Creatinine elevations from baseline at the time of cardiac surgery are associated with postoperative complications

Abstract

Objectives:

Baseline kidney function is a key predictor of postoperative morbidity and mortality. Whether an increased creatinine at the time of surgery, compared with the lowest creatinine in the 3 months before surgery, is associated with poor outcomes has not been evaluated. We examined whether creatinine elevations from “baseline” were associated with adverse postoperative outcomes.

Methods:

A total of 1486 patients who underwent cardiac surgery at the University of Colorado Hospital between January 2011 and May 2016 met inclusion criteria. “Change in creatinine from baseline” was defined as the difference between the immediate presurgical creatinine value and the lowest creatinine value within 3 months preceding surgery. Outcomes evaluated were in-hospital mortality, postoperative infection, postoperative stroke, development of stage 3 acute kidney injury, intensive care unit length of stay, and hospital length of stay. Outcomes were adjusted using a balancing score to account for differences in patient characteristics.

Results:

There were significant increases in the odds of postoperative infection (odds ratio, 1.17; confidence interval, 1.02–1.34; per 0.1 mg/dL increase in creatinine), stage 3 acute kidney injury (odds ratio, 1.44; confidence interval; 1.18–1.75), intensive care unit length of stay (odds ratio, 1.13; confidence interval, 1.01–1.26), and hospital length of stay (odds ratio, 1.09; confidence interval, 1.05–1.13). There was a significant increase in mortality in the unadjusted analysis, although not after adjustment using a balancing score. There was no association with postoperative stroke.

Conclusions:

Elevations in creatinine at the time of surgery above the “baseline” level are associated with increased postoperative morbidity. Baseline creatinine should be established before surgery, and small changes in creatinine should trigger heightened vigilance in the postoperative period. (J Thorac Cardiovasc Surg 2020;■:1–10)

Cardiac surgery–associated acute kidney injury (CSA-AKI) is a serious and common complication of cardiac surgery that has been shown to significantly and independently increase rates of morbidity and mortality.¹ It occurs in numerous settings, such as after cardiogenic shock,² acute myocardial infarction,^3,4 cardiac catheterization,^5,6 and contrast administration,⁷ and complicates as many as 42% of cases while increasing mortality 3- to 8-fold.⁸ Also, CSA-AKI has been associated with increased rates of infection,⁹ prolonged intensive care unit (ICU) length of stay (LOS), and prolonged hospital LOS.¹⁰ In studies with longer follow-up, CSA-AKI has been shown to increase rates of chronic kidney disease (CKD) and mortality.^11,12

As a result of the significant increases in morbidity and mortality associated with CSA-AKI, a substantial number of publications have addressed potential risk factors for CSA-AKI development.^13–15 Myriad patient-related factors (age, gender, comorbidities) procedural factors (cardiopulmonary bypass time, type of procedure, intraoperative blood products, procedural hypotension) and postoperative risk factors (nephrotoxins, low cardiac output, ventricular assist device placement) have been described. Besides, novel acute kidney injury (AKI) biomarkers have been used to risk-stratify patients going into surgery or after surgery, with variable results.¹ Preoperative creatinine, in particular, has been investigated in numerous studies and is one of the most powerful predictors of CSA-AKI, and operative mortality increases inversely with declining glomerular filtration rate (GFR).^16,17

Although poor outcomes associated with reduced GFR are well documented, a risk factor that has not been previously investigated, to our knowledge, is the presence of acute creatinine elevations from baseline at the time of surgery. In this retrospective study, we compared changes in the preoperative creatinine from “baseline” (lowest value in the 3 months preceding surgery). We hypothesized that increased preoperative creatinine from baseline, independent of the absolute creatinine value, would be associated with higher rates of adverse outcomes, including in-hospital mortality, postoperative infection, postoperative stage 3 AKI, and prolonged ICU and hospital LOS.

