Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis

Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

Cutting out Cholecystectomy on Index Hospitalization Leads to Increased Readmission Rates, Morbidity, Mortality and Cost

Biliary tract diseases that are not adequately treated on index hospitalization are linked to worse outcomes, including high readmission rates. Delays in care for conditions such as choledocholithiasis, gallstone pancreatitis, and cholecystitis often occur due to multiple reasons, and this delay is under-appreciated as a source of morbidity and mortality. Our study is based on the latest Nationwide Readmissions Database review and evaluated the effects of postponing definitive management to a subsequent visit. The study shows a higher 30-day readmission rate in addition to increased mortality rate, intubation rate, vasopressor use in this patient population and significantly added financial burden.

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.

Implementation of noninvasive neurally adjusted ventilatory assist in pediatric acute respiratory failure: a controlled before-after quality improvement study

Backgrounds Pediatric noninvasive neurally adjusted ventilatory assist (NIV-NAVA) has been shown to improve patient-ventilator interaction but no data on clinical outcomes are available. Aim of this study was to compare NIV-NAVA with noninvasive pressure support (NIV-PS) in children with acute hypoxemic respiratory failure (AHRF), in a single-center before-after study. A cohort of thirty-four NIV-PS patients (before group) admitted to our PICU within the 2 years prior NAVA introduction was compared with a cohort of thirty children treated with NIV-NAVA during implementation phase (after group). The primary end-point was intubation rate between groups. Days on mechanical ventilation, number of invasive devices, nosocomial infections, PICU/hospital length of stay (LOS), and physiological parameters at 2 and 24 h after admission were considered. Results Intubation rate was lower in the NIV-NAVA group as compared to the NIV-PS group (p = 0.006). Patients treated with NIV-NAVA required fewer invasive devices (p = 0.032) and had lower incidence of ventilator-acquired pneumonia (p = 0.004) and shorter PICU (p = 0.032) and hospital LOS (p = 0.013). At 2 h, NIV-NAVA compared with NIV-PS resulted in higher paO2:FIO2 (p = 0.017), lower paCO2 (p = 0.002), RR (p = 0.026), and HR (p = 0.009). Conclusions Early NIV-NAVA vs NIV-PS was associated to lower intubation rate and shorter PICU and hospital LOS. Further studies are needed in order to confirm these preliminary data.

Comparison of patients with acute ischemic stroke with and without COVID-19

Objectives: Information on the incidence of acute ischemic stroke (AIS), which is an important cause of morbidity and mortality, its association with COVID-19, and its course in infected patients in this pandemic period is limited. In this study, it was aimed to compare the demographic, clinical and stroke characteristics, and the laboratory, prognosis and mortality findings of patients with AIS with and without COVID-19. Methods: This study included 43 patients with a positive nasopharyngeal PCR test who were followed up for AIS, and 70 patients without COVID-19 who were followed up for AIS during the same period from the Konya Numune State Hospital, Turkey. Results: Poor prognosis and mortality were found to be significantly higher in the AIS group with COVID-19 compared with the non-COVID-19 AIS group. In the AIS group with COVID-19, a higher rate of intensive care unit (ICU) need (40% vs. 5%), higher intubation rate (35% vs. 3%) and longer hospital stay (12.9 ± 10.8 vs. 6.6 ± 4.0 days) were observed. In the laboratory examinations, C-reactive protein, ferritin, D-dimer, troponin, and lactate dehydrogenase levels were found to be significantly higher in patients with AIS who were positive for COVID-19. An increase in D-dimer, ferritin and thrombocytopenia were found to be associated with mortality in the COVID-19 positive AIS group. Conclusion: Patients with AIS and COVID-19 had a higher rate of ICU need, higher intubation rate, longer hospital stay, higher mortality, and poorer prognosis than those without COVID-19. High levels of ferritin, D-dimer and fibrin degradation products were associated with a poor prognosis.

