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Renal Failure, 2013; 35(2): 210215 Copyright © Informa Healthcare USA, Inc. ISSN 0886-022X print/1525-6049 online DOI: 10.3109/0886022X.2012.747139 CLINICAL STUDY The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery Fulya G. Akkucuk, Meral Kanbak, Banu Ayhan, Bilge Celebioglu and Ulku Aypar Department of Anesthesiology and Reanimation, Faculty of Medicine, Hacettepe University, Ankara, Turkey Abstract Background: Experience with hydroxyethyl starch (HES) in children is limited. This study was conducted to observe the effects of HES or Ringers lactate (RL) usage as the priming solution on renal functions in children undergoing cardiac surgery. Methods: After ethical committee approval and parent informed consent, 24 patients were included in this prospective, randomized study. During cardiopulmonary bypass (CPB), Group I received RL and Group II received HES (130/0.4) as priming solution. Serum creatinine, blood urea nitrogen (BUN), β2-microglobulin, cystatin C, and urinary albumin and creatinine, serum, and urine electrolytes were analyzed after the induction (T1), before CPB (T2), during CPB (T3), after CPB (T4), at the end of the operation (T5), on 24th hour (T6), and on 48th hour postoperatively (T7). Fractional sodium excretion (FENa), urinary albumin/creatinine ratio, and creatinine clearance were calculated. Drainage, urine output, inotropes, diuretics, and blood requirements were recorded. Results: In both the groups, β2-microglobulin was decreased during CPB and cystatin C was decreased at T3,T4, and T5 periods (p < 0.05) and the levels remained within the normal range. Creatinine clearance did not differ in the HES group, but increased in the RL group (p < 0.05). Urine albumin/creatinine ratio was increased (p < 0.05) after CPB in the HES group, and it increased at T3, T4, and T5 in the RL group (p < 0.05). There were no differences in cystatin C, β2-microglobulin, FENa, urine albumin/creatinine ratio, creatinine clearance, total fluid amount, urine output, drainage, and inotropic and diuretic requirements between the groups. Conclusion: We conclude that usage of HES (130/0.4) did not have negative effects on renal function, and it can be used as a priming solution in pediatric patients undergoing cardiac surgery. Keywords: children, cardiac surgery, priming solution, HES (130/0.4), renal failure INTRODUCTION Renal dysfunction is the most critical complication after the cardiac surgery and its occurrence is more common in surgeries with cardiopulmonary bypass (CPB). Besides subclinical and temporary renal damages, renal failures that require dialysis can emerge. Also, mortality rate related to hemodialysis is increased. Moreover, hos- pitalization period and medical costs tend to increase due to acute kidney injury (AKI) and dialysis. 1 In patients who underwent surgery with CPB, panen- dothelial damage related to systemic inflammatory response is observed frequently. As a consequence, pro- tein loss, increased endothelial permeability, and inter- stitial edema can emerge. Fluid loss from intravascular area to interstitial area leads to hypovolemia. During CPB, renal blood flow and vascular resistance decrease by 30%. 1 Hypoperfusion is the main reason of renal failure, resulting in renal ischemia. Emboli, renal ischemia, reperfusion injury, and pigments are the main reasons of renal damages during CPB. Ischemiareperfusion- dependent AKI and nephropathy, and circular arrest episodes, are thought to be related to decreased cardiac output in perioperative and prolonged bypass duration. Ischemiareperfusion damage affects not only tubules and glomeruli, but also renal vessels. In children, elevated perfusion rates are required due to increased metabolic requirements, which also show destructive effects on the structural blood components. Although the CPB technology is advancing, CPB circuits are too large for pediatric population, and these circuits lead to critical decrease in the structural components of blood, coagulation factors, and other plasma proteins. In newborns and children, oliguric renal failure after CPB is very common. 2 Address correspondence to Banu Ayhan, Faculty of Medicine, Department of Anesthesiology and Reanimation, Hacettepe University, 06100 Sihhiye, Ankara, Turkey. Tel: þ90-312-3051207; GSM: þ90-532-2969290; Fax: þ90-312-3109600; E-mail: [email protected] Received 27 July 2012; Revised 31 October 2012; Accepted 3 November 2012 210 Ren Fail Downloaded from informahealthcare.com by Dicle Univ. on 11/05/14 For personal use only.

