Extracorporeal membrane oxygenation support for life-threatening acute severe status asthmaticus.

INTRODUCTION: Status asthmaticus is a life-threatening condition characterized by progressive respiratory failure due to asthma that is unresponsive to standard therapeutic measures. We used extracorporeal membrane oxygenation (ECMO) to treat patients with near-fatal status asthamticus who did not respond to aggressive medical therapies and mechanical ventilation under controlled permissive hypercapnia. MATERIALS AND METHODS: Between January 2011 and October 2015, we treated 16 adult patients with status asthmaticus (8 women, 8 men, mean age: 50.5±10.6years) with veno-venous ECMO (13 patients) or veno-arterial (3 patients). Patients failed to respond to conventional therapies despite receiving the most aggressive therapies, including maximal medical treatments, mechanical ventilation under controlled permissive hypercapnia and general anesthetics. RESULTS: Mean time spent on ECMO was 300±11.8 hours (range 36-384 hours). PaO2, PaCO2 and pH showed significant improvement promptly after ECMO initiation p=0.014, 0.001 and <0.001, respectively, and such values remained significantly improved after ECMO, p=0.004 and 0.001 and <0.001, respectively. The mean time of ventilation after decannulation until extubation was 175±145.66 hours and the median time to intensive care unit discharge after decannulation was 234±110.30 hours. All 16 patients survived without neurological sequelae. CONCLUSIONS: ECMO could provide adjunctive pulmonary support for intubated asthmatic patients who remain severely acidotic and hypercarbic despite aggressive conventional therapy. ECMO should be considered as an early treatment in patients with status asthmaticus whose gas exchange cannot be satisfactorily maintained by conventional therapy for providing adequate gas change and preventing lung injury from the ventilation.

A numerical model of blood oxygenation during veno-venous ECMO: analysis of the interplay between blood oxygenation and its delivery parameters.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an important tool in the management of most severe forms of acute respiratory failure. The determinants and management of oxygen delivery in patients treated with VV-ECMO is a complex topic. The physiological principles of oxygenation on VV-ECMO are reviewed in many textbooks. However a numerical model is an additional instrument to be used in understanding and exploring this intricate subject matter. We present a numerical model of blood oxygenation during VV-ECMO. Using this model we examined the role and impact of each determinant on blood oxygenation. The numerical analysis of variation and interplay between each oxygenation determinants during VV-ECMO is presented in graphical form. These results corroborate all the findings of previous studies. The proposed numerical model facilitates understanding of oxygenation physiology during VV-ECMO; it can be used for a medical simulation system and for teaching the principles of oxygenation during VV-ECMO.

The actual role of cardiocirculatory assistance in heart-failure treatment as destination therapy and bridge to life.

Patients with end-stage heart failure have poor quality of life and a poor prognosis, and are usually burdened by symptoms at rest, need for frequent hospital admissions, complex pharmacologic therapies, and 1-year mortality rate of about 50%. Therapeutic options are scarce and not amenable to all. Only few patients can be transplanted. In recent years, technological progress has made available mechanical devices capable of providing short/medium- and long-term circulatory assistance. Clinical evidence of long-term survival without device-related adverse events using latest-generation small axial pumps allows evaluation of its use in patients with contraindications or inaccessibility to transplantation.

Extracorporeal membrane oxygenation for refractory, life-threatening, and herpes simplex virus 1-induced acute respiratory distress syndrome. Our experience and literature review.

