Prognostic factors for patients with hematologic malignancies admitted to the intensive care unit: is allogeneic transplantation still a risk factor?

The rate of intensive care unit (ICU) mortality in patients with hematologic malignancies is high. The risk factors for this were inconsistent across several previous studies, and there is currently no accepted consensus around risk factors for these patients. We aimed to identify which prognostic factors were associated with ICU mortality in critically ill patients with hematologic malignancies, nearly half of which were allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. In addition, we aimed to compare the characteristics and clinical outcomes of patients with and without allogenic allo-HSCT. In total, 217 patients with hematologic malignancies were enrolled consecutive, 119 (54.8%) of whom underwent HSCT (allo-HSCT: n = 115). All survivors were followed up with until August 1, 2022. The rate of ICU mortality in this cohort was 54.4%: 55.5 and 53.1% for the patients with and without HSCT, respectively (p = 0.724). The probabilities of survival after ICU admission were also comparable between the patients who had allo-HSCT and those who did not. A multivariable analysis revealed that cerebrovascular disease, hyperlactic acidemia on the day of ICU admission, lower platelet count, use of vasoactive drugs, and absence of noninvasive ventilation on the day of ICU admission were independent risk factors for ICU mortality. For patients with three to five of these risk factors, the rate of ICU mortality was as high as 84.6%, which was significantly higher than that of other patients. In this study, the ICU mortality rate in patients with hematologic malignancies was still high, particularly for those with multiple risk factors. However, allo-HSCT was not found to be a risk factor for ICU mortality.

Validation of a Chinese version critical-care pain observation tool in nonintubated and intubated critically ill patients: Two cross-sectional studies.

AIMS AND OBJECTIVES: To validate the Chinese version of the Critical-Care Pain Observation Tool (CPOT) in nonintubated and intubated ICU patients. BACKGROUND: While CPOT was found to have the best psychometric properties among objective pain assessment scales, there is no Chinese version CPOT for nonintubated patients. DESIGN: Cross-sectional design was used in these two observational studies. METHODS: Seventy-six nonintubated patients and 53 intubated patients were assessed to examine internal consistency, criterion-related and discriminative validity of CPOT in the first study. Pain assessment during low pain condition as well as increased pain condition was performed by Numeric Rating Scale (NRS) and the Chinese version COPT. Forty nonintubated patients and 43 intubated patients were assessed to examine inter-rater reliability in the second study. A bedside nurse and a researcher independently executed paired pain assessments with CPOT in the same conditions. The STROBE Statement was followed to guide these studies. RESULTS: The Cronbach's α in nonintubated patients and intubated patients was 0.903-0.930 and 0.868-0.870. The intraclass correlation coefficients (ICCs) in nonintubated patients ranged from 0.959-0.982, and the ICC in intubated patients ranged from 0.947-0.959, confirming the inter-rater reliability. The moderately positive Pearson's correlations between CPOT and NRS scores (r = 0.757-0.838 in nonintubated patients, r = 0.574-0.705 in intubated patients) indicated the criterion-related validity. A significant increase in CPOT scores in the increased pain condition compared with those acquired in the low pain condition verified the discriminative validity. CONCLUSIONS: The Chinese version of CPOT was presented to be valid and reliable for both nonintubated and intubated critically ill adults, which could be applicable for pain assessment in patients in ICU. RELEVANCE TO CLINICAL PRACTICE: This study provides an applicable pain assessment tool for both nonintubated patients and intubated patients in ICU.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

[The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock].

OBJECTIVE: To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock. METHODS: Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded. RESULTS: ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [µg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (µg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05). CONCLUSIONS: Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.

[The prognostic value of N-terminal pro-B-type natriuretic peptide in patients with severe sepsis and septic shock].

