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Eur J Cardiothorac Surg 2007;31:1022-1028. doi:10.1016/j.ejcts.2007.03.001
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Continuous veno-venous hemodiafiltration in children after cardiac surgery

Anna Jandera, Marcin Tkaczyka,*, Izabela Pagowska-Klimekb, Witold Pietrzykowskic, Jacek Mollc, Wojciech Krajewskib, Michal Nowickia

a Department of Nephrology and Dialysis, Polish Mother's Memorial Hospital Research Institute, 281/289 Rzgowska Street, 93-338 Lódz, Poland
b Intensive Care Unit, Polish Mother's Memorial Hospital Research Institute, Lódz, Poland
c Department of Cardiac Surgery, Polish Mother's Memorial Hospital Research Institute, Lódz, Poland

Received 6 November 2006; received in revised form 28 February 2007; accepted 1 March 2007.

* Corresponding author. Tel.: +48 42 2712001; fax: +48 42 2711381. (Email: mtkaczyk{at}uni.lodz.pl).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objective: Acute renal failure (ARF) is still a frequent complication following extensive cardiac surgery. Renal replacement therapy (RRT) modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT), although the experience with the latter is still highly limited in the infants. Methods: We describe our results with continuous veno-venous hemodiafiltration (CVVHDF) in 25 children (15 males, 10 females) who underwent CRRT from 2001 to 2006 and were retrospectively reviewed. Results: We performed continuous veno-venous hemodiafiltration (CVHDF) using PRISMA (Hospal). The mean age at the onset of CRRT was 26 months (ranging from 7 days to 11.2 years) and the mean body weight was 14 kg. The mean duration of RRT was 67 h (8–243 h) with ultrafiltration rate 4.9 ml/(h kg); the mean filter ‘lifetime’ was 31.5 h. Anticoagulation was achieved with non-fractioned heparin infusion (21/25 cases) and enoxaparin (2/16). The mean creatinine concentrations at the beginning, 24, 48 and 72 h were as follows: 171, 100, 65 and 88 µmol/l. Of these 25 treated children, 19 died in the postoperative period (8 during CVVHDF). The mortality rate for the entire group was 76%. The main cause of death was cardiac failure and sepsis with multiorgan dysfunction (MODS). The main complication during CRRT was bleeding, transient hypothermia, thrombocytopenia and filter clotting which occurred in about one-third of the patients. Conclusions: We conclude that CVVHDF may be an alternative method of renal support for critically ill children after cardiac surgery in experienced centers, but a significant number of specific complications should be taken into account.

Key Words: Acute renal failure • Cardiac surgery • Hemodiafiltration • Children • Mortality • Dialysis


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Significant advancement in surgical treatment in critically ill children with congenital cardiac disease has led to dramatic increase in acute renal failure (ARF) [1]. Cardiac surgery patients are especially prone to ARF development due to low cardiac output, postoperative massive hemolysis and septic complications [2,3]. The incidence of ARF in postoperative period after cardiac surgery with cardiopulmonary bypass (CPB) was assessed by several authors to range between 2.7 and 9%, with survival rate ranging from 21 to 70% [3–6]. Risk factors for mortality include increasing underlying complexity of the congenital heart disease and poor cardiac function [1,2,3,5,7]. Often, low cardiac output induces multiorgan dysfunction (MODS) [1].

An appropriate renal replacement therapy for pediatric patients with ARF requires special considerations not commonly encountered in the treatment of adult patients. In contrast to adult intensive care unit (ICU) patients, peritoneal dialysis is traditionally recommended for children with post-cardiac surgery acute renal failure, especially in the case of very young patients [2,4]. Hemodialysis has not been accepted widely because of difficulties in obtaining an adequate vascular access and hemodynamic instability [3,8].

