Effects of adding the second drainage cannula in severely hypoxemic patients supported with VV ECMO due to COVID-19-associated ARDS.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a recognized method of support in patients with severe and refractory acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. While veno-venous (VV) ECMO is the most common type, some patients with severe hypoxemia may require modifications to the ECMO circuit. In this study, we aimed to investigate the effects of adding a second drainage cannula to the circuit in patients with refractory hypoxemia, on their gas exchange, mechanical ventilation, ECMO settings, and clinical outcomes. METHODS: We conducted an observational retrospective study based on a single-center institutional registry including all consecutive cases of COVID-19 patients requiring ECMO admitted to the Centre of Extracorporeal Therapies in Warsaw between March 1, 2020 and March 1, 2022. We selected patients who had an additional drainage cannula inserted. Changes in ECMO and ventilator settings, blood oxygenation, and hemodynamic parameters, as well as clinical outcomes were assessed. RESULTS: Of 138 VV ECMO patients, 12 (9%) patients met the inclusion criteria. Ten patients (83%) were men, and mean age was 42.2 ± 6.8. An addition of drainage cannula resulted in a significant raise in ECMO blood flow (4.77 ± 0.44 to 5.94 ± 0.81 [L/min]; p = 0.001), and the ratio of ECMO blood flow to ECMO pump rotations per minute (RPM), whereas the raise in ECMO RPM alone was not statistically significant (3432 ± 258 to 3673 ± 340 [1/min]; p = 0.064). We observed a significant drop in ventilator FiO2 and a raise in PaO2 to FiO2 ratio, while blood lactates did not change significantly. Nine patients died in hospital, one was referred to lung transplantation center, two were discharged uneventfully. CONCLUSIONS: The use of an additional drainage cannula in severe ARDS associated with COVID-19 allows for an increased ECMO blood flow and improved oxygenation. However, we observed no further improvement in lung-protective ventilation and poor survival.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

COVID-19 and Extracorporeal Membrane Oxygenation.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.

Impact of the Organizational Model Adopted during the COVID-19 Pandemic on the Perceived Safety of Intensive Care Unit Staff.

BACKGROUND: The SARS-CoV-2 pandemic had a devastating health, social, and economic effect on the population. Organizational, technical and structural operations aimed at protecting staff, outpatients and inpatients were implemented in an Italian hospital with a COVID-19 dedicated intensive care unit. The impact of the organizational model adopted on the perceived safety among staff was evaluated. METHODS: Descriptive, structured and voluntary, anonymous, non-funded, self-administered cross-sectional surveys on the impact of the organizational model adopted during COVID-19 on the perceived safety among staff. RESULTS: Response rate to the survey was 67.4% (153 completed surveys). A total of 91 (59%) of respondents had more than three years of ICU experience, while 16 (10%) were employed for less than one year. Group stratification according to profession: 74 nurses (48%); 12 medical-doctors (7%); 11 physiotherapists (7%); 35 nurses-aides (22%); 5 radiology-technicians (3%); 3 housekeeping (1%); 13 other (8%). The organizational model implemented at ISMETT made them feel safe during their workday. A total of 113 (84%) agreed or strongly agreed with the sense of security resulting from the implemented measures. A vast majority of respondents perceived COVID-19 as a dangerous and deadly disease (94%) not only for themselves but even more as vectors towards their families (79%). A total of 55% of staff took isolation measures and moved away from their home by changing personal habits. The organizational model was perceived overall as appropriate (91%) to guarantee their health. CONCLUSION: The vast majority of respondents perceived the overall model applied during an unexpected, emergency situation as appropriate.

Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS. METHODS: This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications. RESULTS: Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients. CONCLUSION: In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference. TRIAL REGISTRATION NUMBER: NCT05080933 , retrospectively registered.

Immunological and Hematological Response in COVID-19.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. Through the renin-angiotensin system, the virus may impact the lung circulation, but the expression on endothelium may conduct to its activation and further systemic damage. While precise mechanisms underlying these phenomena remain to be further clarified, the understanding of the disease, its clinical course, as well as its immunological and hematological implications is of paramount importance in this phase of the pandemic. METHODS: This review summarizes the evidence gathered until 12 June; electronic databases were screened for pertinent reports on coronavirus and inflammatory and hematological changes. Search was conducted by two independent investigators; keywords used were "SARS-CoV-2," "COVID-19," "inflammation," "immunological," and "therapy." RESULTS: The viral infection is able to trigger an excessive immune response in predisposed individuals, which can result in a "cytokine storm" that presents an hyperinflammation state able to determine tissue damage and vascular damage. An explosive production of proinflammatory cytokines such as TNF-α IL-1ß and others occurs, greatly exaggerating the generation of molecule-damaging reactive oxygen species. These changes are often followed by alterations in hematological parameters. Elucidating those changes in SARS-CoV-2-infected patients could help to understand the pathophysiology of disease and may provide early clues to diagnosis. Several studies have shown that hematological parameters are markers of disease severity and suggest that they mediate disease progression. According to the available literature, the primary hematological symptoms-associated COVID-19, and which distinguish patients with severe disease from patients with nonsevere disease, are lymphocytopenia, thrombocytopenia, and a significant increase in D-dimer levels. CONCLUSIONS: SARS-CoV-2 infection triggers a complex response altering inflammatory, hematological, and coagulation parameters. Measuring these alterations at certain time points may help identify patients at high risk of disease progression and monitor the disease severity.

