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Extracorporeal life support (ECLS or ECMO) is standard treatment for severe respiratory failure but poses many contraindications to future lung transplantation. The solution to this dilemma is the implantable gas exchange device (IGED) or artificial lung. Preliminary efforts to create such an artificial lung have been made since 1970 and include designs involving single devices, intravascular devices (i.e., IVOX), and combination heart-lung devices. Stringent requirements govern the design of such a device, the most important of which are high gas exchange efficiency, low resistance to blood flow, and size. This paper describes such a device. It incorporates large diameter inflow and outflow ports in close proximity and a low resistance wound hollow fiber core encapsulated in a compliant outer shell which conserves the work of the right ventricle. In a large animal model (adult sheep) this device was connected in line with the main pulmonary artery in series with the native lungs. This configuration has the advantages of using the lungs as an embolic filter, perfusing the lungs with fully oxygenated blood, and maintaining the integrity of the anatomy necessary for transplant. Laboratory experiments have run > 8 h. Preliminary data show that the animals have remained hemodynamically stable while the devices have supported the animals completely by supplying 100% O2 saturation with PO2 values ranging from 250-350 mm Hg. Additionally, this model makes possible the study of respiratory failure without introducing other variables such as extracorporeal circuits or pumps. The other metabolic, endocrine, and reticuloendothelial functions of normal and injured lungs can now be studied more precisely by excluding these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma leakage through microporous membrane oxygenators is a well known complication of prolonged extracorporeal circulation. The authors hypothesized that adsorption of bipolar plasma molecules, such as phospholipids on the microporous membrane, results in formation of a hydrophilic layer over the hydrophobic surface of the membrane; this, in turn, leads to plasma leakage at normal surface tensions. A lipid phosphorus assay was used to measure phospholipid adsorption onto the fibers of microporous membrane oxygenators tested under a variety of experimental conditions. Adsorption of phospholipids on the microporous membrane was concentration dependent. Reproducible plasma leakage occurred both in vitro and in vivo, and the time to leakage was dependent on the concentration of phospholipids adsorbed upon the microporous membrane. Based upon these results, the authors conclude that adsorption of phospholipids contributes to the development of plasma leakage through microporous membrane oxygenators.

Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF.

Closed-circuit spirometry techniques were used to study gas exchange (oxygen and carbon dioxide transport) across the native lung and membrane lung in ten neonates treated with extracorporeal membrane oxygenation (ECMO). Initially there was negligible oxygen transport across the native lung (0.4 +/- 0.4 mL/kg/min). An increase in native lung oxygen transport (2.0 +/- 1.5 mL/kg/min) at low ventilator settings and high levels of extracorporeal support heralded recovery of the native lung and predicted weaning from ECMO. Measurement of oxygen consumption and carbon dioxide production permitted the energy expenditure to be calculated in these critically ill neonates. The metabolic rates varied widely in each neonate over time and among neonates. (mean 57 +/- 11 kcal/kg/d, range 38 to 80 kcal/kg/d). This emphasizes the need to determine energy expenditure in order to guide nutritional support.

Twenty-four to 48 hr veno-arterial bypass with microporous membrane oxygenators causes moderate progressive thrombocytopenia associated with decreased platelet function, no significant change in clotting factors, fibrinogen, or the fibrinolytic system, and minimal change in white blood count, differential, and plasma hemoglobin. These effects are identical to those seen in previous studies following the same protocol with solid silicone rubber membrane oxygenators. Microporous membrane is suitable for prolonged extracorporeal support systems. This study suggests that the deleterious effects of a direct blood gas interface are caused by continuous renewal of the surface rather than the nature of the interface itself.

ECMO support has been evaluated in 29 newborn infants with respiratory failure. Lung function improved in 16 and 13 surivived. Important technical factors include venoarterial bypass with full support capability, careful measurement and treatment of coagulation and platelet status, and a skilled and experienced team. Detecting high risk infants early in life is important. Intracranial bleeding is the most common cause of death.

Sixteen moribund newborn infants with respiratory failure were treated with extracorporeal membrane oxygenation (ECMO) for 1 to 8 days. Cannulation via the right jugular vein and carotid artery was used to establish venoarterial-cardiopulmonary bypass. High flow (80 percent of cardiac output) allowed decreasing FIO2 and airway pressure. Diagnoses and results were as follows: respiratory distress syndrome, four patients (two improved, one survived); meconium aspiration syndrome, eight patients (four improved, three survived); persistent fetal circulation (some with diaphragmatic hernia), four patients (three improved, two survived). Intracranial bleeding occurred in 43 percent, accounting for most of the deaths. In a parallel series of 21 infants treated with conventional ventilator therapy, the mortality rate was 90 percent and intracranial bleeding occurred in 57 percent. ECMO provided life support and gains time in newborn respiratory failure. In high mortality risk infants, the rate of survival is higher and intracranial bleeding lower with ECMO than with optimal ventilator management.

