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.

[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.