OBJECTIVE: To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with severe sepsis and septic shock. METHODS: In a prospective study, clinical data of 50 patients with severe sepsis and septic shock were analyzed. Plasma NT-proBNP level was measured at 0, 24, 48 and 72 hours after admission to the intensive care unit (ICU) of a university hospital. Patients were divided into survival group and non-survival group according to 30-day mortality rate. The dynamic variation of plasma NT-proBNP level was observed and the difference of plasma NT-proBNP levels between two groups was compared. The predictive value of NT-proBNP on mortality was evaluated by receiver operating characteristic (ROC) curves. The potential confounding factors on NT-proBNP were assessed with linear regression analysis. RESULTS: NT-proBNP levels (µg/L)at 0 hour after admission to ICU [20.86(14.28,23.92)] were significantly higher in non-survival group (n=20) compared with survival group [ n=30, 10.02 (5.58, 16.41), P<0.01], and the difference persisted to 72 hours [19.68 (13.90, 24.02) vs. 9.24 (4.30, 11.81), P<0.01], but there was no statistical difference of NT-proBNP levels among four time points. In the ROC curves for NT-proBNP at admission, the area under the curve(AUC) for hospital mortality was 0.842, and 95% confidence interval (CI) was 0.764-0.922, P<0.01. NT-proBNP greater than 13.30 µg/L at admission was an independent indicator of mortality (sensitivity 80.6%, specificity 70.2%). Linear regression analysis revealed that the oxygenation index (PaO(2)/FiO(2), r=-0.839, P=0.003), platelet count (PLT, r=-0.803, P=0.032), and sequential organ failure assessment (SOFA) scores at 0 hour after admission to ICU (r=0.874, P<0.001) had independent effects on NT-proBNP values at admission. CONCLUSION: Plasma NT-proBNP level is a valuable prognostic factor for severe sepsis and septic shock patients.

[Retrospective analysis of invasive fungal infection in surgical intensive care unit].

OBJECTIVE: To conduct a retrospective analysis of the invasive fungal infection (IFI) in surgical intensive care unit (SICU). METHODS: The IFI data of the patients who were admitted in SICU during January 2003 to December 2008 was retrospectively analyzed. A total of 3743 patients were admitted into SICU. Among them, 271 patient's SICU duration was more than 48 hours, who had fungi examination. RESULTS: Seventy-five patients were diagnosed IFI, the morbidity was 2.00% (75/3743), the incidence of fungemia was 0.27% (10/3743), the mortality of IFI patients was 49.33% (37/75). The morbidity rate of each year was almost the same. The mortality of 2007 and 2008 was higher than before (both P < 0.05). Thirty-four of all the 75 IFI patients got urinary tract infected, 37 got fungal pneumonia, 10 got fungemia, 1 got catheter-related fungal infection, 2 got fungal infection in abdomen, 2 got biliary tract infected. Eighty-six fungi strains which caused fungal infection were spotted. Candida albicans was the most common isolate (46.51%). Other isolates were Candida glabrata (22.09%), Candida tropicalis (13.95%), Candida parapsilosis (8.14%), Candida krusei (3.49%), Trichosporon (4.65%), Aspergillus (1.16%). Assist ventilation, combination of bacterial infection, treatment by broad spectrum antibiotics or more than three kinds of antibiotics were the most important risk factors of IFI in SICU. Prophylactic antifungal treatment may be useful. CONCLUSION: The morbidity of IFI in our SICU was comparatively low, and the same of the incidence of fungemia. The mortality of IFI patients was markedly high. The main sites of infection were lung and urinary tract, and the pathogenic fungi strains were mostly Candidas. Assist ventilation, combination of bacterial infection, broad spectrum antibiotics treatment were the most important risk factors of IFI in SICU.

Prognostic Implications of Preoperative Pneumonia for Geriatric Patients Undergoing Hip Fracture Surgery or Arthroplasty.

