Robert H. Bartlett

Extracorporeal Life Support for Severe Acute Respiratory Distress Syndrome in Adults

Objective:Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. Methods:We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio ≤100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung “rest” at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. Results:During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH ≤7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. Conclusion:Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.

Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases.

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

Extracorporeal Membrane Oxygenation to Aid Cardiopulmonary Resuscitation in Infants and Children

Background— Extracorporeal membrane oxygenation (ECMO) has been used to support cardiorespiratory function during pediatric cardiopulmonary resuscitation (CPR). We report on outcomes and predictors of in-hospital mortality after ECMO used to support CPR (E-CPR). Methods and Results— Outcomes for patients aged <18 years using E-CPR were analyzed with data from the Extracorporeal Life Support Organization, and predictors of in-hospital mortality were determined. Of 26 242 ECMO uses reported, 695 (2.6%) were for E-CPR (n=682 patients). Survival to hospital discharge was 38%. In a multivariable model, pre-ECMO factors such as cardiac disease (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31 to 0.82) and neonatal respiratory disease (OR 0.28, 95% CI 0.12 to 0.66), white race (OR 0.65, 95% CI 0.45 to 0.94), and pre-ECMO arterial blood pH >7.17 (OR 0.50, 95% CI 0.30 to 0.84) were associated with decreased odds of mortality. During ECMO, renal dysfunction (OR 1.89, 95% CI 1.17 to 3.03), pulmonary hemorrhage (OR 2.23, 95% CI 1.11 to 4.50), neurological injury (OR 2.79, 95% CI 1.55 to 5.02), CPR during ECMO (OR 3.06, 95% CI 1.42 to 6.58), and arterial blood pH <7.2 (OR 2.23, 95% CI 1.23 to 4.06) were associated with increased odds of mortality. Conclusions— ECMO used to support CPR rescued one third of patients in whom death was otherwise certain. Patient diagnosis, absence of severe metabolic acidosis before ECMO support, and uncomplicated ECMO course were associated with improved survival.

Liquid ventilation in adults, children, and full-term neonates

We evaluated the safety and efficacy of partial liquid ventilation in a series of 19 adults, children, and neonates who were in respiratory failure and on extracorporeal life support. During partial liquid ventilation, the alveolar-arterial oxygen difference decreased from 590 (SE 25) to 471 (42) mm Hg (p = 0.0002) and static pulmonary compliance increased from 0.18 (0.04) to 0.29 (0.04) mL cm H2O-1 kg-1 (p = 0.0002). 11 patients (58%) survived. These preliminary data suggest that partial liquid ventilation can be safely used in patients with severe respiratory failure and may improve lung function.

Review of A Large Clinical Series: Association of Cumulative Fluid Balance on Outcome in Acute Lung Injury: A Retrospective Review of the ARDSnet Tidal Volume Study Cohort:

Objective: To evaluate the independent influence of fluid balance on outcomes for patients with acute lung injury. Design: Secondary analysis of a prospective cohort study conducted between March 1996 and March 1999. Setting: The study involved 10 academic clinical centers (with 24 hospitals and 75 Intensive Care Units). Patients: All patients for whom fluid balance data existed (844) from the 902 patients enrolled in the National Heart Lung Blood Institutes ARDS Network ventilator-tidal volume trial. Interventions: The study had no interventions. Measurements/Results: On the first day of study enrollment, 683 patients were, on average, more than 3.5 L in positive fluid balance compared to 161 patients in negative fluid balance (P < .001). Cumulative negative fluid balance on day 4 of the study was associated with an independently lower hospital mortality (OR, 0.50; 95% CI, 0.28-0.89; P < .001) more ventilator and intensive care unit—free days. Conclusions: Negative cumulative fluid balance at day 4 of acute lung injury is associated with significantly lower mortality, independent of other measures of severity of illness.

Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

Outcome of pediatric patients treated with extracorporeal life support after cardiac surgery

BACKGROUND Extracorporeal life support (ECLS) has been used for over two decades in select patients after cardiac surgery. We previously described factors associated with death in this population. We now review our recent experience to reassess factors related to mortality. METHODS All pediatric patients who received ECLS support within 7 days after surgery between July 1995 and June 2001 were examined to describe clinical features associated with survival. We compared the results with our prior report to assess changes in practice and outcome. RESULTS Seventy-four patients were followed. Fifty percent survived to discharge. Hospital survival was not significantly related to patient age, cannulation site, or indication. Thirty-five percent of patients required hemofiltration while on ECLS and were significantly less likely to survive (23% vs 65%). A multivariate analysis combining all children from our prior report with the present cohort revealed that patients who received hemofiltration were five times more likely to die (odds ratio 5.01, 95% confidence interval 2.11-11.88). Children with an adequate two-ventricular repair had lower risk of death (odds ratio 0.42, 95% confidence interval 0.19-0.91) after adjusting for patient age, study period, and hours elapsed before initiation of ECLS after surgery. CONCLUSIONS Patients with an adequate two-ventricle repair have significantly higher hospital survival, whereas those with single ventricle physiology or need for dialysis have decreased survival.

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

Background:We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viabili

Association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality: Analysis of the extracorporeal life support organization registry

RATIONALE Recent pediatric studies suggest a survival benefit exists for higher-volume extracorporeal membrane oxygenation (ECMO) centers. OBJECTIVES To determine if higher annual ECMO patient volume is associated with lower case-mix-adjusted hospital mortality rate. METHODS We retrospectively analyzed an international registry of ECMO support from 1989 to 2013. Patients were separated into three age groups: neonatal (0-28 d), pediatric (29 d to <18 yr), and adult (≥18 yr). The measure of hospital ECMO volume was age group-specific and adjusted for patient-level case-mix and hospital-level variance using multivariable hierarchical logistic regression modeling. The primary outcome was death before hospital discharge. A subgroup analysis was conducted for 2008-2013. MEASUREMENTS AND MAIN RESULTS From 1989 to 2013, a total of 290 centers provided ECMO support to 56,222 patients (30,909 neonates, 14,725 children, and 10,588 adults). Annual ECMO mortality rates varied widely across ECMO centers: the interquartile range was 18-50% for neonates, 25-66% for pediatrics, and 33-92% for adults. For 1989-2013, higher age group-specific ECMO volume was associated with lower odds of ECMO mortality for neonates and adults but not for pediatric cases. In 2008-2013, the volume-outcome association remained statistically significant only among adults. Patients receiving ECMO at hospitals with more than 30 adult annual ECMO cases had significantly lower odds of mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.46-0.80) compared with adults receiving ECMO at hospitals with less than six annual cases. CONCLUSIONS In this international, case-mix-adjusted analysis, higher annual hospital ECMO volume was associated with lower mortality in 1989-2013 for neonates and adults; the association among adults persisted in 2008-2013.

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

ObjectiveThe authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BackgroundThe efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). MethodsA stable model of lung injury was induced in 12 young sheep weighing 16.4 ± 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bjjugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. Main FindingsPhysiologic shunt (Qps/Q1) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 ± 10%; GV = 93 ± 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (Cγ) was significantly increased in the LV group when compared with the GV group (LV = 1.04 ± 0.19 mL/cm H2O/kg; GV = 0.41 ± 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50− to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV =14 ± 5 mL/kg/min; GV = 87 ± 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals.