Pulmonary volume-feedback and ventilatory pattern after bilateral lung transplantation using neurally adjusted ventilatory assist ventilation.

BACKGROUND: Bilateral lung transplantation results in pulmonary vagal denervation, which potentially alters respiratory drive, volume-feedback, and ventilatory pattern. We hypothesised that Neurally Adjusted Ventilatory Assist (NAVA) ventilation, which is driven by diaphragm electrical activity (EAdi), would reveal whether vagally mediated pulmonary-volume feedback is preserved in the early phases after bilateral lung transplantation. METHODS: We prospectively studied bilateral lung transplant recipients within 48 h of surgery. Subjects were ventilated with NAVA and randomised to receive 3 ventilatory modes (baseline NAVA, 50%, and 150% of baseline NAVA values) and 2 PEEP levels (6 and 12 cm H2O). We recorded airway pressure, flow, and EAdi. RESULTS: We studied 30 subjects (37% female; age: 37 (27-56) yr), of whom 19 (63%) had stable EAdi. The baseline NAVA level was 0.6 (0.2-1.0) cm H2O µV-1. Tripling NAVA level increased the ventilatory peak pressure over PEEP by 6.3 (1.8), 7.6 (2.4), and 8.7 (3.2) cm H2O, at 50%, 100%, and 150% of baseline NAVA level, respectively (P<0.001). EAdi peak decreased by 10.1 (9.0), 9.5 (9.4) and 8.8 µV (8.7) (P<0.001), accompanied by small increases in tidal volume, 8.3 (3.0), 8.7 (3.6), and 8.9 (3.3) ml kg-1 donor's predicted body weight at 50%, 100%, and 150% of baseline NAVA levels, respectively (P<0.001). Doubling PEEP did not affect tidal volume. CONCLUSIONS: NAVA ventilation was feasible in the majority of patients during the early postoperative period after bilateral lung transplantation. Despite surgical vagotomy distal to the bronchial anastomoses, bilateral lung transplant recipients maintained an unmodified respiratory pattern in response to variations in ventilatory assistance and PEEP. CLINICAL TRIAL REGISTRATION: NCT03367221.

Extracorporeal Chloride Removal by Electrodialysis. A Novel Approach to Correct Acidemia.

Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.

Practical Clinical Application of an Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Distress Syndrome and Acute on Chronic Respiratory Failure.

We retrospectively reviewed the medical records of 11 patients supported with a veno-venous low-flow extracorporeal carbon dioxide (CO2) removal (ECCO2R) device featuring a large gas exchange surface membrane lung (ML) (i.e., 1.8 m). Seven patients suffered from exacerbation of a chronic pulmonary disease, while four subjects were affected by acute respiratory distress syndrome (ARDS). Twenty-four hours of ECCO2R treatment reduced arterial PCO2 from 63 ± 12 to 54 ± 11 mm Hg (p < 0.01), increased arterial pH from 7.29 ± 0.07 to 7.39 ± 0.06 (p < 0.01), and decreased respiratory rate from 32 ± 10 to 21 ± 8 bpm (p < 0.05). Extracorporeal blood flow and CO2 removal were 333 ± 37 and 94 ± 18 ml/min, respectively. The median duration of ECCO2R treatment was 7 days (6.5-9.5). All four ARDS patients were invasively ventilated at the time of treatment start, no one was extubated and they all died. Among the seven patients with exacerbation of chronic pulmonary diseases, four were managed with noninvasive ventilation at ECCO2R institution, while three were extubated after starting the extracorporeal treatment. No one of these seven patients was intubated or re-intubated after ECCO2R institution and five (71%) survived to hospital discharge. A low-flow ECCO2R device with a large surface ML removes a relevant amount of CO2 resulting in a decreased arterial PCO2, an increased arterial pH, and in a reduced ventilatory load.

Application of prone position in hypoxaemic patients supported by veno-venous ECMO.

