Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China.

BACKGROUND: Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). OBJECTIVE: To identify whether corticosteroids were beneficial to COVID-19 patients. METHODS: A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. RESULTS: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. CONCLUSION: Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.

Impact of Shenfu injection on a composite of organ dysfunction development in critically ill patients with coronavirus disease 2019 (COVID-19): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to determine the protection provided by Shenfu injection (a traditional Chinese medicine) against development of organ dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19). TRIAL DESIGN: This study is a multicenter, randomized, controlled, open-label, two-arm ratio 1:1, parallel group clinical trial. PARTICIPANTS: The patients, who are aged from 18 to 75 years old, with a confirmed or suspected diagnosis of severe or critical COVID-19, will be consecutively recruited in the study, according to the guideline on diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers. The study is conducted in 11 ICUs of designated hospitals for COVID-19, located in 5 cities of China. INTERVENTION AND COMPARATOR: The enrolled patients will randomly receive 100 ml SFI (study group) or identical volume of saline (control group) twice a day for seven consecutive days. Patients in the both groups will be given usual care and the necessary supportive therapies as recommended by the latest edition of the management guidelines for COVID-19 (the 7th version so far). MAIN OUTCOMES: The primary endpoint is a composite of newly developed or exacerbated organ dysfunction. This is defined as an increase in the sequential organ failure assessment (SOFA) score of two or more, indicating sepsis and involvement of at least one organ. The SOFA score will be measured for the 14 days after enrolment from the baseline (the score at randomization). The secondary endpoints are shown below: • SOFA score in total • Pneumonia severity index score • Dosage of vasoactive drugs • Ventilation free days within 28 days • Length of stay in intensive care unit • Total hospital costs to treat the patient • 28-day mortality • The incidence of adverse drug events related to SFI RANDOMISATION: The block randomization codes were generated by SAS V.9.1 for allocation of participants in this study. The ratio of random distribution is 1:1. The sealed envelope method is used for allocation concealment. BLINDING (MASKING): The patients and statistical personnel analyzing study data are both blinded. The blinding of group assignment is not adopted for the medical staff. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study is expected to recruit 300 patients with COVID-19, (150 in each group). TRIAL STATUS: Protocol version 2.0, February 15, 2020. Patient recruitment started on February 25, and will end on August 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000030043. Registered February 21, 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49866 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study.

INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study.

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.

Tracheostomy in 80 COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies. Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days). Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3-27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy. Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

[The study of hypertonic saline and hydroxyethyl starch treating severe sepsis].

OBJECTIVE: To evaluate the effect of 7.5% hypertonic saline (HS) and 6% hydroxyethyl starch (HES) 130/0.4 on early fluid resuscitation for severe sepsis. METHODS: Prospective randomized control trial was carried out in intensive care unit (ICU) of the Affiliated Hospital of Jianghan University. One hundred and thirty five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7.5% HS and 6% HES 130/0.4 500 ml, those in HES group received lactated Ringer solution following 6% HES 130/0.4 500 ml, and those in the lactated Ringer group (RL group) received lactated Ringer solution only.Mean arterial pressure (MAP), oxygenation index (PaO2/FiO2),arterial lactate (Lac),lactate clearance rate, acute physiology and chronic health evaluation II(APACHEII) score,fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome (MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission. RESULTS: At 6 hours after ICU admission,MAP[mm Hg (1 mm Hg=0.133 kPa): 68.7 ± 3.0], PaO2/FiO2(mm Hg: 262.2 ± 17.4), lactate clearance rate [(21 ± 4)%] in HS+HES group were significantly higher than those in HES group [MAP: 63.8 ± 3.5,PaO(2)/FiO(2): 252.0 ± 21.2, lactate clearance rate: (11 ± 2)%] and RL group [MAP: 62.6 ± 3.6, PaO2/FiO2:248.4 ± 17.0,lactate clearance rate: (9 ± 1)%, all P <0.01]. Arterial Lac in HS+HES group (mmol/L: 3.5 ± 0.7) was significantly lower than that in HES group (4.1 ± 0.7) and RL group (4.0 ± 0.7, both P <0.01). There was no significant difference in APACHE II score between HS+HES group (13.2 ± 1.9) and HES group (14.0 ± 1.6), and the APACHEII score in HS+HES group was significantly lower than that in RL group (15.2 ± 1.7, P <0.01). At 24 hours after ICU admission, PaO2/FiO2 (mm Hg: 303.3 ± 17.3) was significantly higher in HS+HES group than that in HES group (282.9 ± 21.1) and RL group (268.9 ± 15.2, both P <0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHEII score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group (ml, 6 hours: 1 877.8 ± 215.2, 24 hours: 5 475.6 ± 208.8) was markedly less than that in HES group (6 hours: 2 505.6 ± 276.2, 24 hours: 6 383.3 ± 287.4) and RL group (6 hours: 3 496.7 ± 325.5,24 hours: 7 439.6 ± 229.6), yet urine output in HS+HES group (ml, 6 hours: 294.2 ± 36.9, 24 hours : 2 793.8 ± 37.1) was significantly higher than that in HES group (6 hours: 248.9 ± 25.3, 24 hours : 2 248.9 ± 25.3) and RL group (6 hours: 178.9 ± 14.8, 24 hours: 2 000.4 ± 147.0, all P <0.01). The incidence of MODS in HS+HES group (6.7%) was statistically lower than that in RL group (28.9%, P <0.05), while no obvious difference was found between HS+HES group and HES group (17.8%, P >0.05). There was no significant difference in mortality among three groups (HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P >0.05). CONCLUSION: 7.5%HS and 6%HES 130/0.4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS.

