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Clinical Outcomes–Devices

Pulsatile ECMO in Neonates and Infants: First European Clinical Experience with a New Device

Agati, Salvatore*; Mignosa, Carmelo*; Ciccarello, Giuseppe; Dario, Salvo; Ündar, Akif§

Author Information
doi: 10.1097/01.mat.0000171711.48788.2d
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Abstract

Extracorporeal membrane oxygenation (ECMO) for postcardiotomy heart failure has largely been limited to pediatric patients.1–8 Adults with cardiac failure have other available options, including a pulsatile or nonpulsatile ventricular assist device and the intraaortic balloon pump (IABP). These types of support have a somewhat limited application in neonates and infants9,10 because of availability of appropriately sized devices. ECMO support can be used in almost any patient, and has been used extensively for cardiac support in patients with cardiac failure after surgery for congenital heart disease.

Several investigators have suggested that pulsatile flow is more beneficial than conventional nonpulsatile perfusion during acute or chronic mechanical circulatory support.11–20 However, several hundred investigators have claimed that there were no differences in vital organ recovery between the two different perfusion modes.21–24 Although the controversy over the benefits of pulsatility still continues, the pro-nonpulsatile flow investigators can only claim that there is no difference between perfusion modalities, whereas the pro-pulsatile flow investigators can show the real benefits of pulsatility during acute or chronic cardiac support.11,20

The objectives of this investigation were to report on the first European experience of pediatric ECMO with a new pulsatile flow device, the Medos DeltaStream DP1, and to compare the outcomes of patients after pulsatile and nonpulsatile support.

Materials and Methods

Medos DeltaStream DP1

The Medos DeltaStream DP1 blood pump system (Medos AG, Stolberg, Germany) is used for pumping human blood in extracorporeal circuits. Normal areas of application include temporary cardiovascular support during and after open-heart surgery. The system is equipped with intelligent control and safety technology featuring a large number of internal and external sensors. Intelligent control permits the user to adjust the speed control, the pulsatile flow option, zero-flow mode (no backflow) and to limit the inlet pressure into the pump. Safety features include a flow sensor, four pressure sensors, level sensor, air bubble detector, and pump function monitoring (temperature sensor, speed sensor, and output measurement). The system is operated using membrane keys, a touchscreen, and an actuating wheel. The DeltaStream DP1 is an extracorporeal rotary blood pump. With its integrated drive unit (motor), it can be used very close to the patient.

The DeltaStream DP1 features a diagonal-flow impeller (Figure 1), and can be used for both continuous and pulsatile output. The pulsation frequency can be adjusted in steps of 5 bpm between 40 and 90 bpm. The systolic/diastolic ratio can be set from 30/70 to 70/30, in steps of 5%. The pump has a length of 150 mm, a diameter of 40 mm, a priming volume of approximately 30 ml, a weight of 280 g, and high pumping capacity in a compact design. A temperature sensor and speed sensors are integrated in the pump. The pump has a delivery rate of up to 8 l/min and a speed range of 100–10,000 rpm. The maximum achievable pressure differential is 600 mm Hg. It has an embedded, long, cylindrical electromotor with an electromechanical efficiency of up to 90%. The motor is surrounded by an annular flow path providing sufficient motor cooling by the blood flow. The DeltaStream DP1 works with moving magnets and stationary coils attached to the housing. Hence, there is no air gap between the coils and blood with a motor of this type. A thermo-element is fixed onto the motor surface for temperature measurement. The motor and the blood chamber are separated by a polymeric seal. The impeller is positioned between the pump inlet and the motor housing and is supplied with washout holes (Figure 2). After successful in vitro tests and animal experiments with sheep, the DeltaStream DP1 was approved for clinical use by the Certification Body of the TÜV Product Service (EC Certificate No. G1 01 04 15007 017).

Figure 1.
Figure 1.:
Schematic view of the Medos DeltaStream DP1.
Figure 2.
Figure 2.:
Overview of the inlet part of the Medos DeltaStream DP1.

Patients

Between January 2002 and December 2004, 420 patients underwent surgery for congenital heart disease on cardiopulmonary bypass (CPB) at our institution. During this period, 10 patients required ECMO support for acute postcardiotomy heart failure. Seven patients (median age 7 days, range 1–70 days), were supported by the Biomedicus centrifugal pump (Medtronic, Minneapolis, MN) (median support time 95 hours), whereas the Medos DeltaStream DP1 was used in the last three patients (aged 1 month, 1 year, and 12 years). The diagnoses were late-referral transposition of the great arteries (two patients), hypoplastic left heart syndrome (two patients), Tetralogy of Fallot (TOF) (two patients), double-outlet right ventricle (one patient), pulmonary atresia and ventricular septal defect (VSD; one patient), congenital mitral insufficiency (one patient), and severe aortic valve insufficiency plus aneurism of the ascending aorta after neonatal arterial switch operation for transposition of the great arteries plus VSD (one patient). The last two patients were intraoperatively switched to pulsatile flow using the Medos DP1 as an ECMO device to manage acute postcardiotomy heart failure. The 12-year-old patient first received a pediatric IABP; on the 56th postoperative hour, he was switched to pulsatile ECMO due to progressive hemodynamic deterioration. All ECMO patients received nonheparin-coated circuits; two neonatal patients received Lilliput 1 (Dideco, Mirandola, Italy), and Quadrox D (Jostra, Germany) oxygenators were used in the 12-year-old patient.