MATERIALS AND METHODS

Study Population

We conducted a retrospective chart review from January 2011 to May 2016 using the University of Colorado Society of Thoracic Surgeons (STS) database. Institutional review board approval was obtained from the University of Colorado with a waiver of informed consent. Subjects were included if they were aged 18 years or more, underwent nonemergency cardiac surgery at the University of Colorado Hospital, and had at least 1 preoperative creatinine value available. We excluded subjects for the following reasons: (1) infection at the time of surgery or within 48 hours after surgery; (2) need for dialysis at the time of surgery; (3) end-stage renal disease; (4) left ventricular assist device placements; (5) patients in cardiogenic shock; and (6) procedures performed for infective endocarditis, aortic dissection, or heart transplant. These criteria were designed to capture stable, nonemergency patients who would likely have only mild deviations from “baseline” (lowest value within 3 months) at the time of surgery.

Predictor Variable

The predictor variable was the change in creatinine from the “baseline” value to the presurgical value, treated as a continuous variable. Baseline creatinine was defined as the minimum creatinine value within 3 months of surgery. The presurgical value was collected before the induction of general anesthesia in the operating room or induction area. In Tables 1 and 2, the population is grouped into 3 categories based on the change in creatinine (creatinine difference <0.1 mg/dL, creatinine difference 0.1–0.29 mg/dL, and creatinine difference ≥0.3 mg/dL). These cut-points were chosen on the basis of the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI, in which stage 1 disease is an increase of 0.3 mg/dL or greater.

TABLE 1.

Baseline characteristics of patients divided into 3 groups based on the degree of creatinine elevation at the time of surgery from baseline

Characteristics	Creatinine increase <0.1 mg/dL (n = 1082)	Creatinine increase 0.1–0.29 mg/dL (n = 313)	P value	Creatinine increase ≥0.3 mg/dL (n = 91)	P value
Female	328 (30.3)	92 (29.3)	.73	27 (29.7)	.95
Age, y, mean (SD)	63 (14.1)	63 (13.1)	.46	64.0 (16.5)	.46
Race/ethnicity			.08		<.001
White	851	230		60 (65.9)
Hispanic	124	56		11 (12.1)
Black	63	19		16 (17.6)
Other/unknown	44	8		4 (4.4)
Body mass index, mean (SD)	28.3 (6.1)	28.5 (6.5)	.50	28.8 (6.6)	.50
Comorbidities
Sleep apnea	207 (19.1)	64 (20.5)	.26	17 (18.7)	.96
Hypertension	765 (70.7)	239 (76.4)	.046	75 (82.4)	<.001
Diabetes mellitus	289 (26.7)	131 (41.9)	<.001	41 (45.1)	<.001
Chronic lung disease	234 (21.6)	83 (26.5)	.52	30 (33.0)	.02
Liver disease	29 (2.7)	9 (2.9)	.86	5 (5.5)	.11
Cancer within 5 y	97 (9.0)	35 (11.2)	.25	15 (16.5)	.046
Peripheral vascular disease	72 (6.7)	29 (9.3)	.12	11 (12.1)	.048
Cerebrovascular disease	125 (11.6)	38 (12.1)	.79	9 (9.9)	.66
Dyslipidemia	633 (58.5)	194 (62.0)	.30	63 (69.2)	.03
Congestive heart failure	452(41.7)	155 (49.5)	.01	51 (56.0)	.01
CKD	199 (18.4)	38 (12.1)	.009	33 (36.3)	<.001
Baseline GFR, mean (SD)	79.3 (24.3)	87.1 (27.1)	<.001	76.5 (34.8)	.29
Peak creatinine 72 h, median (IQR)	1.1 (0.9–1.3)	1.1 (0.9–1.5)	.03	1.4 (1.1–2.0)	<.001
Smoker at time of surgery	267 (24.7)	94 (30.3)	.59	22 (24.2)	.38
History of recent IV drug abuse	48 (4.4)	8 (2.6)	.64	3 (3.3)	.76
Last hematocrit, mean (SD)	41.3 (5.3)	40.2 (6.3)	.003	38.5 (6.5)	<.001
Last white blood cell count, mean (SD)	7.2 (2.3)	7.6 (2.7)	.01	7.7 (2.9)	.046
Cardiopulmonary bypass time, median (IQR)	124(79–167)	119 (78–162)	.43	122 (73–188)	.44
Ejection fraction, median (IQR)	57 (45–65)	59 (45–65)	.39	55 (38–64)	.10
Surgical time, h, median (IQR)	6.1 (4.9–7.4)	6.2 (5.0–7.3)	.82	6.3 (5.1–8.1)	.13
Intraoperative blood products	366 (33.8)	112(35.8)	.48	34 (37.4)	.45
Steroid use	34 (3.1)	15 (4.8)	.17	4 (4.4)	.50
Previous cardiovascular intervention	355 (32.8)	107 (34.2)	.67	31 (34.1)	.75
Surgical type			.009		.47
Aortic aneurysm repair	129 (11.9)	18 (5.7)		7 (7.7)
Valve surgery	324 (29.9)	83 (26.8)		22 (21.2)
Coronary artery bypass	295 (27.3)	110(35.0)		28 (30.8)
TAVR/TEVAR	103 (9.5)	34(10.8)		11 (12.1)
Combined	162 (15.0)	49 (15.6)		14 (15.4)
Other	69 (6.4)	19 (6.1)		9 (9.9)

