Evaluation of air handling in a new generation neonatal oxygenator with integral arterial filter.

Prime volume of the cardiopulmonary bypass circuit may lead to significant hemodilution and the potential need for blood products for all patients, but may be more critical in the pediatric and, specifically, the neonatal patient. We report on the first use of the Terumo CAPIOX FX05 (Baby-FX) oxygenator with integral arterial filter, prime volume 43 ml, evaluating performance and air-handling of six Baby-FX versus thirteen Baby-RX oxygenators. The Terumo Baby-FX primes and performs as easily as the Baby-RX series. A significant prime component in the neonatal CPB circuit can be the arterial line filter (ALF). Removal of the ALF may lead to significant reduction in prime volume, decreased exposure to foreign surfaces with subsequent reduction in inflammation, and potential elimination or reduction in blood product exposures.

Multicenter experience with perventricular device closure of muscular ventricular septal defects.

Hybrid procedures are becoming increasingly important, especially in the management of congenital heart lesions for which there are no ideal surgical or interventional options. This report describes a multicenter experience with perventricular muscular venticular septal defect (VSD) device closure. Three groups of patients (n = 12) were identified: infants with isolated muscular VSDs (n = 2), neonates with aortic coarctation and muscular VSDs (n = 3) or patients with muscular VSDs and other complex cardiac lesions (n = 2), and patients with muscular VSDs and pulmonary artery bands (n = 5). Via a sternotomy or a subxyphoid approach, the right ventricle (RV) free wall was punctured under transesophageal echocardiography guidance. A guidewire was introduced across the largest defect. A short delivery sheath was positioned in the left ventricle cavity. An Amplatzer muscular VSD occluding device was deployed across the VSD. Cardiopulmonary bypass was needed only for repair of concomitant lesions, such as double-outlet right ventricle, aortic coarctation, or pulmonary artery band removal. No complications were encountered using this technique. Discharge echocardiograms showed either mild or no significant shunting across the ventricular septum. At a median follow-up of 12 months, all patients were asymptomatic and 2 patients had mild residual ventricular level shunts. Perventricular closure of muscular VSDs is safe and effective for a variety of patients with muscular VSDs.

Four-year prospective study of pulmonary venous thrombosis after lung transplantation.

The objective of this study was to prospectively assess pulmonary venous anastomosis by transesophageal echocardiography after lung transplantation. Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. Eighty-seven consecutive adult lung transplant recipients underwent transesophageal echocardiography within 48 hours after surgery. Thrombosis of a pulmonary vein was diagnosed in 13 (15%) of 87 patients in the early postoperative period after lung transplantation. Mean thrombus width was 0.9 +/- 0.4 cm (range, 0.5 to 1.7 cm), with an average peak flow velocity at the site of obstruction of 127 +/- 23 cm/s (range, 90 to 150 cm/s). Five patients with pulmonary vein thrombosis died in the perioperative period, yielding a 90-day mortality rate of 38%. Larger thrombus size and greater acceleration of flow through a narrowed pulmonary vein correlated with poor clinical outcome. During each year of the study, the incidence of pulmonary vein thrombosis declined progressively. Pulmonary vein thrombosis is a potentially ominous complication in the early postoperative period after lung transplantation. Transesophageal echocardiography is a valuable tool for detecting abnormalities of the pulmonary venous anastomosis. Thrombus size and flow velocity at the anastomotic site may guide prognosis and clinical management. Complications of the pulmonary venous anastomosis are in part technical in nature.

Regression of pulmonary arteriovenous malformations following heart transplantation.

Pulmonary arteriovenous malformations (PAVMs) can occur following caval to pulmonary artery connection, Glenn and/or Fontan procedure, leading to severe cyanosis and exercise intolerance. It is unknown whether these abnormalities regress or persist following heart transplantation (HTx). Twenty patients with failed Fontan or Glenn procedures were screened for PAVMs prior to HTx by contrast echocardiography, selective pulmonary angiography, and pulmonary venous desaturation. Age at transplant, diagnosis, previous operations, time from Glenn to transplant, systemic oxygenation, hemoglobin level, and ventricular function were determined. The clinical course after HTx was characterized in three patients with significant PAVMs. Indications for HTx were exercise intolerance and severe cyanosis in one patient, and cyanosis and ventricular dysfunction in two. Pre-HTx, mean systemic saturation was 67%; mean pulmonary venous wedge saturation was 81%. Post-HTx, oxygen saturations were normal (> 96%) at 14, 40, and 180 days. Contrast echocardiography, performed 1 month to 3.3 yrs after HTx, showed no intrapulmonary shunting in two patients and minimal shunting in one. One patient suffered an embolic stroke from right-to-left shunting post-HTx. All patients are alive and well 35, 71, and 73 months post-HTx. In patients with single ventricle physiology, PAVMs are not an absolute contraindication to HTx. Heart-lung transplant may not be required for these patients.

