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Background: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury., Methods: Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8., Results: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001)., Conclusions: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.

Objective: To present a series of 30 adult trauma patients who received extracorporeal life support (ECLS) for pulmonary failure and to retrospectively review variables related to their outcome., Methods: In a Level I trauma center between 1989 and 1997, ECLS with continuous heparin anticoagulation was instituted in 30 injured patients older than 15 years. Indication was for an estimated mortality risk greater than 80%, defined by a PaO2: FIO2 ratio less than 100 on 100% FIO2, despite pressure-mode inverse ratio ventilation, optimal positive end-expiratory pressure, reasonable diuresis, transfusion, and prone positioning. Retrospective analysis included demographic information (age, gender, Injury Severity Score, injury mechanism), pulmonary physiologic and gas-exchange values (pre-ECLS ventilator days [VENT days], PaO2:FIO2 ratio, mixed venous oxygen saturation [SvO2], and blood gas), pre-ECLS cardiopulmonary resuscitation, complications of ECLS (bleeding, circuit problems, leukopenia, infection, pneumothorax, acute renal failure, and pressors on ECLS), and survival., Results: The subjects were 26.3+/-2.1 years old (range, 15-59 years), 50% male, and had blunt injury in 83.3%. Pulmonary recovery sufficient to wean the patient from ECLS occurred in 17 patients (56.7%), and 50% survived to discharge. Fewer VENT days and more normal SvO2 were associated with survival. The presence of acute renal failure and the need for venoarterial support (venoarterial bypass) were more common in the patients who died. Bleeding complications (requiring intervention or additional transfusion) occurred in 58.6% of patients and were not associated with mortality. Early use of ECLS (VENT days < or = 5) was associated with an odds ratio of 7.2 for survival. Fewer VENT days was independently associated with survival in a logistic regression model (p = 0.029). Age, Injury Severity Score, and PaO2:FIO2 ratio were not related to outcome., Conclusion: ECLS has been safely used in adult trauma patients with multiple injuries and severe pulmonary failure. In our series, early implementation of ECLS was associated with improved survival. Although this may represent selection bias for less intractable forms of acute respiratory distress syndrome, it is our experience that early institution of ECLS may lead to improved oxygen delivery, diminished ventilator-induced lung injury, and improved survival.

Patients with acute hepatic failure (AHF) have elevated levels of inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Recently, we have shown selective hemodiafiltration with albumin dialysis, as an extracorporeal liver support device (ECLVS), to be effective in the clearance of multiple toxins that are elevated in AHF. Our objective was to evaluate whether ECLVS would be effective in the clearance of TNF-alpha and IL-6. An in vitro continuous hemodiafiltration circuit was used with single pass counter-current dialysis. A known amount of recombinant rat TNF-alpha and IL-6 was added to heparinized bovine blood and filtered across a polyalkyl sulfone hemofilter using matched filtration and dialysate flow rates. During 4 hours, the serial TNF-alpha and IL-6 concentrations were measured in the circulating blood, and the content of each cytokine was calculated using mass balance. For each cytokine, clearance was determined for two dialysate groups at constant temperature and pH (group 1: dialysate = 0.9 normal saline, n = 5; group 2: dialysate = albumin 2 gm/dl, n = 5). Analysis of data was performed using ANOVA and Student's t-test. There was improved clearance of TNF-alpha and IL-6 when albumin was used in the dialysate (81+/-0.09% of the initial TNF-alpha and 77+/-0.04% of the IL-6 quantities) compared with when 0.9 normal saline was used as the dialysate (58+/-0.14% of the initial TNF-alpha and 56+/-0.18% of the IL-6 quantities); p < 0.03. An ECLVS utilizing hemodiafiltration with albumin dialysis is more effective than conventional hemofiltration in the clearance of TNF-alpha and IL-6 and, therefore, may benefit patients with acute hepatic failure.

Traditionally, adult sepsis has been considered a contraindication to extracorporeal life support (ECLS). The objective of this study was to review the authors' institutional experience with a subgroup of adult patients requiring ECLS for severe respiratory failure and sepsis. Hospital records from 100 consecutive adult patients with respiratory failure placed on ECLS between 1990 and 1996 were retrospectively reviewed. Patients with sepsis as a primary indication were identified, and blood culture data reviewed. Data were analyzed with t tests and chi-square and are presented as mean +/- standard deviation. Multiple logistic regression determined the impact of sepsis and positive blood cultures (PBCs) on survival. Fourteen patients required ECLS for sepsis; 36 had PBCs during hospitalization (15 before or during ECLS). Septic patients had lower pre-ECLS PaO2/FIO2 ratios (septic: 53 +/- 14 mmHg, nonseptic: 70 +/- 68 mmHg, p = 0.04). Patients with PBCs before or during ECLS were younger (PBC: 29 +/- 6 years, no PBC: 35 +/- 13 years, p = 0.003), remained on ECLS longer (PBC: 485 +/- 336 hours, no PBC: 232 +/- 212 hours, p = 0.01), and were more frequently cannulated within 12 hours (PBC: 15/15, no PBC 60/85 p = 0.02). Neither group differed in organ dysfunction (incidence or type), frequency of respiratory recovery, or survival. Neither sepsis nor positive blood cultures were independently predictive of mortality. Sepsis and positive blood cultures do not adversely affect outcome in adult patients with respiratory failure requiring ECLS.

