Download Reoperation for Bleeding in Patients Undergoing Coronary Artery

Reoperation for Bleeding in Patients Undergoing Coronary
Artery Bypass Surgery
Incidence, Risk Factors, Time Trends, and Outcomes
Rajendra H. Mehta, MD, MS; Shubin Sheng, MS; Sean M. O’Brien, PhD; Frederick L. Grover, MD;
James S. Gammie, MD; T. Bruce Ferguson, MD; Eric D. Peterson, MD, MPH; on behalf of the
Society of Thoracic Surgeons National Cardiac Surgery Database Investigators
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Background—Reoperation for bleeding represents an important complication in patients undergoing coronary artery
bypass surgery (CABG). Yet, few studies have characterized risk factors and patient outcomes of this event.
Methods and Results—We evaluated 528 686 CABG patients at ⬎800 hospitals in the Society of Thoracic Surgeons
National Cardiac Database (2004 to 2007). Clinical features and in-hospital outcomes were evaluated in patients with
and without reoperation for bleeding after CABG. Logistic regression was used to identify predictors of risk of this event
and to estimate weights for an additive risk score. A total of 12 652 CABG patients (2.4%) required reoperation for
bleeding. These rates remained fairly stable over time (2.2%, 2.3%, 2.5%, and 2.4% from 2004 to 2007, respectively).
Although overall operative mortality was 4.5-fold higher in patients requiring reoperation for bleeding versus those who
did not (2.0% versus 9.1%), this mortality risk declined significantly over time (11.3%, 9.5%, 8.8%, and 8.2% from 2004
to 2007, respectively, P for trend⫽0.0006). Factors associated with higher risk for reoperation were identified by
multivariable analysis (c statistic⫽0.60) and summarized into a simple bedside risk score. The risk-score performed well
when tested in the validation set (Hosmer-Lemeshow P⫽0.16).
Conclusions—Reoperation for bleeding remains an important morbid event after CABG. Nonetheless, death in patients
with this complication has decreased over time. Our risk tool should allow estimation of patients risk for reoperation
for bleeding and promote preventive measures when feasible in this at-risk group. (Circ Cardiovasc Qual Outcomes.
2009;2:583-590.)
Key Words: bypass 䡲 coronary disease 䡲 bleeding 䡲 outcomes 䡲 reoperation
R
eoperation for bleeding is required in 2.3% to 8%
patients undergoing coronary artery bypass graft
(CABG) surgery.1–9 Prior studies have characterized the
morbidity and mortality and risk factors associated with the
need for reoperation for bleeding after CABG.1– 4,7–9 However, this information tends to be derived single tertiary
center reports1–3,5,7–9 or from selected regional consortium.4,6
Additionally, these studies also preceded the use of more
potent antithrombotic therapies such as clopidogrel and glycoprotein IIb/IIIa inhibitors that have been shown to increase
reoperation for bleeding in patients undergoing CABG.10 –12
Thus, the incidence, risk factors, and outcomes of patients
requiring reoperation after CABG in contemporary community practice at large in recent era are not known.
Using the data from the Society of Thoracic Surgeons
National Cardiac Surgery Database (STS NCD),13–15 we
sought to (1) characterize the clinical features and in-hospital
outcomes of patients undergoing CABG requiring reoperation for bleeding; (2) identify trends in reoperations and
mortality in patients with this event; (3) explore the underlying plausible mechanisms for these trends; (4) identify
preoperative clinical variables associated with the risk of this
event; and (5) create a bedside tool to estimate the risk of this
event.
Methods
STS NCD
The formation, rationale, and methodology of the STS NCD have
been previously published.13–15 Briefly, this registry was initiated in
1986 with a goal to provide participants with their risk-adjusted
outcomes compared to the national experience. This information is
used by member institutions as a part of their continuous quality
improvement efforts to help design strategies to improve their
outcomes.
Patient Population
We analyzed data on patients aged ⱖ20 and ⱕ99 years undergoing
isolated CABG from January 1, 2004, through December 31, 2007,
at participating sites. Patients undergoing isolated or concomitant
Received February 16, 2009; accepted July 29, 2009.
From the Duke Clinical Research Institute (R.H.M., S.S., S.M.O., E.D.P.), Durham, NC; University of Colorado Health Sciences Center (F.L.G.),
Denver, Colo; University of Maryland Medical Center (J.S.G.), Baltimore, Md; and East Carolina University (T.B.F.), Greenville, NC.
