mg/dL) *^ Liver disease *^ +
Dialysis ^
+
Congestive heart failure *^
Acute myocardial infarction +
STS predicted risk of mortality (%) *^ +
Elective ^
Surgery type
Isolated MV +
Combination *^
+
Intraoperative blood units *^
+
6 (4–8) 7 (6–12) 12 (7–24) Postoperative length of stay (days) *^ AV, aortic valve; CABG, coronary artery bypass graft; MV, mitral valve; STS, Society of Thoracic Surgeons Significant differences (P < 0.05): * Reoperation only vs. Neither, ^ Blood only vs. Neither, + Both vs. Neither
9 (7–22)
Figure Legends FIGURE 1: Percent of patients with reoperations for bleeding across the 10 centers in the state FIGURE 2: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 1 (neither reoperation or substantial transfusion) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 3: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 3 (substantial transfusion alone) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 4: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 2 (reoperation alone) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 5: Results of multivariable analyses for Group 3 (substantial transfusion alone) versus Group 2 (reoperation alone) presenting odds ratios and 95% confidence intervals for each outcome measure
S0003-4975(19)31895-8
DOI:
https://doi.org/10.1016/j.athoracsur.2019.10.076
Reference:
ATS 33322
To appear in:
The Annals of Thoracic Surgery
Received Date: 4 February 2019 Revised Date:
23 August 2019
Accepted Date: 1 October 2019
Please cite this article as: Pasrija C, Ghoreishi M, Whitman G, Ad N, Alejo DE, Holmes SD, Schena S, Salenger R, Mazzeffi MA, Fonner CE, Taylor B, on behalf of the Investigators for the Maryland Cardiac Surgery Quality Initiative, Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery, The Annals of Thoracic Surgery (2020), doi: https://doi.org/10.1016/j.athoracsur.2019.10.076. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
Mitigating the Risk: Transfusion or Reoperation for Bleeding After Cardiac Surgery Running Head: Transfusion or Reop for Bleeding
Chetan Pasrija, MD1, Mehrdad Ghoreishi, MD1, Glenn Whitman, MD2, Niv Ad, MD1, Diane E Alejo, BA2, Sari D. Holmes, PhD1, Stefano Schena, MD2, Rawn Salenger, MD1, Michael A Mazzeffi, MD4, Clifford E Fonner, BA3, Bradley Taylor, MD, MPH1; on behalf of the Investigators for the Maryland Cardiac Surgery Quality Initiative
1
University of Maryland School of Medicine, Division of Cardiac Surgery. Baltimore, MD
2
The Johns Hopkins Medical Institutions, Division of Cardiac Surgery. Baltimore, MD
3
Maryland Cardiac Surgery Quality Initiative. Baltimore, MD
4
University of Maryland School of Medicine, Department of Anesthesiology. Baltimore, MD Oral Presentation at the Society of Thoracic Surgeons 55th Annual Meeting
Word Count: 4329 Address for Correspondence: Chetan Pasrija, MD University of Maryland, Division of Cardiac Surgery 110 S Paca St, 7th Floor Baltimore, MD 21201 Email: [email protected]
Abstract Background: Several studies have established morbidity associated with bleeding after cardiac surgery. While reoperation has been implicated as the marker for this morbidity, there remains limited understanding regarding relative morbidities of reoperation and substantial transfusion. Methods. The Society of Thoracic Surgeons (STS) Maryland adult cardiac surgery database (7/20119/2018) was reviewed (N=23,240). Substantial transfusion was defined as requiring greater than the reoperation group median red blood cells (RBC; 5 units) and non-RBCs (4 units). Patients were stratified into 4 subgroups: Group 1, no reoperation without substantial transfusion (n=22,365); Group 2, reoperation without substantial transfusion (n=351); Group 3, no reoperation with substantial transfusion (n=350); and Group 4, reoperation with substantial transfusion (n=167). Operative morbidity and mortality were compared. Results. Reoperation patients were older with a higher STS predicted risk of mortality(1.8% vs. 1.2%, P<0.001). Multivariable analysis demonstrated that Group 4 (reoperation with substantial transfusion) increased the odds of renal failure (OR=7.36, P<0.001), stroke (OR=3.24, P=0.002), and operative mortality (OR=8.68, P<0.001) compared with Group 1 (neither reoperation or substantial transfusion). Both Group 2 (reoperation alone) and Group 3 (substantial transfusion alone) increased the odds of mortality and renal failure compared to Group 1. However, Group 3 had greater risk for renal failure (OR=3.48, P<0.001) and mortality (OR=2.91, P<0.001) than Group 2. Conclusions. While reoperation for bleeding is associated with morbidity after cardiac surgery, substantial transfusion without reoperation appears to increase morbidity compared to a limitedtransfusion reoperative approach. Better timing for reoperation and guided transfusion approaches may mitigate morbidity compared to substantial transfusion alone. Word Count: 250
