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Ann Thorac Surg 2002;73:1670-1677
© 2002 The Society of Thoracic Surgeons
a Pediatric and Congenital Heart Surgery, Cleveland Clinic Childrens Hospital, Cleveland, Ohio, USA
* Address reprint requests to Dr Duncan, The Cleveland Clinic Foundation, Pediatric and Congenital Heart Surgery/M41, 9500 Euclid Ave, Cleveland, OH 44195 USA
e-mail: duncanb{at}ccf.org
| Abstract |
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| Introduction |
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This review examines several relevant areas of mechanical circulatory support for children. The first section compares the attributes of ECMO and VAD that may give either modality an advantage in a specific clinical situation, analyzes their effects on ventricular recovery, and examines the long-term outcome of children supported by either modality. The second section examines innovative uses for ECMO, namely, rapid resuscitation ECMO for children suffering cardiac arrest and ECMO for the treatment of acute fulminant myocarditis. The third section examines the current state-of-the-art for pediatric VAD technology, including centrifugal systems that have been available for some time, as well as recently introduced pulsatile, paracorporeal systems that are gaining increasingly wide application. The final section looks to the future by examining a number of promising devices that are miniaturized systems under development for adults that may also be used for pediatric patients.
| A comparison of ECMO versus VAD support for pediatric cardiac disease |
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To further optimize the chances of ventricular recovery during support, the effect of ECMO on myocardial oxygenation must be appreciated and appropriately managed. For most cannula configurations used for venoarterial ECMO, oxygenated blood from the arterial cannula fails to reach the coronary sinuses if there is any appreciable ventricular ejection with coronary arterial blood flow provided by the left ventricle [1012]. If there is significant pulmonary parenchymal disease or if mechanical ventilation is withheld during ECMO support, hypoxic blood returning to the left ventricle may provide the sole source of coronary perfusion with deleterious effects on ventricular function and recovery [13]. Provision of oxygenated blood flow to the coronary arteries is easily accomplished by continuing to provide moderate levels of ventilation during ECMO support. This insures that fully oxygenated pulmonary venous blood returns to the left atrium and serves as the source of coronary perfusion. With these modifications for the conduct of ECMO support, recovery of ventricular function may be anticipated in patients with even the most profound myocardial dysfunction [1, 14].
Long-term follow-up of pediatric cardiac patients requiring ECMO or VADs
Numerous reports have demonstrated that in-hospital survival rates of 40% to 80% are possible for children who require mechanical circulatory support for cardiac indications [1, 15, 16]. Data are available that describe the long-term outcome for children requiring ECMO for primary respiratory failure [1719]; however, little information is available regarding the long-term outlook and quality of life for children who have survived mechanical circulatory support for cardiac indications.
The long-term follow-up of children with cardiac disease who required mechanical circulatory support during a decade of experience at Childrens Hospital, Boston was recently analyzed [20]. Thirty-seven children (26 ECMO and 11 VAD survivors) were followed for an average of more than 4 years. Only a single patient died in either group for an overall long-term survival of 95%. Eighty percent of the patients in both groups were described as exhibiting good to excellent general health. Ninety percent of the patients were in New York Heart Association class I or II, and echocardiographic evaluation of ventricular function was normal in all of the ECMO-supported patients and in 90% of the VAD-supported patients.
Poor neurologic outcomes were more common in ECMO- than VAD-supported patients. More than 60% of the ECMO-supported patients demonstrated moderate to severe neurologic impairment, whereas only 20% of the VAD survivors demonstrated the same degree of neurologic impairment. Adverse neurologic outcomes were associated with low weight when support was originally instituted and with the duration of hypothermic circulatory arrest in the children that received cardiac operations. Adverse neurologic outcomes were not associated with pre-support cardiac arrest, carotid cannulation, or carotid reconstruction.
