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Pediatric Anesthesiology: Research Report

Cardiac Catheterization and Postoperative Acute Kidney Failure in Congenital Heart Pediatric Patients

Bianchi, Paolo MD*; Carboni, Giovanni CCP*; Pesce, Giorgia MD*; Isgrò, Giuseppe MD*; Carlucci, Concetta MD*; Frigiola, Alessandro MD; Giamberti, Alessandro MD; Ranucci, Marco MD, FESC*

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doi: 10.1213/ANE.0b013e318299a7da
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Acute renal failure (ARF) is a well-known and severe complication of cardiac surgery and is associated with significant morbidity, mortality, and cost increasing in the perioperative period and beyond. In pediatric cardiac surgery, its incidence is reported between 15% and 40% depending on the different definitions of ARF.1–4

Several general pathophysiological processes are thought to play a role in acute kidney injury (AKI) after cardiac surgery. The available evidence suggests that they are likely to involve different mechanisms and/or pathways,5 including the effects of exogenous and endogenous toxins, metabolic factors, ischemia–reperfusion injury, neurohormonal activation, inflammation, and oxidative stress. The hemodynamic impairment which is often associated with cardiac surgery may also play a role in the determination of ARF.6,7

Contrast-induced nephropathy (CIN) is a common and unique type of toxin-induced ARF. Acute nephropathy due to radiocontrast exposure is a well-known complication after cardiac catheterization and is associated with increased mortality in adults.8 Some authors demonstrated that cardiac operations performed on the day of the angiography and large contrast media use are risk factors for ARF in adults,9–12 even if this finding was not confirmed in other studies.13

Angiographic examination in pediatric congenital heart patients is often part of the diagnostic and sometimes therapeutic process. Some of these patients may need a cardiac operation in close succession with the angiography, therefore being theoretically prone to the double insult of contrast media and cardiac operation. Despite the many angiographic procedures performed in pediatric patients for complex congenital heart disease, there are too few studies investigating contrast media as a risk factor for AKI in cardiac surgery. The present study investigated the impact of 2 angiography-related factors (amount of contrast media and time interval between angiography and surgery) on postoperative ARF in pediatric congenital heart patients undergoing cardiac angiography and surgery in succession during the same hospital stay.


This was a retrospective study of prospectively collected data. The study design was approved by the local ethics committee (ASL Milano 2, Melegnano, Milan, Italy), and the need for informed patient consent was waived.

Data Collection and Patient Population

Since the year 2000, all patients undergoing cardiac operations are routinely included in our institutional database. Since 2003, angiographic data of congenital heart patients are routinely included in a separate database.

As a preliminary step, we retrieved data on pediatric (≤12 years) patients who received a cardiac operation from January 2003 through December 2011. This produced a dataset of 1937 patients. Subsequently, we retrieved the angiographic data of those who received an angiographic study up to 14 days before surgery at our institution. This cross-procedure produced a dataset of 347 patients. Seventy patients were subsequently excluded due to missing data in either the surgical and/or the angiographic database. The final patient study population was 277 patients, pooled into a single dataset by merging the 2 databases.

Angiography, Demographics, Patient Profile, and Operative Details

All cardiac angiographies were performed at a variable time interval before surgery, in our catheterization laboratory, using monoplane x-ray equipment. Angiographic data included in the dataset were: date of the angiography, type of contrast media used, and its amount (milliliters per kilogram), as assessed from the patients’ files and the angiographic report. All patients received the same type of contrast media (Iomeprol, Iomeron®, Bracco, Milan, Italy) at different iodine concentrations (300 or 350 mg/mL). To account for the different iodine concentrations, the amount of contrast media used was expressed in terms of iodine dose (grams per kilogram). Iomeprol is a nonionic, monomeric iodinated contrast medium. Unlike the older ionic agents, iomeprol has low chemotoxicity, osmolality and viscosity, and high water solubility. Iomeprol-induced changes in variables of renal function (serum creatinine levels, blood urea nitrogen, and urinary albumin excretion) occur within 24 hours after the dose.14

Based on the date of the surgical operation, the interval time between the angiography and the surgical operation was defined (days). Operation on the same day of the angiography was coded as interval 0; subsequent intervals were 1 day, 2 days, 3 to 6 days, and 7 or more days.