Values less than .05 are in bold. SD, Standard deviation; CKD, chronic kidney disease; GFR, glomerular filtration rate; IQR, interquartile range; IV, intravenous; TAVR, transcatheter aortic valve replacement; TEVAR, thoracic endovascular aortic aneurysm repair

TABLE 2.

Adverse outcomes by difference in creatinine between presurgical and baseline values

	Creatinine increase <0.1 mg/dL	Creatinine increase 0.1–0.29 mg/dL	Creatinine increase ≥0.3 mg/dL
	(n = 1082)	(n = 313)	(n = 91)
Adverse outcome	N (%)	N (%)	N (%)	P value*
In-hospital mortality	15 (1.4)	9 (2.9)	4 (4.4)	.043
Total infection	68 (6.3)	43 (13.7)	12 (13.3)	<.0001
Deep SSI	8 (0.7)	8 (2.5)	0(0)	.01
Positive culture	37 (3.4)	22 (7.0)	4 (4.4)	.02
Pneumonia	33 (3.0)	19 (6.1)	9 (10.0)	.01
Stage 3 AKI	23 (2.1)	12 (3.8)	11 (12.2)	<.0001
Stroke	19 (1.8)	9 (2.9)	3 (3.3)	.13
ICU stay >72 h	379 (35.0)	133 (42.4)	44 (48.4)	.007
Hospital LOS, d, median (IQR)	7 (5–10)	9 (6–14)	10 (7–17)	<.0001

Values less than .05 are in bold. SSI, Surgical site infection; AKI, acute kidney injury; ICU, intensive care unit; LOS, length of stay; IQR, interquartile range.

^*P values are Fisher exact for categorical outcomes and Wilcoxon rank-sum for continuous outcome. P values < .05 are in bold.

Outcomes

The primary outcome was in-hospital mortality. Secondary outcomes included postoperative infection, postoperative stroke, postoperative stage 3 AKI, ICU LOS greater than 72 hours, and hospital LOS. Postoperative infection was defined as a new surgical site infection (deep or superficial), positive blood or urine culture, or imaging suggestive of new-onset pneumonia. Stage III AKI was defined using KDIGO guidelines as a tripling of creatinine from baseline, an absolute creatinine 4.0 mg/dL or more, or initiation of dialysis.¹⁸ Of note, these criteria also define “renal failure” within the STS database.

Statistical Analysis

Mean ± standard deviation or counts and percentages were used to describe the distribution of continuous and categoric variables, respectively. For continuous variables with non-normal distributions, median with interquartile ranges are given. Chi-square, analysis of variance, or Kruskal-Wallis tests were used as appropriate.

