A review of 100 patients transported on extracorporeal life support.

Between May 1990 and January 1999, 100 patients (68 adult, 32 pediatric) with severe respiratory or cardiac instability were successfully transported to the University of Michigan Medical Center on extracorporeal life support. Diagnoses included adult respiratory distress syndrome (n = 78), cardiac failure (n = 7), sepsis (n = 7), asthma (n = 5), respiratory distress syndrome (of newborn) (n = 2), and airway compromise (n = 1). Of the patients, 53 were supported with venovenous bypass and 47 with venoarterial bypass. Patients were transported by ground ambulance (n = 80), helicopter (n = 15), or fixed-wing aircraft (n = 5). The median transport distance was 44 miles (range 2-790 miles), and the median transport time was 5 hours and 30 minutes (range: 1 h 33 min to 16 h 6 min). Sixty-six patients (66%) survived to discharge. One death occurred during cannulation, and two patients died before cannulation began. Complications that occurred during transport included 10 cases of electrical failure, 3 cases of circuit tubing leakage, and 1 case each of circuit rupture, membrane lung thrombosis, and membrane lung leakage. None of the complications occurring during transport had an adverse effect on outcome. We conclude that the long distance transport of patients on extracorporeal life support can be safely accomplished and is an effective option for the unstable patient with severe respiratory or cardiac failure.

Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.

BACKGROUND: Renal cell therapy in conjunction with continuous hemofiltration techniques may provide important cellular metabolic activities to patients with acute renal failure (ARF) and may thereby change the natural history of this disorder. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) human renal proximal tubule cells provides an opportunity to evaluate this form of therapy in patients with ARF in the intensive care unit. METHODS: Nine patients with ARF and multi-organ systems failure (MOSF) have been treated so far with a tissue-engineered kidney in an FDA-approved Phase I/II clinical study currently underway. Acute physiologic parameters and serum cytokine levels were assessed before, during and after treatment with a bioartificial kidney. RESULTS: Use of the RAD in this clinical setting demonstrates maintenance of cell viability and functionality. Cardiovascular stability appears to be maintained during RAD treatment. Human tubule cells in the RAD demonstrated differentiated metabolic and endocrinologic activity. Acute physiologic and plasma cytokine data demonstrate that renal cell therapy is associated with rapid and variable responses in patients with ARF and MOSF. CONCLUSION: The initial clinical experience with the bioartificial kidney and the RAD suggests that renal tubule cell therapy may provide a dynamic and individualized treatment program as assessed by acute physiologic and biochemical indices.

Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure.

BACKGROUND: Acute renal failure (ARF) in intensive care unit patients continues to have mortality rates exceeding 70%, despite hemodialysis or continuous renal replacement therapy (CRRT). The delivery of cellular metabolic function to CRRT may provide more complete renal replacement therapy, thereby changing the natural history of this disease process. An FDA-approved Phase I/II clinical trial on 10 patients has been completed, and demonstrated that this experimental treatment can be delivered safely for up to 24 hours. METHODS: The bioartificial kidney is a synthetic hemofilter connected in series with a bioreactor cartridge containing approximately 10(9) human proximal tubule cells, as a renal tubule assist device (RAD), within an extracorporeal perfusion circuit utilizing standard hemofiltration pump systems. All 10 patients had ARF and multiorgan failure (MOF), with predicted hospital mortality rates averaging above 85%. RESULTS: Data indicate that the RAD maintains viability, durability, and functionality in this ex vivo clinical setting. The device also demonstrated differentiated metabolic and endocrinologic activity, with glutathione degradation and endocrinologic conversion of 25-OH-D(3) to 1,25-(OH)(2)-D(3). All but one treated patient with more than a 3-day follow-up in the intensive care unit showed improvement as assessed by acute physiologic scores 1 to 7 days following therapy. Six of the 10 treated patients survived past 30 days. One patient expired within 12 hours after RAD treatment due to his family's request to withdraw ventilatory life support. Three other patients died due to complications from acute or chronic comorbidities unrelated to ARF or RAD therapy. Plasma cytokine levels suggest that RAD therapy produced dynamic and individualized responses in patients. For the subset of patients who had excessive proinflammatory levels, RAD treatment resulted in significant declines in granulocyte colony stimulating factor (G-CSF), interleukin (IL)-6, IL-10, and IL-6/IL-10 ratios. CONCLUSION: The addition of human renal tubule cell therapy to CRRT has been accomplished and demonstrates metabolic activity with systemic effects in patients with ARF and MOF. These initial clinical results are encouraging, so that a randomized, controlled Phase II clinical trial is underway to further assess the clinical safety and efficacy of this new therapeutic approach.

Extracorporal life support for pulmonary hemorrhage in children: a case series.

OBJECTIVE: To examine the use and outcome of extracorporeal life support in children with severe respiratory failure caused by pulmonary hemorrhage. DESIGN: Retrospective case series report. SETTING: Pediatric intensive care unit in a university children's hospital. PATIENTS: Eight patients <19 yrs of age who required extracorporeal life support for severe respiratory failure associated with pulmonary hemorrhage. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support. MEASUREMENTS: Ventilatory support parameters and systemic PaO2/FiO2 ratio before extracorporeal life support, time on extracorporeal life support, number of ventilator days, number of intensive care unit days, number of hospital days, continued bleeding on extracorporeal life support, and survival. MAIN RESULTS: All patients had resolution of their pulmonary hemorrhage within 24 hrs. All patients survived to decannulation, extubation, and hospital discharge. All patients are alive, with follow-up times ranging from 1 to 10 yrs. CONCLUSIONS: Extracorporeal life support is not contraindicated in patients with severe respiratory failure with associated pulmonary hemorrhage and may be a life-sustaining supportive therapy.

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 < or =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 < or =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.