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Page 1: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

Renal Failure, 2013; 35(2): 210–215Copyright © Informa Healthcare USA, Inc.ISSN 0886-022X print/1525-6049 onlineDOI: 10.3109/0886022X.2012.747139

CLINICAL STUDY

The Effect of HES (130/0.4) Usage as the Priming Solution on RenalFunction in Children Undergoing Cardiac Surgery

Fulya G. Akkucuk, Meral Kanbak, Banu Ayhan, Bilge Celebioglu and Ulku Aypar

Department of Anesthesiology and Reanimation, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Abstract

Background: Experience with hydroxyethyl starch (HES) in children is limited. This study was conducted to observe theeffects of HES or Ringer’s lactate (RL) usage as the priming solution on renal functions in children undergoing cardiacsurgery. Methods: After ethical committee approval and parent informed consent, 24 patients were included in thisprospective, randomized study. During cardiopulmonary bypass (CPB), Group I received RL and Group II received HES(130/0.4) as priming solution. Serum creatinine, blood urea nitrogen (BUN), β2-microglobulin, cystatin C, and urinaryalbumin and creatinine, serum, and urine electrolytes were analyzed after the induction (T1), before CPB (T2), during CPB(T3), after CPB (T4), at the end of the operation (T5), on 24th hour (T6), and on 48th hour postoperatively (T7). Fractionalsodium excretion (FENa), urinary albumin/creatinine ratio, and creatinine clearance were calculated. Drainage, urineoutput, inotropes, diuretics, and blood requirements were recorded. Results: In both the groups, β2-microglobulin wasdecreased during CPB and cystatin C was decreased at T3,T4, and T5 periods (p < 0.05) and the levels remained withinthe normal range. Creatinine clearance did not differ in the HES group, but increased in the RL group (p < 0.05). Urinealbumin/creatinine ratio was increased (p < 0.05) after CPB in the HES group, and it increased at T3, T4, and T5 in the RLgroup (p < 0.05). There were no differences in cystatin C, β2-microglobulin, FENa, urine albumin/creatinine ratio,creatinine clearance, total fluid amount, urine output, drainage, and inotropic and diuretic requirements between thegroups. Conclusion: We conclude that usage of HES (130/0.4) did not have negative effects on renal function, and it canbe used as a priming solution in pediatric patients undergoing cardiac surgery.

Keywords: children, cardiac surgery, priming solution, HES (130/0.4), renal failure

INTRODUCTION

Renal dysfunction is the most critical complication afterthe cardiac surgery and its occurrence is more commonin surgeries with cardiopulmonary bypass (CPB).Besides subclinical and temporary renal damages, renalfailures that require dialysis can emerge. Also, mortalityrate related to hemodialysis is increased. Moreover, hos-pitalization period andmedical costs tend to increase dueto acute kidney injury (AKI) and dialysis.1

In patients who underwent surgery with CPB, panen-dothelial damage related to systemic inflammatoryresponse is observed frequently. As a consequence, pro-tein loss, increased endothelial permeability, and inter-stitial edema can emerge. Fluid loss from intravasculararea to interstitial area leads to hypovolemia. DuringCPB, renal blood flow and vascular resistance decreaseby 30%.1 Hypoperfusion is the main reason of renal

failure, resulting in renal ischemia. Emboli, renal ischemia,reperfusion injury, and pigments are the main reasons ofrenal damages during CPB. Ischemia–reperfusion-dependent AKI and nephropathy, and circular arrestepisodes, are thought to be related to decreased cardiacoutput in perioperative and prolonged bypass duration.Ischemia–reperfusion damage affects not only tubulesand glomeruli, but also renal vessels.

In children, elevated perfusion rates are required dueto increased metabolic requirements, which also showdestructive effects on the structural blood components.Although the CPB technology is advancing, CPB circuitsare too large for pediatric population, and these circuitslead to critical decrease in the structural components ofblood, coagulation factors, and other plasma proteins.In newborns and children, oliguric renal failure afterCPB is very common.2

Address correspondence to Banu Ayhan, Faculty of Medicine, Department of Anesthesiology and Reanimation, Hacettepe University, 06100Sihhiye, Ankara, Turkey. Tel:þ90-312-3051207; GSM:þ90-532-2969290; Fax:þ90-312-3109600; E-mail: [email protected]

Received 27 July 2012; Revised 31 October 2012; Accepted 3 November 2012

210

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Page 2: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

The purpose of colloid usage during CPB is to sustainosmotic pressure to avoid fluid loss from tissues anddecrease fluid retention. Hydroxyethyl starch (HES)solution is widely used as intravascular volume dilatorand priming solution in CPB in adult patients.3 It hasbeen claimed that AKI risk is increased during hypovo-lemia treatment with HES. Therefore, the effects of HESon kidney functions are still investigated.4 Although low-molecular-weight HES (130/0.4) solution does not affectkidneys, its effects on children are yet to be investigated.In this study, we aimed to observe the effects of HES(130/0.4) usage, as a priming solution, on the renal func-tions in child patients undergoing open heart surgery.

