Respiratory Function Tolerance of Rats with Vaying Degrees of Thoracic Volume Reduction.

OBJECTIVE: To compare the effects of respiratory function on different degrees of reduced thoracic volume and evaluate the tolerance of rats with reduced thoracic volume, and to assess the feasibility of thoracic volume as a measure of the severity of rib fractures. METHODS: A total of 24 10-week-old female Sprague-Dawley (SD) rats were randomly divided into four groups (n = 6 in each group) according to the displacement degree of bilateral rib fractures (2, 4, 6, and 8 mm). The respiratory function of the rats（Tidal volume, Inspiration time, Expiration time, Breath rate, Minute volume, Peak inspiration flow) measured via whole-body barometric plethysmography before and after operation for 14 consecutive days. Respiratory function parameters of each group were analyzed. Chest CT scans were performed before and 14 days after operation, after that we reconstructed three-dimensional of the thoracic and lung and measured their volumes by computer software. We calculated the percentage of thoracic and lung volume reduction after operation. RESULTS: At the 14th day after the operation, the decline of thoracic volume rates of in the 2, 4, 6, and 8 mm groups were 5.20%, 9.01%, 16.67%, and 20.74%, respectively. The 8 mm group showed a significant reduction in lung volume. The postoperative tidal volumes were lower in each of the groups than the baseline values before the operation. The tidal volume of the 2 mm group gradually recovered after the operation and returned to a normal level (1.54 ± 0.07 mL) at 14th day after the operation. The tidal volume of the 4, 6, and 8 mm groups recovered gradually after the operation, but did not return to baseline level at the 14th day. In particular, the tidal volume of the 8 mm group was significantly lower than that of the other groups during the 14 days (1.23 ± 0.12 mL, p < 0.05). There were no significant changes in the inspiratory and expiratory times, peak inspiratory and expiratory flows, respiratory rate, and minute ventilation during the 14 days after the operation in each group. CONCLUSIONS: Displaced rib fractures lead to thoracic collapse and reduced thoracic volume, which can affect tidal volume in rats. The greater the decrease of thoracic volume, the more obvious the decrease of early tidal volume. The thoracic volume can be used as an objective parameter to evaluate the severity of multiple rib fractures. Early operation to restore thoracic volume may improve early respiratory function. Decreased thoracic volume affected respiratory function and can be compensated and recovered in the long term.

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.

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.

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.

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.

Myocardial injury after surgery is a risk factor for weaning failure from mechanical ventilation in critical patients undergoing major abdominal surgery.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery. METHODS: This retrospective study was conducted in the Department of Critical Care Medicine of Peking University People's Hospital. The subjects were all critically ill patients who underwent major abdominal surgery between January 2011 and December 2013. Clinical and laboratory parameters during the perioperative period were investigated. Backward stepwise regression analysis was performed to evaluate MINS relative to the rate of weaning failure. Age, hypertension, chronic renal disease, left ventricular ejection fraction before surgery, Acute Physiologic and Chronic Health Evaluation II score, pleural effusion, pneumonia, acute kidney injury, duration of mechanical ventilation before weaning and the level of albumin after surgery were treated as independent variables. RESULTS: This study included 381 patients, of whom 274 were successfully weaned. MINS was observed in 42.0% of the patients. The MINS incidence was significantly higher in patients who failed to be weaned compared to patients who were successfully weaned (56.1% versus 36.5%; P<0.001). Independent predictive factors of weaning failure were MINS, age, lower left ventricular ejection fraction before surgery and lower serum albumin level after surgery. The MINS odds ratio was 4.098 (95% confidence interval, 1.07 to 15.6; P = 0.04). The patients who were successfully weaned had shorter hospital stay lengths and a higher survival rate than those who failed to be weaned. CONCLUSION: MINS is a risk factor for weaning failure from mechanical ventilation in critical patients who have undergone major abdominal surgery, independent of age, lower left ventricular ejection fraction before surgery and lower serum albumin levels after surgery.

Pretreatment with interleukin-33 reduces warm hepatic ischemia/reperfusion injury in mice.

BACKGROUND: Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion (I/R) injury. METHODS: Male BALB/c mice ((22 ± 3) g) were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups: control group (laparotomy only, without blocking blood supply) and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups: control, model (injection of rabbit IgG polyclonal antibody), recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-4, IL-5, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were measured. RESULTS: Levels of IL-33 mRNA and protein did not change during ischemia (P > 0.05) but increased significantly during reperfusion (P < 0.05). After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-γ and TNF-α were significantly increased (P < 0.05), and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-γ decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-γ levels compared with controls (P < 0.05). There was no change in the level of TNF-α. CONCLUSION: IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Th1 to Th2 shift.

[Analysis of 565 cases of liver transplantation at a single transplantation center].

