Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

BACKGROUND: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). METHODS: In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure--(Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. RESULTS: During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). CONCLUSIONS: The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

Respiratory dialysis with an active-mixing extracorporeal carbon dioxide removal system in a chronic sheep study.

PURPOSE: The objective of this study was to demonstrate the safety and performance of a unique extracorporeal carbon dioxide removal system (Hemolung, ALung Technologies, Pittsburgh, PA) which incorporates active mixing to improve gas exchange efficiency, reduce exposure of blood to the circuit, and provide partial respiratory support at dialysis-like settings. METHODS: An animal study was conducted using eight domestic crossbred sheep, 6-18 months of age and 49-115 kg in weight. The sheep were sedated and intubated, and a 15.5-Fr dual lumen catheter was inserted into the right jugular vein. The catheter was connected to the extracorporeal circuit primed with heparinized saline, and flow immediately initiated. The animals were then awakened and encouraged to stand. The animals were supported in a stanchion and monitored around the clock. Anticoagulation was maintained with heparin to achieve an aPTT of 46-70 s. RESULTS: Measurements included blood flow rate through the device, carbon dioxide exchange rate, pump speed and sweep gas flow rate. Safety and biocompatibility measurements included but were not limited to plasma-free hemoglobin, hematocrit, white blood cell count, platelet count and fibrinogen. The Hemolung removed clinically significant amounts of carbon dioxide, more than 50 ml/min, at low blood flows of 350-450 ml/min, with minimal adverse effects. CONCLUSIONS: The results of 8-day trials in awake and standing sheep supported by the Hemolung demonstrated that this device can consistently achieve clinically relevant levels of carbon dioxide removal without failure and without significant risk of adverse reactions.

Permanent, nonleaching antibacterial surfaces. 1. Synthesis by atom transfer radical polymerization.

We have grown an antimicrobial polymer directly on the surfaces of glass and paper using atom transfer radical polymerization (ATRP). The method described here results in potentially permanent nonleaching antibacterial surfaces without the need to chemically graft the antimicrobial material to the substratum. The tertiary amine 2-(dimethylamino)ethyl methacrylate was polymerized directly onto Whatman #1 filter paper or glass slides via atom transfer radical polymerization. Following the polymerization, the tertiary amino groups were quaternized using an alkyl halide to produce a large concentration of quaternary ammonium groups on the polymer-modified surfaces. Incubating the modified materials with either Escherichia coli or Bacillus subtilis demonstrated that the modified surfaces had substantial antimicrobial capacity. The permanence of the antimicrobial activity was demonstrated through repeated use of a modified glass without significant loss of activity. Quaternary amines are believed to cause cell death by disrupting cell membranes allowing release of the intracellular contents. Atomic force microscopic imaging of cells on modified glass surfaces supports this hypothesis.