Benjamin S. Bryner

Two Decades' Experience With Interfacility Transport on Extracorporeal Membrane Oxygenation

BACKGROUND Interfacility transport of patients on extracorporeal membrane oxygenation (ECMO) has been performed in large numbers at only a few programs. Limited data are available on outcomes after ECMO transport to justify expanding or discontinuing these programs. METHODS This was a retrospective review of a 20-year, single-institution experience with interhospital ECMO transport as well as a systematic review of reports of transfers of patients on ECMO. Results of both were compared with historical data from the international registry of the Extracorporeal Life Support Organization (ELSO). RESULTS Between 1990 and 2012, ECMO was used to facilitate transport of 221 patients to our institution, and 135 (62%) survived to discharge. Review of an additional 27 case series describing ECMO transport of 643 patients showed an overall survival of 61%. After stratifying by age and primary indication for ECMO, survival of transported patients was not significantly different compared with all ECMO patients in the ELSO registry, with the exception of pediatric patients treated for respiratory failure (transported patients in this category had higher survival than those in the ELSO registry). CONCLUSIONS Interfacility transport on ECMO is feasible and can be accomplished safely in the critically ill. Survival of transported patients is comparable to age-matched and treatment-matched ECMO patients at large.

Congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: does timing of repair matter?

PURPOSE Severe congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) is associated with high mortality. Timing of CDH repair relative to ECMO therapy remains controversial. Our hypothesis was that survival would significantly differ between those who underwent repair during ECMO and those who underwent repair after ECMO therapy. METHODS We examined deidentified data from the CDH study group (CDHSG) registry from 1995 to 2005 on patients who underwent repair and ECMO therapy (n = 636). We used Cox regression analysis to assess differences in survival between those who underwent repair during and after ECMO. RESULTS Five covariates were significantly associated with mortality as follows: timing of repair relative to ECMO (P = .03), defect side (P = .01), ECMO run length (P < .01), need for patch repair (P = .03), birth weight (P < .01), and Apgar score at 5 minutes (P = .03). Birth year, inborn vs transfer status, diaphragmatic agenesis, age at repair, and presence of cardiac or chromosomal abnormalities were not associated with survival. Repair after ECMO therapy was associated with increased survival relative to repair on ECMO (hazard ratio, 1.407; P = .03). CONCLUSION These data suggest that CDH repair after ECMO therapy is associated with improved survival compared to repair on ECMO, despite controlling for factors associated with the severity of CDH.

Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Neonates: Lessons Learned

PURPOSE We sought to characterize our recent experience with thoracoscopic congenital diaphragmatic hernia (CDH) repair and identify patient selection factors. METHODS We reviewed the medical records of full-term neonatal (<1 month of age) patients who underwent thoracoscopic CDH repair between 2004 and 2008 (n = 15). We obtained data on prenatal diagnosis, characteristics of the CDH and repair, complications, and outcome. RESULTS All patients were stabilized preoperatively and underwent repair at an average of 5.7 +/- 1.3 days. Six patients were prenatally diagnosed, including the 5 inborn. Thirteen defects were left-sided. All were intubated shortly after birth and 2 required extracorporeal membrane oxygenation (ECMO). Twelve of 15 (80%) patients underwent successful thoracoscopic primary repair, including 1 of the patients who required ECMO prior to repair. Conversion to open repair occurred in 3 of 15 (20%) patients because of the need for patch closure or intraoperative instability. Among those converted to open, all had left-sided CDH defects and 3 had stomach herniation (of 5 such patients). Patients spent an average of 6.9 +/- 1.0 days on the ventilator following repair. The average time until full-enteral feeding was 16.7 +/- 2.25 days, and average length of hospital stay was 23.8 +/- 2.73 days. All patients survived to discharge, and average length of follow-up was 15.3 +/- 3.6 months. CONCLUSIONS Thoracoscopic repair of CDH is a safe, effective strategy in patients who have undergone prior stabilization. Stomach herniation is associated with, but does not categorically predict, conversion to open repair. ECMO use prior to repair should not be an absolute contraindication to thoracoscopic repair.

An extracorporeal artificial placenta supports extremely premature lambs for 1 week

PURPOSE The treatment of extreme prematurity remains an unsolved problem. We developed an artificial placenta (AP) based on extracorporeal life support (ECLS) that simulates the intrauterine environment and provides gas exchange without mechanical ventilation (MV) and compared it to the current standard of neonatal care. METHODS Extremely premature lambs (110-120 days; term=145d) were used. AP lambs (n=9) were cannulated (jugular drainage, umbilical vein reinfusion) for ECLS. Control lambs (n=7) were intubated, ventilated, given surfactant, and transitioned to high-frequency oscillatory ventilation. All lambs received parenteral nutrition, antibiotics, and steroids. Hemodynamics, blood gases, hemoglobin, and circuit flows were measured. RESULTS Four premature lambs survived for 1 week on the AP, with one surviving 6 days. Adequate oxygenation and ventilation were provided by the AP. The MV lambs survived 2-8 hours. Each of these lambs experienced a transient improvement with surfactant, but developed progressive hypercapnea and hypoxia despite high airway pressures and HFOV. CONCLUSIONS Extremely premature lambs were supported for 1 week with the AP with hemodynamic stability and adequate gas exchange. Mechanically ventilated lambs succumbed within 8 hours. Further studies will assess control of fetal circulation and organ maturation on the AP.

