Prospective, randomized evaluation of the efficacy of fibrin sealant as a topical hemostatic agent at the cannulation site in neonates undergoing extracorporeal membrane oxygenation.

BACKGROUND: The topical hemostatic effect of fibrin sealant that has been solvent/detergent treated and plasminogen depleted was evaluated in a multicenter prospective, randomized controlled study at the cannulation site wound of infants undergoing extracorporeal membrane oxygenation (ECMO). METHODS: The test group received standard cauterization and Fibrin sealant, while the control group was given cauterization alone to control hemostasis at this site. Efficacy data were available on 173 randomized study subjects of whom 149 met study entry criteria. All were managed according to standard ECMO practice. RESULTS: Fibrin sealant reduced the risk of bleeding, was associated with less shed blood, and was associated with shorter duration of hemorrhage. Further, control infants showed an increased bleeding risk with less depressed fibrinogen levels and prothrombin time elevations >18 seconds prior to ECMO. CONCLUSION: Fibrin sealant is useful as a topical hemostatic agent in patients with coagulopathy not responding to standard surgical techniques.

Neutrophil and cytokine activation with neonatal extracorporeal membrane oxygenation.

OBJECTIVE: To determine whether extracorporeal membrane oxygenation (ECMO), like cardiopulmonary bypass, produces systemic inflammatory responses that could potentiate organ injury in infants with respiratory failure. STUDY DESIGN: We evaluated the effects of neonatal ECMO on neutrophil surface adherence proteins, elastase release, and cytokine levels in blood samples from 15 patients before and during ECMO, and from banked blood and ECMO circuit blood before cannulation. Neutrophil elastase, tumor necrosis factor alpha, and interleukin types 1 beta, 6, and 8 were measured. Chest radiographs were evaluated by a radiologist using a lung injury score in blinded fashion. RESULTS: Primed ECMO circuit blood, in comparison with patient pre-ECMO blood, demonstrated marked up-regulation of CD11b (mean fluorescence intensity 1660 +/- 109 vs 361 +/- 81; p < 0.001 (mean +/- SEM)), shedding of L-selectin (mean fluorescence intensity 10 +/- 2 vs 89 +/- 38; p < 0.01), and elevated elastase levels (349 +/- 76 vs 154 ng/ml +/- 38; p < 0.001), consistent with neutrophil activation. During ECMO, neutrophil CD11b levels increased but L-selectin was not significantly shed. Concentrations of circulating neutrophil elastase increase significantly during ECMO. Corrected circulating quantities of interleukin-8 also rose significantly, but the responses of tumor necrosis factor alpha and interleukin-1 beta were minimal. Radiographic lung injury scores worsened with the initiation of ECMO (median score: 6 before ECMO vs 11 in first hour of ECMO; p = 0.012), in conjunction with indicators of neutrophil activation. CONCLUSION: Neonates with respiratory failure have activation of the inflammatory cascade. ECMO incites additional neutrophil and cytokine activation in association with early pulmonary deterioration. Routine leukodepletion of blood for circuit priming to remove activated neutrophils may be beneficial.

Long-term dual perfusion of isolated human placental lobules with improved oxygenation for infectious diseases research.

An improved method for long-term perfusion of the isolated human term placental lobule has been developed to investigate the maternofetal transfer of infectious agents, in particular the human immunodeficiency virus (HIV). The purpose of this paper is to describe those modifications that allow for substantially prolonged perfusions in in a biohazard environment. The method described has been adapted from previous models. The perfusion apparatus has been modified for use within a biohazard hood, and, intravenous bags contain the medium for circulation of perfusates in closed circuits. A Mera Silox-S 0.3 membrane oxygenator delivers more oxygen to the tissue, and, Electromedic Cardioplegia heat exchangers warm the perfusate prior to oxygenation. Viability criteria (glucose consumption, lactate production, de novo production of human placental lactogen (hPL), volume loss, flow, temperature, pressure, oxygen transfer, carbon dioxide production, absence of IgM transfer and light and electron microscopy) demonstrate that the placental tissue remains in a functional state throughout the perfusion. Oxygen and glucose consumption are both stable over time; lactate levels remain constant; and hPL continues to be produced. These significant modifications of the perfusion system have permitted the investigators to increase the duration of perfusion to 48 h while preserving normal metabolic function of ultrastructurally intact tissue as demonstrated by ultra structural observations. This perfusion model device provides biohazard precautions and may be applied to other studies of placental physiology.