OBJECTIVE: To report outcomes of geriatric patients undergoing hip fracture surgery or arthroplasty with or without preoperative pneumonia and to evaluate the influence of pneumonia severity on patient prognosis. METHODS: In this single center retrospective study, we included geriatric patients (≥60 years old) who had undergone hip fracture surgery or arthroplasty at Peking University People's Hospital from January 2008 to September 2018. Patients with fractures caused by neoplasms or patients with incomplete clinical data were excluded. Using logistic regression and the CURB-65 (confusion, uremia, respiratory rate, blood pressure, and age ≥65 years) score as a prediction tool of 1-year mortality, the effect of preoperative pneumonia on 1-year mortality was evaluated. Survival of patients with different response to pneumonia-specific therapy and survival of patients with different pneumonia severity (evaluated with CURB-65 score) were analyzed using Cox regression. RESULTS: A total of 1386 patients were included; among them, 109 patients (7.86%) were diagnosed with preoperative pneumonia. Outcomes were evaluated in August 2019 (at least 1 year after surgery for all patients). Compared to patients without preoperative pneumonia, patients with this condition had higher 30-day mortality (11.9% vs 5%, P = 0.002) and 1-year mortality rates (33.9% vs 16.3%, P < 0.001) and higher incidence of acute heart failure (7.3% vs 3.4%, P = 0.034) and acute kidney injury (5.5% vs 1.8%, P = 0.009). In multivariate regression, preoperative pneumonia was identified as an independent predictor of 1-year mortality (odds ratio [OR], 1.45; 95% confidence interval [CI] 1.39-3.52; P = 0.021), with other factors including age (≥84 years, OR, 1.46; 95% CI 1.08-1.60; P = 0.027), body mass index (<18.5 kg/m2 , OR 2.23; 95% CI 1.52-3.17, P < 0.001), anesthesia type (regional, OR 0.87; 95% CI 0.19-0.97, P = 0.042), preoperative pneumonia (OR 1.45; 95% CI 1.39-3.52; P = 0.002), congestive heart failure (OR 2.05, 95% CI 1.57-6.21, P < 0.001), chronic kidney disease (OR 1.73; 95% CI 1.50-2.62; P < 0.001). There was a trend of increased 1-year mortality as the CURB-65 score elevated (P for trend = 0.006). Cox regression reveals a higher risk of mortality in patient with preoperative pneumonia, especially in patients with no radiologic improvements after therapy (log-rank, P = 0.035). Analysis of the impact of pneumonia severity on patient survival using Cox regression reveals that a CURB-65 score ≥3 indicated a lower rate of survival (CURB-65 score of 3: hazard ratio [HR] 3.12, 95% CI 1.39-7.03, P = 0.006; score of 4: HR 3.41, 95% CI 1.69-6.92, P = 0.001; score of 5: HR 6.28, 95% CI 2.95-13.35, P < 0.001). CONCLUSION: In this single center retrospective study, preoperative pneumonia was identified as an independent risk factor of 1-year mortality in geriatric patients undergoing hip fracture surgery or arthroplasty. A CURB-65 score ≥3 indicated a higher risk of mortality.

[Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock].

OBJECTIVE: To evaluate the value of B-type natriuretic peptide (BNP) in predicting the outcome of severe sepsis and septic shock patients. METHODS: One hundred and two patients with severe sepsis and septic shock were prospectively observed. Plasma BNP level was measured at 24th hour after admission to intensive care unit (ICU) of a university hospital. The data of clinical features, 28-day mortality, acute physiology and chronic health evaluation II (APACHE II) scores and the length of stay (LOS) in ICU were collected. The patients were divided into survival group and non-survival group. The survival group was further divided into BNP elevated group and BNP normal group. RESULTS: APACHE II scores were significantly higher in non-survivors (39 patients) compared with survivors (63 patients, 28.9+/-5.9 vs. 20.2+/-5.4, P<0.01), but there were no statistical difference of white blood cell count and blood lactic levels between two groups. BNP levels were significantly higher in non-survivors compared with survivors [(1,451.3+/-531.7) ng/L vs. (394.5+/-81.7) ng/L, P<0.01]; BNP greater than 681.4 ng/L at first 24th hour was an independent indicator of mortality (sensitivity 91.4%, specificity 80.3%). In survivals, the LOS in ICU was significantly higher in BNP elevated group (48 patients) than BNP normal group [15 patients, (23.7+/-7.5) days vs. (14.9+/-5.1) days, P<0.05), but APACHE II scores showed no statistical difference between two groups. CONCLUSION: Plasma BNP level is a valuable prognostic factor for severe sepsis and septic shock patients.

Impact of individualized active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.

Purpose: Active surveillance of carbapenem-resistant Enterobacteriaceae (CRE) may contribute to the decline of the infection rate. Individualized active surveillance of CRE could cost less than screening all patients. However, the impact of individualized active surveillance on the CRE infection rate in intensive care units (ICUs) has not been well described. Patients and methods: We retrospectively studied the clinical data of all patients admitted in the ICUs of a tertiary-care hospital in China from 2015 to 2017 during two periods, before and after the implementation of individualized active surveillance. During period 1 (January 2015-April 2016), no screening protocol was used. During period 2 (May 2016-December 2017), we implemented active CRE screening for selected patients according to their clinical characteristics. The trend of CRE rate infection was analyzed by a joinpoint regression model, and multivariate analysis was performed to analyze the association of active surveillance, Acute Physiology and Chronic Health Evaluation (APACHE) II score, prior antimicrobial use, length of mechanical ventilation (MV) before infection, and other risk factors with CRE infection rate. Results: A total of 5,372 patients were included. After assessing the patients' clinical characteristics, 72.3% (3,882/5,372) were considered to be at high risk of CRE infection. During period 1, the infection percent of CRE increased by 13.04% every month (95% CI: 5.2-21.5). During period 2, the infection rate decreased (monthly percent change, -3.57%; 95% CI -6.9 to -0.1, P<0.05). Multivariate analysis showed that individualized active surveillance (odds ratio, 0.146; 95% CI, 0.061-0.347; P<0.001) was associated with a reduction of the CRE infection rate, whereas APACHE II score, prior antimicrobial use, and length of MV before infection were independent risk factors. Conclusion: Individualized active surveillance may be associated with a reduction of the overall CRE infection rate in ICUs.

