Asian Cardiovasc Thorac Ann 2007;15:376-380
© 2007 Asia Publishing EXchange Ltd
Continuous Hemodiafiltration During Cardiopulmonary Bypass in Infants
Naoki Yoshimura, MD,
Yoshihiro Oshima, MD,
Masahiro Yoshida, MD,
Hirohisa Murakami, MD,
Hironori Matsuhisa, MD,
Masahiro Yamaguchi, MD
Department of Cardiothoracic Surgery, Kobe Children’s Hospital, Kobe, Japan
For reprint information contact: Naoki Yoshimura, MD, Tel: 81 76 434 7330, Fax: 81 76 434 5032, Email: ynaoki{at}med.u-toyama.ac.jp, First Department of Surgery, University of Toyama, School of Medicine, 2630, Sugitani, Toyama 930-0194, Japan.
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ABSTRACT
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The homologous blood prime in cardiopulmonary bypass circuits contributes a significant electrolyte and metabolite load in small infants. The efficacy of hemofiltration and continuous hemodiafiltration of the blood prime in preventing metabolic disturbances in small infants was compared in two groups of 60 patients each. Blood pH, base excess, and calcium concentrations decreased during cardiopulmonary bypass in the hemofiltration group. The acid-base balance was well preserved during cardiopulmonary bypass by continuous hemodiafiltration. This therapeutic strategy may confer an advantage in maintaining more physiological conditions during cardiopulmonary bypass in small infants.
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INTRODUCTION
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Despite miniaturized oxygenators and improvements in cardiopulmonary bypass (CPB) systems, homologous blood components must be used to prime the circuit to maintain the hematocrit and osmotic pressure during CPB in neonates and small infants. The homologous blood prime in CPB circuits contributes a significant electrolyte and metabolite load that may cause unfavorable metabolic responses.1,2 Moreover, some inflammatory or vasoactive substances in the blood prime are also activated at the start of CPB, which may have some deleterious effects on neonates and small infants.3–6 Recently, ultrafiltration of the blood prime before CPB was reported as a new technique to reduce the inflammatory response as well as to adjust pH and the concentrations of electrolytes.7,8 In 1994, we started using hemofiltration (HF) of the blood prime and confirmed that it attenuates the hemodynamic impairment and unphysiologic concentrations of electrolytes at the start of CPB. In 2002, we modified the technique so that continuous hemodiafiltration (CHDF) was carried out both before and during CPB. In this study, we compared the efficacy of HF and CHDF in preventing metabolic disturbances due to CPB in neonates and small infants.
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PATIENTS AND METHODS
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One hundred and twenty neonates and small infants who had a variety of congenital heart defects were enrolled in this study. Sixty consecutive patients who underwent open heart surgery using CPB with CHDF (CHDF group) from October 2002 to December 2004 were compared retrospectively with 60 patients who had undergone an operation using CPB with hemofiltrated blood prime (HF group) from September 2000 to October 2002. During these periods, the strategy for performing CPB in neonates and small infants did not change. The preoperative diagnoses in each group are listed in Table 1
. All patients weighed < 6 kg, and there was no difference in mean body weight between the two groups. Approval from the local ethics committee was obtained, as was informed consent from the parents or guardians of all participating patients.
