Early versus late awake prone positioning in non-intubated patients with COVID-19.

BACKGROUND: Awake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP. METHODS: Post hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate. RESULTS: We included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8-12.82) vs 36.35 (30.2-75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0-9.05) and 3.0 (1.09-5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%, p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0-1.95], p = 0.001), intubation (OR 10.65 [95% CI 2.77-40.91], p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0-1.04], p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23-31.1], p = 0.027) were associated with increased mortality. CONCLUSIONS: Early initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival. Trial registration ClinicalTrials.gov NCT04325906.

Mechanical Ventilation Strategy Guided by Transpulmonary Pressure in Severe Acute Respiratory Distress Syndrome Treated With Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Previous studies have suggested that adjusting ventilator settings based on transpulmonary pressure measurements may minimize ventilator-induced lung injury, but this has never been investigated in patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation. We aimed to evaluate whether a transpulmonary pressure-guided ventilation strategy would increase the proportion of patients successfully weaned from venovenous extracorporeal membrane oxygenation support in patients with severe acute respiratory distress syndrome. DESIGN: Single-center, prospective, randomized controlled trial. SETTING: Sixteen-bed, respiratory ICU at a tertiary academic medical center. PATIENTS: Severe acute respiratory distress syndrome patients receiving venovenous extracorporeal membrane oxygenation. INTERVENTIONS: One-hundred four patients were randomized to transpulmonary pressure-guided ventilation group (n = 52) or lung rest strategy group (n = 52) groups. Two patients had cardiac arrest during establishment of venovenous extracorporeal membrane oxygenation in the lung rest group did not receive the assigned intervention. Thus, 102 patients were included in the analysis. MEASUREMENTS AND MAIN RESULTS: The proportion of patients successfully weaned from venovenous extracorporeal membrane oxygenation in the transpulmonary pressure-guided group was significantly higher than that in the lung rest group (71.2% vs 48.0%; p = 0.017). Compared with the lung rest group, driving pressure, tidal volumes, and mechanical power were significantly lower, and positive end-expiratory pressure was significantly higher, in the transpulmonary pressure-guided group during venovenous extracorporeal membrane oxygenation support. In the transpulmonary pressure-guided group, levels of interleukin-1ß, interleukin-6, and interleukin-8 were significantly lower, and interleukin-10 was significantly higher, than those of the lung rest group over time. Lung density was significantly lower in the transpulmonary pressure-guided group after venovenous extracorporeal membrane oxygenation support than in the lung rest group. CONCLUSIONS: A transpulmonary pressure-guided ventilation strategy could increase the proportion of patients with severe acute respiratory distress syndrome successfully weaned from venovenous extracorporeal membrane oxygenation.

Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients.

The purpose of this study was to assess the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for the diagnosis of severe respiratory diseases based on interpretation of sequencing results. BALF samples were harvested and used for mNGS as well as microbiological detection. Infectious bacteria or fungi were defined according to relative abundance and number of unique reads. We performed mNGS on 35 BALF samples from 32 patients. The positive rate reached 100% in the mNGS analysis of nine immunocompromised patients. Compared with the culture method, mNGS had a diagnostic sensitivity of 88.89% and a specificity of 74.07% with an agreement rate of 77.78% between these two methods. Compared with the smear method and PCR, mNGS had a diagnostic sensitivity of 77.78% and a specificity of 70.00%. In 13 cases, detection results were positive by mNGS but negative by culture/smear and PCR. The mNGS findings in 11/32 (34.4%) cases led to changes in treatment strategies. Linear regression analysis showed that diversity was significantly correlated with interval between disease onset and sampling. Dynamic changes in reads could indirectly reflect therapeutic effectiveness. BALF mNGS improves sensitivity of pathogen detection and provides guidance in clinical practice. Potential pathogens can be identified based on relative abundance and number of unique reads.

