Christian Karagiannidis

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.

Combination of high frequency oscillatory ventilation and interventional lung assist in severe acute respiratory distress syndrome

BACKGROUND The combination of high-frequency oscillatory ventilation (HFOV) and extracorporeal carbon dioxide removal with the interventional lung assist (iLA) in severe acute respiratory distress syndrome (ARDS) represents a novel treatment option. METHODS The study used a retrospective single-center analysis of 21 consecutive adult patients with severe ARDS, ventilated with HFOV/iLA. Efficiency, side effects, and outcome of combined treatment are presented as median (interquartile range). MEASUREMENTS AND MAIN RESULTS The following were used to determine patient characteristics: sequential organ failure assessment score, 14; simplified acute physiology score II, 41; and Murray score, 4. The duration of combined treatment was 6 days. The blood flow through the iLA was 1.9 L/min. The Pao(2)/inspired fraction of oxygen ratio increased from 61 (47-86) to 98 (67-116) within 2 hours and to 106 (70-135) mm Hg at 24 hours. Paco(2) decreased from 58 (50-76) to 37 (29-47) mm Hg at 2 hours with normalization of pH 7.28 (7.16-7.36) to 7.43 (7.33-7.49) after 2 hours associated with hemodynamic stabilization. In 6 patients, complications due to iLA treatment were observed, and in 3 patients, complications associated with HFOV were seen. Weaning from HFOV/iLA was successful in 10 patients. The 30-day mortality rate was 43%, and hospital mortality rate was 57%. CONCLUSION The combination of HFOV/iLA is an option in severe pulmonary failure if conventional ventilation fails and pumpdriven extracorporeal membrane oxygenation therapy is not available.

Veno-venous extracorporeal CO2 removal improves pulmonary hypertension in acute exacerbation of severe COPD.

Dear Editor, Acute exacerbation of chronic obstructive pulmonary disease (COPD) typically leads to acute hypercapnic respiratory failure with respiratory acidosis, which requires the augmentation of alveolar ventilation by mechanical support. At best, non-invasive ventilation is implemented early in these patients as it reduces intubation rate and intubation-related complications, and, importantly, mortality. Recently, veno-venous extracorporeal CO2 removal (vv-ECCO2R) has been shown to rapidly correct even severe respiratory acidosis [1], and this technique is currently under investigation as an adjunct to treat severe COPD patients. Here, vvECCO2R is aimed at avoiding intubation or at reducing the time spent on invasive mechanical ventilation [2]. In ARDS patients there is some new evidence that vv-ECCO2R provides additional benefit by decreasing elevated systolic pulmonary artery pressure (PAPsys) both in animals [3] and in patients, where this effect reportedly depends on the amount of CO2 removed [4]. Even though a strong correlation between pulmonary artery dilatation and severe COPD exacerbation was shown previously [5], the clinical consequences of an increased PAP occurring during COPD exacerbation are still unclear, and the impact of vv-ECCO2R on PAP in COPD exacerbation still needs to be elucidated. We report on five patients (mean age 52 ± 13 years, four female) with severe COPD exacerbation and invasive mechanical ventilation following intubation, in whom vv-ECCO2R was initiated to reduce intubation time and in whom pulmonary artery catheterization was used for regular hemodynamic monitoring. All patients had failed at least two spontaneous breathing trials within 48 h before vv-ECCO2R was considered according to the study protocol of the ‘‘PALP-COPD Trial’’ ( www.clinicaltrials.gov: NCT02107222), which is planned to start in the near future. During vv-ECCO2R mean PAP decreased from 36.8 ± 5.6 (baseline) to 27.0 ± 7.0 (15 min), to 26.6 ± 6.1 (30 min), to 24.4 ± 3.4 (45 min), and, eventually, to 22.8 ± 2.8 (60 min) mmHg (Fig. 1), while ventilator settings used for invasive ventilation were adapted accordingly. The mean blood flow used for vvECCO2R was 2.0 ± 0.5 L/min, and the mean sweep gas flow was 7.6 ± 1.7 L/min using a FiO2 of 1.0. During 60 min of vv-ECCO2R mean PaCO2 decreased from 95.0 ± 25.8 to 53.2 ± 13.7 mmHg, while mean pH increased from 7.27 ± 0.08 to 7.49 ± 0.09. At baseline mean cardiac index (CI) was 4.0 ± 0.49 L/ min/m and mean wedge pressure was 16.4 ± 2.9 mmHg, while further CI measurements during vv-ECCO2R were not reliable as a result of the artificially induced jet blood flow next to the right atrium. Finally, all patients were extubated successfully; one patient had to be reintubated and required tracheostomy and prolonged weaning. To our knowledge, this case series shows for the first time that vvECCO2R has not only the potential to rapidly correct respiratory acidosis by lowering high PaCO2 values but also to reduce elevated mean PAP values in severe COPD significantly. Mean PAP values were substantially elevated in our patients with exacerbated COPD and could be normalized within 1 h of vv-ECCO2R. This may be of major clinical importance given the known deleterious effects of acute pulmonary hypertension in patients

