Accepted Manuscript Impact of Early and Intensive Continuous Veno-Venous Hemofiltration on Patients with Cardiogenic Shock and Acute Kidney Injury following Cardiac Surgery Szu-Yuan Li, MD Wu-Chang Yang, MD Chiao-Lin Chuang, MD PII:

S0022-5223(14)00527-3

DOI:

10.1016/j.jtcvs.2014.05.006

Reference:

YMTC 8592

To appear in:

The Journal of Thoracic and Cardiovascular Surgery

Received Date: 18 February 2014 Revised Date:

24 April 2014

Accepted Date: 2 May 2014

Please cite this article as: Li S-Y, Yang W-C, Chuang C-L, Impact of Early and Intensive Continuous Veno-Venous Hemofiltration on Patients with Cardiogenic Shock and Acute Kidney Injury following Cardiac Surgery, The Journal of Thoracic and Cardiovascular Surgery (2014), doi: 10.1016/ j.jtcvs.2014.05.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.

ACCEPTED MANUSCRIPT

Impact of Early and Intensive Continuous Veno-Venous Hemofiltration on Patients with Cardiogenic Shock and Acute Kidney Injury following

RI PT

Cardiac Surgery

Szu-Yuan Li, MD a, Wu-Chang Yang, MD a, and Chiao-Lin Chuang, MD b

Division of aNephrology and bGeneral Medicine, Department of Medicine, Taipei Veterans

M AN U

SC

General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan

Corresponding author: Chiao-Lin Chuang, M.D.

Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital,

TE D

Taipei, Taiwan

No.201, Sec 2, Shih-Pai Road, Taipei 11217, Taiwan Tel: 886-2-28712121 ext 3522;

EP

Fax: 886-2-28757809

AC C

E-mail:[email protected]

Word count: 2588

Financial support:

This work was supported by grant V102-E2-002, V102-B-016 and V95-B1-009 from Taipei veterans General Hospital. NSC 101-2314-B-075-038 and NSC 102-2633-B-075 -001 from National Science Council Taiwan 1

ACCEPTED MANUSCRIPT

Abstract Background Continuous renal replacement therapy (CRRT) is currently the mainstay of renal support to the critically ill patients. However, the optimal intensity of CRRT remains debated due to

RI PT

heterogeneity of study population and CRRT techniques across centers. This study aimed to investigate the beneficial effects of early and intensive continuous veno-venous hemofiltration on post-cardiotomy shock patients.

SC

Methods and Results

Patients who received CRRT due to cardiogenic shock and acute kidney injury (AKI) after

M AN U

cardiac surgery from January 2003 to December 2007 were retrospectively recruited. They were divided to two groups according to the delivered dosage of hemofiltration. Mean duration between ICU admission and initiation of Continuous veno-venous hemofiltration (CVVH) was 1.4 ± 0.8 days. The all-cause mortality by day 30 was 73.3% in low dose group

TE D

and 45.4% in high dose group (p = 0.002). The in-hospital mortality rate was 82.2% and 61.8%, respectively (p = 0.02). There was no significant difference in renal recovery of survivors between two groups.

EP

Conclusions

AC C

In patients developing post-operative cardiogenic shock and AKI following cardiac surgery, early higher dose of CVVH was associated with better in-hospital and long-term survival. Moreover, the beneficial impact of intensive treatment might be more critical in the early peri-operative period. Key words:

Acute kidney injury (AKI), Continuous veno-venous hemofiltration (CVVH), Cardiogenic shock, Cardiac surgery

2

ACCEPTED MANUSCRIPT Ultra-mini abstract Continuous renal replacement therapy (CRRT) is currently the mainstay of renal support to the critically ill patients. However, the optimal intensity of CRRT remains debated among patients developing post-operative cardiogenic shock and AKI following cardiac surgery,

RI PT

Current study indicates early higher dose of CRRT is associated with better in-hospital and

AC C

EP

TE D

M AN U

SC

long-term survival.

