Incremental development and miniaturization of a cardiopulmonary bypass (CPB) system have enabled us to perform open-heart surgery without blood transfusion in selected pediatric patients. However, a challenge still remains in neonatal open-heart surgery, for which blood prime is inevitable to maintain the optimal hematocrit level because of the considerable mismatch between the patient’s body size and CPB circuit volume. Efforts toward reduction in the circuit volume and subsequently the amount of blood transfusion are of great importance. Studies have shown that inflammatory response and subsequent organ edema increased in an exponential fashion as the amount of priming volume and blood transfusion increased.1,2 Stored blood products also trigger inflammatory response, unbalanced electrolytes, and metabolic acidosis3,4; therefore, reducing the amount of stored blood use has potential positive impacts on minimizing transfusion-related adverse effects in neonates.
Efforts have been made to miniaturize the CPB circuit, including a vacuum- or kinetic-assisted venous drainage system to downsize venous cannulae,5–8 a retrograde autologous priming,9 and elimination of an arterial line filter and blood cardioplegia system.7,8 As a result, open-heart surgery in a 2.2 kg patient with total anomalous pulmonary venous return has recently been done without blood transfusion.10 However, some of the techniques to minimize CPB volume, such as elimination of an arterial line filter and employment of a vacuum drainage system, might pose potential risks of serious complications, including deleterious air emboli. In keeping with safety standards, we attempted to miniaturize the CPB circuit for neonates during the last 5 years. In this article, we report our retrospective analysis of the impact of staged miniaturization of the CPB circuit on hemodynamics and blood transfusion requirement in neonatal open-heart surgery.
Patients and Methods
We conducted a retrospective study of 102 neonates who underwent cardiac surgery from June 2002 to December 2006 at Okayama University Hospital, Okayama, Japan. The Institutional Review Board approved this retrospective study, and patient consent was waived for the study. We divided the entire cohort into three groups based on the type of oxygenator and tube size: group 1 (n = 28, from June 2002 to March 2003), Dideco 902 oxygenator (priming volume, 105 ml) (D902 Lilliput 2, Dideco, Mirandola, Italy) + 5/16" arterial and venous line; group 2 (n = 29, from April 2003 to December 2003), Dideco 901 oxygenator (priming volume, 60 ml) (D901 Lilliput 1, Dideco, Mirandola, Italy) + 1/4" arterial and venous line; group 3 (n = 45, from January 2004 to December 2006), Dideco 901 oxygenator + 3/16" arterial and 1/4" venous line. An arterial filter (Dideco D736 Newborn, Mirandola, Italy), of which the priming volume was 40 ml, was employed in all groups. According to our institutional priming protocol, a CPB circuit was filled with 500 ml of acetate Ringer’s solution, 2,000 units of heparin, and citrate-phosphate-dextrose-buffered packed red blood cells (520 ml in group 1; 260 ml in groups 2 and 3). The primed blood was then hemofiltrated using a polysulfon hemoconcentrator (Aquastream 04, JMS, Tokyo, Japan) at 250 ml/min using a negative pressure of 100 mm Hg with 1,000 ml of acetate Ringer’s solution. The mean fluid volume of approximately 1,300 ml was filtrated. After hemofiltration, mannitol (4 ml/kg), bicarbonate sodium, and 25% albumin of 50 ml were administrated. The roller pump system (HAS, MERA, Tokyo, Japan) was used throughout the study period, and the flow rate was maintained at 150 ml/kg/min. Hematocrit was maintained between 25% and 28% during CPB, and additional blood transfusion was performed to maintain the target hematocrit level. Modified ultrafiltration was routinely performed immediately after termination of CPB.
The amount of the priming volume and hematocrit in the priming circuit were compared among the groups. The amounts of blood transfusion and bicarbonate sodium added at priming and during CPB were compared. Blood pressures at baseline and at 3 minutes after initiation of CPB, and the percentage drop in blood pressure at 3 minutes after initiation of CPB compared with the baseline values were also compared.
The perfusion records and operative reports for all patients were reviewed. Results were expressed as the mean ± standard deviation. Statistically significant differences among groups were determined by one-way analysis of variance, followed by a post hoc test using the Scheffe’s test for multiple comparisons. Comparisons within groups were made by Wilcoxon’s signed-rank test. A p value of < 0.05 was considered statistically significant.
The baseline parameters including age, body weight, CPB time, and flow rate did not differ among the groups (Table 1). The priming volumes in groups 2 and 3 were significantly lower compared with those in group 1; however, there was no difference between groups 2 and 3 (Table 2). Hematocrit at prime in group 2 was significantly lower than in the other two groups. The amounts of blood transfusion at prime and during CPB in groups 2 and 3 were significantly smaller compared with group 1, which subsequently contributed to reduction in the total amount of blood transfusion (Table 3). Bicarbonate sodium use to adjust pH during CPB in groups 2 and 3 was significantly decreased compared with group 1 (group 1: 54 ± 11 ml, group 2: 27 ± 7 ml, group 3: 30 ± 5 ml, p < 0.05). There were no differences in baseline blood pressure, blood pressure at 3 min after initiation of CPB (Figure 1), and the percentage drop in blood pressure (group 1, 36% ± 17%; group 2, 36% ± 16%; group 3, 38% ± 17%, p = NS).
