Initiation Of Invasive Mechanical Ventilation Research Articles

Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study

ABSTRACT Background Since the end of 2022, Azvudine was widely used to treat hospitalized novel coronavirus disease 2019 (COVID-19) patients in China. However, data on the clinical effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. Methods From 1 November 2022 to 1 July 2023, we conducted a single-center retrospective cohort study based on hospitalized COVID-19 patients from a tertiary hospital in Shihezi, China, recruiting laboratory-confirmed hospitalized patients with SARS-CoV-2 infection. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients undergone usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use upon admission, and complete blood cell count. The primary outcomes were all-cause death and PCC at short-term (60 days) post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on the matched covariates. Results A total of 2,639 hospitalized patients diagnosed with COVID-19 were initially identified, and 2,069 patients were screened following the exclusion criteria. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was lower in the Azvudine group than in the control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significant lower risk of death and the use of Azvudine was associated with a reduced risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses indicated a significant effectiveness of Azvudine against the risk of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical difference were not observed between Azvudine group and control group in the invasive mechanical ventilation and short-term and long-term PCC. Conclusions The present findings indicate that receipt of Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection a in real-world setting. Further research is urgently needed to validate the effectiveness of Azvudine on the PCC.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study

Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Early detection of deterioration in COVID-19 patients by continuous ward respiratory rate monitoring: a pilot prospective cohort study.

Tachypnea is among the earliest signs of pulmonary decompensation. Contactless continuous respiratory rate monitoring might be useful in isolated COVID-19 patients admitted in wards. We therefore aimed to determine whether continuous monitoring of respiratory patterns in hospitalized patients with COVID-19 predicts subsequent need for increased respiratory support. Single-center pilot prospective cohort study in COVID-19 patients who were cared for in routine wards. COVID-19 patients who had at least one escalation of pulmonary management were matched to three non-escalated patients. Contactless respiratory monitoring was instituted after patients enrolled, and continued for 15 days unless hospital discharge, initiation of invasive mechanical ventilation, or death occurred. Clinicians were blinded to respiratory rate data from the continuous monitor. The exposures were respiratory features over rolling periods of 30 min, 24 h, and 72 h before respiratory care escalation. The primary outcome was a subsequent escalation in ventilatory support beyond a Venturi mask. Among 125 included patients, 13 exhibited at least one escalation and were each matched to three non-escalated patients. A total of 28 escalation events were matched to 84 non-escalation episodes. The 30-min mean respiratory rate in escalated patients was 23 breaths per minute (bpm) ranging from 13 to 40 bpm, similar to the 22 bpm in non-escalated patients, although with less variability (range 14 to 31 bpm). However, higher respiratory rate variability, especially skewness over 1 day, was associated with higher incidence of escalation events. Our overall model, based on continuous data, had a moderate accuracy with an AUC 0.81 (95%CI: 0.73, 0.88) and a good specificity 0.93 (95%CI: 0.87, 0.99). Our pilot observational study suggests that respiratory rate variability as detected with continuous monitoring is associated with subsequent care escalation during the following 24 h. Continuous respiratory monitoring thus appears to be a valuable increment over intermittent monitoring. Our study was the initial evaluation of Circadia contactless respiratory monitoring in COVID-19 patients who are at special risk of pulmonary deterioration. The major limitation is that the analysis was largely post hoc and thus needs to be confirmed in an out-of-sample population.

Convalescent Plasma for Covid-19–Induced ARDS in Mechanically Ventilated Patients

BackgroundPassive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19–induced acute respiratory distress syndrome (ARDS).MethodsIn this open-label trial, we randomly assigned adult patients with Covid-19–induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28.ResultsA total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P=0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.ConclusionsThe administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19–induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.)

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients

BackgroundCritically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets.MethodsThe PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models.DiscussionThe PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04633421. Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.

The role of ROX index-based intubation in COVID-19 pneumonia: a cross-sectional comparison and retrospective survival analysis.

