Technical Advances in the Field of ECMO.

Although the fundamentals of extracorporeal membrane oxygenation (ECMO) have not changed in 3 decades, the technical elements continue to improve and have evolved from an assemblage of individual components to more integrated systems with added features, enhanced safety, and improved maneuverability. The introduction of polymethylpentene (PMP) fiber technology has expanded the development of artificial membranes that have low resistance, are more biocompatible, and can be used for extended durations. Extracorporeal carbon dioxide removal techniques continue to be enhanced as stand alone technology and modified renal dialysis systems are introduced. Research continues in the development of compact and wearable artificial lungs that are intended to support patients for prolonged periods (eg, patients awaiting lung transplantation). The use of high-fidelity simulation training has become a standard and important method for reinforcing technical skills, refining troubleshooting sequences, and enhancing team interactions. Modifications to mannequins and ECMO systems coupled with clinical and physiologic scenarios will help achieve greater realism and enhance learning. ECMO technology continues to improve, with adaptability and versatility being essential attributes.

Characterization of Ribavirin Aerosol With Small Particle Aerosol Generator and Vibrating Mesh Micropump Aerosol Technologies.

BACKGROUND: Ribavirin is an antiviral drug that can be administered by inhalation. Despite advancements in the oral delivery of this medication, there has been a renewed interested in delivering ribavirin via the pulmonary system. Although data are not conclusive that inhaled ribavirin improves outcomes, we set out to determine whether delivery by a newer generation nebulizer, the vibrating mesh micropump, was as effective as the recommended small-particle aerosol generator system. METHODS: We compared the physicochemical makeup and concentrations of ribavirin before and after nebulization with 0.9% NaCl and sterile water. An Andersen cascade impactor was used to determine particle size distribution and mass median aerodynamic diameter, and an absolute filter was used to measure total aerosol emitted output and inhaled dose during mechanical ventilation and spontaneous breathing. Ribavirin was analyzed and quantified using high-performance liquid chromatography with tandem mass spectrometric detection. RESULTS: Ribavirin was found to be stable in both 0.9% aqueous NaCl and sterile water with an r(2) value of 0.96 and identical coefficients of variation with no difference in drug concentration before and after nebulization with the vibrating mesh micropump. The small-particle aerosol generator produced a smaller mass median aerodynamic diameter (1.84 µm) than the vibrating mesh micropump (3.63 µm, P = .02); however, there was no significant difference in the proportion of drug mass in the 0.7-4.7-µm particle range. Total drug delivery was similar with the small-particle aerosol generator and vibrating mesh micropump in both spontaneously breathing (P = .77) and mechanical ventilation (P = .48) models. CONCLUSIONS: The vibrating mesh micropump nebulizer may provide an effective alternative to the small-particle aerosol generator in administration of ribavirin using NaCl or sterile water, both on and off the ventilator. Further clinical studies are needed to compare efficacy.

Diverse Morbidity and Mortality Among Infants Treated with Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is utilized for cardiopulmonary failure. We aimed to qualify and quantify the predictors of morbidity and mortality in infants requiring VA-ECMO. METHODS: Data was collected from 170 centers participating in the extracorporeal life support organization (ELSO) registry. Relationships between in-hospital mortality and risk factors were assessed using logistic regression. Survival was defined as being discharged from the hospital. RESULTS: Six hundred and sixty-two eligible records were reviewed. Mortality occurred in 303 (46%) infants. Congenital diaphragmatic hernia patients (OR=3.83, 95% CI 1.96-7.49, p<0.001), cardiac failure with associated shock (OR= 2.90, 95% CI 1.46-5.77, p=0.002), and pulmonary failure including respiratory distress syndrome (OR=4.06, 95% CI 1.72-9.58, p=0.001) had the highest odds of mortality in this cohort. Birth weight (BW) < 3 kg (OR=1.83, 95% CI 1.21-2.78, p=0.004), E-CPR (OR=3.35, 95% CI 1.57-7.15, p=0.002), hemofiltration (OR=2.04, 95% CI 1.32-3.16, p=0.001), and dialysis (OR=6.13, 95% CI 1.70-22.1, p<0.001) were all independent predictors of mortality. CONCLUSION: Infants requiring VA-ECMO experience diverse sequelae and their mortality are high.

Pulmonary deadspace and postoperative outcomes in neonates undergoing stage 1 palliation operation for single ventricle heart disease.