Due to improvements in the vascular access and machines with volumetric control for accurate ultrafiltration, the spectrum of dialysis renal replacement therapy modalities has widened recently [5]. The extracorporeal continuous modalities include continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodiafiltration (CVVHDF), slow continuous ultrafiltration (SCUF) or continuous veno-venous hemodialysis (CVVHD) [5]. These techniques offer continuous, slow detoxication, well-controlled ultrafiltration rate, effective clearance of all cardiopulmonary toxic substances, e.g. myocardial depressing factor (MDF), and can be performed on hemodynamically unstable patients with heart failure. In the adult population, continuous methods of renal replacement therapy were recognized as equal or even superior to classical hemodialysis in ICU settings [9]. It has still not been established whether they can be alternative procedures for critically ill children. The aim of our observational, single-center study was to describe the use of continuous veno-venous hemodiafiltration in small children with acute renal failure after cardiac surgery.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1 Study design
We analyzed retrospectively the clinical data of 25 children who required dialysis therapy after cardiac surgery with CPB in the ICU of tertiary pediatric hospital from September 2001 to January 2006. The patients’ files were reviewed for cardiorespiratory parameters and physiological variables at the start of CVVHDF and during dialysis, diagnosis of low cardiac output syndrome, type of cardiac malformation and surgery procedures, duration of CPB and aorta cross-clumping, need for inotropic support, preoperative renal function assessment (serum creatinine, urea), acute renal failure details (the presence of MODS, time from the surgery), RRT (indications, equipment, anticoagulation, duration of treatment, metabolic efficacy described by serum creatinine and urea concentration) and the final outcome: renal function recovery and overall survival rate.

Pediatric Risk of Mortality Score III (PRISM III) was retrospectively calculated on the basis of patients’ files [10]. The risk of surgical procedure was assessed for each patient according to Basic (BAS) and Comprehensive Aristotle Scores (CAS) [11].

The inclusion criteria were outlined as follows: age below 16 years, an open-heart surgery and acute renal failure that required dialysis treatment. Patients with pre-existing chronic renal failure or congenital renal anomalies were excluded from further analysis. The definition of acute renal failure was based on a 100% rise in serum creatinine concentration, oliguria (less than 1.0 ml/(kg h) in infants and 0.5 ml/(kg h) in older children) [4]. The criteria for renal replacement therapy consisted of further increase in serum creatinine and persistent oliguria refractory to an aggressive use of diuretics (furosemide infusions 1 mg/(kg h)) over 4 h. The choice of the type of dialysis depended on the clinical status of the patient (hemodynamic stability, signs of fluid overload, presence of coagulation disorders, history of abdominal surgery), emergency of the procedure (need for urgent correction of hyperkalemia or fluid overload) and ultrafiltration requirements. In cases of emergency application of RRT, symptoms of low cardiac output (LCOS), coagulation disorders or previous abdominal surgery CVVHDF was applied.

In our ICU, the diagnosis of low cardiac output syndrome was established on the criteria defined by Hoffman et al. [12]. This definition consists of clinical signs (tachycardia, poor peripheral perfusion, oliguria, cardiac arrest), need for a 100% increase in existing pharmacological support or administration of new agent, metabolic acidosis with an increase in base deficit of >4. Each time, the diagnosis of LCOS was recorded in patient's medical files.

The dialysis treatment was weaned in patients with satisfactory urine output (at least 2 ml/(kg h)), stable biochemical markers of renal function and adequate fluid balance.

2.2 Patients
During the observation period, 2006 children underwent cardiac surgery in our center, with 4–9% rate of unfavorable outcome, depending on the year of analysis. Among them, extracorporeal circulation was applied in 1308 cases of open-heart surgery. Dialysis-dependent acute renal failure was noted in 76 cases, which constitutes 5.8% of the total number of patients treated with extracorporeal circulation.

The study involved 25 patients (15 male, 10 female) aged from 7 days to 11.2 years (average age of 46 months) and having body weight of 14 kg (25–75th percentile: 8.4–14 kg). The basic clinical parameters are presented in Table 1 . The median values of selected scores were as follows: PRISM III score 26.84 points, BAS 9.6 points, CAS 18.94 points. All patients required inotropic support. Diagnosis of LCOS was established in 21 cases.


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  		Table 1 Clinical characteristics of patients with acute renal failure treated with CVVHDF
 
The cardiopulmonary bypass time ranged between 61 and 300 min (median value of 96 min). The median value of aorta clumping time was 42.5 min (range: 25–109 min).