We report our first experience of treating an immunocompetent adult patient with acute respiratory distress syndrome (ARDS) due to type 1 herpes simplex (HSV1) pneumonitis, using extracorporeal membrane oxygenation (ECMO). Similar cases reported in literature are reviewed as well. The therapeutic options for this particular complication are discussed. Pneumonia caused by HSV1 is a rare finding in immunocompetent individuals; it occurs more often in immunosuppressed and ventilated patients. It is a severe illness; therefore, early diagnosis and initiation of treatment are imperative. Diagnosis is based on cytologic and histologic findings, viral cultures, or serologic methods. This condition can be reversible; however, often, it can progress into refractory ARDS with limited therapeutic options available. We demonstrate the causative role of HSV1 in refractory ARDS of a previously healthy 18-year-old man who presented to the intensive care unit with acute respiratory distress after a week of flulike syndrome. Due to severe hypoxemia and hypercarbia, the patient required mechanical ventilation and later emergent blood oxygenation with extracorporeal support. For the first time in this condition, we used venovenous ECMO management, to rest the lung, sustain blood oxygenation and end-organ oxygen delivery, and promote potential lung recovery. During ECMO and after our etiologic diagnosis, specific therapy was introduced. After viral negativization, corticosteroid therapy (Meduri protocol) was initiated. Extracorporeal membrane oxygenation allowed us to initiate therapy while maintaining end-organ oxygenation and support the patient until lung recovery. After 18 days of ECMO, our patient recovered completely. Near-normal lung structures and functions were documented on a chest x-ray/computed tomography, thoracic ultrasonography, and pulmonary functional tests at hospital discharge and at a 1-year follow-up. Data suggest that severe pulmonary involvement in HVS1 infection associated with septicemia/shock is a rare but often fatal in immunocompetent adult as well. We suggest that ECMO might be the selected treatment for severe refractory ARDS in this clinical scenario. It seems to be an effective and useful ultimate therapeutic strategy for preventing death and furthermore permitting near-full pulmonary function recovery.

Intractable cardiogenic shock in stress cardiomyopathy with left ventricular outflow tract obstruction: is extra-corporeal life support the best treatment?

We report the use of extra-corporeal cardiopulmonary support (ECLS), in a case of complicating refractory severe cardiogenic shock, in a patient with Tako-tsubo cardiomyopathy (TC). Tako-tsubo cardiomyopathy syndrome is characterized by left ventricular (LV) wall motion abnormalities, usually without coronary artery disease, mimicking the diagnosis of acute coronary syndrome. This ventricular dysfunction is typically reversible in the acute phase, though it can progress into refractory cardiogenic shock with limited therapeutic options available. Here, we report for the first time in a Tako-tsubo patient with refractory cardiogenic shock, the use of ECLS treatment in order to unload the heart, sustain circulation and end-organ perfusion, and promote potential ventricular recovery. Extra-corporeal life support allowed inotropic drug weaning while maintaining end-organ function and supported the patient until myocardial recovery. The patient recovered completely, and a normal LV ejection fraction was documented by 2D echocardiography on day 7. From our experience, ECLS can be an appropriate treatment for severe refractory cardiogenic shock in patients with TC. Extra-corporeal life support was an effective ultimate solution.

Extracorporeal life support as ultimate strategy for refractory severe cardiogenic shock induced by Tako-tsubo cardiomyopathy: a new effective therapeutic option.

We report a possible new therapeutic strategy, using extracorporeal cardiopulmonary support (ECLS), for severe refractory cardiogenic shock (SRCS) in a patient with Tako-tsubo cardiomyopathy (TC). TC is a syndrome characterized by left ventricular wall motion abnormalities, without coronary artery disease, mimicking the diagnosis of acute coronary syndrome. This ventricular dysfunction can be reversible; however, it can progress into refractory cardiogenic shock with limited therapeutic options available. For the first time in a Tako-tsubo patient with refractory cardiogenic shock, we used ECLS treatment in order to rest the heart, sustain circulation and end-organ perfusion, and promote potential ventricular recovery. ECLS might be the selected treatment for SRCS in patients with TC, and seems to be an effective and useful ultimate therapeutic strategy for preventing death.

Cellular cardiomyoplasty into infracted swine's hearts by retrograde infusion through the venous coronary sinus: An experimental study.

OBJECTIVES: The aim was to create a model of myocardial infarction with a borderline myocardial impairment which would enable evaluation of the retrograde cellular cardiomyoplasty through the venous coronary sinus in a large animal model. MATERIALS AND METHODS: Fifteen (study group) and 10 juvenile farm pigs (control group) underwent distal left anterior descending artery ligation. One month later the study group animals underwent sternotomy and a murine myoblastic line C2-C12 was injected at a constant pressure of 30mmHg, into the coronary sinus. Thirty days later all animals that survived from both groups underwent transthoracic echocardiography and 99Tc scintigraphy and were later euthanized and specimens were taken for microscopic evaluation. RESULTS: Cardiac output decreased significantly after ligation (p<0.001) and increased significantly after cardiomyoplasty (p<0.001). In all animals, the surgical induction of myocardial infarction caused a marked decline in the echocardiographic values of cardiac function; however, the cardiac function and dimensions were significantly improved in the study group after cardiomyoplasty versus the control group. All animals undergoing cardiomyoplasty demonstrated a significant reduction of the perfusion deficit in the left anterior descending artery territory, instead such data remained unchanged in the control group. The histological examination demonstrated the engrafted myoblasts could be distinguished from the activated fibroblasts in the scar tissue because they never showed any signs of collagen secretion and fiber buildup. CONCLUSIONS: In conclusion, the venous retrograde delivery route through the coronary sinus is safe and effective, providing a significant improvement in function and viability.