The statistical analysis evaluated the change in creatinine from baseline to presurgical value as a continuous variable in a balancing score-adjusted analysis, which was used because of a low event rate especially for the primary outcome (in-hospital mortality), which would otherwise limit the number of variables that could be used in a typical multivariable model. The R² value for the model was 0.035, with a P value of less than .0001.

The balancing score was derived from a linear regression in which the dependent variable was the difference in creatinine between the preoperative value and the “baseline” value, and the independent variables were age, gender, preoperative white blood cell count, preoperative hematocrit, prior cardiovascular intervention, history of chronic lung disease, estimated GFR calculated using the Modification of Diet in Renal Disease equation with the “baseline” (lowest value in 3 months) creatinine, and surgical type. Surgical types were aneurysm repair, valve surgery, coronary artery bypass, transcatheter aortic valve replacement, thoracic endovascular aortic aneurysm repair, combined (which featured elements of >1 category), or other, which were all other surgeries recorded within the STS database. These variables were chosen a priori for this analysis based on their known associations with mortality, postoperative infection, and postoperative AKI.¹⁹ Patients with a negative difference (a preoperative value lower than “baseline” value) were set to 0. This balancing score was then used as a covariate in a logistic regression along with the difference preoperative creatinine compared with “baseline” to evaluate the association of creatinine difference and primary and secondary outcomes. Odds ratios (ORs) were calculated per 0.1 mg/dL change in creatinine from baseline. C-index or R² values were calculated for categoric and continuous outcomes as appropriate to assess goodness of fit. Sensitivity analyses using an alternative definition of baseline creatinine (median 3-month creatinine) and evaluating only patients with a doubling of creatinine from baseline at the time of surgery were planned but could not be completed because of insufficient N values. All statistical tests were considered significant at a 2-sided P< .05. All analyses were performed using SAS software version 9.4 (SAS Inc, Cary, NC).

RESULTS

Baseline Characteristics

A total of 2362 patients underwent cardiac surgery during the study period, of whom 1486 met inclusion criteria (Figure 1). Baseline characteristics for patients with a creatinine change from baseline less than 0.1 mg/dL, a change of 0.1 to 0.29 mg/dL, and a change of 0.3 mg/dL or greater are shown in Table 1. The notable differences between the groups include a higher percentage of African American patients in the highest change group, higher rates of hypertension and diabetes, higher rates of CKD (although not lower estimated GFR), and lower hematocrit levels. Surgical factors, including cardiopulmonary bypass time, surgical time, intraoperative blood product administration, and surgical type, were not significantly different among the groups.

FIGURE 1.

Study cohort selection. The flow diagram depicts the details of patients screened and reasons for patient exclusion. ESRD, End-stage renal disease; AKI, acute kidney injury; LVAD, left ventricular assist device.

Operative Outcomes

Outcomes data are listed in Table 2. There were higher event rates for all outcomes as the deviation from baseline became greater. Stroke was not significantly different in any group, but all other outcomes were significantly greater in the group with the highest deviation from baseline creatinine. Patients with small deviations from baseline (0.1–0.29 mg/dL) also had significantly higher rates of postoperative morbidity.

Adjusted Outcomes

After balancing score–adjusted modeling, there were significant increases in the odds of all primary and secondary outcomes except postoperative stroke. As shown in Table 3, with changes of 0.1 mg/dL, the odds of mortality increased 27%, the odds of postoperative infection increased 21%, and the odds of stage 3 AKI increased by 34%. Adjusted outcomes are represented in a Forest plot in Figure 2. A graphical summary of the methods and results is provided in Figure 3.

TABLE 3.