MATERIALS AND METHODS

After Local Medical Research Ethics Committeeapproval and parent informed consent, 24 patients aged2–16 years were included in this prospective, randomizedstudy. Patients with preoperative serum creatinine valueabove 1.5 mg/dL, heart failure, liver failure [aspartatetransaminase (AST) > 40 unit/L, alanine aminotransfer-ase (ALT) > 40 unit/L], insulin-dependent diabetes mel-litus (DM), history of cardiac surgery, allergies,corticosteroids, nonsteroidal anti-inflammatory drugs,and chronic furosemide usage were excluded from thestudy. Also, patients who were operated in emergencyconditions were not included in the study.

A partof thepatients received intravenous(IV)accessandthesepatientswereanesthetizedwith thiopental5mg/kg; theremaining patients received Sevoflurane anesthesia induc-tion,andthenIVaccess.Tracheal intubationwascarriedoutafter vecuroniumbromide0.1mg/kg and fentanyl 2–3μg/kginjection. Anesthesia maintenance was sustained bySevoflurane 1.5–2% and 50% O2–50% air combinations.Electrocardiogram (ECG), partial oxygen saturation(SpO2), arterial blood pressure, central venous pressure(CVP), and urine output weremonitored in all the patients.

The patients were divided into two randomized groupsaccording to the priming solution used in the CPB:Group I and Group II. Each group included 12 patients.In Group I, RL solution was used as priming solution,whereas in Group II, HES (130/0.4) solution was used.

CPB was performed using modified De Bakey rollerpump, membrane oxygenator (Dideco membraneD-901 or D-902 according to weight of the patient),nonpulsatile blood flow (2.4 mL/m2), and moderatehypothermia (28–32�C) and mean perfusion pressurewas kept between 40 and 50 mmHg duringCPB. Mannitol 20% 1 g/kg was added to the primingvolume. Hematocrit level was kept above 24% forpatients with weight >10 kg and 30% for patients with<10 kg. When the adequate hemodynamic wereobtained, the patients were weaned from CPB. Heparinwas neutralized with protamine. Erythrocyte suspensionwas applied to achieve hemoglobin level above 10 g/dL.

All the patients were administered to Cardiac SurgeryIntensive Care Unit (ICU) after the operation. The

patients with normal body temperature, normal hemo-dynamics, and controlled bleeding were separated fromthe mechanical ventilation.

Demographic and clinical data (age, sex, weight,operation duration, CPB duration, and aortic cross-clamping time), ICU duration, and hospitalization dura-tion were recorded for all the patients.

Laboratory parameters of blood and urine sampleswere collected and evaluated after the induction (T1),before CPB (T2), on the 20th minute of CPB (T3), afterCPB (T4), at the end of the operation (T5), on 24thhour (T6), and on 48th hour postoperatively (T7) inall patients. Hemodynamic parameters including systolicarterial pressure (SAP), diastolic arterial pressure(DAP), mean arterial pressure (MAP), heart rate, andCVP were recorded at the same time except the CPB.

Blood samples were analyzed for hematocrit andserum electrolytes [sodium (Na), potassium (K), chlor-ide (Cl)], creatinine, blood urea nitrogen (BUN),β2-microglobulin, and cystatin C levels at T1–T7. Todetermine cystatin C and β2-microglobulin levels, bloodsamples were centrifuged and kept in �20�C until themeasurement time. Blood samples were then thawed inroom temperature and cystatin C levels were measuredusing particle-enhanced immunoturbidimetric test, andβ2-microglobulin levels were measured using two-phasechemiluminescent immunoassay test. Blood neutrophillevels were analyzed at T1, T5, T6, and T7 periods.

In the urine samples collected from the patients, thefollowing urine electrolytes were monitored: Na, K, Cl,albumin, and creatinine. Fractional sodium excretion(FENa) value was determined by using the formula:(urine Na � plasma creatinine � 100)/(urine creatinine� plasma Na) at T1–T7 periods. Urine albumin/creati-nine ratio was calculated to determine the glomerulardamage at the same time. Creatinine clearance was deter-mined at T1, T5, T6, and T7 periods according to thefollowing formula: Cr. Clearance (mL/min) ¼ [(140 – age) � (body weight)]/[serum creatinine(mg/dL) � 72].

Total fluid administration, urine output, fresh frozenplasma and erythrocyte suspension amount, inotropicand diuretic requirements, and drainage amount fromchest tube were recorded at the end of the operation, on24th and 48th hours postoperatively, in all the patients.The first stage of AKI was defined by at least one of thefollowing criteria: an increase in serum creatinine of atleast 50% above baseline, an absolute increase in serumcreatinine of at least 0.3 mg/dL, and/or a urine output<0.5 mL/kg/h for at least 6 hours.