Mechanical Ventricular Assistance as Destination Therapy for End-Stage Heart Failure: Has it Become a First Line Therapy?

UNLABELLED: Patients with end-stage heart failure have poor quality of life and prognosis. Therapeutic options are scarce and are not available for all. Only few patients can be transplanted every year. Several medical and surgical strategies have shown limited ability to influence prognosis and quality of life. In the past years, technological progress has realized devices capable of providing appropriate hemodynamic stabilization and recovery of secondary organ failure. Recently, these devices have been assessed as definitive treatment for patients who do not qualify for transplantation or/and instead to transplantation ("destination therapy"). This indication is increasingly considered following the results of newest clinical study reporting long-term survival without device correlated adverse events using last generation devices, and acceptable quality of life. The current knowledge about destination therapy and some original data from the DAVID Study (an Italian multicenter prospective study designed to evaluate the patient's survival rate and quality of life of patients implanted with these new devices as long-term support or destination therapy) are summarized herein. KEY POINTS: -End-stage heart failure (NYHA class IV or stage D) is a vastly growing problem, with a poor prognosis and limited therapeutic options.-Heart Transplantation is nowadays the "gold standard" treatment albeit its inability to serve to the current demand let alone the future one.-The REMATCH study has demonstrated that first generation implantable devices, even with their high number of complications (infectious and thromboembolic events), allowed an improvement of quality and duration of life compared to medical therapy. Further studies have shown that the evolution of VAD technology has reduced device-related complications and consequently improved survival and quality of life of patients with results, according to some authors, similar to cardiac transplantation at least at 2 years from the implantation.-Biotechnology advancements have led to the creation of a new generation of implantable mechanical assist devices: the continuous-flow rotary pumps. Recently entered into clinical use, they seem to represent a promising solution to end -stage-heart failure allowing long-term assistance and an adequate standard of living (Destination Therapy/Bridge to Life).-The DAVID Study, an Italian multicenter prospective study, reports encouraging results in terms of late outcome and quality of life in patients implanted with newest continuous-flow devices as destination therapy. More and more numerous studies are needed to confirm our initial data and for laying the foundations for this new therapeutic frontier face to cardiac transplantation.

Inverted-Takotsubo cardiomyopathy: severe refractory heart failure in poly-trauma patients saved by emergency extracorporeal life support.

OBJECTIVES: The sequelae of severe poly-trauma may include myocardial dysfunction followed by acute heart failure and death. Inverted-Takotsubo cardiomyopathy (ITC) is a variant of stress cardiomyopathy, characterized by a contractile abnormality with extensive left ventricular circumferential dyskinesia or akinesia with a hyperkinetic apex. We report our experience with refractory cardiogenic shock and/or cardiac arrest, treated with extracorporeal life support. METHODS: From June 2008 to December 2011, we treated 4 adult poly-trauma patients (3 men, 1 woman, mean age: 27.7 ± 13.5 years, mean ISS score 53.2 ± 15.9) with veno-arterial (V-A) extracorporeal life support for cardiopulmonary failure/cardiac arrest refractory to conventional treatment, due to inverted-Takotsubo cardiomyopathy. We used a miniaturized extracorporeal life support (ECLS) device. RESULTS: ITC myocardial dysfunction appeared 15.4 ± 11.6 h after intensive care unit admission and rapidly evolved to refractory cardiopulmonary failure and cardiac arrest (within 4.8 ± 2.5 h of the onset). At ECLS, initiation median pH was 7.12 ± 0.14 (6.91-7.25), median lactate was 6.7 ± 2.8 (4-10) mmol/l and median vasoactive-inotropic score was 192.1 ± 50.6 µg/kg/min. Tissue perfusion improved significantly within 4 h on ECLS. Cardiac function improved gradually but consistently. Initial median ejection fraction was 14.2 ± 4.7% and median global longitudinal strain test was -7.4 ± 4.7. At complete cardiac recovery, they were 62.73 ± 7.8 and -18.43 ± 2.4%, respectively. After that, 2 patients survived and were sent to neurological rehabilitation before hospital discharge. In the other 2 cases, post-traumatic cerebral death occurred and they underwent organ explantation. CONCLUSIONS: Rapid heparin-free ECLS may improve outcome in the most severe cases of poly-traumatized patients demonstrating refractory inverted-Takotsubo cardiomyopathy.

