key: cord-0027861-b0sax5no authors: Bai, Linfu; Ding, Fei; Xiong, Weiming; Shu, Weiwei; Jiang, Lei; Liu, Yuliang; Duan, Jun title: Early assessment of the efficacy of noninvasive ventilation tested by HACOR score to avoid delayed intubation in patients with moderate to severe ARDS date: 2022-02-24 journal: Ther Adv Respir Dis DOI: 10.1177/17534666221081042 sha: af05cd10c245662d0c6547725697d25d1775fdd1 doc_id: 27861 cord_uid: b0sax5no BACKGROUND: Use of noninvasive ventilation (NIV) in patients with moderate to severe ARDS is controversial. We aimed to use HACOR (combination of heart rate, acidosis, consciousness, oxygenation and respiratory rate) score to comprehensively assess the efficacy of NIV in ARDS patients with PaO(2)/FiO(2) ⩽ 150 mmHg. METHODS: Secondary analysis was performed using the data collected from two databases. We screened the ARDS patients who used NIV as a first-line therapy. Patients with PaO(2)/FiO(2) ⩽ 150 mmHg were enrolled. NIV failure was defined as requirement of intubation. RESULTS: A total of 224 moderate to severe ARDS patients who used NIV as a first-line therapy were enrolled. Of them, 125 patients (56%) experienced NIV failure and received intubation. Among the intubated patients, the survivor had shorter time from initiation of NIV to intubation than nonsurvivors (median 10 vs 22 h, p < 0.01). The median differences of HACOR score before and 1–2 h of NIV were 1 point (interquartile range: 0–3). We defined the patients with △HACOR >1 as responders (n = 102) and the rest to non-responders (n = 122). Compared to non-responders, the responders had higher HACOR score before NIV. However, the HACOR score was lower in the responders than non-responders after 1–2 h, 12 h, and 24 h of NIV. The responders also had lower NIV failure rate (36% vs 72%, p < 0.01) and lower 28-day mortality (32% vs 47%, p = 0.04) than non-responders. CONCLUSIONS: NIV failure was high among patients with moderate to severe ARDS. Delayed intubation is associated with increased mortality. The reduction of HACOR score after 1–2 h of NIV can identify the patients who respond well to NIV. to die than those who directly received invasive mechanical ventilation among the cases with PaO 2 / FiO 2 ⩽ 150 mmHg. 2 However, not all the ARDS patients with PaO 2 /FiO 2 ⩽ 150 mmHg require intubation. Assessment of the patients who respond well to NIV can reduce unnecessary intubation and ventilator-associated complications. The HACOR (assessed by heart rate, acidosis, consciousness, oxygenation and respiratory rate) score has high predictive power to distinguish NIV success and failure among patients with acute respiratory failure. [8] [9] [10] However, the impact of HACOR score on NIV outcomes in ARDS patients with PaO 2 /FiO 2 ⩽ 150 mmHg is unclear. Here, we aimed to assess the moderate to severe ARDS patients who respond well to NIV with the use of HACOR score. This was a secondary analysis of the data came from two previous published articles. 8, 11 In Duan et al'.s 8 study, the data were prospectively collected from June 2011 to June 2016 in a respiratory intensive care unit (ICU). A total of 807 patients with hypoxemic respiratory failure received NIV as a first-line therapy. Of them, 130 cases were diagnosed as ARDS and considered to be eligible in current study. In Shu et al'.s 11 study, the data were prospectively collected from September 2017 to December 2019 in 17 ICUs in China. A total of 3754 patients were screened, and 345 ARDS patients who received NIV as a first-line therapy were candidates. As the aim of current study is focused on ARDS patients with PaO 2 /FiO 2 ⩽ 150 mmHg, 221 cases with mild to moderate ARDS were excluded ( Figure 1 ). Another 30 cases with treatment limitation were also excluded. Therefore, a total of 224 patients were enrolled to final analyses. The study protocol was approved by the local ethics committee and institutional review board (the First Affiliated Hospital of Chongqing Medical University, NO. 2021-414). As this was a secondary analysis, the informed consent was waived. The management of NIV has been described in previously published articles. 