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.

The utility of the Rapid Emergency Medicine Score (REMS) compared with three other early warning scores in predicting in-hospital mortality among COVID-19 patients in the emergency department: a multicenter validation study.

BACKGROUND: Many early warning scores (EWSs) have been validated to prognosticate adverse outcomes of COVID-19 in the Emergency Department (ED), including the quick Sequential Organ Failure Assessment (qSOFA), the Modified Early Warning Score (MEWS), and the National Early Warning Score (NEWS). However, the Rapid Emergency Medicine Score (REMS) has not been widely validated for this purpose. We aimed to assess and compare the prognostic utility of REMS with that of qSOFA, MEWS, and NEWS for predicting mortality in emergency COVID-19 patients. METHODS: We conducted a multi-center retrospective study at five EDs of various levels of care in Thailand. Adult patients visiting the ED who tested positive for COVID-19 prior to ED arrival or within the index hospital visit between January and December 2021 were included. Their EWSs at ED arrival were calculated and analysed. The primary outcome was all-cause in-hospital mortality. The secondary outcome was mechanical ventilation. RESULTS: A total of 978 patients were included in the study; 254 (26%) died at hospital discharge, and 155 (15.8%) were intubated. REMS yielded the highest discrimination capacity for in-hospital mortality (the area under the receiver operator characteristics curves (AUROC) 0.771 (95% confidence interval (CI) 0.738, 0.804)), which was significantly higher than qSOFA (AUROC 0.620 (95%CI 0.589, 0.651); p < 0.001), MEWS (AUROC 0.657 (95%CI 0.619, 0.694); p < 0.001), and NEWS (AUROC 0.732 (95%CI 0.697, 0.767); p = 0.037). REMS was also the best EWS in terms of calibration, overall model performance, and balanced diagnostic accuracy indices at its optimal cutoff. REMS also performed better than other EWSs for mechanical ventilation. CONCLUSION: REMS was the early warning score with the highest prognostic utility as it outperformed qSOFA, MEWS, and NEWS in predicting in-hospital mortality in COVID-19 patients in the ED.

Clinical factors associated with adverse clinical outcomes in elderly versus non-elderly COVID-19 emergency patients: a multi-center observational study.

BACKGROUND: The COVID-19 pandemic has caused over 6 million deaths worldwide. The elderly accounted for a large proportion of patients with their mortality rate largely higher than the non-elderly. However, limited studies have explored clinical factors associated with poor clinical outcomes in this important population. Therefore, this study aimed to determine factors independently associated with adverse clinical outcomes among COVID-19 elderly patients. METHODS: We conducted a multicenter observational study at five emergency departments (EDs) in Thailand. Patients over 18 years old diagnosed with COVID-19 between January and December 2021 were included. We classified patients into elderly (age ≥ 65 years) and non-elderly (age < 65 years). The primary clinical outcome was in-hospital mortality. The secondary outcomes were endotracheal intubation and intensive care unit admission. We identified independent factors associating with these outcomes both in the whole population and separately by age group using multivariate logistic regression models. RESULTS: A total of 978 patients were included, 519 (53.1%) were elderly and 459 (46.9%) were non-elderly, and 254 (26%) died at hospital discharge. The mortality rate was significantly higher in the elderly group (39.1% versus 14.3%, p<0.001)). In the elderly, age (adjusted odds ratio (aOR) 1.13; 95% confidence interval (CI) 1.1-1.2; p<0.001), male sex (aOR 3.64; 95%CI 1.5-8.8; p=0.004), do-not-resuscitate (DNR) status (aOR 12.46; 95%CI 3.8-40.7; p<0.001), diastolic blood pressure (aOR 0.96; 95%CI 0.9-1.0; p=0.002), body temperature (aOR 1.74; 95%CI 1.0-2.9; p=0.036), and Glasgow Coma Scale (GCS) score (aOR 0.71; 95%CI 0.5-1.0; p=0.026) were independent baseline and physiologic factors associated with in-hospital mortality. Only DNR status and GCS score were associated with in-hospital mortality in both the elderly and non-elderly, as well as the overall population. Lower total bilirubin was independently associated with in-hospital mortality in the elderly (aOR 0.34; 95%CI 0.1-0.9; p=0.035), while a higher level was associated with the outcome in the non-elderly. C-reactive protein (CRP) was the only laboratory factor independently associated with all three study outcomes in the elderly (aOR for in-hospital mortality 1.01; 95%CI 1.0-1.0; p=0.006). CONCLUSION: Important clinical factors associated with in-hospital mortality in elderly COVID-19 patients were age, sex, DNR status, diastolic blood pressure, body temperature, GCS score, total bilirubin, and CRP. These parameters may aid in triage and ED disposition decision-making in this very important patient population during times of limited resources during the COVID-19 pandemic.