Correspondence to Rajendra H. Mehta, MD, Box 17969, Duke Clinical Research Institute, Durham, NC 27715. E-mail [email protected]
© 2009 American Heart Association, Inc.
Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org
583
DOI: 10.1161/CIRCOUTCOMES.109.858811
584
Circ Cardiovasc Qual Outcomes
November 2009
valve, congenital heart, or aortic surgery were excluded from the
analysis. We also excluded patients if they had missing information
on few key variables (ie, age, gender, status of surgery, surgery date,
and hospital number).
Bedside Tool
Summary statistics are presented as frequency and percentage, or as
median and interquartile range. ␹2 test was used for comparing
categorical variables and Wilcoxon rank sum test for continuous
variables, both tests were stratum adjusted by participant ID. The
Cochran-Mantel-Haenszel test was used for the analysis of trends.
In addition, we created a bedside tool which allows a crude estimate
of risk of reoperation for bleeding to be calculated using simple
addition based on a minimal number of explanatory variables. To
choose variables for the bedside tool, we identified the smallest
subset of predictors that were able to capture at least 90% of
variation in the predicted log-odds of reoperation as estimated by the
logistic predictive model described above. Regression coefficients
were then converted to whole integers by multiplying the coefficients
by a factor of 10 and rounding to the nearest integer to create a
bedside risk prediction tool. For each possible risk score, the risk of
reoperation for bleeding was estimated by averaging the predicted
values from the logistic predictive model among all patients having
the same risk score. Validation of risk score tool was performed by
comparing observed mortality in the validation set versus expected
mortality among risk score categories. The heterogeneity of the risk
of this event among patients having the same risk score was assessed
by plotting the distribution of predicted risk based on the full model
within risk score subgroups. Calibration of model was assessed by
Hosmer-Lemeshow test statistic.
Time Trends in Bleeding Risk
Missing Data
Time trends in risk-adjusted bleeding rates were assessed using a
nonparsimonious multivariable logistic regression model with adjustment for 26 patient preoperative characteristics. Variables for this
model were selected based on the previously published STS mortality model as well as clinical experience of factors and treatments
known to be associated with increased risk of this event.14 These
variables included age; gender; race; body surface area; hypertension; diabetes; immunosuppressive therapy; peripheral vascular disease; chronic lung disease; cerebrovascular disease; atrial fibrillation; baseline myocardial infarction, unstable angina, creatinine,
heart failure, shock, dialysis, and left ventricular ejection fraction;
left main disease; number of coronary artery disease; number of prior
cardiac operations; percutaneous coronary interventions ⬍6 hours of
CABG; intraaortic balloon pump; status of surgery; year of operation
and use of oral antiplatelet agents and intravenous glycoprotein
IIb/IIIa receptor antagonists ⬍24 hours of surgery. To account for
clustering of outcomes within hospitals, the model was fitted using
generalized estimating equation methodology with an exchangeable
working correlation structure and empirical sandwich standard error
estimates.
Records with missing values of gender (0.01%), hospital number
(0.002%), and operative status (0.07%) were excluded from all data
presented here. Among the variables that were used for multivariable
analysis, missing data were highest for ejection fraction (4.5%).
Information for the remaining variables in the multivariable analyses
was missing in ⬍1%. Missing values of body surface area (0.49%)
were imputed to gender-specific median values. Ejection fraction
was imputed to the conditional median after stratifying by gender,
status, and heart failure. Missing values of categorical risk factors
were defaulted to their most common value which in most cases was
“not present.” All analyses were performed using SAS 9.1 (SAS
Institute) software.
Data Definitions
The STS NCD collects information on reoperation for bleeding as
repeat surgery needed for bleeding or cardiac tamponade either
before hospital discharge or between hospital discharge and within
30 days of their index operation if discharged earlier than 30 days.
Information on all other adverse events was ascertained as inhospital events. Detailed definitions of risk factors and adverse
events were as provided on the STS web site (www.sts.org).