8, 11 The attending physicians initiated the use of NIV based on the journals.sagepub.com/home/tar 3 following criteria: clinical presentation of respiratory distress at rest (such as active contraction of the accessory inspiratory muscles, paradoxical abdominal motion, or respiratory rate more than 25 breaths/min), PaO 2 < 60 mmHg at room air or PaO 2 /FiO 2 < 300 mmHg with supplemental oxygen. The face mask as the first choice was used to connect the patient to the ventilator. The positive-end expiratory pressure (PEEP) was maintained at 4-8 cmH 2 O and inspiratory pressure was maintained around 15 cmH 2 O. If the patient failed to tolerate the pressure of 15 cmH 2 O, it was decreased. The lowest pressure of 8 cmH 2 O was allowed. The fraction of inspiration oxygen was set to achieve peripheral oxygen saturation more than 92%. The upper limit of saturation was not predetermined. But it was limited no more than 98% in most of the participated centers. If the respiratory failure was reversed, the weaning from NIV was performed. However, if the respiratory failure was worsened, the intubation for invasive mechanical ventilation was considered. The NIV failure was defined as requirement of intubation. The criteria of intubation were referenced previous standards. 8, 11 The HACOR score was assessed before, and after 1-2 h, 12 h and 24 h of NIV. 8 It included five variables (heart rate, acidosis, consciousness, oxygenation and respiratory rate To assess the efficacy of NIV, the differences of HACOR score before and 1-2 h of NIV were calculated. Given the previous study used the increase of oxygenation more than the median value after prone position to define the response to prone position in ARDS patients, we classified the patients with △HACOR larger than the median value to responsible group and the rest to nonresponsible group. 12 The Kaplan-Meier curve was used to analyze the cumulative 28-day survival probability and the difference between two groups was analyzed by log-rank test. A p value less than 0.05 was considered to be statistical significance. Among the 224 moderate to severe ARDS patients, NIV failure occurred in 125 cases (56%). All the patients with NIV failure received intubation for invasive mechanical ventilation. Among the intubated patients, we recorded 43 survivors and 82 non-survivors at 28 days (Table 1 ). There were no differences in age, sex and APACHE II score between survivors and nonsurvivors. The vital signs, arterial blood gas tests and HACOR score collected before and after 1-2 h of NIV were also no differences between the two groups. The survivors only had lower proportion of pulmonary ARDS (70% vs 90%, p < 0.01) on the terms of demographics. The time from NIV initiation to intubation was median 10 h (IQR: 2-22) in survivors ( Figure 2 ). However, it increased to 22 h (IQR: 5-77) in nonsurvivors. The crude odds ratio (OR) of death at 28 days was 1.015 per one hour delayed intubation (95% confidence interval (CI): 1.004-1.026). When the OR was adjusted by age, sex, disease severity, origin of ARDS, comorbid conditions, vital signs, arterial blood gas tests, ventilator parameters and HACOR score, it was 1.015 (95%CI: 1.001-1.029). The differences of HACOR score before and after 1-2 h of NIV were summarized in supplementary Figure 1 . The median value was 1 (IQR: 0-3). In the total cohort, patients with △HACOR >1 were defined as responders (n = 102) and those with △HACOR ⩽ 1 as non-responders (n = 122). The responders had lower proportion of pulmonary ARDS (63% vs 84%, p < 0.01) than nonresponders (Table 2) . Before NIV, the HACOR score was higher (7.7 ± 2.7 vs 6.7 ± 2.0, p < 0.01) in responders than that in non-responders ( Figure 3 ). However, the HACOR score was lower in responders after 1-2 h, 12 h, and 24 h of NIV (3.7 ± 2.8 vs 7.3 ± 2.9, p < 0.01; 3.4 ± 2.5 vs 5.5 ± 2.4 p < 0.01; and 2.6 ± 2.7 vs 5.2 ± 2.8, p < 0.01, respectively). The reduction of respiratory rate and heart rate after 1-2 h, 12 h and 24 h of NIV was faster in responders than that in non-responders ( Figure 4 ). The PaO 2 /FiO 2 in responders was also improved faster. The NIV failure rate was 36% in responders, which was much lower than non-responders (72%). The 28-day mortality was also lower in responders (32% vs 47%, p = 0.04). Current study shows that 56% of ARDS patients with PaO 2 /FiO 2 less than 150 mm Hg experienced NIV failure. Delayed intubation is associated with increased mortality. After 1-2 h of NIV, 46% of patients respond well to NIV assessed by HACOR score. The responders were associated with decreased NIV failure and 28-day mortality. Previous studies have reported that delayed intubation leads to increase in mortality. [13] [14] [15] [16] Among the patients who received high-flow nasal cannula, ICU mortality was 39.2% in patients who experienced intubation less than 48 h; however, it increased to 66.7% in those beyond 48 h. 15 Among the patients who received NIV due to de novo acute respiratory failure, the time from NIV initiation to intubation was 32 h in survivors, but it increased to 78 h in nonsurvivors. 