Unadjusted and balancing score–adjusted adverse outcomes for presurgical acute kidney injury, defined as continuous difference from baseline with odds ratios for 0.1 mg/dL change

Adverse outcome*	OR (95% CI)	P value	C index/R2
In-hospital mortality
Unadjusted	1.34 (1.16–1.56)	<.0001	0.611
Balancing score adjusted†	1.27 (1.06–1.51)	.008	0.666
Infection
Unadjusted	1.27 (1.15–1.40)	<.0001	0.617
Balancing score adjusted†	1.21 (1.09–1.35)	<.001	0.652
Stroke
Unadjusted	1.17 (0.98–1.40)	.08	0.585
Balancing score adjusted†	1.14 (0.94–1.39)	.17	0.593
Renal failure
Unadjusted	1.38 (1.21–1.58)	<.0001	0.676
Balancing score adjusted†	1.34 (1.16–1.55)	<.0001	0.731
ICU stay >72 h
Unadjusted	1.17 (1.08–1.27)	<.001	0.547
Balancing score adjusted†	1.14 (1.05–1.24)	.002	0.615
Hospital LOS‡
Unadjusted	1.13 (1.10–1.15)	<.0001	0.068
Balancing score adjusted†	1.11 (1.08–1.13)	<.0001	0.105

Values less than .05 are in bold. OR, Odds ratio; CI, confidence interval; ICU, intensive care unit; LOS, length of stay.

^*Single predictor is difference between presurgical creatinine and the “baseline” (lowest value in 3 months) as a continuous variable.

^†Model was constructed using creatinine difference plus a balancing score as the 2 variables.

^‡A negative binomial model was used for this outcome and fit statistic of R².

FIGURE 2.

Forest plot showing OR and 95% CIs for in-hospital mortality postoperative infection, stage 3 AKI, postoperative stroke, prolonged ICU LOS, and prolonged hospital LOS based on the change in preoperative creatinine level from the baseline value. Also shown are rates of primary and secondary outcomes in patients based on the degree of creatinine increase from the baseline value. Data are displayed as numbers and percentages, except where indicated. *Mean and interquartile range. CI, Confidence interval; ICU, intensive care unit; LOS, length of stay.

FIGURE 3.

Graphical overview of the methods and results of the study. OR, Odds ratio; CI, confidence interval; AKI, acute kidney injury; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; LOS, length of stay.

DISCUSSION

In this study, we demonstrate that an increase in creatinine from baseline at the time of surgery is independently associated with increased rates of serious postoperative complications, including mortality, postoperative infection, postoperative stage 3 AKI, and prolonged ICU and hospital LOS. Furthermore, we show that the increase in creatinine from baseline provides prognostic value beyond the baseline GFR alone.

Postoperative AKI is a serious complication of cardiac surgery and has been associated with significant increases in morbidity and mortality. A meta-analysis of 91 international studies showed that the overall rate of CSA-AKI was 22.3% and that 61% of cases were KDIGO stage 1, defined as an increase in creatinine of 0.3 mg/dL or greater, with a ratio of creatinine to a baseline of less than 2.0. The overall mortality in CSA-AKI was 10.6% compared with 1.4% in patients without AKI. The pooled OR for mortality was 7.0 for all CSA-AKI and 4.0 for patients with stage 1 disease.²⁰ Therefore, “mild” cases of AKI are associated with significant increases in mortality.

Likewise, postoperative AKI is associated with substantially increased rates of postoperative complications. In the same meta-analysis of 91 international studies, Hu and colleagues²⁰ showed that both ICU LOS and hospital LOS are higher in patients with CSA-AKI (5.4 and 15 days vs 2.2 and 10.5 days in the non-AKI group, respectively). Multiple studies have demonstrated an association between CSA-AKI and subsequent infection. Thakar and colleagues⁹ analyzed 24,660 patients and found that the development of AKI increased infection rates to 58.5% if dialysis was required and to 23.7% in those not requiring dialysis. Stage 1 AKI has been shown to increase risk, as demonstrated by SooHoo and colleagues²¹ in a pediatric population undergoing cardiac surgery. Finally, postoperative AKI has been associated with long-term consequences after discharge, including higher rates of CKD, CHF, infection, and death.^22–24 It is clear that increases in creatinine in the postoperative setting are a robust negative prognostic marker.

