Meta-Analysis of Ventilated versus Spontaneously Breathing Patients in Predicting Fluid Responsiveness by Inferior Vena Cava Variation

Purpose: Respiratory variation in inferior vena cava (ΔIVC) has been extensively studied in predicting fluid responsiveness, but the results are conflicting. We performed a systemic review and meta-analysis of studies aiming at investigating the diagnostic accuracy of ΔIVC in predicting fluid responsiveness. Methods: MEDLINE, EMBASE, Cochrane Database and Web of Science were screened for relevant original and review articles from inception to July 2016. The meta-analysis determined the pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under the ROC curve (AUROC). In addition, subgroup analyses were performed in mechanically ventilated patients and spontaneously breathing patients. Results: A total of 20 studies involving 635 patients were included. Cutoff values of ΔIVC varied from 12% to 42%, the pooled sensitivity and specificity was 0.68 (0.62 - 0.75) and 0.80 (0.75 - 0.85), respectively. The DOR was 14.2 (6.0 - 33.6) and the AUROC was 0.86 (0.78 - 0.93). Subgroup analysis showed better diagnostic performance in patients on mechanical ventilation than in spontaneously breathing patients with higher sensitivity (0.75 vs. 0.56), specificity (0.82 vs. 0.78), DOR (22.9 vs. 7.9) and AUROC (0.90 vs. 0.80). The best threshold of ΔIVC in patients on mechanical ventilation was IVC distensibility index (ΔIVC ≥17% ±4%), compared to IVC collapsibility index (ΔcIVC ≥33% ±12%) in spontaneously breathing patients. Conclusion: ΔIVC is not an accurate predictor of fluid responsiveness in patients with acute circulatory failure. In patients on mechanical ventilation, the predicting ability of ΔIVC was moderate with acceptable sensitivity and specificity;in spontaneously breathing patients, the specificity remains acceptable but its sensitivity is poor.

Tigecycline Use in Surgical Intensive Care Unit for the Treatment of Complicated Intra-Abdominal Infections: A Real-World Study

OBJECTIVES: To describe real-world use of tigecycline in cIAIs patients. METHODS: A retrospective, observational study enrolled cIAIs patients hospitalized in The First Affiliated Hospital, Sun Yat-sen University from January 1, 2013 to June 30, 2017 was conducted. Patients’ data were collected and matched based on age, gender, and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score according to receiving first-line, later-line, or no tigecycline during hospitalization. RESULTS: Data were collected for 52 patients. 82.6% were male. Mean age was 57.8 years and APACHE II score was 14.8. The incidence of both extended-spectrum beta-lactamase producing and carbapenem-resistant pathogens was high on initial culture;however, few patients received first-line tigecycline. No significant difference in mortality rate was identified among first-line, later-line and no tigecycline users. Of surviving patients, shorter hospital length of stay was observed for patients receiving first- vs later-line or no tigecycline, respectively. ICU length-of-stay was shorter in patients receiving first- vs later-line or no tigecycline. CONCLUSIONS: First-line tigecycline use was rare in our surgical intensive care unit. Resistant organisms were commonly cultured from initial specimens. Although these results are limited by small patient numbers and single center, our results suggest that early tigecycline use may have significant benefits with similar mortality. Further research is warranted to demonstrate the values of early tigecycline use in cIAIs patients.

Efficacy and Safety Study of CA330 Hemadsorption Device on IL-6 Removal in Septic Patients: Study Protocol of a Multicenter Randomized Controlled Trial

Background: Sepsis persists to be the leading cause of morbidity and mortality worldwide with the huge cost of health care resources. Besides adequate antibiotics and infectious source control, definitive therapy is still being studied. The activation of multiple pro- and anti-inflammatory mediators plays a key role in the sepsis process. The application of adsorption may help deactivate and decrease the peak elevation of these mediators in the earlier course of sepsis, when levels of endotoxins and cytokines are extremely high. However, the clinical evidence to support hemadsorption for removing endotoxins and/or pro-inflammatory mediators in sepsis remains incompetent and controversial. In this study protocol, we aimed to test the efficacy of removing cytokines and the safety of a new hemadsorption device, CA330, in septic patients. Design: This is a multicenter randomized controlled clinical trial enrolling 8 tertiary hospitals in China. A total of 144 patients will be randomly divided into the experimental group and the control group according to the ratio of 1:1. The primary endpoint is the reduction rate of IL-6 serum concentration between the initiation of the first adsorption and end with the second adsorption. Discussion: To our knowledge, this clinical trial is the first to evaluate the efficacy and safety of the CA330 hemadsorption device in sepsis patients. Our study will raise the level of evidence for the treatment of sepsis patients with hemadsorption.