Statistical Analysis
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Risk-Adjusted Mortality
Mortality rates for patients needing reoperation were adjusted to
account for risk factors present at the time of the initial operation. A
nonparsimonious logistic regression model was developed for this
purpose that included all factors listed above for the reoperation
model with the exception of year of surgery and the use of oral
antiplatelet agents and intravenous glycoprotein IIb/IIIa receptor
antagonists ⬍24 hours of surgery. We treated operative mortality as
the dependent (outcome) variable. Indirectly standardized mortality
rates were then calculated as the observed number of deaths divided
by the model-predicted number of deaths multiplied by the overall
mortality rate in the study sample.
Development of Predictive Models
We also developed a parsimonious logistic regression model that can
be used to predict an individual patient’s risk of reoperation for
bleeding using a small number of predictor variables. Parsimony was
felt to be desirable to reduce the data collection burden for users of
the model and to facilitate ease-of-use at the patient’s bedside. We
used 80% of the sample for the development of the model and the
remaining 20% of the sample for model validation. To enhance
usability, continuous variables were assumed to have a linear
relationship (age [in 5-year increments], body mass index) or
categorized (serum creatinine, left ventricular ejection fraction).
Nonsignificant variables were eliminated using a backwards
selection algorithm with a P⫽0.05 stopping rule.
Results
Baseline Clinical Characteristics of Patients
Undergoing CABG Needing Reoperation
for Bleeding
Repeat surgery for bleeding was required in 12 652 (2.39%)
of 528 686 patients undergoing CABG. Patients needing
reoperation for bleeding were significantly older, males,
nonwhites with lower body mass index with higher comorbid
conditions (Table 1). Similarly, preoperative features portending adverse prognosis (ie, myocardial infarction ⱕ24
hours of surgery, congestive heart failure, cardiogenic shock,
lower creatinine clearance) were also significantly higher in
this cohort. The use of potent antiplatelet agent (ie, thienopyridine or glycoprotein IIb/IIIa agent) within 24 hours before
the operation was significantly higher in patients needing
reoperation for bleeding. More patients who underwent emergent or emergent salvage surgery required reoperation for
bleeding. Cardiopulmonary bypass use and the median pump
and cross-clamp times were marginally higher among patients requiring reoperation for bleeding, whereas internal
mammary artery bypass conduit use was less frequent among
these patients. There was modest direct relationship between
perfusion time and the rates of reoperation for bleeding
(r⫽0.69). Reoperation for bleeding was required in 2.07% of
patients undergoing off-pump CABG and in 2.47% of patients undergoing on-pump CABG (adjusted rates 2.06%
versus 2.46%, P⬍0.0001). In patients who did receive clopidogrel before surgery, reoperation for bleeding was lower in
Mehta et al
Table 1.
Reoperation for Bleeding After CABG
585
Patient Characteristics
Characteristics
Overall
No Reoperation for Bleeding
Reoperation for Bleeding
Sample size
528 686
516 034
12 652
P Value
Demographics
Age, median (IQR), y
65 (57–73)
65 (57–73)
68 (59–76)
Females, n (%)
