key: cord-0051356-ljvizen9 authors: Ni, Zhong; Wang, Kaige; Wang, Ting; Ni, Yuenan; Huang, Wei; Zhu, Ping; Fan, Tao; Wang, Ye; Wang, Bo; Deng, Jun; Qian, Zhicheng; Liu, Jiasheng; Cai, Wenhao; Xu, Shanling; Du, Yu; Wang, Gang; Liang, Zongan; Li, Weimin; Luo, Jianfei; Luo, Fengming; Liu, Dan title: The efficacy of early prone or lateral positioning in severe COVID-19 patients: A single-center prospective cohort date: 2020-09-28 journal: Precis Clin Med DOI: 10.1093/pcmedi/pbaa034 sha: 392fce113232f926d702b109e92600e9d421c7e4 doc_id: 51356 cord_uid: ljvizen9 BACKGROUND: Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated severe COVID-19 patients has never been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated severe COVID-19 patients. METHODS: This was a single-center, prospective observational study in consecutive severe COVID-19 patients managed in a provisional ICU at Renmin Hospital of Wuhan University during January 31(st) to February 15(th), 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior part of the lungs were included. Early position intervention (prone or lateral) was commenced for > 4 hours daily for 10 days, while others had standard care. RESULTS: The baseline parameters were comparable between position intervention group (n = 17) and standard care group (n = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO(2)/FiO(2) (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (−9, 95 CI −15 to −3) during first 7 days. It also facilitated absorption of lung lesions and reduced patients of high National Early Warning Score 2 (≥ 7) on days 7 and 14 with a trend toward fastened clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups. CONCLUSIONS: This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated severe COVID-19 patients and warrants further randomized trials. admission (2) . The rate of invasive mechanical ventilation and mortality of severe COVID-19 patients remains high, partially attributed to delayed admission and intervention during the outbreak (3, 4) . Despite several endeavors of randomized, placebo-controlled trial of Lopinavir-Ritonavir (5) and compassionate use of Remdesivir (6) , chloroquine (7), convalescent plasma (8) , there remains no approved pharmacological treatment with definite efficacy for this devastating disease. Prone positioning has been shown to improve oxygenation and reduce complications and mortality in moderate-to-severe ARDS patients with invasive mechanical ventilation (9, 10) . Likewise, lateral positioning was associated with improved pulmonary gas exchange and drainage of secretions in critically ill patients, albeit its efficacy was inconclusive (11). The objective of this study was to investigate the impact of early prone or lateral positioning on oxygenation improvement, lung lesion absorption, and other clinical outcomes in awake severe COVID-19 patients. This prospective, observational cohort study, was designed, conducted and Three attending physicians independently securitized eligibility of patients for recruitment (Z.L., J.L., and T.W.). If there was a disagreement, final decision was made by the medical team leader (D.L.). All patients received standard care according to the interim guidance version 4 issued by the NHC of China (14) . According to whether received position intervention, these patients were divided into two groups: Standard care group: the standard care comprised supplemental oxygen and ventilation, antivirals (ribavirin or arbidor), antibiotics, anticoagulants, and glucocorticoids, as necessary, based on patients' clinical condition. In this group, no position intervention was introduced. unaware of the study design. The principle of discharge was based on relief of symptoms, obvious absorption of inflammation in chest CT, abatement of fever, and viral clearance with throat swabs for two consecutive times more than 24 hours apart. The data collection process followed quality assurance and standard operating procedures developed by senior authors (W.L., J.L., F.L., and D.L.). Two researchers (Z.L. and J.L.) independently started data collection at enrollment from electronic medical records independently using pre-defined pro forma. Data quality were checked by a third researcher (T.W.). These data contained epidemiological, virologic, clinical, laboratory, microbiological, radiological characteristics, disease severity indices, respiratory support method, pharmacological treatment, and other management details. The primary outcome was oxygenation improvement, determined by cumulative adjusted mean difference of SpO 2 /FiO 2 (served as oxygen saturation index), Respiratory rate-Oxygenation (ROX) index, and Borg scale between position intervention and standard care. scoring system was used to quantitatively estimate the pulmonary involvement of all abnormalities on the basis of the area involved (19) . Each of the 5 lung lobes was visually scored from 0 to 5 as previous study: 0, no involvement; 1, < 5% involvement; 2, 25% involvement; 3, 26%-49% involvement; 4, 50%-75% involvement; 5, > 75% involvement. The total CT score was the sum of the individual lobar scores and ranged from 0 (no involvement) to 25 (maximum involvement) (20) . The changes were stratified into obvious absorption (absorption proportion > 30%) and