Chinese critical care certified course in intensive care unit: a nationwide-based analysis.

BACKGROUND: A training program for intensive care unit (ICU) physicians entitled "Chinese Critical Care Certified Course" (5 C) started in China in 2009, intending to improve the quality of intensive care provision. This study aimed to explore the associations between the 5 C certification of physicians and the quality of intensive care provision in China. METHODS: This nationwide analysis collected data regarding 5 C-certified physicians between 2009 and 2019. Fifteen ICU quality control indicators (three structural, four procedural, and eight outcome-based) were collected from the Chinese National Report on the Services, Quality, and Safety in Medical Care System. Provinces were stratified into three groups based on the cumulative number of 5 C certified physicians per million population. RESULTS: A total of 20,985 (80.41%) physicians from 3,425 public hospitals in 30 Chinese provinces were 5 C certified. The deep vein thrombosis (DVT) prophylaxis rate in the high 5 C physician-number provinces was significantly higher than in the intermediate 5 C physician-number provinces (67.6% vs. 55.1%, p = 0.043), while ventilator-associated pneumonia (VAP) rate in the low 5 C physician-number provinces was significantly higher than in the high 5 C physician-number provinces (14.9% vs. 8.9%, p = 0.031). CONCLUSIONS: The higher number of 5 C-certified physicians per million population seemed to be associated with higher DVT prophylaxis rates and lower VAP rates in China, suggesting that the 5 C program might have a beneficial impact on the quality of intensive care provision.

Renal hemodynamic evaluation protocol based on the pathophysiological mechanism of acute kidney injury: Critical Care UltraSound Guided-A(KI)BCDE.

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

Impact of Fluid Balance on Mortality Is Mediated by Fluid Accumulation Index in Sepsis: A Cohort Study.

Fluid balance (FB) is associated with poor sepsis outcomes; however, it cannot accurately reflect the dynamic fluid accumulation status. Here, we explored a new index, the FB to fluid intake ratio (FB/FI), for evaluating dynamic fluid accumulation in sepsis. FB/FI values within 48 hours were recorded. Their association with in-hospital mortality was investigated using logistic regression and mediation analyses of data from 7,839 patients. In extended logistic models, a linear association was found between FB and mortality (odds ratio [OR]: 1.05-1.08, p < 0.001). However, this association became non-significant after the adjustment of FB/FI (OR: 1.00, 95% confidence interval [CI]: 0.98-1.02). For FB/FI and mortality, a cut-off value of 0.25 was defined. In the spline function logistic model, FB/FI > 0.25 was significantly associated with increased mortality (OR: 4.46, 95% CI: 2.92-6.80), whereas FB/FI ≤ 0.25 was not. For the FB/FI > 0.25 subgroup, mediation analysis was used to clarify the relationship between FB, FB/FI, and mortality. We observed that the direct effect of FB was non-significant (adjusted coefficient: -0.001, 95% CI: -0.005 to 0.002) while the indirect effect was significant (adjusted coefficient: 0.009, 95% CI: 0.006-0.011). In the FB/FI ≤ 0.25 subgroup, both the FB volume (0.9 ± 0.7 vs. -2.0 ± 1.9, p < 0.001) and the FB/FI ratio (0.14 ± 0.07 vs. -0.77 ± 1.60, p < 0.001) were significantly higher in patients with FB > 0 than those with FB ≤ 0. However, both the crude and adjusted comparisons of hospital mortality were non-significant. Similar associations were observed in septic shock patients. FB/FI > 0.25 is a significant risk factor for mortality in sepsis, while FB/FI ≤ 0.25 is not. The association between FB and mortality is completely mediated by this new fluid accumulation index. More comprehensive indices are required for evaluating dynamic fluid status in sepsis.

[Efficacies of fluid resuscitation as guided by lactate clearance rate and central venous oxygen saturation in patients with septic shock].