Epidemiology of Sepsis-3 in a sub-district of Beijing: secondary analysis of a population-based database.

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.

[Candida species distribution in the patients with high risk of deep fungal infections and relevant risk factors: a prospective cohort study].

OBJECTIVE: To study the distribution of Candida spp. in the patients with high-risk of fungal infection and the risk factors of deep candidiasis. METHODS: A prospective cohort study was performed among 440 consecutive hospitalized patients admitted to the hematology wards, geriatric wards, and ICUs from May 2004 to April 2005. Stool, urine, and saliva were cultured during the period 72 - 96 h after hospitalization for the first time and then once a week till the patient was discharged or by the end of the sixth week. If deep fungal infection was suspected culture of blood, sputum, bacterium-free body fluid, and/or biopsy specimens were cultured. Medical records were reviewed to analyze the possible risk factors. RESULTS: 426 strains of Candida spp. were isolated from 152 patients, with Candida albicans accounting for 67.4% and other Candida spp for 32.6%. 61 patients were discovered to express Candida colonization. The major species isolated from patients with Candida colonization was Candida albicans. The risk factors identified included two or more broad-spectrum antibiotic administration (odds ratio 16.204; 95% confidence interval, 2.005 to 130.980), Candida colonization (10.636; 3.743 to 30.222), and urinary canal administration (4.285; 1.399 to 13.127). CONCLUSION: Candida albicans is still the major organism isolated from the high risk fungal infection patients. Two or more broad-spectrum antibiotic administration, Candida colonization, and urinary canal administration are proved to be the risk factors, with the broad-spectrum antibiotic administration exhibiting more influence than Candida colonization and urinary canal administration.

Acute kidney injury is an independent risk factor for myocardial injury after noncardiac surgery in critical patients.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) contributes to mortality and morbidity. However, risk factors accelerating its development remain unclear. The aim of this study was to identify the incidence and risk factors of MINS. METHODS: A retrospective and observational cohort study of critical patients (n=1087) after noncardiac surgery was carried out at a large and tertiary university hospital from January 2012 to January 2013. The clinical data including medical history as well as intraoperative and postoperative variables were recorded. The primary outcome was the occurrence of MINS. Secondary outcomes included 30-day all-cause mortality and the incidence of 30-day major adverse cardiac events (MACE) after surgery. The risk factors of MINS in critical patients were analyzed using logistic regression. RESULTS: MINS had occurred in 188 (17.3%) of the 1087 critical patients. Fifty-seven patients (5.2%) had postoperative acute kidney injury (AKI), wherein stage 1 accounted for 82.5% (47/57), stage 2 accounted for 12.3% (7/57), and stage 3 accounted for 5.3% (3/57). The independent risk factors of MINS in critical patients were emergency surgery (odds ratio [OR], 2.64; 95% confidence interval [CI], 1.60-4.35; P<.001), a longer time of operation (OR, 1.10; 95% CI, 1.03-1.17; P=.004), postoperative AKI (OR, 2.09; 95% CI, 1.15-3.79; P=.015), vasopressor drugs used within 24 hours after operation (OR, 2.27; 95% CI, 1.40-3.67; P=.001), and a higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.05; 95% CI, 1.02-1.08; P=.002). All-cause mortality and MACE after surgery were not related to postoperative AKI (P=.544 for mortality; P=.663 for MACE). CONCLUSIONS: The incidence of MINS in critical patients is high. Postoperative AKI is an independent risk factor of MINS in critical patients. It is recommended that postoperative kidney functions be routinely assessed in all critical patients after noncardiac surgery.

Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock: A Prospective Randomized Pilot Study.

BACKGROUND: The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients. METHODS: Patients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured. RESULTS: Clinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [ P = 0.255] and 4% vs. 16% [ P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P= 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P= 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P= 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P= 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P= 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group. CONCLUSIONS: Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.

The immunoprotective activity of interleukin-33 in mouse model of cecal ligation and puncture-induced sepsis.

