Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

ICU strain and outcome in COVID-19 patients-A multicenter retrospective observational study.

PURPOSE: To compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality. METHODS: In a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality. RESULTS: 640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 --0.31] vs. 1.18 [-0.34-1.29] SD when compared to mean COVID-19 admission in each center during study period, P<0.001). Patients admitted during the second wave were older, had more profound hypoxemia and lower SOFA. High flow nasal cannula was more frequently used during the second wave (68% vs. 39%, P<0.001) and intubation was less frequent (46% vs. 69%, P<0.001). Neither 28-day mortality (30% vs. 26%, P = 0.12) nor hospital mortality (37% vs. 31%, P = 0.27) differed between first and second wave. Overweight and obesity were associated with lower 28-day mortality while older age, underlying chronic kidney disease, severity at ICU admission as assessed by SOFA score and ICU strain were associated with higher 28-day mortality. ICU strain was not associated with hospital mortality. CONCLUSION: The characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.

Coronavirus disease 2019 in immunocompromised patients: a comprehensive review of coronavirus disease 2019 in hematopoietic stem cell recipients.

PURPOSE OF REVIEW: Immunocompromised patients are notably vulnerable to severe coronavirus disease 2019. This review summarizes COVID-19 features and outcomes in autologous and allogeneic hematopoietic stem cell transplantation (HSCT) recipients. RECENT FINDINGS: Recent findings suggest that HSCT recipients exhibit a high burden of comorbidities and COVID-19 clinical features almost similar to the general COVID population. Furthermore, HSCT recipients exhibit a protracted SARS-CoV-2 shedding, prolonging duration of symptoms and promoting the generation of highly mutated viruses. Last, most of studies report a higher COVID-19 mortality in HSCT recipients, mainly driven by age, comorbidities, time from transplantation, and immunosuppression because of both treatments and underlying hematological malignancy. SUMMARY: Further studies are warranted to determine the proper impact of HSCT-related immune disorders on COVID-19 outcomes, and to evaluate specific treatments and vaccination strategy in this high-risk population. Taken together, those findings emphasize the need for more rigorous surveillance and preemptive measures for all HSCT recipients.

Imbalance of von Willebrand factor and ADAMTS13 axis is rather a biomarker of strong inflammation and endothelial damage than a cause of thrombotic process in critically ill COVID-19 patients.

BACKGROUND: Critically ill patients with coronavirus disease 2019 (COVID-19) are prone to developing macrothrombosis and microthrombosis. COVID-19 has been reported to be rarely associated with thrombotic microangiopathies. A disintegrin and metalloprotease with thrombospondin type I repeats, member 13 (ADAMTS13) severe deficiency, the hallmark of thrombotic thrombocytopenic purpura (TTP), induces the formation of platelet, unusually large von Willebrand factor (VWF) multimer microthrombi. In immune-mediated TTP, ADAMTS13 adopts specifically an open conformation. The VWF/ADAMTS13 couple may contribute to the microthrombi formation in pulmonary alveolar capillaries in COVID-19. OBJECTIVE: To investigate clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis, and ADAMTS13 conformation in critically ill COVID-19 patients at admission. METHODS: Fifty three critically ill COVID-19 patients were enrolled between March 18 and May 9 2020 in a monocentric hospital. RESULTS: The median age was 59 years and the male-to-female ratio was 2.8/1. We reported seven pulmonary embolisms and 15 deaths. Biological investigations showed increased fibrinogen and factor V levels, and strongly increased D-dimers correlated with mortality. No patient presented severe thrombocytopenia nor microangiopathic hemolytic anemia. An imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels (strongly elevated VWF/ADAMTS13 ratio) was correlated with mortality. Three patients had a partial quantitative deficiency in ADAMTS13. We also reported a closed conformation of ADAMTS13 in all patients, reinforcing the specificity of an open conformation of ADAMTS13 as a hallmark of TTP. CONCLUSION: We suggest that slightly decreased or normal ADAMTS13 activity and highly elevated VWF are rather biomarkers reflecting both the strong inflammation and the endothelial damage rather than drivers of the thrombotic process of COVID-19.