INTRODUCTION: Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is an advanced respiratory care therapy allowing replacement of pulmonary gas exchange. Despite VV-ECMO support, some patients may remain hypoxaemic. A possible therapeutic procedure for these patients is the application of prone positioning. OBJECTIVE: The primary aim of the present study was to investigate modification of the PaO2/FiO2 ratio, in VV-ECMO patients with refractory hypoxaemia. The secondary aim was to evaluate the safety and feasibility of prone positioning for patients with severe Adult Respiratory Distress Syndrome supported by ECMO. METHODS: We retrospectively reviewed the electronic records and charts of all patients supported by VV-ECMO who experienced at least one pronation. Complications related with prone positioning were also recorded. First PaO2/FiO2 ratio was analysed during four different time steps: before pronation, one hour after pronation, at the end of pronation and one hour after returning to supine. RESULTS: A total of 45 prone positioning manoeuvers were performed in 14 VV-ECMO patients from November 2009 to November 2014. The median duration of prone positioning cycles was 8 hours (IQR 6-10). No accidental dislodgement of intravascular lines, endotracheal tubes, chest tubes or a decrease in ECMO blood flow was observed. During the first prone positioning for each patient, the median PaO2/FiO2 ratio recorded was 123 (IQR 82-135), 152 (93-185), 149 (90-186) and 113 (74-182), during PRE-supine step, 1 h-prone positioning step, END-prone positioning step, and POST-supine step respectively. CONCLUSIONS: The application of prone positioning during VV-ECMO has shown to be a safe and reliable technique when performed in a recognised ECMO centre with the appropriately trained staff and standard procedures.

A mathematical model of oxygenation during venovenous extracorporeal membrane oxygenation support.

PURPOSE: To develop a mathematical model of oxygenation during venovenous extracorporeal membrane oxygenation (vv-ECMO). MATERIAL AND METHODS: Total oxygen consumption, cardiac output, blood flow, recirculation, intrapulmonary shunt, hemoglobin, natural lung, and membrane lung oxygen fractions were chosen as inputs. Content, partial pressure, and hemoglobin saturation of oxygen in arterial, venous, pulmonary, and extracorporeal blood were outputs. To assess accuracy and predictive power of the model, we retrospectively analyzed data of 25 vv-ECMO patients. We compiled 2 software (with numerical, 2D and 3D graphical outputs) to study the impact of each variable on oxygenation. RESULTS: The model showed high accuracy and predictive power. Raising blood flow and oxygen fraction to the membrane lung or reducing total oxygen consumption improves arterial and venous oxygenation, especially in severe cases; raising oxygen fraction to the natural lung improves oxygenation only in milder cases; raising hemoglobin always improves oxygenation, especially in the venous district; recirculation fraction severely impairs oxygenation. In severely ill patients, increasing cardiac output worsens arterial oxygenation but enhances venous oxygenation. Oxygen saturation of ECMO inlet is critical to evaluate the appropriateness of oxygen delivery. CONCLUSIONS: The model with the software can be a useful teaching tool and a valuable decision-making aid for the management of hypoxic patients supported by vv-ECMO.

Safe ECMO femoral decannulation by placement of inferior vena cava filter via internal jugular vein.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment in patients with cardiogenic shock or cardiac arrest caused by massive pulmonary embolism. In these patients, positioning an inferior vena cava filter is often advisable, especially if deep venous thrombosis is not resolved at the time of the ECMO suspension. Moreover, in ECMO patients, a high incidence of deep venous thrombosis at the site of venous cannulation has been reported, and massive pulmonary embolism following ECMO decannulation has been described. Nonetheless, an inferior vena cava filter cannot be positioned as long as an ECMO cannula is inside the inferior vena cava. Thus, we developed a strategy to allow placement of an inferior vena cava filter through the internal jugular concurrently with the removal of the femoral venous ECMO cannula. In two women supported by veno-arterial ECMO for cardiac arrest secondary to pulmonary embolism, this novel approach allowed for safe ECMO decannulation.