ROX index versus HACOR scale in predicting success and failure of high-flow nasal cannula in the emergency department for patients with acute hypoxemic respiratory failure: a prospective observational study.

BACKGROUND: High-flow nasal cannula has been a promising initial respiratory support measure for patients with acute hypoxemic respiratory failure (AHRF) in the emergency department (ED). However, delayed detection of HFNC failure is associated with increased mortality. The ROX index is a tool that can help predict HFNC success. Nonetheless, its utility in ED patients is limited, and no studies have compared it with the HACOR scale, another tool that may be as accurate in predicting HFNC failure. Therefore, we aimed to compare the prognostic utility of the ROX index and the HACOR scale in emergency AHRF patients. METHODS: This prospective observational study was conducted at the ED of Siriraj Hospital, Thailand, between August 2018 and February 2020. Adult patients with AHRF requiring HFNC in the ED were included. The ROX index and the HACOR scale were measured at 1, 2, and 6 h after HFNC initiation. The primary outcome was HFNC success, defined as no intolerance or escalation towards mechanical ventilation or non-invasive ventilation within 48 h. RESULTS: A total of 75 patients were enrolled; 52 (69.3%) had a successful treatment. The ROX index was higher in the success group, while the HACOR scale was lower at all timepoints. The ROX index yielded generally higher discrimination capacity based on the area under the receiver operating characteristic curve (AUROC) than the HACOR scale [AUROC at 1, 2, and 6 h = 0.815, 0.784, 0.853 for ROX in predicting HFNC success and 0.733, 0.690, and 0.764 for HACOR in predicting HFNC failure]. The ROX index measured at 6 h at the cut-point of 4.88 had 92.98% sensitivity, 61.11% specificity, 88.33% positive predictive value, and 73.33% negative predictive value with a diagnostic accuracy of 85.33%. CONCLUSION: The ROX index had superior prognostic utility in predicting HFNC outcome (success/failure) compared to the HACOR scale in patients with AHRF in the ED setting. Moreover, it is less complex and more efficient to be employed at bedside. Therefore, the ROX index is a more appropriate tool to guide further management and potential escalation therapy for AHRF patients with HFNC therapy initiated in the ED.

Parallel-group, randomised, controlled, non-inferiority trial of high-flow nasal cannula versus non-invasive ventilation for emergency patients with acute cardiogenic pulmonary oedema: study protocol.

INTRODUCTION: High-flow nasal cannula (HFNC) is an innovative oxygen-delivering technique, which has been shown to effectively decrease the intubation risk in patients with hypoxaemic respiratory failure of various aetiologies compared with conventional oxygen therapy. Also, it has proved to be non-inferior to non-invasive positive pressure ventilation (NIPPV) in patients with hypoxaemic respiratory failure primarily due to pneumonia. Evidence on its benefits compared with NIPPV, which is the standard of care for patients with acute cardiogenic pulmonary oedema (ACPE) with hypoxaemic respiratory distress, is limited. Therefore, we planned this study to investigate the effects of HFNC compared with NIPPV for emergency patients with ACPE. METHODS AND ANALYSIS: In this single-centred, non-blinded, parallel-group, randomised, controlled, non-inferiority trial, we will randomly allocate 240 patients visiting the emergency department with ACPE in a 1:1 ratio to receive either HFNC or NIPPV for at least 4 hours using computer-generated mixed-block randomisation concealed by sealed opaque envelopes. The primary outcome is the intubation rate in 72 hours after randomisation. The main secondary outcomes are intolerance rate, mortality rate and treatment failure rate (a composite of intolerance, intubation and mortality). The outcome assessors and data analysts will be blinded to the intervention. These categorical outcomes will be analysed by calculating the risk ratio. Interim analyses evaluating the primary outcome will be performed after half of the expected sample size are recruited. ETHICS AND DISSEMINATION: This study protocol has been approved by the Siriraj Institutional Review Board (study ID: Si 271/2021). It has been granted the Siriraj Research and Development Fund. All participants or their authorised third parties will provide written informed consent prior to trial inclusion. The study results will be published in a peer-reviewed international journal and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: TCTR20210413001.

