Aspects on extracorporeal life support for severe acute respiratory failure with special reference to the influenza A/H1N1 2009 pandemic

Extracorporeal membrane oxygenation provides pulmonary and circulatory support. First abandoned from the majority of the intensive care community because of disappointing results in several trials (with questionable methods), it experienced a renaissance during the H1N1 influenza pandemic in 2009/2010. Today, it is a widely accepted therapy option for the sickest respiratory failure patients, with survival rates between 50% and 80%, depending on the mode and the center where it is performed. But there is still a lack of high quality randomized trials to answer the question whether ECMO is superior to conventional mechanical ventilation in severe respiratory failure. But such trials are very difficult to perform mainly due to ethical reasons because a randomization to death is not acceptable for the majority of health care professionals. The question we have to ask ourselves today is not whether ECMO should be performed but how it should be performed, and here there is still a lot of work to do. In this thesis, several aspects on extracorporeal life support for severe respiratory failure were investigated. Paper I describes the treatment strategies and short-term outcome of 13 patients with refractory severe respiratory failure due to infection with influenza A H1N1 2009 at the ECMO Department at the Karolinska University Hospital. All patients survived, and 12 were still alive 3 months after discharge from ECMO. In paper II the ECMOnet score is presented. It was developed by the Italian ECMOnet, and the 13 patients treated due to H1N1 infection in paper I were included in an external validation group for this score. It has a high accuracy for the prediction of mortality risk in the patients treated with venovenous ECMO for H1N1 respiratory failure. The probability of correctly classifying patients with this score was 75%, where a score of 4.5 was the most appropriate cutoff for prediction of mortality risk. In the external validation group, the score had a good capacity to distinguish survivors from non-survivors. Paper III is a neurocognitive long-term follow-up study of seven of the patients presented in paper I. The studied showed that despite prolonged episodes of hypoxemia, cognitive functioning was normal in all patients and that there were no hypoxic cerebral lesions. Severe respiratory failure is a hyperinflammatory condition, and neutrophil granulocytes play a key role in its development and progress. In paper IV, we explored the hypothesis that the change in proportions of mature and immature neutrophils could be used as a prognostic parameter during the course of ECMO treatment, but due to a low number of included patients, no strong conclusion could be drawn. The systematic review presented in paper V is a result of question that arose in paper III, namely whether hypoxemia during the course of acute respiratory failure or ECMO treatment per se is associated with short- and long-term cognitive dysfunction in survivors. There are no high quality studies addressing this question, and it is therefore still not clear whether there is a causal relationship between hypoxemia and cognitive impairment. New studies are needed to investigate this important question because it is evident that different treatment strategies of acute respiratory failure have an impact on survival

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Extrakorporale Membranoxygenierung (ECMO) zur Behandlung des schweren respiratorischen Versagens am ECMO Zentrum Karolinska

Zwischen Juli 2009 und Januar 2010 wurden 13 Patienten mit bestätigter A/H1N1 Infektion und respiratorischem Versagen am ECMO Zentrum Karolinska mit ECMO behandelt. 12 Patienten wurden im einweisenden Krankenhaus von unserem Transportteam kanüliert und nach Stockholm transportiert. Bei einem Patienten wurde die ECMO Behandlung in unserer Klinik begonnen. Zwölf Patienten waren drei Monate nach Entlassung aus dem Krankenhaus am Leben. Mit ECMO kann eine hohe Überlebensrate im schwersten respiratorischen Versagen, ausgelöst durch eine Infektion mit pandemischem Influenza Virus A/H1N1 2009, erzielt werden. Um gute Resultate mit dieser Behandlungsform erzielen zu können, sollte diese vornehmlich zentralisiert an eigens dafür spezialisierten Einrichtungen durchgeführt werde

Do we have scientific evidence about the effect of hypoxaemia on cognitive outcome in adult patients with severe acute respiratory failure?

Do we have scientific evidence about the effect of hypoxaemia on cognitive outcome in adult patients with severe acute respiratory failure

Clinical and laboratory signs of haemophagocytic lymphohistiocytosis associated with pandemic influenza A (H1N1) infection in patients needing extracorporeal membrane oxygenation A retrospective observational study

BACKGROUND: Severe pandemic influenza has been associated with the hyperinflammatory condition secondary haemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: To determine the frequency, degree, character and possible cause of influenza-associated HLH in critically ill patients with severe acute respiratory distress syndrome due to influenza A (H1N1) infection requiring extracorporeal membrane oxygenation (ECMO) support at our hospital. DESIGN: A retrospective observational study. PATIENTS AND SETTING: Medical data were retrieved retrospectively from 11 consenting patients of thirteen adults infected with pandemic influenza A (H1N1) 2009 requiring ECMO between July 2009 and January 2010 at the ECMO Centre of Karolinska University Hospital, Stockholm, Sweden. All patients were evaluated for HLH using HLH-2004 criteria and HScore. RESULTS: Eleven patients (median age 31 years) were included in the study and all survived. All patients showed signs of multiple organ dysfunction and pronounced inflammation, more severe in the four patients with HLH who had significantly higher peak serum concentrations of ferritin (P = 0.024), alkaline phosphatase (P = 0.012) and gamma-glutamyl transferase (P = 0.024), lower concentration of albumin (P = 0.0086) and more frequently hepatomegaly (P = 0.048). Abnormal lymphocyte cytotoxicity (lytic units &lt;10) and a low proportion of natural killer (NK) cells were observed in three of four patients with HLH. Notably, we found a significant inverse correlation between serum ferritin concentration and NK cell and cytotoxic T lymphocyte percentages (r(s) = -0.74, P = 0.0013 and r(s) = -0.79, P = 0.0025, respectively). One HLH patient received HLH-directed cytotoxic therapy, another intravenous immunoglobulin and the other two no specific HLH-directed therapy. CONCLUSION: Critically ill patients, including healthy young adults, with pandemic influenza may develop HLH and should be monitored for signs of hyperinflammation and increasing organ dysfunction, and evaluated promptly for HLH because HLH-directed therapy may then be beneficial. The association of low NK percentages with hyperferritinaemia may suggest a role for reduced NK cell numbers, possibly also cytotoxic T lymphocytes, and subsequently reduced lymphocyte cytotoxicity, in the pathogenesis of hyperinflammation and secondary HLH

Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: The ECMOnet score

Purpose: The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation. Methods: This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines. Results: The survival rate in patients treated with ECMO was 68 %. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR = 1.52, 95 % CI 1.12-2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52-3.52, p &lt; 0.001), creatinine (OR = 7.38, 95 % CI 1.43-38.11, p = 0.02) and hematocrit values (OR = 0.82, 95 % CI 0.72-0.94, p = 0.006); and mean arterial pressure (OR = 0.92, 95 % CI 0.88-0.97, p &lt; 0.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis (c = 0.857, 95 % CI 0.754-0.959, p &lt; 0.001) and by an independent external validation analysis (c = 0.694, 95 % CI 0.562-0.826, p = 0.004). Conclusions: Mortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure. \uc2\ua9 2012 Springer-Verlag Berlin Heidelberg and ESICM