Early diagnosis and appropriate respiratory support for Mycoplasma pneumoniae pneumonia associated acute respiratory distress syndrome in young and adult patients: a case series from two centers.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community acquired pneumonia (CAP). Establishing an early diagnosis of M. pneumoniae pneumonia in patients with acute respiratory distress syndrome (ARDS) may have important therapeutic implications. METHODS: We describe diagnosis and management of M. pneumoniae pneumonia induced ARDS in a case series of adults and youth hospitalized with radiographically confirmed CAP prospectively enrolled in an observational cohort study in two university teaching hospitals, from November 2017 to October 2019. RESULTS: In all 10 patients, early and rapid diagnosis for severe M. pneumoniae pneumonia with ARDS was achieved with polymerase chain reaction (PCR) or metagenomic next-generation sequencing (mNGS) testing of samples from the lower respiratory tract or pleural effusion. The average PaO2/FiO2 of all patients was 180 mmHg. Of the 10 cases, 4 cases had moderate ARDS (100 mmHg ≤ PaO2/FiO2 < 200 mmHg) and 3 cases had severe ARDS (PaO2/FiO2 < 100 mmHg). High flow nasal cannula (HFNC) was applied in all patients, though only two patients were sufficiently supported with HFNC. Invasive mechanical ventilation (IMV) was required in 5 patients. High resistance (median 15 L/cmH2O/s) and low compliance (median 38 ml/cmH2O) was observed in 4 cases. In these 4 cases, recruitment maneuvers (RM) were applied, with 1 patient demonstrating no response to RM. Prone positioning were applied in 4 cases. Two cases needed ECMO support with median support duration of 5.5 days. No patient in our case series received corticosteroid therapy. All patients were survived and were discharged from hospital. CONCLUSIONS: Early and rapid diagnosis of severe M. pneumoniae pneumonia with ARDS can be achieved with PCR/mNGS tests in samples from the lower respiratory tract or pleural effusion. In our case series, half of M. pneumoniae pneumonia induced ARDS cases were adequately supported with HFNC or NIV, while half of cases required intubation. RM and prone position were effective in 30% of intubated cases, and 20% needed ECMO support. When early anti-mycoplasmal antibiotics were given together with sufficient respiratory support, the survival rate was high with no need for corticosteroid use.

Correction to: The role of high load herpes simplex virus in patients with mechanical ventilation: a real hospital acquired viral lung infection needs antiviral therapy?

An amendment to this paper has been published and can be accessed via the original article.

Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study.

BACKGROUND: Previous studies suggest that prone positioning (PP) can increase PaO2/FiO2 and reduce mortality in moderate to severe acute respiratory distress syndrome (ARDS). The aim of our study was to determine whether the early use of PP combined with non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) can avoid the need for intubation in moderate to severe ARDS patients. METHODS: This prospective observational cohort study was performed in two teaching hospitals. Non-intubated moderate to severe ARDS patients were included and were placed in PP with NIV or with HFNC. The efficacy in improving oxygenation with four support methods-HFNC, HFNC+PP, NIV, NIV+PP-were evaluated by blood gas analysis. The primary outcome was the rate of intubation. RESULTS: Between January 2018 and April 2019, 20 ARDS patients were enrolled. The main causes of ARDS were pneumonia due to influenza (9 cases, 45%) and other viruses (2 cases, 10%). Ten cases were moderate ARDS and 10 cases were severe. Eleven patients avoided intubation (success group), and 9 patients were intubated (failure group). All 7 patients with a PaO2/FiO2 < 100 mmHg on NIV required intubation. PaO2/FiO2 in HFNC+PP were significantly higher in the success group than in the failure group (125 ± 41 mmHg vs 119 ± 19 mmHg, P = 0.043). PaO2/FiO2 demonstrated an upward trend in patients with all four support strategies: HFNC < HFNC+PP ≤ NIV < NIV+PP. The average duration for PP was 2 h twice daily. CONCLUSIONS: Early application of PP with HFNC, especially in patients with moderate ARDS and baseline SpO2 > 95%, may help avoid intubation. The PP was well tolerated, and the efficacy on PaO2/FiO2 of the four support strategies was HFNC < HFNC+PP ≤ NIV < NIV+PP. Severe ARDS patients were not appropriate candidates for HFNC/NIV+PP. TRIAL REGISTRATION: ChiCTR, ChiCTR1900023564. Registered 1 June 2019 (retrospectively registered).