Objective: The authors retrospectively reviewed their experience with extracorporeal life support (ECLS) in 100 adult patients with severe respiratory failure (ARF) to define techniques, characterize its efficacy and utilization, and determine predictors of outcome., Summary Background Data: Extracorporeal life support maintains gas exchange during ARF, providing diseased lungs an optimal environment in which to heal. Extracorporeal life support has been successful in the treatment of respiratory failure in infants and children. In 1990, the authors instituted a standardized protocol for treatment of severe ARF in adults, which included ECLS when less invasive methods failed., Methods: From January 1990 to July 1996, the authors used ECLS for 100 adults with severe acute hypoxemic respiratory failure (n = 94): paO2/FiO2 ratio of 55.7+/-15.9, transpulmonary shunt (Qs/Qt) of 52+/-22%, or acute hypercarbic respiratory failure (n = 6): paCO2 84.0+/-31.5 mmHg, despite and after maximal conventional ventilation. The technique included venovenous percutaneous access, lung "rest," transport on ECLS, minimal anticoagulation, hemofiltration, and optimal systemic oxygen delivery., Results: Overall hospital survival was 54%. The duration of ECLS was 271.9+/-248.6 hours. Primary diagnoses included pneumonia (49 cases, 53% survived), adult respiratory distress syndrome (45 cases, 51 % survived), and airway support (6 cases, 83% survived). Multivariate logistic regression modeling identified the following pre-ECLS variables significant independent predictors of outcome: 1) pre-ECLS days of mechanical ventilation (p = 0.0003), 2) pre-ECLS paO2/FiO2 ratio (p = 0.002), and 3) age (years) (p = 0.005). Modeling of variables during ECLS showed that no mechanical complications were independent predictors of outcome, and the only patient-related complications associated with outcome were the presence of renal failure (p < 0.0001) and significant surgical site bleeding (p = 0.0005)., Conclusions: Extracorporeal life support provides life support for ARF in adults, allowing time for injured lungs to recover. In 100 patients selected for high mortality risk despite and after optimal conventional treatment, 54% survived. Extracorporeal life support is extraordinary but reasonable treatment in severe adult respiratory failure. Predictors of survival exist that may be useful for patient prognostication and design of future prospective studies.

Extraction of protein bound liver failure toxins, such as unconjugated bilirubin, short chain fatty acids, and aromatic amino acids has been reported using hemodiafiltration with albumin in the dialysate, but the characteristics of such a system have not been described. Therefore, bilirubin clearance using albumin dialysate hemodiafiltration was evaluated in the setting of different dialysate albumin concentrations, varying temperature and pH. An in vitro continuous hemodiafiltration circuit was used with single pass countercurrent dialysis. Unconjugated bilirubin was added to bovine blood and filtered across a polyalkyl sulfone (PAS) hemofilter using matched filtration and dialysate flow rates. The serial bilirubin content was measured and first order clearance kinetics verified. The clearance rate constants were calculated for three dialysate groups of different albumin concentration at constant temperature and pH (group 1: 10 g/dl albumin, n = 5; 2 g/dl albumin, n = 5; normal saline, n = 5), and three groups of different temperature and pH at constant albumin dialysate concentration (group 2: pH = 7.0, temperature = 20 degrees C, n = 5; pH = 7.5, temperature = 20 degrees C, n = 5; pH = 7.0, temperature = 40 degrees C, n = 5). Comparisons were made with ANOVA and Tukey post hoc analysis. When albumin was used in the dialysate, the 2 g/dl group cleared bilirubin 3.1 times faster than saline alone (p = 0.001), and the 10 g/dl group was superior to both (p = 0.001). There were no measurable differences between the 2 g/dl groups at the various temperatures tested (p = 0.08), but the clearance was less at a pH of 7.5 (p = 0.015). The clearance of unconjugated bilirubin is greatly enhanced with the use of albumin containing dialysates when compared to traditional crystalloid hemodiafiltration, is greater at lower pH, and seems to be unaffected by temperature.