Lymphocyte apoptosis plays a pivotal role in sepsis-induced immunosuppression and is the primary cause of high mortality rates. Interleukin-33 is a member of the interleukin-1 family that is involved in the polarization of T cells toward a T helper 2-cell phenotype and may regulate apoptotic cell death. The objective of the present study was to assess the effects of interleukin-33 on T lymphocyte apoptosis in sepsis and determine the mechanisms involved. Sepsis was induced in C57BL/6 mice via a cecal ligation and puncture. Mice were infused with recombinant interleukin-33 protein at 1h and 6h after surgery. The mortality rates were evaluated over the subsequent 7 days. In a separate experiment, mice were sacrificed 24h after surgery. Bacterial burdens in the blood and peritoneal cavity were calculated to assess the bacterial clearance. Liver, lung and renal pathology were observed via transmission electron microscopy. The serum levels of interleukin-6, interleukin-10, interleukin-17, interferon-γ and tumor necrosis factor-α were measured via enzyme-linked immunosorbent assays. The number of T and B lymphocytes, the percentage of apoptotic cells and the expression of Fas, Bcl-2, caspase-3, caspase-8 and caspase-9 in CD3(+) T lymphocytes were analyzed by flow cytometry. Interleukin-33 enhanced bacterial clearance, attenuated the severity of organ damage and improved the survival of septic mice. Interleukin-33 decreased the levels of interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α, and it increased the levels of interleukin-17. Interleukin-33 also inhibited the apoptosis of CD4(+) and CD8(+) T lymphocytes and CD19(+) B cells in the spleen. The number of CD3(+) T cells was higher and the expression of active caspase-3, caspase-8 and caspase-9 was lower in the interleukin-33 group compared to the CLP group. The expression of Fas was lower and the expression of Bcl-2 was higher in the interleukin-33 group than in the CLP group. Interleukin-33 prevented apoptosis of T lymphocytes and improved survival in a mouse model of sepsis.

Reliability and validity of the Chinese version of the behavioral pain scale in intubated and non-intubated critically ill patients: Two cross-sectional studies.

BACKGROUND: Self-report pain assessment scales may be inappropriate when critically ill patients are incapable of adequate communication because of sedation or mechanical ventilation. The Behavioral Pain Scale (BPS, for intubated patients) and the BPS-non intubated (BPS-NI, for non-intubated patients) measure objective behavioral indicators of pain in non-communicating critically ill patients. OBJECTIVES: To develop a Chinese version of the BPS combining the original version of the BPS and BPS-NI suitable for pain assessment among critically ill patients and to determine its reliability and validity. DESIGN: Two cross-sectional studies. SETTINGS: A 15-bed surgical intensive care unit (ICU) in a teaching hospital in Beijing, China. PARTICIPANTS: In the first study, 129 patients (53 intubated and 76 non-intubated) were recruited; in the second study, 83 (43 intubated and 40 non-intubated) were recruited. METHODS: The Chinese version of the BPS (BPS-C) was developed via rigorous translation methods, including double back-translation and content validation involving 13 clinical experts. Internal consistency, discriminative validity, and criterion-related validity were established using the BPS-C and the Numeric Rating Scale (NRS). The BPS-C and NRS were used to assess pain in 53 intubated and 76 non-intubated post-abdominal surgery patients during low pain exposure and increased pain exposure in the first study. To establish interrater reliability, a researcher and a bedside nurse independently performed 172 paired assessments in 43 intubated patients and 160 paired assessments in 40 non-intubated patients with the BPS-C under the same conditions in the second study. RESULTS: The BPS-C achieved conceptual and semantic equivalence with the original tool. Internal consistency was established through Cronbach's alpha (α=0.724-0.743 in intubated patients, α=0.701-0.762 in non-intubated patients). Interrater reliability was confirmed through the intraclass correlation coefficients (ICCs), which ranged from 0.962 to 1.000 in both intubated and non-intubated patients with high agreement percentages (95.3-100.0% in intubated and 95.0-100.0% in non-intubated patients). BPS-C scores during increased exposure to pain were significantly higher than those obtained during low exposure to pain, indicating discriminative validity. Criterion-related validity was confirmed by strong positive correlations between BPS-C and NRS scores (Pearson's correlations r=0.815-0.937 for intubated patients, Pearson's correlations r=0.755-0.899 for non-intubated patients). CONCLUSIONS: The Chinese version of the BPS (BPS-C) is appropriate for pain assessment among intubated and non-intubated ICU patients.

Value of Kidney Disease Improving Global Outcomes Urine Output Criteria in Critically Ill Patients: A Secondary Analysis of a Multicenter Prospective Cohort Study.

BACKGROUND: Urine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr). METHODS: We conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses. RESULTS: The prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality. CONCLUSION: UO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.