Patient data included in the dataset were: age (years or months); gender; weight (kilograms); height (centimeters); preoperative hematocrit (%) and serum creatinine value (milligrams per deciliter) assessed at baseline (before the angiographic procedure); and type of congenital heart defect. Based on serum creatinine value, age, weight, and height, the baseline creatinine clearance was calculated according to the following equation:15

where the factor k is 0.33 for infants with low birth weight, 0.45 for infants aged 1 to 52 weeks, and 0.55 for children aged 1 to 13 years.

Operative data included redo operations; urgent surgical operation; complexity of the operation based on the Risk Adjusted for Congenital Heart Surgery (RACHS) system,16 the use of cardiopulmonary bypass (CPB), the duration of CPB (minutes) and aortic cross-clamp time (minutes), the use of deep hypothermic cardiac arrest, and the nadir hematocrit (%) on CPB. For patients operated without CPB, the duration of CPB and aortic cross-clamp time was coded 0 minutes. For patients operated on CPB without aortic cross-clamp, the aortic cross-clamp time was coded 0 minutes.

The presence of a postoperative low cardiac output syndrome (LCOS), defined as the need for major inotropic support (dopamine ≥5 µg·kg−1·min−1 and/or epinephrine ≥0.05 µg·kg−1·min−1) longer than 48 postoperative hours, was considered within the possible covariates determining renal dysfunction.

Red blood cell transfusions were included in the analysis as well, provided that they were used during surgery or within the following 48 hours.

Outcome Data

The investigation of renal function after the surgical operation was based on the peak serum creatinine value (milligrams per deciliter) within the first 48 hours after the operation. The nadir creatinine clearance was calculated according to an already reported equation.15

Patients were assigned to 4 different levels of postoperative renal function based on the pediatric Risk, Injury, Failure, Loss of function, End stage (pRIFLE) grading system reported in Table 1.17 For each of these levels, the relevant angiography data were measured and compared. For the purposes of the present study, the renal outcome of interest was defined as pRIFLE grade 3 (acute renal failure). Operative (30 days) mortality was analyzed for the different grades of renal dysfunction.

Table 1
Table 1:
Pediatric RIFLE Criteria for Acute Renal Dysfunction

Statistical Analysis

Data are shown as number (%) or mean (SD) for normally distributed variables, or median (interquartile range) for nonnormally distributed continuous variables.

The univariate association between risk factors (angiographic data and other covariates) and the renal outcome (ARF) was investigated using a Student t test, a Mann-Whitney U test, a Pearson χ2, or Fisher exact test when appropriate. Subsequently, multivariable models were built based on a logistic regression analyses, producing odds ratios with 95% confidence intervals. The factors being univariately associated (P < 0.1) with the renal outcome were tested in the multivariable model. To avoid overfitting of the logistic regression model, a maximum number of 1 independent risk factor per each 10 events was admitted to the model. Linearity assumption for continuous variables was tested, and if not confirmed, adequate cutoff points were identified using coordinate points of c-statistics. C-statistics and Hosmer-Lemeshow statistics were used to check for accuracy and calibration of the multivariable model.

For all the statistical tests, a P value <0.05 was considered statistically significant. All calculations were performed using a statistical package (SPSS 13.0, Chicago, IL).


Demographics, angiography, operative details, and renal outcome of the patient population are reported in Table 2. According to the pRIFLE score, 177 (63.9%) patients suffered some degree of postoperative renal dysfunction, with 49 (17.7%) AKI and 55 (19.9%) ARF events. The operative mortality rate was 2% in patients without renal dysfunction, 4.1% for patients graded “risk,” 6.1% for grade “injury,” and 12.7% for grade “failure.” The operative mortality rate was significantly (P = 0.015) higher in patients with ARF than in patients without ARF (3.6%). The interval time between angiography and surgery (Fig. 1 and Table 3) did not demonstrate any association with the pRIFLE grade.

Figure 1
Figure 1:
Distribution of pRIFLE risk, injury, and failure, according to the interval between angiography and surgical operation. pRIFLE = Pediatric Risk, Injury, Failure, Loss of function, End stage.
Table 2
Table 2:
Demographics, Angiographic, and Operative Details of the Patient Population
Table 3
Table 3:
Univariate Analysis for Acute Renal Failure

The mean amount of contrast media was 3.2 ± 2.4 g/kg. There were no differences with respect to the amount of contrast media used in patients with no events, pRIFLE grade risk, and injury (Fig. 2). Conversely (Table 3), patients with acute kidney failure received a significantly (P < 0.001) higher dose of iodine contrast media (4.6 ± 2.6 g/kg) with respect to all the others (2.8 ± 2.2 g/kg). The univariate association between the amount of contrast dose and the onset of a postoperative ARF was explored with a logistic regression analysis. The amount of iodine administered on angiography was significantly (P = 0.001) associated with the ARF incidence, with an odds ratio of 1.31 (95% confidence interval, 1.16–1.48).