Right-sided congenital diaphragmatic hernia: high utilization of extracorporeal membrane oxygenation and high survival

PURPOSE The purpose of the study was to assess the treatment strategies and outcome of right-sided congenital diaphragmatic hernia (R-CDH), particularly extracorporeal membrane oxygenation (ECMO). METHODS We reviewed the cases of 42 patients treated for R-CDH at our institution from 1991 to 2006. We gathered demographic information, documented ECMO use and the type of surgical repair, and compared outcomes with predicted survival as calculated by the CDH Study Groups equation. RESULTS Of the 35 patients included in our statistical analysis (7 were excluded), 12 (34%) were born at our institution, all of whom were prenatally diagnosed with R-CDH. Nineteen patients (54%) required ECMO therapy. Extracorporeal membrane oxygenation was initiated after repair of the R-CDH in 2 patients (11%). Of those patients who went on ECMO before repair, 4 patients (21%) were repaired on ECMO, 9 patients (47%) underwent repair after ECMO, and 4 patients (21%) underwent ECMO but died before their R-CDH could be repaired. Primary repair of the diaphragm was possible in 15 cases (56%), and primary closure of the abdominal incision was possible in 15 of the 23 open repairs (65%). The mean predicted survival for all 35 patients was 63%, whereas 28 (80%) actually survived. Logistic regression showed a significant association between the presence of cardiac defects and mortality (odds ratio = 0.008, P = .014). CONCLUSIONS Our data suggest that patients with R-CDH have high ECMO utilization and may experience greater relative benefit from ECMO as evidenced by their higher-than-expected overall survival. Extracorporeal membrane oxygenation may be found to have a distinctive role in managing R-CDH. More high-powered series are needed to elucidate differences between R-CDH and left-sided CDH that may dictate alternate forms of management.

Chylothorax after congenital diaphragmatic hernia repair

PURPOSE Chylothorax after congenital diaphragmatic hernia (CDH) repair contributes significantly to morbidity. Our aim was to identify factors contributing to chylothorax and effective treatment strategies. METHODS We reviewed 171 patients with CDH from 1997 to 2008 and analyzed hernia characteristics, extracorporeal membrane oxygenation (ECMO) use, operative details, and treatment approaches for chylothorax. RESULTS Ten (7%) patients developed chylothorax; all were left sided. Using univariate analysis, prenatal diagnosis, ECMO use, and patch repair were associated with development of chylothorax. Logistic regression analysis showed that patch repair was the only variable predictive of chylothorax (P = .028; confidence interval, 0.032-0.823). Although survival was not affected, patients with chylothorax had a significant increase in ventilator days and length of stay (t = 3.57; P = .000; t = 2.74; P = .007). All received thoracostomy and total parenteral nutrition. Six patients received octreotide, 5 of whom required pleurectomy because of failed medical management; the remaining patient died of overwhelming sepsis. CONCLUSIONS The incidence of chylothorax at our institution was relatively low. Patch repair was associated with the formation of chylothorax. Morbidity was substantial, but survival was not significantly affected. Total parenteral nutrition and thoracostomy were appropriate initial treatments. Octreotide was not an effective adjunct. Refractory cases were successfully treated with pleurectomy.

The Effect of Ex Situ Perfusion in a Swine Limb Vascularized Composite Tissue Allograft on Survival up to 24 Hours

PURPOSE To test the potential for the ex situ limb perfusion system to prolong limb allograft survival up to 24 hours. METHODS We used 20 swine for the study. In group 1 (control), 4 limbs were perfused with heparin solution and preserved at 4°C for 6 hours. In group 2, 4 limbs were perfused with autologous blood at 27°C to 32°C for 24 hours. In both groups, limbs were transplanted orthotopically to recipients and monitored for 12 hours. In addition to perfusion parameters, we recorded perfusate gases and electrolytes (pH, pCO2, pO2, O2 saturation, Na, K, Cl, Ca, HCO3, glucose, and lactate) and obtained functional electrostimulation hourly throughout the experiment. Histology samples were obtained for TUNEL staining and single-muscle fiber contractility testing. RESULTS In both groups, hemodynamic variables of circulation remained stable throughout the experiment. Neuromuscular electrical stimulation remained intact until the end of reperfusion in group 2 vs no response in group 1. In group 2, a gradual increase in lactate levels during pump perfusion returned to normal after transplantation. Compared with the contralateral limb in group 2, single-muscle fiber contractility testing showed no significant difference at the end of the experiment. CONCLUSIONS We demonstrated extended limb survival up to 24 hours using normothermic pulsatile perfusion and autologous blood. CLINICAL RELEVANCE Successful prolongation of limb survival using ex situ perfusion methods provides with more time for revascularization of an extremity.

