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Invited Editorial

Pulsatile Versus Nonpulsatile Cardiopulmonary Bypass Procedures in Neonates and Infants: From Bench to Clinical Practice

Ündar, Akif

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doi: 10.1097/01.mat.0000178215.34588.98
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Over the past decade, mortality rates after pediatric cardiopulmonary bypass (CPB) procedures have been significantly reduced,1,2 but morbidity is still a major clinical problem. In particular, high-risk cardiac patients suffer cerebral, renal, and myocardial dysfunction after CPB.3–5 Major factors, such as deep hypothermic circulatory arrest, ischemia/reperfusion, systemic inflammatory response syndrome, and nonpulsatile flow, all have a direct impact on vital organ injury. Several investigations now focus on minimizing the adverse effects of CPB in high-risk patients.6–12

We have been extensively involved over the past 10 years in research projects related to the use of pulsatile perfusion for minimizing vital organ injury during and after CPB procedures.11–22 This is a summary of our past 10 years of experience on this particular subject.

Energy Equivalent Pressure and Surplus Hemodynamic Energy Formulas

To make direct and meaningful comparisons between different modes of perfusion or different types of pulsatility, the precise quantification of pressure flow waveforms is a necessity, not an option.15–26 We have repeatedly suggested that investigators should quantify the pressure-flow waveforms in terms of hemodynamic energy levels in addition to the pulse pressure.15,18–22,25,26 The generation of pulsatile flow depends on an energy gradient.18–26 Several investigators, including members of our group, have also documented that energy equivalent pressure. Surplus hemodynamic energy formulas are adequate for precise quantification of pulsatile and nonpulsatile pressure-flow waveforms during acute and chronic cardiac support.15,27–31

Energy Equivalent Pressure (EEP) Formula

Shepard’s EEP formula 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 cycle23:

where f is the pump flow rate, p is the arterial pressure (mm Hg), and dt is the increment in time. The EEP is calculated in mm Hg.

Surplus Hemodynamic Energy (SHE) Formula

Surplus hemodynamic energy is calculated by multiplying the difference between the EEP and the mean arterial pressure (MAP) by 1,332.

Under adequate pulsatility, the EEP is always greater than the MAP. The difference between the EEP and the MAP is the extra energy (Figure 1). The SHE equals the extra energy in terms of energy units.

Figure 1.
Figure 1.:
Diagram of the energy equivalent pressure and the surplus hemodynamic energy.

Bench studies and animal experiments

To generate adequate pulsatility, bench studies with different types of pumps and oxygenators are a must. Each component of the extracorporeal circuit, including pumps, membrane oxygenators, arterial filters, and aortic cannula, plays a vital role in generating adequate pulsatile flow. They must be carefully selected for pulsatile flow studies and tested for suitability with pulsatile flow.13–15,31

Pulsatile pumps

We have already tested almost all of the pediatric heart-lung machines in terms of hemodynamic energy levels.15,31 We have clearly shown that most of the pulsatile pumps we tested do generate adequate hemodynamic energy levels. However, one of the pulsatile pumps failed to generate any extra hemodynamic energy when compared with nonpulsatile pumps.15,31 None of the nonpulsatile pumps generated any surplus hemodynamic energy (Figure 2). A detailed investigation of different pumps and hemodynamic energy levels can be found in our other publications.15,31

Figure 2.
Figure 2.:
Surplus hemodynamic energy (SHE) in piglets during normothermic CPB. PPP, physiologic pulsatile pump (n = 7); Jostra-PR, Jostra-HL 20 pulsatile roller pump (n = 6); SIII-PR, Stockert SIII pulsatile roller pump (n = 6), Mast-PR, Stockert SIII mast-mounted pulsatile roller pump with a miniature roller head (n = 7); Mast-NP, Stockert SIII mast-mounted nonpulsatile roller pump (n = 7); CAPS-NP, Stockert CAPS nonpulsatile roller pump (n = 7).

Membrane oxygenators

Because the membrane oxygenator is placed after the pump, the pressure drop of the membrane has a direct impact on the quality of the pulsatility delivered by the pulsatile pump.13,14,32,33 Hollow-fiber membrane oxygenators have significantly lower pressure drops and are more suitable for use with pulsatile pumps than flat-sheet membrane oxygenators.13,14,32,33 However, the structure and engineering designs of hollow-fiber membrane oxygenators may also have a direct impact on the quality of the pulsatility.13,14,33 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 as compared to adult patients (150–200 ml·kg–1·min–1vs. 50 ml·kg–1·min–1).34,35

Arterial Cannulas

Because the sizes of the cannulas are significantly smaller, the geometry of the cannula has a direct impact on the quality of the pulsatility for pediatric patients.13,14 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.13,14

Impact of Perfusion Modes on Cerebral Hemodynamics

We investigated the impact of perfusion modes on cerebral hemodynamics with 60 minutes of deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model.13,17 Twelve piglets (n = 6 in each group), with a mean weight of 3 kg, underwent 60 minutes of DHCA and 45 minutes of rewarming. Global and regional cerebral blood flow, cerebral metabolic rate of oxygen, cerebral oxygen delivery, and cerebral vascular resistance were determined before DHCA at a cerebral perfusion pressure of 55 mm Hg, and after DHCA at cerebral perfusion pressures of 55, 40, and 70 mm Hg.