Statistical AnalysisThe statistical analysis of the data was processed by SPSS15.0 program. Shapiro–Wilk test was used to determinethe distribution pattern of the data. t Test was used fornormally distributed data, and Mann–Whitney U testwas used for independently distributed data to compare

© 2013 Informa Healthcare USA, Inc.

HES (130/0.4) as Priming Solution and Renal Function 211

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Page 3: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

the two groups. Friedman two-way analysis of variancetest was used to compare the time parameters of both thegroups. In the case of difference, Wilcoxon signed-ranktest was applied to compare the time parameters of boththe groups. Chi-square test was applied to analyze thecategorical data. Significance level was set to p < 0.05.

RESULTS

Twenty four patients were included in the study. Therewere no differences between the groups regarding age,gender, aortic cross-clamping time, operation, CPB,ICU duration, and hospitalization time (Table 1).There was no difference in the SAP, DAP, MAP, andCVP records between the groups. Only the heart rate wasfound to be increased (p < 0.05) in the RL group at T4and at the end of the operation (T5).

Serum and urine electrolyte levels also did not differsignificantly between the groups. β2-Microglobulinlevels were found to be decreased at T3 in both thegroups when compared with T1 (p < 0.05). There wereno differences between the two groups (Table 2).

Cystatin C levels were decreased in both the groups atT3, T4, and T5 compared with basal levels (p < 0.05)(Table 3). All the determined β2-microglobulin and cysta-tin C levels were in the normal range. The normal β2-microglobulin levels were in the range 1010–1730 ng/dL5

and the normal cystatin C levels were specified between0.63 and 1.33 mg/L in children (1–16 years old).6

Serum creatinine, BUN, urine albumin, and urinecreatinine levels did not differ significantly between thegroups. Calculated FENa levels did not differ betweenthe RL and HES groups (Figure 1).

While creatinine clearance values did not differ in theHES group, they were increased significantly in the RLgroup on 24th and 48th hours postoperatively comparedwith the T1 (p < 0.05). There were no differencesbetween the groups (Figure 2).

While Urine albumin/creatinine ratio was increasedsignificantly (p < 0.05) only after CPB in the HESgroup, significant increase was observed during CPBtoo at the end of the operation (T3, T4, and T5) in theRL group (p < 0.05) when compared with basal level.The ratio did not differ significantly between the groups(Table 4).

Total fluid administration, total urine output, drainageamount from chest tube and erythrocyte suspension (ES)and fresh frozen plasma (FFP) support did not differsignificantly between the two groups (p > 0.05),(Table 5).

Table 1. Demographic and clinical data of Groups I and II(mean � SD).

Group I (RL) Group II (HES)

Age (year) 5.1 � 3.7 3.9 � 1.7Gender (F/M) 7/5 6/6Weight (kg) 16.2 � 8.8 13.5 � 4.5Operation duration (min) 203.3 � 57.3 214.5 � 57.9CPB duration (min) 73.8 � 40.9 65.6 � 29.2Aortic clamp duration (min) 52.5 � 36.2 42.3 � 26.2ICU duration (day) 3 � 2.8 2.5 � 2.2Hospitalization duration (day) 5.9 � 3.2 5 � 2.3

Table 3. Cystatin C levels of the RL andHES groups (mean� SD)(mg/L).

Group I (RL) Group II (HES)

T1 0.82 � 0.19 1.01 � 0.18T2 0.91 � 0.19 0.96 � 0.21T3 0.61 � 0.12� 0.71 � 0.11�

T4 0.67 � 0.16� 0.82 � 0.13�

T5 0.67 � 0.16� 0.82 � 0.12�

T6 0.84 � 0.14 0.96 � 0.21T7 0.81 � 0.16 0.95 � 0.18

Note: �p < 0.05 within the group, compared to (T1) period.

FENa (%)

1.2

1

0.8

0.6

0.4

0.2

0

T1 T2 T3 T4 T5 T6 T7

RL

HES

Figure 1. FENa levels in the RL and HES groups (%).

CCr(mL/min)

**120

100

80

60

40

20

0

T1 T5 T6 T7

RL

HES

Figure 2. Creatinine clearance levels in the RL and HES groups.Note: �p < 0.05 within the group, compared to (T1) period.

Table 2. β2-Microglobulin levels (mean � SD) (ng/dL).