Extracorporeal membrane oxygenation (ECMO) was used in the treatment of 100 newborn infants with respiratory failure in three phases: Phase I (50 moribund patients to determine safety, efficacy, and risks); Phase II (30 high risk patients to compare ECMO to conventional ventilation); and Phase III (20 moderate to high risk patients, the current protocol). Seventy-two patients survived including 54% in Phase I, 90% in Phase II, and 90% in Phase III. The major complication was intracranial bleeding, which occurred in 89% of premature infants (less than 35 weeks) and 15% of full-term infants. Best survival results were in persistent fetal circulation (10, 10 survived), followed by congenital diaphragmatic hernia (9, 7 survived), meconium aspiration (44, 37 survived), respiratory distress syndrome (26, 13 survived), and sepsis (8, 3 survived). There were seven late deaths; in follow-up, 63% are normal or near normal, 17% had moderate to severe central nervous system dysfunction, and 8% had severe pulmonary dysfunction. ECMO is now used in several neonatal centers as the treatment of choice for full-term infants with respiratory failure that is unresponsive to conventional management. The success of this technique establishes prolonged extracorporeal circulation as a definitive means of treatment in reversible vital organ failure.

In a national registry, data were collected on 715 newborn patients with severe respiratory failure supported by extracorporeal membrane oxygenation (ECMO) in 18 neonatal centers. This represents almost all infants treated with ECMO between 1980 and 1987. Eighty-one percent of the patients survived. This result is statistically significantly better than any other treatment which produces less than 78.4% survival. The most common diagnoses were meconium aspiration (310 patients, 91% survived), respiratory distress syndrome (96 patients, 78% survived), diaphragmatic hernia (121 patients, 65% survived), and sepsis (64 patients, 72% survived). Average pre-ECMO characteristics were: age 59 hours; PaO2 42 torr, PaCO2 41 torr, pH 7.40; ventilator settings FiO2 1.0, pressure 45/4 cmH2O, rate 93. Technical complications occurred in 23.1%, and physiologic complications occurred in 65.6%. Results improved with experience. Survival rate for the first ten patients from each center was 73.5% compared to 83.7% for all subsequent patients. Survival rate did not, however, significantly differ after an institutional experience of 20 patients. These observations were made on a large cohort that could not be accumulated at an individual center. These results indicate that ECMO and lung rest is appropriate and successful treatment for newborn respiratory failure unresponsive to other means of management, and that almost all respiratory failure is reversible in near-term neonates.

The authors designed and tested a 14F outside diameter thin-walled double lumen catheter (DLC) for neonatal venovenous (VV) extracorporeal membrane oxygenation (ECMO). In vitro tests with water and dye solution showed capacity of the drainage lumen was 1,096 ml/min at 100 cm siphon, and pressure drop across the perfusion lumen was 300 mmHg at 500 ml/min flow. Recirculation at 500 ml/min flow ranged from 5 to 29%, depending upon simulated cardiac output. The highest serum hemoglobin during 12 hour 400 ml/min flow VV bypass in five dogs was 49 mg/dl. Typical oxygen transport in four dogs was 25 cc/min at 400 ml/min flow. This catheter is well suited for clinical VV ECMO in neonates.

ECMO is capable of safely supporting respiration and circulation in newborns with severe respiratory failure and a moribund clinical presentation. The results thus far suggest that term infants with respiratory failure are the best candidates for ECMO, with a survival rate of 83 per cent. Infants under 35 weeks' gestation have a very high incidence of intracranial hemorrhage. Consequently, we do not currently accept them for ECMO treatment. The outcome of the survivors is largely determined by the clinical condition before ECMO and by major complications. Research must be directed toward cost effectiveness, timing and earlier use, alternative vascular access, cannula and circuit design, and expanded indications.