3

ACCEPTED MANUSCRIPT

Introduction Acute kidney injury (AKI) remains a dreaded complication of cardiac surgery despite substantial advances in surgical techniques, anesthesia management and cardiopulmonary bypass equipment. The causes of AKI after cardiac surgical intervention included

RI PT

hypovolemia, systemic inflammation, anemia, hypotension, and hypoxemia as well as direct ischemia in the case of operations involving vascular interruption.1 Depending on the population studied and the criteria used for definition, the frequency of AKI following

SC

cardiac surgery ranged between 0.7% and 31%, and 5~7% of patients require renal replacement therapy (RRT).2-4 Although tremendous innovation in supportive care and RRT

M AN U

over the last decade, the mortality rate of AKI necessitating RRT remains extremely high, in excess of 50%.5, 6

Instead of traditional intermittent hemodialysis, continuous renal replacement therapy (CRRT) has now emerged as the leading form of RRT for AKI patients in the intensive care

TE D

unit (ICU) worldwide owing to less treatment related hemodynamic instability, more steady acid-base and electrolyte correction, and subtend fluid removal theoretically. In the past decade, several studies conducted on endotoxemic animals revealed improved hemodynamics

EP

and cytokine removal with high-volume CRRT.7-9 In addition, some single-center clinical

AC C

studies advocated a RRT dose-survival relationship, suggesting the beneficial effect of CRRT intensity > 35 ml/kg/hr.10,

11

However, current large, multi-center, randomized controlled

clinical trials failed to support the putative superiority of intensive CRRT in either survival or renal recovery.12-14 This discrepancy might result from the clinical heterogeneity of study population and practice variation in the application of CRRT across centers. Hence, we conducted a case control study focused on post-cardiotomy shock patients who are homogeneity in disease characteristics, timing to initiating RRT, and RRT modality and aimed to analyze whether intensive CRRT will improve clinical outcome. 4

ACCEPTED MANUSCRIPT

Materials and Methods Study subjects This is a retrospective case-control study approved by the Taipei Veterans General

RI PT

Hospital institutional review board. And the institutional review board waived the need for written informed consent from the participants. From January 2003 to December 2007, adult patients who developed dialysis-requiring AKI following cardiac surgery at Taipei Veterans

SC

General Hospital were recruited. Patients who were hemodynamic stable or under chronic

M AN U

dialysis for end-stage kidney disease were ineligible for this study (Figure 1).

Data collection

Demographic data were obtained from medical records. Biochemistry data such as hemoglobin, albumin, blood urea nitrogen, and creatinine were routinely obtained before

TE D

surgery. Baseline estimated glomerular filtration rate (eGFR) was calculated by the Cockcroft-Gault formula as follows for men: (140-age) x (body weight in kg) / (0.814 x serum creatinine in µmol/L). In women, the value was multiplied by 0.85.15 Type of surgery,

EP

duration of cardiopulmonary bypass, post-operative requirement of intra-aortic balloon

AC C

pumping (IABP) and extracorporeal membrane oxygenation (ECMO) were obtained from surgical records. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment score (SOFA) score, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), central venous pressure, time to CRRT initiation, dosage of inotropic agents and continuous veno-venous hemofiltration (CVVH), length of stay in ICU, and in-hospital mortality were assessed from medical records. Diagnosis of sepsis was made according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.16 5

ACCEPTED MANUSCRIPT

CVVH setting and dosage All patients were admitted to ICU immediately after surgery. Inotropic support was prescribed when mean arterial pressure was < 60mm Hg. The indications for RRT were as

RI PT

following: oligouria (urine output < 240 ml/12h) despite fluid resuscitation and intravenous diuretic treatment, hyperkalemia > 6.5 mmol/L, severe acidosis (pH < 7.2), or pulmonary edema. Timing to initiating or terminating RRT and dosage of CVVH were decided by the

SC

consulting nephrologists. CVVH was accomplished using blood flow rates of 100-150 ml/min through a double-lumen 12 Fr catheter inserted into femoral vein. Bicarbonate-based

M AN U

replacement fluid was administered in pre-dilution mode at a dynamically adjusted rate to achieve the desired fluid balance. The amount of effluent was used as proxy for treatment dosage. Patients were transitioned from CVVH to intermittent hemodialysis at the judgment of nephrologists if they became hemodynamically stable. Recovery of renal function was

TE D

based on assessment of urine output and biochemical data.

