Correction: Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

[This corrects the article DOI: 10.1371/journal.pone.0261234.].

Comparison of ROX index (SpO2/FIO2 ratio/respiratory rate) with a modified dynamic index incorporating PaO2/FIO2 ratio and heart rate to predict high flow nasal cannula outcomes among patients with acute respiratory failure: a single centre retrospective study.

BACKGROUND: High flow nasal cannula (HFNC) is increasingly being used to support patients with acute respiratory failure (ARF) and to avoid need for intubation. However, almost one third of the patients do not respond and require escalation of respiratory support. Previously, ROX index (SpO2/FIO2 [SF] ratio/respiratory rate) has been validated among pneumonia patients to facilitate early recognition of patients likely to fail HFNC and therefore, benefit from timely interventions. However, it has been postulated that incorporation of PaO2/FIO2 (PF) ratio from arterial blood gas (ABG) analysis may better predict the outcome of HFNC compared to indices that utilizes SF ratio. Similarly, heart rate increase after HFNC therapy initiation has been found to be associated with HFNC failure. Therefore, we aimed to compare ROX index with a new modified index to predict HFNC outcomes among ARF patients. MATERIALS AND METHODS: This single centre 2-year retrospective study included ARF patients of varying etiologies treated with HFNC. The modified index incorporated heart rate and substituted PF ratio for SF ratio in addition to respiratory rate. We named the index POX-HR and calculated Delta POX-HR index as the difference pre- and post-HFNC initiation POX-HR. We also recorded ROX index at the time when post-HFNC initiation ABG was done ('post-HFNC initiation ROX') and calculated Delta ROX. HFNC success was defined as no need of escalation of respiratory support or discharged to ward within 48 h of HFNC initiation, or successful wean off HFNC for at least 12 h. Evaluation was performed using area under the receiver operating characteristic curve (AUROC) and cut-offs assessed for prediction of HFNC outcomes. RESULTS: One hundred eleven patients were initiated on HFNC for ARF, of whom 72 patients (64.9%) had HFNC success. Patients with HFNC failure had significantly lower values for all the indices. At median of 3.33 h (IQR 1.48-7.24 h), Delta POX-HR demonstrated the best prediction accuracy (AUROC 0.813, 95% CI 0.726-0.900). A Delta POX-HR > 0.1 was significantly associated with a lower risk of HFNC failure. CONCLUSIONS: Our proposed modified dynamic index (Delta POX-HR) may facilitate early and accurate prediction of HFNC outcomes compared to ROX index among ARF patients of varied etiologies.

Expanding the utility of the ROX index among patients with acute hypoxemic respiratory failure.

BACKGROUND: Delaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction. METHODS: This was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation. RESULTS: HFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64-0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57-0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55-0.69)] and one hour later [AUC 0.63 (95% CI 0.56-0.70)]. CONCLUSION: The ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

High-flow nasal cannula therapy: A multicentred survey of the practices among physicians and respiratory therapists in Singapore.

BACKGROUND: Use of high-flow nasal cannula (HFNC) has become a regular intervention in the intensive care units especially in patients coming in with hypoxaemic respiratory failure. Clinical practices may differ from published literature. OBJECTIVES: The objective of this study was to determine the clinical practices of physicians and respiratory therapists (RTs) on the use of HFNC. METHODS: A retrospective observational study looking at medical records on HFNC usage from January 2015 to September 2017 was performed and was followed by a series of questions related to HFNC practices. The survey involved physicians and RTs in intensive care units from multiple centres in Singapore from January to April 2018. Indications and thresholds for HFNC usage with titration and weaning practices were compared with the retrospective observational study data. RESULTS: One hundred twenty-three recipients (69.9%) responded to the survey and reported postextubation (87.8%), pneumonia in nonimmunocompromised (65.9%), and pneumonia in immunocompromised (61.8%) patients as the top three indications for HFNC. Of all, 39.8% of respondents wanted to use HFNC for palliative intent. Similar practices were observed in the retrospective study with the large cohort of 63% patients (483 of the total 768 patients) where HFNC was used for acute hypoxaemic respiratory failure and 274 (35.7%) patients to facilitate extubation. The survey suggested that respondents would initiate HFNC at a lower fraction of inspired oxygen (FiO2), higher partial pressure of oxygen to FiO2 ratio, and higher oxygen saturation to FiO2 ratio for nonpneumonia patients than patients with pneumonia. RTs were less likely to start HFNC for patients suffering from pneumonia and interstitial lung disease than physicians. RTs also preferred adjustment of FiO2 to improve oxygen saturations and noninvasive ventilation for rescue. CONCLUSIONS: Among the different intensive care units surveyed, the indications and thresholds for the initiation of HFNC differed in the clinical practices of physicians and RTs.

Predictors and outcomes of high-flow nasal cannula failure following extubation: A multicentre observational study.