Continuous non‐invasive PCO2 monitoring in weaning patients: Transcutaneous is advantageous over end‐tidal PCO2

Continuous partial pressure of carbon dioxide (PCO2) assessment is essential for the success of mechanical ventilation (MV). Non‐invasive end‐tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) measurements serve as alternatives to the gold standard arterial PCO2 (PaCO2) method, but their eligibility in critical care is unclear.

Extrakorporale CO2-Elimination (ECCO2R): von der Pathophysiologie zur klinischen Anwendung beim hyperkapnischen respiratorischen Versagen

Extracorporeal CO2 removal (ECCO2R) is becoming an increasingly established treatment option for patients with acute severe hypercapnic respiratory failure. Technically, pumpless arterio-venous systems using the natural arterio-venous pressure gradient and also pump-driven veno-venous systems are available. Here, veno-venous ECCO2R has become the preferred technique, as settings for arterio-venous ECCO2R are restricted and side effects are more common with arterio-venous ECCO2R. Using veno-venous ECCO2R with blood flow rates up to 450 ml/min 60 to 80 ml CO2 can be removed per minute corresponding to 20 to 30 % of the total amount of CO2 production. However, in case of very severe hypercapnic respiratory failure with severe respiratory acidosis (pH 7.1 or less) blood flow rates of around 1000 ml/min are required for compensating severe respiratory acidosis corresponding to the elimination of 50 to 60 % of the total amount of CO2 production. Relevant side effects include the activation of blood coagulation and associated bleeding complications. Two recent case-control studies in severely exacerbated COPD patients could demonstrate that intubation rates can be reduced by the application of ECCO2R, but this was associated with non-ignorable side effects. Therefore, randomized controlled trials are urgently needed to more precisely establish the risks and benefits of ECCO2R when aimed at avoiding intubation.

The ECMOnet score: a useful tool not to be taken absolutely

Dear Editor, We read with great interest the article by Pappalardo and colleagues [1], and very much appreciate their effort in identifying predictors of mortality in patients on ECMO with lung failure induced by H1N1-influenza-A using the newly developed ECMOnet score. We congratulate the authors and all participating centers on the achievement of a nationwide database for these patients, which opens up new approaches to collectively improving the outcome in these patients. Predicting the risk of mortality is important and desirable in guiding the use of restricted treatment resources such as ECMO. It is not an easy undertaking, as very high accuracy is needed to avoid the grave consequences of an incorrect decision. We agree with the authors that ventilatory and blood gas parameters before ECMO cannot sufficiently predict the final outcome in a patient on ECMO, which may be explained by the fact that the extracorporeal device will support and partly substitute for respiratory function. In our own cohort of 38 patients with H1N1influenza-A and the need for venovenous ECMO since 2009 (Table 1), in addition to common respiratory parameters we tested static compliance (CRS) and corrected expired volume per minute (VEcorr), because a recent post hoc analysis showed that either a CRS of 20 ml/cm H2O or less or a VEcorr of at least 13 l/min in combination with a PaO2/FiO2 of 100 mm Hg or less identifies a higher risk subgroup [2, 3]. However, this may not be true for patients on ECMO, as we could not see a difference in our small sample. Failure of extrapulmonary organs may be a more important predictor, which is mirrored in two parameters of the new ECMOnet score, bilirubin and creatinine. In addition, hospital length of stay before ECMO institution was found to be a predictor of death, which parallels information from the ELSO database, that length of ventilation before ECMO is associated with a worse outcome [4]. This parameter might be falsified, if H1N1 is acquired in hospital, as we have seen in several referred cases. Parameter 4 (hematocrit) and parameter 5 (mean arterial pressure) may be iatrogenically corrected by blood transfusions and vasopressors, and we wonder whether this was taken into account when calculating the score. In our cohort, further major contributors to a poor outcome were chronic

Quality of life and life satisfaction are severely impaired in patients with long-term invasive ventilation following ICU treatment and unsuccessful weaning