16 In our study, we also found that the survivors were received intubation earlier than nonsurvivors among the patients who experienced NIV failure. Per one hour delayed intubation was associated with 1.019fold increase in 28-day mortality. These results validate the viewpoint that delayed intubation is associated with increased mortality. Early intubation is a potential strategy to reduce mortality. Noninvasive strategies appear safe and effective in patient with PaO 2 /FiO 2 > 150 mmHg, while they can yield delayed intubation with increased mortality in a significant proportion of cases with PaO 2 /FiO 2 ⩽ 150 mmHg. 17 However, in clinical practices, the use of NIV in ARDS patients with PaO 2 /FiO 2 ⩽ 150 mmHg is not rare. Among the ARDS patients who received NIV as a first-line therapy, the proportion of PaO 2 /FiO 2 ⩽ 150 mmHg was 49.29%. 2 Among the moderate to severe ARDS patients, the mortality was higher in the cases who received NIV as a first-line therapy than those who directly received invasive mechanical ventilation. The most likely reason for increased mortality is delayed intubation. Early identification of the patients who respond well to NIV is crucial. Current study used the HACOR score to assess the efficacy of NIV in moderate to severe ARDS patients and found that reduction of HACOR score more than 1 point after 1-2 h of NIV had the ability to identify the patients who responded well or badly to NIV. Among the non-responders, early termination of NIV and performance of intubation is potential to reduce mortality. In clinical practices, it is common to assess the efficacy of NIV by several clinical variables, e.g. respiratory rate, heart rate, oxygenation et al. 8, 18 However, how to comprehensively assess the efficacy of NIV is lacking. The HACOR was scored by five easily obtained variables (heart rate, acidosis, consciousness, oxygenation, and respiratory rate), and the importance of each variable was ranked by the weights. 8 Therefore, it has the potential to assess the efficacy of NIV. Current study shows the benefits on reduction of NIV failure and 28-day mortality among patients who respond well to NIV assessed by HACOR score after 1-2 h of NIV. It indicates that the HACOR score is a promising scale to manage NIV patients with moderate to severe ARDS. This study has several limitations. First, this is a secondary analysis of previous collected data. The performance of intubation was decided by the attending physician's discretions. Delayed intubation is inevitable. Second, we only reported how to assess the efficacy of NIV using HACOR score after 1-2 h of intervention. The efficacy beyond 2 h of NIV is unclear. Third, the risk of NIV failure is high in moderate to severe ARDS patients. The reduction of HACOR score only reflects a relatively lower risk of NIV failure. Combination of other variables to assess the efficacy of NIV is required. Although the use of NIV in ARDS patients with PaO 2 /FiO 2 ⩽ 150 mmHg is not encouraged, the proportion reaches 50% in the whole ARDS patients who used NIV as a first-line therapy. Delayed intubation is associated with 28-day mortality. Reduction of HACOR scores more than 1 point after 1-2 h of NIV can assess the patients who respond well to NIV. The responders are associated with a reduction of NIV failure and 28-day mortality. ALI and ARDS: challenges and advances Noninvasive ventilation of patients with acute respiratory distress syndrome. 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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article. https://orcid.org/0000-0003-1685-0117 Supplemental material for this article is available online.