Oxygenation strategy during acute respiratory failure in immunocompromised patients.

Acute respiratory failure (ARF) in immunocompromised patients remains challenging to treat. A large number of case require admission to intensive care unit (ICU) where mortality remains high. Oxygenation without intubation is important in this setting. This review summarizes recent studies assessing oxygenation devices for immunocompromised patients. Previous studies showed that non-invasive ventilation (NIV) has been associated with lower intubation and mortality rates. Indeed, in recent years, the outcomes of immunocompromised patients admitted to the ICU have improved. In the most recent randomized controlled trials, including immunocompromised patients admitted to the ICU with ARF, neither NIV nor high-flow nasal oxygen (HFNO) could reduce the mortality rate. In this setting, other strategies need to be tested to decrease the mortality rate. Early admission strategy and avoiding late failure of oxygenation strategy have been assessed in retrospective studies. However, objective criteria are still lacking to clearly discriminate time to admission or time to intubation. Also, diagnosis strategy may have an impact on intubation or mortality rates. On the other hand, lack of diagnosis has been associated with a higher mortality rate. In conclusion, improving outcomes in immunocompromised patients with ARF may include strategies other than the oxygenation strategy alone. This review discusses other unresolved questions to decrease mortality after ICU admission in such patients.

Accuracy of P0.1 measurements performed by ICU ventilators: a bench study.

BACKGROUND: Occlusion pressure at 100 ms (P0.1), defined as the negative pressure measured 100 ms after the initiation of an inspiratory effort performed against a closed respiratory circuit, has been shown to be well correlated with central respiratory drive and respiratory effort. Automated P0.1 measurement is available on modern ventilators. However, the reliability of this measurement has never been studied. This bench study aimed at assessing the accuracy of P0.1 measurements automatically performed by different ICU ventilators. METHODS: Five ventilators set in pressure support mode were tested using a two-chamber test lung model simulating spontaneous breathing. P0.1 automatically displayed on the ventilator screen (P0.1vent) was recorded at three levels of simulated inspiratory effort corresponding to P0.1 of 2.5, 5 and 10 cm H2O measured directly at the test lung and considered as the reference values of P0.1 (P0.1ref). The pressure drop after 100 ms was measured offline on the airway pressure-time curves recorded during the automated P0.1 measurements (P0.1aw). P0.1vent was compared to P0.1ref and to P0.1aw. To assess the potential impact of the circuit length, P0.1 were also measured with circuits of different lengths (P0.1circuit). RESULTS: Variations of P0.1vent correlated well with variations of P0.1ref. Overall, P0.1vent underestimated P0.1ref except for the Löwenstein® ventilator at P0.1ref 2.5 cm H2O and for the Getinge group® ventilator at P0.1ref 10 cm H2O. The agreement between P0.1vent and P0.1ref assessed with the Bland-Altman method gave a mean bias of - 1.3 cm H2O (limits of agreement: 1 and - 3.7 cm H2O). Analysis of airway pressure-time and flow-time curves showed that all the tested ventilators except the Getinge group® ventilator performed an occlusion of at least 100 ms to measure P0.1. The agreement between P0.1vent and P0.1aw assessed with the Bland-Altman method gave a mean bias of 0.5 cm H2O (limits of agreement: 2.4 and - 1.4 cm H2O). The circuit's length impacted P0.1 measurements' values. A longer circuit was associated with lower P0.1circuit values. CONCLUSION: P0.1vent relative changes are well correlated to P0.1ref changes in all the tested ventilators. Accuracy of absolute values of P0.1vent varies according to the ventilator model. Overall, P0.1vent underestimates P0.1ref. The length of the circuit may partially explain P0.1vent underestimation.