Venovenous extracorporeal membrane oxygenation affects renal function.

OBJECTIVE: We evaluated the effect of venovenous extracorporeal membrane oxygenation (ECMO) on renal function and fluid balance in neonates with severe respiratory failure. DESIGN: We retrospectively reviewed the charts of 30 consecutive patients who met criteria for treatment with ECMO. Twelve were managed without ECMO (comparison group) and 18 were treated with venovenous ECMO (treatment group). SETTING: The study was conducted in a single level III neonatal intensive care unit in a regional children's hospital accepting medical and surgical neonatal transfers. Our hospital does not have an inborn service. PATIENTS: Neonates were included if their gestational age was more than 34 weeks, they weighed more than 2 kg, and their respiratory failure was severe enough to warrant consideration of ECMO as a mode of support. All the neonates in this study were treated with high-frequency ventilation before being considered for ECMO; none were treated with nitric oxide. Criteria used to determine whether a neonate was a candidate for ECMO included: (1) alveolar-arterial oxygen difference greater than 60 kPa (610 torr) for 8 hours; (2) alveolar-arterial oxygen difference greater than 59 kPa (605 torr) and a peak airway pressure greater than 3.7 kPa (38 cm H2O) for 4 hours; (3) oxygenation index greater than 40 on three of five postductal blood gases obtained at least 30 minutes apart and unstable patient condition; or (4) refractory, severe respiratory failure with sudden decompensation (partial pressure of arterial oxygen 3.4 kPa or lower, 35 torr) despite maximal medical management for 2 hours. We did not include patients with congenital diaphragmatic hernia. MAIN RESULTS: There were no differences between the groups in gestational age, birth weight, age at admission, gender, or diagnoses. Over the course of the 108 hours reviewed for each case, neonates treated with ECMO had higher positive fluid balance (P < .001), lower urine flow rates (P < .01), and higher blood urea nitrogen (P < .01) and creatinine (P < .01) levels than neonates managed without ECMO. There were no differences in mean blood pressure, protein intake, serum albumin, or use of diuretic therapy that might explain the differences between the groups. CONCLUSION: We conclude that venovenous ECMO is associated with transient impairment in renal function and marked fluid retention.

Preferential use of venovenous extracorporeal membrane oxygenation for congenital diaphragmatic hernia.

Acute respiratory failure (ARF) secondary to congenital diaphragmatic hernia (CDH), unresponsive to maximal medical management, has traditionally been treated with venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Venovenous (VV) ECMO offers several benefits over VA ECMO including preserved pulmonary blood flow, preservation of the carotid artery, and pulsatile flow. However, use of the VV modality has not been widespread because of concerns of the cardiac instability during bypass, and because only one double-lumen (DL) catheter size is available in the United States. The authors hypothesize that VV ECMO is a safe and effective treatment for CDH, symptomatic at birth, and report a single institution experience of preferential VV use for CDH. Over an 18-month period, 14 patients with CDH were placed on ECMO after maximal medical management failed, including high-frequency ventilation and nitric oxide in some cases. Ability to place the 14 Fr DL catheter was the sole criteria for VA or VV selection. Nine patients were successfully placed on VV and 5 on VA; no VV patient required conversion to VA. The two groups of patients were similar with respect to degree of illness, birth weight, EGA, time on and age at start of ECMO. Overall survival for this series was 64%: 66% in the VV group and 60% in the VA group. Two patients in the VV group were found to have congenital heart disease incompatible with life, were withdrawn from therapy and allowed to die, and are listed as treatment failures. The authors conclude that CDH patients receive adequate oxygenation and show hemodynamic stability on VV ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of acute perinatal asphyxia or meconium aspiration to produce persistent pulmonary hypertension in a neonatal baboon model.

OBJECTIVE: Our purpose was to determine whether perinatal asphyxia or meconium aspiration, or both, can produce the physiologic and histologic pulmonary vascular changes associated with the meconium aspiration syndrome. STUDY DESIGN: Twenty neonatal baboons were studied in four groups: 1, control; 2, meconium aspiration; 3, asphyxia (intermittent cord compression); and 4, asphyxia with meconium aspiration. Animals were ventilated for 24 hours under ketamine, diazepam, and pancuronium. Data were analyzed by means of mixed model analysis of measures. RESULTS: Meconium significantly impaired oxygenation (p < 0.001), whereas concurrent asphyxia moderated this effect (p < 0.034). Meconium also increased the need for ventilatory support (p < 0.002). No animal had persistent pulmonary hypertension; neither systemic nor pulmonary systolic pressures differed statistically between the groups. No animal showed evidence of abnormal pulmonary arteriolar muscularization. CONCLUSION: Sublethal perinatal asphyxia or meconium aspiration were insufficient to produce either the physiologic or histologic changes of severe meconium aspiration syndrome. It is unlikely that intrapartum fetal distress alone can produce this syndrome in human neonates.