These results are reassuring in that children with heart disease who survive to hospital discharge after requiring ECMO or VAD support demonstrate favorable long-term survival, overall general health, and cardiac outcomes. The relatively higher rates of neurologic complications in the ECMO-supported group are concerning and appear to be due to multiple causes in critically ill neonates. These results may suggest an advantage for VAD support, possibly because of decreased requirements for anticoagulation with less risk of neurologic complications such as intracranial hemorrhage. However, these results must also be interpreted with the understanding that the ECMO-supported group in this study had a higher proportion of critically ill neonates with more complex underlying cardiac conditions [1]. Nevertheless, the potential for greater neurologic risk in ECMO-supported patients should be appreciated and appropriate management, such as carefully controlling anticoagulation, should be routine.
| Current issues in pediatric cardiac ECMO |
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One such system utilizes a modified ECMO circuit, an organized team of personnel to perform cannulation, and a streamlined priming process [14]. The "rapid resuscitation" ECMO circuit is maintained, vacuum and CO2-primed, in the intensive care unit and is portable with a battery power supply allowing it to be quickly used in any location throughout the hospital. If standard cardiopulmonary resuscitation is unsuccessful within 10 minutes of cardiac arrest, the circuit is moved to the patients bedside and crystalloid priming is initiated while cannulation is proceeding. If cannulation is completed before blood products are available ECMO flow is initiated with a crystalloid-primed circuit and blood products are added when available. The excess crystalloid volume is removed as blood is added to the circuit using exchange transfusions by hand and performing ultrafiltration after the hemodynamics have stabilized. Establishing a normal cardiac output with ECMO is the most critical factor for successful resuscitation of these children, even if the hematocrit is low when support is initiated due to the use of a crystalloid-primed circuit.
This approach was used for 11 pediatric cardiac patients who suffered cardiac arrest. Nine of these 11 patients were postoperative cardiac surgical patients; 1 patient had a cardiac arrest prior to surgery; and 1 patient had a cardiac arrest in the cardiac catheterization laboratory [14]. All patients were undergoing cardiopulmonary resuscitation at the time of ECMO cannulation. The median duration of cardiopulmonary resuscitation for these 11 patients was 55 minutes (range, 15 to 103 minutes) compared with a median duration of cardiopulmonary resuscitation of 90 minutes (range, 45 to 200 minutes) for seven historical controls resuscitated with conventional means before the utilization of the rapid resuscitation system. All but 1 of the 11 rapid resuscitation patients were able to be weaned from ECMO with 7 patients (64%) surviving to hospital discharge compared with two survivors (29%) of the seven historical controls.
Jacobs and coworkers [22] reported results for a particularly innovative rapid resuscitation system that uses a hollow-fiber oxygenator to facilitate priming. The circuit uses a centrifugal pump, short lengths of quarter-inch tubing, and is heparin bonded throughout. This system is fully portable and requires a priming volume of 250 mL. The use of the centrifugal pump eliminates the need for gravity drainage, which allows the use of shorter tubing lengths and provides greater portability. The simplicity of the circuit facilitates priming and minimizes trauma to blood elements, while the heparin bonding results in less blood loss. The authors reported their results with this system in 23 children with cardiac disease, most of whom had undergone cardiac surgery. All patients had support instituted with a crystalloid-primed circuit. The simplicity of this system and avoidance of the blood-priming step enabled set-up time to be as brief as 5 minutes. The duration of cardiopulmonary resuscitation was only 12 minutes for the 4 patients in this series who suffered cardiac arrest before cannulation. Using this system, the overall survival in this series was 48% with all 4 of the cardiac arrest patients surviving to hospital discharge.
These reports support the concept that pediatric cardiac patients who suffer cardiac arrest are often salvageable and deserve an aggressive approach with prompt institution of ECMO if conventional resuscitative measures fail. Rapid institution of circulatory support with modified ECMO systems can be lifesaving with improved preservation of end-organ function in these patients.
