Identifying Clinical Phenotypes in Moderate to Severe Acute Respiratory Distress Syndrome Related to COVID-19: The COVADIS Study.

Objectives: Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19. Methods: We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes. Results: We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2. Conclusions: In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Impact of COVID-19 on nursing time in intensive care units in Belgium.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on nursing practice in intensive care unit and consequently, on workload. OBJECTIVE: To assess the nurse-patient ratio required by COVID-19 patients and to identify the factors that influence nursing in this context. DESIGN: This study was a retrospective observational study that evaluated the ratio using the Nursing Activities Score (NAS). SETTING: Three Belgian French-speaking hospitals, including five ICUs. Patients included COVID-19 and non-COVID-19 patients. MEASUREMENTS AND MAIN RESULTS: The study included 95 COVID-19 patients and 1604 non-COVID-19 patients (control group) resulting in 905 and 5453 NAS measures, respectively. The NAS was significantly higher among the COVID-19 patients than in the control group (p = <0.0001). In the COVID-19 group, these higher scores were also observed per shift and uniformly across the three hospitals. COVID-19 patients required more time in the activities of monitoring and titration (χ2 = 457.60, p = <0.0001), mobilisation (χ2 = 161.21, p = <0.0001), and hygiene (χ2 = 557.77, p = <0.0001). Factors influencing nursing time measured by NAS in the COVID-19 patients were age <65 years old (p = 0.23), the use of continuous venovenous hemofiltration (p = 0.002), a high APACHE II score (p = 0.006) and patient death (p = 0.002). A COVID-19 diagnosis was independently associated with an increase in nursing time (OR = 4.8, 95% CI:3.6-6.4). CONCLUSIONS: Patients hospitalised in the ICU due to COVID-19 require significantly more nursing time and need an average ratio of almost 1:1.

Characteristics and outcomes of acute respiratory distress syndrome related to COVID-19 in Belgian and French intensive care units according to antiviral strategies: the COVADIS multicentre observational study.

BACKGROUND: Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). METHODS: Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into "patients still ventilated or dead at day 28" versus "patients weaned and alive at day 28". RESULTS: We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0-13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18-1.25); OR 0.96 (0.47-2.02) and OR 1.43 (0.53-4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16-5.59). CONCLUSION: In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT.

Factors Associated With Pulmonary Embolism Among Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: A Multicenter Study Among 375 Patients.

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

A case report of rigidity and recurrent lower limb myoclonus: progressive encephalomyelitis rigidity and myoclonus syndrome, a chameleon.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome is a rare neurological condition. Its clinical characteristics include axial and limb muscle rigidity, myoclonus, painful spasms and hyperekplexia. Diagnosis of this disease can be very challenging and optimal long-term treatment is unclear. CASE PRESENTATION: We report a case of a 62 year old patient admitted for repetitive myoclonus and rigidity in the lower limbs progressing since 10 years, associated with a fluctuating encephalopathy requiring stays in Intensive Care Unit. Multiple diagnostics and treatment were proposed, unsuccessfully, before the diagnosis of PERM syndrome was established. In association with the clinical presentation, a strong positive result for GAD (glutamic acid decarboxylase) antibodies lead to the diagnosis of PERM syndrome. CONCLUSIONS: PERM syndrome is a rare disease and its diagnosis is not easy. Once the diagnosis is established, the correct treatment should follow and could be lifesaving, regardless of a delayed diagnosis. Maintenance of long-term oral corticotherapy is suggested to prevent relapses.

Uncontrolled bleeding of the gastrointestinal tract.

PURPOSE OF REVIEW: Acute gastrointestinal bleeding is a frequent emergency situation, whose incidence will likely rise as a result of the increasing use of direct anticoagulants and of the medical progresses resulting in longer life expectancy with underlying comorbidities. Updated guidelines and improvements in the diagnostic and therapeutic tools are now available and will likely improve the management of massive gastrointestinal bleeding in the near future. RECENT FINDINGS: The assessment of severity has been improved by validated scores useable upon admission. Massive blood transfusion protocols and specific care in case of bleeding of patients treated with direct anticoagulants, including concentrates of coagulation factors and monoclonal antibodies are now available. The endoscopic management has been facilitated by the use of hemostatic powders and by the use of self-expanding metal stents in case of variceal hemorrhage. New diagnostic tools include emergency video-capsule endoscopy, multiphasic computed tomography angiography and enterography. SUMMARY: The implementation of multidisciplinary diagnostic and therapeutic algorithms for the management of massive bleeding requires a close collaboration between emergency physicians, intensivists, endoscopists, radiologists and surgeons. A sequential strategy involving each of these specialists is desirable for a successful management of acute and massive gastrointestinal bleeding.