143 303 (27.1)
140 136 (27.2)
3167 (25.0)
Whites, n (%)
450 862 (85.3)
440 331 (85.3)
10 531 (83.2)
BMI, median (IQR), kg/m2
28.6 (26–33)
28.6 (26–33)
27.4 (25–31)
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
Medical history
Hypertension, n (%)
429 184 (81.2)
418 861 (81.2)
10 323 (81.6)
0.4412
Diabetes mellitus, n (%)
198 771 (37.6)
194 448 (37.7)
4323 (34.2)
⬍0.0001
Current smoker, n (%)
129 829 (24.6)
126 915 (24.6)
2914 (23.0)
⬍0.0001
Hypercholesterolemia, n (%)
414 403 (78.4)
404 713 (78.4)
9690 (76.6)
⬍0.0001
Chronic lung disease, n (%)
112 561 (21.3)
109 622 (21.2)
2939 (23.2)
⬍0.0001
30 089 (5.7)
29 044 (5.6)
1045 (8.3)
⬍0.0001
Preoperative renal failure, n (%)
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Preoperative dialysis, n (%)
1.8
1.7
2.5
⬍0.0001
Stroke, n (%)
37 642 (7.1)
36 550 (7.1)
1092 (8.6)
⬍0.0001
Immunosuppressive treatment, n (%)
10 517 (2.0)
10 147 (2.0)
370 (2.9)
⬍0.0001
Peripheral vascular disease, n (%)
80 511 (15.2)
78 266 (15.2)
2245 (17.7)
⬍0.0001
Cerebrovascular disease, n (%)
72 497 (13.7)
70 376 (13.6)
2121 (16.8)
⬍0.0001
Prior CABG, n, (%)
21 704 (4.1)
21 001 (4.1)
703 (5.6)
⬍0.0001
114 664 (21.7)
111 653 (21.6)
3011 (23.8)
⬍0.0001
126 705 (24.0)
123 287 (23.9)
3418 (27.0)
⬍0.0001
Prior PCI, n (%)
Preoperative cardiac status and angiographic
findings
MI within 7 days
Cardiogenic shock
2.0
1.9
4.2
⬍0.0001
PCI ⬍6 h of CABG
1.0
1.0
1.9
⬍0.0001
⬍0.0001
CHF
13.3
13.2
16.7
Serum creatinine, median (IQR), mg/dl
528 686 (1.0 关0.9–1.2兴)
516 034 (1.0 关0.9–1.2兴)
12 652 (1.1 关0.9–1.3兴)
⬍0.0001
Glomerular filtration rate, ml/min/1.73m2
523 146 (73.1 关59–88兴)
510 648 (73.1 关59–88兴)
12 528 (69.7 关55–86兴)
⬍0.0001
Mitral regurgitation (moderate or severe), n (%)
Aortic stenosis, n (%)
14 750 (2.8)
14 214 (2.8)
536 (4.2)
⬍0.0001
8494 (1.6)
8218 (1.6)
276 (2.2)
⬍0.0001
⬍0.0001
Left main disease ⬎50%, n (%)
162 299 (30.7)
158 142 (30.7)
4157 (32.9)
Coronary artery disease ⱖ2 vessels, n (%)
526 601 (99.6)
513 990 (99.6)
12 611 (99.7)
528 686 (50 关45–50兴)
516 034 (50 关45–50兴)
401 113 (75.9)
391 243 (75.8)
LVEF, median (IQR), %
512 652 (0 关40–50兴)
0.1532
⬍0.0001
Preoperative medications
Aspirin, n (%)
9870 (78.0)
Both, n (%)
6390 (1.2)
6071 (1.2)
Only glycoprotein IIb/IIIa antagonists, n (%)
22 017 (4.2)
21 429 (4.2)
588 (4.7)
Only thienopyridines, n (%)
48 787 (9.2)
47 128 (9.1)
1659 (13.1)
451 492 (85.4)
441 406 (85.5)
Neither, n (%)
Coumadin, n (%)
Any intravenous anticoagulant, n (%)
⬍0.0001
⬍0.0001
Thienopyridines and/or glycoprotein IIb/IIIa
antagonists, n (%)
319 (2.5)
10 086 (79.7)
2.4
⬍0.0001
185 868 (35.2)
180 972 (35.1)
4896 (38.7)
⬍0.0001
1177 (0.22)
1080 (0.21)
97 (0.77)
2.4
3.0
Operative details
⬍0.0001
Status of surgery
Emergent salvage, n (%)
Emergent, n (%)
24 586 (4.7)
23 560 (4.6)
1026 (8.1)
Urgent, n (%)
250 651 (47.4)
244 472 (47.4)
6172 (48.8)
Elective, n (%)
251 921 (47.7)
246 578 (47.8)
5343 (42.3)
423 677 (80.1)
413 196 (80.1)
10 481 (82.8)
Cardiopulmonary bypass, n (%)
Perfusion time, Median (IQR), min
Internal mammary artery graft, n (%)
420 672 (91 关71–116兴)
480 581 (90.9)
410 238 (91 关71–116兴)
469 641 (91.0)
10 434 (97 关74–125兴)
10 940 (86.5)
⬍0.0001
⬍0.0001
⬍0.0001
IABP indicates intraaortic balloon pump; IQR, interquartile range; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; MI, myocardial
infarction; and CHF, congestive heart failure.
586
Circ Cardiovasc Qual Outcomes
Table 2.
