Incidence and Risk Factors of Acute Kidney Injury After Thoracic Aortic Surgery for Acute Dissection

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1 ADULT CARDIAC Incidence and Risk Factors of Acute Kidney Injury After Thoracic Aortic Surgery for Acute Dissection Go Un Roh, MD, Jong Wha Lee, MD, Sang Beom Nam, MD, Jonghoon Lee, MD, Jong-rim Choi, MD, and Yon Hee Shim, MD, PhD Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Background. Previous studies have reported a high incidence of acute kidney injury (AKI) after thoracic aortic surgery in heterogeneous patient cohorts, including various aortic diseases and the use of deep hypothermic circulatory arrest. Moderate hypothermia with cerebral perfusion makes deep hypothermia nonessential, but can make end organs susceptible to ischemia during circulatory arrest. We investigated the incidence and risk factors of AKI after thoracic aortic surgery with and without moderate hypothermic circulatory arrest for acute dissection. Methods. We reviewed the medical records of 98 patients undergoing graft replacement of the thoracic aorta for acute dissection between 2008 and 2011 at a university hospital. Acute kidney injury was defined by RIFLE criteria, which is based on serum creatinine or glomerular filtration rate. Results. The mean age was years. The surgical procedures, 96% of which were emergencies, involved the ascending aorta (67%), aortic arch (41%), descending aorta (41%), and aortic valve (5%). Moderate hypothermic circulatory arrest was performed in 75%. The overall incidence of AKI was 54%, and 11% of 98 patients required renal replacement therapy. Thirty-day mortality increased with AKI severity (p 0.002). Independent risk factors for AKI were long cardiopulmonary bypass duration (>180 minutes; odds ratio, 7.50; p 0.008) and preoperative serum creatinine level (odds ratio, 8.43; p 0.016). Conclusions. Acute kidney injury was common after thoracic aortic surgery for acute dissection with or without moderate hypothermic circulatory arrest and worsened 30-day mortality. Prolonged cardiopulmonary bypass and increased preoperative serum creatinine were independent risk factors for AKI, but moderate hypothermic circulatory arrest was not. (Ann Thorac Surg 2012;94:766 71) 2012 by The Society of Thoracic Surgeons Acute kidney injury (AKI) after cardiothoracic surgery is common and increases mortality [1 3]. The overall incidence of AKI after aortic surgery has been reported to be high compared with other cardiac surgeries [2, 4, 5]. Even though mild to moderate degrees of AKI are common, 2% to 8% of the patients after aortic surgery require renal replacement therapy (RRT) [6 9], which is associated with elevated short-term mortality of up to 64% [6, 7, 10]. Acute kidney injury also affects long-term mortality, even for patients with partial and complete recovery [2]. The incidence of AKI after thoracic aortic surgery ranges from 18% to 55% according to the definition of AKI and aortic pathology [7, 9, 11]. RIFLE criteria, developed by the Acute Dialysis Quality Initiative group to stratify AKI into three stages, have been validated in patients undergoing a variety of cardiothoracic surgeries [4, 8, 9] and enable comparison between studies in various cohorts. Acute dissection of the thoracic aorta is associated with a significantly increased risk of AKI Accepted for publication April 16, Address correspondence to Dr Shim, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul , Republic of Korea; tren125@yuhs.ac. owing to its clinical presentation, which necessitates emergency operation and organ malperfusion [12]. Therefore, the percentage of patients with acute dissection included in a study may affect the incidence of AKI. However, there are few data on the incidence of AKI in a homogeneous population of patients with acute aortic dissection. In addition to preoperative risk factors, thoracic aortic surgery itself is one of the independent risk factors for AKI because of the complexity of the procedures including circulatory arrest [8]. Deep hypothermia during circulatory arrest renders the brain resistant to ischemia, but also provokes serious side effects, such as coagulopathy and organ dysfunction. Selective cerebral perfusion makes deep hypothermia nonessential for brain protection. Moderate hypothermia, however, makes organs vulnerable to ischemia during circulatory arrest, even if organs other than the brain are able to tolerate it. Many previous studies on postoperative AKI have enrolled patients with deep hypothermic circulatory arrest, and there is little data regarding AKI after moderate hypothermic circulatory arrest [13]. Using the RIFLE criteria, this retrospective study was designed to evaluate the incidence and