The most frequent cardiac malformation in this group was hypoplastic left heart syndrome, 8/25, during the first or next stages of the surgical treatment (Table 2 ). These patients developed ARF after cardiac surgery, but some additional risk factors were also present: nephrotoxic drugs in three children or radiocotrast injury (after cardiac catheterization) in one child.


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  		Table 2 Clinical characteristics of patients undergoing CVVHDF
 
In all the patients, CVVHD was commenced when they fulfilled the criteria described above. The period between the surgery and the dialysis treatment ranged from 1 h to 10 days (median of 48 h). All the children were given inotropic drugs (dopamine, dobutamine or epinephrine). The average number of the drugs was two—before commencement of dialysis, at 24, 48, 72 h. For the blood access, double lumen 6.5–8.5 Fr catheters were placed in the internal jugular (n = 12), femoral (n = 9) or subclavian veins (n = 4).

2.3 Hemodiafiltration
All the procedures were performed with the Prisma® (Hospal) machine with Prisma M10 (0.042 m2) or M60 (0.6 m2) or M100 (0.9 m2) pre-sets (Hospal). Hemosol (Gambro) bicarbonate solution served as a replacement and dialysate fluids with additional potassium supplementation, when required. The pediatric lines were used with the priming of either 5% albumin solutions or blood.

2.4 Laboratory data
Biochemical markers were measured automatically with Cobas Mira and Integra analyzers (Roche Diagnostics, Switzerland). Serum creatinine was measured by a modified Jaffe method (buffered, without protein removal, compensated in serum). Serum albumin concentration was assessed with Paragon (Dade-Behring, Germany). The concentration of hemoglobin and platelet count were assessed with of CellDyn 1700 (Abbott, USA).

2.5 Statistical analysis
All data are presented as median and 25–75th interquartile range. Statistical analysis was performed with the Fisher exact test and non-parametric tests (Mann–Whitney two-sample rank test, Wilcoxon matched-pair test and ANOVA Friedman test). Correlation between selected parameters was assessed by the Spearman rank correlation coefficient. The p-values of less than 0.05 were considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
Among 25 children treated by CVVHDF, 8 died during the procedure (32%), but overall survival rate was 24% (6/25). The cardiac dysfunction, and not the acute renal insufficiency, was the most common (90%) cause of death.

3.1 Indication for the dialysis
Among the patients who were qualified to CVVHDF, 20 showed doubled initial serum creatinine, 19 showed anuria, 8 showed significant fluid overload, and 19 showed signs of MODS (before starting the dialysis). Sepsis was detected in four of them as a comorbid condition before commencement of the CVVHDF.

3.2 Details of the CVVHDF procedure
The CVVHDF was started immediately after the placement of central venous catheter in the ICU settings. The Hospal M60 sets were used in 20 children, M100 in 4, whereas M10 was used in 1 child. The blood flow was set at 132 ml/(min m2) BSA (25–75 percentile: 104–164 ml/(h m2) BSA), replacement at 421 ml/(h m2) BSA (25–75 percentile: 337–619 ml/(h m2) BSA) and dialysate at 769 ml/(h m2) BSA (25–75 percentile: 541–1125 ml/(h m2) BSA) (Table 3 ). Most patients (21/25) received heparin as anticoagulation. Fourteen of them received bolus dose of 0.29 mg/kg (25–75th interquartile range: 0.23–0.55), whereas six were left without it. The following heparin infusion rate was 0.24 mg/(kg h) (25–75th interquartile range: 0.13–0.35). The target activated clotting (ACT) time before filtration was achieved between 180 and 250 s by titrating the infusion dose (Table 3). In seven patients, protamine sulfate solution was added after filtration. Two patients received enoxaparin boluses every 4 h and two were dialyzed without heparine due to coagulation disturbances.


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  		Table 3 Details of the CVVHDF
 
The lifetime of a single filter was 31.5 h (25–75th interquartile range: 24–65). We changed the sets because of clotting, according to the indication of the manufacturer (72 h—only in about 17% of filters) or when stopping the procedure. We calculated that the shortening of the lifetime of the filter could double the costs of disposable materials. The overall duration of the procedure ranged from 8 to 243 h (median value of 63 h.).

