Marco Giani

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.

Regional blood acidification enhances extracorporeal carbon dioxide removal: a 48-hour animal study

Background:Extracorporeal carbon dioxide removal has been proposed to achieve protective ventilation in patients at risk for ventilator-induced lung injury. In an acute study, the authors previously described an extracorporeal carbon dioxide removal technique enhanced by regional extracorporeal blood acidification. The current study evaluates efficacy and feasibility of such technology applied for 48 h. Methods:Ten pigs were connected to a low-flow veno-venous extracorporeal circuit (blood flow rate, 0.25 l/min) including a membrane lung. Blood acidification was achieved in eight pigs by continuous infusion of 2.5 mEq/min of lactic acid at the membrane lung inlet. The acid infusion was interrupted for 1 h at the 24 and 48 h. Two control pigs did not receive acidification. At baseline and every 8 h thereafter, the authors measured blood lactate, gases, chemistry, and the amount of carbon dioxide removed by the membrane lung (VCO2ML). The authors also measured erythrocyte metabolites and selected cytokines. Histological and metalloproteinases analyses were performed on selected organs. Results:Blood acidification consistently increased VCO2ML by 62 to 78%, from 79 ± 13 to 128 ± 22 ml/min at baseline, from 60 ± 8 to 101 ± 16 ml/min at 24 h, and from 54 ± 6 to 96 ± 16 ml/min at 48 h. During regional acidification, arterial pH decreased slightly (average reduction, 0.04), whereas arterial lactate remained lower than 4 mEq/l. No sign of organ and erythrocyte damage was recorded. Conclusion:Infusion of lactic acid at the membrane lung inlet consistently increased VCO2ML providing a safe removal of carbon dioxide from only 250 ml/min extracorporeal blood flow in amounts equivalent to 50% production of an adult man.

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.

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.

Newer Indications and Challenges

Technological development of extracorporeal systems of the last 30 years led to extremely improved high-flow venoarterial or venovenous extracorporeal systems for cardiovascular support and refractory hypoxia and to less invasive low-flow systems for extracorporeal CO2 removal.

ION-EXCHANGE RESIN ANTICOAGULATION: EXPERIMENTAL DATA OF A NOVEL EXTRACORPOREAL REGIONAL ANTICOAGULATION TECHNIQUE

Regional anticoagulation has been introduced to avoid the complications of systemic anticoagulation. The most diffuse technique for regional anticoagulation is the infusion of citrate, which exerts its anticoagulative effect by chelating calcium, an essential factor of coagulation. Despite being a “regional” anticoagulation technique, a major fraction of the infused citrate reaches the patient systemic circulation and may cause toxicity. For this reason this technique can be applied only to extracorporeal blood flows lower than ~150-180 ml/min, to limit the amount of infused citrate. Ion exchange resins are polymers which contain acidic or basic functional groups able to exchange counter-ions. We have developed a regional anticoagulation technique featuring a cation exchange resin, which exchanges calcium with sodium and thus reduces plasmatic calcium levels.

Extracorporeal Selective Chloride Removal By Electrodialysis: An Innovative Treatment For Respiratory and Metabolic Acidosis

Acidosis is a frequent disorder among critically ill patients. When patient compensatory responses fail to restore a normal pH, administration of sodium bicarbonate (NaHCO3) or renal replacement therapy may be required. Intravenous NaHCO3 increases plasma Strong Ion Difference ([SID] = [Na+] + [K+] - [Cl-]) and HCO3- concentration by raising Na+ concentration. Although effective, this treatment is not devoid of complications, such as hypernatremia, hyperosmolarity and fluid overloading[1]. Selective chloride (Cl-) removal, by increasing SID in an alternative way, may allow a rapid correction of acidosis without altering plasma osmolality and Na+ concentration.

Interhospital ground transportation of severe acute respiratory distress syndrome patients on extracorporeal membrane oxygenation: Monza's experience

Severe acute respiratory distress syndrome (ARDS) patient transportation is an extremely high-risk procedure. We report our experience in transferring these patients to our centre while on extracorporeal membrane oxygenation (ECMO).