Coronavirus disease 2019 (COVID-19) patients with acute respiratory failure who experience delayed initiation of invasive mechanical ventilation have poor outcomes. The lack of objective measures to define the timing of intubation is an area of concern. We investigated the effect of timing of intubation based on respiratory rate-oxygenation (ROX) index on the outcomes of COVID-19 pneumonia. This was a retrospective cross-sectional study performed in a tertiary care teaching hospital in Kerala, India. Patients with COVID-19 pneumonia who were intubated were grouped into early intubation (within 12 hours of ROX index <4.88) or delayed intubation (12 hours or more hours after ROX <4.88). A total of 58 patients was included in the study after exclusions. Among them, 20 patients were intubated early, and 38 patients were intubated 12 hours after ROX index <4.88. The mean age of the study population was 57±14 years, and 55.0% of the patients were male; diabetes mellitus (48.3%) and hypertension (50.0%) were the most common comorbidities. The early intubation group had 88.2% successful extubation, while only 11.8% of the delayed group had successful extubation (P<0.001). Survival was also significantly more frequent in the early intubation group. Early intubation within 12 hours of ROX index <4.88 was associated with improved extubation and survival in patients with COVID-19 pneumonia.

Noninvasive Ventilation Alone Cannot Solve COVID-19 Respiratory Failure.

The respiratory management of severe coronavirus disease (COVID-19) acute hypoxemic respiratory failure has vacillated since the onset of the pandemic. Initially the consensus was to favor early intubation and initiation of invasive mechanical ventilation. Noninvasive ventilation modalities, which include continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP), and humidified high flow oxygen were avoided. This was done to reduce aerosol generation risking infection in others and unrestricted tidal volumes causing injurious transpulmonary pressures.

Signatures of illness in children requiring unplanned intubation in the pediatric intensive care unit: A retrospective cohort machine-learning study.

Acute respiratory failure requiring the initiation of invasive mechanical ventilation remains commonplace in the pediatric intensive care unit (PICU). Early recognition of patients at risk for respiratory failure may provide clinicians with the opportunity to intervene and potentially improve outcomes. Through the development of a random forest model to identify patients at risk for requiring unplanned intubation, we tested the hypothesis that subtle signatures of illness are present in physiological and biochemical time series of PICU patients in the early stages of respiratory decompensation. We included 116 unplanned intubation events as recorded in the National Emergency Airway Registry for Children in 92 PICU admissions over a 29-month period at our institution. We observed that children have a physiologic signature of illness preceding unplanned intubation in the PICU. Generally, it comprises younger age, and abnormalities in electrolyte, hematologic and vital sign parameters. Additionally, given the heterogeneity of the PICU patient population, we found differences in the presentation among the major patient groups - medical, cardiac surgical, and non-cardiac surgical. At four hours prior to the event, our random forest model demonstrated an area under the receiver operating characteristic curve of 0.766 (0.738 for medical, 0.755 for cardiac surgical, and 0.797 for non-cardiac surgical patients). The multivariable statistical models that captured the physiological and biochemical dynamics leading up to the event of urgent unplanned intubation in a PICU can be repurposed for bedside risk prediction.

Clinical outcomes according to timing to invasive ventilation due to noninvasive ventilation failure in children

ObjectiveNoninvasive ventilation (NIV) failure it has been associated to worst clinical outcomes due to a delay in intubation and initiation of invasive mechanical ventilation (IMV). There is a lack of evidence in pediatric patients regarding this topic. The objective was to deter-mine the association between duration of IMV and length of stay, with duration of NIV prior tointubation/IMV in pediatric patients. DesignA prospective cohort study since January 2015 to October 2019. SettingA pediatric intensive care unit. PatientsChildren under 15 years with acute respiratory failure who failed to noninvasive ventilation. InterventionsNone. Main variables of interestDemographic variables, pediatric index of mortality (PIM2), pediatric acute respiratory distress syndrome (PARDS) diagnosis, IMV and NIV duration, PICU LOS were registered and intrahospital mortality. ResultsA total of 109 patients with a median (IQR) age of 7 (3–14) months were included. The main diagnosis was pneumonia (89.9%). PARDS was diagnosed in 37.6% of the sample. No association was found between NIV duration and duration of IMV after Kaplan–Meier analysis (Log rank P = .479). There was no significant difference between PICU LOS (P = .253) or hospital LOS (P = 0.669), when categorized by NIV duration before intubation. PARDS diagnosis was associated to an increased length of invasive ventilation (HR: 0.64 [95% IC: 0.42–0.99]). ConclusionsNo association was found between NIV duration prior to intubation and duration of invasive ventilation in critical pediatric patients with acute respiratory failure.

