Impact of frailty on clinical outcomes in patients with and without COVID-19 pneumonitis admitted to intensive care units in Australia and New Zealand: A retrospective registry data analysis (preprint)

Background It is unclear if the impact of frailty on mortality differs between patients with viral pneumonitis due to COVID-19 or other causes. We aimed to determine if a difference exists between patients with and without COVID-19 pneumonitis.Methods This multicenter, retrospective, cohort study using the Australian and New Zealand Intensive Care Society Adult Patient Database included patients aged ≥ 16 years admitted to 153 ICUs between 01/012020 and 12/31/2021 with admission diagnostic codes for viral pneumonia or acute respiratory distress syndrome, and clinical frailty scale (CFS). The primary outcome was hospital mortality.Results 4,620 patients were studied, 3,077 (66.6%) had COVID-19. The patients with COVID-19 were younger (median [IQR] 57.0 [44.7–68.3] vs. 66.1 [52.0-76.2]; p < 0.001) and less frail (median [IQR] CFS 3 [2–4] vs. 4 [3–5]; p < 0.001), than non-COVID-19 patients. The overall hospital mortality was similar between the patients with and without COVID-19 (14.7% vs. 14.9%; p = 0.82). Frailty alone as a predictor of mortality showed only moderate discrimination in differentiating survivors from those who died but was similar between patients with and without COVID-19 (AUROC 0.68 vs 0.66; p = 0.42). Increasing frailty scores were associated with hospital mortality, after adjusting for Australian and New Zealand Risk-of-Death score and sex. However, the effect of frailty was similar in patients with and without COVID-19 (OR = 1.29; 95%CI 1.19–1.41 vs. OR = 1.24; 95%CI 1.11–1.37).Conclusion The presence of frailty was an independent risk factor for mortality. However, the impact of frailty on outcomes was similar in COVID-19 patients compared to other causes of viral pneumonitis.Trial Registration: Not applicable

A Novel Barrier Device and Method for Protection against Airborne Pathogens During Endotracheal Intubation (preprint)

ABSTRACT Background The risk of SARS-CoV-2 transmission to healthcare workers increases during aerosol-generating procedures such as endotracheal intubation. Objectives We tested the effectiveness of a novel barrier mouthpiece in reducing clinician exposure to aerosols and droplets during endotracheal intubation. Design A prospective case control study was carried out, with a single operator performing eight simulated intubations with and without the device on two different high-fidelity manikin models which produced aerosols and droplets. Setting The study was performed during June 2020, at the Clinical Skills Development Service, Brisbane, Australia. Interventions Simulated scenarios included 1) intubation during cardiopulmonary resuscitation 2) intubation while pre-oxygenating via high flow nasal cannula. Photographic images were obtained during each intubation and digitally analyzed using ImageJ v2.1.0/1.53c. Patients Not applicable. Main outcome measures Aerosol and droplets were quantified using pixel counts. Overall results were expressed as means (± SD), with comparisons between groups made using a two-tailed Student’s T-test under the assumption of unequal variances. A P value of ≤ 0.05 was considered as statistically significant. Results First pass intubation was achieved in all scenarios, with and without the barrier device. Pixel counts demonstrated significant overall reduction in aerosol and droplet exposure when the barrier device was used during intubation [Mean (SD) count:509 (860) vs 10169 (11600); P=0.014]. The highest exposure risk to airborne particles was observed during simulated induction, prior to laryngoscopy and intubation. Conclusions The novel barrier device was effective in reducing environmental exposure to aerosols and droplets during intubation without negatively affecting first pass intubation. The highest risk of exposure to airborne particles was during induction, before intubation takes place. Clinical trials are indicated to further test the feasibility and efficacy of this device. Trial registration Not applicable. KEY POINTS This prospective, preclinical study represents a pilot trial of a novel barrier mouthpiece for reducing clinician exposure to aerosols and droplets during endotracheal intubation. In eight simulated intubations with and without the barrier mouthpiece, the device proved effective in reducing environmental exposure to aerosols and droplets (measured in pixels) during intubation, without negatively affecting first pass intubation. The novel barrier mouthpiece represents a possible solution for reducing the risk of respiratory pathogen transmission during endotracheal intubation without hampering the procedure itself, although larger preclinical and clinical trials are necessary.

