Interact CardioVasc Thorac Surg 2008;7:969-972. doi:10.1510/icvts.2008.179333
© 2008 European Association of Cardio-Thoracic Surgery
Work in progress report - Cardiopulmonary bypass |
Bicarbonate buffered ultrafiltration leads to a physiologic priming solution in pediatric cardiac surgery
Wilhelm Alexander Osthausa,*,
Jan Sieversa,
Thomas Breymannb and
Robert Suempelmanna
a Klinik fuer Anaesthesiologie und Intensivmedizin, OE 8050, Medizinische Hochschule Hannover, Carl- Neuberg- Str.1, D- 30625, Hannover, Germany
b Klinik fuer Herz-, Thorax-, Transplantations- und Gefaeßchirurgie, Medizinische Hochschule Hannover, Hannover, Germany
Received 5 March 2008;
received in revised form 11 July 2008;
accepted 14 July 2008
 Conflict of Interest Policy: This study was sponsored by B. Braun AG, Melsungen, Germany and Life Systems, Medizintechnik-Service GmbH, Hamburg, Germany. The authors have no conflicts of interest that are directly relevant to the content of this study.
Corresponding author. Tel.: +49 511 532 9088; fax: +49 511 532 9048.
E-mail address: Osthaus.Alexander{at}MH-Hannover.de (W.A. Osthaus).
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Abstract
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Pediatric cardiopulmonary bypass (CPB) involves a high ratio of priming blood volume to patient blood volume. The composition of packed red blood cells (RBCs) is very unphysiological in terms of acid-base, electrolyte and metabolite values. Therefore, we tested the hypothesis whether ultrafiltration of the prime and replacement with bicarbonate buffered hemofiltration solution (BB-HS) is sufficient for reducing the metabolic load and reaching a physiologic state. For planned surgery of congenital heart defects with cardiopulmonary bypass, 20 CPB circuits were primed with BB-HS, gelatin and 1 unit of RBCs. The fluid was hemofiltrated using an ultrahemofilter at 300 ml/min until approximately 1000 ml of ultrafiltrate was restored with BB-HS. Blood gas analyses were obtained from the priming blood, once before and once after bicarbonate buffered ultrafiltration (BBUF). The measured substrates decreased significantly (P<0.001) after BBUF (glucose from 13.0±2.6 to 6.3±1.0 and lactate from 3.8±1.5 to 2.3±1.0 mmol/l). Acid-base parameters increased (P<0.001) to normal or high normal values (pH from 7.01±0.09 to 7.68±0.12; HCO3 from 12.1±2.4 to 25.4±3.6 mmol/l and BE from –15.4±3.6 to –0.8±3.7 mmol/l). Even the electrolytes sodium, potassium and calcium changed significantly (P<0.001) toward the physiologic range. BBUF is an efficient method of reducing the metabolic load of priming. After BBUF, even the electrolyte and acid-base balance reached a physiologic state, which is important for minimizing electrolyte and acid-base disturbances after initiation of CPB.
Key Words: Cardiopulmonary bypass; Congenital heart disease; Ultrafiltration; Priming volume; Metabolic load
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1. Introduction
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Pediatric cardiopulmonary bypass (CPB) involves a high ratio of prime volume to patient blood volume. The transfusion of a clear fluid prime from the circuit would cause hemodilution and induce severe anemia, especially in infants and neonates. Therefore, it is considered necessary to add packed red blood cells (RBCs) to the CPB circuit prime in order to maintain hemoglobin levels and the oxygen carrying capacity of the child's circulatory system. Unfortunately, the composition of RBCs is very unphysiological with acid-base, electrolyte and metabolite values far outside the normal range [1]. Preservation of RBCs in citrate-phosphate-dextrose-buffered (CPD) and saline-adenine-glucose-mannitol (SAG-M) solutions lead to high glucose levels, as nutrition for the red blood cell metabolism during storage, and a low pH caused by citric acid of the preservative solution and bicarbonate dilution. During prolonged storage, pH values fell further because the stored RBCs metabolize glucose to lactic acid and pyruvic acid, and the accumulated hydrogen ions are buffered by bicarbonate, leading to decreased bicarbonate and increased carbon dioxide concentrations. The increase in potassium and the decrease in sodium are due to paralysis of the membrane sodium-potassium pumps at the cold storage temperature of 4 °C with resultant leakage of potassium from the cells [2]. Few studies have used hemofiltration of the circuit prime prior to initiation of CPB to normalize electrolyte balance (particularly potassium and pH) and reduce inflammatory mediator concentrations [3–5]. Hemofiltration solutions based on normal saline could lead to hyperchloremic metabolic acidosis. So a more physiologic hemofiltration solution might be beneficial when a physiologic priming solution is to be achieved.