Staphylococcus aureus Pneumonia in the Community.

Staphylococcus aureus is an emergent etiology of community-acquired pneumonia (CAP) over the past 2 decades, with severe community-acquired pneumonia (SCAP) caused by methicillin-resistant S. aureus (MRSA) leading to critical illness and death. S. aureus colonization is associated with a high incidence of pneumonia. Panton-Valentine leukocidin (PVL) is one of the most important virulence factors of S. aureus associated with serious complications. In recent years, community-associated MRSA (CA-MRSA) clones that caused infections in young adults and healthy individuals with no exposure to health care settings and no classical risk factors have emerged. Clinical features at admission including concurrent influenza infection, hemoptysis, multilobar infiltrates, and neutropenia should suggest S. aureus CAP. Sputum Gram stains, cultures (or tracheobronchial aspirates or bronchoalveolar lavage in mechanically ventilated patients), polymerase chain reaction (nasopharyngeal or oropharyngeal or lower respiratory tract specimens), and two sets of blood cultures should be obtained from patients presenting with severe S. aureus CAP. For CAP due to methicillin-susceptible S. aureus, first-line therapy is usually cefazolin, oxacillin, or ceftaroline. For CA-MRSA pneumonia, linezolid is recommended. If vancomycin or teicoplanin are used, combination with clindamycin or rifampicin should be considered in cases of PVL-positive MRSA CAP.

Successful management of refractory respiratory failure caused by avian influenza H7N9 and secondary organizing pneumonia: a case report and literature review.

BACKGROUD: Organizing pneumonia (OP) is a rare complication of influenza infection that has substantial morbidity. We report the first case of OP associated with avian influenza H7N9 infection that had significant improvement with corticosteroid treatment. CASE PRESENTATION: A 35-year-old male admitted to intensive care unit because of respiratory failure. He was diagnosed as severe pneumonia caused by avian influenza H7N9 viral infection. After initial clinical improvement supported by extracorporeal membrane oxygenation (ECMO), the patient's condition worsened with persistent fever, refractory hypoxemia. Chest x-rays and computed tomographies showed areas of consolidation and ground glass opacification. Although OP was suspected and 1 mg/kg methylprednisolone was used, the patient's condition didn't improved considerably. An open lung biopsy was performed, and histopathological examination of the specimen was compatible with OP. The patient was treated with methylprednisolone 1.5 mg/kg for 5 days. ECMO was weaned on day 15, and he was discharged on day 71 with good lung recovery. CONCLUSIONS: To the best of our knowledge, this was the first case of successful management of refractory severe respiratory failure caused by avian influenza H7N9 infection complicated with OP. Refractory hypoxia with clinical manifestation and radiological findings compatible with OP, a differential diagnosis should be considered among patients at the second or third week of influenza H7N9 infection, especially in patients with clinical condition deteriorated after the primary influenza pneumonia was controlled. And a steroid dose of methylprednisolone 1.5 mg/kg may be suggested for treatment of OP associated with avian influenza H7N9 infection.

A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome.

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.

Is Bulpa criteria suitable for the diagnosis of probable invasive pulmonary Aspergillosis in critically ill patients with chronic obstructive pulmonary disease? A comparative study with EORTC/ MSG and ICU criteria.

