Eur J Cardiothorac Surg 2007;32:286-290. doi:10.1016/j.ejcts.2007.04.032
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Mild and moderate renal dysfunction: impact on short-term outcome
Caterina Simona,*,
Remo Lucianib,
Fabio Capuanoa,
Antonio Micelia,
Antonino Roscitanoa,
Euclide Tonellia,
Riccardo Sinatraa
a Department of Cardiac Surgery, St. Andrea Hospital, University of Rome "La Sapienza", Italy
b Department of Nephrology, St. Andrea Hospital, University of Rome "La Sapienza", Italy
Received 16 February 2007;
received in revised form 23 April 2007;
accepted 23 April 2007.
* Corresponding author. Address: Department of Cardiothoracic Surgery, St. Andrea Hospital, Rome 00189, Italy. Tel.: +39 0633775310; fax: +39 0633775483. (Email: caterinasimon{at}hotmail.com).
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Abstract
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Background: Preoperative renal dysfunction is an important risk factor in cardiac surgery. Thus, the association between creatinine clearance (ClCr) and mechanical ventilation time and ICU length of stay, independent of other established preoperative risk indicators, was analyzed. Methods: In our study, 156 consecutive patients underwent open-heart surgery at the Department of Cardiac Surgery, University Hospital St. Andrea, Rome, and were prospectively studied for the relation between the ClCr, using the formula develop by Cockroft and Gault, and ICU length of stay and mechanical ventilation time. The 156 patients were divided into two groups in relation of ClCr: group A (n
= 78) ClCr < 70 ml/min; group B (n
= 78) ClCr > 70 ml/min. Results: In multivariate analysis, ICU length of stay was influenced by ClCr < 70 ml/min, hypertension and COPD. ICU stay was median 48 h (range 24–72) in group A versus 24 h (range 20.7–44) in group B (p
= 0.0001). In multivariate analysis, only ClCr < 70 ml/min and EuroScore were associated with increasing VAM. VAM was median 8 h (range 5.7–13.2) in group A versus 6 h (range 4–10) in group B (p
= 0.001). Conclusions: Our study demonstrates that after short-term outcome follow-up, preoperative mild renal dysfunction is an independent predictor of ICU length of stay and mechanical ventilation time.
Key Words: Cardiac • Coronary artery bypass grafts • On-pump
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1. Introduction
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Postoperative acute renal failure (ARF) is a well-known complication of cardiac surgery [1]. The incidence varies between 5 and 31% [2–9]. ARF requiring dialysis, after open-heart surgery, develops in 1–5% of patients and is strongly associated with postoperative morbidity and mortality [10]. The indications for dialysis include uremia, volume overload, or biochemical abnormalities and are based on clinical judgment. The overall mortality after open-heart surgery ranges between 2 and 8% [11]. The incidence of ARF is dependent on the particular type of CPB surgery. Typical coronary artery bypass grafting has the lowest incidence of ARF 2.5% and ARF-D 1%, followed by valvular surgery with an incidence of ARF 4.6% and of ARF-D 3.3% [12]. The risk for mortality, however, increases exponentially among patients who develop postoperative ARF, with mortality rates in excess of 60% [2]. Many reports have described the outcome of coronary artery bypass surgery in patients with end-stage renal disease [7,9]. However, there has been limited number of reports about outcome of patients with mild to moderate renal failure not on dialysis [3,13–17]. ARF is linked to multiple postoperative complications leading to prolonged hospitalization and increased costs. The use of continuous renal replacement therapy (CRRT) is a rare but devastating complication of cardiac surgery. Its incidence is reported to be from 2 to 15% with an associated mortality of 40–80% [15]. In patients with ARF-D, the incidence of serious infections, including sepsis, was 58.5% as compared with 3.3% in all patients who underwent CPB. While plasma creatinine level is a highly specific marker of renal impairment, it may be insensitive to mild and moderate degrees of renal dysfunction because it depends on many non-renal factors including muscle mass, gender and metabolism [18–22]. So we decided to estimate renal dysfunction with ClCr using the formula develop by Cockroft and Gault [16]. The aim of this study was to investigate the impact of mild and moderate renal dysfunction on the short-term outcome of patient undergoing open-heart surgery at our institution.