Reoperation for bleeding is an uncommon but morbid event after cardiac surgery. Recent studies have demonstrated that it is necessary in 2 to 6% of patients, and is associated with 3 to 7-fold increase in operative mortality (1-4). Due to this substantial increase in mortality, the Society of Thoracic Surgeons (STS) has deemed surgical re-exploration to be a critical adult cardiac surgery performance measure, in line with stroke, deep sternal wound infection, postoperative renal failure, and prolonged intubation (5). In order to reduce the incidence of surgical re-exploration, bleeding after cardiac surgery may be treated medically with blood product transfusions, reserving reoperation for refractory cases. However, the morbidity of allogeneic blood product transfusions have been well-established, with an increased risk of transfusion-related acute lung injury, infection, and renal failure, among other morbidities (6-9). Since these appear to correlate with the quantity of products transfused, patients receiving a considerable amount of blood products for bleeding are at the highest risk of these complications (10). The impact of substantial transfusion for bleeding compared to an early, guided reoperative approach without substantial blood transfusion is currently poorly understood. We hypothesized that bleeding after cardiac surgery treated either medically with substantial blood transfusions alone, or surgically but after administration of considerable blood products, would increase morbidity and mortality compared to a guided reoperative approach prior to the administration of substantial blood products. Patients and Methods Study Population The STS statewide database for Maryland was reviewed between July 1, 2011 and September 30, 2018 for patients who underwent adult cardiac surgery including isolated coronary artery bypass grafting (CABG), isolated mitral valve repair/replacement, isolated aortic valve repair/replacement, or a combination of the above operations. Patients were included in the cohort for this study if their procedure was eligible for STS predicted risk scoring and data on reoperation for bleeding were available. There were 23,240 eligible patients, including 518 patients with reoperation for bleeding. Patients were then stratified into 4 groups based on reoperation for bleeding and substantial transfusion. The substantial transfusion cohort was defined based on the median amount of red blood cell (RBC) units and non-RBC
units transfused in the reoperation for bleeding group of patients. Consequently, greater than 5 units of RBC and greater than 4 units of non-RBC products transfused postoperatively was defined as substantial transfusion. The 4 study groups included: 1) patients without reoperation for bleeding and without substantial transfusion (Group 1; -Reop/-Blood); 2) patients with reoperation for bleeding without substantial transfusion (Group 2; +Reop/-Blood); 3) patients without reoperation for bleeding and with substantial transfusion (Group 3; -Reop/+Blood); 4) patients who required reoperation for bleeding and substantial transfusion (Group 4; +Reop/+Blood). Outcomes The primary outcome for this study was STS-defined 30-day mortality. Secondary outcome measures were also STS-defined and included: renal failure (3× increase in serum creatinine from baseline or rise in creatinine to >4 mg/dL with a minimum increase of 0.5 mg/dL, or new need for hemodialysis), stroke, short length of stay (LOS; discharged alive and within 5 days of surgery), prolonged LOS (>14 days), and readmission within 30 days. Statistical Analysis All analyses were conducted with SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY) and the alpha level was set at P < 0.05, two-tailed. Continuous variables are presented as median (interquartile range [IQR]) and categorical variables are presented as frequency (percent). Some variables had missing values and in those cases percentages are presented out of the total valid sample size. Patient and surgical characteristics were compared between the 4 study groups using the Kruskal-Wallis test with Bonferroni correction for continuous variables and Chi-square tests for categorical variables. Group contrast comparisons for categorical variables with significant overall group differences were conducted using univariate logistic regression analyses with Group 1 as the reference. Multivariable logistic regression was conducted to examine the impact of the 4 study groups on STS-defined outcome measures after adjustment for age, gender, race, outcome-specific STS predicted risk score, status (elective vs nonelective), preoperative hematocrit, type of procedure (isolated CABG, isolated AV, isolated MV,