Group I (RL) Group II (HES)

T1 1395.9 � 247.8 1669.9 � 401.9T2 1467.4 � 250.3 1622.4 � 406.4T3 961.4 � 181.1� 1137.7 � 279.9�

T4 1224.2 � 260.8 1500.2 � 301.9T5 1208.7 � 265.5 1476.7 � 381.8T6 1285.3 � 299.6 1569.4 � 936.3T7 1267.3 � 316.7 1305.8 � 293.2

Note: �p < 0.05 within the group, compared to (T1) period.

Renal Failure

212 F.G. Akkucuk et al.

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Page 4: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

Diuretic (furosemide) was applied to four patients inthe HES group and five patients in the RL group.Diuretic usage statistics did not differ significantlybetween the groups (p > 0.05).

Inotropic support (dopamine) was required for twopatients in the HES group and two patients in the RLgroup. Inotropic requirements did not differ significantlybetween the groups.

Neutrophil levels were increased at the end of the opera-tion (T5) and still higher on the 48th hour postoperatively(T6, T7) compared to the basal levels (T1) in both withinthe groups (p < 0.05). The comparison level of the twogroups did not show significant difference when com-pared between the two groups (p > 0.05)(Table 6).

As the priming solution, 391,417 � 207,25 mL RLwas used in the RL group and 316,67� 86,164 mLHES(130/0.4) in the HES group (Table 7).

We did not observe any renal dysfunction (an increasein serum creatinine of at least 50% above baseline, anabsolute increase in serum creatinine of at least 0.3 mg/dL, and/or a urine output <0.5 mL/kg/h for at least6 hours) in both the groups.

DISCUSSION

We evaluated HES (130/0.4) usage as priming solutionon subclinical and clinical renal functions on pediatricpatients undergoing cardiac surgery. We compared HESandRL solutions. Both the groups were similar regardingto demographic and clinical data.

In pediatric age group, acute renal failure (ARF) wasthe most commonly observed complication of CPB andshowed poor prognosis.7 In a study conducted byChesney and colleagues,8 among 248 infant patients,20 patients developed ARF, 6 patients required dialysis,and 13 patients were lost. In another study conducted byRidgen and colleagues,9 the risk factors that lead to ARFdevelopment after CPB were investigated in pediatricpatients. The research team concluded that complexityof cardiac diseases, risky nature of cardiac surgery andlong CPB period, chronic hypoxia and acidosis as theresult of already existing diseases, and heart failureobserved in early terms increased the incidence of post-operative ARF. The group reported a significant increasein ARF ratio, especially in newborn patients. It was alsostated that in pediatric patients, already existing diseasesand age were more crucial parameters for determiningthe postoperative renal failure than bypass time periodalone.

In our study, none of the patients developed renalfailure or required dialysis.

During CPB, the contact between the blood compo-nents and synthetic surfaces released the inflammatorymediators, which led to endothelial permeabilityincrease.10–12 Furthermore, several changes wereobserved in intravascular volume status and intravascularfluid during the bypass.13,14 One of the disadvantages ofthe hemodilution is that it decreases the intravascularosmotic pressure and leads to interstitial edema forma-tion. Especially, the crystalloid fluids can increase theextracellular fluid volume and cause massive interstitialfluid volume expansion.

Colloids are able to stay in the intravascular compart-ment for a long time and sustain normovolemia withsmall amounts. Thus, they do not cause excess fluidvolume.15 Therefore, to provide osmotic pressure, andreduce the fluid escape to tissue and fluid retention,fluids that have high oncotic pressure (HES, albumin,and gelatin) were selected as the priming solutions.These solutions can prevent capillary escape, whichleads to fluid escape to tissue intervals, and tissueedema, which is caused by decreased oncotic pressureduring CPB.16,17

Table 4. Urine albumin/creatinine ratios in patients (mean � SD)(μg/mg).

Group I (RL) Group II (HES)

T1 33.5 � 30.1 48.4 � 76.1T2 53.9 � 69.8 51.2 � 42.5T3 95.6 � 117.1� 75.7 � 70.1T4 127.6 � 105.1� 163.3 � 249.8�

T5 171.7 � 189.9� 108.5 � 84.1T6 69.8 � 124.7 37.9 � 32.8T7 33.4 � 24.7 65.1 � 93.3

Note: �p < 0.05 within the group, compared to (T1) period.

Table 5. Fluid balance of Groups I and II (mean � SD)(�103/μL).

Group I (RL) Group II (HES)

Drainage (mL) 192.1 � 109.1 236.6 � 127.2Urinary output (mL) 1642.5 � 839.1 1176.2 � 648.1Total fluid (mL) 1795.8 � 890.5 1488.3 � 390.3Erythrocyte susp (mL) 242.5 � 218.5 159.5 � 94.3Fresh frozen plm (mL) 224.2 � 167.4 210.4 � 149.5

Table 6. Neutrophil levels in the RL and HES groups (mean� SD) (�103/μL).

