Matthias Lubnow

Pumpless extracorporeal interventional lung assist in patients with acute respiratory distress syndrome: a prospective pilot study

IntroductionPumpless interventional lung assist (iLA) is used in patients with acute respiratory distress syndrome (ARDS) aimed at improving extracorporeal gas exchange with a membrane integrated in a passive arteriovenous shunt. In previous studies, feasibility and safety of the iLA system was demonstrated, but no survival benefit was observed. In the present pilot study we tested the hypothesis that timely initiation of iLA using clear algorithms and an improved cannulation technique will positively influence complication rates and management of lung protective ventilation.MethodsiLA was implemented in 51 patients from multiple aetiologies meeting ARDS-criteria (American-European Consensus) for more than 12 hours. Initiation of iLA followed an algorithm for screening, careful evaluation and insertion technique. Patients with cardiac insufficiency or severe peripheral vascular disease were not considered suitable for iLA. Arterial and venous cannulae were inserted using a new strategy (ultrasound evaluation of vessels by an experienced team, using cannulae of reduced diameter). The incidence of complications and the effects on tidal volumes and inspiratory plateau pressures were primary outcome parameters, while oxygenation improvement and carbon dioxide removal capabilities were secondary study parameters.ResultsInitiation of iLA resulted in a marked removal in arterial carbon dioxide allowing a rapid reduction in tidal volume (≤ 6 ml/kg) and inspiratory plateau pressure. Adverse events occurred in 6 patients (11.9%). The hospital mortality rate was 49%.ConclusionsThe use of an indication algorithm for iLA in early ARDS, combined with a refined application technique was associated with efficient carbon dioxide removal and a reduced incidence of adverse events. iLA could serve as an extracorporeal assist to support mechanical ventilation by enabling low tidal volume and a reduced inspiratory plateau pressure.

A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure.

IntroductionMortality of severe acute respiratory distress syndrome in adults is still unacceptably high. Extracorporeal membrane oxygenation (ECMO) could represent an important treatment option, if complications were reduced by new technical developments.MethodsEfficiency, side effects and outcome of treatment with a new miniaturized device for veno-venous extracorporeal gas transfer were analysed in 60 consecutive patients with life-threatening respiratory failure.ResultsA rapid increase of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) from 64 (48 to 86) mmHg to 120 (84 to 171) mmHg and a decrease of PaCO2 from 63 (50 to 80) mmHg to 33 (29 to 39) mmHg were observed after start of the extracorporeal support (P < 0.001). Gas exchange capacity of the device averaged 155 (116 to 182) mL/min for oxygen and 210 (164 to 251) mL/min for carbon dioxide. Ventilatory parameters were reduced to a highly protective mode, allowing a fast reduction of tidal volume from 495 (401 to 570) mL to 336 (292 to 404) mL (P < 0.001) and of peak inspiratory pressure from 36 (32 to 40) cmH2O to 31 (28 to 35) cmH2O (P < 0.001). Transfusion requirements averaged 0.8 (0.4 to 1.8) units of red blood cells per day. Sixty-two percent of patients were weaned from the extracorporeal system, and 45% survived to discharge.ConclusionsVeno-venous extracorporeal membrane oxygenation with a new miniaturized device supports gas transfer effectively, allows for highly protective ventilation and is very reliable. Modern ECMO technology extends treatment opportunities in severe lung failure.

Kidney injury molecule-1 and N-acetyl-ß-d-glucosaminidase in chronic heart failure: possible biomarkers of cardiorenal syndrome

Patients with chronic heart failure are often characterized by impaired renal function, also referred to as cardiorenal syndrome (CRS). The aim of this study was to assess whether novel markers of kidney injury are elevated in chronic heart failure and CRS.

Venovenous extracorporeal membrane oxygenation for acute lung failure in adults

BACKGROUND Acute lung failure (ALF) is an increasing problem that can be treated with venovenous extracorporeal membrane oxygenation (vv-ECMO). This report summarizes prospectively collected data of an institutional experience with vv-ECMO. METHODS From January 2007 to December 2010, 176 patients (mean age, 48 ± 16; range, 14-78 years) with ALF refractory to conventional therapy were supported with vv-ECMO. The general indication for vv-ECMO was a partial oxygen pressure/fraction of inspired oxygen (Fio(2)) < 80 mm Hg under a Fio(2) of 1.0, a positive end-expiratory pressure of 18 cm H(2)O, and refractory respiratory acidosis (pH < 7.25), despite optimization of conservative therapy. RESULTS All patients underwent peripheral cannulation. In 59 cases, vv-ECMO was placed in another facility with ECMO transport by helicopter or ambulance. The mean vv-ECMO support interval was 12 ± 9.0 days (range, 1-67 days). During ECMO, 12 patients (7%) could be extubated and stepwise mobilized. Cannula-related complications during long-term support occurred in 14%, which was mostly minor bleeding. Overall survival was 56%: 58 patients (33%) died during mechanical support, and 20 (11%) died after weaning from the system. The best outcome was noted in trauma patients. Risk factors were mainly advanced age and multiorgan failure. CONCLUSION Modern vv-ECMO is an excellent treatment in patients with severe ALF and should be more liberally used.