Ion-Exchange Resin Anticoagulation (I-ERA): A Novel Extracorporeal Technique for Regional Anticoagulation.

BACKGROUND: Extracorporeal treatments always require blood anticoagulation. We tested feasibility and efficacy of a novel technique for regional extracorporeal blood anticoagulation based on calcium removal by ion-exchange resins (i-ER), called ion-exchange resin anticoagulation (i-ERA). METHODS: Eight swine were connected to a veno-venous extracorporeal circuit comprising a hemodiafilter and an i-ER. Blood flow was 150 mL/min. Hemodiafiltrate was generated at 975 mL/min and passed through the i-ER. A fraction of the calcium-free hemodiafiltrate was returned to the hemodiafilter (675 mL/min), while the remaining was recirculated prior the hemodiafilter (300 mL/min) to dilute blood entering the hemodiafilter. A calcium replacement solution was continuously infused. Two hours after i-ERA start, blood was sampled from inlet, before the hemodiafilter (prehemodiafilter blood) and from outlet of the extracorporeal circuit for ionized calcium (iCa) concentration and thromboelastography (TEG). Arterial blood was collected for blood gas analyses, electrolytes concentrations, and plasma free hemoglobin. Hemodynamics and ventilation were monitored. RESULTS: i-ERA reduced iCa from 1.28 ±â€Š0.05 mmol/L (inlet) to 0.47 ±â€Š0.03 mmol/L (prehemodiafilter blood) and 0.25 ±â€Š0.03 mmol/L (outlet). Prehemodiafilter blood and outlet samples showed no sign of clot formation (reaction time (R) >60 min; maximal amplitude (MA) = 0 (0-0) mm), while blood-inlet had normal coagulation (R = 8.5 (5.8-10.2) min; MA = 65.2 (63.2-68.7) mm). Arterial gas analyses and electrolytes concentrations, hemodynamics, and ventilation were unchanged. No hemolysis was recorded. CONCLUSIONS: In a swine model, i-ERA proved feasible and effective in reducing iCa and preventing clot formation with TEG analyses. Further studies are warranted to evaluate the long-term efficacy and safety of i-ERA. LEVEL OF EVIDENCE: V-therapeutic animal experiment.

Extracorporeal CO2 Removal by Respiratory Electrodialysis: An In Vitro Study.

We previously described a highly efficient extracorporeal CO2 removal technique called respiratory electrodialysis (R-ED). Respiratory electrodialysis was composed of a hemodiafilter and a membrane lung (ML) positioned along the extracorporeal blood circuit, and an electrodialysis (ED) cell positioned on the hemodiafiltrate. The ED regionally increased blood chloride concentration to convert bicarbonate to CO2 upstream the ML, thus enhancing ML CO2 extraction (VCO2ML). In this in vitro study, with an aqueous polyelectrolytic carbonated solution mimicking blood, we tested a new R-ED setup, featuring an ML positioned on the hemodiafiltrate after the ED, at increasing ED current levels (0, 2, 4, 6, and 8 A). We measured VCO2ML, electrolytes concentrations, and pH of the extracorporeal circuit. Raising levels of ED-current increased chloride concentration from 107.5 ± 1.6 to 114.6 ± 1.3 mEq/L (0 vs. 8 A, p < 0.001) and reduced pH from 7.48 ± 0.01 to 6.51 ± 0.05 (0 vs. 8 A, p < 0.001) of the hemodiafiltrate entering the ML. Subsequently, VCO2ML increased from 27 ± 1.7 to 91.3 ± 1.5 ml/min (0 vs. 8 A, p < 0.001). Respiratory electrodialysis is efficient in increasing VCO2ML of an extracorporeal circuit featuring an ML perfused by hemodiafiltrate. During R-ED, the VCO2ML can be significantly enhanced by increasing the ED current.

Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: A retrospective study.