Deleterious effects of telescoped bronchial anastomosis in single and bilateral lung transplantation.

PURPOSE: To compare complication rates of telescoped versus end-to-end bronchial anastomoses in single and bilateral lung transplantation. METHODS: One hundred and thirty adult lung transplant recipients were evaluated during a seven-year period for the presence of three types of major bronchial anastomotic complications (ischemia, dehiscence, and severe stenosis). Surgical technique, clinical course, and mortality in all patients were reviewed retrospectively. RESULTS: The three major complications, ischemia, dehiscence, and severe stenosis, were observed in 13 (32%), 10 (24%), and 13 (32%), respectively, of 41 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis, occurred in 25 (19%), 14 (10%), and 11 (8%) of 135 end-to end anastomoses. These differences were statistically significant for the occurrence of dehiscence and severe stenosis (p=0.0350 and 0.0004, respectively), and not statistically significant for ischemia (p=0.0846). Five (12%) telescoped anastomoses required stent placement as compared with six (4%) end-to end anastomoses (p=0.1313). Early postoperative pneumonia was more common in the telescoped anastomosis group (57%) as compared to the end-to-end group (35%; p=0.0271). There was a trend to shorter survival in the telescoped anastomosis group (mean survival 1172+/-149 d) as compared to the end-to-end group (mean survival 1542+/-126 d), but these differences did not achieve statistical significance (p=0.2400). CONCLUSION: In single and bilateral lung transplants, telescoped anastomoses are associated with a higher incidence of bronchial anastomotic complications and postoperative pneumonia than end-to-end anastomoses.

Implantable left ventricular assist devices can successfully bridge adolescent patients to transplant.

BACKGROUND: Left ventricular assist devices (LVAD) have been used successfully as a life-sustaining bridge to transplantation in adults with end-stage heart failure. Long-term implantable cardiac assist devices for smaller adolescent patients are not yet available in the United States. METHODS: This study reviews the experience with patients less than 21 years old that received HeartMate LVADs (TCI) at our institution. Twelve patients were implanted with 13 LVADs. The patients ranged in age from 11 to 20 years (mean 16 years). Body surface area ranged from 1.4 to 2.2 m2 (mean 1.8 m2). Patients were selected for LVAD placement based on eligibility for heart transplant and evidence of end-organ dysfunction. Device placement in small patients was facilitated with prosthetic graft abdominal wall closure. No patient received systemic anticoagulation. RESULTS: The duration of LVAD support ranged from 0 to 397 days (mean 123 days). Seven of the 8 patients eligible for discharge from the hospital with a vented-electric LVAD were supported at home while awaiting transplantation. Outcomes of LVAD support were: LVAD explantation in 2 cases (15%), expiration with LVAD in place in 3 cases (23%), and successful transplantation in 8 cases (62%). Complications included 4 patients with systemic infection, 3 re-operations for hemorrhage, 1 embolic event, and 1 intraoperative air embolus that proved fatal. One explanted patient required a subsequent LVAD and the other expired 4 months after explantation. Six of the 8 transplanted patients are alive and well with follow-up ranging from 8 to 43 months. CONCLUSIONS: Adolescent patients with heart failure can be successfully supported on a long-term basis to heart transplantation with the HeartMate LVAD. The wearable device allows for discharge home while awaiting transplantation. Device explantation without subsequent transplantation can be unpredictable. The incidence of thromboembolism remains low despite the absence of systemic anticoagulation. The technique of prosthetic graft closure of the abdominal wall facilitates the use of this device in smaller patients.

Influence of lung injury on early postoperative survival after lung transplantation.

