Luigi Castagna

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.

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.

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.

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.

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.

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 ± 0.05 mmol/L (inlet) to 0.47 ± 0.03 mmol/L (prehemodiafilter blood) and 0.25 ± 0.03 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.

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.

Respiratory Monitoring of the ECMO Patient

Venovenous extracorporeal membrane oxygenation by modifying venous blood gas content can totally or partially substitute the gas exchange functions of patient lungs, therefore respiratory monitoring always needs to take into account the extracorporeal gas exchange and the hemodynamic. Few literature data are available, therefore local experiences are critical; in our ICU, we commonly monitor patients undergoing vv-ECMO with a Swan-Ganz catheter with continuous monitoring of mixed venous blood saturation. In addition to arterial and venous blood gas data, we daily withdraw blood at the ECMO inlet and outlet to perform a global assessment of the patient. We are therefore able to distinguish the oxygenation relative to native lung and extracorporeal support, the intrapulmonary shunt, and several other parameters that allow us to assess the state of the patient’s lungs and guide us in preventing further damage to an already compromised lung parenchyma. New technologies are becoming standard practice at the bedside and are helping us in this challenging task that is also becoming increasingly difficult given the expansion of fields of application of the extracorporeal support.