In retrospective review of survivors of neonatal extracorporeal membrane oxygenation, eight patients with varying degrees of right hemispheric brain injury were identified. The extent of preextracorporeal membrane oxygenation hypoxia and ischemia was documented: five of eight patients had arterial PO2 values of less than 40 mm Hg, seven of eight required dopamine for blood pressure support, and five of eight required cardiopulmonary resuscitation. Two patients had proven neurologic abnormalities before extracorporeal membrane oxygenation. Postextracorporeal membrane oxygenation CT brain scans showed right hemispheric focal abnormalities in three patients. Seven infants had neuromotor abnormalities which were lateralizing in nature; all were left sided, suggesting right-sided brain injury. EEGs showed an increased incidence of slowing and attenuation over the right hemisphere. These findings indicate that right-sided brain abnormalities exist after extracorporeal membrane oxygenation and that carotid artery ligation for extracorporeal membrane oxygenation is not without risk.

Extracorporeal membrane oxygenation, using venoarterial or venovenous perfusion, is a safe and effective procedure in the term of near-term infant with life-threatening respiratory failure. Without extracorporeal membrane oxygenation, due to the severity of their disease, these children are at high risk for neurologic damage, chronic lung disease, and death. Because survival is not expected without extracorporeal membrane oxygenation therapy, there is no corresponding control group to which these survivors may be compared. In this report, we reviewed the outcome at 1 to 3 years in the first 14 survivors of extracorporeal membrane oxygenation treated at our institution. Seven of 14 neonatal extracorporeal membrane oxygenation survivors (50%) were normal or near normal at between 1 and 3 years of age. Ten (71%) had normal mental ability. We conclude that in neonates with high mortality risk from respiratory failure, near-normal growth and development can be expected in the majority who survive with extracorporeal membrane oxygenation treatment.

Extracorporeal membrane oxygenation (ECMO) has been successful (greater than 80% survival) in 35 centers in greater than 900 newborns with severe respiratory failure having an estimated mortality of greater than 80% on conventional management. During the last 3 years we have treated 79 newborns with 74 survivors (94%). Their diagnoses included meconium aspiration, persistent fetal circulation, respiratory distress syndrome, congenital diaphragmatic hernia, and sepsis. Seven patients (9%) had life-threatening intrathoracic complications requiring emergent intervention while on ECMO: tension hemothorax (3), tension pneumothorax (2), and pericardial tamponade (2). Pericardial tamponade and tension hemothorax and pneumothorax show a similar pathophysiology of increasing intrapericardial pressure and decreasing venous return. Perfusion is initially maintained by the nonpulsatile flow of the ECMO circuit before further decrease in venous return results in decreasing ECMO flow and progressive hemodynamic deterioration. Each of the seven patients demonstrated a clinical triad that includes increasing PaO2 and decreasing peripheral perfusion (as evidenced by decreasing pulse pressure and decreasing SvO2) followed by decreasing ECMO flow with progressive deterioration. The diagnoses were confirmed by transillumination, chest x-ray, or cardiac echocardiogram. Initial emergent placement of a percutaneous drainage catheter was temporizing in all seven cases. However, four patients required emergent thoracotomy for definitive treatment while still on ECMO. All seven patients were weaned from ECMO and are short-term survivors (6 months to 3.5 years). As use of ECMO for newborn severe respiratory failure increases, responsible physicians must be familiar with life-threatening intrathoracic complications and appropriate treatment strategies.

Extracorporeal membrane oxygenators (ECMO) can give total respiratory support for neonates with PPHN without the barotrauma of hyperventilation. ECMO has resulted in survival of infants with PPHN who had been unresponsive to maximal ventilatory and medical support.

Neonates with severe but reversible pulmonary disease may require therapy beyond conventional ventilatory care. Extracorporeal membrane oxygenation (ECMO) serves as a temporary artificial lung for such infants. Since anticoagulation with systemic heparin is required in the extracorporeal circuit, antecedent hemorrhage may be exacerbated or new hemorrhage precipitated in ECMO patients. While the "usual" periventricular/intraventricular hemorrhage seen in a premature infant may develop, contrasting hemorrhages of unusual extent, uncommon location, or demonstrating unique alterations in internal sonographic character may be precipitated, presumably due to the requisite anticoagulation. Representative examples of such variations are presented along with guidelines for the use of cranial sonography in selecting and monitoring ECMO patients.