combination procedure), length of surgery, and intraoperative units of blood. The STS risk score for morbidity/mortality was used for the analysis of readmission within 30 days since there is no specific STS predicted risk for readmission. Secondary analyses compared patients with early (≤24 hours) and late (>24 hours) timing of reoperation for bleeding on outcome measures using Chi-square or Fisher’s Exact tests. Results Overall Patient Characteristics In this sample, most patients did not require a reoperation for bleeding (n = 22,722; 98%). The incidence of reoperation for bleeding was 2% (n = 518). There was heterogeneity across hospitals in the state regarding incidence of reoperation for bleeding, but no center had an incidence greater than 3% (Figure 1). Those who required reoperation for bleeding were older, more likely to be dialysis-dependent, and have congestive heart failure. Moreover, these patients were less likely to have diabetes or dyslipidemia (Table 1). Patients who required reoperation for bleeding were more likely to have had a valve procedure, either isolated or in combination, and less likely to have undergone an isolated CABG (Table 1). For the 4 study group analyses, most patients were categorized into Group 1 (-Reop/-Blood, n = 22,365) with 351 patients in Group 2 (+Reop/-Blood), 350 patients in Group 3 (-Reop/+Blood), and 167 patients in Group 4 (+Reop/+Blood). There were 7 patients who were missing postoperative blood product transfusion data and could not be stratified into the 4 study groups, but none had a reoperation for bleeding. Preoperative patient and surgical characteristics were different between Group 1 and the other groups. Specifically, Group 1 was younger, less likely to be dialysis-dependent and in congestive heart failure, and more likely to have diabetes and elective status (Table 2). Group 1 was also more likely to have isolated CABG and less likely to have a combination surgical procedure than the other 3 groups. Median units of postoperative blood products transfused was 0 (0–1) in Group 1, which was significantly less than Group 2 (5 [2–8], P < 0.001), Group 3 (16 [12–23], P < 0.001), and Group 4 (20 [14–28], P < 0.001). Median postoperative RBC units was 0 (0–1) in Group 1, which was significantly less than Group 2 (3 [1–4], P < 0.001), Group 3 (7 [5–10], P < 0.001), and Group 4 (8 [6–12], P < 0.001). Median
postoperative non-RBC units was 0 (0–0) in Group 1, which was significantly less than Group 2 (2 [0–4], P < 0.001), Group 3 (8 [6–13], P < 0.001), and Group 4 (11 [6–16], P < 0.001). Differences in postoperative blood products transfused were also significantly different between Groups 2 and 3 (P < 0.001), as well as Groups 2 and 4 (P < 0.001). Impact of Both Reoperation and Transfusion The incidence of mortality within 30 days was 1.5% in Group 1 (n = 329), 6% in Group 2 (n = 21), 20% in Group 3 (n = 70), and 19% in Group 4 (n = 31). After multivariable adjustment, patients with reoperation for bleeding plus substantial transfusion (Group 4) had significantly greater risk for renal failure (OR = 7.36, P < 0.001), stroke (OR = 3.24, P = 0.002), prolonged LOS (OR = 6.08, P < 0.001), readmission within 30 days (OR = 1.65, P = 0.036), and mortality within 30 days (OR = 8.68, P < 0.001) compared with Group 1 (Figure 2). Group 4 also had reduced odds of short LOS (OR = 0.19, P < 0.001). There were no significant differences in outcomes between Group 3 and Group 4 (Figure 3) indicating that patients with substantial transfusion alone had similar outcomes to those with substantial transfusion who also underwent a reoperation for bleeding. Impact of Transfusion in Reoperation Patients Within all patients who required reoperation for bleeding, the impact of transfusion was examined by comparing those with (Group 4) and without substantial transfusion (Group 2). After multivariable adjustment, Group 4 had greater risk for renal failure (OR = 2.19, P = 0.026), prolonged LOS (OR = 2.41, P < 0.001), and mortality within 30 days (OR = 2.81, P = 0.002) compared with Group 2 (Figure 4). Transfusion Alone vs Reoperation Alone In multivariable analysis, the reoperation for bleeding alone (Group 2) and substantial transfusion alone (Group 3) groups had increased risk of mortality (Group 2: OR = 3.09, P < 0.001; Group 3: OR = 8.97, P < 0.001), renal failure (Group 2: OR = 3.37, P < 0.001; Group 3: OR = 11.71, P < 0.001), and prolonged LOS (Group 2: OR = 2.52, P < 0.001; Group 3: OR = 6.71, P < 0.001) compared with Group 1. Both Group 2 and Group 3 also had reduced odds for short LOS compared with Group 1 (Group 2: OR = 0.34, P < 0.001; Group 3: OR = 0.18, P < 0.001). However, when comparing the two groups, Group 3 was