BACKGROUND: Three diagnostic criteria have been proposed used for invasive pulmonary aspergillosis (IPA) diagnosis, namely EORTC/ MSG criteria, Bulpa criteria and intensive care unit (ICU) criteria. The Bulpa criteria were proposed to diagnose IPA in chronic obstructive pulmonary disease (COPD) patients specially. Our aim is to verify that whether the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients compared with the other two criteria. METHODS: We included critically ill COPD patients admitted to the ICU from April 2006 to August 2013. Patients were classified into four populations: population one (n1 = 59) comprised all included patients; population two (n2 = 24) comprised patients with positive mycological findings (both positive cultures and positive serologic tests); population three (n3 = 18) comprised patients with positive lower respiratory tracts (LRTs) isolation; and population four (n4 = 5) comprised proven IPA patients with histopathology. Patients in four groups were diagnosed as probable IPA using three criteria respectively, and the "diagnostic rate" of each criteria were compared with each other. Then, the reasons for differences in "diagnostic rate" were analyzed in population two. Finally, the modified Bulpa criteria were proposed. RESULTS: Bulpa criteria yielded the highest "diagnostic rate" of probable IPA followed by the ICU criteria, while the EORTC/ MSG criteria provided the lowest rates in four populations (the "diagnostic rate" of probable IPA was 33.9%, 16.9% and 6.8% in population one, p = 0.001; 83.3%, 41.7% and 16.7% in population two, p < 0.001; 100%, 55.6% and 22.2% in population three, p < 0.001; 100%, 60% and 20% in population four, p = 0.036). The reasons for the highest "diagnostic rate" by Bulpa criteria were its less strict requirements regarding the doses/courses of steroid use and typical computed tomography (CT) findings. Finally, the modified Bulpa criteria for probable IPA were proposed for critically ill COPD patients admitted to ICU, mainly involving revised interpretations of microbiological findings. CONCLUSIONS: Among the existing three criteria, the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients admitted to ICU. A modified criteria maybe proposed for better diagnosis,and its clinical validity need to be verified in future studies.

Successful rescue combination of extracorporeal membrane oxygenation, high-frequency oscillatory ventilation and prone positioning for the management of severe methicillin-resistant Staphylococcus aureus pneumonia complicated by pneumothorax: a case report and literature review.

BACKGROUND: To describe the experience of combination therapy with extracorporeal membrane oxygenation(ECMO), high-frequency oscillatory ventilation(HFOV) and prone positioning in treating severe respiratory failure caused by community acquired methicillin resistant Staphylococcus aureus(CA-MRSA). CASE PRESENTATION: A 30-year-old female presented with fever and dyspnea for 3 days. She was diagnosed CA-MRSA pneumonia complicated by severe respiratory failure, pneumothorax and neutropenia. Venovenous ECMO was applied within 8 h of the pneumothorax diagnosis. For amelioration of ventilator-induced lung injury, HFOV and prone positioning were combined with ECMO. The patient's condition improved considerably. ECMO was weaned on day 19, and she was discharged on day 48 with good lung recovery. CONCLUSIONS: To the best of our knowledge, this was the first case in which ECMO was combined with HFOV and prone positioning to treat severe necrotic CA-MRSA pneumonia complicated with pneumothorax. This combination therapy may provide safe respiratory support, may minimize the risk of barotrauma, and provide better drainage of secretions in patients with necrotizing pneumonia.

Successful treatment of severe Pneumocystis pneumonia in an immunosuppressed patient using caspofungin combined with clindamycin: a case report and literature review.

BACKGROUND: Pneumocystis jirovecii is responsible for Pneumocystis pneumonia (PCP), which occurs almost exclusively in immunocompromised individuals. Trimethoprim-sulfamethoxazole (TMP-SMZ) is regarded as the first-line treatment and prophylaxis for P. jirovecii infection, but the frequency of adverse reactions and newly emerged antibiotic resistance limit its use. CASE PRESENTATION: Ulcerations and hemorrhages involving the tongue were noted secondary to TMP-SMZ desensitization against PCP in a 46-year-old male who had previously been diagnosed with IgA nephropathy and sustained prolonged corticosteroid therapy. There was an urgent need for an alternative regimen due to the severe response to TMP-SMZ. The patient was successfully treated with a combination therapy of caspofungin and clindamycin. CONCLUSION: Caspofungin combined with clindamycin is an optional treatment for PCP when treatment with TMP-SMZ fails or in patients who cannot tolerate TMP-SMZ.