Multiple studies have also demonstrated that the creatinine level before surgery is one of the most powerful predictors of postoperative morbidity and mortality. In a study of approximately 500,000 patients from the STS database, operative mortality increased inversely with declining renal function from 1.3% for those with normal renal function to 9.3% for patients with severe CKD.¹⁷ As a result of these robust findings, baseline creatinine is a prominent component within many risk prediction scores including the STS and European System for Cardiac Operative Risk Evaluation calculations.

In contrast to studies evaluating the impact of postoperative AKI or preoperative creatinine value, our study specifically looks at the creatinine change from baseline at the time of surgery. As an example, take 2 patients with identical baseline characteristics, each with a preoperative creatinine value of 1.2 mg/dL. If 1 patient has a baseline creatinine of 1.2 mg/dL (and is therefore at baseline) and the other has a baseline creatinine of 0.6 mg/dL (and therefore has an increased creatinine from baseline), this study suggests that the patient with the deviation from baseline is more likely to experience postoperative morbidity and mortality. Our model adjusted for baseline GFR, suggesting that the change in creatinine provides prognostic data beyond the baseline creatinine alone.

It is notable that in our study most preoperative elevations of creatinine from baseline were mild and would have been considered stage 1 AKI using the KDIGO definition or would not have met KDIGO criteria at all. We calculated ORs based on an increase of 0.1 mg/dL and found that each 0.1 mg/dL increase in creatinine is associated with a 20% to 30% increase in the odds of morbidity or mortality. These findings would suggest that “mild” changes from baseline should not be quickly dismissed. The relatively outsized impact of small creatinine changes may shed light on the underlying pathophysiologic mechanism. Notably, neither the overall operative time nor cardiopulmonary bypass time was significantly different in the patients with elevated creatinine from baseline, nor were there increased transfusions, suggesting that these findings are not due to increased surgical complexity or intraoperative complications. Rather, a relatively mild increase in creatinine could function as a “first hit” that when exacerbated by the “second-hit” of surgery can synergistically lead to clinical decompensation.

Regarding infection in particular, postoperative AKI has been associated with immune dysfunction. Although the causality and mechanisms of this association remain to be ascertained, it is possible that presurgical creatinine elevations similarly impair the immune system and therefore could predispose to infection. Further research into the mechanism of AKI and immune dysfunction is needed.

To our knowledge, the change in creatinine from baseline to the preoperative value has not previously been examined as a prognostic marker. The lack of previous studies may be because a preoperative creatinine baseline is often not established before surgery. Large national databases such as the STS database only record the presurgical creatinine value, making comparisons with a prior baseline impossible. On the basis of our findings, we believe it is important to determine a patient’s creatinine before the day of surgery, perhaps at the time of surgical consent for elective procedures. This would allow for a later comparison of the presurgical creatinine to the baseline value and would yield additional prognostic value, as well as the potential for earlier interventions in these cases.

Although this study shows the prognostic utility of measuring creatinine changes from baseline at the time of surgery, there remain questions about what to do in this population to reduce postoperative morbidity and mortality. Some recently published studies suggest that the heightened vigilance and the use of KDIGO-based bundles may be able to improve outcomes. The recent PrevAKI trial showed that in a population of postsurgical patients with an elevated tissue inhibitor of metalloproteinase 2 and insulin-like growth factor–binding protein 7, the implementation of a KDIGO-based bundle that consisted of (1) avoidance of nephrotoxic agents; (2) discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the first 48 hours after surgery; (3) close monitoring of serum creatinine and urine output; (4) avoidance of hyperglycemia for the first 72 hours after surgery; (5) consideration of alternatives to radiocontrast agents; and (6) close hemodynamic monitoring by using a pulse contour cardiac output catheter with an optimization of the volume status and hemodynamic parameters according to a prespecified algorithm was able to dramatically reduce the rates of CSA-AKI compared with standard care alone (55.1% vs 71.1%, 95% confidence interval (CI), 5.5–27.9, P = .004).²⁵ The implementation of this bundle in presurgical patients with AKI could improve surgical outcomes in this population. Additional interventions such as limiting cardiopulmonary bypass time should also be considered.²⁶ Further research is needed to determine if these interventions improve outcomes in this population.