Extracorporeal life support in patients with severe trauma: an advanced treatment strategy for refractory clinical settings.

OBJECTIVES: Major trauma is a leading cause of death, particularly among young patients. New strategies in management are needed to improve poor outcomes in cases of severe trauma. Extracorporeal life support (ECLS) has proven to be effective in acute cardiopulmonary failure of different causes, even when conventional therapies fail. We report our initial experience with ECLS as a rescue therapy in severely polytraumatized patients in a refractory clinical setting. This study identifies the pre-ECLS characteristics of patients to predict the appropriateness of ECLS treatment. METHODS: From December 2008 to May 2012, 375 patients with polytrauma were treated in the Careggi Teaching Hospital, a tertiary-level referral trauma center. Our ECLS team was alerted on 30 patients and applied ECLS in 18 adult patients with trauma. We adopted venoarterial ECLS in 14 patients with cardiopulmonary failure with refractory shock and venovenous ECLS in 4 patients with isolated refractory acute respiratory failure. RESULTS: ECLS was initiated at a mean of 359.176 ± 216.606 (145-950) minutes from trauma. In 4 patients, the ECLS treatment failed because of an incapability to maintain adequate ECLS flow and perfusion. In 14 patients, efficiently supported by ECLS, the cardiac index, mean arterial pressure, blood lactate concentration, arterial oxygen tension, arterial carbon dioxide tension, and pH showed significant improvement, with normal values reached at 3.5 ± 1.5 hours. CONCLUSIONS: From our data, ECLS seems to be a valuable option to resuscitate patients with severe trauma when conventional therapies are insufficient. ECLS is safe, feasible, and effective in providing hemodynamic support and blood gas exchange.

A new formula for determining arterial oxygen saturation during venovenous extracorporeal oxygenation.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used to treat severe forms of acute respiratory distress syndrome (ARDS). VV-ECMO management may be confusing due to the lack of information about the interplay between the determinant parameters and their impact on oxygenation. We found a relationship between arterial oxygen saturation (SaO(2)) and its relevant parameters. The aim of this study was to assess the validity of this model. METHODS: We report our experience in 17 patients under VV-ECMO for severe ARDS. We compared, at two different levels of pump flow, SaO(2) and the oxygen saturation measured in the pulmonary artery (SpaO(2)) with the predicted saturation using the formula: SpaO(2) = (EF/CO)SmO(2) + (1 - EF/CO)SvO(2) + 10(-2)PmO(2), where PF is pump flow, R is recirculation, EF is effective flow [= (1 - R)PF], SmO(2) is saturation of the oxygenator outgoing blood, CO is cardiac output, SvO(2) is saturation of mixed venous blood, and PmO(2) is oxygen partial pressure of the oxygenator outgoing blood. RESULTS: There was no significant difference between predicted and measured SpaO(2): the mean predicted and measured SpaO(2) values were 90.7 ± 2.8 % and 90.4 ± 2.7 % , respectively (p = 0.696, r = 0.966). Bland-Altman analysis showed good agreement between predicted and measured SpaO(2). Predicted SpaO(2) and SaO(2) was well correlated (r = 0.80). CONCLUSIONS: We have presented an explicit relationship between SaO(2) and its direct determinants during VV-ECMO. Good agreement was found with the measured values of SaO(2), but the model remains to be fully validated before its use in clinical practice.

Atypical clinic presentation of pandemic influenza A successfully rescued by extracorporeal membrane oxygenation - Our experience and review of the literature.

The novel pandemic influenza A (H1N1) caused an epidemic of critical illness, and some patients developed severe acute respiratory distress syndrome (ARDS) or severe cardiopulmonary failure despite the use of conventional management. Extracorporeal membrane oxygenation (ECMO) support may successfully rescue these severely ill patients. We demonstrate the causative role of H1N1 in refractory ARDS of a previously healthy 15-year-old man who presented to the intensive care unit with a hypoxic and persistent cardiogenic shock refractory to conventional management as the leading symptom of influenza A. Because of compromised cardiopulmonary function, venovenous ECMO was applied 24 h after admission. Despite that the patient was manifesting heart failure, we decided the placement of venovenous ECMO because we believed that the real problem was the uncontrollable hypoxia and hypercapnia. A normal left ventricular ejection fraction was documented on a 2D echocardiography on day 2. The patient, after 6 days of ECMO, recovered completely and was successfully weaned from the mechanical ventilator on the 9th day after admission. The patient was discharged from the hospital on the 15th day. This experience showed that ECMO can be lifesaving for severe H1N1 infection also in patients with atypical clinical presentation of influenza.