Global and Regional Cerebral Blood Flow

Global cerebral blood flow was significantly higher in the pulsatile group at all experimental stages (Figure 3). Blood flow in the cerebellum, basal ganglia, brain stem, and right and left hemispheres resembled global cerebral blood flow (Figures 4–8).

Figure 3.
Figure 3.:
Global cerebral blood flow during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest, CBF, cerebral blood flow.
Figure 4.
Figure 4.:
Cerebellum blood flow during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest.
Figure 5.
Figure 5.:
Basal ganglia blood flow during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest.
Figure 6.
Figure 6.:
Brain stem blood flow during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest.
Figure 7.
Figure 7.:
Right hemisphere blood flow during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. (p = pulsatile; NP = nonpulsatile; CPP = cerebral perfusion pressure; DHCA = deep hypothermic circulatory arrest).
Figure 8.
Figure 8.:
Left hemisphere blood flow during pulsatile versus nonpulsatile perfusion (Mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest.

Cerebral Metabolic Rate of Oxygen

Pulsatile perfusion significantly improved the cerebral metabolic rate of oxygen at all four experimental stages before and after DHCA (Figure 9).

Figure 9.
Figure 9.:
Cerebral metabolic rate of oxygen during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest; CMRO2, cerebral metabolic rate of oxygen.

Cerebral Oxygen Delivery

Cerebral oxygen delivery levels were significantly higher in the pulsatile group when compared with nonpulsatile group levels at all experimental stages (Figure 10).

Figure 10.
Figure 10.:
Cerebral oxygen delivery during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest.

Cerebral Vascular Resistance

Nonpulsatile flow significantly increased the CVR when compared with the pulsatile flow at all experimental stages (Figure 11).

Figure 11.
Figure 11.:
Cerebral vascular resistance during pulsatile versus nonpulsatile perfusion (mean ± SEM). *p < 0.05 P vs. NP, †p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within pulsatile group; ‡p < 0.05 vs. pre-DHCA at CPP = 55 mm Hg within nonpulsatile group. P, pulsatile; NP, nonpulsatile; CPP, cerebral perfusion pressure; DHCA, deep hypothermic circulatory arrest; CVR = cerebral vascular resistance.

Impact of Perfusion Modes on Myocardial and Renal Blood Flow

In experiment after experiment, with pulsatile roller pumps or physiologic pulsatile pumps, we have repeatedly shown that pulsatile perfusion maintains better myocardial blood flow when compared to conventional nonpulsatile roller pumps.11,12 More importantly, we have also discovered that only 30 minutes after weaning from CPB, myocardial blood flow reaches baseline levels in the pulsatile group while myocardial blood flow decreases 50% when compared with the baseline levels in the nonpulsatile group.11,12

We have shown that renal blood flow was maintained much better at all experimental stages in the pulsatile group (with a pulsatile roller or a hydraulically driven physiologic pulsatile pump) compared with the nonpulsatile group before and afer DHCA and after CPB. Renal blood flow after CPB was threefold higher in the pulsatile group as compared with the nonpulsatile group.12

Survey Results for the Use of Pulsatile Perfusion in Pediatric Patients

During the First International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion, we conducted a preliminary survey of the use of pulsatile flow in pediatric cardiac patients and received 51 responses. Sixty-five percent of all respondents have a heart-lung machine with a pulsatile flow option in their operating rooms. Although 42% use pulsatile flow in their institutions, only 12% use pulsatile flow routinely and 24% only for selected cases. Of the respondents, 16% completed at least one research protocol related to pulsatile flow in pediatric patients, and all concluded that pulsatile flow was better than nonpulsatile flow; however, only 13% of them published the results in a scientific peer-review journal. Sixty-seven percent of the respondents would like to participate in a multi-center clinical trial with pulsatile flow in pediatric patients.

Clinical Trials

All of the publications showing the benefits of pulsatile flow in pediatric patients were conducted in the late 1980s or earlier.36–38 Although dozens of recent investigations have documented that pulsatile flow significantly minimizes cerebral, myocardial, and renal injury during CPB procedures, most of the results were from animal experiments or from CPB procedures in adults, not from neonates and infants.11,12,17,39–43 To make direct comparisons between pulsatile and nonpulsatile flow, there is now a need for multicenter randomized clinical trials in pediatric patients. We have also published guidelines with a step-by-step approach to use pulsatile flow in pediatric and adult patients.20

We truly believe that with current pulsatile roller pumps and hollow fiber membrane oxygenators, it is possible to generate adequate pulsatility for quicker end-organ recovery in pediatric patients.

References

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