risk factors of AKI after graft replacement of the thoracic aorta with and without moderate hypothermic circulatory arrest for acute dissection by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 Ann Thorac Surg ROH ET AL 2012;94: AKI AFTER THORACIC AORTIC SURGERY Patients and Methods After institutional review board approval (approval no, ), we reviewed electronic medical records and laboratory results of all patients who underwent thoracic aortic surgery with cardiopulmonary bypass (CPB) as a result of acute dissection at Gangnam Severance Hospital between March 2008 and April The need for informed consent was waived for this study. Patients who were on RRT before surgery were excluded because of the difficulty in measuring the progression of renal dysfunction. Patients who died during or within 24 hours after surgery were also excluded because their mortality was not associated with renal dysfunction and the data were inappropriate for the evaluation of postoperative renal dysfunction. If multiple operations were performed during this period, only the data from the first operation were included. If there was more than one result for a given variable, the worst value was taken. Demographic and perioperative variables known to possibly be related to postoperative renal dysfunction were included. Demographic variables included age, sex, body mass index, previous medical history (hypertension, diabetes, cerebrovascular disease, myocardial infarction, cardiac operation, chronic lung disease, and peripheral vascular disease), and surgical status (emergency or elective, history of causative trauma). Operation-related variables were the specific surgical procedure performed, the duration of CPB and aortic cross-clamping, and the use and duration of moderate hypothermic circulatory arrest. Laboratory variables included preoperative hemoglobin and serum creatinine (scr) level before and after surgery up to postoperative day 7. Perioperative hemodynamic variables including mean arterial pressure and cardiac index at admission, during the operation, and at the time of intensive care unit (ICU) admission were also analyzed. Postoperative variables included reoperation, packed red blood cell transfusion in the ICU, duration of mechanical ventilation, ICU stay, initiation of RRT, and 30-day mortality. Acute kidney injury was defined according to the RIFLE criteria [9, 14]. The RIFLE criteria (Table 1) classify AKI by severity based on the maximal change in serum creatinine level and glomerular filtration rate until postoperative day 7 compared with preoperative baseline values. It is also defined by urine output; however, urine output was not used in this study because retrospectively collected data have the potential to be inaccurate. The Table 1. RIFLE Criteria for Acute Kidney Injury [14] 767 variables were analyzed according to the severity of AKI to identify the risk factors for AKI after thoracic aortic surgery with CPB for acute dissection. Operative Procedures Anesthesia was induced with midazolam, sufentanil, and rocuronium and maintained with sevoflurane, remifentanil, and rocuronium. Standard monitoring with transcutaneous cerebral oximetry and transesophageal echocardiography was applied in all cases. Invasive monitoring included pulmonary artery catheterization and cannulation of the radial artery, femoral artery, or both. All operations were initiated with right axillary arterial cannulation. The femoral artery and right atrial appendage were cannulated for CPB, and CPB was performed at 2.2 to 2.5 L min 1 m 2. If circulatory arrest was required for surgical conditions, cooling was performed to target a rectal temperature of 28 C. In cases in which circulatory arrest was planned, aortic cross-clamping was not applied until distal reconstruction of aorta was completed. Once the distal reconstruction was complete, the aortic graft was clamped proximally. During circulatory arrest, antegrade cerebral perfusion through the right axillary artery with clamping of the innominate and left common carotid arteries was performed to maintain cerebral oximetry saturation within 10% change of baseline values. If cerebral oximetry saturation decreased 10% or greater below baseline values, especially on the left, cerebral perfusion through the left common carotid artery was added. Intermittent lower body perfusion was initiated through the femoral artery after 15 minutes of circulatory arrest and performed for 1 minute every 15 minutes until distal reconstruction of the aorta was complete. Statistical Analysis Values are expressed as mean standard deviation or the number of patients (%), as appropriate. One-way analysis of variance and Fisher s exact test were used to compare continuous and categorical