Challenges in the Extracorporeal Membrane Oxygenation Era.

In the last decade, the use of extracorporeal membrane oxygenation (ECMO) has significantly increased [...].

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.

Endoscopy at Bedside in Isolated Patients with Severe COVID-19: Our Approach during the Pandemic

The COVID-19 pandemic changed the management of emergency medicine and those complications that needed interventional procedures, such as endoscopy or other radiological procedures. At the beginning of the outbreak, there were no exploitable recommendations regarding the proper policy to apply for limiting the virus spread during endoscopy. Between the first and the second wave, the approach regarding interventional procedures changed, due to higher awareness and newly defined protocols, even if different among the health centers. Patients with severe COVID-19 may develop major gastrointestinal complications or require nutritional support, so interventional procedures are required at bedside, even if patients are in isolated rooms. Our tertiary center admitted 95 patients with severe COVID-19 at our ICU-dedicated department until May 2021, and 56% of them died. Among them, 61 endoscopic procedures were performed, mainly gastroscopies (81.96%) followed by colonoscopies (11.47%) and other more advanced procedures (6.55%). Our approach aimed to adapt and create COVID-related protocols, dedicated itineraries, and rooms in a separate department with the prospect to easily organize complete and safe endoscopic theaters at the COVID-ICU department.

Tracheostomy management in patients with severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: an International Multicenter Retrospective Study.

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.

Apneic Tracheostomy in COVID-19 Patients on Veno-Venous Extracorporeal Membrane Oxygenation.

COVID-19 creates an impressive burden for intensive care units in terms of need for advanced respiratory care, with a huge number of acute respiratory distress syndromes (ARDS) requiring prolonged mechanical ventilation. In some cases, this proves to be insufficient, with a refractory respiratory failure calling for an extracorporeal approach (veno-venous ECMO). In this scenario, most of these patients need an early tracheostomy procedure to be carried out, which creates the risk of distribution of aerosol particles, possibly leading to personnel infection. The use of apneic tracheostomy has been proposed for COVID-19 patients, but in case of ECMO it may produce lung derecruitment, severe hypoxemia, and sudden worsening of respiratory mechanics. We developed an apneic tracheostomy technique and applied it in over 32 patients supported by veno-venous ECMO. We present data showing the safety and feasibility of this technique in terms of patient care and personnel protection. Gas exchange and pH did not show statistically significant changes after the tracheostomy, nor did respiratory mechanics data or the need for inspiratory pressure and FiO2. The use of apneic tracheostomy was a safe option for patient care during ECMO and reduced the possibility of virus spreading.

Vitamin D in critical care: where are we now and what is next?

PURPOSE OF REVIEW: To summarize the recent evidence on the role of vitamin D deficiency in critically ill patients and emerging data claiming a role of vitamin D in COVID-19. RECENT FINDINGS: Vitamin D is a strong predictor for worse outcomes in critically ill patients, and as well in COVID-19. The vitamin D content in typical nutrition regimes is lower than what is recommended for the general population. Although its supplementation has been shown to reduce respiratory tract infections, asthma exacerbations and mortality risk in noncritically ill patients, its role in the acute setting is not yet clear. Several small intervention trials have shown interesting results in COVID-19, and larger studies are ongoing. SUMMARY: Although research on this topic is still ongoing, it appears reasonable to recommend at least the standard vitamin dose for the healthy population (600--800 IU of native vitamin D3). Many questions remain on the actual role, the best metabolite, regime, and so forth. However, the role for vitamin D in bone health is clear. Elderly ICU survivors have a high risk for osteoporosis/fractures, so at least in this population, an optimal vitamin D status should be targeted.

Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials.

Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2-3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials.

ECMO Retrieval over the Mediterranean Sea: Extending Hospital Arms.

The retrieval and transport of patients from peripheral hospitals to high volume extracorporeal membrane oxygenation (ECMO) centers aims to reduce complications and improve survival. In Sicily (Italy), our institute houses a mobile ECMO team that serves a population of around 10 million people for a vast area in southern Italy and Malta. This observational, descriptive study includes all patients that required veno-venous (V-V) ECMO and transport by a mobile team between October 2009 and May 2020. Linear and multiple logistic regressions were applied to explore the risk factors for mortality in the ICU. Kaplan-Meier estimates were generated to predict the survival in patients transported by helicopter or ambulance, and the two cohorts were compared according to their baseline characteristics. Of 122 patients transported, 89 (73%) survived to ICU discharge (50 (41%) patients were transported by ambulance, and 72 (59%) were transported by helicopter). Independent predictive factors associated with mortality in a stepwise multiple regression model were prone positioning, acute kidney injury, and the number of days spent on mechanical ventilation (MV). Kaplan-Meier estimates for survival favored the helicopter cohort (79%) rather than the ambulance cohort (64%). Patients transported by helicopter had better pre-ECMO profiles, with shorter hospital and ICU stays, a shorter duration of MV use, and higher RESP scores, which indicate better survival probabilities. ECMO transport can be carried out safely over long distances; in rural areas with underdeveloped roads, transportation via helicopter or ambulance can extend the arm of the hospital to remote areas. Early ECMO initiation can be crucial in improving survival outcomes, and when transportation is the limiting factor to starting ECMO support, it should be attempted at the earliest logistical stage possible.

COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.