The utility of the 1-hour high-sensitivity cardiac troponin T algorithm compared with and combined with five early rule-out scores in high-acuity chest pain emergency patients.

BACKGROUND: Although the 0/1 h high-sensitivity cardiac troponin T (0/1 hs-cTnT) algorithm and many risk scores have been validated for use in emergency departments (EDs), their utility in high-acuity ED patients has not been validated. We aimed to validate the 0/1 hs-cTnT algorithm and the HEART, TIMI, GRACE, T-MACS and NOTR risk scores before and after combining the 0/1 algorithm in high-acuity ED chest pain patients. METHODS: A prospective observational study was conducted in the high-acuity ED of Siriraj Hospital, a tertiary hospital in Bangkok, Thailand. Adult patients with chest pain were enrolled between November 2018 and November 2019. The primary outcome was 30-day major adverse cardiac events (30-day MACE), defined as a composite of mortality, acute myocardial infarction, significant coronary stenosis and revascularization procedures. RESULTS: Of 350 recruited patients, 59 (16.9%) developed 30-day MACE. For the 0/1 hs-cTnT algorithm, sensitivity and negative predictive value (NPV) were 91.3% (95%CI 79.2-97.6%) and 97.2% (95%CI 93.2-98.9%), respectively. Specificity and positive predictive value were 79.6% (95%CI 72.8-85.2%) and 53.9% (95%CI 46.2-61.3%), respectively. Of the risk scores, the HEART score had the highest area under the receiver operator characteristic curve (0.74 [95%CI 0.68-0.81]). Combining the 0/1 hs-cTnT algorithm, a TIMI score cut-off of ≤1 had the best sensitivity and NPV (both 100%) and identified the greatest proportion of patients (24.3%) suitable for safe discharge. CONCLUSION: The 0/1 hs-cTnT algorithm may be feasible in Asian high-acuity ED patients. The HEART score outperformed other scores in predicting 30-day MACE. Combining the 0/1 hs-cTnT algorithm with a TIMI cut-off score ≤ 1 had the best rule-out performance.

Nasal High-flow Oxygen Versus Conventional Oxygen Therapy for Acute Severe Asthma Patients: A Pilot Randomized Controlled Trial.

BACKGROUND: Nasal high flow (NHF) has demonstrated efficacy in relieving dyspnea in various patients with hypoxemic and hypercapnic respiratory failure. It may also reduce dyspnea in patients with acute severe asthma in the emergency department (ED). The aim of the study was to compare the efficacy of NHF with conventional oxygen therapy (COT) in improving dyspnea in acute severe asthma patients with hypoxemia in the ED. METHODS: This pilot nonblinded randomized controlled trial was conducted involving 37 patients aged ≥ 18 years with acute severe asthma and hypoxemia in the ED of Siriraj Hospital, Bangkok, Thailand (TCTR20180926003). The participants were randomly allocated to receive either COT (n = 18) or NHF (n = 19) for 120 minutes. The primary outcome was comparing the intervention effects on the patients' degree of dyspnea measured using the modified Borg scale (MBS). The secondary outcomes were comparing the interventions based on the numeric rating scale (NRS) of dyspnea, the dyspnea scale assessing accessory muscle use, vital signs, and blood gas results. RESULTS: The intention-to-treat analysis included 37 patients (COT group n = 18 and NHF group n = 19). The baseline mean MBS was 7.8 in both groups. At 120 minutes, the mean (±SD) MBSs in patients receiving COT and NHF were 3.3 (±2.5) and 1.4 (±2.5), respectively (mean difference = 1.9 [95% CI = 0.2 to 3.8], p = 0.043). The trends in NRS and dyspnea score results were similar to those of MBS. Respiratory rates were lower with NHF (mean difference = 4.7 [95% CI = 1.5 to 7.8], p = 0.001). No between- or within-group differences in blood gas results were found. CONCLUSION: Nasal high flow reduced the severity of dyspnea and respiratory rate in hypoxemic patients with acute severe asthma in the ED.

Role of Point-of-Care Testing in Reducing Time to Treatment Decision-Making in Urgency Patients: A Randomized Controlled Trial.