ECMO for the treatment of acute, fulminant myocarditis
Indications for the institution of ECMO in patients with myocarditis should be based on the clinical response to intensive care unit management. Most patients that are considered for ECMO support are receiving high dose inotrope infusions with endotracheal intubation and muscle paralysis. If evidence of a low cardiac output state persists, clinically manifest as oliguria, poor cutaneous perfusion, and hypotension, ECMO should be strongly considered. The need for escalating inotrope doses accompanied by significant ventricular ectopy is an especially lethal combination that suggests mechanical circulatory support will be required because of the tendency of these patients to develop sudden and intractable ventricular fibrillation.
The survival rate for children that require mechanical circulatory support for myocarditis is relatively good in most reports [15, 2328]. The Extracorporeal Life Support Organization registry [29] reports that myocarditis has the highest survival of any diagnostic group requiring ECMO with 58% of these patients being successfully weaned from support. A recent multiinstitutional review of 15 patients with viral myocarditis supported by ECMO (12 patients) or VADs (3 patients) demonstrated an overall survival rate of 80% [30]. In this experience, ECMO was felt to be a better choice than VAD for acute support because of the option of peripheral cannulation, maintaining an intact chest cavity. Nine of the 15 patients were weaned from support with 7 of these nine patients surviving (78%), while the remaining 6 patients were successfully bridged to transplantation with 5 survivors (83%). An especially important finding was that all nontransplanted survivors are currently alive with normal ventricular function. Historically it was believed that a significant percentage of children with acute myocarditis would be expected to develop dilated cardiomyopathy with the ultimate need for cardiac transplantation [31]. This study suggests that children with acute fulminant myocarditis have an overall favorable outcome and a significant degree of disease reversibility if successfully supported during the acute phase of illness.
The reasons for better long-term outcomes and a decreased incidence of progression to dilated cardiomyopathy in patients most severely affected with myocarditis remains unexplained; however, mechanical circulatory support may contribute to the improved long-term outcomes in these children. In patients with dilated cardiomyopathy, prolonged mechanical circulatory support may result in ultimate recovery of ventricular function because of favorable influences on the neurohormonal cardiovascular milieu and unloading of the left ventricle resulting in normalization of ventricular geometry through "reverse remodeling" [32]. The institution of mechanical circulatory support in patients with acute fulminant myocarditis can favorably impact these same factors resulting in ventricular recovery over a much shorter time course, which is a process that has been described as "rapid reverse remodeling" [30]. In these most severe cases of myocarditis, mechanical circulatory support provides the ultimate form of physiologic rest similar to simple bed rest and oxygen used to support less severe cases. It is compelling to speculate that normalization of ventricular geometry and function by the early institution of support may help to prevent the development of dilated cardiomyopathy.
Based on these results the optimal approach for children presenting with acute fulminant myocarditis may be to provide mechanical circulatory support, even if required for prolonged periods, in anticipation of eventual ventricular recovery. Previous reports have documented full return of ventricular function in young adults with myocarditis after weeks or months of mechanical support [33, 34]. Pulsatile paracorporeal VAD systems that allow extended periods of support have been used successfully in pediatric patients in Europe and have demonstrated the feasibility of this approach (see below) [35, 36]. Prolonged mechanical circulatory support in a larger number of pediatric patients with fulminant myocarditis may reveal that the capability of supporting these children for weeks or months will allow return of native ventricular function, thereby avoiding transplantation in virtually all of these children.
| Current status of VADs for pediatric cardiac disease |
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Pulsatile pediatric VADs: heartmate, thoratec and the ABIOMED BVS 5000
Several groups have successfully provided pulsatile mechanical circulatory support for older children utilizing systems designed primarily for adult applications [41, 4547]. Helman and colleagues [47] described the use of the Heartmate VAD (Thermocardiosystems, Woburn, MA) in 12 adolescent patients, the majority of whom had idiopathic dilated cardiomyopathy. The ages of these patients (range, 11 to 20 years) and their body surface areas (range, 1.4 to 2.2 m2) allowed the use of this device. Wound closure was facilitated by the placement of a polytetrafluoroethylene patch for the abdomen and delayed sternal closure. As in the adult experience with the Heartmate VAD, the majority of patients supported by the vented electric model were able to be discharged home with resumption of normal activities.