The COVID-19 pandemic: the effect on airway Management in non-COVID emergency patients

Background During the COVID-19 outbreak, healthcare providers might have avoided droplet/aerosol-generating procedures, such as non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) due to the concern of themselves being infected. We hypothesized that this change of practice could have also occurred to other non-COVID-infected patients in the Emergency Department (ED). Methods A retrospective analytic study was conducted in the ED of Siriraj Hospital, Bangkok, Thailand, including adult patients presenting with signs and symptoms of respiratory distress between 1 March and 30 April 2020 (the COVID period). A comparison group using the same inclusion criteria was retrieved from 1 March to 30 April 2019 (the pre-COVID period). The primary outcome was rate of NIV and HFNC use. The secondary outcomes were rate of intubation, failure of NIV and HFNC, complications, and mortality. Results A total of 360 and 333 patients were included during the pre-COVID and COVID periods, respectively. After adjusting for baseline differences, patients in the COVID period were less likely to receive either NIV or HFNC than the pre-COVID period (adjusted OR 0.52 [95%CI 0.29–0.92]). Overall, intubation rate was similar between the two study periods. However, patients in respiratory distress with pulmonary edema had a relatively higher intubation rate in the COVID period. There were higher failure rates of NIV and HFNC, more infectious complications, and a higher rate of mortality in the pre-COVID period. Conclusion During the COVID-19 pandemic, the overall usage of NIV and HFNC in emergency non-COVID patients decreased. Although not affecting the overall intubation rate, this change of practice could have affected some groups of patients. Therefore, treatment decisions based on a balance between the benefits to the patients and the safety of healthcare providers should be made.

Prone Positioning Is Safe and May Reduce the Rate of Intubation in Selected COVID-19 Patients Receiving High-Flow Nasal Oxygen Therapy

Background: Patients with COVID-19 may experience hypoxemic Acute Respiratory Failure (hARF) requiring O2-therapy by High-Flow Nasal Cannula (HFNO). Although Prone Positioning (PP) may improve oxygenation in COVID-19 non-intubated patients, the results on its clinical efficacy are controversial. The present study aims to prospectively investigate whether PP may reduce the need for endotracheal intubation (ETI) in patients with COVID-19 receiving HFNO. Methods: All consecutive unselected adult patients with bilateral lung opacities on chest X-ray receiving HFNO after admission to a SARS-CoV-2 Respiratory Intermediate Care Unit (RICU) were considered eligible. Patients who successfully passed an initial PP trial (success group) underwent PP for periods ≥ 2 h twice a day, while receiving HFNO. The study’s primary endpoint was the intubation rate during the stay in the RICU. Results: Ninety-three patients were included in the study. PP was feasible and safe in 50 (54%) patients. Sixteen (17.2%) patients received ETI and 27 (29%) escalated respiratory support, resulting in a mortality rate of 9/93 (9.7%). The length of hospital stay was 18 (6–75) days. In 41/50 (80%) of subjects who passed the trial and underwent PP, its use was associated with clinical benefit and survival without escalation of therapy. Conclusions: PP is feasible and safe in over 50% of COVID-19 patients receiving HFNO for hARF. Randomized trials are required to confirm that PP has the potential to reduce intubation rate.

Efficacy of High-flow Nasal Cannula Oxygen Therapy in Patients with Mild Hypercapnia

Objectives: To investigate the indications of high-flow nasal cannula (HFNC) oxygen therapy among patients with mild hypercapnia and to explore the predictors of intubation when HFNC fails.Methods: This retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients with mild hypercapnia (45<PaCO2≤60 mmHg) received either HFNC or noninvasive ventilation (NIV) oxygen therapy. Propensity score matching (PSM) was implemented to increase between-group comparability. The Kaplan-Meier method was used to estimate overall survival and cumulative intubation rates, while 28-day mortality, 48-hour and 28-day intubation rates were compared using the Chi-square test. The predictive performances of HR/SpO2 and the ROX index (the ratio of SpO2/FiO2 to respiratory rate) at 4 hours were assessed regarding HFNC failure, which was determined if intubation was given within 48 hours after the initiation of oxygen therapy. The area under the receiver operating characteristic curve (AUC) for HR/SpO2 and the ROX index were calculated and compared.Results: A total of 524,520 inpatient hospitalization records were screened, 106 patients in HFNC group and 106 patients in NIV group were successfully matched. No significant difference in 48-hour intubation rate between the HFNC group and the NIV group (14.2% vs. 8.5%, P=0.278); patients receiving HFNC had higher 28-day intubation rate (26.4% vs. 14.2%, P=0.029), higher 28-day mortality (17.9% vs. 8.5%, P=0.043), longer ICU length of stay (4.4 vs. 3.3 days, P=0.019), compared to those of NIV group. The AUC of HR/SpO2 at 4 hours after the initiation of HFNC yielded around 0.660 for predicting 48-hour intubation, greater than that of the ROX index with an AUC of 0.589 (P<0.01).Conclusions: HFNC therapy cannot completely replace NIV for patients with mild hypercapnia. As opposed to the ROX index, a modest, yet improved predictive performance is demonstrated using HR/SpO2 in predicting the failure of HFNC among these patients.