Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update.

The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

A microfluidic device for real-time on-demand intravenous oxygen delivery.

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

The use of eculizumab in ventilator-dependent myasthenia gravis patients.

INTRODUCTION/AIMS: Eculizumab has been shown to be efficacious in acetylcholine receptor antibody-positive (AChR+ ) Myasthenia Gravis Foundation of America (MGFA) class II, III, and IV generalized myasthenia gravis (gMG) patients. However, it has not been studied in MGFA class V gMG patients. METHODS: We report three AChR+ , refractory, MGFA class V gMG patients treated with eculizumab. MGFA class, MG-Composite (MGC) score and MG Activities of Daily Living (MG-ADL) score were assessed before and after eculizumab. RESULTS: Two of three gMG patients, refractory to intravenous immunoglobulin, plasmapheresis, prednisone, and (in one case) rituximab, showed a robust response to eculizumab with marked improvement in MGFA, MG-ADL, and MGC measures. The third patient showed a partial response to eculizumab but remained on noninvasive ventilation and gastrostomy intubation. Patients 1 and 2 achieved minimal manifestation status at week 4 and week 6, respectively, and showed continued improvement on MG-ADL and MGC scores through weeks 55 and 43, respectively, with eculizumab. The third patient showed a partial response at week 10, followed by a slight decline in his MG-ADL score, but noted a slow but an incomplete improvement afterward on MG-ADL and MGC scores, possibly due to delayed eculizumab infusion. DISCUSSION: Eculizumab may play a role in the treatment of patients with MGFA class V, refractory gMG. Larger studies are required to provide further evidence.

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.

Incidence, Characteristics, and Outcomes of Ventilator-associated Events during the COVID-19 Pandemic.

Rationale: Ventilator-associated event (VAE) surveillance provides an objective means to measure and compare complications that develop during mechanical ventilation by identifying patients with sustained increases in ventilator settings after a period of stable or decreasing ventilator settings. The impact of the coronavirus disease (COVID-19) pandemic on VAE rates and characteristics is unknown. Objectives: To compare the incidence, causes, and outcomes of VAE during the COVID-19 pandemic year versus prepandemic years and among ventilated patients with and without COVID-19. Methods: In this retrospective cohort study of mechanically ventilated adults at four academic and community hospitals in Massachusetts, we compared VAE incidence rates between March 1 and August 31 for each year from 2017 to 2020 (corresponding to the time frame of the pandemic first wave in 2020) and among COVID-19-positive and COVID-19-negative patients in 2020. The medical records of 200 randomly selected patients with VAEs in 2020 (100 with COVID-19 and 100 without COVID-19) were analyzed to compare conditions precipitating VAEs in patients with versus without COVID-19. Results: VAEs per 100 episodes of mechanical ventilation were more common in 2020 than in prior years (11.2 vs. 6.7; P < 0.01) but the rate of VAEs per 1,000 ventilator-days was similar (14.2 vs. 12.7; P = 0.08). VAEs were more frequent in COVID-19-positive patients than in COVID-19-negative patients in 2020 (29.0 vs. 7.1 per 100 ventilator episodes [P < 0.01] and 17.2 vs. 12.2 per 1,000 ventilator-days [P < 0.01]). Compared with patients without COVID-19 with VAEs, patients with COVID-19 and VAEs had similar rates of infection-related ventilator-associated complications, longer median durations of mechanical ventilation (22 vs. 14 d; P < 0.01), and similar in-hospital mortality (30% vs. 38%; P = 0.15). Progressive acute respiratory distress syndrome (ARDS) accounted for 53% of VAEs in patients with COVID-19, whereas it accounted for 14% of VAEs among patients without COVID-19. Conclusions: VAE rates per 100 episodes of mechanical ventilation and per 1,000 ventilator-days were higher among COVID-19-positive patients than among COVID-19-negative patients. Over 50% of VAEs in patients with COVID-19 were caused by progressive ARDS, whereas less than 15% of VAEs in patients without COVID-19 were caused by progressive ARDS. These findings provide insight into the natural history of COVID-19 in ventilated patients and may inform targeted strategies to mitigate complications in this population.

Simultaneous ventilation in the Covid-19 pandemic. A bench study.

