Comparing nasopharyngeal apnoeic oxygenation at 18 l/min to preoxygenation alone in obese patients - A randomised controlled study.

STUDY OBJECTIVE: Investigate a low-cost, nasopharyngeal apnoeic oxygenation technique, establish its efficacy, and compare it to preoxygenation only in an obese population. The study's hypothesis was that nasopharyngeal apnoeic oxygenation at 18 l.min-1 would significantly prolong safe apnoea time compared to preoxygenation alone. DESIGN: Randomised controlled study. SETTING: Theatre complex of a resource constrained hospital. PATIENTS: 30 adult, obese (BMI ≥ 35 kg.m-2) patients presenting for elective surgery. Patients with limiting cardio-respiratory disease, suspected difficult airway, risk of aspiration, and that were pregnant, were excluded. Patients were allocated by block randomisation in a 1:2 ratio to a preoxygenation-only (No-AO) and an intervention group (NPA-O2). INTERVENTIONS: All patients were preoxygenated to an Et-O2 > 80%, followed by a standardised induction. The intervention group received oxygen at 18 l.min-1 via the nasopharyngeal catheter intervention. The desaturation process was documented until an SpO2 of 92% or 600 s was reached. MEASUREMENTS: Baseline demographic and clinical characteristics were collected. The primary outcome was safe apnoea time, defined as the time taken to desaturate to an SpO2 of 92%. Secondary outcomes were rate of carbon dioxide accumulation and factors affecting the risk of desaturation. MAIN RESULTS: The study was conducted in a morbidly obese population (NoAO = 41,1 kg.m-2; NPA-O2 = 42,5 kg.m-2). The risk of desaturation was signifantly lower in the intervention group (Hazzard Ratio = 0,072, 95% CI[0,019-0,283]) (Log-Rank test, p < 0.001). The median safe apnoea time was significantly longer in the intervention group (NoAO = 262 s [IQR 190-316]; NPA-O2 = 600 s [IQR 600-600]) (Mann-Whitney-U test, p < 0.001). The mean rate of CO2 accumalation was significantly slower in the intervention group (NoAO = 0,47 ± 0,14 kPa.min-1; NPA-O2 = 0,3 ± 0,09 kPa.min-1) (t-test, p = 0.003). There were no statistically significant risk factors associated with an increased risk of desaturation found. CONCLUSIONS: Nasopharyngeal apnoeic oxygenation at 18 l/min prolongs safe apnoea time, compared to preoxygenation alone, and reduces the risk of desaturation in morbidly obese patients. CLINICAL TRIAL REGISTRATION: PACTR202202665252087; WC/202004/007.

Ratio of Oxygen Saturation to Inspired Oxygen, ROX Index, Modified ROX Index to Predict High Flow Cannula Success in COVID-19 Patients: Multicenter Validation Study.

INTRODUCTION: High-flow nasal cannula (HFNC) is a respiratory support measure for coronavirus 2019 (COVID-19) patients that has been increasingly used in the emergency department (ED). Although the respiratory rate oxygenation (ROX) index can predict HFNC success, its utility in emergency COVID-19 patients has not been well-established. Also, no studies have compared it to its simpler component, the oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 [SF]) ratio, or its modified version incorporating heart rate. Therefore, we aimed to compare the utility of the SF ratio, the ROX index (SF ratio/respiratory rate), and the modified ROX index (ROX index/heart rate) in predicting HFNC success in emergency COVID-19 patients. METHODS: We conducted this multicenter retrospective study at five EDs in Thailand between January-December 2021. Adult patients with COVID-19 treated with HFNC in the ED were included. The three study parameters were recorded at 0 and 2 hours. The primary outcome was HFNC success, defined as no requirement of mechanical ventilation at HFNC termination. RESULTS: A total of 173 patients were recruited; 55 (31.8%) had successful treatment. The two-hour SF ratio yielded the highest discrimination capacity (AUROC 0.651, 95% CI 0.558-0.744), followed by two-hour ROX and modified ROX indices (AUROC 0.612 and 0.606, respectively). The two-hour SF ratio also had the best calibration and overall model performance. At its optimal cut-point of 128.19, it gave a balanced sensitivity (65.3%) and specificity (61.8%). The two-hour SF≥128.19 was also significantly and independently associated with HFNC failure (adjusted odds ratio 0.29, 95% CI 0.13-0.65; P=0.003). CONCLUSION: The SF ratio predicted HFNC success better than the ROX and modified ROX indices in ED patients with COVID-19. With its simplicity and efficiency, it may be the appropriate tool to guide management and ED disposition for COVID-19 patients receiving HFNC in the ED.

Risk of air and surface contamination during application of different noninvasive respiratory support for patients with COVID-19.