The pump prime volume was 270–500 mL. One or 2 units of packed red blood cells were used to prime the bypass circuit in both groups. Banked blood, 72–120 hours old, was used in all patients. Acetate Ringer’s solution (Veen F; Nikken Chemicals Co., Tokyo, Japan) and/or 5% v/v albumin solution were added in a volume calculated to achieve a hematocrit of 30% on bypass. The circuit for CPB consisted of a roller pump and a membrane oxygenator (D901 Liliput 1; Dideco, Mirandola, Italy, or BABY-RX; Terumo Co., Tokyo, Japan). The perfusion flow was maintained between 2.2 and 2.6 mL·min–1·m–2. Mild to moderate hypothermia was induced in all patients. Deep hypothermic circulatory arrest was not used in this series. During the rewarming period, trinitroglycerin and chlorpromazine hydrochloride were given as afterload-reducing agents. Myocardial protection was achieved with intermittent cold blood cardioplegia and terminal warm blood cardioplegia in all patients.9
In the HF group, a polyacrylonitrile ultrafilter (PANFLO APF-03S, Asahi Medical Co., Tokyo, Japan) with an effective membrane area of 0.3 m2, a priming volume of 33 mL, a luminal diameter of 250 µm, and a membrane thickness of 35 µm was used. The ultrafilter was inserted between the arterial line of the bypass circuit and the cardiotomy reservoir. For each unit of red blood cell prime, 1,000 mL of the HF solution, containing 140.0 mEq·L–1 Na+, 2.0 mEq·L–1 K+, 3.5 mEq·L–1 Ca2+, 1.5 mEq·L–1 Mg2+, 107.0 mEq·L–1 Cl–, and 40.0 mEq·L–1 acetate (Sublood, Fuso Ltd., Osaka, Japan), was added to the pump circuit, and the same volume of fluid was hemofiltrated before initiation of CPB. Conventional ultrafiltration was started from the rewarming phase of CPB at a rate adjusted to reach a hematocrit > 30% on termination of CPB. Continuous hemodiafiltration was performed with the same PANFLO ultrafilter used in the HF group. The system was connected between the arterial line and the cardiotomy reservoir. The blood flow rate was 50 mL·min–1, and the ultrafiltration balance was set at zero. The blood flow and dialysis fluid balance were controlled by CHDF apparatus (JUN-500; Ube Ltd., Tokyo, Japan). Hemofiltration solution containing 140.0 mEq·L–1 Na+, 2.0 mEq·L–1 K+, 3.5 mEq·L–1 Ca2+, 1.0 mEq·L–1 Mg2+, 111.0 mEq·L–1 Cl–, 3.5 mEq·L–1 acetate, 35.0 mEq·L–1 bicarbonate, and 100.0 mg·dL–1 glucose (Sublood B; Fuso Ltd., Osaka, Japan) was used at a flow rate of 1,000 mL·hr–1. In both HF and CHDF groups, modified ultrafiltration was performed after the termination of CPB.
Samples for blood gas and electrolyte analyses were obtained from the arterial line of the bypass circuit at 10, 40, 70 and 100 min after the initiation of CPB, and from an indwelling arterial cannula just after termination of CPB. Samples were also obtained from the prime after HF or CHDF.
All values are expressed as mean ± standard deviation. An unpaired t test was used to evaluate differences in each clinical variable between the two groups. Differences in parameters between groups at each time during CPB were assessed by a factorial analysis of variance. Statistical significance was tested at the 95% confidence level.
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RESULTS
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There were 3 early deaths in the CHDF group, and 4 in the HF group. Six patients died from cardiac failure, and one died from pulmonary hypertensive crisis. There were no significant differences between the two groups in terms of sodium bicarbonate requirement (1.0 ± 3.0 mL in CHDF group vs 1.5 ± 5.1 mL in HF group) and urine output (14.9 ± 10.8 mL·kg–1·hr–1 in CHDF group vs 17.1 ± 13.1 mL·kg–1·hr–1 in HF group) during CPB. The serum lactate concentration at the end of the operation did not differ between the groups (2.28 ± 1.56 mmol·L–1 in the CHDF group vs 2.63 ± 2.87 mmol·L–1 in the HF group). Maximum doses of inotropic agents after the operation (dopamine: 8.7 ± 2.0 µg·kg–1·min–1 in CHDF group vs 8.3 ± 2.2 µg·kg–1·min–1 in HF group; dobutamine: 5.4 ± 3.3 µg·kg–1·min–1 in CHDF group vs 4.5 ± 2.5 µg·kg–1·min–1 in HF group), duration of mechanical ventilatory support (3.4 ± 1.8 days in CHDF group vs 5.9 ± 6.7 days in HF group), and intensive care unit stay (8.5 ± 3.2 days in CHDF group vs 11.9 ± 7.7 days in HF group) were not significantly different between the groups.
Arterial blood pH levels are shown in Figure 1. The pH levels were lower in the HF group than the CHDF group at 40 and 70 min after the initiation of CPB, and on completion of CPB. Changes in base excess during and just after CPB are depicted in Figure 2. The base excess levels were maintained within the normal range during CPB in the CHDF group, whereas they decreased in the HF group; there were significant differences between the 2 groups at 40, 70, and 100 min after the initiation of CPB, and at the completion of CPB. The concentrations of electrolytes are shown in Figure 3. A significant difference was noticed between the groups with respect to calcium and potassium levels during CPB, whereas no difference was observed in sodium levels. The mean serum calcium concentrations were maintained within the physiologic range during CPB in the CHDF group, whereas they gradually decreased in the HF group. The mean serum potassium concentrations gradually increased during CPB in the HF group. The serum osmolarity in both groups changed within the physiologic range during CPB (Figure 4).