During the 6-year enrolling period, two kinds of CVVH machines were applied at Taipei Veterans General Hospital. Before 2005, we had only the first-generation dedicated CRRT

EP

machines which achieved pre-dilutional hemofiltration about 1000~1200 ml/hr. The device

AC C

was composed by AK-10 hemodialysis machine (Gambro, Sweden) for blood pumping and infusion pump for fluid balance. Since January 2005, the Prisma machines (Hospal-Gambro, Switzerland) were available and routinely prescribed pre-dilutional hemofiltration of 3000 ml/hr. After a 3 month of overlapping period, all AKI patients with unstable hemodynamics received CVVH by the Prisma machines.

Patients Follow-up

6

ACCEPTED MANUSCRIPT In June 2010, the renal function and vital status of all patients were collected from medical records of the outpatient clinic or by telephone interviews, or both. When a patient had died during follow-up, the date of death was established.

RI PT

Statistical Analysis

Normally distributed continuous data were expressed as mean ± standard deviation and analyzed by the Student’s t test. Numeric data which were not normally distributed were

SC

expressed as median and interquartile range and analyzed by the Mann-Whitney U test. Statistical analysis was performed with SPSS 20.0 software. Survival rate of two groups were

M AN U

calculated using the Kaplan-Meier method and compared by the log-rank test. Multi-variate stepwise logistic regression was performed to analyze the independent risk factors of in-hospital mortality. Risk factors with a p value less than 0.1 in uni-variate analysis were entered into multi-variate analysis. All probabilities were two tailed, and significance was

TE D

determined at a p value of less than 0.05.

Results

EP

Basic characteristics of study population

AC C

One hundred and forty-two patients were included with a mean age of 69.6 ± 12.1 years old. All patients needed the postoperative supports of mechanical ventilation and inotropic agents supplement. Mean SOFA score, APACHE II score, and EuroSCORE II were 16.4 ± 2.4, 27.8 ± 5.2, and 43.8±18.9 %, respectively. Among them, 45 patients received lower dose of CVVH (18.1 ± 3.6 ml/kg/hr) and 97 subjects received high dose of CVVH (45.2 ± 7.9 ml/min/hr). Mean duration between ICU admission and initiation of CVVH was 1.4 ± 0.8 days. There was no statistical difference in basic characteristics between two groups (Table 1). 7

ACCEPTED MANUSCRIPT

Clinical outcome The numbers of open heart surgery and members of surgical team remained consistent in our hospital during study period. There was comparable mortality rate and CRRT-requiring

RI PT

rate before and after year 2005 (Figure 2). The in-hospital mortality rate was 82.2% (n = 37) in low dose group and 61.8 % (n = 60) in high dose group (p = 0.02). The lengths of ICU stay and hospital stay were longer in the high dose group (Table 2). Uni-variate logistic regression

SC

identified nine risk factors of in-hospital mortality, including age, male gender, emergent operation, hemoglobin, albumin, CVVH dosage, EuroSCORE II, postoperative requirement

M AN U

of IABP and ECMO (all p < 0.05). Consequently, these factors were included in a multi-variate logistic model and identified the independent risk factors of in-hospital mortality, including age, sepsis, low dose of CVVH, EuroSCORE II, postoperative requirement of IABP and ECMO (Table 3). The Kaplan-Meier survival curves were shown in

TE D

Figure 3.

Overall, 8 patients from low dose group and 37 patients from high dose group survived and discharged from hospital. Of them, 50% (n = 4) of survivors from low dose group and 19% (n

EP

= 7) of survivors from high dose group required long-term hemodialysis after discharge.

0.172).

AC C

There was no statistically significant difference in renal recovery between two groups (p =

Evolution of impact of CVVH dosage on survival Most mortality events occurred within one month after surgery. The beneficial impact of intensive CVVH was highest in the peri-operative day and consequently declined with time. After multi-variate logistic regression adjustment, the odds ratio of low dose CVVH against

8

ACCEPTED MANUSCRIPT high dose CVVH at 3 days, 1 week, 2 weeks, 1 month, and 3 months following surgery were 13.4, 7.7, 3.8, 3.3, and 2.6, respectively.