OBJECTIVES: We compared the risk of environmental contamination among patients with COVID-19 who received high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and conventional oxygen therapy (COT) via nasal cannula for respiratory failure. METHODS: Air was sampled from the hospital isolation rooms with 12 air changes/hr where 26 patients with COVID-19 received HFNC (up to 60 l/min, n = 6), NIV (n = 6), or COT (up to 5 l/min of oxygen, n = 14). Surface samples were collected from 16 patients during air sampling. RESULTS: Viral RNA was detected at comparable frequency in air samples collected from patients receiving HFNC (3/54, 5.6%), NIV (1/54, 1.9%), and COT (4/117, 3.4%) (P = 0.579). Similarly, the risk of surface contamination was comparable among patients receiving HFNC (3/46, 6.5%), NIV (14/72, 19.4%), and COT (8/59, 13.6%) (P = 0.143). An increment in the cyclic thresholds of the upper respiratory specimen prior to air sampling was associated with a reduced SARS-CoV-2 detection risk in air (odds ratio 0.83 [95% confidence interval 0.69-0.96], P = 0.027) by univariate logistic regression. CONCLUSION: No increased risk of environmental contamination in the isolation rooms was observed in the use of HFNC and NIV vs COT among patients with COVID-19 with respiratory failure. Higher viral load in the respiratory samples was associated with positive air samples.

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Choice of respiratory therapy for COVID-19 patients with acute hypoxemic respiratory failure: a retrospective case series study.

Background: In the treatment of acute hypoxemic respiratory failure (AHRF) due to coronavirus 2019 (COVID-19), physicians choose respiratory management ranging from low-flow oxygen therapy to more invasive methods, depending on the severity of the patient's symptoms. Recently, the ratio of oxygen saturation (ROX) index has been proposed as a clinical indicator to support the decision for either high-flow nasal cannulation (HFNC) or mechanical ventilation (MV). However, the reported cut-off value of the ROX index ranges widely from 2.7 to 5.9. The objective of this study was to identify indices to achieve empirical physician decisions for MV initiation, providing insights to shorten the delay from HFNC to MV. We retrospectively analyzed the ROX index 6 hours after initiating HFNC and lung infiltration volume (LIV) calculated from chest computed tomography (CT) images in COVID-19 patients with AHRF. Methods: We retrospectively analyzed the data for 59 COVID-19 patients with AHRF in our facility to determine the cut-off value of the ROX index for respiratory therapeutic decisions and the significance of radiological evaluation of pneumonia severity. The physicians chose either HFNC or MV, and the outcomes were retrospectively analyzed using the ROX index for initiating HFNC. LIV was calculated using chest CT images at admission. Results: Among the 59 patients who required high-flow oxygen therapy with HFNC at admission, 24 were later transitioned to MV; the remaining 35 patients recovered. Four of the 24 patients in the MV group died, and the ROX index values of these patients were 9.8, 7.3, 5.4, and 3.0, respectively. These index values indicated that the ROX index of half of the patients who died was higher than the reported cut-off values of the ROX index, which range from 2.7-5.99. The cut-off value of the ROX index 6 hours after the start of HFNC, which was used to classify the management of HFNC or MV as a physician's clinical decision, was approximately 6.1. The LIV cut-off value on chest CT between HFNC and MV was 35.5%. Using both the ROX index and LIV, the cut-off classifying HFNC or MV was obtained using the equation, LIV = 4.26 × (ROX index) + 7.89. The area under the receiver operating characteristic curve, as an evaluation metric of the classification, improved to 0.94 with a sensitivity of 0.79 and specificity of 0.91 using both the ROX index and LIV. Conclusion: Physicians' empirical decisions associated with the choice of respiratory therapy for HFNC oxygen therapy or MV can be supported by the combination of the ROX index and the LIV index calculated from chest CT images.

Physiometric Response to High-Flow Nasal Cannula Support in Acute Bronchiolitis.