OBJECTIVES: To identify the various risk factors for early (90 day) mortality after lung transplantation and to evaluate the relationship between lung injury and postoperative survival. METHODS: 152 recipients of single (100) or bilateral (52) lung allografts were evaluated for the presence of postoperative lung injury assessed by a composite four-component lung injury score. Preoperative variables, postoperative course, and mortality were reviewed retrospectively. RESULTS: There was a high risk of death during the first 90 d after transplantation, followed by a decline in risk during the remainder of the first postoperative year. By univariate analysis, lung injury score (p = 0.0001), chest radiograph score (p = 0.0001), and hypoxemia (PaO2/FIO2) ratio (p = 0.0002) were the most statistically significant risk factors for 90-day mortality. Other parameters such as length of intensive care stay (p = 0.0175), length of intubation (p = 0.0212), and preoperative diagnosis of pulmonary fibrosis (p = 0.0123) were also significant risk factors for 90-day mortality. By multivariable analysis, only lung injury score (p = 0.0001) was a statistically significant risk factor for 90-day mortality. The risk of 90-day mortality increased by a factor of 4.4 for each 1 point increment in lung injury score. However, none of the analyzed preoperative or postoperative variables were able to statistically predict lung injury score. CONCLUSIONS: Postoperative lung injury is the most important risk factor for early postoperative mortality after lung transplantation.

Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery.

BACKGROUND: Recent investigations at our institution have studied a variety of vasodilatory shock states that are characterized by vasopressin deficiency and pressor hypersensitivity to the exogenous hormone. Our experience in adults prompted the use of arginine-vasopressin (AVP) in a similar group of critically ill children. METHODS AND RESULTS: This report describes our early experience (from February 1997 through April 1998) in 11 profoundly ill infants and children (5 male, 6 female) ages 3 days to 15 years (median, 35 days) treated with AVP for hypotension after cardiac surgery which was refractory to standard cardiopressors. Although underlying heart disease was present (congenital heart defects in 10 and dilated cardiomyopathy in 1), only 2 patients had severely depressed cardiac function as demonstrated by 2D echocardiogram before administration of AVP. All patients were intubated and receiving multiple catecholamine pressors and inotropes, including dobutamine (n=10), epinephrine (n=8), milrinone (n=7), and dopamine (n=4) before receiving AVP. Five patients received AVP intraoperatively immediately after cardiopulmonary bypass, 5 in the intensive care unit within 12 hours of surgery, and 1 on postoperative day 2 for hypotension associated with sepsis. The dose of AVP was adjusted for patient size and ranged from 0.0003 to 0.002 U. kg(-1). min(-1). During the first hour of treatment with AVP, systolic blood pressure rose from 65+/-14 to 87+/-17 mm Hg (P<0. 0001; n=11), and epinephrine administration was decreased in 5 of 8 patients and increased in 1. Plasma AVP levels before treatment were available in 3 patients and demonstrated AVP depletion (median, 4.4 pg/mL; n=3). All 9 children with vasodilatory shock survived their intensive care unit stay. The 2 patients who received AVP in the setting of poor cardiac function died, despite transient improvement in blood pressure. CONCLUSIONS: Infants and children with low blood pressure and adequate cardiac function after cardiac surgery respond to the pressor action of exogenous AVP. AVP deficiency may contribute to this hypotensive condition.

Outcome after orthotopic cardiac transplantation in adults with congenital heart disease.