OBJECTIVES: Increased pulmonary dead space fraction (VD/VT) has been associated with prolonged mechanical ventilation after surgery for congenital heart disease. The association of VD/VT with clinical outcomes in neonates undergoing stage 1 palliation for single ventricle congenital heart disease has not been reported. We describe changes in VD/VT, differences in VD/VT based on shunt type (right ventricle to pulmonary artery conduit vs modified Blalock-Taussing shunt) and association of VD/VT with postoperative outcomes in patients undergoing stage 1 palliation. DESIGN: Retrospective chart review for demographic, hemodynamics, outcome information, and VD/VT values were collected at 6-hour intervals during the first 48 postoperative hours in neonates undergoing stage 1 palliation. VD/VT was calculated using mixed expired CO2 (PeCO2) obtained from capnography and paired arterial blood gas CO2 values. SETTING: Cardiac ICU in a tertiary care pediatric hospital. PATIENTS: Newborns with single ventricle congenital heart disease undergoing stage 1 palliation during 2003-2004. MEASUREMENTS AND MAIN RESULTS: Of the 51 patients, 31 had right ventricle to pulmonary artery and 20 had Blalock-Taussing shunt. Although VD/VT was lower in the Blalock-Taussing shunt group over all time points (p = 0.02), maximal VD/VT on day 1 (0.49 ± 0.07) and on day 2 (0.46 ± 0.08) were not different between the shunt groups. VD/VT decreased significantly over time in both shunt groups (p = 0.001 for right ventricle to pulmonary artery; p < 0.001 for Blalock-Taussing shunt). Higher maximal VD/VT during first 48 postoperative hours was independently associated with fewer ventilator (ß = -26.6; p = 0.035) and hospital-free days in the first month after stage 1 palliation (ß = -40.4; p = 0.002) after adjusting for potential confounders in a multivariable linear regression model. CONCLUSIONS: Increased pulmonary dead space exists early after stage 1 palliation operation for single ventricle congenital heart disease. Higher VD/VT during the first 48 postoperative hours was associated with longer duration of ventilation and hospital LOS and may be a useful marker of postoperative outcomes in this population.

The addition of a membrane oxygenator to a ventricular assist device in a patient with acute respiratory distress syndrome.

A 12-year-old boy with Marfan's syndrome required a biventricular assist device (VAD) after an aortic root replacement. The patient developed acute respiratory distress syndrome and required escalating ventilator support. We hypothesized that the addition of a membrane oxygenator in series with the assist device would improve gas exchange and allow for a more lung-protective ventilator approach. A membrane oxygenator was placed in series with the right VAD resulting in a blood path of right atrium to VAD to oxygenator to pulmonary artery. Circuit function was gauged by monitoring flow and oxygenator pressures and periodic circuit inspections and oxygenator blood gases. Heparin was titrated to maintain unfractionated antifactor Xa levels of .3-.7 IU/mL and partial thromboplastin time of 60-80 seconds. The initial sweep gas supplying the oxygenator was 5 L/min at an F1O2 of 1.0, which achieved a pH > 7.40 and a PF ratio > 250. The pre- and post-oxygenator pressures were 55-60 mmHg and 45-50 mmHg, respectively, and the measured flow at the oxygenator outlet was 2.0-2.2 L/min. The patient was changed from high-frequency oscillatory ventilation to pressure-controlled synchronized intermittent ventilation with pH maintained at 7.35-7.40 and PF ratio > 250. Paralytics were discontinued and the patient's neurologic condition was deemed intact. The patient hemorrhaged after a sternal closure and required transfusions and antifibrinolytics that led to thrombus in the membrane and membrane circuitry, which were replaced without incident. The patient's respiratory status remained stable; however, his overall condition worsened as a result of additional organ dysfunction and septicemia, and he did not survive. The addition of a membrane oxygenator to a VAD is feasible and supplements gas exchange permitting the use of more lung protective ventilation.

Factors associated with survival in pediatric extracorporeal membrane oxygenation--a single-center experience.