COVID-19 pandemic sets the healthcare system to a shortage of ventilators. We aimed at assessing tidal volume (VT) delivery and air recirculation during expiration when one ventilator is divided into 2 test-lungs. The study was performed in a research laboratory in a medical ICU of a University hospital. An ICU (V500) and a lower-level ventilator (Elisée 350) were attached to two test-lungs (QuickLung) through a dedicated flow-splitter. A 50 mL/cmH2O Compliance (C) and 5 cmH2O/L/s Resistance (R) were set in both A and B test-lungs (A C50R5 / B C50R5, step1), A C50-R20 / B C20-R20 (step 2), A C20-R20 / B C10-R20 (step 3), and A C50-R20 / B C20-R5 (step 4). Each ventilator was set in volume and pressure control mode to deliver 800mL VT. We assessed VT from a pneumotachograph placed immediately before each lung, pendelluft air, and expiratory resistance (circuit and valve). Values are median (1st-3rd quartiles) and compared between ventilators by non-parametric tests. Between Elisée 350 and V500 in volume control VT in A/B test- lungs were 381/387 vs. 412/433 mL in step 1, 501/270 vs. 492/370 mL in step 2, 509/237 vs. 496/332 mL in step 3, and 496/281 vs. 480/329 mL in step 4. In pressure control the corresponding values were 373/336 vs. 430/414 mL, 416/185 vs. 322/234 mL, 193/108 vs. 176/ 92 mL and 422/201 vs. 481/329mL, respectively (P<0.001 between ventilators at each step for each volume). Pendelluft air volume ranged between 0.7 to 37.8 ml and negatively correlated with expiratory resistance in steps 2 and 3. The lower-level ventilator performed closely to the ICU ventilator. In the clinical setting, these findings suggest that, due to dependence of VT to C, pressure control should be preferred to maintain adequate VT at least in one patient when C and/or R changes abruptly and monitoring of VT should be done carefully. Increasing expiratory resistance should reduce pendelluft volume.

Emergency ventilator for COVID-19.

The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient's peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.

A systematic review and meta-analysis of the use of renin-angiotensin system drugs and COVID-19 clinical outcomes: What is the evidence so far?

Conflicting evidence exists about the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID-19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID-19-related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta-analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID-19 were included. Studies' quality was appraised using the Newcastle-Ottawa Scale. Data were analyzed using the random-effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I2 statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID-19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15), and hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization among USA studies (OR:1.59; 95%CI:1.03,2.44), peer-reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID-19 infection (OR:0.24; 95%CI: 0.17,0.34). In conclusion, high-quality evidence exists for the effect of ACEIs/ARBs on some COVID-19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.

Incidence of Barotrauma in Patients With COVID-19 Pneumonia During Prolonged Invasive Mechanical Ventilation - A Case-Control Study.

BACKGROUND: SARS-CoV2 can cause pulmonary failure requiring prolonged invasive mechanical ventilation (MV). Lung protective ventilation strategies are recommended in order to minimize ventilator induced lung injury. Whether patients with COVID-19 have the same risk for complications including barotrauma is still unknown. Therefore, we investigated barotrauma in patients with COVID-19 pneumonia requiring prolonged MV. METHODS: All patients meeting diagnosis criteria for ARDS according to the Berlin Definition, with PCR positive SARS-CoV2 infection and prolonged mechanical ventilation, defined as ≥2 days, treated at our ARDS referral center between March and April 2020 were included in a retrospective registry analysis. Complications were detected by manual review of all patient data including respiratory data, imaging studies, and patient files. RESULTS: A total of 20 patients with severe COVID-19 pulmonary failure (Overall characteristics: median age: 61 years, female gender 6, median duration of MV 22 days) were analyzed. Eight patients (40%) developed severe barotrauma during MV (after median 18 days, range: 1-32) including pneumothorax (5/20), pneumomediastinum (5/20), pneumopericard (1/20), and extended subcutaneous emphysema (5/20). Median respirator settings 24 hours before barotrauma were: Peak inspiratory pressure (Ppeak) 29 cm H2O (range: 27-35), positive end-expiratory pressure (PEEP) 14 cm H2O (range: 5-24), tidal volume (VT) 5.4ml/kg predicted body weight (range 0.4-8.6), plateau pressure (Pplateau) 27 cm H2O (range: 19-30). Mechanical ventilation was significantly more invasive on several occasions in patients without barotrauma. CONCLUSION: Barotrauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data suggest that barotrauma in COVID-19 may occur even when following recommendations for lung protective MV.

Reusable respirators as personal protective equipment during ENT surgery.

BACKGROUND: Robust personal protective equipment is essential in preventing the transmission of coronavirus disease 2019 to head and neck surgeons who are routinely involved in aerosol generating procedures. OBJECTIVE: This paper describes the collective experience, across 3 institutes, of using a reusable half-face respirator in 72 head and neck surgery cases. METHOD: Cost analysis was performed to demonstrate the financial implications of using a reusable respirator compared to single-use filtering facepiece code 3 masks. CONCLUSION: The reusable respirator is a cost-effective alternative to disposable filtering facepiece code 3 respirators. Supplying reusable respirators to individual staff members may increase the likelihood of them having appropriate personal protective equipment during their clinical duties.