Incidence and Impact of Ventilator Associated Multidrug Resistant Pneumonia in Patients with SARS-COV2.

Introduction Ventilator Associated Pneumonia (VAP) is associated with significant cost, morbidity, and mortality. There is limited data on the incidence of VAP, appropriate antibiotic timing, and the impact of multidrug resistant VAP in intubated Coronavirus disease-19 (COVID-19) patients. Methods A retrospective study was conducted at 2 tertiary urban academic centers involving 132 COVID-19 patients requiring invasive mechanical ventilation (IMV). The epidemiology of VAP, the impact of prior empiric antibiotic administration on the development of Multidrug Resistant Organism (MDRO) infections, and the impact of VAP on patient outcomes were studied. Results The average age of the patients was 60.58% were males, 70% were African-Americans and two-thirds of patients had diabetes, hypertension, or heart disease. The average Body Mass Index (BMI) was 32.9. Forty-one patients (27%) developed VAP. Patients with VAP had a significantly higher Sequential Organ Failure Assessment (SOFA) score prior to Intensive Care Unit (ICU) admission. Sixty percent received empiric antibiotics before initiation of IMV, mostly on hospital admission, and 81% received empiric antibiotics at the time of intubation. The administration of empiric antibiotics was not associated with a higher prevalence of VAP. The prevalence of VAP was 22 per 1000 days on ventilation. No difference in mortality was seen between VAP and non-VAP groups at 49% and 57% respectively (p = 0.4). VAP was associated with increased ICU length of stay (LOS), 30 vs. 16 days (p < 0.001), and longer hospital LOS 35 vs. 17 days (p < 0.001). 40% of VAPs were caused by MDROs. The most common organism was Staphylococcus aureus (28%), with almost half (48%) being methicillin resistant Staphylococcus aureus (MRSA). Conclusion VAP was a common complication of patients intubated for COVID-19 pneumonia. Most patients received empiric antibiotics upon the hospital and/or ICU admission. There was a 40% incidence of multidrug resistant pneumonia. Patients who developed VAP had almost twice as long hospital and ICU LOS.

Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study

BackgroundData on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes associated with molnupiravir or nirmatrelvir–ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant.MethodsWe analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between Feb 26 and April 26, 2022. Data were extracted from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. Patients were eligible for inclusion if their admission date was within 3 days before or after confirmation of their COVID-19 diagnosis. Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir–ritonavir use, or had severe renal or severe liver impairment were excluded. Patients who received the oral antivirals molnupiravir or nirmatrelvir–ritonavir were matched with controls using propensity-score matching in a ratio of 1:1. The primary outcome was all-cause mortality and secondary outcomes included a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit [ICU] admission, or the need for oxygen therapy) and each of these individual disease progression outcomes, and time to reaching a low viral burden (RT-PCR cycle threshold value ≥30). For each event outcome, crude incidence rates were calculated and hazard ratios (HRs) estimated using Cox regression models.FindingsWe identified 40 776 patients hospitalised with SARS-CoV-2 infection during the study period, with a mean follow-up of 41·3 days (total 925 713 person-days). After exclusions and propensity-score matching, we included 1856 molnupiravir recipients and 1856 matched controls, and 890 nirmatrelvir-ritonavir recipients and 890 matched controls. A lower risk of all-cause mortality was observed in molnupiravir recipients (crude incidence rate per 10 000 person-days 19·98 events [95% CI 16·91–23·45]) versus matched controls (38·07 events [33·85–42·67]; HR 0·48 [95% CI 0·40–0·59], p<0·0001) and in nirmatrelvir–ritonavir recipients (10·28 events [7·03–14·51]) versus matched controls (26·47 events [21·34–32·46]; HR 0·34 [0·23–0·50], p<0·0001). Oral antiviral recipients also had lower risks of the composite disease progression outcome (molnupiravir HR 0·60 [95% CI 0·52–0·69], p<0·0001; nirmatrelvir–ritonavir 0·57 [0·45–0·72], p<0·0001) and need for oxygen therapy (molnupiravir 0·69 [0·57–0·83], p=0·0001; nirmatrelvir–ritonavir 0·73 [0·54–0·97], p=0·032) compared with controls. Time to achieving a low viral burden was significantly shorter among oral antiviral recipients than matched controls (molnupiravir HR 1·38 [95% CI 1·15–1·64], p=0·0005; nirmatrelvir–ritonavir 1·38 [1·07–1·79], p=0·013). Significant differences in initiation of IMV and ICU admission were not found.InterpretationDuring a wave of SARS-CoV-2 omicron BA.2, initiation of novel oral antiviral treatments in hospitalised patients not requiring oxygen therapy on admission showed substantial clinical benefit. Our findings support the early use of oral antivirals in this population of patients.FundingHealth and Medical Research Fund (Health Bureau, Government of the Hong Kong Special Administrative Region).TranslationFor the Chinese translation of the abstract see Supplementary Materials section.