Group I (RL) Group II (HES)

T1 4.48 � 2.64 3.88 � 1.48T5 8.5 � 3.4� 9.4 � 4.7�

T6 8.4 � 1.8� 10.1 � 4.2�

T7 8.4 � 3.2� 7.9 � 2.2�

Notes: All data are presented as mean � SD.*p < 0.05.

Table 7. ES and RL/HES amounts added into priming solution(mean � SD) (mL).

Added amount (mL) Group I (RL) Group II (HES)

ES 216.67 � 126.73 245.83 � 75.25RL/HES 391.417 � 207.25 316.67 � 86.164

© 2013 Informa Healthcare USA, Inc.

HES (130/0.4) as Priming Solution and Renal Function 213

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Page 5: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

Several studies that used albumin and HES as primingsolutions indicate that conservation of colloid osmoticpressure during CPB reduced the fluid amount accumu-lated between the tissues.18 Also, colloidal priming solu-tion usage reduced the total blood volume andintraoperative fluid requirement.17

Tiryakioglu and colleagues19 compared the RL andHES 130/0.4 usage as the priming solution on adultpatients and observed that BUN and serum creatininelevels were higher in the HES 130/0.4 group atpostoperative 24th hour. The research group evaluatedthe possible negative effects of HES 130/0.4 on renalfunctions, but serious renal damages or failures werenot observed in patients. Even though the urea and crea-tinine levels were higher compared with the controlgroup, the levels were in the normal range. Also, serumelectrolyte levels such as Na, K, Cl, and Ca did not differsignificantly between the groups.

In our study, we did not find significant differencesbetween the creatinine levels of both the groups. Also,urine and serum electrolytes did not show significantdifference between the groups.

Ooi and colleagues20 conducted a research on 90 adultpatients who underwent coronary artery bypass graftsurgery. Forty-five patients received 6% HES 130/0.4(Voluven) and another 45 were given 4% succinylatedgelatin (Gelofusine) as the priming solution for the CPBcircuit as well as for volume replacement. They com-pared the coagulation parameters and changes in therenal functions. The study demonstrated that HES 130/0.4 did not have negative effects on renal functions andcoagulation parameters. It was concluded that 6%HES130/0.4 is a safe alternative colloid for priming theCPB circuit and volume replacement in patients under-going coronary artery bypass surgery.

Cystatin C is a cysteine protease inhibitor that issynthesized by nucleated cells and subsequently releasedin the blood stream, especially after renal injury. Recenttrials suggested that cystatin C has clinical utility in theearly detection of cardiac surgery associated AKI and itwas superior to serum creatinine.21

Herrero-Morin and colleagues5 performed a study toidentify the renal failures by comparing serum creatinineto cystatin and β2-microglobulin on child patients admi-nistered to ICU. Serum cystatin C and β2-microglobulinare more reliable and convenient markers than creatinineto identify ARF and minor differences in glomerularfiltration rate (GFR). Unlike the other biomarkers, cysta-tin C is not affected by inflammatory, immunologic, andneoplastic disturbances.22 Also, because of the difficul-ties during urine sample collection from children andurine loss during this procedure, cystatin C is acceptedto be a better biomarker than serum creatinine to deter-mine the renal function progresses in pediatric popula-tion.5 In pediatric population, cystatin C concentrationlevels are elevated after birth, but started to decreasequickly in the following weeks. In children between 1and 16 years of age, the normal range of cystatin C is

determined as 0.63–1.33 mg/L.5,6 Therefore, we mon-itored cystatin C and β2-microglobulin levels in ourstudy.

In our study, the levels of cystatin C were significantlydecreased during CPB, after CPB, and after the opera-tion in both the groups. We observed that measuredcystatin C levels remained within normal range for allthe study periods in both the groups.

When we examined β2-microglobulin levels, weobserved that β2-microglobulin levels were found to bedecreased during CPB in both the groups when com-pared with baseline. There were no differences betweenthe two groups and all the levels were within the normalrange. Since β2-microglobulin levels did not increaseand remained within the normal range, we consideredthat there was no renal tubular damage.

During CPB, neutrophils and vascular endotheliumwere shown to be activated via upregulation of adhesionmolecules such as CD11b and CD4 and thought to playan important role on pathophysiology of renal complica-tions.23,24 HES solution can decrease vascular perme-ability and inflammatory response activation during CPBby preventing leukocyte adhesion and chemotaxis.25 Inour study, increase in both the groups was detected asexpected. However, there were no significant differencesbetween the groups.

Haneda and colleagues26 claimed that colloidal solu-tions should be added to priming solutions in treatmentof pediatric patients. In their retrospective study, theydemonstrated that fluid balance of colloid hemodilutionwas superior to crystalloid hemodilution.