found to have greater risk for renal failure (OR = 3.48, P < 0.001), prolonged LOS (OR = 2.66, P < 0.001), and mortality within 30 days (OR = 2.91, P < 0.001), as well as reduced odds for short LOS (OR = 0.53, P = 0.009; Figure 5) compared with Group 2. Optimal Reoperation Timing The timing of reoperation for bleeding was early (≤24 hours) in 86% of patients (n = 445) and these patients had lower incidence of renal failure (7% vs 21%, P < 0.001), prolonged LOS (18% vs 51%, P < 0.001), and mortality within 30 days (8% vs 22%, P < 0.001) and greater incidence of short LOS (21% vs 3%, P < 0.001) compared to late reoperation for bleeding. Comment This study provides further evidence that reoperation for bleeding after cardiac surgery is highly morbid. However, these data also suggest that medically treated bleeding, with extensive blood product transfusion and without reoperation, increases morbidity and mortality compared to a guided reoperative approach prior to the administration of numerous blood products. Late reoperation, greater than 24 hours after operation, appears to be particularly morbid, with a 14% increase in 30-day mortality. The impact of reoperation after cardiac surgery has been well-studied over the past two decades. Vivacqua et al. demonstrated that the risk of morbidity and mortality increases with the number of RBCs transfused, but reoperation for bleeding heightened the risk of morbidity and mortality for any number of transfused RBCs (11). In a large single center review, Ruel and colleagues found that the observed-toexpected mortality ratio increased from 0.7 in patients who were not re-explored, and 1.8 in those who were re-explored (2). This group also found that reoperation and intraoperative blood product transfusion independently contributed to perioperative mortality. The present study, similar to the above studies, also demonstrates that bleeding and reoperation after cardiac surgery are morbid. However, in previous analyses, direct comparisons of the morbidity associated with medically treated bleeding utilizing substantial blood transfusions, reoperation without substantial transfusion, and reoperation with substantial transfusion have been limited (12, 13). This study suggests that, among patients with
postoperative bleeding, an early, guided approach to reoperation may mitigate morbidity compared to an observational strategy associated with considerable blood transfusion. Given the morbidity and mortality associated with reoperation for bleeding, the STS has established surgical re-exploration as an important measure of hospital and surgeon quality (5). While these data support the notion that reoperation is a morbid event, this quality measure may dissuade surgeons from returning to the operating room early and expeditiously. Instead, surgeons may opt to transfuse this cohort of patients until the bleeding subsides, reserving reoperation for patients who continue to bleed despite significant transfusion. This study suggests that, within the cohort of bleeding patients after cardiac surgery, early, guided reoperation may, in fact, be the desired strategy to limit morbidity. On the other hand, substantial transfusion appears to be the more morbid treatment strategy. While future studies are needed to confirm and expand upon these findings, these data suggest that substantial transfusion after cardiac surgery should be added as a quality measure, in conjunction or potentially even in place of surgical re-exploration. While individual center thresholds vary, centers included in this study support the findings of this study: guided, early reoperation prior to the administration of numerous blood products may mitigate morbidity associated with bleeding after cardiac surgery. The etiology underlying the morbidity of substantial transfusions is likely multifactorial, including the impact of allogeneic blood product transfusion and hemodynamic effects of a large volume of clotted blood within the mediastinum. Several studies have established the negative impact of allogeneic blood product transfusion, and in particular, massive transfusion. Massive transfusion increases the odds of transfusion-related acute lung injury by 450%, with increased mechanical ventilation time and end-organ failure (14). Moreover, given that each RBC unit can contain approximately one million donor leukocytes, massive transfusion leads to immune dysfunction leading to infection and sepsis (15). Outside of the impact of blood product transfusion, large volume clotted blood within the mediastinum can have subtle hemodynamic effects leading to low cardiac output and high venous pressure, also resulting in endorgan dysfunction and ultimately, mortality. Still, this study is unable to evaluate mechanisms of