variables, respectively, among RIFLE classes. Logistic regression models were used to identify univariate and multivariate predictors for AKI. Univariate logistic regression analysis was used first to identify possible risk factors for AKI, and the multivariate model included variables that were significant on univariate analysis. For all analyses, a probability value of less than 0.05 was considered statistically significant. We used SAS 9.1 software (SAS Institute, Inc, Cary, NC) to analyze the data. ADULT CARDIAC Category Compared With Baseline Serum Creatinine (scr) Increase GFR Decrease Risk 1.5-fold 25% Injury 2-fold 50% Failure 3-fold or baseline scr 4 mg/ dl or acute rise 0.5 mg/dl 75% GFR glomerular filtration rate. Results A total of 98 patients were included after the exclusion of 12 patients (1 incomplete data, 4 preoperative RRT, 7 deaths during or within 48 hours after surgery). The median age was 55 years (range, 22 to 80 years), and 71 (72%) of these patients were men. Medical histories included hypertension (54%), diabetes (3%), cerebrovascular disease (4%), previous myocardial infarction (1%),

3 ADULT CARDIAC 768 ROH ET AL Ann Thorac Surg AKI AFTER THORACIC AORTIC SURGERY 2012;94: Table 2. Demographic and Clinical Characteristics Categorized by RIFLE Classification (n 98) Variable No AKI AKI Risk Injury Failure p Value a p Value b Patient population 45 (46%) 30 (31%) 18 (18%) 5 (5%) Demographics Age (y) Sex (male) 32 (33%) 19 (19%) 15 (15%) 5 (5%) Body mass index (kg/m 2 ) Medical history Hypertension 20 (20%) 20 (20%) 10 (10%) 3 (3%) Diabetes 1 (1%) 2 (2%) 0 (0%) 0 (0%) Cerebrovascular disease 2 (2%) 1 (1%) 1 (1%) 0 (1%) 1 1 Previous MI 0 (0%) 0 (0%) 1 (1%) 0 (0%) Previous cardiac operation 2 (2%) 3 (3%) 0 (0%) 0 (0%) Preoperative laboratory data Serum creatinine (mg/dl) Hemoglobin (g/dl) prbc transfusion in ICU Perioperative hemodynamic data MAP at admission CI at ICU admission Reoperation 1 (1%) 1 (1%) 1 (1%) 3 (3%) a Comparing patients without AKI to all patients with AKI. b Comparing patients within four subgroups (no AKI, risk, injury, and failure). AKI acute kidney injury; CI cardiac index; ICU intensive care unit; MAP mean arterial pressure; MI myocardial infarction; prbc packed red blood cell. and previous cardiac operation (5%). No patient had chronic lung disease or peripheral vascular disease diagnosed before surgery. Surgical procedures included the aortic root or ascending aorta in 66 patients (67%), the aortic arch in 40 patients (41%), the descending thoracic aorta in 40 patients (41%), and aortic valve in 4 patients (5%). Ninety-four patients (96%) underwent emergency operations, including three trauma cases. Six patients (6%) underwent a second operation. The mean CPB duration was minutes, and 56 patients (57%) underwent CPB longer than 180 minutes. The mean duration of aortic cross-clamping was minutes, and 55 patients (56%) had aortic cross-clamping longer than 75 minutes. Moderate hypothermic circulatory arrest was applied in 73 patients (74%) for a mean duration of minutes. The duration of circulatory arrest was longer than 55 minutes in 34 patients (35%). With respect to preoperative renal function, preoperative scr was mg/dl, and 20 patients (20%) had an scr level greater than 1.2 mg/dl. Among the 98 patients, 53 patients (54%) exhibited AKI, including 30 patients (31%) in RIFLE class R, 18 patients (18%) in class I, and 5 patients (5.%) in class F. Eleven patients (11%) required RRT. Patient characteristics and perioperative variables according to the RIFLE class are presented in Tables 2 and 3. There were significant differences between patients with no AKI and patients with AKI for any RIFLE class in terms of preoperative scr level, cardiac index at ICU admission, and CPB duration. Within the four subgroups, there were significant differences in scr, cardiac index at ICU admission, aortic arch operation, CPB duration, and the use of moderate hypothermic circulatory arrest. High RIFLE class was associated with poor outcome, including the requirement for RRT and 30-day mortality. Thirty-day mortality was 27% (3 of 11 patients) in the patients undergoing RRT and 3% (3 of 87 patients) in patients who did not receive RRT. Table 4 shows the results of univariate analysis of risk factors for AKI within all RIFLE classes. In the multivariate analysis, CPB duration longer than 180 minutes and preoperative scr level were identified as independent risk factors for postoperative AKI (Table 5). Preoperative scr level (odds ratio, infinity; 95% confidence interval, 3.49 to infinity; p ) and transfusion of packed red blood cell in the ICU (odds ratio, 2.92; 95% confidence interval, 1.32 to 6.46; p ) were identified as risk factors for RRT in the multivariate analysis. Comment This retrospective study determined the incidence and risk factors for AKI, defined by RIFLE criteria, after graft replacement of the thoracic aorta with and without moderate hypothermic circulatory arrest for acute dissection. Of 98 patients, 53 patients (54%) experienced AKI of any classification and 11 patients (11%) required RRT. Multivariate logistic regression analysis revealed that preoperative scr level and CPB duration longer than 180 minutes were independent risk factors for AKI, but