BackgroundHealth-related quality of life (HRQL), life satisfaction, living conditions, patients’ attitudes towards life and death, expectations, beliefs and unmet needs are all poorly understood aspects associated with patients receiving invasive home mechanical ventilation (HMV) following ICU treatment and unsuccessful weaning. Therefore, the present study aimed to assess (1) HRQL, (2) life satisfaction and (3) patients’ perspectives on life and death associated with invasive HMV as the consequence of unsuccessful weaning.ResultsPatients undergoing invasive HMV with full technical supply and maximal patient care were screened over a 1-year period and assessed in their home environment. The study comprised the following: (1) detailed information on specific aspects of daily life, (2) self-evaluation of 23 specific daily life aspects, (3) HRQL assessment using the Severe Respiratory Insufficiency Questionnaire, (4) open interviews about the patient’s living situation, HRQL, unsolved problems, treatment options, dying and the concept of an afterlife. Out of 112 patients admitted to a specialized weaning centre, 50 were discharged with invasive HMV and 25 out of these (14 COPD and 11 neuromuscular patients) were ultimately enrolled. HRQL and life satisfaction were severely impaired, despite maximal patient care and full supply of technical aids. The most important areas of dissatisfaction identified were mobility, communication, social contact and care dependency. Importantly, 32% of patients would have elected to die in hindsight rather than receive invasive HMV.ConclusionsDespite maximal patient care and a full supply of technical aids, both HRQL and life satisfaction are severely impaired in many invasive HMV patients who have failed prolonged weaning. These findings raise ethical concerns about the use of long-term invasive HMV following unsuccessful weaning.

Assessment of silent spaces at different PEEP levels by electrical impedance tomography in severe COPD

Electrical impedance tomography (EIT) is a novel method to monitor regional lung function. For this purpose, 32 surface electrodes are placed around the human thorax. Weak alternating currents are applied via two of these electrodes and the resulting potentials are measured at the remaining electrodes. From the measured voltages, real-time images are calculated which show the distribution of electrical impedance within the body representing functions rather than structures. Using EIT these lungs can be analysed on a regional basis with respect to the following risk factors: collapse, at risk of becoming atelectatic or overdistension. Identifying these lung areas of particular clinical relevance by EIT may help to find the best individual PEEP level for each patient.

Expiratory time constants by electrical impedance tomography in hypoxemic and hypercapnic acute lung failure - a feasibility study

During relaxed breathing expiration can be compared to a RC-circuit with R being the airway resistance, C the respiratory system compliance and τ = R∙C the expiratory time constant. For the adult respiratory system, the normal τ is around 0.8 s. Different lung pathologies have different time constants. Two common disease types are the acute respiratory distress syndrome (ARDS) and the chronic obstructive pulmonary disease (COPD). ARDS is characterized by stiff or noncompliant lungs with low compliance and normal or lower resistance which results in shorter τ. COPD is characterized by impaired airflow or high airways resistance and high compliance which results higher τ. τ reveals information about respiratory mechanics and the time required for the lungs to empty. Traditional pulmonary function tests provide global information only. EIT is a non-invasive real-time imaging technology which determines changes of lung volumes on a regional basis assuming that local impedance changes are proportional to local changes in lung volume. Pikkemaat [1] introduced the method to calculate regional τ, what we improved and applied in 10 patients.

German-wide prospective DACAPO cohort of survivors of the acute respiratory distress syndrome (ARDS): a cohort profile

Purpose While most research focuses on the association between medical characteristics and residual morbidity of survivors of the acute respiratory distress syndrome (ARDS), little is known about the relation between potentially modifiable intensive care unit (ICU) features and the course of health-related quality of life (HRQoL). Accordingly, the DACAPO study was set up to elucidate the influence of quality of intensive care on HRQoL and return to work (RtW) in survivors of ARDS. The continued follow-up of these former ICU patients leads to the establishment of the DACAPO (survivor) cohort. Participants Sixty-one ICUs all over Germany recruited patients with ARDS between September 2014 and April 2016. Inclusion criteria were: (1) age older than 18 years and (2) ARDS diagnosis according to the ‘Berlin definition’. No further inclusion or exclusion criteria were applied. 1225 patients with ARDS could be included in the DACAPO ICU sample. Subsequently, the 876 survivors at ICU discharge form the actual DACAPO cohort. Findings to date The recruitment of the participants of the DACAPO cohort and the baseline data collection has been completed. The care-related data of the DACAPO cohort reveal a high proportion of adverse events (in particular, hypoglycaemia and reintubation). However, evidence-based supportive measures were applied frequently. Future plans Three months, 6 months and 1 year after ICU admission a follow-up assessment is conducted. The instruments of the follow-up questionnaires comprise the domains: (A) HRQoL, (B) RtW, (C) general disability, (D) psychiatric symptoms and (E) social support. Additionally, an annual follow-up of the DACAPO cohort focusing on HRQoL, psychiatric symptoms and healthcare utilisation will be conducted. Furthermore, several add-on projects affecting medical issues are envisaged. Trial registration number NCT02637011.