Prediction of mortality in adult patients with severe acute lung failure receiving veno-venous extracorporeal membrane oxygenation: a prospective observational study

IntroductionVeno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.MethodsEstablished mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models.ResultsIn the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and hemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.ConclusionsWhile pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.

Extracorporeal Circulatory Systems as a Bridge to Lung Transplantation at Remote Transplant Centers

BACKGROUND Worsening of lung function in patients awaiting lung transplantation can lead to ventilation-refractory hypoxemia or hypercapnia and respiratory acidosis. This report describes the successful use of different extracorporeal circulatory systems as a bridge to transplantation at remote centers. METHODS Between January 2003 and December 2009, we had 10 requests for implantation of extracorporeal circulatory systems (pumpless extracorporeal lung assist [PECLA] or extracorporeal membrane oxygenation [ECMO]) in patients decompensating on the waiting list to bridge to transplantation at three different transplant centers between 150 km and 570 km apart. Cannulas were inserted percutaneously with Seldingers technique. RESULTS The median patient age was 36 years (range, 24 to 53). Three patients were supported with PECLA and 7 with ECMO. The median duration of support was 23 days (range, 5 to 73). Two patients were initially provided with ECMO and then changed to PECLA after hemodynamic stabilization in the face of persisting pulmonary failure. Two patients died of multiorgan failure on ECMO while on the waiting list. One PECLA patient was successfully weaned and waiting for LTx. Before transplantation, 5 patients (4 PECLA and 1 ECMO) were successfully weaned from mechanical ventilation, and 3 PECLA patients were successfully weaned from the system. Seven patients were successfully bridged and transplanted. Five of 7 patients were discharged from the transplant centers. CONCLUSIONS This report suggests that implantation of extracorporeal circulatory systems is a safe method to bridge patients decompensating on the waiting list for transplantation. Support intervals of several weeks are possible.

High-sensitive troponin T in chronic heart failure correlates with severity of symptoms, left ventricular dysfunction and prognosis independently from N-terminal pro-b-type natriuretic peptide.

Abstract Background: Troponin T is an established marker of myocardial ischemia. We speculated that the role of the new high-sensitive troponin T (hs-cTnT) might expand towards non-ischemic myocardial disease, indicate disease severity and allow for prognostication in chronic heart failure. Methods: Hs-cTnT (Roche Diagnostics, Mannheim, Germany) was assessed in 233 individuals with chronic heart failure (n=149) or healthy controls (n=84). Results: Hs-cTnT was significantly elevated in patients with chronic heart failure [0.018 ng/mL, interquartile range (IQR) 0.009–0.036 ng/mL, vs. controls 0.003 ng/mL, 0.003–0.003 ng/mL, p<0.001] and positively correlated with N-terminal pro-b-type natriuretic peptide (NT-proBNP) (r=0.79, p<0.001). Hs-cTnT increased stepwise and signitificantly according to clinical (NYHA stage) as well as functional (LV ejection fraction, fluid retention) severity (each p<0.001). At a binary cutpoint of 0.014 ng/mL, hs-TropT was a significant predictor of all-cause mortality and all-cause mortality or rehospitalization for congestive heart failure (each p≤0.01). Of note, the prognostic value of hs-TropT was independent and additive to that of NT-proBNP. Conclusions: Hs-cTnT increases stepwise with the severity of symptoms and LV dysfunction and offers important prognostic information in chronic heart failure, independently from and additive to NT-proBNP. The utility of hs-cTnT expands beyond acute myocardial ischemia and towards chronic heart failure.

First experience with the new portable extracorporeal membrane oxygenation system Cardiohelp for severe respiratory failure in adults.