stable or deterioration (absorption proportion ≤ 30%, without absorption or lesion enlargement). The time to clinical improvement was defined as the time from enrollment to an improvement of two points on a seven-category ordinal scale or live discharge from the hospital, whichever came first (21). Adverse events for position intervention included hemodynamic instability and pressure sore (9, 22) . Continuous variables are presented as mean (SD) or median (IQR), Intention-to-treat analysis was additionally performed to verify our results. Statistical analysis was performed using the R statistical computing environment (version 3.63). A two-sided P value of 0.05 or less was considered to be statistically significant. The patient selection process is described in Figure 1 . Tables E1-3 ). There were no significant differences between position intervention group and standard care group in terms of baseline demographics, time to admission, oxygenation status, severity indices, and laboratory markers (Table 1) . There were also no significant differences for respiratory support, antivirals, antibiotics, anticoagulants, and glucocorticoids (and duration) between the two groups ( Table 2) (Figure 2A ). This was accompanied by significantly increased ROX index ( Figure 2B ) and decreased Borg scale ( Figure 2C ) since day 3 with a cumulative value of 26 (95% CI 9-43) and -9 (95% CI -15 to -3), respectively. All these findings are suggestive early position intervention effectively improved oxygenation and reduced dyspnea as compared to standard care. Chest imaging showed that the CT score for lung lesion was significantly reduced in both groups ( Figure 3A) , with position intervention group: 9.9 ± 1.9, after vs. 17.2 ± 5.6, before (P < 0.001) and standard care group: 10.9 ± 2, after vs. 14 ± 6, before (P < 0.015). In corroborate with improved oxygenation, early position intervention was also associated with more patients had apparent lung lesion absorption (16/17, 94% vs. 11/35, 31%, P < 0.001; Figure 3B and Table 2 ). Representative chest CT images of a patient who underwent prone positioning are presented in Figure 3C . The proportion of patients with high NEWS2 (≥ 7) in the position intervention group was significantly lower on days 7 (11.8% vs. 51.4%, P = 0.009) and 14 (11,8% vs. 21.2%, P = 0.007) than those who were in the standard care group ( Table 2) No significant difference in rate of intubation avoidance, virus shedding, and length of hospital stay was observed between the two groups ( Table 2) . No adverse events occurred during the study. Results for clinical outcomes were unaltered between the two groups when intention-to-treat analysis was performed (Supplementary Figure E2 and Table E4 -5). This was the first study to evaluate the efficacy and safety for early use of protect against them to progress to severe ARDS and avoid intubation. A recent meta-analysis has shown a longer prone positioning time (12 hours or more) was associated with lower mortality in patients with moderate to severe ARDS (9) . However, since it was difficult for our patients to hold the unusual position for 12 hours, a 4-hour positioning procedure was adopted. It appeared that this procedure was well tolerated by the 17 out of 20 patients, even in patients with comorbid cardiovascular and lung diseases. The reason for 3 dropped out patients were mainly due to subjective incompliance rather than actual intolerance or disease severity. Patient education and encouragement may further improve tolerability and reduce nursing burdens especially for the scarce ICU resources during this global pandemic (24) . In this study, we used the oxygen saturation index (SpO 2 /FiO 2 ) to evaluate the oxygenation level of the patients. SpO 2 /FiO 2 is reliable noninvasive surrogate maker for PaO 2 /FiO 2 (25, 26) and is more practical for continuous oxygenation monitoring in awake COVID-19 patients. ROX index was calculated by SpO 2 /FiO 2 to RR and was reported to have an additive effect on the accuracy for discriminating between succeeded and failed patients who received high-flow nasal cannula oxygen therapy (27, 28) . Here we used the ROX index to help assessing the clinical improvement or deterioration. Borg scale was recommended measures for breathlessness from 0 to 10 score (16) . 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Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS National Institutes of Health /National Heart L, Blood Institute P, Early Treatment of Acute Lung Injury N. Nonlinear Imputation of PaO2/FIO2 From SpO2/FIO2 Among Mechanically Ventilated Patients in the ICU: A Prospective, Observational Study Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome Effect of body position and inclination in supine and prone position on respiratory mechanics in acute respiratory distress syndrome PT, second, median (IQR) Definition of abbreviations: COPD=Chronic obstructive pulmonary disease; PaO 2 /FiO 2 = partial pressure of arterial oxygen to fraction of inspired oxygen ratio; PSI=Pneumonia Severity Index ALT=alanine transaminase; AST=aspartate aminotransferase; LDH=lactate dehydrogenase; CK-MB=creatine kinase myocardial band BNP= B-type natriuretic peptide; CRP=C-reactive protein The authors declare no competing interests.