November 2009
Outcomes
Overall
No Reoperation
for Bleeding
Reoperation
for Bleeding
P Value
Operative mortality, n (%)
11 223 (2.1)
10 072 (2.0)
1151 (9.1)
⬍0.0001
Total mortality, n (%)
12 327 (2.3)
11 115 (2.2)
1212 (9.6)
⬍0.0001
6479 (1.2)
6148 (1.2)
331 (2.6)
⬍0.0001
Characteristics
Sample size, n (%)
Permanent stroke, n (%)
215 (1.7)
⬍0.0001
Prolonged ventilation, n (%)
53 465 (10.1)
48 106 (9.3)
5359 (42.4)
⬍0.0001
Pneumonia, n (%)
16 560 (3.1)
15 455 (3.0)
1105 (8.7)
⬍0.0001
Perioperative myocardial infarction, n (%)
6037 (1.1)
5822 (1.1)
966 (0.18)
287 (0.06)
679 (5.37)
⬍0.0001
Any blood product use, n (%)
312 819 (59.2)
300 634 (58.3)
12 185 (96.3)
⬍0.0001
Any RBC transfusion given, n (%)
285 496 (54.0)
273 705 (53.0)
11 791 (93.2)
⬍0.0001
Any platelet transfusion, n (%)
116 259 (22.0)
106 824 (20.7)
9435 (74.6)
⬍0.0001
Any fresh frozen plasma, n (%)
93 187 (17.6)
84 130 (16.3)
9057 (71.6)
⬍0.0001
Any cryoprecipitate, n (%)
21 117 (4.0)
17 292 (3.4)
3825 (30.2)
⬍0.0001
IABP use, n (%)
52 772 (10.0)
50 348 (9.8)
2424 (20.2)
⬍0.0001
Cardiac tamponade, n (%)
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Deep sternal wound infection, n (%)
1982 (0.4)
1768 (0.3)
214 (1.7)
⬍0.0001
Septicemia, n (%)
5227 (1.0)
4739 (0.9)
488 (3.8)
⬍0.0001
Postoperative length of stay, median (IQR), d
527 276 (5.0 关4–7兴)
514 661 (5.0 关4–7兴)
12 615 (7 关5–12兴)
⬍0.0001
RBC indicates red blood cell; IABP, intraaortic balloon pump; and IQR, interquartile range.
the off-pump CABG patients compared with those undergoing on-pump CABG (3.68% versus 3.23%, P⬍0.001).
In-Hospital Outcomes
Reoperation for bleeding after CABG was associated with
worse outcomes compared with those without this event
(Table 2). Those requiring reoperation were at higher risk for
permanent stroke (2.2-fold), pneumonia (2.9-fold), septicemia (4.3-fold), and the need for prolonged ventilation (ⱖ48
hours; 4.6-fold). Operative mortality was ⬎4.5-fold in patients needing reoperation for bleeding. Even after adjusting
for baseline confounders, mortality remained higher among
patients needing reoperation for bleeding compared with
those not requiring this (adjusted rates, 5.92% versus 1.97%,
P⬍0.0001).
Reoperation for bleeding was also fairly constant over this
period (2.21%, 2.34%, 2.49%, and 2.42% for years 2004
through 2007, respectively). This clinically insignificant
trend for increasing need for reoperation for bleeding over
time persisted even when adjusted for baseline confounders
(odds ratio, 1.04; 95% CI, 0.96 to 1.12 for 2005; odds ratio,
1.09; 95% CI, 1.00 to 1.18 for 2006; odds ratio, 1.07; 95% CI,
0.97 to 1.17 for 2004 [referent]).
Mortality over the study period improved in overall patients undergoing CABG, but particularly among those needing reoperation for bleeding (Figure 1).
Risk Prediction Model and Bedside Risk Tool
Factors independently associated with reoperation for bleeding in patients undergoing CABG are shown in Table 3 (c
Time Trends for Reoperation for Bleeding and
Outcomes in Patients Undergoing CABG From
2004 to 2007
There were some minor shifts in the risk profiles of patients
undergoing CABG overtime. For example, there was a
clinically insignificant small increase in preprocedural thienopyridines use (9.1%, 8.9%, 9.7%, and 9.2% for years 2004
to 2007, respectively, P for trend 0.0018) and a decline in
glycoprotein IIb/IIIa use over the study period (4.4%, 4.5%,
4.0%, and 3.9% for years 2004 to 2007 respectively, P for
trend ⬍0.0001). The rates of emergent salvage or emergent
operations; proportion of patients undergoing CABG ⬍24
hours of a myocardial infarction and rates of off-pump CABG
remained stable over the study period. Overall, the risk
profile of patients receiving CABG remained stable over the
4-year study period (predicted mortality risk 2.1%, 2.2%,
2.1%, and 2.1%, for 2004 to 2007; respectively).