OBJECTIVES: To describe the rate of high-flow nasal cannula (HFNC) nonresponse and paired physiometric responses (changes [∆] in heart rate [HR] and respiratory rate [RR]) before and after HFNC initiation in hospitalized children with bronchiolitis. METHODS: We performed a single-center, prospective descriptive study in a PICU within a quaternary referral center, assessing children aged ≤2 years admitted for bronchiolitis on HFNC from November 2017 to March 2020. We excluded for cystic fibrosis, airway anomalies, pulmonary hypertension, tracheostomy, neuromuscular disease, congenital heart disease, or preadmission intubation. Primary outcomes were paired ∆ and %∆ in HR and RR before and after HFNC initiation. Secondary outcomes were HFNC nonresponse rate (ie, intubation or transition to noninvasive positive pressure ventilation). Analyses included χ2, Student's t, Wilcoxon rank, and paired testing. RESULTS: Of the 172 children studied, 56 (32.6%) experienced HFNC nonresponse at a median of 14.4 (interquartile range: 4.8-36) hours and 11 (6.4%) were intubated. Nonresponders had a greater frequency of bacterial pneumonia, but otherwise no major differences in demographics, comorbidities, or viral pathogens were noted. Responders experienced reductions in both %ΔRR (-17.1% ± 15.8% vs +5.3% ± 22.3%) and %ΔHR (-6.5% ± 10.5% vs 0% ± 10.9%) compared with nonresponders. CONCLUSIONS: In this prospective, observational cohort study, we provide baseline data describing expected physiologic changes after initiation of HFNC for children admitted to the PICU for bronchiolitis. In our descriptive analysis, patients with comorbid bacterial pneumonia appear to be at additional risk for subsequent HFNC nonresponse.

Prolonged non-invasive respiratory supports in a COVID-19 patient with severe acute hypoxemic respiratory failure.

A pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 was declared in 2020. Severe cases were characterized by the development of acute hypoxemic respiratory failure (AHRF) requiring advanced respiratory support. However, intensive care units (ICU) were saturated, and many patients had to be treated out of ICU. This case describes a 75-year-old man affected by AHRF due to Coronavirus Disease 2019 (COVID-19), hospitalized in a high-dependency unit, with PaO2/FiO2 <100 for 28 consecutive days. An experienced team with respiratory physiotherapists was in charge of the noninvasive ventilatory support (NIVS). The patient required permanent NIVS with continuous positive airway pressure, non-invasive ventilation, high flow nasal oxygen and body positioning. He was weaned from NIVS after 37 days and started exercise training afterwards. The patient was discharged at home with low-flow oxygen therapy. This case represents an example of a successful treatment of AHRF with the still controversial noninvasive respiratory support in one patient with COVID-19.

Predicting the successful application of high-flow nasal oxygen cannula in patients with COVID-19 respiratory failure: a retrospective analysis.

BACKGROUND: The right time of high-flow nasal cannulas (HFNCs) application in COVID-19 patients with acute respiratory failure remains uncertain. RESEARCH DESIGN AND METHODS: In this retrospective study, COVID-19-infected adult patients with hypoxemic respiratory failure were enrolled. Their baseline epidemiological data and respiratory failure related parameters, including the Ventilation in COVID-19 Estimation (VICE), and the ratio of oxygen saturation (ROX index), were recorded. The primary outcome measured was the 28-day mortality. RESULTS: A total of 69 patients were enrolled. Fifty-four (78%) patients who intubated and received invasive mechanical ventilatory (MV) support on day 1 were enrolled in the MV group. The remaining fifteen (22%) patients received HFNC initially (HFNC group), in which, ten (66%) patients were not intubated during hospitalization were belong to HFNC-success group and five (33%) of these patients were intubated later due to disease progression were attributed to HFNC-failure group. Compared with those in the MV group, those in the HFNC group had a lower mortality rate (6.7% vs. 40.7%, p = 0.0138). There were no differences in baseline characteristics among the two groups; however, the HFNC group had a lower VICE score (0.105 [0.049-0.269] vs. 0.260 [0.126-0.693], p = 0.0092) and higher ROX index (5.3 [5.1-10.7] vs. 4.3 [3.9-4.9], p = 0.0007) than the MV group. The ROX index was higher in the HFNC success group immediately before (p = 0.0136) and up to 12 hours of HFNC therapy than in the HFNC failure group. CONCLUSIONS: Early intubation may be considered in patients with a higher VICE score or a lower ROX index. The ROX score during HFNCs use can provide an early warning sign of treatment failure. Further investigations are warranted to confirm these results.

High flow nasal cannulas (HFNCs) were widely used in patients with COVID-19 infection related hypoxemic respiratory failure. However, there were concerns about its failure and related delayed intubation may be associated with a higher mortality rate. This retrospective study revealed patients with higher baseline disease severity and higher VICE scores may be treated with primary invasive mechanical ventilation. On the contrary, if their baseline VICE score is low and ROX index is high, HFNCs treatment might be safely applied initially. The trends of serial ROX index values during HFNC use could be a reliable periscope to predict the HFNC therapy outcome, therefore avoided delayed intubation.

High-flow nasal cannula reduces intubation rate in patients with COVID-19 with acute respiratory failure: a meta-analysis and systematic review.