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2. Material and methods
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Seventy-eight consecutive patients undergoing adult cardiac operation with ClCr less than 70 ml/min (group A) and 78 consecutive patients with ClCr more than 70 ml/min (group B) between January 2005 and June 2005 were studied prospectively. The mean age was 70.2 ± 8.3 group A versus 60.9 ± 9.7 group B. The data of these patients were prospectively collected in a dedicated database. The exclusion criteria were complicated perioperative and postoperative courses: in hospital death, IABP or other mechanical assist device, use of massive inotropic drugs, reoperation for hemorrhage or sternal complications, respiratory failure. Preoperative data were collected during the patient's admission as a part of routine clinical practice on the variables shown in Table 1
. The ClCr was estimated using the equations developed by Cockroft and Gault: creatinine clearance = (140 – age) x weight (kg)/(serum creatinine x 72 [x0.85 for women] [16]. Although no single normal value of ClCr is applicable to all patients, 70 ml/min is commonly accepted as the lowest normal value for all ages and both genders, in accordance with the U.S. National Kidney Foundation guidelines [23]. ARF was defined as patients with a postoperative serum creatinine level greater than 2.0 g/dl, an ‘ARF score’ > 6 and patients requiring dialysis therapy or hemofiltration before hospital discharge. We used the ‘ARF score’ developed by the Cleveland clinic Foundation [11]; this score is formed by four risk categories of increasing severity (score 0–2, 3–5, 6–8 and 9–13) to develop ARF after open-heart surgery. Operative mortality was defined as death within 30 days of the operation or during the same hospitalization. Low cardiac output syndrome (LCOS) was defined as the need for postoperative IABP and/or inotropic support, for any length of time, in the intensive care unit. Radial and pulmonary arterial catheters were introduced under local anesthesia. After standard anesthesia, a median sternotomy was performed followed by routine aortic and right atrial cannulation or bicaval cannulation in relationship of the kind of operation. Standard CPB technique was carried out using membrane oxygenators and moderate systemic hypothermia (32 °C). Mean arterial blood pressure was kept between 50 and 70 mmHg. Myocardial protection was achieved by antegrade mild hypothermia blood cardioplegia that was repeated every 20 min. Heparin was administered 3.0 mg/kg. Heparin was neutralized with protamine, in a ratio of 1:3, within 10 min after the end of CPB. Patients with coronary artery disease were 48 (61%) in group A versus 60 (77%) in group B. Other cardiac diseases included mitral valve disease in 3 (4%) patients in group A versus 3 (4%) in group B, aortic valve disease in 14 (18%) patients in group A versus 6 (8%) in group B, double valve disease in 4 (5%) patients in group A versus 5 (6%) in group B, other cardiac diseases in 9 (11%) in group A versus 4 (5%) in group B (Table 2
). During CPB, the hematocrit level was maintained between 0.20 and 0.25, pump flow rates between 2.0 and 2.5 l/(min m2) and mean arterial pressure about 65 mmHg. Creatinine, hemoglobin, blood gases and electrolytes were measured from arterial blood samples using standard laboratory techniques. Creatinine clearance was calculated following the Cockroft and Gault formula.
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3. Statistical analysis
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Continuous data with normal distribution are given as mean ± standard deviation, otherwise as median with range interquartiles. The normality of data distribution was tested by the Kolmogorov–Smirnov test, and the data were log transformed when abnormal. The data were analyzed using the following statistical methods where appropriate: Chi-square test, Fisher's exact test, Student's t-test. The variables with a p value less than 0.10 at univariate analysis were entered in a stepwise multiple linear regression analysis to identify the independent predictors of VAM and ICU stay. A p-value less than 0.05 was considered significant. The data were statistically analyzed using SPSS 13.0 software (SPSS Inc., Chicago, IL).
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4. Results
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One hundred and fifty-six patients who underwent cardiac surgery in St. Andrea hospital in 2005 with mild and moderate renal dysfunction were divided into two groups. Group A (n
= 78) <70 ml/min ClCr and group B (n
= 78) >70 ml/min ClCr. The mean creatinine (±SD) was 1.3 ± 0.5 in group A versus 0.9 ± 0.2 in group B. Twenty-eight patients were females (36%) in group A versus 11 (14%) in group B (p
= 0.003). Mean age was 70.2 ± 8.3 in group A versus 60.9 ± 9.7 in group B (p
= 0.0001). In univariate analysis, worsening renal function (ClCr < 70 ml/min) (p
= 0.0001) as well as EuroScore (p
= 0.002) and ARF score (p
= 0.001) was associated with increasing VAM (Table 3
). In multiple linear regression analysis, only ClCr < 70 ml/min (p
= 0.02) and EuroScore (p
= 0.023) were associated with increasing VAM (Table 3). In univariate analysis, ICU length of stay was associated with gender (p
= 0.002), ClCr < 70 ml/min (p
= 0.001), EuroScore (p
= 0.002), ARF score (p
= 0.0001) and hypertension (p
= 0.032) (Table 4
). In multiple linear regression analysis, ICU length of stay was influenced by ClCr < 70 ml/min, hypertension (p
= 0.003), COPD (p
= 0.049) and postoperatively dialysis (p
= 0.0001) (Table 4).