Figure 1. Trends in operative mortality in patients undergoing
CABG over time (2004 to 2007). Overall CABG indicates in overall patients undergoing CABG; ReOP, in patients needing reoperation for bleeding; Un-Adj, unadjusted; and Adj, adjusted.
Mehta et al
Table 3. Parsimonious Logistic Regression Model Showing
Preoperative Factors Associated With the Need for Reoperation
for Bleeding After CABG
Variable
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Odds Ratio
95% CI
Age ⱖ60 y
1.02
(1.02–1.02)
Body surface area
0.39
(0.33–0.45)
Body surface area squared
1.98
(1.53–2.57)
Nonwhite
1.16
(1.08–1.24)
Urgent surgery
1.09
(1.04–1.15)
Emergent surgery
1.50
(1.34–1.67)
Emergent salvage surgery
2.08
(1.68–2.58)
Preoperative serum creatinine–continuous
variable
1.50
(1.34–1.67)
Male
1.39
(1.32–1.47)
Preoperative dialysis
2.15
(1.78–2.60)
Thienopyridines ⬍24 h of CABG
1.46
(1.37–1.56)
Thienopyridine and glycoprotein IIb/IIIa
receptor antagonists ⬍24 h of CABG
1.89
(1.66–2.16)
Intraaortic balloon pump or inotropic support
1.25
(1.16–1.35)
Nondiabetics
1.16
(1.11–1.21)
3 vessel coronary artery disease
1.12
(1.07–1.18)
Previous cardiovascular interventions
1.35
(1.24–1.46)
Cerebrovascular disease
1.12
(1.06–1.19)
Immunosuppressive therapy
1.36
(1.21–1.53)
Cardiogenic shock
1.23
(1.09–1.39)
Congestive heart failure
1.09
(1.03–1.15)
Chronic lung disease-moderate to severe
1.11
(1.03–1.19)
Peripheral vascular disease
1.07
(1.01–1.14)
PCI ⬍6 hours of CABG
1.20
(1.01–1.42)
c index
0.60
PCI indicates percutaneous coronary intervention.
index, 0.60). The Hosmer-Lemeshow probability value of the
full model was 0.19 providing little evidence of poor fit and
suggesting high concordance between predicted and observed
values. The simplified model coefficients were converted to
an additive risk score (Figure 2). Figure 3 displays a comparison between predicted risk of reoperation for bleeding
based on bedside risk tool and observed rates in the risk score
categories in the validation set. The risk score tool performed
well in the validation set with good concordance between
predicted values in the risk categories and the observed risk in
this sample (Hosmer-Lemeshow P⫽0.16). Figure 4 displays
the variability between the estimate of risk based on the full
model and the estimated risk determined by the bedside risk
tool in various risk score categories in the derivation data-set.
The average absolute difference between the risks calculated
by full model compared with estimates based on the risk
scores was 0.30%. Overall there was good correlation between the estimation of risk with risk score and that estimated
based on the full model (correlation coefficient 0.95).
Discussion
Findings of Current Investigation
Our study provides a national perspective on the need for
reoperation for bleeding after CABG in recent contemporary
Reoperation for Bleeding After CABG
587
practice when ubiquitous use of potent antithrombotic agents
is a norm. Our data found that the incidence of this event is
low (2.4%) and remained fairly constant overtime. Nonetheless, reoperation for bleeding remained strongly associated
with greater morbidity and mortality even after accounting
for baseline confounding factors. Although reoperation for
bleeding was needed in ⬍1 of every 40 patients undergoing
CABG, this event was associated with 1 of every 10 deaths in
these patients (10.3% of all CABG deaths). Most impressively, there was a significant decline in mortality over time
in patients with this complication.
Our data provide some insight into the potential mechanisms for the stable risk of reoperation for bleeding in these
patients. Unlike prior studies from the STS NCD15 and the
Northern New England Cardiovascular Disease Study
Group,16 we did not find an increasing risk of patients
undergoing CABG in recent times. Similarly, factors shown
to be associated with an increased risk of reoperation for
bleeding4,5,8,9 (ie, the rates of emergent or emergent salvage
procedures), CABG ⬍24 hours of myocardial infarction and
on-pump (versus off-pump) CABG remained stable over the
study period. The rates of thienopyridine use before CABG
also remained unchanged over this time. Thus, the overall
stable risk of patients undergoing CABG in general along
with stable rates of predictive factors for increased risk of
reoperation described above may explain in part the stable
incidence of reoperation for bleeding in patients undergoing
CABG.