As a major part of the efforts toward establishment of less invasive open-heart surgery in neonates, we attempted to miniaturize the CPB circuit without compromising safety standards such as placement of arterial filter. In the current study, we evaluated the impact of our staged miniaturization of a CPB circuit during the last 5 years on blood transfusion requirement and blood pressure in neonatal open-heart surgery. The miniaturization of a CPB circuit by downsizing the oxygenator and tubes resulted in significant reduction in the priming volume and subsequent total use of blood and bicarbonate sodium. Miniaturization of the CPB circuit, however, had a minimal impact on blood pressure and avoidance of initial drop in blood pressure at initiation of CPB.
Despite the efforts to reduce the prime volume during the 5 years, our current system still has a relatively high priming volume of approximately 320 ml, which was much higher than those reported in previous studies.5–10 To use a newly developed smaller oxygenator, which has been shown to have the equivalent overall performance to the conventional neonatal and infant oxygenators, is a simple and definitely an effective means to eliminate the priming volume up to 30 ml from our system. Placing the reservoir and main pump closer to a patient using a remote pump head system would also be effective to reduce additional priming volume.11 In addition, we noticed that the current distance between a patient and the pump system in our institute is not close enough, and a joint effort by surgeons and perfusionists can eliminate the tube length. Using these techniques, we believe that it may be possible to eliminate 80–100 ml of the priming volume from our system during the next few years, making the priming volume of our system around 220–250 ml.
A consistent policy of miniaturization in our institute is to maintain the safety standards of the pump system. Some institutes eliminate an arterial filter from their system.7,8 We can easily understand that elimination of an arterial filter, which has at least a priming volume of 40 ml, is a simple means to reduce the total priming volume. Although the efficacy of the arterial filter to trap microbubbles has not fully been elucidated, it is also a fact that we never know how many microbubbles can pass through an oxygenator and migrate into the patient’s body. If we balance the value of eliminating an additional 40 ml from the pump system with the risk of deleterious air emboli, we do not hesitate to keep using an arterial filter as an essential apparatus of our pump system. We have also been skeptical of using a vacuum-assisted venous system, which is a relatively common means to diminish the priming volume by reducing the tube length and diameter.7,12 A previous study showed that a considerable number of microbubbles migrated into the patient’s body when using a vacuum-assisted drainage system.13 We will continue our efforts to accomplish miniaturization of the pump system while maintaining essential safety standards.
Recent miniaturization of the CPB circuit made transfusion-free open-heart surgery possible even in small children < 5 kg7,11; however, the minimal hematocrit of around 16%–20% was noted in those studies,5,11,14 leading us to a question what is the lowest hematocrit acceptable to maintain cardiopulmonary and neurological functions. Both adult14 and pediatric11 clinical studies demonstrated that no postoperative neurological deficits and liver/kidney dysfunctions occurred with the lowest hematocrit of 16%–20% during CPB. On the other hand, a comprehensive clinical investigation by Jonas et al. 15 showed that the superior neurological outcome was found in the higher hematocrit group, in which the mean hematocrit was 27% during CPB, in children undergoing open-heart surgery under deep hypothermic circulatory arrest. We essentially agree with Jonas et al. that a relatively high hematocrit helps to maintain appropriate oxygen delivery to the brain and other major organs in neonatal open-heart surgery. One of the ultimate goals of miniaturization of the CPB circuit is to achieve asanguineous open-heart surgery, thereby minimizing surgical stresses in neonates and small infants; however, we should not apply transfusion-free CPB too aggressively with an incompletely miniaturized pump system, which might result in substantial hemodilution posing patients risks. Because considerable hemodilution is still unavoidable with our system, we will routinely perform blood prime until we establish a sophisticated CPB system small enough to minimize hemodilution and sustain appropriate hematocrit level, which would be a truly less invasive pump system.
There are certain limitations in this study. No inflammatory mediators were measured in this study; therefore, the impact of reduction in the amount of blood transfusion on systemic inflammatory response is uncertain. Also, clinical outcomes including the length of ventilation or intensive care unit stay were not analyzed, and further study should be designed to elucidate the effects of miniaturization on early and long-term outcomes in neonates undergoing open-heart surgery.
Staged miniaturization of a CPB circuit resulted in decreased priming volume and subsequently reduced blood and bicarbonate sodium use. Downsizing the lines in the setting of a relatively small oxygenator did not provide further miniaturization. Utilization of new technologies, including a newly developed miniature oxygenator or remote pump head system should be considered to achieve further miniaturization and potential transfusion-free open-heart surgery in neonates and small infants.
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Copyright © 2007 by the American Society for Artificial Internal Organs
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