BACKGROUND: Advances in surgical and medical management have greatly improved long-term survival rates in patients with congenital heart disease (CHD). As these patients reach adulthood, myocardial dysfunction can occur, leading to cardiac transplantation. METHODS AND RESULTS: We reviewed the pretransplantation and posttransplantation courses of 24 patients >18 years old (mean age, 26 years; range, 18 to 56 years) with CHD who received a transplant between January 1985 and September 1998. The relation between preoperative and perioperative risk factors for complications and death was assessed. Single ventricle was the pretransplantation diagnosis for 12 patients (50%), and d-transposition of the great vessels was the diagnosis for 4 patients (16%). Twenty-two patients had a mean of 2 previous operations. At cardiac transplantation, additional surgical procedures were required to correct extracardiac lesions in 18 patients (75%). Refractory heart failure was present in 22 patients, significant cyanosis was present in 7, and protein-losing enteropathy was present in 4. There were 5 early deaths due to bleeding (n=3) and infection (n=2). The Kaplan-Meier survival rate after cardiac transplantation was 79% at 1 year and 60% at 5 years. No anatomic or surgical risk factor was predictive of death. The outcome of patients with CHD who received a transplant was compared with that for patients without CHD (n=788). Mean bypass and ischemic times were significantly longer in patients with CHD than in patients without CHD. Survival rates after transplantation did not differ significantly between patients with and those without CHD (P=0.83). CONCLUSIONS: Successful cardiac transplantation is obtainable in adults with complex CHD, with an outcome similar to that of patients without CHD. A detailed assessment of cardiac anatomy and careful surgical planning are essential to the pretransplantation and posttransplantation management of these patients.

Long-term survival after cardiac retransplantation: a twenty-year single-center experience.

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.

Preliminary experience with mycophenolate mofetil used after lung transplantation.

This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.

Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation.

Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of lung allografts are a major risk factor for the subsequent development of obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution between 1990 and 1996. Using Kaplan-Meier product limit estimate analysis, there was a 50% probability of grade A2 or A3 rejection by 1 yr after transplant. By univariate analysis, the only significant predictor of early high-grade rejections was the presence of one or more mismatches at the HLA-DR locus (p = 0.038). This association was confirmed using the Cox proportional hazards model for multivariable analysis, with HLA-DR locus mismatch being the only risk factor identified for high-grade rejection (p = 0.036). Using repeated rejection analysis, recipients with one or more matches at the HLA-DR locus had a lower cumulative rate of grade A2 or A3 rejections during the first year compared with recipients with no matches at the HLA-DR locus (0.73 versus 1.32). In addition, recipients with one or more HLA-B locus matches had a lower cumulative rate of grade A2 or A3 rejections in the first year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30). These results indicate that mismatches between donors and recipients at the HLA-DR and HLA-B loci are important risk factors for early high-grade rejections after lung transplantation. Immunosuppressive protocols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acute rejections in recipients of lung transplants, and may directly impact on the time to onset of OB.

Mechanical forces contribute to neonatal lung growth: the influence of altered diaphragm function in piglets.

Neonatal lung growth is controlled in part by mechanical forces. Altered mechanical forces precipitated by phrenectomy or prosthetic replacement of the diaphragm result in altered thoracic volume relationships, which, in turn, change lung distending pressures and or thoracic volume. These effects might contribute to regional lung growth. We postulated a relationship between altered thoracic mechanical forces and changes in lung growth and asked if altered diaphragm function influenced regional lung growth. Piglets (28d, 7-8kg), were assigned to left transthoracic phrenectomy (P), prosthetic diaphragm replacement (PDR), or sham (S), (n = 6). After a mean 10 days, piglets were studied with tracheostomy and regional pleural pressure transducers. Integrated lung volumes (LV) were recorded with intrapleural pressure (Pip). Dynamic compliance (Cdyn) was calculated (dV/dP). After sacrifice continuous pressure volume (P/V) curves were generated. Lungs were then cut into 4 quadrants based on relationship to R/L bronchus and processed for DNA content and total protein indexes. Analysis of data were made within and between groups. Body weight and gain were similar in all. LV, Pip, Cdyn, and P/V were not significantly different in PDR and P compared with S. Pip differences between thoracic regions within each group were significant for PDR and showed LU less than RU, LL less than RL (P less than 0.05). RU and RL Pip in the PDR group were the same as S. Pip in the P group were decreased in the RU, LU, and LL but only the LL approached significance. Whole lung wet weights were decreased (P less than .05) in P compared to PDR and S.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital diaphragmatic hernia, extracorporeal membrane oxygenation, and death: a spectrum of etiologies.