In contrast, we can only speculate the reasons for the
decline in mortality associated with reoperation for bleeding.
This decrease may have been partially related to the growing
awareness of the potential detrimental bleeding related side
effects of not only aspirin, but also the newer antiplatelet and
antithrombotic agents,10 –12 avoidance of CABG when feasible in stable patients until after the effect of these agents wear
off, the increasing experience of surgeons in the management
of these patients, meticulous hemostasis during surgery, the
use of appropriate blood products along with ⑀ amino caproic
acid, aprotinin, or desmopressin in the perioperative period,17
and use of recently collected (rather than old) blood products18 when needed. Additionally, the quality improvement
effort as part of the ongoing participation in STS NCD may
also have contributed to this decline in mortality over time.
Finally, we also developed a parsimonious predictive
model to identify patients with increased risk of reoperation
for bleeding after CABG. This may be potentially useful to
physicians in estimating patient-specific risk for reoperation
for bleeding before undertaking the operation, for counseling
during informed consent process as well as to promote
preventive measures when feasible in this at-risk group. More
importantly, this outcome varied across different centers that
have different case-mix. Thus, the current risk tool specific to
reoperation for bleeding would allow risk adjusted comparisons of different sites. This would facilitate targeted quality
improvement initiatives at sites with high rates of reoperation.
Unlike prior studies that have demonstrated increased risk
for reoperation with preoperative aspirin in patients undergoing CABG,19 we found no such risk with the use of aspirin
⬍24 hours before CABG. These findings are consistent with
588
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November 2009
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Figure 2. Bedside risk tool (Normogram) to estimate the need for reoperation in patients undergoing CABG. BSA indicates body surface area; IABP, intraaortic balloon pump; ADPi, adenosine diphosphate receptor blockers; GPIIb/IIIa, glycoprotein IIb/IIIa receptor antagonists; and CV, cardiovascular.
that of a recent review which showed no increased perioperative risk of bleeding requiring reoperation with aspirin among
observational studies and increased risk only with doses ⱖ325
mg per day among patients in randomized trials.20
We point out that although based on large number of
patients undergoing CABG with more than 12 000 events (a
much larger number than any of the previously published
studies), the ability of our model was only fair in discriminating between patients needing versus those not needing
reoperation for bleeding, highlighting the difficulty and
challenge in accurately identifying such patients preoperatively. Many factors such as surgeon’s experience or the
threshold for taking back patient to the operating room, the
rapidity of bleeding, patients underlying hemodynamics,
other patient comorbidities, the response to conservative
medical treatments including transfusion and antifibrinolytic
agents, etc that were not collected in the STS NCD may have
partially accounted for this lack of good discriminatory
ability. Despite this drawback, our risk score performed well
Figure 3. Predicted mortality based on bedside risk tool and
observed rates in the risk score categories in the validation set.
in the independent validation set and provided reasonable
estimate of the risk of this event.
Comparisons With Prior Studies
Many previous studies have provided insights into the need
for reoperation for bleeding and have reported an incidence
that varied from 2.3% to 8.0%.1–12 Our estimate of this risk is
on the lower side (2.4%) of that described in these studies and
perhaps reflects a stable estimate of the risk in community at
large. Nonetheless, our data concurs with these previous
studies in that reoperation for bleeding increases morbidity
and mortality in patients undergoing CABG and remains an
important target for improving outcomes.
Important differences between these previous studies and
our investigation exist. Most prior studies involved patients at
a single center 1–3,5,7,12 or those from a regional consortium
involving few institutions,4,6 thus with few patients and fewer
Figure 4. The estimated risk based on the full model (5% to
95% range) and the average estimated risk determined by the
bedside risk tool in various risk score categories in the derivation set. Vertical bars represent 5th to 95th percentiles of the
predicted risk calculated using the full model.