Intracranial hemorrhage is a complication of extracorporeal membrane oxygenation for the treatment of neonatal respiratory failure. A retrospective review of 35 neonates treated with extracorporeal membrane oxygenation was performed; ten had intracranial hemorrhage. Infants with intracranial hemorrhage had lower birth weights and were gestationally younger than infants with intracranial hemorrhage. Eight of eight neonates of less than 35 weeks' gestational age sustained intracranial hemorrhage. Six died immediately after extracorporeal membrane oxygenation was stopped. Two lived less than 1 year. Two of 27 neonates older than 34 weeks' gestational age sustained intracranial hemorrhage. One child is normal, the other died at 18 months of age. Based on the results of this study, the risk of intracranial hemorrhage appears low in neonates of greater than 34 weeks' gestational age who undergo extracorporeal membrane oxygenation treatment for severe respiratory failure. The use of extracorporeal membrane oxygenation, as it is presently performed, is contraindicated in neonates of less than 35 weeks' gestational age because of the risk of intracranial hemorrhage.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) has been successful in support of neonates with respiratory failure but requires right common carotid artery ligation. While no short-term neurologic complications have resulted from neonatal carotid ligation, late complications may occur. For both VA ECMO and venovenous (VV) ECMO, blood is drained from the right atrium via a right internal jugular cannula, oxygenated by a membrane lung, and returned to the patient. VV ECMO spares the carotid by perfusing the oxygenated blood into a vein. VV ECMO gave total respiratory support to three neonates with respiratory failure and each infant survived. In comparison with three similar VA ECMO patients, the VV patients required higher ECMO circuit flow rates and had lower systemic arterial Po2s. Length of time on ECMO, length of hospital stay, and neurologic outcome were similar in the VV and VA patients. Differences among the patients were related to their primary disease rather than to the mode of ECMO support. The VV patients had cannulation of the femoral vein for perfusion of oxygenated blood. Late complications may occur from femoral vein ligation as well as from carotid ligation so long-term follow-up is needed to assess these two ECMO techniques.

ECMO may be used clinically in selected cases to provide life support when all other modes of therapy have been exhausted. Survival of moribund patients has been demonstrated. Results might be improved if the severity of the disease is recognized and defined early in the clinical course to prevent the development of irreversible complications. ECMO requires a large, fully trained team to interface with the attending physicians and nursing staff in providing complete life support. The ECMO team provides continued evaluation of the status and treatment of the patient, detection of complications, and correction of any minor or major emergency. It also conducts laboratory and clinical research programs in pulmonary insufficiency as an adjunct to clinical life-support research.

We have used prolonged extracorporeal membrane oxygenation (ECMO) in the treatment of 13 moribund infants (including 9 neonates), with 4 survivors (3 neonates). Successfully treated cases include post-operative cardiac failure, infant respiratory distress syndrome, massive meconium aspiration, and persistent fetal circulation. All cases have been managed with veno-arterial bypass at flow rates of 80-100 cc/Kg/min. Carotid cannulation for arterial access and careful control of heparin anticoagulation based on whole blood activated clotting time are among the techniques which have contributed to this success. Progressive pulmonary or cardiac failure has been the major problem in older infants, intracranial bleeding is the major problem in neonates. Both of these problems could be minimized by instituting ECMO earlier in the clinical course, but this awaits development of reliable early predictors of mortality.

Patients with acute respiratory failure who have high mortality risk can be analyzed according to the methods outlined above. Some (but not all) of the high mortality risk patients can be identified early in the course of respiratory failure. Temporary support with ECMO is indicated in these patients if there are no signs of irreversible damage.

Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to "rest." We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) has been successful in the treatment of newborns less than 1 week of age and greater than 2000 gm birthweight with respiratory failure resistant to current medical and surgical management. While VA ECMO supports the heart as well as the lungs, it has the disadvantage of requiring carotid artery ligation and the possibility of perfusing air bubbles or particles into the arterial tree. We have treated 11 newborns with respiratory failure with venovenous (VV) ECMO returning the oxygenated blood to a cannula in the distal iliac vein. We compared these patients with 16 patients treated during the same period of time with VA ECMO. Three of the 11 VV patients required conversion to VA ECMO because of inadequate oxygenation and unstable hemodynamic situations. Ten of the 11 VV patients survived. Eleven of the 16 VA patients survived. The better survival in these patients treated with VV ECMO is attributed to their more favorable initial condition compared to patients treated with VA ECMO. The disadvantages of VV ECMO include a longer operative time to place the cannulas, groin wound problems, and persistent leg swelling along with the necessity to convert some patients to VA ECMO. Although this experience demonstrates that newborns with severe respiratory failure can be supported with VV ECMO, the complications and lack of practical advantages over VA lead us to recommend VA ECMO for routine clinical use at present.