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Figure 1. Changes in arterial blood pH levels. CHDF = continuous hemodiafiltration, HF = hemofiltration. T1 = after CHDF or HF, T2 = 10 min after start of CPB, T3 = 40 min after start of CPB, T4 = 70 min after start of CPB, T5 = 100 min after start of CPB, T6 = at end of CPB.
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Figure 2. Changes in the base excess (BE) levels. CHDF = continuous hemodiafiltration, HF = hemofiltration. T1 = after CHDF or HF, T2 = 10 min after start of CPB, T3 = 40 min after start of CPB, T4 = 70 min after start of CPB, T5 = 100 min after start of CPB, T6 = at end of CPB.
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Figure 3. (A) Changes in mean serum calcium concentration. (B) Changes in mean serum potassium concentration. (C) Changes in mean serum sodium concentration. CHDF = continuous hemodiafiltration, HF = hemofiltration. T1 = after CHDF or HF, T2 = 10 min after start of CPB, T3 = 40 min after start of CPB, T4 = 70 min after start of CPB, T5 = 100 min after start of CPB, T6 = at end of CPB.
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Figure 4. Changes in mean serum osmolarity. CHDF = continuous hemodiafiltration, HF = hemofiltration. T1 = after CHDF or HF, T2 = 10 min after start of CPB, T3 = 40 min after start of CPB, T4 = 70 min after start of CPB, T5 = 100 min after start of CPB, T6 = at end of CPB.
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DISCUSSION
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Cardiopulmonary bypass is still associated with a high morbidity and mortality in neonates and small infants. Some patients undergo a dramatic inflammatory reaction, leaving them with tissue edema, pulmonary dysfunction, and poor cardiac performance.3,6,10,11 Improved methods of CPB for neonates and small infants must be developed if the field of pediatric cardiac surgery is to progress to its full potential. A large prime volume and a small patient can lead to an unfavorable metabolic response, therefore, current efforts in many institutions have been directed toward reducing the prime volume.7 In addition to prime volume, the priming fluid is of major importance in determining the metabolic response to cardiac operations in such patients. The priming fluid is composed of citrate-phosphate-dextrose stored blood, crystalloid solution, and other additives. The stored blood has high concentrations of potassium and sodium, a low concentration of calcium, and a tendency to develop metabolic acidosis.7,12
Recently, several studies reported some favorable effects of HF of the priming fluid before CPB in small children. Ridley and colleagues7 demonstrated that HF of the priming fluid and replacement with a balanced electrolyte solution results in delivery to the patient of a reasonably physiologic substrate load. Nagashima and colleagues8 showed that HF of the priming blood reduced inflammatory mediators and adjusted the concentrations of electrolytes, resulting in attenuation of hemodynamic impairment and pulmonary dysfunction after CPB in neonates with transposition of the great arteries. In 1994, we started HF of the blood prime before CPB to reduce the deleterious effects at the onset of CPB in neonates and small infants. We confirmed that this attenuated hemodynamic impairment and unphysiologic concentrations of electrolytes at the onset of CPB. However, we observed that metabolic imbalances developed during CPB in some cases. We modified the technique in 2002 so that CHDF was carried out before and during CPB to improve the physiologic status in neonates and small infants. This study compared the effect of CHDF with HF during CPB in pediatric cardiac operations.