morbidity associated with transfusion compared to reoperation, and additional studies are needed to better understand these differences. Numerous definitions have been proposed for significant transfusion associated with bleeding after cardiac surgery, ranging from any transfusion of a non-RBC blood product to greater than 10 RBC and 10 non-RBC transfusions for massive bleeding (16-18). In an effort to standardize definitions for bleeding, the Bleeding Academic Research Consortium (BARC) established evidence-based bleeding classifications (19). CABG-related bleeding was considered any perioperative intracranial hemorrhage, reoperation, transfusion greater than 5 units within 48 hours, or chest tube output greater than 2L within 24 hours. However, given the limitations of this retrospective database analysis, we were unable to quantify chest tube output or define transfusion within pre-specified time periods. We, therefore, utilized the median number of RBCs and non-RBC blood products within the cohort of patients who were reexplored as the threshold for substantial transfusion. This definition has potential limitations for generalizability. For instance, there may be bleeding patients after cardiac surgery who were not included in the substantial transfusion cohort but still benefit from an early reoperation. Still, we controlled for known factors associated with blood transfusion, such as preoperative hemoglobin, and excluded patients at high risk for needing substantial blood transfusions outside of acute postoperative bleeding, such as those on mechanical circulatory support. Prospective studies are needed to evaluate exact bleeding cutoffs, where the morbidity of continued transfusion is greater than that of surgical re-exploration. At several of our institutions, patients at high-risk for considerable bleeding are monitored in the operating room after skin closure for 30 to 60 minutes. While thresholds to re-explore vary, this strategy allows for early re-exploration prior to the administration of a substantial amount of blood products. Limitations This study is a retrospective cohort analysis with the associated limitations. While we performed a multivariable analysis to control for differences in patients, those who required a reoperation or numerous blood transfusions may have unaccounted morbidities that contributed to their bad outcome. There may also be residual confounding between the specific groups, as patients within Group 3 may have had
unaccounted reasons for not undergoing a reoperation. Given the limitations of a database analysis, we are unable to evaluate granular data such as chest tube output prior to reoperation. While this study suggests that reoperation and/or substantial transfusion after cardiac surgery increases morbidity and mortality, we are unable to definitively establish a causal relationship between reoperation, transfusion, and morbidity. Importantly, bleeding after cardiac surgery is a multifactorial problem, with several contributing factors. This study suggests that timing of reoperation and the administration of numerous blood transfusions are morbid, but given its retrospective nature, does not account for intrinsic patient coagulopathy, hemostasis management techniques, or use of anti-fibrinolytics. Future, prospective studies are needed to establish a protocol-driven, guided reoperative approach, where morbidity is minimized by surgical re-exploration or limited blood transfusion, when appropriate. A standardized protocol for assessment and treatment of bleeding will be necessary to account for surgical-team and patient differences. Conclusion While reoperation for bleeding is associated with morbidity after cardiac surgery, substantial transfusion without reoperation appears to increase morbidity compared to a limited-transfusion reoperative approach. Early, guided reoperation approaches may mitigate the adverse impact and thus, morbidity, of substantial transfusion. Studies standardizing timing and indications for reoperation are needed to optimize outcomes for patients with postoperative bleeding.
References 1.
Ranucci M, Bozzetti G, Ditta A, Cotza M, Carboni G, Ballotta A. Surgical reexploration after
cardiac operations: Why a worse outcome? Ann Thorac Surg 2008;86(5):1557-1562. 2.
Ruel M, Chan V, Boodhwani M et al. How detrimental is reexploration for bleeding after cardiac
surgery? J Thorac Cardiovasc Surg 2017;154(3):927-935. 3.