Study Limitations

Our study has several important limitations. The results of our single-center retrospective study need to be duplicated in larger multicenter studies. Given the retrospective nature of this study, other confounding factors may be present that were not accounted for in the analysis. Because of the low event rate in our population, especially with regard to mortality, a balancing score–adjusted analysis was used, which may not fully account for all confounding factors. There is a lack of consensus currently regarding how to define baseline creatinine. We did not have a sufficiently large database to evaluate the use of median creatinine as opposed to the lowest creatinine over 3 months, but previous studies suggest that the definition of baseline creatinine can significantly modify outcomes.²⁷

Likewise, we do not have data regarding when the lowest creatinine value occurred before surgery. A creatinine level taken too close to surgery may not provide sufficient time for changes to become apparent. We also do not have details on the timing of events that may have occurred between the baseline and preoperative creatinine values, such as the use of intravenous contrast in computed tomography imaging or cardiac catheterization procedures.

CONCLUSIONS

Our study demonstrates that a preoperative increase in creatinine from baseline, independent of baseline GFR, is associated with higher rates of serious adverse outcomes, including mortality, postoperative infection, postoperative stage III AKI, and prolonged ICU and hospital LOS. On the basis of these findings, we would advocate for laboratory tests before the surgical date to establish a baseline creatinine, especially in elective cases. Small preoperative changes in creatinine from the baseline, and especially changes greater than 0.3 mg/dL, should trigger heightened vigilance in the postoperative period. Future studies should evaluate whether specific interventions such as the implementation of a KDIGO-based care bundle improve outcomes in this population.

CENTRAL MESSAGE.

Acute creatinine elevations at the time of surgery are associated with increased postoperative infection, stage 3 AKI, ICU LOS, and hospital LOS in patients undergoing cardiac surgery.

PERSPECTIVE.

Acute creatinine elevations at the time of cardiac from “baseline” (lowest value in 3 months before surgery) are independently associated with poor postoperative outcomes. Baseline creatinine should be established before surgery, and even small changes in creatinine should trigger heightened vigilance in the postoperative period.

Abbreviations and Acronyms

CI

confidence interval

CKD

chronic kidney disease

CSA-AKI

cardiac surgery–associated acute kidney injury

GFR

glomerular filtration rate

ICU

intensive care unit

KDIGO

Kidney Disease Improving Global Outcomes

LOS

length of stay

STS

Society of Thoracic Surgeons

Discussion

Dr Joelle Coletta. Our next presentation from the University of Colorado is entitled, “Preoperative Creatinine Elevation Increases the Risk of Mortality, Postoperative Infection, and Prolonged ICU Stay After Cardiac Surgery.”

Speaker. We know that postoperative AKI is a serious complication of cardiac surgery that increases rates of morbidity and mortality. We also know preoperatively that CKD increases rates of postoperative morbidity and mortality, but preoperative acute changes in creatinine have not been as well evaluated. Our clinical question for this study was whether acute increases in creatinine at the time of surgery lead to higher rates of postoperative morbidity and mortality. Our hypothesis was that they would.

To answer this clinical question, we did a retrospective cohort analysis looking at approximately 1600 patients who underwent nonemergency cardiac surgery between 2012 and 2016. We excluded emergency cases, active infection, and patients with renal disease and AKI on dialysis at the time of surgery. Our predictor variable was the change in creatinine from baseline and baseline being defined as the lowest creatinine within 3 months of the surgery as a continuous variable. We did a multivariable analysis to adjust for covariates. Specifically, the variables we adjusted for included demographic variables, the Charlson score to account for comorbidities, preoperative risk factors including the presence of shock, ejection fraction, and laboratory values, and intraoperative factors. I want to point out that we did adjust for baseline estimated GFR to account for the presence of CKD, and we did account for perfusion time and the type of surgery.