Characteristics and Factors Associated With Mortality in Patients With Coronavirus Disease 2019 and Pneumothorax.

ObjectiveTo describe the incidence, clinical characteristics, and factors associated with mortality in patients hospitalized for coronavirus disease 2019 (COVID-19) in whom pneumothorax developed.Patients and MethodsThis study was a retrospective analysis conducted using a large administrative database of adult patients hospitalized for COVID-19 in the United States from February 1, 2020, to June 10, 2021. We characterized the clinical features of patients in whom pneumothorax developed and the factors associated with mortality and stratified pneumothorax by the timing of the initiation of invasive mechanical ventilation (IMV) and by the time of hospital admission (early versus late).ResultsA total of 811,065 adult patients had a positive test result for severe acute respiratory syndrome coronavirus 2, of whom 103,858 (12.8%) were hospitalized. Pneumothorax occurred in 1915 patients (0.24% overall and 1.84% among hospitalized patients). Over time, the use of steroids and remdesivir increased, whereas the use of IMV, pneumothorax rates, and mortality decreased. The clinical characteristics associated with pneumothorax were male sex; the receipt of IMV; and treatment with steroids, remdesivir, or convalescent plasma. Most patients with pneumothorax received IMV, but pneumothorax developed before the initiation of IMV and/or early during hospitalization in majority. Multivariable analysis revealed that pneumothorax increased the risk of death (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.06-1.24). In patients who did not receive IMV, pneumothorax led to nearly twice the mortality (aHR, 1.99; 95% CI, 1.56-2.54). Increased mortality was also noted when pneumothorax occurred before IMV (aHR, 1.37; 95% CI, 1.11-1.69) and within 7 days of hospital admission (aHR, 1.60; 95% CI, 1.29-1.98).ConclusionThe overall incidence of pneumothorax in patients hospitalized for COVID-19 was low. Pneumothorax is an independent risk factor for death.

Different Methods to Improve the Monitoring of Noninvasive Respiratory Support of Patients with Severe Pneumonia/ARDS Due to COVID-19: An Update

The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical–radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (Ppl) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical–physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Tracheostomy timing and clinical outcomes in ventilated COVID-19 patients: a systematic review and meta-analysis

BackgroundThe association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients’ outcomes.MethodsWe searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model.ResultsFourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD − 9.08 days, 95% CI − 10.91 to − 7.26 days, p < 0.01) and duration of ICU stay (1224 patients; MD − 9.41 days, 95% CI − 12.36 to − 6.46 days, p < 0.01). Mortality was reported for 2343 patients and was comparable between groups (OR 1.09, 95% CI 0.79–1.51, p = 0.59).ConclusionsThe results of this meta-analysis suggest that, compared with late tracheostomy, early tracheostomy in COVID-19 patients was associated with shorter duration of IMV and ICU stay without modifying the mortality rate. These findings may have important implications to improve ICU availability during the COVID-19 pandemic.Trial registration The protocol was registered at INPLASY (INPLASY202180088).