Therefore, we tested the hypothesis whether pre-washing of the priming solution by means of hemofiltration and replacement with physiological bicarbonate buffered balanced electrolyte solution is a sufficient method of reducing the metabolic load and reaching a physiologic state.
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2. Methods
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A prospective study was carried out on 20 CPB circuits prior to initiation of bypass. The CPB for pediatric open heart surgery is prepared in a standardized fashion including the following steps: calibration of the arterial sensor, leakage test of the heat exchanger by using the pressure system, followed by assembly of the CBP circuit. Thereafter, in this study, the circuit was primed with a bicarbonate buffered hemofiltration solution (BB-HS) (Duosol®, B.Braun, Melsungen, Germany), followed by 10 min circulation. After replacing the pre-bypass filter, gelatin 4% (Gelafundin® 4%, B.Braun, Melsungen, Germany) and one unit of CPD-buffered RBCs in SAG-M solution (stored at 4 °C) were added. The fluid was hemofiltrated using an ultrahemofilter (ME HF0S 0070, Medos AG, Langenselbold, Germany) at 300 ml min–1 with 150–180 mmHg of positive pressure. When approximately 1000 ml of ultrafiltrate was restored with BB-HS, 2000 I.U. of heparin (Liquemin, Hoffmann-La Roche AG, Grenzach-Wyhlen, Germany) and 3–5 ml/kg of mannitol (Mannitol-Infusionslösung 20, Serumwerk Bernburg, Bernburg, Germany) were added.
The same heart-lung machine (SIII, Stoeckert, Munich, Germany) and CPB circuit set-up were used for all tested priming solutions (Fig. 1). Every single CPB circuit consisted of a heparin-coated open system with a hard shell reservoir and an oxygenator (Hilite 1000 or 2800, Medos AG, Langenselbold, Germany), which is used for flows up to 1 or 2.8 l/min, respectively.
BB-HS is developed for continuous hemofiltration in intensive care patients with acute renal failure. It consists of two chambers, a large one with 4445 ml and a small one with 555 ml, which has to be conflated and mixed to receive the final solution. The composition of the final hemofiltration solution is close to the physiological values of extracellular fluid (Table 1).
Blood gas analyses were obtained from the RBCs, from the priming solution including the RBCs, once before and once after the hemofiltration procedure. The CPB circuit samples were drawn from the arterial line within the circuit. Blood samples were taken for immediate blood gas analysis using a standard blood gas oximetry system (Rapidlab 860, Siemens Healthcare Diagnostics, Bad Nauheim, Germany).
All measured data are presented as mean values±S.D. After testing for normal distribution using the Shapiro–Wilk test, we used a paired t-test to compare the mean values of the groups before and after BBUF. A P-value of <0.05 was considered statistically significant. Recorded data were analyzed using the SPSS software for Windows (version 9.0 SPSS Inc., Chicago, IL, USA).
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3. Results
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The investigated technique was utilized in 20 CPB circuits. BBUF of the priming solution caused significant changes in nearly all measured parameters (Table 2).
3.1. Acid-base-balance
Prior to BBUF, the priming solution had a low pH (7.01±0.09), actual bicarbonate (HCO3) (12.1±2.4 mmol l–1) and base excess (BE) (–15.4±3.6 mmol l–1). After BBUF, the measured parameters significantly increased (P<0.001) to normal or high normal values (pH 7.68±0.12; HCO3 25.4±3.6 mmol l–1; BE –0.8±3.7 mmol l–1).
3.2. Electrolytes
Apart from chloride (103±9 before vs. 103±3 mmol l–1 after BBUF; P=0.89) even the electrolyte concentrations changed significantly after BBUF (P<0.001) toward the physiologic range (sodium from 131±7 to 140±3 mmol l–1; potassium from 5.0±1.9 to 2.6±0.3 mmol l–1; calcium from 0.41±0.16 to 0.84±0.15 mmol l–1).
3.3. Substrates
The measured substrates glucose and lactate both significantly decreased (P<0.001) after BBUF (glucose from 13.0±2.6 to 6.3±1.0 mmol l–1; lactate from 3.8±1.5 to 2.3±1.0 mmol l–1) (Fig. 2).
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Fig. 2. Substrate concentrations; RBC; red blood cells; BBUF; bicarbonate buffered ultrafiltration; *P<0.001 priming solution before vs. after BBUF.
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Furthermore, BBUF caused a significant increase in hemoglobin from 9.6±2.2 to 11.1±2.4 g dl–1 (P=0.004) and hematocrit from 29.8±6.7 to 34.1±7.3% (P=0.004).