McBride and colleagues [45] and Korfer and colleagues [46] each described large adult series using the Thoratec VAD (Thoratec Laboratories Corp, Berkeley, CA) with a few implantations in adolescents as young as 11 years of age. Ashton and coworkers [41] used the ABIOMED BVS 5000 (ABIOMED, Inc, Danvers, MA) in 4 older children. These authors noted that this system was quite effective in providing temporary circulatory support if the patients body surface area was greater than 1.2 m2 and flows of more than 2 L per minute could be achieved.
Pulsatile pediatric VADs: MEDOS HIA VAD and the berlin heart vad
Despite success for older children with pulsatile systems that are intended for adult use, a significant void exists for implantable, pulsatile, mechanical circulatory support options for small children. These adult devices are unsafe for all but the largest children because of the low pump rates that have to be used in small children resulting in inadequate pump washout and an excessive thromboembolic risk [41, 48].
The MEDOS HIA VAD (MEDOS Medizintechnik AG, Stolberg, Germany) and the Berlin Heart VAD (Berlin Heart AG, Berlin, Germany) are two pulsatile VAD systems that are suitable for the entire age range of pediatric patients including neonates [49, 50]. Both are paracorporeal systems that use pneumatically driven, thin membrane pumps to provide pulsatile flow. Inlet and outlet valves are tri-leaflet and constructed from polyurethane. Both systems are available in a variety of pump sizes (10, 30, 50, and 80 mL) with the smallest pump sizes suitable for infant support.
Konertz and coworkers [35], described a series of 6 children supported by the MEDOS HIA VAD. The patients ages in this report ranged from 5 days to 8 years, and the patients weights ranged from 3.1 to 20 kg. Aspirin and intravenous heparin (activated clotting time, 180 to 220 seconds) were used for anticoagulation. Complications were those common to all types of mechanical circulatory support, including 1 patient who required mediastinal exploration for bleeding. One child suffered a transient cerebrovascular accident accompanied by visualization of thrombus in the pump. The clear polyurethane pump housing allowed thrombus to be seen easily and led to a pump change. Four of the 6 patients in this series (67%) survived to hospital discharge, including 2 patients that were bridged to transplantation and 2 patients that had return of ventricular function sufficient for device weaning.
Features of this system that the authors found advantageous included low priming volumes and pulsatile flow that accounted for decreased capillary leak during support. In addition, there was no need for trained personnel beyond intensive care unit nursing for the maintenance of the circuit as opposed to ECMO, which usually requires trained technicians at the bedside for monitoring of the device. Finally, due to the paracorporeal design of the system, the patients in this report were able to be extubated and ambulated, and they were able to attain some degree of normal daily activities. This resulted in improvement in the physiologic state of these children by the time transplantation occurred. Other authors [28, 51] have reported similar results with the MEDOS system. The report by Sidiropoulos and coworkers [51] noted that the Bio-Pump centrifugal VAD provided easier aortic cannulation in neonates with transposition of the great arteries after the LeCompte maneuver as part of the arterial switch operation. The MEDOS system had problems with angulation of the aortic cannula in these patients.
Experience with the Berlin Heart VAD in pediatric patients has produced similar excellent results. Ishino and colleagues [48] reported 14 children who were supported with the Berlin Heart VAD. The average age of these patients was 10 months (range, 2 weeks to 15 years) with an average weight of 14.9 kg (range, 3.2 to 52 kg). Eleven of these patients were bridged to transplantation, whereas 3 patients were bridged to recovery. Anticoagulation was provided with intravenous heparin maintaining the activated clotting time at 160 to 180 seconds. Complications included mediastinal exploration for bleeding in 6 patients and 3 pump changes for thrombus visualized in the pump. As was the case for the MEDOS system, the clear pump housing of the Berlin Heart VAD allowed early detection of thrombus and elective pump change. Two patients suffered cerebrovascular accidents. Eight of the 11 bridge to transplant patients (73%) were successfully transplanted with 4 survivors (36%), whereas 1 of the 3 bridge to recovery patients (33%) survived to hospital discharge.