INTRODUCTION: Shortening emergency department (ED) visit time can reduce ED crowding, morbidity and mortality, and improve patient satisfaction. Point-of-care testing (POCT) has the potential to decrease laboratory turnaround time, possibly leading to shorter time to decision-making and ED length of stay (LOS). We aimed to determine whether the implementation of POCT could reduce time to decision-making and ED LOS. METHODS: We conducted a randomized control trial at the Urgency Room of Siriraj Hospital in Bangkok, Thailand. Patients triaged as level 3 or 4 were randomized to either the POCT or central laboratory testing (CLT) group. Primary outcomes were time to decision-making and ED LOS, which we compared using Mann-Whitney-Wilcoxon test. RESULTS: We enrolled a total of 248 patients: 124 in the POCT and 124 in the CLT group. The median time from arrival to decision was significantly shorter in the POCT group (106.5 minutes (interquartile [IQR] 78.3-140) vs 204.5 minutes (IQR 165-244), p <0.001). The median ED LOS of the POCT group was also shorter (240 minutes (IQR 161.3-410) vs 395.5 minutes (IQR 278.5-641.3), p <0.001). CONCLUSION: Using a point-of-care testing system could decrease time to decision-making and ED LOS, which could in turn reduce ED crowding.

High-Flow Nasal Cannula Versus Conventional Oxygen Therapy in Relieving Dyspnea in Emergency Palliative Patients With Do-Not-Intubate Status: A Randomized Crossover Study.

STUDY OBJECTIVE: Palliative patients often visit the emergency department (ED) with respiratory distress during their end-of-life period. The goal of management is alleviating dyspnea and providing comfort. High-flow nasal cannula may be an alternative oxygen-delivering method for palliative patients with do-not-intubate status. We therefore aim to compare the efficacy of high-flow nasal cannula with conventional oxygen therapy in improving dyspnea of palliative patients with do-not-intubate status who have hypoxemic respiratory failure in the ED. METHODS: This randomized, nonblinded, crossover study was conducted with 48 palliative patients aged 18 years or older with do-not-intubate status who presented with hypoxemic respiratory failure to the ED of Siriraj Hospital, Bangkok, Thailand. The participants were randomly allocated to conventional oxygen therapy for 60 minutes, followed by high-flow nasal cannula for 60 minutes (n=24) or vice versa (n=24). The primary outcome was modified Borg scale score. The secondary outcomes were numeric rating scale score of dyspnea and vital signs. RESULTS: Intention-to-treat analysis included 44 patients, 22 in each group. Baseline mean modified Borg scale score was 7.6 (SD 2.2) (conventional oxygen therapy first) and 8.2 (SD 1.8) (high-flow nasal cannula first). At 60 minutes, mean modified Borg scale score in patients receiving conventional oxygen therapy and high-flow nasal cannula was 4.9 (standard of mean 0.3) and 2.9 (standard of mean 0.3), respectively (mean difference 2.0; 95% confidence interval 1.4 to 2.6). Results for the numeric rating scale score of dyspnea were similar to those for the modified Borg scale score. Respiratory rates were lower with high-flow nasal cannula (mean difference 5.9; 95% confidence interval 3.5 to 8.3), and high-flow nasal cannula was associated with a significantly lower first-hour morphine dose. CONCLUSION: High-flow nasal cannula was superior to conventional oxygen therapy in reducing the severity of dyspnea in the first hour of treatment in patients with do-not-intubate status and hypoxemic respiratory failure.

Effects of high-flow nasal cannula and non-invasive ventilation on inspiratory effort in hypercapnic patients with chronic obstructive pulmonary disease: a preliminary study.