AIM: We aimed to examine outcomes of extracorporeal membrane oxygenation (ECMO) therapy in the pediatric population and identify pre-ECMO and on-ECMO characteristics that are associated with survival. METHODS: We retrospectively reviewed the ECMO records at our institution between 1999 and 2008 and selected pediatric patients who were cannulated for respiratory failure or hemodynamic instability resistant to conventional interventions. We recorded details of pre-ECMO clinical characteristics, including blood gas variables and mechanical ventilatory support, and details of ECMO therapy including survival off ECMO and to hospital discharge. Predictors of survival were analyzed using logistic regression modeling and a prediction algorithm was developed. RESULTS: Of the 445 ECMO runs, data from 58 consecutive patients were analyzed: 57% were successfully decannulated, and 48% survived to discharge from the hospital. The cohort included 32 (55%) female patients, 22 postoperative patients (38%), and 15 (26%) with an immunosuppressive condition, with a median age of 5 years and weight 19.5 kg, The mean duration of pre-ECMO respiratory support was 3 days, in the form of high-frequency oscillatory ventilation (n = 28, 48%) and conventional mechanical ventilation (n = 13, 22%). The median duration (interquartile range) of ECMO support was 142 hours (60, 321) or 5.9 days. Pre-ECMO pH above 7.2 (P < .001) and oxygenation index below 35 (P = .021) were associated with the highest survival rates. Pre-ECMO PaCO(2) and duration of mechanical ventilation were not associated with survival. CONCLUSIONS: Based on our results, ECMO therapy should be considered early in children with oxygenation index greater than 35 with worsening metabolic status. The restriction of ECMO based on ventilator days alone needs to be revisited in this era of lung protective ventilation.

Rapid-response extracorporeal membrane oxygenation to support cardiopulmonary resuscitation in children with cardiac disease.

BACKGROUND: Survival of children with in-hospital cardiac arrest that does not respond to conventional cardiopulmonary resuscitation (CPR) is poor. We report on survival and early neurological outcomes of children with heart disease supported with rapid-response extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation (ECPR). METHODS AND RESULTS: Children with heart disease supported with ECPR were identified from our ECMO database. Demographic, CPR, and ECMO details associated with mortality were evaluated using multivariable logistic regression. Pediatric overall performance category and pediatric cerebral performance category scores were assigned to ECPR survivors to assess neurological outcomes. There were 180 ECPR runs in 172 patients. Eighty-eight patients (51%) survived to discharge. Survival in patients who underwent ECPR after cardiac surgery (54%) did not differ from nonsurgical patients (46%). Survival did not vary by cardiac diagnosis and CPR duration did not differ between survivors and nonsurvivors. Factors associated with mortality included noncardiac structural or chromosomal abnormalities (OR, 3.2; 95% CI, 1.3-7.9), use of blood-primed ECMO circuit (OR, 7.1; 95% CI, 1.4-36), and arterial pH <7.00 after ECMO deployment (OR, 6.0; 95% CI, 2.1-17.4). Development of end-organ injury on ECMO and longer ECMO duration were associated with increased mortality. Of pediatric overall performance category/pediatric cerebral performance category scores assigned to survivors, 75% had scores ≤2, indicating no to mild neurological injury. CONCLUSIONS: ECPR may promote survival in children with cardiac disease experiencing cardiac arrest unresponsive to conventional CPR with favorable early neurological outcomes. CPR duration was not associated with mortality, whereas patients with metabolic acidosis and noncardiac structural or chromosomal anomalies had higher mortality.

Respiratory distress associated with inadequate mechanical ventilator flow response in a neonate with congenital diaphragmatic hernia.

The incidence of congenital diaphragmatic hernia has been reported as 0.17-0.66 per 1,000 births. Despite advances in neonatal intensive care, congenital diaphragmatic hernia is associated with high mortality and morbidity. We report a neonate who was born with a left congenital diaphragmatic hernia and underwent surgical repair. The lack of ventilator flow response and flow cycling was identified via interpretation of the ventilator graphic and clinical assessment. Presumably, the ventilator failed to respond to the patient's peak inspiratory flow demand, despite the clinician's setting the highest peak flow available. A time-cycled pressure-limited mode with adjustable peak flow rate was the only option that met the infant's flow requirement, and alleviated the respiratory distress. This clinical finding follows bench research that raises the concern that so called "cradle-to-grave" ventilators may not optimally support all neonates.

Extracorporeal membrane oxygenation for neonatal respiratory failure.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass adapted for long-term use. Blood is drained from the patient, pumped through an artificial lung or membrane where gas exchange is augmented, and then re-infused back to the patient. ECMO provides support for the neonate with severe respiratory failure so that potentially deleterious ventilator settings can be minimized and the disease process given time to resolve. Survival rates and long-term neurodevelopmental outcomes in newborns supported with ECMO for hypoxemic respiratory failure remain favorable, although the use of ECMO has decreased in the most recent decade because of the availability of alternative treatment options.