4 Ann Thorac Surg ROH ET AL ;94: AKI AFTER THORACIC AORTIC SURGERY Table 3. Operative Details and Short-Term Outcomes Categorized by RIFLE Classification (n 98) AKI Variable No AKI Risk Injury Failure p Value a p Value b ADULT CARDIAC Operative procedures Ascending aorta 31 (32%) 22 (22%) 12 (12%) 1 (1%) Aortic arch 17 (17%) 18 (18%) 2 (2%) 3 (3%) Descending aorta 17 (17%) 13 (13%) 7 (7%) 3 (3%) Aortic valve 3 (3%) 2 (2%) 1 (1%) 0 (0%) 1 1 CPB-related profiles CPB duration (min) ACC duration (min) Use of MHCA 29 (30%) 23 (23%) 17 (17%) 4 (4%) Duration of MHCA (min) Complications and short-term outcomes Renal replacement therapy 0 (0%) 1 (1%) 7 (7%) 3 (3%) Ventilator care (hours) ICU stay (days) day-mortality 1 (1%) 0 (0%) 3 (3%) 2 (2%) a Comparing patients without AKI to all patients with AKI. b Comparing patients within four subgroups (no AKI, risk, injury, and failure). ACC aorta cross-clamping; AKI acute kidney injury; CPB cardiopulmonary bypass; ICU intensive care unit; MHCA moderate hypothermic circulatory arrest. moderate hypothermic circulatory arrest was not. Thirtyday mortality increased with increasing AKI severity. The incidence of postoperative AKI in our study was comparable to that found in two previous studies that used RIFLE criteria [2, 9]. Hobson and colleagues [2] reported an incidence of AKI after aortic surgery of 55%, which is similar to our results. Although there were little data regarding the patients characteristics in that study, the study cohort was presumably heterogeneous in terms of diagnosis and surgical status [2]. Another study reported an AKI incidence of 48% among 267 patients after aortic arch surgery with deep hypothermic circulatory arrest, including 36% of emergency operations and 36% of acute dissections [9]. However, a recent report by Englberger and associates [7] showed a relatively low incidence of AKI (17.7%) and RRT (2.1%) in 851 patients undergoing elective thoracic aortic surgery with and without deep hypothermic circulatory arrest. In that study, both emergency surgery and acute dissection, which are known independent risk factors for postoperative AKI [12], were excluded. Considering the fact that our patient cohort underwent emergent thoracic aortic surgery as a result of acute dissection, the incidence of AKI (54%) is not surprising. Thirty-day mortality in patients with AKI was 9% (5 of 53 patients) and increased with each stratification of RIFLE criteria (R, 0%; I, 17%; F, 40%); however, the overall 30-day mortality was 6% (6 of 98 patients), which is low compared with values reported in two previous studies of thoracic aortic surgery (11.1% and 13.5%, respectively) [9, 11]. Previous studies have documented that AKI after cardiothoracic surgery, even in its mild form, worsens short-term outcomes such as 30- or 90-day mortality, morbidity, and cost [4, 8, 15 18]. Moreover, AKI increases 10-year mortality regardless of renal recovery at discharge [2]. Therefore, identifying risk factors and preventing postoperative AKI is an essential part of improving outcomes. The logistic regression model identified preoperative scr level as an independent risk factor for AKI and RRT, which is consistent with previous reports [9, 10, 16, 17]. The present study revealed a linear relationship between preoperative scr and AKI development. An admission scr that was greater than scr predicted by the Modification of Diet in Renal Disease formula was found to be a risk factor for AKI in aortic arch surgery [9]. Bove and coworkers [10] showed that preoperative renal impairment defined as an scr greater than 1.4 mg/dl is associated with moderate to severe AKI. In addition to scr level, a long CPB duration ( 180 minutes) was identified as another risk factor for AKI, as has been demonstrated previously [7 10]. However, another study reported that CPB time does not affect the development of AKI [6]. These controversies might be attributed to confounding factors in heterogeneous patient cohorts. In accordance with other studies, our findings demonstrated that moderate hypothermia for circulatory arrest was not associated with AKI [13, 19]. Moderate hypothermic circulatory arrest in our study was used in 73 patients (75%). The duration of circulatory arrest and target rectal temperature were minutes and 28 C, respectively. Urbanski and colleagues [13] reported that moderate hypothermia is safe and effective for organ protection during circulatory arrest in nonemergent aortic arch surgery with low mortality and morbidity. Although the incidence of AKI was unknown in that study, the incidence of RRT was much lower (1.4%) than it was in our study (11%, 11 of 98 patients), probably owing to the