Aukerman and colleagues27 demonstrated that albu-min addition to priming solution in pediatric patients ledto less increase in the off-pump weight. Another studywith albumin conducted by Riegger and colleagues28

demonstrated that off-pump weight was similar.However, blood transfusion requirement was increased.

Loeffelbein and colleagues29 examined the effects ofalbumin in priming solutions and impact of FFP onrenal functions after CPB, by evaluating protein excretionin urine, creatinine, and creatinine clearance in newbornsand infants. As the result, intraoperative renal functionswere found to be distorted in both the groups but notin the significant levels. Also, protein loss in postoperativeand creatinine clearance levels did not differ significantly.

When the intraoperative and postoperative urine sam-ples were examined, no significant differences werefound in microalbumin, creatinine, and creatinine clear-ance levels. Furthermore, we determined urinary albu-min/creatinine ratio to assess glomerular damage. Eventhough the two groups did not show significant differ-ence, we determined a significant increase within thelevels of the RL group during CPB and it increasedafter operation and it was decreased on postoperative24th hours. Albumin/creatinine (Alb/Cr) ratio wasincreased only after CPB in the HES group. But, therewas no any difference between the two groups regardingelevated levels of FENa and any changes were not

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Page 6: The Effect of HES (130/0.4) Usage as the Priming Solution on Renal Function in Children Undergoing Cardiac Surgery

determined in the levels of β2-microglobulin in the sametime intervals. Therefore, these findings suggested thatonly an increase in Alb/Cr ratio levels is not sufficient forthe diagnosis of transient tubulointerstitium damage.Weconsider glomerular edema related to interstitial volumeincrease and nephron ischemia as a reason.

In our study, inotropic (dopamine) and diuretic(furosemide) usage did not differ significantly in thetwo groups.

The studies in the literature that was based on HES130/0.4 usage in CPB to understand its effects on renalfunctions were based on adult patients. In those studies,it was found that HES 130/0.4 usage as the primingsolution was reliable. We used HES 130/0.4 solution aspriming solution in pediatric CPB patients and tried toexamine the effects on renal functions. In both thegroups, we did not detect any renal functional difference.We also did not observe any negative effects of HES 130/0.4 on kidney functions.

We conclude that HES 130/0.4 usage as the pumppriming solutions in pediatric patients who are under-going cardiac surgery did not show any negative effectson renal functions and it can be used safely as the CPBpriming solution in pediatric patients undergoing cardiacsurgery.

Declaration of interest: The authors report no con-flicts of interest. The authors alone are responsible for thecontent and writing of the paper.

This study was financially supported by theDepartment of Anesthesiology and Reanimation,Hacettepe University, Faculty of Medicine.

REFERENCES

[1] Arora P, Kolli H, Nainani N, Nader N, Lohr J. Preventable riskfactors for acute kidney injury in patients undergoing cardiacsurgery. J Cardiothorac Vasc Anesth. 2012;26(4):687–697. Epub2012 Apr 18.

[2] Davies LK. Cardiopulmonary bypass in infants and children:how is it different? J Cardiothorac Vasc Anesth. 1999;13(3):330–345.

[3] Chong Sung K, Kum Suk P, Mi Ja Y, Kyoung Ok K. Effects ofintravascular volume therapy using hydroxyethyl starch (130/0.4) on post-operative bleeding and transfusion requirementsin children undergoing cardiac surgery: a randomized clinicaltrial. Acta Anaesthesiol Scand. 2006;50(1):108–111.

[4] Wyckoff T, Augoustides JG. Advances in acute kidney injuryassociated with cardiac surgery: the unfolding revolution in earlydetection. J Cardiothorac Vasc Anesth. 2012;26(2):340–345.

[5] Herrero-Morin JD, Malaga S, Fernandez N. Cystatin C andbeta2-microglobulin: markers of glomerular filtration in criti-cally ill children. Crit Care. 2007;11(3):R59.

[6] Finney H, Newman DJ, Thakkar H, Fell JM, Price CP.Reference ranges for plasma cystatin C and creatinine measure-ments in premature infants, neonates, and older children. ArchDis Child. 2000;82(1):71–75.

[7] Ogg CS, Cameron JS. Cardiovascular surgery and the kidney.Guys Hosp Rep. 1969;118(1):85–103.

[8] Chesney RW, Kaplan BS, Freedom RM. Acute renal failure: animportant complication of cardiac surgery in infants. J Pediatr.1975;87(3):381–388.

[9] Rigden SP, Barrat TM, Dillon MJ. Acute renal failurecomplicating cardiopulmonary bypass surgery. Arch Dis Child.1982;57(6):425–430.