Factors influence survival among patients with cardiogenic shock and CRRT-requiring

RI PT

AKI after cardiac surgery

Comparing the background difference between survivors and non-survivors, we found age, hemoglobin, albumin, the requirement of IABP or ECMO, the CVVH dosage, length of

SC

hospital stay, and EuroSCORE II are associated with patient survival (Table 4). There was no significant difference in diabetes, urgent surgery, Pre-dialysis eGFR, APACHE II and SOFA

M AN U

score between survivors and non-survivors.

Discussion

It has been well accepted that dialysis dosage affected mortality and morbidity in chronic

TE D

peritoneal and hemodialysis patients. Thereby, the dosage of RRT was also thought to play a potential role for outcomes in patients with AKI. The development and introduction of CRRT represented a critically important change in patient management in the ICU. In addition to

EP

superior metabolic control than other forms of RRT, CRRT also allows a better fluid balance

AC C

and thus provides a platform for more aggressive nutritional support, having possible favorable effects on immune function and overall outcome.17 Accordingly, CRRT is ideally suited for AKI patients with significant cardiac diseases. In patients undergoing cardiac surgery, AKI is usually associated either with inflammatory response or with cardiogenic dysfunction. In this clinical context, CRRT may reduce left ventricular end diastolic pressure by optimizing the Frank-Starling relationship and improving myocardial performance by removing excessive fluid and circulating myocardial depressants.18, 19 However, very few data are available in the literatures regarding impact of CVVH dosage for AKI and 9

ACCEPTED MANUSCRIPT cardiogenic shock after cardiac surgery. Although recently published randomized studies failed to detect improvement in mortality with more intensive RRT, lack of survival benefit does not imply that low dose and high dose CRRT are completely equivalent.12-14 In fact, in the subgroup analysis, it seemed that the most critically ill patients with hemodynamic

RI PT

instability (cardiovascular SOFA score = 3 or 4) or sepsis might benefit from more intensive therapy.13, 14 In this regard, our current study recruited critically ill patients with consistent disease characteristics, onset of AKI, as well as RRT modality after cardiac surgery and

SC

disclosed significant outcome improvement after higher dose of CVVH.

Apart from survival rate, recovery of renal function and length of ICU stay were also

M AN U

postulated important indicators of clinical outcome. In contrast with previous studies, our results showed a trend toward better renal recovery in patients receiving higher dose of CVVH. The chronic dialysis rate in survivors from high dose group and low dose group was 19% and 50%, respectively. However, this difference did not reach statically significant due

TE D

to limited case number. Interestingly, our results demonstrated longer length of ICU stay and hospital stay in high dose group despite similar length of ICU stay and hospital stay between two groups of survivors. Plausibly, this discrepancy might derive from a very high mortality

EP

rate in patients receiving low dose of CVVH, especially during the first postoperative week.

AC C

It is worth pointing out that SOFA and APACHE II score are comparable between survivors and non-survivors (Table 4). This may be explained by the fact that patients in our study were comparable in basic characteristics, including the very high scores values. Hence, good discrimination between survivors and non-survivors would be dependent on post-operative parameters, including the requirement of IABP or ECMO. Furthermore, it should be taken into account whether organ function improves after better post-operative management, such as higher CVVH dosage. Usually, the trend of score was progressively declining in survivors while non-survivors had stable higher 10

ACCEPTED MANUSCRIPT score. Accordingly, serial measurement of SOFA and APACHE II score might be more useful in predicting the outcome. Furthermore, consistent with previous report,20 we observed a chronological change in the beneficial impact of intensive CVVH. The Odds ratio for low dose of CVVH reached up

RI PT

to13.4 in the first 3 days following surgery and declined gradually. This pattern implied that CRRT dosage would make a tremendous contribution to sudden onset of severe insults or inflammatory storm owing to complicated peri-operative course, while play a more limited

SC

role to the refractory illness following support care. This hypothesis was partly supported by the finding that two studies with negative effect of intensive dose on outcome had a long time

M AN U

from the ICU admission to initiation of RRT (6 and 8 days in average).13, 14 This duration is significantly later than the 1.4 days reported by a worldwide practice survey.21 It is logical to assume that early intensive RRT might remove more inflammatory mediators from body pool and decrease downstream inflammatory storm. In fact, some previous studies have shown the

TE D

survival benefit of early CRRT in severe acute renal failure after cardiac surgery.17, 22, 23 From this standpoint, another key element of intensive CRRT treatment for critically ill patients would be early initiation. This calls for multidisciplinary collaboration among cardiac

AC C

EP

surgeons, intensivists, nephrologists, and allied personnel involved in patient care.