Extracorporeal membrane oxygenation service at Egleston: two years' experience.

Extracorporeal membrane oxygenation (ECMO) is a perfusion support procedure that has been used to treat more than 7,000 patients with life threatening cardiac and/or respiratory failure. After 6 months of training and preparation, an ECMO service was opened on January 2, 1991, in Egleston Children's Hospital at Emory University. During the first 2 years, 96 neonatal, 31 pediatric, and 8 cardiac patients have been referred for possible ECMO. Of these 135 patients, 21 had disqualifying conditions. Sixty-four were considered candidates for ECMO but were able to be supported using less invasive therapies; only one of these died. Fifty patients were treated with ECMO of whom 39 survived (78%). Survival rates for neonatal, pediatric, and cardiac cases as separate groups as well as for each diagnostic category within these groups compare favorably with those reported by the international ELSO Registry. Notable in this series is the fact that 26/35 neonatal patients and 7/10 pediatric patients were successfully supported using venovenous (VV) rather than venoarterial (VA) perfusion, with the major indication for venoarterial ECMO being inability to introduce the 14F venovenous catheter into the patient's internal jugular vein. No patient initially managed with VV ECMO required conversion to VA. It is anticipated that avoidance of carotid ligation along with other innovations, such as the impending commercial availability of heparin-coated ECMO circuits, will make ECMO a highly attractive and appropriate therapy for an increasing number of high risk neonatal and pediatric patients in our state and region.

Effects of venovenous extracorporeal membrane oxygenation on cardiac performance as determined by echocardiographic measurements.

We evaluated the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cardiac performance by echocardiographic measurements in 15 infants. Heart rate and blood pressure were also recorded. Echocardiographic measurements included aortic and pulmonary peak blood flow velocities, pulmonary time to peak velocity, left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, and peak systolic wall stress before, during, and after venovenous ECMO. Pre-ECMO echocardiograms showed borderline or normal indexes of cardiac function. After initiation of venovenous ECMO, all infants had normalization and no infant had deterioration of cardiac performance. The inotropic agents dopamine and dobutamine were decreased from average doses of 12 and 3.6 micrograms/kg per minute, respectively, to 3.7 and 1.3 micrograms/kg per minute, respectively, within 8.8 hours of the institution of venovenous ECMO. During this time the mean arterial pressure remained stable, and the heart rate decreased (169 +/- 21 vs 136 +/- 15 beats/min; p < 0.001). During the course of ECMO there were no changes in left ventricular shortening fraction, velocity of circumferential fiber shortening corrected for heart rate, or aortic peak blood flow velocities. Pulmonary artery peak blood flow velocity (69 +/- 22 vs 92 +/- 28 cm/sec; p = 0.04) and pulmonary time to peak velocity improved (47 +/- 11 vs 65 +/- 16 msec; p = 0.026). We conclude that venovenous ECMO does not have deleterious effects on cardiac performance.

Efficacy of venovenous extracorporeal membrane oxygenation for neonates with respiratory and circulatory compromise.

We report a 12-month experience at Egleston Children's Hospital in Atlanta, Ga., with a protocol under which venovenous extracorporeal membrane oxygenation (ECMO) was used instead of venoarterial ECMO. Fifty-five newborn infants were referred for ECMO, four of whom had disqualifying conditions (all four died). Thirty-one infants were supported without recourse to ECMO, one of whom died. Of the 20 remaining patients, three were placed on a venoarterial ECMO regimen because of our early uncertainty about the efficacy of venovenous ECMO or because of technical constraints. All other patients (n = 17), including three with congenital diaphragmatic hernia, were supported with venovenous perfusion. No patient begun on a venovenous ECMO regimen required conversion to venoarterial bypass. Before ECMO, venovenous patients required an average dopamine dose of 16 micrograms/kg per minute and an average dobutamine dose of 6 micrograms/kg per minute. Of 15 patients studied before ECMO, three had significantly impaired contractility, and all had evidence of pulmonary hypertension on an echocardiogram. Mean blood pressure did not change while heart rate fell from 172 to 146 beats/min during the first 2 hours of ECMO and vasoactive drug doses were reduced. Of the 17 venovenous ECMO patients, 15 (88%) survived. We conclude that neonatal patients with severe hypoxia and substantial circulatory compromise can be effectively supported by venovenous ECMO in most cases.