Clinical and laboratory predictors at ICU admission affecting course of illness and mortality rates in a tertiary COVID-19 center

BackgroundSurvival rates of critically ill COVID-19 patients are affected by various clinical features and laboratory parameters at ICU admission. Some of these predictors are universal but others may be population specific. ObjectiveTo determine utility of baseline clinical and laboratory parameters in a multivariate regression model to predict outcomes in critically ill COVID-19 patients in a tertiary hospital in Croatia. Methods692 critically ill COVID-19 patients treated during a 10-month period were included in this retrospective observational trial to assess the risk factors determining mortality rates. Various anthropometric features, comorbidities, laboratory parameters, clinical features and therapeutic interventions were included in the analysis. ICU mortality rates and length of ICU stay were primary endpoints analyzed in this study. ResultsAfter multivariate adjustment, only the SOFA score, PaO2/FiO2 and history of arterial hypertension had an effect on ICU mortality, as well as the need to initiate invasive mechanical ventilation. Increase in PaO2/FiO2 over the first 7 days was present in survivors, while reverse applied to SOFA. Length of ICU stay was 9 (4–14) days. Factors affecting survival times were admission from wards, congestive heart failure, invasive mechanical ventilation, bacterial superinfections, age > 75 years, SOFA score, and serum ferritin, CRP and IL-6 values at ICU admission. ConclusionElevated inflammatory biomarkers and SOFA score at ICU admission were detected as significant predictors of ICU mortality in this cohort, while initiation of invasive mechanical ventilation is the most relevant interventional mortality risk factor in critically ill COVID-19 patients.

Mortality in patients receiving prolonged invasive mechanical ventilation time in the emergency department: A retrospective cohort study.

Background:Patients waiting for intensive care unit (ICU) admission cause emergency department (ED) crowding and have an increased risk of mortality and length of stay (LOS) in hospital, which increase the hospitalization cost. This study aimed to investigate the correlation between mortality and invasive mechanical ventilation (IMV) time in patients in the ED.Methods:A retrospective cohort study was conducted in patients who received IMV in the ED of Ramathibodi Hospital. The correlation between mortality at 28 days after intubation and IMV time in the ED was analyzed. The cutoff time was analyzed to determine prolonged and nonprolonged IMV times. ICU ventilation time, length of ICU stay, and LOS in the hospital were also analyzed to determine their correlations between IMV time in the ED.Results:In this study, 302 patients were enrolled, 71 died, and 231 survived 28 days after receiving IMV in the ED. We found that the duration of >12 h of IMV in the ED increased the 28-day mortality rate by 1.98 times (P = 0.036). No correlations were found between IMV time in the ED and ventilation time in the ICU, length of ICU stay, and LOS in the hospital.Conclusion:More than 12 h of IMV time in the ED correlated with mortality at 28 days after initiation of IMV. No associations were found between prolonged IMV time in the ED with ventilation time in the ICU, length of ICU stay, and LOS in the hospital.

Acute Respiratory Failure and Mechanical Ventilation in Women With COVID-19 During Pregnancy: Best Clinical Practices.

Symptomatic pregnant women with coronavirus disease-2019 (COVID-19) are at increased risk of severe disease and death compared with symptomatic nonpregnant females of reproductive age. Among those who become critically ill, profound acute hypoxemic respiratory failure is the dominant finding. Significant morbidity and mortality from COVID-19 are largely due to acute viral pneumonia that evolves to acute respiratory distress syndrome. Admission of these patients with critical disease to an intensive care unit and initiation of invasive mechanical ventilation may be indicated. Effective ventilatory support can be challenging in the COVID-19 patient population, even more so when the need occurs in a woman during pregnancy. Key respiratory changes during pregnancy are reviewed. Principles related to maternal-fetal oxygen transport, assessment of ventilation and oxygenation status, and oxygenation goals are also reviewed. Selected concepts related to mechanical ventilatory support for the woman with COVID-19 and acute respiratory failure during pregnancy are presented including indications for ventilatory support, noninvasive support, and invasive ventilator management. Challenges in providing care to this patient population are identified as well as strategies to address them going forward.