Patient 1.

A 1-year-old girl was referred to our institution for severe congenital mitral valve insufficiency with impaired left ventricular function. She had previously received mitral surgery. The mitral incompetence was secondary to restrictive movements of the subvalvular apparatus. She underwent mitral valvuloplasty with papillary muscle splitting, chordal fenestration, commissurotomy, and edge-to-edge repair. The immediate repair appeared to be satisfactory. She remained with chest opened on maximum inotropic support. Continuous venovenous ultrafiltration was started due to acute renal insufficiency. On the fifth postoperative day, her clinical condition declined due to acute mitral insufficiency. It was decided to replace the mitral valve. A reverse #21 aortic bioprosthetic valve (EPIC, St. Jude Medical, St. Paul, MN) was used in the mitral position. Weaning from CPB was unsuccessful, despite high-dosage inotropic support. The patient was then switched to pulsatile ECMO.

Patient 2.

A 1-month-old girl was referred for pulmonary atresia VSD and Major Aorto Pulmonary Collateral Arteries (MAPCAs). As a neonate, she was elected for staged palliation with a right modified Blalock-Taussig shunt and transannular patch. At 1 month, she was readmitted for unifocalization and VSD closure. Even in this case, after unsuccessful weaning from CPB and despite adequate therapy, it was decided to switch the patient to pulsatile ECMO.

Patient 3.

A 12-year-old boy with a medical history of transposition of the great arteries plus VSD and coarctation surgically corrected during neonatal life was referred for severe aortic valve insufficiency plus aneurism of the ascending aorta and left ventricular dysfunction. He was scheduled for aortic root replacement with #21 Medtronic Freestyle (Medtronic, Minneapolis, MN). Weaning from CPB was difficult despite inotropic support. To evaluate patency of the reimplanted single coronary ostia, angiography was performed on the first postoperative day and showed a normal coronary flow pattern. The patient was then supported with IABP. On the second postoperative day, we decided to switch the patient to pulsatile ECMO due to hemodynamic instability and progressive end-organ dysfunction.

ECMO Management

During ECMO, the Fio2 dropped to 21%, peak inspiratory pressure was limited to approximately 20–25 cm H2O, and positive end expiratory pressure was maintained at about 3–5 cm H2O. Inotropic support was reduced (dopamine 3 μg/kg/min, enoximone 3 μg /kg/min). When the activated clotting times were 180–200 seconds, a continuous heparin infusion directly into the oxygenator was started. Thromboelastography was used in all patients to optimize anticoagulation protocol. Mild hypothermia (34–35° C) was used, and a continuous furosemide infusion (0.5 mg/kg) was instituted to promote negative balance. A red blood cell transfusion (15–25 ml/kg) was administered to maintain a hematocrit of about 35%. The platelet count was maintained at 150,000 mm3 to control bleeding and decrease the risk of cerebral hemorrhage. In both patients, regional tissue oxygenation was continuously measured by frontal cerebral reflectance oximetry probes (rSO2, INVOS; Somanetics, Troy, MI). Continuous sedation and analgesia were obtained with morphine sulfate (50 μg/kg/h) and midazolam (0.1 mg/kg/h). Upon arrival in the intensive care unit, parenteral nutrition was started for adequate caloric support.

Results

Hospital mortality was 40% (4 of 10 patients), and all four deaths were in the nonpulsatile group. The causes of death in these four patients were multiorgan failure, pulmonary hypertension, myocardial infarction, and sepsis, respectively. No late deaths occurred. Two of the patients (aged 1 month and 1 year) assisted on pulsatile flow were successfully weaned after 36 and 53 hours, respectively, and discharged from the hospital after 19 and 34 days. The duration of mechanical circulatory support was significantly longer in the nonpulsatile flow group (median support time 95 hours, range 48–140 hours) compared with the pulsatile flow group (36 and 53 hours). The third patient was successfully transplanted after 8 days of support and discharged on 32nd posttransplant day. After switching to the DP1 pump, the postoperative course in all patients was uneventful and the pump showed good performance in the pulsatile mode (Figure 3) with adequate flow rates according to the Body Surface Area (BSA). Lactate trends showed a rapid normalization from a maximum of 7 mmol/ to 0.6 mmol/l. Laboratory tests for end organ function were repeated every 6 hours. No evidence of organ dysfunction was detected. The pulsatile flow regimen was maintained up to the point when the weaning program began. During weaning, the pump was switched to the nonpulsatile flow mode to evaluate myocardial recovery. All patients were evaluated by transesophageal echocardiography before the pump was removed. Although this preliminary experience doesn’t allow for statistical analysis, clinically it was possible to observe a better outcome in pulsatile flow recipients, with faster lactate recovery (Figure 4), reduced need for inotropic support (pulsatile group: dopamine at renal range plus low dosage enoximone; nonpulsatile group: epinephrine –0.05 to –0.1 μg/kg/min plus dopamine at inotropic dosage in all patients), reduced assistance duration in the cases of myocardial recovery, and smoother intensive care management. Full-time monitoring of cerebral saturation showed normal trends for both cerebral hemispheres. Neither major nor minor thromboembolic adverse events were observed. One patient underwent surgical revision for bleeding. Postremoval macro- and microscopic observation of the pump showed no presence of aggregates or clots or fibrin formation.

