Acute renal failure (ARF) requiring renal replacement therapy (RRT) is a serious complication of cardiac surgery and is associated with an elevated hospital mortality [1-8]. It occurs in 2-5% of patients with mortality rates as high as 90% [4-8].
The aetiology is multifactorial and includes advanced age, pre-existing renal insufficiency, left ventricular impairment, prolonged aortic cross-clamp and cardiopulmonary bypass (CPB) [9,10]. Deleterious factors related to CPB are the systemic inflammatory response, hypoperfusion, loss of pulsatility and myocardial dysfunction [11-14].
The primary objective of this study was to assess long-term survival and quality of life in survivors after ARF and RRT in comparison with case-matched controls. The secondary objective was to evaluate the incidence of ARF with RRT after cardiac surgery, to identify perioperative risk factors for the development of this complication and analyse its impact on perioperative mortality and on length of hospital stay.
The study was carried out according to the principles of the Declaration of Helsinki. The Ethics Committee approved the study protocol. All patients gave written informed consent.
All adult patients undergoing cardiac surgery with CPB in our institution in the period January 1998-July 2003 were included in the study. Exclusion criteria were patients on preoperative dialysis and off-pump procedures. The following data were prospectively registered in a database: patient characteristics, medical history, physical findings, blood chemistry, and length of stay in intensive care unit (ICU) and hospital.
Patients who underwent RRT during their initial hospitalization and left the hospital alive were interviewed by telephone 42 ± 23 months postoperatively. The Medical Outcomes Study Short-Form (MOS-SF 20) general health survey  was administered by one of the investigators. Patients were also asked for the presence of dialysis treatment, hearing impairment (side-effects of loop diuretics), New York Heart Association Status, hospitalizations and cardiac events. The same questionnaire was administered to 42 matched controls (same intervention, age, sex, urgency, reintervention and same expected period of follow-up) who did not receive RRT.
All patients were managed according to a standardized anaesthesia protocol: premedication with morphine 0.1 mg kg−1 and scopolamine 0.25 mg intramuscularly, oral diazepam 5-10 mg 1 h before surgery. A peripheral vein and radial artery were cannulated before induction of anaesthesia. Monitoring consisted of pulse oximetry, 5-lead ECG with automated ST segment analysis, central venous pressure, capnometry and urine output. Anaesthesia was induced with fentanyl 4-7 μg kg−1 and propofol 1-2 mg kg−1 (or sufentanil 0.4-0.7 μg kg1 and midazolam 0.1-0.2 mg kg−1 for the low ejection fraction group). Orotracheal intubation was facilitated by pancuronium (0.1 mg kg−1) in both groups. Anaesthesia was maintained with propofol (2-4 mg kg−1 h−1), isoflurane (end-tidal concentration < 1 MAC) and additional doses of fentanyl up a total of 25 μg kg−1.
Pulmonary artery catheters and intra-aortic balloon pump (IABP) devices were used at the discretion of the respective anaesthesiologist and surgeon in patients with severe left ventricular dysfunction (ejection fraction < 30%), severe pulmonary hypertension or haemodynamic instability. Temperature was monitored with a bladder or rectal probe.
The initial dose of heparin was 300 IU kg−1. The target activated clotting time was greater than 480 s. Heparin was reversed with protamine sulphate at a 1: 1 ratio after decannulation. Non-pulsatile perfusion was used in all patients with the flow rate maintained between 2 and 2.8 L min−1 m2 body surface area. The perfusion circuits were primed with crystalloid solution and mannitol 18% (0.5g kg−1) to achieve a haematocrit ≥ 18% during CPB. Blood oxygen saturation and haematocrit were assessed with a co-oximeter. Alpha-stat blood gas management was used during CPB, with PaCO2 maintained at 4.7-5.3 kPa and PaO2 at 20-33 kPa.
Perioperative left ventricular dysfunction after cardiac surgery and CPB was managed by optimization of heart rate and rhythm, preload, and afterload. Inotropes were started if these manoeuvres were ineffective. Dopamine was the first choice and in the case of persisting low output syndrome epinephrine, and/or enoximone, and/or IABP device were instituted. Loop diuretics were administered early in the course of ARF to convert an oliguric to a non-oliguric state. RRT was initiated early by the attending nephrologist and intensivist. Indication for RRT included at least one of the following: oliguria (urine output <20 mL h−1); creatinine >347 μmol L−1; urea >29.8 mmol L−1. Renal support was provided by continuous veno-venous haemofiltration (Prisma CFM, Hospal Lyon, France) using high flux AN69 membranes with a membrane surface area of 0.60 m2. Vascular access was established by insertion of a double-lumen catheter (Gamcath, Gambro Intern, Sweden) into a femoral, internal jugular or sub-clavian vein. The blood pump was set to deliver 120-150 mL min−1 aiming for an ultrafiltration rate of 1.5-2L h−1 in pre- or post-dilution mode with bicarbonate buffer in the solution. Anticoagulation of the extracorporeal circuit was maintained with the lowest heparin infusion (200-1000 IU h−1) allowing good filter function. No patient had intermittent dialysis in the ICU.