[10] Wan S, LeClerc JL, Vincent JL. Inflammatory response to car-diopulmonary bypass: mechanisms involved and possibletherapeutic strategies. Chest. 1997;112(3):676–692.

[11] Levy JH, Tanaka KA. Inflammatory response to cardiopulmon-ary bypass. Ann Thorac Surg. 2003;75(2):S715–S720.

[12] ChenowethDE, Cooper SW,Hugli TE. Complement activationduring cardiopulmonary bypass: evidence for generation of C3aand C5a anaphylatoxins. N Engl J Med. 1981;304(9):497–503.

[13] Mehlhorn U, Davis KL, Burke EJ. Impact of cardiopulmonarybypass and cardioplegic arrest on myocardial lymphatic func-tion. Am J Physiol. 1995;268(1 Pt 2):H178–H183.

[14] Heltne JK, Bert J, Lund T. Temperature-related fluid extravasa-tion during cardiopulmonary bypass: an analysis of filtrationcoefficients and transcapillary pressures. Acta AnaesthesiolScand. 2002;46(1):51–56.

[15] Base EM, Standl T, Lassnigg A, et al. Efficacy and safety ofhydroxyethyl starch 6% 130/0.4 in a balanced electrolyte solu-tion (Volulyte) during cardiac surgery. J Cardiothorac VascAnesth. 2011;25(3):407–414.

[16] KuitunenAH,HynynenMJ, Vahtera E.Hydroxyethyl starch as apriming solution for cardiopulmonary bypass impairs hemostasisafter cardiac surgery. Anesth Analg. 2004;98(2):291–297.

[17] Rex S, Scholz M, Weyland A. Intra- and extravascular volumestatus in patients undergoing mitral valve replacement: crystal-loid vs. colloid priming of cardiopulmonary bypass. Eur JAnaesthesiol. 2006;23(1):1–9.

[18] Tollofsrud S, Svennevig JL, Breivik H. Fluid balance and pul-monary functions during and after coronary artery bypass sur-gery: ringer’s acetate compared with dextran, polygeline, oralbumin. Acta Anaesthesiol Scand. 1995;39(5):671–677.

[19] Tiryakioglu O, Yıldız G, Vural H. Hydroxyethyl starch versusRinger solution in cardiopulmonary bypass prime solutions(a randomized controlled trial). J Cardiothorac Surg. 2008;3:45.

[20] Ooi JS, Ramzisham AR, ZamrinMD. Is 6% hydroxyethyl starch130/0.4 safe in coronary artery bypass graft surgery? AsianCardiovasc Thorac Ann. 2009;17(4):368–372.

[21] Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C issuperior to serum creatininee as a marker of kidney function: ameta-analysis. Am J Kidney Dis. 2002;40(2):221–226.

[22] NewmaN DJ, Thakkar H, Edwards RG. Serum cystatin C mea-sured by automated immunoassay: a more sensitive marker ofchanges in GFR than serum creatininee. Kidney Int. 1995;47(1):312–318.

[23] Galinanes M, Watson C, Trivedi U. Differential patterns ofneutrophil adhesion molecules during cardiopulmonary bypassin humans. Circulation. 1996;94(Suppl. 9):II364–II369.

[24] Rinder CS, Fontes M, Mathew JP. Neutrophil CD11bupregulation during cardiopulmonary bypass is associated withpostoperative renal injury.Ann Thorac Surg. 2003;75(3):899–905.

[25] Iriz E, Kolbakır F, Akar H. Comparison of hydroxyethyl starchand ringer lactate as a prime solution regarding S-100beta pro-tein levels and informative cognitive tests in cerebral injury. AnnThorac Surg. 2005;79(2):666–671.

[26] Haneda K, Sato S, Ishizawa E. The importance of colloid osmo-tic pressure during open heart surgery in infants. Tohoku J ExpMed. 1985;147(1):65–71.

[27] Aukerman J, Vopel-Lewis T. The relationship between extra-corporeal circuit prime, albumin, and postoperative weight gainin children. J Cardiothorac Vasc Anesth. 1998;12(4):408–414.

[28] Riegger LQ, Voeppel-Lewis T, Kulik TJ. Albumin versus crys-talloid prime solution for cardiopulmonary bypass in youngchildren. Crit Care Med. 2002;30(12):2649–2654.

[29] Loeffelbein F, Zirell U, Benk C. High colloid oncotic pressurepriming of cardiopulmonary bypass in neonates and infants:implications on hemofiltration, weight gain and renal function.Eur J Cardiothorac Surg. 2008;34(3):648–652.

© 2013 Informa Healthcare USA, Inc.

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