PURPOSE: Prone positioning (PP) improves oxygenation and outcome of patients with acute respiratory distress syndrome undergoing invasive ventilation. We evaluated feasibility and efficacy of PP in awake, non-intubated, spontaneously breathing patients with hypoxemic acute respiratory failure (ARF). MATERIAL AND METHODS: We retrospectively studied non-intubated subjects with hypoxemic ARF treated with PP from January 2009 to December 2014. Data were extracted from medical records. Arterial blood gas analyses, respiratory rate, and hemodynamics were retrieved 1 to 2 hours before pronation (step PRE), during PP (step PRONE), and 6 to 8 hours after resupination (step POST). RESULTS: Fifteen non-intubated ARF patients underwent 43 PP procedures. Nine subjects were immunocompromised. Twelve subjects were discharged from hospital, while 3 died. Only 2 maneuvers were interrupted, owing to patient intolerance. No complications were documented. PP did not alter respiratory rate or hemodynamics. In the subset of procedures during which the same positive end expiratory pressure and Fio2 were utilized throughout the pronation cycle (n=18), PP improved oxygenation (Pao2/Fio2 124±50 mmHg, 187±72 mmHg, and 140±61 mmHg, during PRE, PRONE, and POST steps, respectively, P<.001), while pH and Paco2 were unchanged. CONCLUSIONS: PP was feasible and improved oxygenation in non-intubated, spontaneously breathing patients with ARF.

Respiratory Electrodialysis. A Novel, Highly Efficient Extracorporeal CO2 Removal Technique.

RATIONALE: We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED). OBJECTIVES: To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology. METHODS: Five mechanically ventilated swine were connected to a custom-made circuit optimized for R-ED, consisting of a hemofilter, a membrane lung, and an electrodialysis cell. Electrodialysis regionally modulates blood electrolyte concentration to convert bicarbonate to CO2 before entering the membrane lung, enhancing membrane lung CO2 extraction. All animals underwent three repeated experimental sequences, consisting of four steps: baseline (1 h), conventional ECCO2R (2 h), R-ED (2 h), and final NO-ECCO2R (1 h). Blood and gas flow were 250 ml/min and 10 L/min, respectively. Tidal volume was set at 8 ml/kg, and respiratory rate was adjusted to maintain arterial Pco2 at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: During R-ED, chloride and H(+) concentration increased in blood entering the membrane lung, almost doubling CO2 extraction compared with ECCO2R (112 ± 6 vs. 64 ± 5 ml/min, P < 0.001). Compared with baseline, R-ED and ECCO2R reduced minute ventilation by 50% and 27%, respectively. Systemic arterial gas analyses remained stable during the experimental phases. No major complication occurred, but there was an increase in creatinine level. CONCLUSIONS: In this first in vivo application, we proved electrodialysis feasible and effective in increasing membrane lung CO2 extraction. R-ED was more effective than conventional ECCO2R technology in controlling ventilation. Further studies are warranted to assess the safety profile of R-ED, especially regarding kidney function.

Effects on membrane lung gas exchange of an intermittent high gas flow recruitment maneuver: preliminary data in veno-venous ECMO patients.

Gas exchange capabilities of polymethylpentene membrane lungs (MLs) worsen over time. ML deterioration is related to protein deposit and clot formation. Condensation and trapping of water vapor inside ML hollow fibers might affect ML performances as well. Increasing sweep gas flow (GF) could remove such fluid. The purpose of this study was to evaluate the effects on ML gas exchange of a recruitment maneuver (RM) based on a brief increase in GF, during veno-venous ECMO support. Short-term (15 min) effects of 20 RMs were assessed. RM raised ML CO2 removal from 149 ± 37 to 174 ± 41 ml/min (p < 0.001). Conversely, RM did not improve ML O2 transfer (155 ± 31 and 158 ± 31 ml/min before and after RM, respectively). ML outlet pCO2 decreased after RM from 51.2 ± 5.8 to 45.8 ± 5.4 mmHg (p < 0.001), while ML outlet pO2 increased from 520 ± 61 to 555 ± 51 mmHg (p < 0.001). Both ML dead space and shunt fractions decreased from 47.8 ± 15.3 to 29.6 ± 14.7 % (p < 0.001) and from 8.8 ± 4.2 to 7.0 ± 3.8 % (p < 0.001), respectively. Furthermore, a subset of 5 RMs was evaluated on a 6-h time frame. The beneficial effects on ML performances due to the RM gradually diminished and waned over a 6-h interval after the RM. The RM improved ML CO2 removal substantially, albeit temporarily. ML oxygenation performance was marginally affected.