OBJECTIVE: To estimate the efficacies of fluid resuscitations as guided by lactate clearance rate (LC) and central venous oxygen saturation (ScvO2) in patients with septic shock. METHODS: 100 patients diagnosed with septic shock from June 2012 to June 2014 in department of critical care medicine of sixteen hospitals were enrolled. They were randomly divided into two groups of study and control (each n = 50). After a diagnosis of sepsis shock, they were treated symptomatically timely and fluid resuscitation was started as early as possible according to the 2008 Guideline for Managing Sepsis & Septic Shock. Central venous pressure (CVP) ≥ 8 mmHg (1 mmHg = 0.133 kPa), mean arterial pressure (MAP) ≥ 65 mmHg, urine output ≥ 0.5 ml × kg⁻¹ × h⁻¹, ScvO2≥ 70% and LC ≥ 10% (or lactate ≤ 2.0 mmol) served as target values for fluid resuscitation therapy in study group versus CVP ≥ 8 mmHg, MAP ≥ 65 mmHg, urine output ≥ 0.5 ml × kg⁻¹ × h⁻¹ and ScvO2≥ 70% in control group. The general conditions and clinical characteristics, changes in CVP, MAP, urine output, ScvO2, lactate level and/or LC before (0 hour) and every hour (1-6 h) after the start of fluid resuscitation and other related outcome indicators were recorded. RESULTS: No significant difference existed in general data. The 28-day mortality was 40% for study group versus 56% for control group. There was no significant inter-group difference (P > 0.05). The time of mechanical ventilation and length of intensive care unit (ICU) stay were lower in study group than those in control group [mechanical ventilation time (11.200 ± 17.069) vs (15.760 ± 14.215), P = 0.150; length of ICU stay (13.240 ± 17.127) vs (23.980 ± 18.298), P = 0.003]. The 28-day mortality was independently associated with LC and ScvO2reaching target values for fluid resuscitation in study group (χ² = 10.930, P = 0.001) while the 28-day mortality was independently associated with ScvO2reaching target value for fluid resuscitation in control group (χ² = 6.395, P = 0.011). Among all patients, the 28-day mortality was independently associated with ScvO2reaching target value for fluid resuscitation (χ² = 14.530, P = 0.000), but not LC (χ² = 1.175, P = 0.278). CONCLUSION: A combination of LC and ScvO2may serve an index in confirming the endpoint of fluid resuscitation for patients with septic shock. Fluid resuscitation therapy under the guidance of LC and ScvO2is more accurate and reliable than the guidance of ScvO2alone.

Value of plasma brain natriuretic peptide levels for predicting postoperative atrial fibrillation: a systemic review and meta-analysis.

BACKGROUND: Blood natriuretic peptide (NP) levels have been reported to be useful for predicting postoperative atrial fibrillation (AF). We aimed to quantitatively synthesize the current evidence of the accuracy of using NP levels in predicting postoperative AF. METHODS AND RESULTS: Medline, Embase, and reference lists were searched. Studies were included if either brain natriuretic peptide (BNP) or N-terminal pro-b type natriuretic peptide (NT-proBNP) had been evaluated perioperatively to predict postoperative AF. Data were analyzed to obtain summary accuracy estimates. Data from 1,844 patients in 10 studies were analyzed. Summary estimates for the sensitivity and specificity of using NP levels for predicting postoperative AF were 75 % [95 % confidence interval (CI) 67-79 %] and 80 % (95 % CI 62-91 %), respectively. The overall diagnostic odds ratio was 3.28 (95 % CI 2.23-4.84). Subgroup analysis showed that elevated NP levels in the perioperative period were a strong independent predictor of postoperative AF. NT-proBNP appeared to have better predictive value than BNP, as did postoperative assessment over preoperative assessment. BNP had a better correlation with postoperative AF in patients undergoing thoracic surgery than in patients undergoing cardiac surgery. CONCLUSIONS: Perioperative assessment of the natriuretic peptide level in patients undergoing major cardiothoracic surgery could be a valuable diagnostic aid for identifying patients at high risk of developing postoperative AF, and for providing critical clinical information to guide prophylactic antiarrhythmic therapy in the perioperative period.

[Effects of changes of endothelial function on prognosis in patients with severe sepsis].

OBJECTIVE: To explore the changes of brachial flow-mediated vasodilation (FMD), vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1 (sFLT) in patients with severe sepsis and evaluate their prognostic values. METHODS: A total of 128 patients with severe sepsis were consecutively recruited from January 2009 to January 2011 at Intensive Care Unit of Zhejiang Hospital. And their general profiles and clinical characteristics were analyzed. Brachial artery FMD was measured by ultrasound upon admission after a diagnosis of severe sepsis. The plasma levels of VEGF and sFLT were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The average age was (69.0 ± 10.1) years and the 28-day mortality rate stood at 41.4%. Compared with the survivors, the non-survivors had a lower brachial FMD (P < 0.001) and a higher plasma concentration of sFLT (P = 0.006). However, the survivors and non-survivors had a similar plasma level of sFLT (P = 0.32). In addition, brachial FMD was inversely correlated with sFLT (r = -0.39, P < 0.001), but not with plasma VEGF (r = 0.07, P = 0.11). Receiver operating characteristic (ROC) analysis showed that the optimal FMD (sensitivity 81%, specificity 76%) and plasma sFLT (sensitivity 77%, specificity 71%) cutoff values were 4.5% and 398 pg/ml for 28-day mortality respectively. The multiple Logistic regression analysis revealed that brachial FMD (OR = 0.48, 95%CI: 0.22 - 0.81, P = 0.04) and plasma sFLT (OR = 1.86, 95%CI: 1.21 - 3.08, P = 0.02) were independent predictors of 28-day mortality rate. CONCLUSION: Lower brachial FMD and higher plasma sFLT may reflect endothelial function impairment and carry a higher risk of mortality in patients with severe sepsis and have. Non-invasive ultrasonic assessment of flow-mediated dilation is recommended.