Background: Over the last decade, technical improvements in extracorporeal membrane oxygenation (ECMO) equipment have reduced procedure-related complications and have made ECMO an effective option for patients with acute respiratory distress syndrome (ARDS) if conventional therapy fails. Methods: In this report, we present our early experience with the Cardiohelp, a new portable miniaturized ECMO system, in 22 consecutive patients with ARDS. All patients were placed on venovenous ECMO. Cannulas were inserted percutaneously, employing the Seldinger technique. Data were collected prospectively. Results: The median patient age was 47 years (36 to 61). Fifteen patients from regional hospitals were too unstable for conventional transport and were placed on Cardiohelp at the referring hospital and then transported to our institution. The patients were transported by ambulance (n=2) or helicopter (n=13) over a distance of 50-250 km. Cardiohelp support resulted in immediate improvement of gas exchange and highly protective ventilation. The median duration of support was 13 days (8 to 19). An exchange of the device was necessary in 9 patients. Sixteen patients (72.7%) were successfully weaned from ECMO and fifteen patients (68.2%) survived. Device-related complications were not observed. Conclusions: The compact portable ECMO device Cardiohelp is a highly effective method to secure vital gas exchange and to reduce further ventilator-induced lung injury in patients with acute respiratory failure. Crucial technical innovations and ease of device transport and implantation allow location-independent stabilization with consecutive inter-hospital transfer.

Technical Complications during Veno-Venous Extracorporeal Membrane Oxygenation and Their Relevance Predicting a System-Exchange – Retrospective Analysis of 265 Cases

Objectives Technical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO). Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study. Methods Retrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 2009-2013) with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n = 83). Results Values presented as median (interquartile range). Patient age was 50(36–60) years, the SOFA score 11(8–14.3) and the Murray lung injury Score 3.33(3.3–3.7). Cumulative ECMO support time 3411 days, 9(6–15) days per patient. Mechanical failure of the blood pump (n = 5), MO (n = 2) or cannula (n = 1) accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb), serum lactate dehydrogenase (LDH), n = 13) and MO (increase in pressure drop across the MO, n = 16) required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n = 10) and device-related coagulation disorders (n = 32), either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD]), decreased platelet count; n = 24), or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n = 8), which could be reversed after system-exchange. Four MOs were exchanged due to suspicion of infection. Conclusions The majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop across the MO and laboratory parameters (DD, FG, platelets, LDH, frHb). These parameters should be monitored in the daily routine to reduce the risk of unexpected ECMO failure.

Support time-dependent outcome analysis for veno-venous extracorporeal membrane oxygenation §,§§

OBJECTIVE The majority of patients suffering from pulmonary failure refractory to mechanical ventilation require extracorporeal membrane oxygenation (ECMO) support between 1 and 2 weeks. This study was designed to evaluate differences in outcome depending on ECMO duration. METHODS A retrospective analysis on n = 127 patients requiring veno-venous (VV) ECMO support at our institution between April 2006 and March 2010 was applied. The patient population was divided into three groups according to the support duration (A: 0-10 days), 75 patients; B: 11-20 days, 32 patients; C: >21 days, (max. 67 days), 19 patients). Statistical comparisons between groups were calculated. RESULTS Mean age of all patients (♀ = 42 patients ♂=85 patients) was 48 ± 16 years (range 15-78 years). Bilateral pneumonia due to bacterial infection (n = 45 patients) or due to aspiration (n = 19 patients) was the main cause for pulmonary failure, other causes were extrapulmonary sepsis (n = 27 patients), major surgery (n = 17 patients), and severe trauma (n = 12 patients). Mean lung injury score (LIS) according to Murray was 3.4 ± 0.4, and mean sequential organ failure assessment (SOFA) score was 12.6 ± 3.7. Statistical comparisons revealed no significant difference in demographic parameters between groups. VV ECMO support immediately improved oxygenation, within 2h the PaO(2)/FiO(2) ratio rose from 80 ± 42 mm Hg to 129 ± 72 mm Hg (p = 0.001). Overall survival to discharge was 51.2%. There was a statistical difference in survival between groups (A = 59%, B = 31%, C = 52%; p = 0.029). Multivariate logistic regression analysis revealed renal failure (odds ratio (OR) 12.1; confidence interval (CI) 3.9-30.0; p < 0.001) and the use of NO (OR=5.8; CI=1.9-24.9; p=0.002) as risk factors for mortality. Complications consisted of cannula-related complications (14%), bleeding issues (13%), partial vein thrombosis of the cannulated vessels (9.5%), and pumphead failure (1.5%). CONCLUSION VV ECMO in patients suffering from severe lung failure is effective in improving gas exchange with an overall survival of higher than 50%. Prolonged need of ECMO support does not have an impact on survival.