Extracorporeal carbon dioxide removal through ventilation of acidified dialysate: an experimental study.

BACKGROUND: Extracorporeal (EC) carbon dioxide (CO(2)) removal (ECCO(2)R) may be a powerful alternative to ventilation, possibly avoiding the need for mechanical ventilation and endotracheal intubation. We previously reported how an infusion of lactic acid before a membrane lung (ML) effectively enhances ECCO(2)R. We evaluated an innovative ECCO(2)R technique based on ventilation of acidified dialysate. METHODS: Four swine were sedated, mechanically ventilated, and connected to a venovenous dialysis circuit (blood flow, 250 ml/min). The dialysate was recirculated in a closed loop circuit including a ML (gas flow, 10 liters/min) and then returned to the dialyzer. In each animal, 4 different dialysis flows (DF) of 200, 400, 600, and 800 ml/min were evaluated with and without lactic acid infusion (2.5 mEq/min); the sequence was completed 3 times. At the end of each step, we measured the volume of CO(2)R by the ML (V(co2)ML) and collected blood and dialysate samples for gas analyses. RESULTS: Acid infusion substantially increased V(co2)ML, from 33 ± 6 ml/min to 86 ± 7 ml/min. Different DFs had little effect on V(co2)ML, which was only slightly reduced at DF 200 ml/min. The partial pressure of CO(2) of blood passing through the dialysis filter changed from 60.9 ± 3.6 to 37.1 ± 4.8 mm Hg without acidification and to 32.5 ± 5.3 mm Hg with acidification, corresponding to a pH increase of 0.18 ± 0.03 and 0.03 ± 0.04 units, respectively. CONCLUSIONS: Ventilation of acidified dialysate efficiently increased ECCO(2)R of an amount corresponding to 35% to 45% of the total CO(2) production of an adult man from a blood flow as low as 250 ml/min.

An improved Boussignac device for the delivery of non-invasive CPAP: the SUPER-Boussignac.

PURPOSE: The purpose of this study is to describe and test a modified Boussignac system for non-invasive continuous positive airway pressure, aimed at reducing the decrease in inspiratory oxygen fraction (FiO(2)) with higher inspiratory peak flow rates. METHODS: We modified a Boussignac circuit by inserting a T-piece between the Boussignac valve and the face mask. The T-piece was connected to a reservoir balloon receiving oxygen by an independent source. The system was tested in a bench study, consisting of five steps, with increasing inspiratory peak flow rates (V(insp)) Three levels of PEEP were tested: 7, 10 and 13 cmH(2)O. The following devices were tested: Boussignac, Boussignac with reservoir but without supplementary oxygen, Boussignac with reservoir and 10 (SUPER-Boussignac(10)) and 30 l/min (SUPER-Boussignac(30)) of supplementary oxygen. In each step we measured FiO(2), tidal volumes, and airway pressure. RESULTS: FiO(2) increased with PEEP and decreased at increasing V(insp) with all the systems. However, FiO(2) increased with SUPER-Boussignac(10) (7-10%) and with SUPER-Boussignac(30) (10-30%). Moreover, in the latter case, for V(insp) values up to 60 l/min, FiO(2) became independent of V(insp). The SUPER-Boussignac allowed also smaller drop in airway pressure during inspiration and higher tidal volumes. CONCLUSIONS: The SUPER-Boussignac represents a simple way to significantly improve the performance of the Boussignac device.