Mehta RH, Sheng S, O'Brien SM et al. Reoperation for bleeding in patients undergoing coronary
artery bypass surgery: Incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes 2009;2(6):583-590. 4.
Karthik S, Grayson AD, McCarron EE, Pullan DM, Desmond MJ. Reexploration for bleeding
after coronary artery bypass surgery: Risk factors, outcomes, and the effect of time delay. Ann Thorac Surg 2004;78(2):527-534; discussion 534. 5.
Shahian DM, O'Brien SM, Filardo G et al. The Society of Thoracic Surgeons 2008 cardiac
surgery risk models: Part 1--coronary artery bypass grafting surgery. Ann Thorac Surg 2009;88(1 Suppl):S2-22. 6.
Koch CG, Li L, Duncan AI et al. Morbidity and mortality risk associated with red blood cell and
blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34(6):16081616. 7.
Scott BH, Seifert FC, Grimson R. Blood transfusion is associated with increased resource
utilisation, morbidity and mortality in cardiac surgery. Ann Card Anaesth 2008;11(1):15-19. 8.
Vamvakas EC, Blajchman MA. Transfusion-related mortality: The ongoing risks of allogeneic
blood transfusion and the available strategies for their prevention. Blood 2009;113(15):3406-3417. 9.
Popovsky MA. Pulmonary consequences of transfusion: Trali and taco. Transfus Apher Sci
2006;34(3):243-244. 10.
Sihler KC, Napolitano LM. Complications of massive transfusion. Chest 2010;137(1):209-220.
11.
Vivacqua A, Koch CG, Yousuf AM et al. Morbidity of bleeding after cardiac surgery: Is it blood
transfusion, reoperation for bleeding, or both? Ann Thorac Surg 2011;91(6):1780-1790.
12.
Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a
risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg 1996;111(5):10371046. 13.
Dacey LJ, Munoz JJ, Baribeau YR et al. Reexploration for hemorrhage following coronary artery
bypass grafting: Incidence and risk factors. Northern New England cardiovascular disease study group. Arch Surg 1998;133(4):442-447. 14.
Toy P, Gajic O, Bacchetti P et al. Transfusion-related acute lung injury: Incidence and risk
factors. Blood 2012;119(7):1757-1767. 15.
Leal-Noval SR, Rincon-Ferrari MD, Garcia-Curiel A et al. Transfusion of blood components and
postoperative infection in patients undergoing cardiac surgery. Chest 2001;119(5):1461-1468. 16.
Dyke C, Aronson S, Dietrich W et al. Universal definition of perioperative bleeding in adult
cardiac surgery. J Thorac Cardiovasc Surg 2014;147(5):1458-1463 e1451. 17.
Vuylsteke A, Pagel C, Gerrard C et al. The papworth bleeding risk score: A stratification scheme
for identifying cardiac surgery patients at risk of excessive early postoperative bleeding. Eur J Cardiothorac Surg 2011;39(6):924-930. 18.
Ranucci M, Baryshnikova E, Castelvecchio S, Pelissero G, Surgical, Clinical Outcome Research
G. Major bleeding, transfusions, and anemia: The deadly triad of cardiac surgery. Ann Thorac Surg 2013;96(2):478-485. 19.
Mehran R, Rao SV, Bhatt DL et al. Standardized bleeding definitions for cardiovascular clinical
trials: A consensus report from the bleeding academic research consortium. Circulation 2011;123(23):2736-2747.