Study Limitations

There are three limitations to this study. At first, this study was conducted at a single center, which may limit the generalization of its results to other centers. However, the mortality rate and the incidence of dialysis-requiring AKI found in our population compared very well with those from prior studies.20 Second, men were overrepresented in this study population because our center was a veteran hospital. Third, as is true in other retrospective and observational studies, we were unable to detect and analyze all possible factors that could 11

ACCEPTED MANUSCRIPT potentially affect clinical outcomes.

Conclusions Our study indicated that early intensive CVVH was associated with better in-hospital and

RI PT

long-term survival in patients developing post-operative shock in conjunction with AKI following cardiac surgery. Furthermore, the beneficial effect was more prominent in the acute phase of complicated peri-operative period. Taken together, a 'dynamic approach' to RRT

SC

dose, rather than fixed dose, might be more appropriate for critical care because critical illness is usually not a static condition. Prospective studies should be conducted to elucidate

AC C

EP

TE D

M AN U

which mechanisms are associated with the outcome improvement of intensive CRRT.

12

ACCEPTED MANUSCRIPT

Disclosure:

RI PT

Authors have nothing to disclose with regard to commercial support.

Authors' Contributions: Li SY, Yang WC and Chuang CL provided study data, Li SY analyzed the data and wrote the manuscript, Chuang CL edited and reviewed the manuscript.

SC

Chuang CL is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data

AC C

EP

TE D

M AN U

analysis.

13

ACCEPTED MANUSCRIPT

References 1.

Vermeulen Windsant IC, Hanssen SJ, Buurman WA, Jacobs MJ. Cardiovascular surgery and organ damage: time to reconsider the role of hemolysis. J Thorac Cardiovasc Surg.

2.

RI PT

2011; 142: 1-11

Ostermann ME, Taube D, Morgan CJ, Evans TW. Acute renal failure following

3.

SC

cardiopulmonary bypass: a changing picture. Intensive Care Med. 2000; 26: 565-71.

Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP, et al. Acute

4.

M AN U

renal failure following cardiac surgery. Nephrol Dial Transplant. 1999; 14: 1158-62.

Thakar CV, Liangos O, Yared JP, Nelson D, Piedmonte MR, Hariachar S, et al. ARF after open-heart surgery: Influence of gender and race. Am J Kidney Dis. 2003; 41: 742-51.

Zanardo G, Michielon P, Paccagnella A, Rosi P, Calo M, Salandin V, et al. Acute renal

TE D

5.

failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main

6.

EP

risk factors. J Thorac Cardiovasc Surg. 1994; 107: 1489-95. Cruz DN, Ronco C, Katz N. Neutrophil gelatinase–associated lipocalin: A promising

AC C

biomarker for detecting cardiac surgery–associated acute kidney injury. J Thorac Cardiovasc Surg. 2012; 76: 213-20.

7.

Bellomo R, Kellum JA, Gandhi CR, Pinsky MR, Ondulik B. The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia. Am J Respir Crit Care Med. 2000; 161: 1429-36.

8.

Gomez A, Wang R, Unruh H, Light RB, Bose D, Chau T, et al. hemofiltration reverses left ventricular dysfunction during sepsis in dogs. Anesthesiology. 1990; 73: 671-85. 14

ACCEPTED MANUSCRIPT 9.

Grootendorst AF, van Bommel EF, van der Hoven B, van Leengoed LA, van Osta AL. High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig. Intensive Care Med. 1992; 18: 235-40.

10. Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, et al. Effects of

RI PT

different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000; 356: 26-30.

11. Saudan P, Niederberger M, De Seigneux S, Romand J, Pugin J, Perneger T, et al.

acute renal failure. Kidney Int. 2006; 70: 1312-7.

SC

Adding a dialysis dose to continuous hemofiltration increases survival in patients with

M AN U

12. Tolwani AJ, Campbell RC, Stofan BS, Lai KR, Oster RA, Wille KM. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008; 19: 1233-8.

13. Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, et al.

Med. 2008; 359: 7-20.

