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Editorial

An Evaluation of the Benefits of Pulsatile versus Nonpulsatile Perfusion during Cardiopulmonary Bypass Procedures in Pediatric and Adult Cardiac Patients

Ji, Bingyang; Ündar, Akif

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doi: 10.1097/01.mat.0000225266.80021.9b
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Abstract

The controversy over the benefits of pulsatile and nonpulsatile perfusion during cardiopulmonary bypass (CPB) has been ongoing for more than half a century.1–4 In earlier times, nonpulsatile perfusion was regarded as routine perfusion practice during CPB compared with the disadvantages of the pulsatile pump (it could not generate enough pulsatility, was complicated to operate, and increased the possibility of hemolysis). It seemed to be an exciting and satisfying method for people who served in this field, because it saved the lives of thousands of people with heart diseases. However, we had to take into account how many patients were lost by choosing this suboptimal method and how many additional medical resources were required to eliminate the adverse effects. Could we let the situation remain unchanged?

The advent of biomedical engineering has facilitated the development of several safe, simple, reliable, and cost-effective pulsatile pumps5–11 that are easy to set up and operate. With the new heart-lung machines, “one button” is used to alternate two perfusion modes during CPB. Some pulsatile pumps can even be triggered by the electrocardiogram and offer pulsatility not only during cardiac arrest but also during natural heart beating.9,10 Over the past few decades, clinical investigations, as well as animal experiments, have produced overwhelming evidence that pulsatile perfusion during CPB is more beneficial to patients than nonpulsatile flow.9–27 Although it is true that many investigations have failed to determine any difference between the two perfusion modes, their conclusions many have been influenced by a number of issues, such as a lack of understanding of the precise quantification of pressure-flow waveforms, limitations of experimental designs, or the selection of components of the extracorporeal circuit (pumps, membrane oxygenators, and aortic cannulae), without any scientific justification.5–10,28–37

The objective of this investigation was to review the literature published between 1952 and 2006 and reported in the databases of Google and Medline in order to clarify the truths and dispel the myths regarding the mode of perfusion used during open-heart surgery in pediatric and adult patients.

Materials and Methods

A computerized search, covering the period between 1952 and February of 2006, of the Google and Medline databases was conducted. Titles were sought containing the keywords pulsatile CPB, pulsatile flow, and pulsatile perfusion. Literature included the original (written in English or other languages) clinical trials and animal or in vitro experimental studies or invited editorial and review manuscripts on the topic of pulsatile vs. nonpulsatile flow during CPB surgery. Outcomes cited included clinical results and conclusions. Publications reporting on chronic support with different modes of perfusion, some comments on other papers, and some case reports about this topic were excluded.

Results

The search of Google and Medline databases produced a total of 194 papers with titles containing the keywords. Of the 194 publications, 74 were about animal experiments, 85 were about clinical investigations, and 35 were reviews, new device designs, or editorial letters. Direct comparisons of pulsatile and nonpulsatile flow during CPB in either animal or human studies were found in 159 reports.

Based on our literature search, we found considerable evidence that pulsatile flow is superior to nonpulsatile flow during CPB. Several results indicated that some forms of pulsatile flow are no more damaging to red blood cells and platelets than nonpulsatile flow.38–40 Some studies reported significantly lower pulmonary vascular resistance with pulsatile CPB than with nonpulsatile flow,1–4,41–43 and also showed that pulsatile flow generates more hemodynamic energy that improves microcirculation and metabolism when compared with nonpulsatile flow and inhibits edema formation.44–46 Many investigators found that pulsatile flow decreases levels of thyroid hormone,24 plasma vasopressin,47 adrenocortical hormone,48 cortisol,49 catecholamines,50 rennin, angiotensin II,51 and thromboxane. Moreover, we determined that pulsatile flow significantly improves blood flow of the vital organs including the brain,9,52–59 heart,60–63 liver,64 pancreas,65,66 kidney,67–72 and gastrointestinal system73,74; increases lung function75; reduces the systemic inflammatory response syndrome11,76–79; and decreases the incidence of postoperative deaths in pediatric and adult patients.1,12,16,80 Nonpulsatile investigators have claimed only that there is no difference between the pulsatile and nonpulsatile system in terms of end-organ recovery; however, none of them documented that pulsatile flow is worse than nonpulsatile flow.

Discussion

During the past decades, with the development of improved techniques in cardiac surgery and refinement of CPB instruments, the mortality rates following CPB procedures have been significantly decreased.81,82 To date, morbidity is still primarily a clinical problem, especially in high-risk cardiac patients. Major factors include deep-hypothermia circulatory arrest, ischemia/reperfusion, systemic inflammatory response syndrome, and nonpulsatile flow. The mode of perfusion could influence the result of vital organ recovery after CPB.