Figure 2
Figure 2:
Amount of iodine contrast media administered during cardiac angiography according to the presence and severity of postoperative renal dysfunction.

Other possible covariates being univariately associated with peak postoperative ARF were investigated (Table 3). Age, weight, height, newborn state, baseline serum creatinine and baseline creatinine clearance, RACHS score, preoperative hematocrit, redo operation, urgent operation, red blood cell transfusion, and postoperative LCOS were associated with acute kidney failure at a P value <0.1.

A multivariable risk model (stepwise forward logistic regression analysis) was built for ARF. Many of the factors listed in Table 3 suffered from strong intercorrelation. Among age, newborn state, weight, and height, we included age because weight was mathematically coupled with the iodine dose (grams per kilogram). Among baseline serum creatinine and creatinine clearance, we included creatinine clearance because of a higher level of significance (P < 0.001 vs P = 0.033). Lowest temperature on CPB was excluded because many patients were treated without CPB. The other factors were entered in the multivariable model. The final model included 3 independent risk factors for ARF: age, amount of iodine administered, and presence of a postoperative LCOS. Linearity between iodine contrast media dose was tested and confirmed. Conversely, the association between age and ARF incidence was not linear. Acutoff point at 2 years was identified, having a 93% sensitivity and 68% specificity for ARF. The multivariable model was therefore built using this cutoff value for age (Table 4).

Table 4
Table 4:
Multivariable Risk Model for Postoperative Acute Renal Failure

Within this model, the amount of iodine administered on angiography remains an independent predictor for postoperative ARF, with a 16% relative risk increase per each additional grams per kilogram administered. The predictive model based on age <2 years, iodine dose, and LCOS has a good calibration according to the Hosmer-Lemeshow statistics and a very good accuracy (c-statistics) of 0.848. Figure 3 reports the crude and adjusted (for age <2 years and LCOS) predicted ARF rate according to the iodine dose administered for angiography.

Figure 3
Figure 3:
Acute renal failure risk according to the iodine contrast media dose in the crude (continuous line, pink area) and adjusted (dashed line, blue area) models. Colored areas represent the 95% confidence interval.

Given the relationship between iodine dose for angiography and the incidence of ARF, we have performed a sensitivity analysis exploring the upper decile of the patient population (28 patients) receiving the highest iodine dose. In this subset, there were 6 (21.4%) newborns, with 5 (18%) cases urgently referred to surgery, and a median RACHS of 2.0. Cardiac angiographic examinations included diagnostic plus interventional procedure in 9 cases of pulmonary atresia, 2 cases of aortic/arch coarctation, and 1 case of pulmonary artery branches stenosis; diagnostic procedures with or without balloon septectomy in 3 cases of transposition of the great arteries; diagnostic procedures in 2 cases of ventricular septal defect, 4 cases of total anomalous venous return, 3 cases of hypoplastic left heart syndrome, 1 case of tetralogy of Fallot, 1 case of double outlet right ventricle, 1 case of status post Glenn operation, and 1 case of tricuspid atresia.

Overall, this subset of patients had ARF in 11 (39%) cases, with an operative mortality rate of 10.7% (3 patients).


The main findings of our study are (1) renal dysfunction after cardiac operations in pediatric patients is a common feature, with an incidence of 64% of any degree of damage and 20% of ARF according to the pRIFLE score; (2) patients with ARF suffered significantly higher operative mortality than patients without ARF; (3) the amount of contrast media used during preoperative angiographic examination is a determinant of postoperative ARF; and (4) additional risk factors for ARF are age <2 years and postoperative low cardiac output. The deleterious effects of preoperative cardiac angiography should be considered within the complex scenario represented by the multifactorial genesis of postoperative ARF.

Recognized risk factors for the development of ARF after cardiac surgery are: younger age, higher complexity, longer CPB and cross-clamping times, more intraoperative transfusions, and postoperative LCOS.3 A small postoperative increase in serum creatinine predicts ARF in children undergoing cardiac surgery.3,18 Our univariate analysis confirms the importance of the already identified risk factors even adding some others: urgent operation and redo operation. The multivariable model shows, furthermore, the particular role that angiography with large amounts of contrast media play together with postoperative LCOS.