TE D

Intensity of renal support in critically ill patients with acute kidney injury. N Engl J

14. Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al. Intensity of continuous

EP

renal-replacement therapy in critically ill patients. N Engl J Med. 2009; 361: 1627-38.

AC C

15. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16: 31-41. 16. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Critl Care Med. 1992; 20: 864-74. 17. Elahi M, Asopa S, Pflueger A, Hakim N, Matata B. Acute kidney injury following cardiac surgery: impact of early versus late haemofiltration on morbidity and mortality. Eur J Cardiothorac Surg. 2009; 35: 854-63. 15

ACCEPTED MANUSCRIPT 18. Caprioli R, Favilla G, Palmarini D, Comite C, Gemignani R, Rindi P, et al. Automatic continuous venovenous hemodiafiltration in cardiosurgical patients. ASAIO J. 1993; 39: M606-8. 19. Blake P, Hasegawa Y, Khosla MC, Fouad-Tarazi F, Sakura N, Paganini EP. Isolation of

RI PT

"myocardial depressant factor(s)" from the ultrafiltrate of heart failure patients with acute renal failure. ASAIO J. 1996; 42: M911-5.

20. Vidal S, Richebe P, Barandon L, Calderon J, Tafer N, Pouquet O, et al. Evaluation of

SC

continuous veno-venous hemofiltration for the treatment of cardiogenic shock in conjunction with acute renal failure after cardiac surgery. Eur J Cardiothorac Surg.

M AN U

2009; 36: 572-9.

21. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005; 294: 813-8.

TE D

22. Bent P, Tan HK, Bellomo R, Buckmaster J, Doolan L, Hart G, et al. Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery. Ann Thorac Surg. 2001; 71: 832-7.

EP

23. Luckraz H, Gravenor MB, George R, Taylor S, Williams A, Ashraf S, et al. Long and

AC C

short-term outcomes in patients requiring continuous renal replacement therapy post cardiopulmonary bypass. Eur J Cardiothorac Surg. 2005; 27: 906-9.

16

ACCEPTED MANUSCRIPT

Figure Legends Figure 1. Trial profile Figure 2. Numbers of cardiac surgery in Taipei Veterans General Hospital by period

AC C

EP

TE D

M AN U

SC

RI PT

Figure 3. Kaplan-Meier analysis of cumulative survival curves in two groups

17

ACCEPTED MANUSCRIPT Table 1. Baseline characteristics Variables

Low dose group (n = 45)

High dose group (n = 97)

p

Preoperative parameters Age (years) Male gender, % (n) Diabetes, % (n) Body weight (kg) LVEF (%) Hemoglobin (g/L) Albumin (g/L) BUN (mmol/L) Creatinine (mmol/L) eGFR (ml/min/1.73 m2)

69.1±14.0 75.6% (n = 34) 33.3% (n = 15) 63.3±11.3 43±14 120±25 37±5 12.7±7.5 238.7±176.8 32.0 (15.0~48.5)

Operation related parameters Urgent operation, % (n) CABG, % (n) Valve surgery, % (n) Aortic aneurysm repair, % (n) Combined procedures, % (n) ACT (min) CPB time (min)

53.3% (n = 24) 55.6 % (n = 25) 31.1% (n = 14) 20.0% (n = 9) 17.8% (n = 8) 89 (58~130) 160 (128~241)

48.5% (n = 47) 49.4% (n = 48) 35.1% (n =34) 15.4% (n = 15) 25.7% (n = 25) 93 (62~135) 156 (117~275)

0.212 0.589 0.706 0.476 0.394 0.473 0.978

18.1±3.6 4 (2~8) 11.5 ± 2.4 28.6 ± 14.2 81.1±22.7 7.3 (4.9~10.0) 0.3 (0.17~0.40) 46.7% (n = 21) 35.5% (n = 16) 100.0% (n = 45) 15.8 ± 6.7

45.2±7.9 12 (5~20) 12.3 ± 2.2 22.8 ± 10.2 81.4±32.6 7.5 (4.7~11.8) 0.28 (0.12~0.36) 41.2% (n = 40) 30.9% (n = 30) 100.0% (n = 97) 17.3 ± 7.3

52.1±20.4 16.7±2.3 27.5±5.8 42.1 ± 18.2

48.9±20.8 16.3±2.6 28.1±4.7 45.3 ± 19.4