Based on the literature we reviewed about pulsatile vs. nonpulsatile flow during CPB, results very clearly showed that pulsatile flow is more effective than nonpulsatile flow during pediatric and adult CPB procedures. Despite the growing evidence for the possible benefits of pulsatile perfusion, the nonpulsatile mode has been chosen for routine clinical practice during open-heart surgery in the majority of institutions. The problem of clinical acceptance of pulsatile perfusion rests heavily on the controversy reported in the literature, which revolves around some key issues.

Lack of Common Definition or Precise Quantification

To date, we do not have a common definition or precise quantification of pulsatile flow, without which direct and meaningful comparisons of different perfusion modes are impossible.5–10,29–32 Investigators who focus on the topic of pulsatile vs. nonpulsatile flow need a definition because it is commonly believed that pulse pressure is sufficient for direct comparisons. Quantification of pulsatility in terms of pulse pressure is inadequate because the generation of pulsatile flow depends on an energy gradient.5–10,29–32 Therefore, the pump flow and arterial pressure must be included in quantification of different perfusion modes.

The Energy Equivalent Pressure Formula (EEP) is based on the ratio between the area beneath the hemodynamic power curve (∫ fpdt) and the area beneath the pump flow curve (∫ fdt) during each pulse cycle29:

Where f is the pump flow rate, p is the arterial pressure (mm Hg), and dt indicates that the integration is performed over time (t). The unit of the EEP is millimeters of mercury. Therefore, it is possible to compare the EEP with the mean arterial pressure (MAP). The difference between the EEP and MAP is the extra energy generated by each pulsatile or nonpulsatile device. The difference between EEP and MAP in the normal human heart is approximately 10%.

The Surplus Hemodynamic Energy (SHE) formula is calculated by multiplying the difference between the EEP and the MAP by 1332. The SHE equals the extra energy in terms of energy units.

Limitations of Experimental Designs in Some Investigations

In order to make clinically meaningful comparisons, every single component of the bypass circuit must be selected based on its previous performance in different perfusion modes, because not only the pulsatile pump but also the oxygenator and aortic cannula have a direct impact on the quality of the pulsatility during bypass.5–10,83–87

In the pulsatile extracorporeal circulation system, undoubtedly, the pump is the key to the whole system. In view of improved technological advancements, one might have anticipated the development of pumps able to deliver adjustable and reliable pulsatile flow. In the United States, only pumps that have been approved by the US Food and Drug Administration (FDA) can be applied during clinical bypass. All of them generate only diminished pulsatility, not physiologic pulsatility.9,30 We previously tested almost all of the heart-lung machines that have been approved by the FDA in terms of hemodynamic energy levels in the piglet model and found that the pulsatile roller pump with a diminished pulsatile flow is significantly better than nonpulsatile perfusion to recover the vital organs during and after CPB. A detailed investigation of different pumps and hemodynamic energy levels can be found in our previous publications.6–8

Because the membrane oxygenator is regularly placed after the pump, the pressure drop of the membrane has a direct impact on the quality of the pulsatility delivered by the pulsatile pumps.83–86 Hollow-fiber membrane oxygenators have significantly lower pressure drops and are more suitable for use with pulsatile pumps than flat-sheet membrane oxygenators. However, the structure and engineering designs of hollow-fiber membrane oxygenators may also have a direct impact on the quality of the pulsatility.83–86 The pressure drop of the membrane is extremely important for pediatric CPB procedures, because the pump flow rates are significantly higher in neonates and infants than in adult patients (150–200 ml/kg/min vs. 50 ml/kg/min).87,88

The quality of the pulsatility is greatly affected by the length of the arterial cannula tip. An arterial cannula with a shorter tip allows better pulsatility.84 Because the sizes of the cannulas are significantly smaller for pediatric patients, the geometry of the cannula has a direct impact on the quality of the pulsatility.

Both pulsatile and nonpulsatile groups must include patients with similar characteristics including age, weight, body surface area, and severity of surgery.5,10,32,83 It is well documented that more significant vital organ injury occurs in the population of high-risk patients as compared with the low-risk patients during CPB. An effective comparison between pulsatile and nonpulsatile perfusion during clinical practice should focus on the high-risk patients.

Conclusion

In published literature, there is no evidence documenting the adverse effects of pulsatility during pediatric or adult patient CPB. Pro-nonpulsatile investigators can claim only that there is no difference between pulsatile and nonpulsatile perfusion in terms of vital organ recovery. However, we found dozens of papers in the databases reporting that pulsatile flow is better than nonpulsatile flow during CPB. Based on results, we believe that pulsatile perfusion only minimizes these adverse effects; it does not eliminate them totally. When the two perfusion modes are compared in animal models or clinical work, components of the CPB circuit must be carefully chosen for optimal pulsatile flow, and arterial pressure and pump flow waveforms must be quantified in terms of energy equivalent pressure, surplus hemodynamic energy, and total hemodynamic energy levels. When these factors are accounted for, the comparison becomes clinically meaningful. The results in the literature clearly suggest that pulsatile flow is superior to nonpulsatile flow during and after open-heart surgery in pediatric and adult patients.

Acknowledgments

The authors would like to thank Elizabeth Breach for editorial assistance during preparation of this manuscript.

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