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4. Discussion
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Establishment of CPB may produce similar effects as rapid blood transfusion. Massive and rapid transfusion of RBCs may lead to a substantial load of hydrogen ions, carbon dioxide and potassium, associated with hemodynamic instability caused by acid-base and electrolyte disorders [6, 7]. The severe burden of the intermediary metabolites glucose and lactic acid is described as metabolic or substrate load which could lead to neurological disturbances [6–10]. We found that hemofiltration of the prime and replacement with BB-HS substantially reduced the metabolic load. The resulting priming solution has low lactate and normal glucose levels. In contrast, sodium, pH, actual bicarbonate and base excess increased significantly and likewise reached levels within the normal physiological range. We showed that bicarbonate buffered ultrafiltration (BBUF) of the priming blood produces a physiological solution, which is very important to neonates and infants undergoing cardiac surgery for complex congenital heart disease.
Potassium concentrations above 5 mmol l–1 have been shown to cause distinct changes in the electrocardiogram indicating hyperkalemia; and cardiac arrhythmias have been associated with concentrations over 7.5 mmol l–1 [7]. Of note, the highest measured potassium concentration in the prime after BBUF was 3.1 mmol l–1 in our study.
Commonly prepared priming fluids for neonates and infants consist of RBCs in an electrolyte solution, e.g. Ringer's lactate or Plasmalyte, with the addition of a colloid plus sodium bicarbonate, calcium chloride, magnesium, mannitol and heparin [11]. This method cannot eliminate any unwanted substances such as potassium or the preservation substrates of the RBCs, e.g. lactate, citrate, adenine and phosphate. These substrates are only diluted, the acid-base balance is corrected, but lactate or acetate is also added through the crystalloid solution used. This metabolic load puts a burden on the patient prior to a situation of reduced metabolism caused by hypothermia and the metabolic response to surgery. Moreover, the added sodium bicarbonate buffer increased the sodium concentration of the prime to hypernatremic levels, which have been reported to be potentially harmful. During acute onset of hypernatremia, brain shrinkage can cause tearing of the falx and venous sinus leading to subdural, subarachnoidal and parenchymal hemorrhage and thrombosis of small veins and dural sinuses [12].
Therefore, different methods have been developed to reduce the unfavorable effects of stored blood.
Washing the RBCs in a cell saver before addition to the CPB circuit prime is an accepted method of reducing high potassium concentrations and lactate levels [13]. Despite the benefits of pre-washed RBCs, washing with normal saline can result in hyperchloremic metabolic acidosis [14]. The necessary addition of sodium bicarbonate buffer increases the sodium concentration of the prime even further, leading to the complications discussed above. In addition, the red cell washing process may have the potential to further damage the RBCs which could shorten their survival time after transfusion.
Ultrafiltration has also been shown to reduce the adverse effects of stored blood. Performed prior to CBP, ultrafiltration also lowers cytokine production, and this results in significantly reduced inotropic support and shorter duration of ventilator support and ICU stay [4].
Ultrafiltration via a hemofilter results in a negative fluid balance. When the ultrafiltrate is continuously replaced with a physiologic solution, it is called hemofiltration, or, in the context of CPB, zero balanced ultrafiltration. Because of the replacement of the ultrafiltrate, the prime fluid or the patient's blood could be filtrated several times, which increases the effectiveness of the method. The commonly used crystalloid replacement solution for zero balanced ultrafiltration is Plasmalyte, an isotonic electrolyte solution containing acetate as a bicarbonate precursor. We call the method BBUF when the hemofiltration solution contains bicarbonate instead of metabolizable anions. So BBUF is zero balanced ultrafiltration with a bicarbonate buffered hemofiltration solution as replacement solution.
From our point of view, BBUF has several advantages when compared with the previous techniques. Firstly, the resultant priming blood is stripped of the metabolic load. Secondly, the acid-base balance and the electrolyte balance including sodium and potassium are in the physiological range. Thirdly, the method is as effective as and less expensive than the cell saver technique. When the ultrahemofilter is left in the CPB, hemofiltration could be continued during rewarming and blood could be concentrated at the end of CPB. Whether BBUF, when performed during CPB, has equal beneficial effects on inflammatory response and the acid-base balance as zero balanced ultrafiltration [15], was investigated in a further study.
We conclude that hemofiltration of the priming blood and replacement with a physiological bicarbonate buffered hemofiltration solution is an efficient and simple method of reducing the metabolic load for neonates and infants undergoing cardiac surgery for complex congenital heart disease. After BBUF, even the electrolyte and acid-base balance reached a physiologic state, which is the most important condition for minimizing electrolyte and acid-base disturbances after initiation of CPB.
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Acknowledgements
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The CPB circuit management was performed by Joerg Optenhoefel from Life Systems.
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Abstract
1. Introduction