The laboratory and clinical data of CVVHDF efficacy are summarized in Table 4 . We noted a significant decrease in urea and creatinine concentrations during the first 12 h of the procedure (p < 0.05), with further plateau at desired levels. The platelet count was low at the beginning of the procedure, but did not decrease significantly. However, seven (28%) patients received platelet infusions during the treatment.


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  		Table 4 Biochemical and clinical parameters during the first 72 h of hemodiafiltration (median value and 25–75th interquartile range)
 
We observed rapid blood pressure decreases (median 8 mmHg; 25–75th interquartile range: 5–11 mmHg, p = 0.04) 5 min after the commencement of CVVHDF, which were noted in 20 (75%) children, but they were easily compensated with a bolus fluid infusion of 5–10 ml/kg of isotonic solutions or inotropes. During the 72 h of treatment, there were no significant changes in systolic blood pressure values and the number of inotropic drug used. However, there was a tendency toward an increase in SBP during the procedure (Table 4).

Of 25 patients on CVVHDF, 8 (32%) died during the procedure. In 14 children, renal function recovered up to a level that justified the weaning of renal support. Three children were transferred to hemodialysis (one) or peritoneal dialysis (one). That makes 68% survival during CRRT procedure. However, 11 children died later, i.e. after recovery from acute renal failure. This observation decreased the overall survival rate to 24%. We observed no difference in any of the scores that were applied to assess the severity of clinical status or complexity of the surgery between children who survived or those deceased.

3.3 Complications
The most common complications of the CVVHDF were hypothermia below 36.5 °C (8/25) compensated by external heating and significant bleeding (7/25) from respiratory or gastrointestinal tract that forced us to reduce heparin infusion or a protamin sulfate temporary administration. Two patients required antithrombin III infusions due to its deficiency. The blood line malfunction resulting in its replacement was detected in 7/25 children. Thrombocytopenia (blood platelets below 150 G/l) was observed in 23/25 patients before the start of dialysis procedures. In 7/25 cases, platelet concentrates were infused during CVVHDF.

The comparison of initial biochemical parameters between children who survived and those who deceased (Table 5 ) showed only the initial serum urea concentration to be higher in children with unfavorable outcome. The incidence of MODS, anuria or overhydration was comparable in those who died and those who survived. The mean number of inotropes used during the first 72 h of the procedure did not differ between these two groups of patients (2.1 vs 1.9, p = 0.3). When the patients who recovered from ARF (n = 14) were compared with those who failed to do so (n = 8), there was no observable difference concerning any parameters, biochemical or clinical.


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  		Table 5 Clinical and biochemical parameters in CVVHDF survivors and non-survivors (median value and 25–75th interquartile range)
 
Recovery from acute renal failure negatively correlated with time from the cardiopulmonary bypass procedure (r = –0.43, p = 0.033).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The reported incidence of acute renal failure in children after cardiac surgery varies from 1 to 9% [2,4,7]. This condition dramatically decreased the survival among these patients from 95.3% in non-ARF infants to 33.3% [2,4,7]. Baskin et al. [4] described a strong correlation between mortality and a development ARF in these patients (r = 0.7). In our study, among 1308 patients that underwent open-heart surgery in our center, 76 (5.8%) developed dialysis-dependent ARF.

The incidence of ARF requiring dialysis treatment after surgery with CPB has been described to range between 1 and 17%, depending on the complexity of procedure, entry criteria and criteria for commencement of the dialysis treatment [2,7,13–15]. Chan et al. [16], in an analysis with the highest rate of dialysis-dependent ARF, showed that those who were dialyzed had more complicated cardiac disease, longer cardiopulmonary bypass time, lower body weight and required preoperative ventilation more often. Studies based on a larger group of adult patients showed that the incidence of dialysis-dependent ARF in cardiac surgery population was 0.3–4%, but the profile of cardiac malformation in adults differed significantly from children [9,17].

Children often require multiple procedures that differ from those applied in acquired heart diseases in adulthood [3,4]. Due to relatively early diagnosis and prompt therapeutic decisions, the pre-existing other organ impairment was rarely detected in these patients [2,4,7,16]. However, in contrast to other types of general surgery, cardiac patients develop severe postoperative complications (including multiorgan failure) more often due to prolonged low cardiac output and unsuccessful correction or heart muscle malfunction. The survival rate of 21–70% in infants with acute renal failure after cardiac surgery has been reported by several authors [2,3,4]. On the contrary, the development of dialysis-dependent acute renal failure increased the mortality rate up to 79% [2,7,8,17].