BACKGROUND: Non-invasive ventilation (NIV) is preferred as the initial ventilatory support to treat acute hypercapnic respiratory failure in patients with chronic obstructive pulmonary disease (COPD). High-flow nasal cannula (HFNC) may be an alternative method; however, the effects of HFNC in hypercapnic COPD are not well known. This preliminary study aimed at assessing the physiologic effects of HFNC at different flow rates in hypercapnic COPD and to compare it with NIV. METHODS: A prospective physiologic study enrolled 12 hypercapnic COPD patients who had initially required NIV, and were ventilated with HFNC at flow rates increasing from 10 to 50 L/min for 15 min in each step. The primary outcome was the effort to breathe estimated by a simplified esophageal pressure-time product (sPTPes). The other studied variables were respiratory rate, oxygen saturation (SpO2), and transcutaneous CO2 pressure (PtcCO2). RESULTS: Before NIV initiation, the median [interquartile range] pH was 7.36 [7.28-7.37] with a PaCO2 of 51 [42-60] mmHg. sPTPes per minute was significantly lower with HFNC at 30 L/min than 10 and 20 L/min (p < 0.001), and did not significantly differ with NIV (median inspiratory/expiratory positive airway pressure of 11 [10-12] and [5-5] cmH2O, respectively). At 50 L/min, sPTPes per minute increased compared to 30 L/min half of the patients. Respiratory rate was lower (p = 0.003) and SpO2 was higher (p = 0.028) with higher flows (30-50 L/min) compared to flow rate of 10 L/min and not different than with NIV. No significant differences in PtcCO2 between NIV and HFNC at different flow rates were observed (p = 0.335). CONCLUSIONS: Applying HFNC at 30 L/min for a short duration reduces inspiratory effort in comparison to 10 and 20 L/min, and resulted in similar effect than NIV delivered at modest levels of pressure support in hypercapnic COPD with mild to moderate exacerbation. Higher flow rates reduce respiratory rate but sometimes increase the effort to breathe. Using HFNC at 30 L/min in hypercapnic COPD patients should be further evaluated. Trial registration Thai Clinical Trials Registry, TCTR20160902001. Registered 31 August 2016, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=2008 .

High-Flow Nasal Cannula Versus Conventional Oxygen Therapy in Emergency Department Patients With Cardiogenic Pulmonary Edema: A Randomized Controlled Trial.

STUDY OBJECTIVE: High-flow nasal cannula is a new method for delivering high-flow supplemental oxygen for victims of respiratory failure. This randomized controlled trial compares high-flow nasal cannula with conventional oxygen therapy in emergency department (ED) patients with cardiogenic pulmonary edema. METHODS: We conducted an open-label randomized controlled trial in the ED of Siriraj Hospital, Bangkok, Thailand. Patients aged 18 years or older with cardiogenic pulmonary edema were randomly assigned to receive either conventional oxygen therapy or high-flow nasal cannula. The primary outcome was the respiratory rate 60 minutes postintervention. RESULTS: We enrolled 128 participants (65 in the conventional oxygen therapy and 63 in the high-flow nasal cannula groups). Baseline high-flow nasal cannula and conventional oxygen therapy mean respiratory rates were 28.7 breaths/min (SD 3.2) and 28.6 breaths/min (SD 3.5). Mean respiratory rates at 60 minutes postintervention were lower in the high-flow nasal cannula group (21.8 versus 25.1 breaths/min; difference 3.3; 95% confidence interval 1.9 to 4.6). No significant differences were found in the admission rate, ED and hospital lengths of stay, noninvasive ventilation, intubation, or mortality. CONCLUSION: In patients with cardiogenic pulmonary edema in the ED, high-flow nasal cannula therapy may decrease the severity of dyspnea during the first hour of treatment.

Use of High-Flow Nasal Cannula for Acute Dyspnea and Hypoxemia in the Emergency Department.

BACKGROUND: Acute dyspnea and hypoxemia are 2 of the most common problems in the emergency room. Oxygen therapy is an essential supportive treatment to correct these issues. In this study, we investigated the physiologic effects of high-flow nasal oxygen cannula (HFNC) compared with conventional oxygen therapy (COT) in subjects with acute dyspnea and hypoxemia in the emergency room. METHODS: A prospective randomized comparative study was conducted in the emergency department of a university hospital. Forty subjects were randomized to receive HFNC or COT for 1 h. The primary outcome was level of dyspnea, and secondary outcomes included change in breathing frequency, subject comfort, adverse events, and rate of hospitalization. RESULTS: Common causes of acute dyspnea and hypoxemia were congestive heart failure, asthma exacerbation, COPD exacerbation, and pneumonia. HFNC significantly improved dyspnea (2.0 ± 1.8 vs 3.8 ± 2.3, P = .01) and subject comfort (1.6 ± 1.7 vs 3.7 ± 2.4, P = .01) compared with COT. No statistically significant difference in breathing frequency was found between the 2 groups at the end of the study. HFNC was well tolerated, and no serious adverse events were found. The rate of hospitalization in the HFNC group was lower than in the COT group, but there was no statistically significant difference (50% vs 65%, P = .34). CONCLUSIONS: HFNC improved dyspnea and comfort in subjects presenting with acute dyspnea and hypoxemia in the emergency department. HFNC may benefit patients requiring oxygen therapy in the emergency room.