Ex Situ Limb Perfusion System to Extend Vascularized Composite Tissue Allograft Survival in Swine.

Background Organ perfusion systems have successfully been applied in solid organ transplantations. Their use in limb transplantation and replantation has not been widely investigated. In this study, we tested the potential for ex situ perfusion system to prolong limb allograft viability in a swine forelimb amputation/replantation model. Methods Fourteen swine were used. In group 1 (n = 4), we perfused 4 amputated limbs for 12 hours using warm (27°C–32°C) autologous blood. Group 2 (n = 3) served as a cold preservation control group, preserving limbs for 6 hours at 4°C. All limbs were transplanted into healthy swine (n = 7) and observed for another 12 hours. Hemodynamic variables of circulation, as well as perfusate gases and electrolytes (pH, pCO2, pO2, O2 saturation, Na+, K+, Cl−, Ca2+, HCO3−, glucose, lactate) were measured. Muscle samples were used to measure single-muscle fiber contractility. Results In the control group, no microcirculation was observed after 6 hours of cold storage. In the pump perfusion group, all limbs displayed a gradual increase in lactate levels (P < 0.05) during ex situ perfusion that returned to normal after transplantation and reperfusion (P = 0.05). The pH and potassium remained stable throughout the experiment. Single-muscle fiber contractility testing showed near normal contractility at the end of the reperfusion period (P > 0.05). Limb weight did not increase significantly between the end of pump perfusion and reperfusion (P > 0.05). Conclusions We demonstrated the potential to preserve limb allograft using ex vivo circulation. This approach promises to extend the narrow time frame for revascularization of procured extremities in limb transplantation.

Inhaled Nitric Oxide to Improve Oxygenation for Safe Critical Care Transport of Adults With Severe Hypoxemia

BACKGROUND Inhaled nitric oxide (iNO) is a rescue treatment for severe hypoxemia in the intensive care unit setting. OBJECTIVE To evaluate the effectiveness and safety of iNO in adult patients with severe hypoxemia before and during transport to a tertiary care center. METHODS Prospective data were examined in a retrospective cohort study. Patients with severe hypoxemia and cardiopulmonary failure (n=139) at referring hospitals in whom conventional therapy was unsuccessful were treated with iNO in the intensive care units in anticipation of transfer to a tertiary center. Treatment wih iNO was initiated by the critical care transport team in 114 patients and continued in 25 patients. Arterial blood gas analysis was done before and after iNO treatment. RESULTS Patients treated with iNO had significant improvement in oxygenation: mean (SD) for PaO2 increased from 60.7 (20.2) to 72.3 (40.6) mm Hg (P=.008), and mean (SD) for ratio of PaO2 to fraction of inspired oxygen (P:F) increased from 62.4 (26.1) to 73.1 (42.6) (P= .03). Use of iNO was continued through transport in 102 patients, all of whom were transported without complication. The P:F continued to improve, with a mean (SD) of 109.7 (73.8) from 6 to 8 hours after arrival at the tertiary center (P< .001 relative to values both before and after treatment). Among patients treated with iNO, 60.2% survived to discharge. In 35 nonresponders, iNO was discontinued, and 15 patients could not be transferred owing to life-threatening hypoxemia; 2 were later transferred on extracorporeal membrane oxygenation. Of 18 patients transported without iNO, 9 (50%) survived. CONCLUSIONS Use of iNO significantly improves oxygenation of patients with severe hypoxemia and allows safe transfer to a tertiary care center.

Predictors of early lung function in patients with congenital diaphragmatic hernia

PURPOSE Long-term pulmonary outcomes of congenital diaphragmatic hernia (CDH) have demonstrated airflow obstruction in later childhood. We examined pulmonary function data to assess what factors predict lung function in the first three years of life in children with CDH. METHODS This was a retrospective study of patients treated for CDH who underwent infant pulmonary function testing (IPFT) between 2006 and 2012. IPFT was performed using the raised volume rapid thoracoabdominal compression technique and plethysmography. RESULTS Twenty-nine neonates with CDH had IPFTs in the first 3years of life. Their mean predicted survival using the CDH Study Group equation was 63%±4%. Fourteen infants (48%) required extracorporeal membrane oxygenation (ECMO). The mean age at IPFT was 85.1±5weeks. Airflow obstruction was the most common abnormality, seen in 14 subjects. 12 subjects had air trapping, and 9 demonstrated restrictive disease. ECMO (p=0.002), days on the ventilator (p=0.028), and days on oxygen (p=0.023) were associated with restrictive lung disease. CONCLUSION Despite following a group of patients with severe CDH, lung function revealed mild deficits in the first three years of life. Clinical markers of increased severity (ECMO, ventilator days, and prolonged oxygen use) are correlated with reduced lung function.