Mehta et al
events. In contrast, our data involve current contemporary
practice at more than 800 widely varying institutions with a
very large number of patients and events allowing robust
statistical power, thereby increasing the generalizability of
our findings. More importantly, almost all of these studies
predated the more routine use of potent antiplatelet and
antithrombotic agents,1–5,8,9 an important and independent
predictor of this event in this and other studies10 –12 limiting
their applicability in current era. Finally, few of these prior
investigations focused on risk factors associated with increased risk of reoperation4,6,8 or provided a simple risk tool
that could be used in routine practice for estimating risk of
this adverse event in patients undergoing CABG.
Clinical Implications
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Many newer antithrombotic and antiplatelet agents have
completed phase III clinical trials or are on the verge of doing
so and many more are in the early clinical phase of human
studies.21–23 As these agents become engrained in contemporary cardiovascular practice, as accurate identification on
admission of patients requiring reoperation after CABG
remain a major ongoing challenge,24 and because the effectiveness of many therapies is reduced if not given early after
admission,25 exposure to these potent agents before CABG
(an already increasingly older and sicker population) is likely
to increase. This is expected to increase the need for reoperation after CABG. Although the easiest option to minimize
the risk is to avoid exposure to these agents before CABG or
to delay surgery in those exposed until platelet function or
hemostasis have recovered, this approach may not be pragmatic many times and may even have the potential for harm
as well as increasing cost (of hospitalization) while awaiting
CABG. Thus, if outcomes of CABG patients are to be
improved in the future, continued ongoing efforts from
surgical colleagues would be necessary to reduce the risk of
perioperative bleeding. Our study is unable to provide insights into strategies that may be helpful in minimizing the
risk of this adverse event in CABG patients. It is likely that
understanding of the detail pharmocology and the duration of
increased risk conferred by the exposure of these new agents,
meticulous hemostasis in those exposed to these drugs,
vigilance for bleeding, and aggressive management early on
with appropriate blood products and drugs may have the
potential for reducing the need for reoperation for bleeding
after CABG. Whether shorter acting intravenous agents21,22
or the use of novel RNA-aptamer-drug-antidote combination23 or the use of off-pump CABG would allow efficacy
upfront when needed and minimize postoperative bleeding
after CABG remains to be established. Finally, the importance of quality improvement initiatives at individual institutions, regional, or national level to measure this event across
various sites and compare them after accounting for patient
case-mix using the current risk tool, identify the root cause of
the problem at sites with high rates of this event, and then
implement process changes to minimize it cannot be overemphasized to help reduce the risk of this event and improve
outcomes of patients undergoing CABG.
Reoperation for Bleeding After CABG
589
Limitations
Although, the STS NCD now represents a majority of centers
in United States, there is a slight overrepresentation of
participation from larger centers and those with better overall
outcomes. Second, we are only able to analyze risk factors
collected and cannot account for the influence of any unmeasured factors influencing the risk of reoperation for bleeding
in CABG patients. We only had information on the use of
thienopyrines within 24 hours of CABG, but not before this
time. However, this would only have biased our observation
toward null (ie, no increased risk of bleeding with clopidogrel). The current database only allowed for evaluation of
short-term risk, as we did not have any information on
long-term outcomes.
Conclusions
Reoperation for bleeding is an important morbid event after
CABG that has remained stable over time. Fortunately, death
in patients with this adverse event decreased over time at least
among patients undergoing CABG at institutions participating in STS NCD. The future availibility of more potent
antiplatelet agents is expected to increase the risk of reoperation for bleeding in CABG patients further highlighting the
ongoing need for monitoring and quality improvement efforts
at institutional, regional, or national level through initiatives
like the STS NCD to reduce this complication in the hope of
improving ouctomes after CABG. Our risk tool may allow
estimation of patients risk for reoperation for bleeding and
promote preventive measures when feasible in this at-risk
group.
Sources of Funding
This work was funded by the STS NCD.
Disclosures
None.
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Reoperation for Bleeding in Patients Undergoing Coronary Artery Bypass Surgery:
Incidence, Risk Factors, Time Trends, and Outcomes
Rajendra H. Mehta, Shubin Sheng, Sean M. O'Brien, Frederick L. Grover, James S. Gammie, T.
Bruce Ferguson and Eric D. Peterson
on behalf of the Society of Thoracic Surgeons National Cardiac Surgery Database Investigators
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Circ Cardiovasc Qual Outcomes. 2009;2:583-590; originally published online October 6, 2009;
doi: 10.1161/CIRCOUTCOMES.109.858811
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