OBJECTIVE: This study aimed to investigate the effect of high-flow nasal cannula therapy (HFNC) versus conventional oxygen therapy (COT) on intubation rate, 28-day intensive care unit (ICU) mortality, 28-day ventilator-free days (VFDs) and ICU length of stay (ICU LOS) in adult patients with acute respiratory failure (ARF) associated with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Library and Embase up to June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only randomised controlled trials or cohort studies comparing HFNC with COT in patients with COVID-19 were included up to June 2022. Studies conducted on children or pregnant women, and those not published in English were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the titles, abstracts and full texts. Relevant information was extracted and curated in the tables. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials or cohort studies. Meta-analysis was conducted using RevMan V.5.4 computer software using a random effects model with a 95% CI. Heterogeneity was assessed using Cochran's Q test (χ2) and Higgins I2 statistics, with subgroup analyses to account for sources of heterogeneity. RESULTS: Nine studies involving 3370 (1480 received HFNC) were included. HFNC reduced the intubation rate compared with COT (OR 0.44, 95% CI 0.28 to 0.71, p=0.0007), decreased 28-day ICU mortality (OR 0.54, 95% CI 0.30 to 0.97, p=0.04) and improved 28-day VFDs (mean difference (MD) 2.58, 95% CI 1.70 to 3.45, p<0.00001). However, HFNC had no effect on ICU LOS versus COT (MD 0.52, 95% CI -1.01 to 2.06, p=0.50). CONCLUSIONS: Our study indicates that HFNC may reduce intubation rate and 28-day ICU mortality, and improve 28-day VFDs in patients with ARF due to COVID-19 compared with COT. Large-scale randomised controlled trials are necessary to validate our findings. PROSPERO REGISTRATION NUMBER: CRD42022345713.

How long is too long: A retrospective study evaluating the impact of the duration of noninvasive oxygenation support strategies (high flow nasal cannula & BiPAP) on mortality in invasive mechanically ventilated patients with COVID-19.

BACKGROUND/AIM: We investigated the association of noninvasive oxygenation support [high flow nasal cannula (HFNC) and BiPAP], timing of invasive mechanical ventilation (IMV), and inpatient mortality among patients hospitalized with COVID-19. METHODS: Retrospective chart review study of patients hospitalized with COVID-19 (ICD-10 code U07.1) and received IMV from March 2020-October 2021. Charlson comorbidity index (CCI) was calculated; Obesity defined as body mass index (BMI) ≥ 30 kg/m2; morbid obesity was BMI ≥ 40 kg/m2. Clinical parameters/vital signs recorded at time of admission. RESULTS: 709 COVID-19 patients underwent IMV, predominantly admitted from March-May 2020 (45%), average age 62±15 years, 67% male, 37% Hispanic, and 9% from group living settings. 44% had obesity, 11% had morbid obesity, 55% had type II diabetes, 75% had hypertension, and average CCI was 3.65 (SD = 3.11). Crude mortality rate was 56%. Close linear association of age with inpatient-mortality risk was found [OR (95% CI) = 1.35 (1.27-1.44) per 5 years, p<0.0001)]. Patients who died after IMV received noninvasive oxygenation support significantly longer: 5.3 (8.0) vs. 2.7 (SD 4.6) days; longer use was also independently associated with a higher risk of inpatient-mortality: OR = 3.1 (1.8-5.4) for 3-7 days, 7.2 (3.8-13.7) for ≥8 days (reference: 1-2 days) (p<0.0001). The association magnitude varied between age groups: 3-7 days duration (ref: 1-2 days), OR = 4.8 (1.9-12.1) in ≥65 years old vs. 2.1 (1.0-4.6) in <65 years old. Higher mortality risk was associated with higher CCI in patients ≥65 (P = 0.0082); among younger patients, obesity (OR = 1.8 (1.0-3.2) or morbid obesity (OR = 2.8;1.4-5.9) (p<0.05) were associated. No mortality association was found for sex or race. CONCLUSION: Time spent on noninvasive oxygenation support [as defined by high flow nasal cannula (HFNC) and BiPAP] prior to IMV increased mortality risk. Research for the generalizability of our findings to other respiratory failure patient populations is needed.

Coronavirus Disease-2019 in Pregnancy.

Coronavirus disease-2019 (COVID-19) infection during pregnancy is associated with severe complications and adverse effects for the mother, the fetus, and the neonate. The frequency of these outcomes varies according to the region, the gestational age, and the presence of comorbidities. Many COVID-19 interventions, including oxygen therapy, high-flow nasal cannula, and invasive mechanical ventilation, are challenging and require understanding physiologic adaptations of pregnancy. Vaccination is safe during pregnancy and lactation and constitutes the most important intervention to reduce severe disease and complications.

Nasopharyngeal SARS-CoV-2 may not be dispersed by a high-flow nasal cannula.

A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.