Patients were grouped and compared according to the presence or not of ARF and RRT. Preoperative patient characteristics and individual risk factors, intraoperative course and operative outcomes were stored electronically and analysed by use of Epi Info 2002 software (CDC) and SAS software, version 8 (SAS Institute). Data are reported as percentage or as mean ± standard deviation (SD) or, for variables not normally distributed, as median, and 25th-75th percentile (interquartile range, IQR). Dichotomous data were compared by using two-tailed χ2 test with the Yates correction or Fisher's exact test when appropriate. Continuous measures were compared by analysis of variance (ANOVA) or the U-test when appropriate. Two-sided significance tests were used throughout. Stepwise multivariate logistic regression analysis (entry values: P < 0.05) was used to determine the independent predictors of RRT: results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Long-term survival was analysed with the use of Kaplan-Meier estimates. Data on patients who withdrew from follow-up were censored at the time of withdrawal. Incidence of RRT over the years was compared with Bonferroni's test and Student-Newman-Keuls test.
During the study period 7846 patients underwent cardiac surgery (3103 isolated coronary artery bypass graftings and 4743 valvular, aortic arch or combined procedures). ARF requiring RRT developed in 126 patients (1.6%). The yearly incidence did not vary significantly during the study period (Fig. 1).
Median time of mechanical ventilation was 240 h (IQR 108-480) in ARF-RRT patients and 10 h (IQR 8-14) in non-ARF-RRT patients (P < 0.001). Median time of hospital stay was 17 days in ARF-RRT patients (IQR 9-29) and 5 days (IQR 5-7) in non-ARF-RRT patients (P < 0.001).
Forty-two (33.3%) of the patients developing ARF-RRT left the hospital alive (Fig. 2). Twelve of them (28.6%) died during the 42 ± 23 months follow-up period while there were no deaths during the follow-up (42 ± 1 months) in the control group (P = 0.0006). Quality of life of survivors is illustrated in Table 1 together with the case-matched patients who had no RRT. Patients in the study group had a poorer functional status (New York Heart Association) and complained significantly more of deafness.
The in-hospital mortality of patients who developed ARF requiring RRT was 66.7% (84/126) compared with 1.5% (118/7720) in patients who had no need of RRT (P < 0.001). Hospital resource utilization by ARF patients was disproportionately high as shown by the fact that 1.6% of patients utilized 12.8% of ICU resources in terms of ICU stay (median 1 day, IQR 1-2 vs. median 12 days, IQR 6-26; P < 0.0001).
Perioperative variables associated with ARF-RRT development are shown in Table 2. When perioperative variables were included in a multivariate model, emergency surgery, preoperative renal impairment, need for IABP, surgical re-exploration for bleeding, previous cardiac surgery, female gender, low ejection fraction, bleeding >1000 mL, chronic obstructive pulmonary disease and age were independently associated with ARF requiring RRT as shown in Table 3.
The occurrence of postoperative complications is depicted in Table 4.
To our knowledge this is the longest follow-up (42 ± 23 months) of patients surviving RRT after cardiac surgery. Our study confirms the high in-hospital mortality in patients requiring ARF-RRT [1,2] but also demonstrates a reasonable quality of life of survivors.
Other authors have documented the poor short-term outcome of ARF-RRT patients with mortality rates, ranging from 40 to 87.5% [16-24]. However, there is a paucity of data regarding the long-term follow-up of these patients.
Only one study, by Leacche and colleagues , includes a follow-up of this high-risk population with results that differ from ours. In their study, the postoperative mortality (within 30 days or during the same hospitalization) was 72%, overall 1-year survival was 10%, and 64% of the survivors required permanent dialysis. No patient with a single arterial pH reading <7.25, a major gastrointestinal complication, or the requirement for a ventricular assist device before initiation of artificial renal support survived to hospital discharge. The authors concluded that their results suggest a need to re-evaluate the legitimate value of RRT in patients who are either acidotic, require a ventricular assist device, or experience major gastrointestinal complications or stroke, since RRT seems to be futile in most of these patients. In contrast to Leacche and colleagues, we did not exclude patients with preoperative chronic renal impairment and thus probably studied a higher risk population. We found a higher incidence of ARF-RRT (1.6% vs. 0.3%). Although the hospital mortalities were comparable (66.7% in our study vs. 72%), we report a higher long-term survival (17% at 3 years vs. 10% at 1 year) and lower prevalence of survivors on chronic dialysis (9.1% in the present study vs. 64%).
Acute changes in renal function after coronary bypass surgery are not well understood and incompletely characterized, and represent a challenging clinical problem. Nonetheless there are several potential explanations for such a high mortality. The case mix has changed over time to include older and sicker patients . Irreversible postoperative cardiogenic shock may develop, and dialysis is more aggressively applied. The causes of renal dysfunction after cardiac surgery are multifactorial and usually attributed to the use of CPB, cardiovascular compromise, or toxic insults to the kidneys. Non-pulsatile flow, renal hypoperfusion, hypothermia are also thought to have adverse effects on renal function. All of the above explanations may account for the persistently high mortality rate associated with severe ARF after cardiac operations.
Limitations of the present study are acknowledged. The study design was observational and no randomization was introduced. However, the data analysed in the present study were all prospectively collected and entered into a database as part of routine patient management at our institution. There are important prognostic factors that were not included in the analysis, namely ‘early’ vs. ‘late’ RRT, use of diuretics and intraoperative variables like anaesthetic medications, CPB time and aortic cross-clamp time.
In conclusion, we report a large series of patients with ARF-RRT after cardiac operation with the longest follow-up reported in the literature. We confirm the high hospital mortality in this high-risk population and, for the first time, showed a reasonable survival and quality of life in survivors.
We are indebted to Mariano Fichera, RN, Monica Borrelli, RN, Massimiliano Giordano, RN and Marzia Pedrocchi, RN for the care provided to these patients and for the support in data collection and data entry.
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