The authors of this study stated that the pulsatile flow provided by this system allowed for indefinite periods of support, noting that ECMO support is usually limited to approximately 2 weeks because of complications arising from nonpulsatile flow. In this study the longest duration of support was 98 days with the Berlin Heart VAD in a patient that ultimately underwent successful transplantation. These authors also noted the importance of the reversal of renal, hepatic, and pulmonary dysfunction that the support period provided, as well as the need for early extubation and ambulation of these children.
Stiller and colleagues [36] reported the successful use of the Berlin Heart VAD for the support of 4 children with myocarditis. All children in this study had admission ejection fractions less than 12%. The duration of support was 11 to 21 days. Three of the 4 patients were successfully weaned from support, whereas 1 patient was successfully bridged to transplantation. These authors cited fewer bleeding complications with the Berlin Heart VAD compared with ECMO due to reduced anticoagulation and less platelet destruction. In addition, this pulsatile paracorporeal system was clearly superior to ECMO for providing moderate to long-term support while awaiting return of ventricular function or serving as a bridge to transplantation. Several other reports exist detailing the successful use of the Berlin Heart VAD for pediatric patients [50, 52, 53].
| Future devices for pediatric mechanical circulatory support |
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Pneumatic membrane pumps
The Pierce-Donachy pediatric VAD is a small pulsatile system that uses a pneumatically driven membrane sac-type pump [54]. The device is a scaled-down version of the adult system and consists of a pneumatic power unit and a control console. The pump housing and blood sac are manufactured from polyurethane with a stroke volume of 11 mL. The device uses 10 mm bileaflet inflow and outflow valves. This system is a paracorporeal system that would be capable of delivering prolonged, pulsatile circulatory support. Animal studies have revealed acceptable hemodynamics and hemolysis rates.
Miniature centrifugal pumps
Several miniaturized centrifugal pumps are in development as part of implantable circulatory support systems [5567]. The Gyro pump is one such device that may be suitable for implantation in children because of its small size (housing dimensions, 6.5 x 4.5 cm) [56]. Cannulation is accomplished by direct implantation of the inlet cannula into the left ventricular apex with graft cannulation of the descending aorta. The pump housing is manufactured from titanium, and electrical power is translated to the pivot bearing impeller through a magnetic coupling from a separate actuator-driver. The goal of development is to produce a fully implantable system that includes a transcutaneous energy transfer system, an internal battery, and an internal controller. In vivo studies in a calf model demonstrated efficient pump function over a physiologic range of cardiac output and low levels of hemolysis. Problems with pannus formation in the pump inlet are being addressed in further preclinical studies.
Axial flow pumps
These systems generally consist of electromagnetically coupled, integrated motor-impeller pump assemblies [6870]. Inlet flow is achieved by apical ventricular cannulation with outlet cannulation of the ascending or descending aorta. Any device that requires direct apical cannulation currently would be unsuitable for neonatal cardiac support; however, due to the small size of these devices, support for older children might be feasible. All of these systems have undergone extensive animal testing. Three of these devices have been used in adult patients: (1) the MicroMed DeBakey VAD (MicroMed Technology, Inc, The Woodlands, TX) [70]; (2) the Jarvik 2000 Heart, (Jarvik Heart, Inc, New York, NY) [71]; and (3) the Heartmate II LVAD (Thermocardiosystems, Inc, Woburn, MA) [72]. Table 2
provides a summary of the current status of VADs that have been either successfully used for support of pediatric patients or may be used for children in the future.
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