Dose-response association between fluid overload and hospital mortality in patients with sepsis / 中华内科杂志

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.

Epidemiology of Sepsis-3 in a sub-district of Beijing: secondary analysis of a population-based database / 中华医学杂志(英文版)

BACKGROUND@#With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China.@*METHODS@#The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution.@*RESULTS@#Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) CONCLUSIONS:: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China.@*CLINICAL TRIAL REGISTRATION@#NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

Epidemiology of Sepsis-3 in a sub-district of Beijing: secondary analysis of a population-based database / 中华医学杂志(英文版)

Background@#With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China.@*Methods@#The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution.@*Results@#Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001)@*Conclusions@#This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China.@*Clinical trial registration@#NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42 Associated Excess Mortality in Septic Patients: A Systematic Review and Meta-regression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 (hydroxyethyl starch [HES] 130/0.4*) or delta daily fluid balance (i.e., daily fluid balance in HES group over or below control group) with the heterogeneity of risk ratio (RR) for mortality in randomized control trials (RCTs).</p><p><b>METHODS</b>Three databases (PubMed, EMBASE, Cochrane) were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES130/0.4* with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality.</p><p><b>RESULTS</b>A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of HES130/0.4* compared with treatment of control fluids (RR: 1.02, 95% confidence interval: 0.90-1.17; P = 0.73). Heterogeneity was moderate across recruited trials (I2 = 34%, P = 0.13). But, a significant variation was demonstrated in subgroup with crystalloids as control fluids (I2 = 42%, P < 0.1). Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES130/0.4* with mortality (P = 0.298), but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4* (P = 0.079).</p><p><b>CONCLUSIONS</b>Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES130/0.4* associated with excess mortality in septic patients.</p>

Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese intensive care units: a prospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute kidney injury (AKI) has been recognized as a major healthcare problem affecting millions of patients worldwide. However, epidemiologic data concerning AKI in China are still lacking. The objectives of this study were to characterize AKI defined by RIFLE criteria, assess the association with hospital mortality, and evaluate the impact of AKI in the context of other risk factors.</p><p><b>METHODS</b>This prospective multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across mainland China. We excluded patients who were admitted for less than 24 hours (n = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n = 29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There were 1255 patients in the final analysis. AKI was diagnosed and classified according to RIFLE criteria.</p><p><b>RESULTS</b>There were 396 patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179 (14.3%) patients, respectively. Renal function deteriorated in 206 patients (16.4%). In comparison with non AKI patients, patients in the risk class on ICU admission were more likely to progress to the injury class (odds ratio (OR) 3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR 13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.</p><p><b>CONCLUSIONS</b>The prevalence of AKI was high among critically ill patients in Chinese ICUs. In comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission were more susceptibility to progression to class I or class F. The RIFLE criteria were robust and correlated well with clinical deterioration and mortality.</p>

Implementing surviving sepsis campaign bundles in China: a prospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Surviving sepsis campaign (SSC) bundles have been demonstrated to significantly improve survival in sepsis and septic shock patients worldwide. Compliance with these protocols and resultant mortality in sepsis patients was investigated in intensive care units (ICUs) in China.</p><p><b>METHODS</b>Adult patients with severe sepsis or septic shock treated from September 2007 to October 2008 in 11 ICUs of Chinese teaching hospitals were included. The primary outcome was compliance with resuscitation and management bundles. Secondary outcomes included individual bundle protocol impact and the effects of the completed bundle protocol number on 28-day mortality.</p><p><b>RESULTS</b>Overall compliance during 6-hr resuscitation and 24-hour management bundles were 5.5% and 17.4%, respectively, and 28-day mortality was 33.0%. Compliance with protocols for blood cultures before antibiotics (42.2%), central venous pressure ≥ 8 mmHg (65.9%), central venous oxygen saturation ≥ 70% (25.0%), and optimized glucose control (82.1%), were significantly associated with decreased 28-day mortality (P < 0.05). When adjusted for age, acute organ dysfunction, and APACHE II score, compliance with the blood culture before antibiotics protocol produced the most significant decrease in 28-day mortality (OR, 0.33; 95%CI, 0.16 - 0.70; P = 0.004). Compliance with ≥ 5 protocols in the 6-hour resuscitation bundle was also associated with lower 28-day mortality in septic shock patients (OR, 0.17; 95%CI, 0.06 - 0.54; P = 0.001).</p><p><b>CONCLUSIONS</b>Compliance with resuscitation and management bundles is generally poor in China; however, when applied, 6-hour resuscitation bundle are associated with significant reductions in 28-day mortality for sepsis patients.</p>

Clinical efficacy and safety of recruitment maneuver in patients with acute respiratory distress syndrome using low tidal volume ventilation: a multicenter randomized controlled clinical trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The recruitment maneuver (RM) has been shown to improve oxygenation in some patients with acute respiratory distress syndrome. But there is a lack of standardization and lack of clinical studies to prove the improvement on clinical outcome. We conducted this study to evaluate the clinical efficacy and safety of the RM in patients with acute respiratory distress syndrome (ARDS) using low tidal volume ventilation.</p><p><b>METHODS</b>We randomly assigned 110 patients with ARDS from 14 Chinese intensive care units (ICUs) at the tertiary teaching hospitals. Patients with PaO2 ≤ 200 mmHg at FiO2 1.0 and PEEP ≥ 10 cmH2O were included in the study. Patients were randomized into two groups: control group and RM group. The tidal volume was set to 6 - 8 ml per kilogram of predicted body weight (PBW) in both groups. RM was performed by continuous positive airway pressure (CPAP) of 40 cmH2O maintained for 40 seconds. RMs was conducted every eight hours for the first five days, or stopped within five days if the patient reached the weaning standard.</p><p><b>RESULTS</b>One hundred and ten patients had completed the requirements for the primary study goals, 55 from the RM group and 55 control patients. Baseline characteristics remained similar in the two groups. In the RM group the PaO2/FiO2 was significantly increased compared to baseline at 120 minutes after RM on day one and day two (P = 0.007 and P = 0.001). There were no significant differences between the RM and control group in hospital mortality (41.8% vs. 56.4%, P = 0.13), 28-day mortality (29.1% vs. 43.6%, P = 0.11) and ventilator-free days at day 28 (10.8 ± 10.1 vs. 7.4 ± 10.0, P = 0.08). ICU mortality (32.7% vs. 52.7%, P = 0.03), the rate of survival with unassisted breathing for at least 48 consecutive hours at day 28 (58.2% vs. 36.2%, P = 0.02), and nonpulmonary organ failure-free days at day 28 (17.4 ± 11.1 vs. 13.0 ± 12.0, P = 0.03) favored the RM group. There was no significant difference in mean blood pressure and heart rate before RM and at 30, 60, 120 minutes after RM. There was no incidence of barotraumas.</p><p><b>CONCLUSIONS</b>RM was safe and useful for improving oxygenation in patients with ARDS who were ventilated with a low tidal volume, with a beneficial impact on their clinical outcome.</p>