[Value of microalbuminuria in fluid balance after abdominal surgery].

OBJECTIVE: To evaluate the relationship among the microalbuminuria, surgical stress and postoperative fluid balance after abdominal surgery. METHODS: A total of 191 patients undergoing an elective abdominal operation were studied. According to the extent of operative trauma, all patients were divided into 4 groups. GroupI: laparoscopic cholecystectomy (n=64); Group II: laparotomy of cholecyst and biliary tract (n=36); Group III: radical surgery of colorectal cancer (n=43); Group IV: distal subtotal gastrectomy (D2) or total gastectomy (D3) or pancreaticoduodenectomy (n=48). The operative severities were predicated by surgical stress score (SSS). Urine albumin-creatinine ratio (ACR) was measured at both pre- and post-operation. The levels of ACR were compared by ANOVA among these 4 groups. The correlation of ACR and SSS was analyzed. In Groups III and IV, body weight was measured by weight-bed simultaneously. The correlation of variation of ACR at 0 and 6 hours post-operation (ΔACR) and the volume of positive fluid balance in the first 24 hour post-operation were studied. We also compared the varied durations of ACR levels returning to normal or the pre-operative level and body weight reaching peak values. RESULTS: The levels of ACR increased in all groups. The level of ACR was the highest in Group IV and the lowest in Group I, significantly different from the levels of group II and III. There was a significant positive correlation between the increase in ACR and the severity of surgical trauma as measured by SSS. A positive correlation was observed between the volume of positive fluid balance in the first 24 hour post-operation and ΔACR at 0 and 6 hours post-operation. The varied duration of ACR levels returning normal or the pre-operative level was earlier than that of reaching the peak values. CONCLUSION: ACR has a positive correlation with the extent of surgical stress and volume of positive fluid balance. The fact that the ACR comes earlier than the change of body weight indicates that the change of ACR is a more sensitive and simpler parameter than body weight to predict the onset of negative fluid balance.

[Application of B type natriuretic peptide in fluid therapy after major abdominal operations].

OBJECTIVE: To evaluate the values of serum level of B type natriuretic peptide level (BNP) in the prediction of fluid overloading after major abdominal operations. METHODS: The levels of BNP were dynamically monitored in 105 patients during peri-operative period from February 2009 to November 2010. Then comparisons were made with age and the volume of positive fluid balance. RESULTS: A post-operative elevation of BNP was observed in all cases. Among them, the peak level of BNP exceeded 100 ng/L in 32 patients while a normal peak level of BNP was found in 73 patients. Congestive heart failure (CHF) was diagnosed in 5 patients. At every single time point, the volume of positive fluid balance showed no significant difference among the peak level of BNP < 100 ng/L, ≥ 100 ng/L and CHF patients (all P > 0.05). In the group of peak level of BNP ≥ 100 ng/L, the patients received post-operative diuretic and the urine volume increased significantly [(280 ± 55) ml/h vs (82 ± 22) ml/h, P < 0.05]. However, in the group of the peak level of BNP < 100 ng/L, the urine volume showed no difference after dosing of diuretic [(95 ± 18) ml/h vs (89 ± 24) ml/h, P > 0.05]. Single variance analysis showed that the elevated level of BNP was associated with age and concurrent cardiopulmonary diseases (R = 0.87, P = 0.006) but not with the volume of positive fluid balance (R = 0.43, P = 0.080). And multiple variance analysis showed the similar results (R = 0.59, P = 0.020, R = 0.38, P = 0.120). In all cases, the levels of BNP peaked at 12 hours post-operation. However, body weight and the volume of positive fluid balance peaked at 18 - 24 hours post-operation. CONCLUSION: The post-operative level of BNP is associated with age. And a highly elevated level of BNP may predict the occurrence of fluid overloading. An early peak of BNP value may be used as a cut-off point of positive and negative fluid balances.