Extracorporeal Life Support Organization (ELSO) registry data show increased mortality in congenital diaphragmatic hernia (CDH) infants compared with other extracorporeal membrane oxygenation (ECMO) indications. To test the hypothesis that death might be related to various clinical parameters, retrospective data collection was solicited on 175 ECMO-related CDH deaths from 41 American ECMO centers (ELSO Registry 1980 through 1989). Data capture forms were received on 100 of 175 infants representing 29 of 41 centers. After review of all available material, a predominant cause of death was assigned. Other diagnoses were given secondary status. We analyzed arterial blood gas values at 6, 3, and 1 hour pre-ECMO, as well as at the time of highest recorded PO2 (preductal and postductal) and lowest recorded PCO2, and correlated these findings with predominant cause of death. The relationship between individual variables and cause of death was assessed by t test. Multivariate analysis was performed by using a stepwise discriminate procedure. The most common predominant causes of death were brain death (29%), pulmonary hypertension (25%), and pulmonary hypoplasia (17%). Correlation of arterial blood gas values at 6, 3, and 1 hour pre-ECMO with predominant causes of death established the following statistically significant associations (P less than .05): (1) pulmonary hypoplasia and low PO2 at 6 hours pre-ECMO; (2) brain death and low pH at 1 hour pre-ECMO; and (3) pulmonary hypertension and high HCO3- at 1 hour pre-ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal membrane oxygenation for perioperative support in pediatric heart transplantation.

Extracorporeal membrane oxygenation has demonstrated effectiveness for cardiopulmonary support in a variety of clinical situations. This article reviews the cases in which extracorporeal membrane oxygenation was used as an adjunct to pediatric cardiac transplantation. Twenty children, aged 7 days to 17 years, with cardiac failure refractory to conventional therapy received extracorporeal membrane oxygenation for 6 to 192 hours. In 4 cases it was used as a bridge to transplantation; in 10 cases it facilitated resuscitation of the cardiac allograft in the immediate postoperative period; and in 6 cases it complemented therapy for severe rejection in the late postoperative period. Twelve patients survived extracorporeal membrane oxygenation, 7 of whom lived more than 8 months. One long-term survivor was in the bridge-to-transplant group, 4 in the immediate postoperative group, and 2 in the rejection group. All survivors have normal cardiac allograft function. These data suggest that extracorporeal membrane oxygenation can be used to support profound cardiac failure in the pediatric heart transplant patient as a bridge to transplantation, in the resuscitation of the cardiac allograft, or to supplement a rejecting allograft.

Differential effects of alveolar and arterial oxygen tension on pulmonary vasomotor tone in ECMO-perfused, isolated piglet lungs.

Hypoxia is a known stimulant of pulmonary hypertension. We hypothesized graded effects of alveolar (PAO2) and arterial (PaO2) oxygen tension on pulmonary vascular resistance (PVR). A standard in situ, isolated lung preparation was modified by adding an oxygenator to the perfusion circuit with cannulation of the unarrested heart, allowing control of PAO2 and PaO2 in lungs devoid of ischemic injury. Seven anesthetized piglets were prepared with occlusive tracheostomy, ductus arteriosus ligation, and cannulation of the left atrium and main pulmonary artery. Animals were exsanguinated while simultaneously perfusing the lungs with a donor-blood primed extracorporeal membrane oxygenation circuit. Flow, left atrial pressure, pH, and PCO2 were kept constant. PAO2 and PaO2 were altered to establish four different experimental conditions as described by a latin square. PVR was calculated from measurements of pulmonary artery pressure (PAP) before and after introducing an experimental condition. Results show that (1) alveolar hypoxia significantly increases PVR despite arterial hyperoxia; (2) alveolar hypoxia is a more potent stimulus of pulmonary vasoconstriction than arterial hypoxemia; (3) alveolar and arterial oxygen tension are independent, additive effectors of PVR; and (4) recovery from acute hypoxic pulmonary vasoconstriction may be more sensitive to alveolar oxygen tension.

Molecular cloning of the 3'-proximal third of Sendai virus genome.

Portions of the Sendai virus genome were randomly cloned by using virion 50S RNA and calf thymus DNA pentanucleotides as primers. The recombinant clones were probed first with radiolabeled products of an in vitro virion RNA polymerase reaction to locate early message clones and then with a probe from the viral genome 3' end to locate the most 3'-proximal clones. Clones were then ordered from the 3' end of the genome and used to construct a genetic map of the 3'-proximal third of the genome by hybrid-selection of mRNAs. We report that the gene order for this region is 3'-NP - P + C - M-5' and that the genetic loci of the viral P and C proteins cannot be separated by these techniques.