TABLE 1. Patient and surgical characteristics by reoperation for bleeding
No Reoperation for Bleeding (n = 22,722)
Reoperation for Bleeding (n = 518)
P value
Age (years)
66 (58–73)
68 (60–76)
<0.001
Female
6694 (30)
145 (28)
0.468
Caucasian
17016 (76)
386 (76)5
0.867
28.9 (25.5–33.2)
28.3 (24.9–31.6)
<0.001
Diabetes
9648 (43)
186 (36)
0.003
Dyslipidemia
18404 (81)
402 (78)
0.045
Hypertension
18919 (83)
439 (85)
0.399
Creatinine level (mg/dL)
1 (0.8–1.2)
1 (0.9–1.3)
<0.001
Liver disease
825 (4)
28 (5)
0.033
Dialysis
677 (3)
24 (5)
0.030
Chronic pulmonary disease
4210 (19)
95 (18)
0.896
Cerebrovascular disease
3784 (17)
97 (19)
0.207
Congestive heart failure
5962 (26)
168 (33)
0.001
Acute myocardial infarction
5175 (23)
104 (20)
0.159
1.2 (0.6–2.5)
1.8 (0.9–4.1)
<0.001
10211 (45)
229 (44)
0.739
Isolated CABG
15709 (69)
284 (55)
<0.001
Isolated AV
2847 (13)
83 (16)
0.018
Isolated MV
1883 (8)
57 (11)
0.027
Combination
2283 (10)
94 (18)
<0.001
Intraoperative blood units
0 (0–2)
1 (0–5)
<0.001
Postoperative length of stay (days)
6 (4–8)
8 (6-14)
<0.001
Body mass index (kg/m2)
STS predicted risk of mortality (%) Elective Surgery type
AV, aortic valve; CABG, coronary artery bypass graft; MV, mitral valve; STS, Society of Thoracic Surgeons
TABLE 2. Patient and surgical characteristics by four study groups Neither (n=22,365) 66 (58–73)
Reoperation Only (n=351) 67 (59–75)
Blood Only (n=350) 69 (61–77)
Both (n=167) 71 (64–77)
6596 (30)
93 (27)
98 (28)
52 (31)
16747 (76)
265 (76)
265 (76)
121 (74)
29 (26–33)
29 (26–32)
27 (24–31)
27 (24–30)
Diabetes *^
9526 (43)
128 (37)
121 (35)
58 (35)
Dyslipidemia
18129 (81)
272 (78)
270 (77)
130 (78)
18619 (83)
294 (84)
296 (85)
145 (87)
1.0 (0.8–1.2)
1.0 (0.9–1.3)
1.1 (0.9–1.5)
1.1 (0.9–1.3)
800 (4)
21 (6)
25 (7)
7 (4)
650 (3)
14 (4)
26 (7)
10 (6)
Chronic pulmonary disease
4137 (19)
62 (18)
71 (21)
33 (20)
Cerebrovascular disease
3712 (17)
63 (18)
72 (21)
34 (21)
5815 (26)
109 (31)
147 (43)
59 (36)
5097 (23)
66 (19)
78 (22)
38 (23)
1.2 (0.6–2.5)
1.6 (0.9–3.5)
2.8 (1.2–6.9)
2.3 (1.1–5.3)
10078 (45)
168 (48)
130 (37)
61 (37)
Isolated CABG *^+
15515 (69)
194 (55)
189 (54)
90 (54)
Isolated AV
2802 (13)
60 (17)
43 (12)
23 (14)
1848 (8)
35 (10)
35 (10)
22 (13)
2200 (10)
62 (18)
83 (24)
32 (19)
0 (0–2)
1 (0–4)
4 (1–8)
2 (0–6)
Age (years) *^+ Female Caucasian +
Body mass index (kg/m2) ^ +
Hypertension +
Creatinine level (mg/dL) *^ Liver disease *^ +
Dialysis ^
+
Congestive heart failure *^
Acute myocardial infarction +
STS predicted risk of mortality (%) *^ +
Elective ^
Surgery type
Isolated MV +
Combination *^
+
Intraoperative blood units *^
+
6 (4–8) 7 (6–12) 12 (7–24) Postoperative length of stay (days) *^ AV, aortic valve; CABG, coronary artery bypass graft; MV, mitral valve; STS, Society of Thoracic Surgeons Significant differences (P < 0.05): * Reoperation only vs. Neither, ^ Blood only vs. Neither, + Both vs. Neither
9 (7–22)
Figure Legends FIGURE 1: Percent of patients with reoperations for bleeding across the 10 centers in the state FIGURE 2: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 1 (neither reoperation or substantial transfusion) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 3: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 3 (substantial transfusion alone) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 4: Results of multivariable analyses for Group 4 (reoperation with substantial transfusion) versus Group 2 (reoperation alone) presenting odds ratios and 95% confidence intervals for each outcome measure FIGURE 5: Results of multivariable analyses for Group 3 (substantial transfusion alone) versus Group 2 (reoperation alone) presenting odds ratios and 95% confidence intervals for each outcome measure