Comparison of a new venous control device with a bladder box system for use in ECMO.

During extracorporeal membrane oxygenation (ECMO), forward pump flow must not be allowed to exceed the rate of blood drainage from the patient so that excessive negative pressure does not develop within the ECMO circuit or in the patient's right atrium. A distensible reservoir ("bladder") and mechanically actuated electronic switch ("bladder box"), has typically been used for this purpose. If the rate of blood flow from the patient to the pump is insufficient to support the perfusion rate desired and adjustments in volume status and catheter position do not increase blood drainage, the only recourse is to increase the siphon pressure by elevating the patient. At the author's institution, a novel venous control module (VCM), without a reservoir, that can provide increased venous drainage without elevating the patient is used. Using an in vitro model of neonatal ECMO, the authors' compared their VCM to a commercially available "bladder box" system. Pressures were monitored in a collapsible chamber inside a water bath (simulating the right atrium), at the gravitational high point of the ECMO circuit ("neck site") and at the low point of the circuit ("venous site") at flow rates of 100, 450, 900, and 1,300 cc/min. Pump shut-off characteristics for both systems were also measured with either sudden interruption of venous drainage ("cross-clamping") or restriction of venous inflow ("hypovolemia"). Under continuous flow conditions, higher flows could be achieved with the VCM. With acute venous catheter occlusion, instantaneous ("trough") pressures at the neck site were lower, and venous monitoring site pressures were higher with the bladder box system.(ABSTRACT TRUNCATED AT 250 WORDS)

Internal carotid artery blood flow velocities before, during, and after extracorporeal membrane oxygenation.

Blood flow velocities in the internal carotid arteries were studied with pulsed Doppler in 25 neonatal patients (birth weight range, 2600 to 4100 g) who had extracorporeal membrane oxygenation (ECMO). Time averaged mean systolic, mean diastolic, and mean blood flow velocities were calculated. Five infants had right common carotid artery reconstruction. Blood flow velocities measured in 15 healthy full-term infants were used as controls. Findings during ECMO included the following: (1) forward flow in the right internal carotid artery in 50% of the infants; (2) significant increase in the mean diastolic and the mean flow velocities (48% and 128%, respectively) in the left internal carotid artery when compared with pre-ECMO and control infants' values; (3) the elevation in the mean and the mean diastolic velocities was associated with changes in the PaCO2 and with an increase in the diastolic blood pressure; and (4) forward blood velocities in the right internal carotid artery were comparable with blood velocities in the left internal carotid artery and with the blood velocities of control infants. After ECMO, the mean diastolic velocity in the left internal carotid artery decreased significantly, but it remained elevated when compared with pre-ECMO values. Infants with right common carotid reconstruction had blood velocities in the right internal carotid artery comparable with the simultaneous blood velocities in the left internal carotid artery and to the blood velocities of control infants. Twenty-eight percent of the infants had major neuroanatomic lesions. Right or left preponderance was not noted. No association between blood velocity values in the internal carotid arteries or flow direction and the presence or the absence of brain lesions was noted.

Congenital pulmonary alveolar proteinosis: failure of treatment with extracorporeal life support.

Pulmonary alveolar proteinosis, a rare disease in neonates, is characterized by the accumulation of insoluble amorphous material within the alveoli. We describe two pairs of siblings with pulmonary alveolar proteinosis in two otherwise unaffected families. All four patients were term neonates in whom severe pulmonary failure developed within hours after birth; three had mature lung profiles. Radiographic lung markings were characterized by an early granular pattern followed by lung opacification. All patients were treated with extracorporeal life support for periods of 212 to 381 hours, but none survived. Life spans ranged from 16 to 190 days. We speculate that pulmonary alveolar proteinosis in neonates results from a genetic defect in surfactant processing that may not be amenable to conventional or unconventional therapies, including extracorporeal life support.

Extracorporeal membrane oxygenation as a means of stabilizing and transporting high risk neonates.