The outcomes we looked at were in-hospital mortality, postoperative infection, postoperative stroke, development of stage 3 AKI, which corresponds to the STS definition of kidney injury, and prolonged ICU and hospital LOS.

Our results are shown graphically. These are the multivariable adjusted results, so per unit increase in creatinine from the baseline value. As you can see, in-hospital mortality had an approximately 7-fold increase, postoperative infection had an approximately 3.5-fold increase, postoperative AKI had a 6-fold increase, and ICU and hospital LOS were significantly increased. The one result that did not achieve statistical significance was postoperative stroke, which had an OR of approximately 1.

Creatinine at the time of surgery above baseline was associated with increased postoperative morbidity and mortality. We would advocate that surgeons look at a baseline level before operating, and in patients who do have an elevated creatinine, renal optimization and careful operative in perioperative volume hemodynamic management are warranted. We would advocate for future studies to look at specific interventions in these patients to see if we can decrease the rate of morbidity and mortality in this population. I’ll take questions at this time.

Dr Joseph Woo. Thank you for accelerating and making up for the time lost by your senior author.

Dr Coletta. You said potentially delaying for renal optimization would make a difference. In your Abstract, you discuss using the baseline creatinine being the minimum value within the 3 months before surgery, so how do you theorize that delaying surgery is going to improve outcomes if you are comparing with the minimum value in that time period?

Speaker. Yes, and I think specifically it would be important to look at why you think the creatinine is elevated. If for instance you think this is worsening cardiorenal syndrome, you may want to intervene sooner to correct the underlying problem, but if you think the patient is dehydrated going into surgery, taking some time to medically optimize the patient is what we were advocating would be useful.

Dr Coletta. So acute change versus…

Speaker. Yes.

Dr Coletta. Any other questions from the audience?

Dr William I. Brenner. I’m banging the drum. The whole question of pulsatile bypass, higher perfusion pressures during the operation, people seem to think these have faded into irrelevance, but when you have a patient with marginal kidney function, these may be the tipping factors and paying attention to preserving the physiology of the kidneys rather than the whole body, which seems to do okay with nonpulsatile bypass, may be a significant consideration.

Dr David Rabkin. I might have missed it, but how much above baseline creatinine were you looking at for those complications?

Speaker. We didn’t use a specific cut point here. We looked at it as a multivariable or continuous model, but I will say most of the patients who had creatinine elevations were actually mild in the range of 0.1 to 0.3, and fewer than we expected would have met a true AKI cutoff of 0.3.

Dr Rabkin. Right. I can see how if you have an outpatient for an elective case, this is straightforward or if they have an AKI it’s not the right time to operate on them. At Loma Linda, it seems that our inpatients who have non–ST-elevation myocardial infarctions should be revascularized before discharge. They were catheterized on that admission, and a lot of them have a 0.1 bump in creatinine. It’s almost nothing, and you have to weigh that, and you have all the hospital administrators breathing down your neck to get the cases done and try to shorten the preoperative LOS and get the patients in the operating room. You want to cancel them at the last minute, so there is some pressure to get these cases done, but I think the bigger question is what’s going to happen if you wait until their renal function normalizes because there are bad things that can happen depending on their coronary anatomy. I think it’s easy to say for the elective population that you need to optimize them. I’m not sure that it’s a slam dunk to say that patients need to wait until their creatinine normalizes before you intervene.

Speaker. That’s a great point. I don’t think delaying is always the optimal strategy and I would point more to the recently published PrevAKI trial that just came out that implemented a KDIGO-based bundle for care in postoperative AKI or high-risk patients. The way to go may be increased intervention in these patients postoperatively to try to optimize medical management as much as possible rather than delaying the surgery, and that’s probably where I would focus, is getting nephrology involved earlier or something along those lines to try to optimize postoperative management.