Extracorporeal membrane oxygenation: quo vadis?

Extracorporeal membrane oxygenation, a form of artificial circulatory support, continues to evolve beyond its well-established neonatal applications. It is often the most aggressive aspect of treatment algorithms in the management of severe respiratory and cardiac failure. While its use is relatively infrequent and executed in a small number of centers, it remains an important supportive measure while organ function is preserved and restored. Refinements in equipment and techniques continue to develop; patient-selection has changed, in adults and children, and cardiac applications have gained prominence.

The first use of live continuous glucose monitoring in patients on extracorporeal life support.

BACKGROUND: Evidence suggests that glycemic control provides clinical benefit to critically ill patients. The Extracorporeal Glucose Monitoring System (EGMS), Medtronic Minimed, Northridge, CA) has been developed to measure real-time, continuous blood glucose concentrations in patients on extracorporeal bypass. This pilot study reports the first in vitro and in vivo evaluations of EGMS in an extracorporeal circuit. METHODS: In an in vitro study, three EGMS sensors were inserted in a neonatal extracorporeal circuit. Circuit blood glucose levels were altered by saline dilution and dextrose infusion. EGMS sensors were then inserted into the venous return limb of the extracorporeal circuit in a cohort of six critically ill infants on extracorporeal life support (ECLS). Continuous glucose measurements were compared with laboratory and bedside glucose values at predefined intervals. Linear regression analyses and the Clarke error grid were constructed to analyze device accuracy. RESULTS: All three in vitro EGMS sensors recorded real-time data without interruption for 48 h. EGMS glucose measurements closely correlated with reference levels (R (2) = 0.93). EGMS glucose values demonstrated an approximate 7-10 min lag while glucose concentrations were rapidly changing. Eight EGMS devices were inserted into six neonates on ECLS on day of life 6 +/- 3. EGMS correlated well with laboratory glucose (R2 = 0.61) and bedside glucose during a hyperinsulinemic euglycemic clamp (R2 = 0.78). On the Clarke error grid, 98% of readings were within zones A and B using laboratory glucose as reference, and 100% were within zones A and B using bedside glucose measurements. Blood glucose range during the in vitro study was 19-295 mg/dL and during the in vivo study was 80-257 mg/dL. CONCLUSIONS: This pilot study suggests that EGMS is a reliable tool for measuring continuous blood glucose in critically ill patients connected to an extracorporeal circuit, although important limitations exist. Potential applications of this technology include intensive glucose monitoring in patients on ECLS, cardiopulmonary bypass, and renal replacement therapy.

Impact of AMICAR on hemorrhagic complications of ECMO: a ten-year review.

PURPOSE: Preliminary studies have shown aminocaproic acid (AMICAR), an inhibitor of fibrinolysis, reduced the incidence of intracranial hemorrhage and significant surgical site bleeding in patients on extracorporeal membrane oxygenation (ECMO). The purpose of this analysis is to determine if these benefits remain when AMICAR is used in a large population. METHODS: ECMO patients from a single pediatric institution, with routine use of AMICAR for "high-risk" patients, were evaluated retrospectively from 1991 to 2001. Data including diagnosis, duration of support, significant complications, and survival were recorded. These variables were compared with those of the Extracorporeal Life Support Organization (ELSO), an international ECMO registry, using a chi2 test. P less than.05 was deemed significant. RESULTS: ECMO was used 431 times during the 10-year study period. A total of 298 patients received AMICAR, most frequently for surgical procedures. The survival rate was not statistically different in the study group when compared with the ELSO Registry (P =.06). The rate of neonatal intracranial hemorrhage was not significantly different between the 2 groups (P =.133); however, the rate of surgical site bleeding was significantly reduced in the study population (P =.005). Decrease in surgical site bleeding was particularly evident in cardiac patients (P <.001). CONCLUSIONS: In this large experience, use of AMICAR for high-risk patients on ECMO did not appear to alter the rate of neonatal intracranial hemorrhage, but did significantly reduce the incidence of surgical site bleeding. AMICAR remains a valuable tool for the prevention of hemorrhage in patients undergoing operation prior to or while on ECMO.

Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease.

CONTEXT: Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE: To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN: Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING: Urban, tertiary care children's hospital in the United States. PARTICIPANTS: Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION: Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES: Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS: Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS: Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.