INTRODUCTION: Despite adhering to criteria for extubation, up to 20% of intensive care patients require re-intubation, even with use of post-extubation high-flow nasal cannula (HFNC). This study aims to identify independent predictors and outcomes of extubation failure in patients who failed post-extubation HFNC. METHODS: We conducted a multicentre observational study involving 9 adult intensive care units (ICUs) across 5 public hospitals in Singapore. We included patients extubated to HFNC following spontaneous breathing trials. We compared patients who were successfully weaned off HFNC with those who failed HFNC (defined as re-intubation ≤7 days following extubation). Generalised additive logistic regression analysis was used to identify independent risk factors for failed HFNC. RESULTS: Among 244 patients (mean age: 63.92±15.51 years, 65.2% male, median APACHE II score 23.55±7.35), 41 (16.8%) failed HFNC; hypoxia, hypercapnia and excessive secretions were primary reasons. Stroke was an independent predictor of HFNC failure (odds ratio 2.48, 95% confidence interval 1.83-3.37). Failed HFNC, as compared to successful HFNC, was associated with increased median ICU length of stay (14 versus 7 days, P<0.001), ICU mortality (14.6% versus 2.0%, P<0.001) and hospital mortality (29.3% versus 12.3%, P=0.006). CONCLUSION: Post-extubation HFNC failure, especially in patients with stroke as a comorbidity, remains a clinical challenge and predicts poorer clinical outcomes. Our observational study highlights the need for future prospective trials to better identify patients at high risk of post-extubation HFNC failure.

In-hospital cardiac arrest incidence and outcomes in the era of COVID-19: an observational study in a Singapore hospital.

BACKGROUND: COVID-19 pandemic has resulted in significant strain on healthcare resources and this requires diligent resource re-allocation. We aim to describe the incidence and outcomes of in-hospital cardiac arrest (IHCA) during this period as compared to non-pandemic period. METHODS: We conducted a retrospective study in a tertiary care hospital in Singapore. The study compared the incidence and outcomes of code blue activations over a 3-month period from March to May 2020 (COVID-19 period) with the same months in 2019 (pre-COVID-19 period). The primary outcome of the study was the rate of survival to hospital discharge for IHCA. The secondary outcomes included incidence of all code blue activation per 1000 hospital admissions, incidence of IHCA per 1000 hospital admissions. OUTCOMES: The rate of survival to hospital discharge for IHCA was 5.88% in the COVID-19 period as compared to 10.0% in the pre-COVID-19 period [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.26-1.95]. Compared to pre-COVID-19 period, there were more IHCA incidences per 1000 hospital admissions in the COVID-19 period (1.86 vs 1.03; OR, 1.81; 95% CI, 0.78-4.41). CONCLUSIONS: The study observed a trend towards higher incidence of IHCA and lower rate of survival to hospital discharge during COVID-19 pandemic compared to pre-COVID-19 period.

The effect of neuromuscular blocking agents uses in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: With the latest addition from Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) Trial result, the question of mortality benefit from neuromuscular blocking agents (NMBAs) in different studies, remained unanswered. We hypothesize that NMBAs use in moderate to severe acute respiratory distress syndrome (ARDS) does not influence intensive care unit (ICU) mortality. EVIDENCE ACQUISITION: Pubmed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) related to NMBAs infusion in patients with ARDS. The primary outcome was ICU mortality. Secondary outcomes were mortality at day 28 and day 90, oxygenation response to NMBA, ICU length of stay (LOS), ICU Acquired weakness (ICU-AW) and ventilator-free days (VFDs). Meta-analysis was conducted to re-evaluate the effect of NMBAs on patients with ARDS with all randomized controlled trials available. EVIDENCE SYNTHESIS: NMBAs infusion was associated with reduced ICU mortality (relative ratio [RR]: 0.69; 95% confidence-interval [CI]: 0.55-0.88; I2=0%), but not 28 days mortality (RR: 0.76; 95% CI: 0.57-1.0; I2=49%) and 90-day mortality (RR: 0.87; 95% CI: 0.70-1.08; I2=46%). NMBA use was not associated with increased risk of ICU-AW (RR: 1.21; 95% CI, 0.84 to 1.76; I2=34%). CONCLUSIONS: Early 48-hour NMBAs infusion in patients with moderate to severe ARDS was associated with reduced ICU mortality without improvement in oxygenation, VFDs, 28-day and 90-day mortality. It did not contribute significantly to ICU-AW. Based on these results, NMBAs infusion is recommended for moderate to severe ARDS for its short-term benefit in early phase of disease. Prolonged use of NMBAs beyond 48 hours requires further study.

Impact of implementing novel automated code blue activation system on in-hospital cardiac arrest: A single center study.

BACKGROUND: Prompt identification and management of patients having clinical deterioration on wards is one of the key steps to reduce in-hospital cardiac arrests (IHCA). Our organization implemented a novel Automated Code Blue Alert and Activation (ACBAA) system since 1st March 2018. METHODS: We conducted a retrospective before-and-after ACBAA system implementation study in JurongHealth Campus (JHC) of National University Health system (NUHS), Singapore. In JHC, code blue can be activated by both manual activation and ACBAA system activation from 1st March 2018. The ACBAA system will be activated when any of the pre-defined peri-arrest criteria is met. The primary outcome of the study was the incidence of IHCA. The secondary outcome included return of spontaneous circulation (ROSC) of IHCA and in-hospital survival to home discharge of code blue activation. OUTCOMES: The incidence of IHCA per 1000 hospital admissions after-ACBAA system implementation was 14.6% lower than before-ACBAA system though not statistically significant [relative risk (RR): 0.86, 95% confidence interval (CI) 0.55-1.34, P > 0.05]. Compared to the before-ACBAA system period, the after-ACBAA system period had a trend for higher rate of survival to home discharge after IHCA (RR: 2.13, 95% CI 0.65-6.93, P > 0.05) with good neurological outcome. CONCLUSIONS: Implementation of a novel ACBAA system has shown a trend in reducing IHCA incidence. In the era of digitalised healthcare system, the ACBAA system is practical and advisable to implement in order to reduce IHCA. Further studies are required to validate the criteria for peri-arrest code blue activation.