Characteristics and Outcomes of Frail Patients with COVID-19 Admitted to ICU: An Individual Patient Data Meta-Analysis (preprint)

Purpose: Frailty is often used in clinical decision-making for patients with COVID-19, yet studies have found variable influence of frailty on outcomes in those admitted to the intensive care unit (ICU). In this individual patient data meta-analysis, we evaluated the characteristics, and outcomes of frail patients admitted to ICU with COVID-19. Methods: : We contacted the corresponding authors of sixteen eligible studies published between December 1 st 2019 and February 28 th 2021 reporting the clinical frailty scale (CFS) in patients with confirmed COVID-19 admitted to ICU. Individual patient data was obtained from 7 studies. We classified patients as non-frail (CFS=1-4) or frail (CFS=5-8). The primary outcome was hospital mortality. We also compared the use of mechanical ventilation (MV) and the proportion of ICU bed-days between frailty categories. Results: : Of the 2001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and sequential organ failure assessment (SOFA) score, CFS ≥4, use of MV, vasopressors, renal replacement therapy and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in frail patients (65.2% vs. 41.8%; p<0.001), with adjusted mortality increasing with a rising CFS score beyond 3. Younger and non-frail patients were more likely to receive MV. Frail patients spent less time on MV (median days [IQR] 9 [5-16] vs. 11 [6-18]; p=0.012) and accounted for only 12.3% of total ICU bed-days. Conclusion: Frail patients with COVID-19 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with non-frail patients. Frail patients receiving MV were at greater risk of death than non-frail patients. Systematic review registration: Registration protocol in PROSPERO (CRD42020224255).

Extracorporeal Membrane Oxygenation for COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. Methods: : We searched MEDLINE, Embase, Cochrane, and Scopus databases from 1 st December 2019 to 10 th January 2021 for observational studies or randomized clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and metaregression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. Results: : We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI: 32.3%-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI: 30.7%-40.7%, high certainty). Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI: 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI:50.5%-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. Conclusion: Majority of patients received ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1%, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS.PROSPERO CRD42020192627

Extracorporeal Membrane Oxygenation in the Middle East and India During the COVID-19 Pandemic (preprint)

Background: Extracorporeal membrane oxygenation (ECMO) use for severe Coronavirus disease 2019 (COVID-19) patients has evolved during the course of the pandemic. Early uncertainty regarding the role of ECMO during the current pandemic was based on the suboptimal initial experiences. However, more recent data suggests favorable outcomes in COVID-19 patients receiving ECMO support. We aimed to explore the epidemiology and outcomes of ECMO for COVID-19 related cardiopulmonary failure and evaluate outcomes of new centers versus established ones.Methods: This is a retrospective, multicenter international, observational study conducted in (19) ECMO centers in five countries from March 1, 2020, to September 30, 2020. We included 307 patients with COVID-19 who received ECMO for refractory hypoxemia and severe respiratory acidosis with or without circulatory failure. Data collection included Patients characteristics, demographic data, ECMO-related specific data, pre-ECMO patient condition, 24 hours post-ECMO initiation data, and outcome. The primary outcome is survival to home discharge. Secondary outcomes include mortality during ECMO, survival to decannulation, and outcomes stratified by center type in which patients were treated.Findings: Three hundred and seven COVID-19 patients received ECMO support during the study period. The median age was 45 years (37-52 IQR), and 81% were men. 178 (58%) patients survived ECMO, of whom 138 (45%) patients were discharged home, and 40 patients (13%) died post-ECMO decannulation while 128 patients (41.7%) died during ECMO. Patient outcomes in the new centers developed in response to the pandemic were similar to those of established centers.Interpretation: During pandemics, ECMO may provide favorable outcomes in highly select patients as resources allow. Outcomes in ECMO centers established during the pandemic were comparable to existing centers.Funding Statement: None.Declaration of Interests: Kiran Shekar acknowledges research support from the Metro North Hospital and Health Service and the Prince Charles Hospital Foundation. Dr. Brodie receives research support from ALung Technologies. He has been on the medical advisory boards for Baxter, Abiomed, Xenios, and Hemovent and is the President-Elect of the Extracorporeal Life Support Organization (ELSO). Dr. Combes reported receiving grants and personal fees from Maquet, Xenios, and Baxter and serving as the recent past president of the EuroELSO organization. Other authors have no conflict of interest.Ethics Approval Statement: After the SWAAC ELSO steering committee's authorization, IRB approval was obtained from the coordinating center King Saud Medical City in Riyadh - Saudi Arabia. The country representatives obtained IRB approval for each participating center as well.

Prone Positioning of Non-intubated Patients with COVID-19 - A Systematic Review and Meta-analysis (preprint)

Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.Methods: We searched PubMed, Embase and the COVID-19 living systematic review from December 1, 2019 to July 23, 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult patients with COVID-19. Primary outcome measureed was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports during PP, and frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2 (MD 37.6, 95% CI 18.8-56.5); PaO2 (MD 30.4 mmHg, 95% CI 10.9 to 49.9); and SpO2 (MD 5.8%, 95% CI 3.7 to 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95% CI -3.5 to 84.6) vs. 37, 95% CI 17.1 to 56.9). Respiratory rate decreased post-PP (MD -2.9, 95% CI -5.4 to -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. There were no major adverse events reported. Conclusions: Despite the significant variability in frequency and duration of PP and respiratory supports applied, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. The results are limited by lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registration: Registration/protocol in PROSPERO (CRD42020194080).