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5. Comment
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Renal failure after cardiac surgery has a significant influence on postoperative morbidity and mortality. There is a complex interplay of a number of factors explaining renal failure associated with cardiac surgery. There are factors relating to occult renal ischemia caused largely by arteriosclerosis and exacerbated by perioperative reduction of cardiac output, hypotension and resultant hypoperfusion [3]. The kidneys may be damaged by exogenous nephrotoxins such as amoniglycoside antibiotics, diuretics or radiologic contrast media; and endogenous nephrotoxins such as myoglobin, free radicals or pro-inflammatory cytokines. The negative effects of CPB on renal function may be due to several factors such as non-pulsatile flow and inadequate renal perfusion. Preoperative renal risk stratification provides an opportunity to develop strategies of early diagnosis and intervention. The kidneys play a major role in the maintenance of extracellular fluid volume and peripheral vascular resistance. Baseline renal function has been consistently identified as a major predictor for postoperative renal disease. Many studies had tried to identify risk factors for adverse outcomes after cardiac surgery to help clinicians provide special care and adopt better assistance to avoid renal dysfunction. Some studies have suggested that intraoperative factors, such as CPB time and aortic cross clamp time, are important contributors to postoperative ICU length of stay and mechanical ventilation time. This was not the case in this study. In accordance with our paper are the works of Mangano et al. [9], who initially suggested impaired renal function to be an important predictor of postoperative decors and the paper of O’Connor and colleagues [20], who, after an analysis of more than 3000 patients at five centers, found that pre-existing renal failure significantly increased in-hospital mortality after CABG. The results of this study confirm our hypothesis that the association between preoperative renal dysfunction and adverse outcomes is high when ClCr, estimated by the Cockroft and Gault formula, is lower. In patients with normal plasma creatinine levels, we observed that when the ClCr was lower, the probability of ARF post cardiac surgery was higher; ClCr and not creatinine was associated with ICU length of stay and ventilation time. We obtained an inverse correlation between ClCr and short-term outcome, this we did not observe with plasma creatinine. Most previous studies [24–26] assessed the association between renal function and outcome after cardiac surgery by dichotomizing renal function, using a plasma creatinine level >1.6 mg/dl as a cut-off point to diagnose mild renal dysfunction. In summary, it is well know that independent risk factors, for the development of ARF, were increased preoperative creatinine levels, increasing age and body mass index, emergency surgery, diabetes and peripheral vascular disease; but to know renal dysfunction, creatinine clearance is the better parameter, as it is not influenced by non-renal factors including muscle mass, gender and metabolism. The identification of mild and moderate renal dysfunction as a risk factor for adverse outcomes after cardiac surgery is an important component of preoperative care. It helps clinicians provide special care and adopt better assistance to avoid renal dysfunction. The prognostic role of renal disease was also confirmed by Lassnigg et al. [1], who demonstrated that the 30-day mortality of patients who developed a 0–0.5 and >0.5-mg/dl rise in serum creatinine was 2.77- and 18.64-fold higher, respectively, than patients without a change in serum creatinine. It well know that patients with renal disease often have multiple comorbid disorders such as diabetes mellitus, coronary disease and valve disease that could influence the short-term outcome, but this was not our case when the only independent predictor was ClCr > 70 ml/min. A recently published study by Thakar and colleagues [8], which concentrates primarily on the effects of postoperative renal function on short-term outcome, demonstrated a high risk for pulmonary infections in patients with an increase in plasma creatinine level, but we had no pulmonary infection in either of our patients.
Finally, this study was performed in a single center, which may limit the generalization of its results to other center; however, the mortality and rate of postoperative dialysis requirement found in our surgical population compare very well with those from recent large multicenter trials in North America and Europe [27]. Our study shows that estimated ClCr has significant advantages over plasma creatinine level as a predictor of ICU length of stay and mechanical ventilation time after cardiac surgery. This is particularly true for patients with normal plasma creatinine levels who, for any given level of estimated ClCr, have the same ICU length of stay and mechanical ventilation time as patients with elevated plasma creatinine levels. The finding of our study suggests the need for additional evaluation of these patients in order to understand the pathophysiology of the renal impairment and the design of renal protection strategies. Based on these data, we recommend that an estimate of creatinine clearance be used as part of the process of preoperative risk stratification. Further work is required to develop models to integrate such data into existing or novel risk prediction tools. Perhaps more importantly, future studies should determine strategies that can improve the outcome of patients with renal mild and moderate renal dysfunction in this setting.
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Footnotes
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\#9734; Presented in oral communication form at the 16th World Congress of the World Society of Cardiothoracic Surgeons, Ottawa, Canada, August 17–20, 2006.
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Abstract
1. Introduction