CIN is caused by vasoconstriction-mediated renal medullary ischemia and direct toxic damage to renal tubular epithelial cells. Most cases present as nonoliguric ARF, although oliguric renal failure is possible as well.19

Preexisting renal function impairment is the most important risk factor for CIN.20 In our series, preangiography renal function was associated with postoperative ARF only at a univariate level. Conversely, the iodine contrast media dose is an independent risk factor for ARF.

The standard dose of contrast media suggested by some authors is 1 to 5 mL/kg, with high doses considered up to 8 mL/kg.21 This corresponds to a dose of 0.4 to 3.2 g/kg of iodine when the iodine concentration is 400 mg/mL.

In our series, 20% of patients received a dose of iodine contrast media >5 g/kg. These large doses were associated with the most severe cases, requiring prolonged and extensive angiographic examination. Additionally, we must recognize that the use of monoplane x-ray equipment resulted in the need for repeated imaging, therefore leading to the need for larger doses of contrast media. Even if the dose of contrast media used were excessive in some cases, other studies report similar doses in some cases. Senthilnathan et al.22 presented a series of 2321 consecutive patients who underwent cardiac angiography. In their series, the median dose of iodine contrast media was 1.4 g/kg; 25% of the patients received 2.1 g/kg, and a minority of patients received higher doses, up to 6 g/kg of iodine contrast media. Despite this, the authors did not find any renal problems even in patients requiring large doses of contrast medium. However, contrary to our study, their study did not consider the possible effects of a cardiac operation after cardiac angiography. In our series, we could not find a clear relationship between timing of surgery after angiography and postoperative ARF, as observed in adults.6–9 To our knowledge, our study is the only report demonstrating that a high dose of contrast media is a risk factor for postoperative ARF in children.

Ajami et al.23 investigated a population of pediatric cardiac patients undergoing angiography. They described a significant reduction in glomerular filtration rate 48 hours after angiography. A CIN incidence of 18.75% was also found. Niboshi et al.24 found a transient renal tubular dysfunction after angiography. Similarly, Buyan et al.25 and Zo’o et al.26 observed a 15% incidence of CIN in pediatric patients receiving contrast media. All the above studies did not investigate patients who were undergoing cardiac surgery.

Together, these studies stress the deleterious effects of contrast media on renal function of pediatric patients. Given the well-known risk of ARF after cardiac surgery in pediatric patients, our results may be interpreted as the combined insult of contrast media and cardiac surgery on renal function.

As opposed to the vast majority of risk factors identified for ARF after cardiac surgery in pediatric patients (namely, patient’s size and age, complexity of the operation, and perioperative LCOS), the amount of contrast media is a potentially modifiable risk factor. In particular, the use of large doses of contrast media could be extremely unsafe for this group of patients, and any attempt to limit the dose should be made.

There are some limitations to our study. The main limitation is the relatively small amount of patients evaluated. A second limitation is the analysis of retrospectively collected data over a long study period. Furthermore, AKI classification is still not universally defined in pediatric patients, and our results might have been different if other classification methods27 were used. Also, our definition of LCOS was arbitrary and based on retrospective data. Finally, we had to exclude about 25% of the patient population due to a lack of angiographic data, and this may have resulted in selection bias.

Given these limitations, our study generates the hypothesis that avoidance of a large contrast media amount may effectively limit the incidence of ARF in pediatric patients undergoing cardiac surgery after cardiac angiography. This hypothesis is difficult to demonstrate with a randomized control trial, but could be supported in a prospective series where this protective strategy is applied.


Name: Paolo Bianchi, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Paolo Bianchi has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Giovanni Carboni, CCP.

Contribution: This author helped conduct the study.

Attestation: Giovanni Carboni has seen the original study data and approved the final manuscript.

Name: Giorgia Pesce, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Giorgia Pesce has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Giuseppe Isgrò, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Giuseppe Isgrò has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Concetta Carlucci, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Concetta Carlucci has seen the original study data and approved the final manuscript

Name: Alessandro Frigiola, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Alessandro Frigiola has seen the original study data and approved the final manuscript.

Name: Alessandro Giamberti, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Alessandro Giamberti has seen the original study data and approved the final manuscript.

Name: Marco Ranucci, MD, FESC.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Marco Ranucci has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

This manuscript was handled by: Peter J. Davis, MD.


Dr. Andrea Ballotta, MD, specialist in biostatistics, provided consultancy for the statistical analysis.


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