Figure 3.
Figure 3.:
Typical waveforms during Medos DP1 support. Full flow at 90 bpm: (A) patient femoral arterial pressure; (B) arterial cannula pressure monitoring.
Figure 4.
Figure 4.:
Lactate trend during the first 24 hours (mean ± error of the mean).

Discussion

Extracorporeal membrane oxygenation has been found to be a lifesaving therapy in selected groups of patients. Although initially met with skepticism since it was first performed by Hill and subsequently popularized by Bartlett,25 ECMO has been proven to be a useful and effective therapy in the management of neonatal respiratory failure.26,27 Because of the success of ECMO in this population, ECMO has been increasingly applied to other groups of patients with cardiorespiratory failure, including children and adults with respiratory failure and children with cardiac failure, and has even been used as a means of resuscitation.1,25,28

Pulsatility of the circulation has long been considered necessary to sustain normal organ function.29–32 Despite this, acute nonpulsatile CPB support has been used since the early 1950s. In 1955, Wesolowsky and colleagues33suggested that there were no differences in outcomes between nonpulsatile and pulsatile support, which led to the widespread usage of nonpulsatile flow in cardiac surgery. Most studies have investigated short-term or acute support.34–37 Pulsatile flow seems to offer an advantage of reducing shock for acute circulatory support. Acute studies with CPB have demonstrated that pulsatile flow reduces systemic vascular resistance and attenuates the catecholamine response,34 attenuates well-known hypothyroidism,38 improves splanchnic perfusion,39 improves myocardial blood flow,40 and improves clinical outcome.34,35 Reversal of shock is important for acute circulatory support. In 1992, Orime and colleagues11 demonstrated that pulsatility was more effective than nonpulsatility in improving and maintaining function in microcirculation of end organs after shock. They concluded that pulsatile circulatory support may prevent multiorgan failure after shock. According to the available literature, acute circulatory support with nonpulsatile circulation seems to have multiple consequences. Fluid requirements increase despite normal blood volume with the consequence of peripheral malperfusion and lymphedema. Catecholamines are increased with nonpulsatile circulation, which results in increased peripheral vascular resistances. There also seems to be decreased pulmonary capillary perfusion and impaired gas exchange in edematous lung. The advantage of acute pulsatile support is that it maintains lymphatic flow, thereby decreasing interstitial edema. Acute pulsatile support decreases systemic vascular resistance, which improves both peripheral perfusion and pulmonary capillary perfusion. All these advantages are conditions at which shock reversibility begins to occur and are only seen with pulsatile support. The benefits of pulsatile perfusion during cardiac surgery are more heavily debated than ever before.

Recently, a new approach for a comparative study between nonpulsatile and pulsatile support was suggested for precise quantification of pressure-flow waveforms.42 In 2001, Ündar and colleagues43 documented that the difference between the Shepard’s energy equivalent pressure formula and the precannula extracorporeal circuit pressure is 45% with a physiologic pulsatile pump. The difference decreases to 15% with the pulsatile roller pump, and the difference is only 1–2% with the nonpulsatile roller pump. These results clearly suggest that pulsatile perfusion with a physiologic pulsatile pump or a pulsatile roller pump generates significantly higher hemodynamic energy than a nonpulsatile roller pump.43,44 This extra energy is transmitted in all directions, thereby improving red cell flow, plasma flow, and lymph flow.45,46

The major advantages of the Medos DeltaStream DP1 are the pulsatile flow option, the small size, the simple design, and the low energy requirements (compared with pulsatile blood pumps). Low levels of free plasma hemoglobin were found in animal experiments,47 but until now there was no proof of reduced blood trauma clinically with this device. This potential benefit might lead to reduced transfusion requirements. Avoidance of low-flow areas, which typically appear at the rear sides of the impeller, is necessary to obtain low thrombogenicity. Therefore, the impeller is supplied with additional washout holes that suck blood from the rear side of the impeller into the main flow region. This setting avoids both stagnation of blood flow and secondary thrombus formation on the rear side of the impeller.47 By using this impeller design, no thromboembolic events were observed throughout all animal experiments.47

Conclusion

Our results suggest that this particular pulsatile pump system is a superior option for neonates and infants compared with the conventional nonpulsatile Biomedicus system for postcardiotomy heart failure. Further investigations with other paracorporeal pulsatile devices, including the effects of perfusion modalities on systemic inflammation during long-term support, are warranted.

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