Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review.

Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

How to manage isolated tension non-surgical pneumoperitonium during bronchoscopy? A case report.

BACKGROUND: Tension pneumoperitonium is a rare complication during bronchoscopy that can cause acute respiratory and hemodynamic failure, with fatal consequences. Isolated pneumoperitonium during bronchoscopy usually results from ruptures of the abdominal viscera that need surgical repair. Non-surgical pneumoperitoneum (NSP) refers to some pneumoperitoneum that could be relieved without surgery and only by conservative therapy. However, the clinical experience of managing tension pneumoperitonium during bronchoscopy is limited and controversial. CASE SUMMARY: A 51-year-old female was admitted to our hospital for cough with bloody sputum of seven days. On the 8th day of her admission, a bronchoscopy was arranged for bronchial-alveolar lavage to detect possible pathogens in the lower respiratory tract, as oxygen was delivered via a 12 F nasopharyngeal cannula, approximately 5-6 cm from the tip of the catheter, with a flow rate of 5-10 L/min. After four minutes of bronchoscopy, the patient suddenly vomited 20 mL of water, followed by severe abdominal pain, while physical examination revealed obvious abdominal distension, as well as hardness and tenderness of the whole abdomen, which was considered pneumoperitonium, and the bronchoscopy was terminated immediately. A computer tomography scan indicated isolated tension pneumoperitonium, and abdominal decompression was performed with a drainage tube, after which her symptoms were relieved. A multidisciplinary expert consultation discussed her situation and a laparotomy was suggested, but finally refused by her family. She had no signs of peritonitis and was finally discharged 5 d after bronchoscopy with a good recovery. CONCLUSION: The possibility of tension pneumoperitonium during bronchoscopy should be guarded against, and given its serious clinical consequences, cardiopulmonary instability should be treated immediately. Varied strategies could be adopted according to whether it is complicated with pneumothorax or pneumomediastinum, and the presence of peritonitis. When considering NSP, conservative therapy maybe a reasonable option with good recovery. An algorithm for the management of pneumoperitonium during bronchoscopy is proposed, based on the features of the case series reviewed and our case reported.

Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP. METHODS: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care. RESULTS: A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) (P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant. CONCLUSIONS: APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients.

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.

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis.

BACKGROUND: The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA. METHODS: COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA. RESULTS: Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ±â€Š16.12]% vs. [17.92 ±â€Š4.91]%, P = 0.02) and serum IL-17 (17.96 ±â€Š9.59 pg/mL vs. 8.05 ±â€Š4.44 pg/mL, P = 0.02), but blood ([5.18 ±â€Š1.09]% vs. [4.15 ±â€Š0.87]%, P = 0.28) and lung levels of Th17 cells ([1.98 ±â€Š0.83]% vs. [2.03 ±â€Š0.98]%, P = 0.91), lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [9.63 ±â€Š5.98]%, P = 0.49) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 68.70 ±â€Š15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ±â€Š1.09]% vs. [9.21 ±â€Š3.56]%, P = 0.01) and lung Th17 cells ([1.98 ±â€Š0.83]% vs. [6.29 ±â€Š1.11]%, P = 0.01) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 154.90 ±â€Š64.60 pg/mL, P = 0.01) and IL-17 (17.96 ±â€Š9.59 pg/mL vs. 39.81 ±â€Š22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ±â€Š16.12]% vs. [29.86 ±â€Š15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [15.10 ±â€Š2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ±â€Š944,480.43 vs. 892,958.10 ±â€Š686,808.80, t = 2.32, P = 0.02). CONCLUSION: These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.

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.

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.

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.

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.

High-Flow Nasal Cannula: A Promising Oxygen Therapy for Patients with Severe Bronchial Asthma Complicated with Respiratory Failure.

Severe bronchial asthma complicated with respiratory failure, a common critical illness in respiratory medicine, may be life-threatening. High-flow nasal cannula (HFNC) is a novel oxygen therapy technique developed in recent years. HFNC was applied in this study for treating adult patients with severe bronchial asthma complicated with respiratory failure. Its efficacy was analyzed comparatively to conventional oxygen therapy (COT). HFNC and COT were randomly performed based on conventional treatment. The HFNC group was similar to COT-treated patients in terms of response rate, with no significant difference in efficacy between the two groups. In patients with bronchial asthma, effectively increased PO2 and reduced PCO2 were observed after treatment in both groups. However, HFNC was more efficient than COT in elevating PO2 in patients with severe bronchial asthma complicated with respiratory failure, while no statistically significant difference in PCO2 reduction was found between the two groups. Heart rate (HR) and respiratory rate (RR) between the two groups on admission (0 h) and at 2, 8, 24, and 48 h after admission were compared. Both indicators significantly decreased with time. No significant differences in HR and RR were found between the groups at 0, 2, and 8 h after admission. However, these indicators were significantly lower in the HFNC group compared with the COT group at 24 and 48 h after admission. HFNC could significantly elevate PO2 and reduce HR and RR. Thus, it is a promising option for patients with severe bronchial asthma complicated with respiratory failure.

Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies.

BACKGROUND: Evidence supporting corticosteroids adjunctive treatment (CAT) for Pneumocystis jirovecii pneumonia (PCP) in non-HIV patients is highly controversial. We aimed to systematically review the literature and perform a meta-analysis of available data relating to the effect of CAT on mortality of PCP in non-HIV patients. METHODS: We searched Pubmed, Medline, Embase, and Cochrane database from 1989 through 2019. Data on clinical outcomes from non-HIV PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. We analyzed the impact of CAT on mortality of non-HIV PCP in the whole PCP population, those who had hypoxemia (PaO2 < 70 mmHg) and who had respiratory failure (PaO2 < 60 mmHg). RESULTS: In total, 259 articles were identified, and 2518 cases from 16 retrospective observational studies were included. In all non-HIV PCP cases included, there was an association between CAT and increased mortality (odds ratio, 1.37; 95% confidence interval 1.07-1.75; P = 0.01). CAT showed a probable benefit of decreasing mortality in hypoxemic non-HIV PCP patients (odds ratio, 0.69; 95% confidence interval 0.47-1.01; P = 0.05). Furthermore, in a subgroup analysis, CAT showed a significantly lower mortality in non-HIV PCP patients with respiratory failure compared to no CAT (odds ratio, 0.63; 95% confidence interval 0.41-0.95; P = 0.03). CONCLUSIONS: Our meta-analysis suggests that among non-HIV PCP patients with respiratory failure, CAT use may be associated with better clinical outcomes, and it may be associated with increased mortality in unselected non-HIV PCP population. Clinical trials are needed to compare CAT vs no-CAT in non-HIV PCP patients with respiratory failure. Furthermore, CAT use should be withheld in non-HIV PCP patients without hypoxemia.

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).