Cellular retrograde cardiomyoplasty and relaxin therapy for postischemic myocardial repair in a rat model.

We sought to determine whether skeletal myoblasts, wild-type or engineered to express relaxin, might improve myocardial viability and performance in a rat model of chronic myocardial infarction. Our purpose was to investigate a potential new therapy for heart failure. From October 2005 through September 2009, we surgically induced acute myocardial infarction in 80 male Wistar rats. Thirty days after surgery, the rats underwent reoperation for the retrograde coronary venous infusion of skeletal myoblasts, relaxin, or both. The animals were randomly assigned to 4 experimental groups: R1 (the control group, which underwent saline-solution infusion), R2 (systemic relaxin therapy), R3 (myoblast infusion), and R4 (myoblast infusion and systemic relaxin therapy). Echocardiography, positron emission tomography, and cellular and histologic analysis were performed at 4 established time points. Mortality rates were similar among the groups. Postinfarction echocardiographic evaluation revealed similar left ventricular dysfunction. Viable myocardium, evaluated with positron emission tomography, was analogous. After therapy, the echocardiographic values of cardiac function improved significantly (P<0.05) in all groups except R1. Myocardial viability volume increased significantly in groups R3 and R4 (P<0.05) but was unchanged in groups R2 and R1. In group R4, the echocardiographic and positron emission tomographic results improved significantly (P<0.001). Histologic analysis showed that myoblasts settled in regions of ischemic scarring, especially when combined with relaxin. The retrograde venous route is safe, effective, and clinically feasible for cell delivery. Myoblasts and relaxin are better than either alone in terms of myocardial viability and performance improvement.

A novel strategy to improve systemic oxygenation in venovenous extracorporeal membrane oxygenation: the "χ-configuration".

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used in refractory acute respiratory distress syndrome where lung recovery is the primary goal. For its achievement, adequate extracorporeal blood flow and a maximal separation between oxygenated (inflow) and deoxygenated (outflow) blood flow are essential for reducing the recirculation phenomenon. We introduce the χ-configuration, a new cannulation strategy for VV-ECMO. PATIENTS AND METHODS: We report our experience with 30 VV-ECMO consecutive patients: in 16 patients (group NS) we applied the χ-configuration, which consists of a particular right atrial cannula arrangement and a self-made modified inflow cannula, consisting of an outflow multihole venous cannula that was inserted percutaneously through the right femoral vein, into the right atrium, just below on the superior vena cava, and a self-made modified curved inflow cannula (inserted percutaneously through the right internal jugular vein) that, in its terminal segment, permitted the tip to be positioned close to the tricuspid valve. In 14 patients (group C) we applied the standard femoro-jugular VV-ECMO 2-cannula setting. In both groups, efficacy of blood oxygenation was obtained by gas-blood analysis, by blood samples obtained at arterial, central venous, and pulmonary artery lines, and by ECMO inflow and outflow lines. The recirculation fraction was obtained by a specific bedside formula. RESULTS: No differences were noted between groups regarding the pre-ECMO patient characteristics. No complications during cannulation were recorded. In group NS, on-ECMO time, post-ECMO mechanical ventilation time, and ECMO overall results were significantly better than in group C. During high-flow VV-ECMO, pulmonary and systemic arterial oxygen saturation and arterial oxygen tension were significantly higher in group NS, and blood recirculation fraction was significantly lower. CONCLUSIONS: Our data indicate that χ-configuration can be safe, feasible, and more effective than conventional VV-ECMO. It permits near complete drainage of the desaturated blood and a preferential oxygenated blood inflow toward the tricuspid valve, resulting in a significant reduction of recirculation, thereby improving the patient's oxygenation. Our innovative strategy reduces on-ECMO and post-ECMO mechanical ventilation time, gives a faster and better pulmonary recovery, improves survival, and can reduce hospital costs.