1297. Azithromycin vs Beta Lactams in Acute Exacerbations of COPD

BackgroundBacterial infections cause approximately 50% of Acute Exacerbations of COPD (AECOPD). Current guidelines recommend a wide range of antibiotics, but evidence comparing agents is limited. The purpose of this study is to compare the effectiveness of azithromycin to beta lactams in the treatment of hospitalized patients with AECOPD.MethodsA multicenter, retrospective, observational study of adult patients admitted with AECOPD who received at least two consecutive days of either a beta lactam or azithromycin were included. The primary endpoint was treatment failure which is a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, requirement of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. Secondary endpoints included each individual component of the composite endpoint and length of stay.ResultsOf 11,395 patients screened, 595 met the inclusion criteria (428 were treated with azithromycin and 167 patients were treated with a beta lactam). The most common reason for exclusion was the receipt of both azithromycin and beta-lactam in 9857 patients. The patients were similar except the azithromycin group was more likely to be African-American and less likely to have failed an outpatient antibiotic. Treatment failure rate was 19.6% in the azithromycin group and 32.3% in the beta lactam group (P=0.001). Patients in the beta lactam group were more likely to experience in-hospital mortality (P=0.023), require a new antibiotic during admission (P< 0.001), and were more likely to be readmitted within 30 days of discharge due to AECOPD (P=0.032). Length of stay was significantly shorter in the azithromycin group compared to the beta lactam group. There were no statistically significant differences in the rates of adverse events among both groups.ConclusionTreatment failure rate and length of stay were significantly higher in the beta lactam group compared to the azithromycin group. However, there were no differences in the side effect profile among both groups. Further studies should be performed to confirm these findings.Disclosures All Authors: No reported disclosures

Post-COVID-19 Necrotizing Pneumonia in Patients on Invasive Mechanical Ventilation.

(1) Background: Few reports of necrotizing pneumonia in patients with COVID-19 have been published. We have observed an elevated incidence at two hospitals in our city, suggesting this complication is not uncommon, and may have been overlooked. (2) Methods: This article presents a retrospective, descriptive cohort study that was undertaken from 22 March 2020 to 15 June 2021 in two tertiary care hospitals in Medellín, Colombia. All adult patients admitted to the intensive care unit (ICU) for respiratory failure related to confirmed COVID-19, on invasive mechanical ventilation (IMV), with imaging or surgical findings documenting necrotizing pneumonia (NP) were included. (3) Results: Of 936 patients with COVID-19 that required IMV, 42 (4.5%) developed NP. Overall mortality was 57% and in-hospital mortality was 71%, occurring 15–79 days after COVID-19 diagnosis. NP was diagnosed at a median of 27 days after COVID-19 symptom onset and 15.5 days after initiation of IMV. Infections were polymicrobial in 52.4% of patients. Klebsiella pneumoniae (57%) and Pseudomonas aeruginosa (33%) were the most common etiologic agents. Pulmonary embolism (PE) was documented in 13 patients overall (31%), and in 50% of patients who underwent an angioCT. Drainage and/or surgical procedures were performed on 19 patients (45.2%) with a 75% mortality rate. (4) Conclusions: In our experience, NP is a relatively common, albeit neglected, complication in mechanically ventilated COVID-19 patients, possibly originating in poorly vascularized areas of lung parenchyma. Associated mortality is high. Although drainage procedures did not seem to favorably impact patient outcomes, diagnosis and treatment were late events in the overall disease course, suggesting that early recognition and timely treatment could have a positive impact on prognosis.

Rationale and design of the Prone Position and Respiratory Outcomes in Non-intubated COVID-19 PatiEnts: The “PRONE” Study

While benefits of prone position in mechanically-ventilated patients have been well-described, a randomized-control trial to determine the effects of prone positioning in awake, spontaneously-breathing patients with an acute pneumonia has not been previously conducted. Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts: the “PRONE” Study (PRONE) was conducted in non-intubated hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia as defined by respiratory rate ≥ 20/min or an oxyhemoglobin saturation (SpO2) ≤ 93% without supplemental oxygen [1]. The PRONE trial was designed to investigate the effects of prone positioning on need for escalation in respiratory support, as defined by need for transition to a higher acuity level of care, increased fraction of inspired oxygen (FiO2), or the initiation of invasive mechanical ventilation. Secondary objectives were to assess the duration of effect of prone positioning on respiratory parameters such as respiratory rate and SpO2, as well as other outcomes such as time to discharge or transition in level of care.