5 ADULT CARDIAC 770 ROH ET AL Ann Thorac Surg AKI AFTER THORACIC AORTIC SURGERY 2012;94: exclusion of acute dissections. Another study that included 412 cases undergoing aortic arch surgery, 24% of which were emergency surgeries, reported a higher incidence of AKI requiring RRT (4.6%), and moderate hypothermic circulatory arrest was not an independent risk factor for RRT and mortality [19]. Experimental research also demonstrated the safety of moderate hypothermia for end-organ protection during circulatory arrest [20, 21]. Several variables associated with AKI in the univariate analysis were not significant in the multivariate analysis. Although a more than twofold increased risk was detected in the univariate analysis, aortic arch operation and long duration of circulatory arrest ( 55 minutes) were not independent risk factors, similar to those of other studies [9, 16]. In our study, age was not associated with AKI, which is in contrast to other studies [7, 8, 10, 22]. This discrepancy might be attributed to relatively younger age of study cohorts than that of previous reports. We found that 11 patients (11%) required postoperative RRT, and 3 of them (27%) died. The incidence of RRT Table 4. Univariate Analysis of Risk Factors for Acute Kidney Injury Within All RIFLE Classes Variable Odds Ratio 95% CI p Value Demographic data Age Male sex Body mass index Medical history Diabetes Hypertension Cerebrovascular disease Preoperative condition Mean arterial pressure at admission Serum creatinine Serum hemoglobin Operative details Aortic arch operation Cardiopulmonary bypass duration Cardiopulmonary bypass duration 180 min Aorta cross-clamp time Aorta cross-clamp time min Use of MHCA Duration of MHCA min Postoperative condition Cardiac index at ICU admission Transfusion of packed red blood cells in ICU CI confidence interval; ICU intensive care unit; MHCA moderate hypothermic circulatory arrest. Table 5. Multivariate Analysis of Risk Factors for Acute Kidney Injury Within All RIFLE Classes Variable Odds Ratio 95% CI p Value Cardiopulmonary bypass duration 180 min Preoperative serum creatinine level CI confidence interval. was higher in our study than in other studies on thoracic aortic surgery, ranging from 2% to 8% [7, 9, 11]. However, 30-day mortality in other studies was up to twice that observed in this study [6, 9, 10]. Our findings suggest that prompt application of RRT may improve clinical outcomes. However, larger studies are needed to confirm the effect of RRT on outcomes. Elevated scr levels before surgery and increased transfusion of red blood cells in the ICU were identified as risk factors for RRT, similar to the study in aortic arch surgery with deep hypothermic arrest [9]. This study had some limitations. First of all, the relatively small number of patients might have resulted in insufficient statistical power for this retrospective study. However, it did have a homogeneous population. There are little data on postoperative AKI collected from such a homogeneous group of patients undergoing thoracic aortic surgery for acute dissection with moderate hypothermic circulatory arrest. Second, we only used the change in scr level for RIFLE classification because exact data regarding urine output were not available for this retrospective study. This might have resulted in an underestimation of the incidence of AKI. In conclusion, AKI after graft replacement of the thoracic aorta for acute dissection with or without moderate hypothermic circulatory arrest was common and worsened short-term mortality. The elevated preoperative scr level was an independent risk factor for postoperative AKI, and reducing CPB time to less than 180 minutes could reduce AKI. Furthermore, from the perspective of renal impairment, moderate hypothermia was demonstrated to be safe for circulatory arrest to repair thoracic aortic dissection. Special thanks to Hyunsun Lim, PhD, for expert statistical analysis. References Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998;104: Hobson CE, Yavas S, Segal MS, et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 2009;119: Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A. Acute kidney injury: a relevant complication after cardiac surgery. Ann Thorac Surg 2011;92:

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