We found that pH and base excess levels were maintained within the normal ranges during CPB in the CHDF group. Carotti and colleagues13 demonstrated that pH and bicarbonate levels were well preserved during fetal cardiac bypass by the dialytic effect of CHDF in their experimental study. It is well known that metabolic acidosis is associated with many adverse effects such as depression of myocardial contractility, sensitization to arrhythmia, peripheral vasoconstriction, and increased pulmonary vascular resistance.14 Recently, bicarbonate hemodialysis has been increasingly performed in an attempt to treat metabolic acidosis.15 Bicarbonate is a physiological buffer, therefore, plasma bicarbonate concentration and blood pH progressively increase during the dialysis session. In contrast to acetate hemodialysis, bicarbonate hemodialysis does not interfere with gluconeogenesis or lipid synthesis. The buffer source in all modern versions of these therapies has thus been changed to bicarbonate.14 We used a dialysate bicarbonate concentration of 35 mmol·L–1 in this study. Several reports have confirmed that high dialysate bicarbonate (40–42 mmol·L–1) is safe, well tolerated, and better for correction of metabolic acidosis.14,15 We confirmed that bicarbonate CHDF is effective in maintaining the acid-base balance during CPB in neonates and small infants.
The very low serum calcium concentration in the citrate-phosphate-dextrose stored blood used in the pump priming fluid may contribute to hemodynamic instability at the onset of CPB (so called, initial drop).7 In the present study, we did not experience an initial drop, probably because HF or CHDF before CPB adjusted the unphysiologic serum concentration of calcium. Low serum calcium remains a cause for concern because of the theoretical possibility of hypotension and arrhythmias.7 In the CHDF group, serum calcium during CPB was maintained within the physiologic range, whereas it gradually decreased in the HF group. Precise control of serum potassium levels is also critically important in the perioperative management of small patients with congenital heart disease. The mean serum potassium concentration gradually increased during CPB in the HF group. We believe serum potassium should be maintained as low as possible during CPB in neonates and small infants because it can easily increase due to transfusion or oliguria.
One limitation of this study was that the underlying heart condition varied among the patients. Although each patient was in a similar condition during CPB, multiple factors such as severity of heart defects, CPB time, and hemostasis after CPB may have affected postoperative clinical parameters including need for inotropic support, duration of mechanical ventilation, and intensive care unit stay. The serum lactate concentration at the end of the operation did not differ between the 2 groups, despite maintaining a better acid-base balance during CPB in the CHDF group. Thus, it was thought that the hemodynamic state after CPB affected the serum lactate level in each patient. Overall there was no significant difference in postoperative clinical parameters, but we believe that maintaining a better physiologic condition during CPB should have clinical advantages for neonates and small infants.
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REFERENCES
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- Elliott MJ. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 1993;56:1518–22.[Abstract]
- Friesen RH, Campbell DN, Clarke DR, Tornabene MA. Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open heart operations. Ann Thorac Surg 1997;64:1787–9.[Abstract/Free Full Text]
- Wang MJ, Chiu IS, Hsu CM, Wang CM, Lin PL, Chang CI, et al. Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations. Ann Thorac Surg 1996;61:651–6.[Abstract/Free Full Text]
- Journois D, Pouard P, Greeley WJ, Mauriat P, Vouhe P, Safran D. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components. Anesthesiology 1994;81:1181–9.[Medline]
- Journois D, Israel-Biet D, Pouard P, Rolland B, Silvester W, Vouhe P, et al. High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children. Anesthesiology 1996;85:965–76.[Medline]
- Bando K, Vijay P, Turrentine MW, Sharp TG, Means LJ, Ensing GJ, et al. Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study. J Thorac Cardiovasc Surg 1998;115:517–27.[Abstract/Free Full Text]
- Ridley PD, Ratcliffe JM, Alberti KG, Elliott MJ. The metabolic consequences of a "washed" cardiopulmonary bypass pump-priming fluid in children undergoing cardiac operations. J Thorac Cardiovasc Surg 1990;100:528–37.[Abstract]
- Nagashima M, Imai Y, Seo K, Terada M, Aoki M, Shinoka T, et al. Effect of hemofiltrated whole blood pump priming on hemodynamics and respiratory function after the arterial switch operation in neonates. Ann Thorac Surg 2000;70:1901–6.[Abstract/Free Full Text]
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- Carotti A, Emma F, Picca S, Iannace E, Albanese SB, Grigioni M, et al. Inflammatory response to cardiac bypass in ewe fetuses: effects of steroid administration or continuous hemodiafiltration. J Thorac Cardiovasc Surg 2003;126:1839–50.[Abstract/Free Full Text]
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- Kirschbaum B. The effect of hemodialysis on electrolytes and acid-base parameters. Clin Chim Acta 2003;336:109–13.[Medline]
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ABSTRACT
INTRODUCTION