Prone positioning of non-intubated patients with COVID-19 - A Systematic Review and Meta-analysis (preprint)

Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes. Methods: We searched PubMed, Embase and COVID-19 living systematic review from December1st 2019 to July23rd 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult COVID-19 patients. Primary outcome measure was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports, frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2, (MD 37.6, 95%CI 18.8, 56.5); PaO2, , (MD 30.4 mmHg, 95%CI 10.9, 49.9); and SpO2, (MD 5.8%, 95%CI 3.7, 7.9). Patients with a pre-PP PaO2/FiO2 [≤]150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95%CI -3.5, 84.6) vs. 37, 95%CI 17.1, 56.9). Respiratory rate decreased post-PP (MD -2.9, 95%CI -5.4, -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. No major adverse events were reported. Conclusions: Despite significant variability in frequency and duration of PP and respiratory supports, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. Major limitation being lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.

Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection prevention strategies in healthcare workers (preprint)

Background: Clinical guidelines on infection prevention strategies in healthcare workers (HCWs) play an important role in protecting them during the SARS-CoV-2 pandemic. Poorly constructed guidelines that are not comprehensive and are ambiguous may compromise HCWs safety. We aimed to develop and validate a tool to appraise guidelines on infection prevention strategies in HCWs. Methods: A 3-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was utilised. We validated the tool by appraising 40 international, specialty-specific and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. Results: Overall consensus (>75%) was reached at the end of three rounds for all six domains included in the tool. The chosen domains allowed appraisal of guidelines in relation to general characteristics (domain-1), recommendations on engineering (domain-2) and administrative aspects (domain 4-6) of infection prevention, as well as personal protection equipment (PPE) use (domain-3). The appraisal tool performed well across all domains and inter-rater agreement was excellent. All included guidelines performed relatively better in domains 1-3 compared with domains 4-6 and this was more evident in guidelines originating from lower income countries. Conclusion: The guideline appraisal tool was robust and easy to use. Recommendations on engineering aspects of infection prevention, administrative measures that promote optimal PPE use and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high quality HCW infection prevention guidelines during SARS-CoV-2 pandemic and may also provide a framework for future guideline development.

Feasibility of non-invasive nitric oxide inhalation in acute hypoxic respiratory failure: potential role during the COVID-19 pandemic (preprint)

Acute hypoxemic respiratory failure (ARF) is characterized by both lower arterial oxygen and carbon dioxide tensions in the blood. First line treatment for ARF includes oxygen therapy,intially admininstered non invasively using nasal prongs, high flow nasal cannulae or masks. Invasive mechancial ventilation (IMV) is usually reserved for patients who are unable to maintain their airway, those with worsening hypoxemia, or those who develop respiratory muscle fatigue and consequent hypercapnia. Inhaled nitric oxide (iNO) gas is known to improve oxygenation in patients with ARF by manipulating ventilation-perfusion matching. Addition of iNO may potentially alleviate the need for IMV in selected patients. This article demonstrates the feasibility of this technique based on our experience of patients with hypoxemic ARF. This technique may also be considered for patients with hypoxic ARF in setting of COVID-19.

Variations in Personal Protective Equipment Preparedness in Intensive Care Units during the COVID-19 Pandemic: A Survey of Asia-Pacific Countries (preprint)

Objectives: To evaluate PPE-preparedness across intensive care units (ICUs) in 6 Asia-Pacific countries. PPE-preparedness was defined as the adherence to guidelines, training HCWs, procuring PPE stocks and responding appropriately to a suspected case (transportation and admission to hospital). Design: Cross-sectional web-based survey. Setting: ICUs in Australia, New Zealand (NZ), Singapore, Hong Kong (HK), India and Philippines with a 24/7 Emergency/Casualty Department, and capable of mechanically ventilating patients for more than 24 hours. Interventions: Questionnaire sent to intensivists in 633 Level II/III ICUs in 6 Asia-Pacific countries by email, WhatsApp and text messaging. Main outcome measures: 263 intensivists responded, of whom 231 were eligible for analysis. Response rates were 68%-100% in all countries except India, where it was 24%. 97% either conformed to or exceeded WHO recommendations for PPE-practice. 59% employed airborne precautions irrespective of aerosol-generation-procedures. There were variations in negative-pressure room use (highest in HK/Singapore), training (best in NZ), and PPE stock-awareness (best in HK/Singapore/NZ). High-flow-nasal-oxygenation and non-invasive ventilation were not options in most HK (66.7%, 83.3% respectively) and Singapore ICUs (50%, 80% respectively), but were considered in other countries to a greater extent. 38% reported not having specialized airway teams. Showering and buddy-systems were underutilized. Clinical waste disposal training was suboptimal (38%). Conclusions: Most intensivists from six Asia-Pacific countries appeared to be aware of the WHO PPE-guidelines by either conforming to/exceeding the recommendations. Despite this, there were widespread variabilities across ICUs and countries in several domains, particularly related to PPE-training and preparedness. Standardising PPE guidelines may translate to better training, better compliance and policies that improve HCW safety. Adopting low-cost approaches such as buddy-systems should be encouraged. More importantly, better pandemic preparedness and building systems with deeply embedded culture of safety is essential to ensure the safety and well-being of HCWs during such pandemics.