Our study showed that the overall mortality rate (76%) was higher than the one reported by others, despite an adequate metabolic and fluid control [5,18]. Yet, the outcome of children requiring RRT is usually not directly related to the RRT modality, but rather to the seriousness of clinical status (defined by inotrope requirement and severity of congenital heart disease) or criteria of starting the dialysis. All of the described patients required mechanical ventilation, continuous administration of inotropic/vasopressor drugs; 76% developed multiorgan dysfunction. The low survival observed in pediatric patients receiving CRRT has been attributed to the decision to use CRRT in more seriously ill children [19]. It has been shown that the earlier the dialysis is commenced, the lower is the mortality rate [7,16,20]. The only study that compared peritoneal dialysis with continuous hemofiltration was done by Fleming et al. [8], and this gave no-survival advantage of extracorporeal techniques over peritoneal dialysis. As it was clearly showed by Fleming et al. [8], the overall net fluid urea or creatinine removal were higher during hemofiltration and enabled more robust fluid and calorie intake, especially in hypercatabolic patients. In adults, in whom the peritoneal dialysis had little application, there was no difference between intermittent hemodialysis and continuous extracorporeal methods with regard to survival [21]. With the development of cardiac surgery, several studies have reported the use of extracorporeal continuous techniques [22,23]. All these studies showed high mortality rate, but prompt and aggressive use of CRRT has been related to less-unfavorable prognosis.

There were several factors linked to a poor prognosis such as complexity of cardiac lesions, duration of cardiopulmonary bypass, central venous hypertension, hypotension, age and need for dialysis [2,4,16]. Hypoalbuminemia was detected as major a risk factor of death for adult patients [4,24]. The most of recently published papers described low cardiac output, young age, low body weight, associated systemic disorders, pre-existing renal insufficiency or mechanical ventilation before the surgery as additional risk factors, both for the development of ARF and mortality [1,9,20,25]. We observed no difference in any of the scores applied to assess the severity of clinical status or complexity of the surgery between children who survived or those who deceased.

Surprisingly, in our study, the initial serum urea concentration was higher in children who survived and correlated with better survival, but this observation was of limited value due to low number of patients. Recovery from ARF seemed to be related to an earlier start of CVVHDF.

The renal function recovery (regardless of the favorable or unfavorable outcome) was observed in 56% of the patients. Baxter et al. [2] reported that the renal function recovery took place in 50% of cases, which was concordant with our results. However, in the study by Picca et al. [3], the recovery rate was lower (29.5%).

The complications of the CVVHDF procedure in our study concerned 17 out of 25 patients (68%). Most of them were easily managed. The most common complication that we observed was a short-lasting and reversible slope in blood pressure at the beginning of CVVHDF.

The modern modalities of veno-venous hemodiafiltration require definitely less assistance from ICU staff and qualified dialysis nurses. Peritoneal dialysis, although equally efficient, sometimes could become more cumbersome for the staff because of poor drainage due to mechanical reasons. This situation often causes the nephrologists to apply tidal volume dialysis to critically ill children with acute renal failure, but the ultrafiltration rate remained the critical disadvantage. CRRT is a therapy better suited for fluid removal in children with hemodynamic instability, and it is becoming more prevalent in critically ill children. Surveys among US pediatric nephrologists demonstrated increased CRRT use over peritoneal dialysis as the preferred modality for treating pediatric ARF [5]. The main problem with our study rises from the lack of definite criteria for choosing between peritoneal dialysis or hemodiafiltration treatment. The ICU staff had a major role in this choice based on a clinical status or an emergency need of ultrafiltration, or surgeons’ availability.

In conclusion, we suggest that the continuous veno-venous hemodiafiltration is an effective treatment alternative in critically ill children after cardiac surgery. The method provides adequate fluid balance and metabolic control, but still results with a significant number of specific complications and high overall mortality rate.


   Acknowledgments
 
The authors would like to thank Mrs Anna Kaminska for secretarial assistance.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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