Term or near term newborns whose severity of cardiac or respiratory failure makes them candidates for extracorporeal membrane oxygenation (ECMO) are often too unstable to be safely transported to an ECMO-competent center. Faced with a large military and civilian referral population that is distributed across the entire continental United States, the authors have addressed this dilemma by developing a transportable ECMO system that can be taken to the referring hospital in a small transport aircraft. This system was on hand, but was not required, to stabilize and transport the infant in question in four cases. All had uneventful transports. Thirteen infants were placed on ECMO at their referring hospitals, one of whom died shortly after the institution of bypass. The remaining 12 infants were stabilized and transported successfully on ECMO over distances ranging from 17 to 1,437 miles, with 11 of these being long distance air transports. Four patients are long-term survivors. The authors conclude that a properly configured and managed ECMO system can effectively stabilize and transport even extremely ill neonates if the pertinent physiologic and aeromedical considerations are addressed.

Use of umbilical vessels for neonatal ECMO cannulation: possibilities and precautions.

Extracorporeal membrane oxygenation (ECMO) is being employed with increasing frequency for the treatment of neonates with severe cardiac or respiratory failure. The risks related both to carotid artery and jugular vein ligation continue to cause concern. Use of umbilical vessels for vascular access in ECMO could eliminate many of these risks. The experience to date with this approach is summarized, along with case reports of three patients treated at our center in whom the umbilical vein was cannulated to augment venous drainage. One patient died of causes unrelated to umbilical vein cannulation. One had an uneventful ECMO course and is a normal survivor, and one developed a tension hemopericardium as a complication of the umbilical vein cannulation, but is a normal survivor. Potential risks and benefits of this approach are reviewed.

Carotid artery reconstruction following neonatal extracorporeal membrane oxygenation.

Although reconstruction of the right common carotid artery (RCCA) in neonatal extracorporeal membrane oxygenation (ECMO) patients is intuitively attractive, there is little known about prolonged arterial cannulation and how it may affect subsequent vascular repair. A histological study of RCCA segments from neonatal ECMO patients was performed, so that cannulation technique and catheter design could be optimized before proceeding with arterial reconstruction. Circumferential transmural necrosis (CTN) was found in 25 of 31 (80%) arteriotomy specimens in comparison with 2 of 9 (20%) more proximal carotid specimens; the remaining specimens in each group demonstrated either focal subintimal or focal transmural necrosis. CTN was more common in patients with longer ECMO runs (96 +/- 5.9 versus 75 +/- 5.6 hours, P = .009; arteriotomy site), but was independent of cannula size, birthweight, and gestational age. Eleven patients have undergone RCCA reconstruction. Doppler flow studies at 4 to 7 months of follow-up in five patients demonstrated slightly higher right-sided versus left-sided peak systolic, end-diastolic, and mean flow velocities. No neurological or developmental problems could be attributed to vascular reconstruction. In conclusion, RCCA reconstruction is technically feasible, but due to the high prevalence of CTN at the arteriotomy site, excision of this segment is recommended at the time of arterial repair.

High-frequency oscillatory ventilation and extracorporeal membrane oxygenation for the treatment of acute neonatal respiratory failure.

Forty-six (92%) outborn and four (8%) inborn term or near-term neonates were admitted for extracorporeal membrane oxygenation (ECMO) treatment to a neonatal intensive care unit between July 1, 1985, and November 1, 1987. All infants had PAO2-PaO2 greater than or equal to 600 mm Hg in spite of aggressive conventional ventilatory and pharmacologic therapy. All patients were offered rescue treatment with high-frequency oscillatory ventilation (HFOV), and only if there was no improvement in PAO2-PaO2 with HFOV were infants treated using ECMO. Four patients died before receiving an adequate trial of HFOV and before emergency ECMO support could be initiated; 21 patients, all of whom survived to hospital discharge, responded to HFOV; 25 patients ultimately required ECMO therapy for cardiopulmonary support, with 22 (88%) surviving to discharge. Neonates responding to HFOV were of slightly younger gestational age (38 +/- 2 weeks vs 40 +/- 2 weeks, mean +/- SD; P less than .001) and more frequently had clinical evidence of pneumonia (11 of 21 vs 2 of 25; P less than .002). There was no statistically significant difference in outcome with respect to the number of ventilator days, hospital days, or survival between patients responding to HFOV and patients who required ECMO. Morbidity was increased in ECMO patients, with bleeding abnormalities, seizures, and renal failure occurring more frequently than in HFOV-treated infants. Overall, 92% (46 of 50) of the patients were treated with a staged protocol using HFOV before ECMO. A total of 46% (21 of 46) responded to HFOV treatment alone and did not require ECMO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons.

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)