Diagnostic Accuracy of Transthoracic Echocardiography to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill: A Meta-Analysis

Background: Hemodynamic instability is common in critical patients and not all patients respond to fluid challenge, so we need accurate and rapid hemodynamic techniques to help the clinicians to guide fluid treatment. Numerous hemodynamic techniques have been used to predict fluid responsiveness till now. Transthoracic echocardiography (TTE) appears to have the ability to predict fluid responsiveness, but there is no consensus on whether it can be used by passive leg raising (PLR). Methods: We performed a literature search using MEDLINE (source PubMed, from 1947), EMBASE (from 1974) and the Cochrane Database of Systematic Reviews for prospective studies with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results: 7 prospective studies involving 261 patients and 285 boluses were identified. The pooled sensitivity and specificity of TTE are 86% (79% - 91%) and 90% (83% - 94%), respectively. The summary receiver operating characteristic (sROC) curve shows an optimum joint sensitivity and specificity of 0.88, with area under the sROC curve (AUC) of 0.94. The result of diagnostic odds ratio (DOR) is 50.62 (95% confidence interval [CI]: 23.70 - 108.12). The results of positive likelihood ratio (+LR) and negative likelihood ratio (?LR) are 7.07 (95% CI: 4.39 - 11.38) and 0.19 (95% CI: 0.13 - 0.28), which indicated strong diagnostic evidence. Conclusions: TTE is a repeatable and reliable noninvasive tool to predict fluid responsiveness in the critically ill during PLR with good test performance. This meta-analysis brings evidence to employ well-trained clinician-echocardiographers to assess patients’ volume statue via TTE to benefit daily work in intensive care units (ICUs).

Meta-Analysis of Invasive versus Non-Invasive Techniques to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill

Objective: To analyze the accuracy and specificity of recent studies to compare the ability of predicting fluid responsiveness with Passive Leg Raising (PLR) by using invasive or non-invasive techniques during passive leg raising. Data Sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were systematically searched. Study Selection: Clinical trials that reported the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) between the responder and non-responder induced by passive leg raising and Volume Expansion (VE) in critical ill patients were selected. 246 studies were screened, 14 studies were included for data extraction, which met our inclusion criteria. Data Extraction: Data were abstracted on study characteristics, patient population, type and amount of VE, time of VE, definition of responders, position, techniques used for measuring hemodynamic change, number and percentage of responders, the correlation coefficient, sensitivity, specificity, best threshold and area under the ROC curve (AUC). Meta-analytic techniques were used to summarize the data. Data Synthesis: A total of 524 critical ill patients from 14 studies were analyzed. Data are reported as point estimate (95% confidence intervals). The pooled sensitivity and specificity of invasive techniques were 80% (73% - 85%) and 89% (84% - 93%) respectively with the area under the sROC of 0.94. While, the pooled sensitivity and specificity of non-invasive techniques were 88% (84% - 92%) and 91% (86% - 94%) respectively with the area under the sROC of 0.95. The pooled DOR of invasive techniques was 32.2 (13.6 - 76.8), which was much lower than that of non-invasive techniques with the value of 64.3 (33.9 - 121.7). Conclusions: The hemodynamic indexes changes induced by PLR could reliably predict fluid responsiveness. Non-invasive hemodynamic techniques with their accuracy and safety can benefit the daily work in ICUs. Because the number of patients included in the present trials was small, further studies should be undertaken to confirm these findings.

Clinical practice guidelines for nutritional assessment and monitoring of adult ICU patients in China

The Chinese Society of Critical Care Medicine(CSCCM)has developed clinical practice guidelines for nutrition assessment and monitoring for patients in adult intensive care units(ICUs)in China.This guideline focuses on nutrition evaluation and metabolic monitoring to achieve optimal and personalized nutrition therapy for critically ill patients.This guideline was developed by experts in critical care medicine and evidence-based medicine methodology and was developed after a thorough review of the system and a summary of relevant trials or studies published from 2000 to July 2023.A total of 18 recommendations were formed and consensus was reached through discussions and reviews by expert groups in critical care medicine,parenteral and enteral nutrition,and surgery.The recommendations are based on currently available evidence and cover several key fields,including screening and assessment,evaluation and assessment of enteral feeding intolerance,metabolic and nutritional measurement and monitoring during nutrition therapy,and organ function evaluation related to nutrition supply.Each question was analyzed according to the Population,Intervention,Comparison,and Outcome(PICO)principle.In addition,interpretations were provided for four questions that did not reach a consensus but may have potential clinical and research value.The plan is to update this nutrition assessment and monitoring guideline using the international guideline update method within 3–5 years.

Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex

Currently,the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide.COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon(IFN-I)signal,along with limited activation of antiviral immune responses as well as enhanced viral infectivity.Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways.However,it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection.In the current study,we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA(mtDNA),which in turn triggers cGAS to activate IFN-I signaling.As countermeasures,SARS-CoV-2 nucleocapsid(N)protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling.Mechanically,N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation(LLPS),subsequently impairs the double-strand DNA(dsDNA)detection ability of cGAS.Taken together,our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.

新型冠状病毒肺炎后时代:基础疾病带来的巨大挑战

新型冠状病毒流行已经造成全球超五亿人次感染。由于病毒变异等原因,我国基础疾病导致的高龄重症患者明显增加,给临床诊疗带来了巨大的挑战。高龄合并基础疾病患者进展为新型冠状病毒肺炎(简称新冠肺炎)重症或基础疾病重型,预后不佳,采用早期筛查和早期干预,预防高危患者重症化;强调重症规范管理和基础疾病的专科化诊疗,关注肺与肺外器官保护;同时加强营养支持和康复治疗,是降低患者重症率和病死率的关键。

Safety and efficacy of ciprofol vs.propofol for sedation in intensive care unit patients with mechanical ventilation:a multi-center,open label,randomized,phase 2 trial

Background:Ciprofol(HSK3486;Haisco Pharmaceutical Group Co.,Ltd.,Chengdu,China),developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial.The phase 2 trial was designed to investigate the safety,efficacy,and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods:In this multicenter,open label,randomized,propofol positive-controlled,phase 2 trial,39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio.The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min,followed by an initial maintenance infusion rate of 0.30 mg·kg^(-1)·h^(-1),which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg^(-1)·h^(-1),whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min,followed by an initial maintenance infusion rate of 1.50 mg·kg^(-1)·h^(-1),which could be adjusted to 0.30-4.00 mg·kg^(-1)·h^(-1)to achieve-2 to+1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration.Results:Of the 39 enrolled patients,36 completed the trial.The median(min,max)of the average time to sedation compliance values for ciprofol and propofol were 60.0(52.6,60.0)min and 60.0(55.2,60.0)min,with median difference of 0.00(95%confidence interval:0.00,0.00).In total,29(74.4%)patients comprising 18(69.2%)in the ciprofol and 11(84.6%)in the propofol group experienced 86 treatment emergent adverse events(TEAEs),the majority being of severity grade 1 or 2.Drug-and sedation-related TEAEs were hypotension(7.7%vs.23.1%,P=0.310)and sinus bradycardia(3.8%vs.7.7%,P=1.000)in the ciprofol and propofol groups,respectively.The plasma concentration-time curves for ciprofol and propofol were similar.Conclusions:ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration:ClinicalTrials.gov,NCT04147416.

Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019

This consensus focuses on severe and critical coronavi-rus disease 2019(COVID-19)mainly based on the consideration that mortality of severe and critical cases is higher than mild and mo derate cases of COVID-19.Severe patients usually developed dyspnea and/or hypoxemia in a short period of time,and in some cases progressively developed respiratory failure,septic shock,coagulation disorders,and multi-organ dysfunction.

Lung ultrasound:a valuable tool for assessing COVID-19 patients with different severity

To the Editor:Lung ultrasound(LUS)may be a promising technique to assess lung injury from coronavirus disease 2019(COVID-19).However,the LUS characteristics and their assessment value have not been well described.We aimed to explore the LUS characteristics and their assessment value in COVID-19 patients with different levels of disease severity.

Expert consensus on the diagnosis and treatment of severe and critical coronavirus disease 2019(COVID-19)

Introduction Coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),is highly contagious[1]and has developed into a global pan-demic.Up to July 1,2022,COVID-19 has affected>200 coun-tries and regions across the globe and caused 545,226,550 con-firmed cases and 6334,728 deaths,[2]seriously compromising human life,public properties.