[The effects of ω-3 fish oil lipid emulsion on inflammation-immune response and organ function in patients with severe acute pancreatitis].

OBJECTIVE: To investigate the effects of ω-3 fish oil lipid emulsion via vein on the inflammatory response, immune and organ function in patients with severe acute pancreatitis. METHODS: A total of 53 patients with severe acute pancreatitis were randomized into conventional therapy plus fish oil group (FO group) and conventional therapy group (CON group). The patients in FO group were treat with ω-3 fish oil lipid emulsion (0.2 g×kg(-1)×d(-1), 10%) based on conventional therapy for 14 days. The level of C-reactive protein (CRP), TG and TC were detected before treatment and at day 7 and day 14 after treatment. CD(4)(+), CD(4)(+)/CD(8)(+) and C(3), C(4) were also detected at day 1 and day 14 after treatment. At the same time, acute physiology and chronic health evaluation II score (APACHEII score), intra-abdominal pressure, negative fluid balance time, enteral nutrition start-time and ICU stay time were observed and recorded. RESULTS: Forty-five out of 53 patients were finally recruited into results statistics. The level of CD(4)(+), CD(4)(+)/CD(8)(+) and C(3) at day 14 after treatment in FO groups improved significantly than that in the CON group (P < 0.05). The levels of CRP, intra-abdominal pressure and APACHE II score at day 7 and day 14 in FO group descended more obviously than that in the CON group (P < 0.05). The negative liquid balance time in FO group (3.55 ± 0.86)days was obvious shorter than that in CON group (4.61 ± 1.12) days, while enteral nutrition start-time (3.86 ± 1.17) days was significantly earlier compared with CON group (5.30 ± 1.61) days (P < 0.05), however ICU stay time and 28 days mortality rate had no significant difference between the two groups. CONCLUSIONS: ω-3 fish oil lipid emulsion can decrease the inflammatory response and the negative liquid balance time, improve the immune function and restore bowel function in severe acute pancreatitis patients. Therefore, it maybe provide a new and effective means for severe acute pancreatitis.

Low-dose intravenous plus inhaled versus intravenous polymyxin B for the treatment of extensive drug-resistant Gram-negative ventilator-associated pneumonia in the critical illnesses: a multi-center matched case-control study.

BACKGROUND: The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients. METHODS: A retrospective multi-center observational cohort study was performed at eight ICUs between January 1st 2018, and January 1st 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement. RESULTS: 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome. CONCLUSIONS: The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.

Association Between Oxygen Partial Pressure Trajectories and Short-Term Outcomes in Patients With Hemorrhagic Brain Injury.

Objectives: Arterial hyperoxia is reportedly a risk factor for poor outcomes in patients with hemorrhagic brain injury (HBI). However, most previous studies have only evaluated the effects of hyperoxia using static oxygen partial pressure (PaO2) values. This study aimed to investigate the association between overall dynamic oxygenation status and HBI outcomes, using longitudinal PaO2 data. Methods: Data were extracted from the Medical Information Mart for Intensive Care III database. Longitudinal PaO2 data obtained within 72 h of admission to an intensive care unit were analyzed, using a group-based trajectory approach. In-hospital mortality was used as the primary outcomes. Multivariable logistic models were used to explore the association between PaO2 trajectory and outcomes. Results: Data of 2,028 patients with HBI were analyzed. Three PaO2 trajectory types were identified: Traj-1 (mild hyperoxia), Traj-2 (transient severe hyperoxia), and Traj-3 (persistent severe hyperoxia). The initial and maximum PaO2 of patients with Traj-2 and Traj-3 were similar and significantly higher than those of patients with Traj-1. However, PaO2 in patients with Traj-2 decreased more rapidly than in patients with Traj-3. The crude in-hospital mortality was the lowest for patients with Traj-1 and highest for patients with Traj-3 (365/1,303, 209/640, and 43/85 for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001), and the mean Glasgow Coma Scale score at discharge (GCSdis) was highest for patients with Traj-1 and lowest in patients with Traj-3 (13 [7-15], 11 [6-15], and 7 [3-14] for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001). The multivariable model revealed that the risk of death was higher in patients with Traj-3 than in patients with Traj-1 (odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9-5.8) but similar for patients with Traj-1 and Traj-2. Similarly, the logistic analysis indicated the worst neurological outcomes in patients with Traj-3 (OR: 3.6, 95% CI: 2.0-6.4, relative to Traj-1), but similar neurological outcomes for patients in Traj-1 and Traj-2. Conclusion: Persistent, but not transient severe arterial hyperoxia, was associated with poor outcome in patients with HBI.

Novel phenotypes of coronavirus disease: a temperature-based trajectory model.

BACKGROUND: Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients' temperature trajectory. METHOD: A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients' clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes. RESULTS: A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1-4.0; and 3.3, 1.4-8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin. CONCLUSIONS: Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.

Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study.

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study.

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

Fluid Balance in Patients After Cardiac Surgery.

No Abstract.

Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome.

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.