OBJECTIVE: To determine the preventative and curative strategies after liver transplantation by investigating the risk factors on prognosis. METHODS: The data of 565 consecutive patients who underwent orthotopic liver transplantation were retrospectively analyzed with the survival rate and complication morbidity. RESULTS: The follow-up time ranges from 3 to 104 months of all the 565 patients after liver transplantation. From January 2004 to January 2009, the patient survival rates were 91.2% after 1 month, 84.9% after 1 year, 69.2% after 3 years, and 66.1% after 5 years, while they were 87.8%, 73.2%, 60.2%, and 57.7% from May 2000 to December 2003. The patient survival rates were 83.3% after 1 year, 79.8% after 3 years, and 78.5% after 5 years in non-hepatocellular carcimoma (non-HCC) group, while they were 78.4%, 49.1%, and 45.1% in HCC group. In early stage after surgery, the morbidities of re-operation due to intra-abdominal hemorrage, vascular complication, severe infection, acute renal failure and primary graft dysfunction were 1.1%, 1.6%, 13.6%, 7.4%, and 1.2%, while in late stage, the morbidities of HCC recurrence, biliary complications, HBV recurrence, de novo malignancy, chronic graft dysfunction were 40.3%, 6.7%, 2.1%, 0.9%, 0.9%, and 1.1%, respectively. The HCC recurrent rates were 8.1% versus 62.5% in matching Milan criteria group or exceeding Milan criteria group and the median survival time was 19.6 months of all recurrent patients. CONCLUSION: Liver transplantation has been the effective treatment for end stage liver disease. Due to the shortage of graft,we prefer to do operations for the patients without HCC or the patients with HCC but matching Milan Criteria.

HBV infection involving in hepatic progenitor cells expansion in HBV-infected end-stage liver disease.

BACKGROUND/AIMS: In chronic hepatitis B, hepatic progenitor cells (HPCs) activation and ductular reactions occurred in periportal and portal area. However, the association between hepatitis B virus (HBV) infection and HPCs activation remains unknown. We aim to investigate the expansion of HPCs in patients with end-stage chronic hepatitis B and its relationship to HBV infection. METHODOLOGY: Liver biopsy specimens from 16 cases of end-stage liver disease caused by chronic hepatitis B were studied. The quantities of serum HBV DNA were available in 13 patients. The number of HPCs and the area of ductular reactions were quantitively analyzed on the cytokeratin 7 (CK7)-stained sections. Double-staining combined either HBsAg or HBcAg with CK7 were performed to assess the histological relationship between HBV infection and HPCs activation. RESULTS: All of the sections showed liver cirrhosis and severe inflammation (HAI ranged from 12 to 17). The number of HPCs correlated with the area of ductular reactions positively. Multivariate analysis showed that serum HBV DNA level was independently associated with HPCs activation and ductular reactions. Moreover, the expression area of HBsAg in liver tissue correlated with HPCs activation positively. CONCLUSIONS: In end-stage of chronic hepatitis B, the expansion of hepatic progenitor cells and ductular reactions were extensive. HBV infection may be involved in the proliferation of progenitor cells in cirrhotic environments.

[Risk factors of renal failure in the early post-liver transplantation period].

OBJECTIVE: To study the risk factors of renal failure in the early post-liver transplantation period. METHODS: 92 consecutive liver transplantation cases were reviewed and a multi-factor analysis of presumed risk factors of early post-transplantation period renal failure was conducted. The factors analyzed were total bilirubin level, prothrombin activity, onset of structural renal disease, onset of gastrointestinal hemorrhage, whether the patient underwent large-volume paracentesis, or underwent plasmapheresis therapy, needed renal replacement therapy, the operation method used, the bleeding volume during operation and the immunosuppressive agents used. RESULTS: Of the 92 patients, 29 (31.5%) developed acute renal failure (ARF) in the early postoperative period. Multi-factor analysis revealed a high pre-transplantation serum creatinine level and low prothrombin activity as risk factors for development of ARF. CONCLUSION: ARF is a frequent medical complication after liver transplantation. A high pre-transplantation serum creatinine level and low prothrombin activity are risk factors of its development.

[The diagnosis and treatment of hepatic artery complications in 107 cases of orthotopic liver transplantation].

OBJECTIVE: To investigate the diagnosis and managements of hepatic artery complications in orthotopic liver transplantation. METHODS: The clinical data of 107 consecutive orthotopic liver transplantation patients was reviewed retrospectively to assess the risk factors and the diagnosis and treatment of the vascular complications. RESULTS: The incidence of the artery related complications in orthotopic liver transplantation was associated with the quality of the donor organ artery and the reconstruction way of donor-recipient artery intimately. The main hepatic artery related complications were hepatic artery thrombosis and stenosis. The incidence of the vascular complications was 6.54%, and the mortality rate was 85.7%. CONCLUSIONS: The main influence factors of vascular complications were the quality of the donor organ artery and the reconstruction way of donor-recipient artery. The key steps of organ salvaging and the patients' life saving were early diagnosis and treatment of those complications.

[Venovenous bypass in 54 liver transplantations].

OBJECTIVES: To summarize hemodynamic and metabolic changes during bypass, and to evaluate the bypass in liver transplantation. METHODS: Fifty-four patients underwent orthotopic liver transplantation with venovenous bypass from May 2000 to May 2002. Their clinical features were analysed. RESULTS: SHR, MAP, CVP, CO, PaO(2), PaCO(2), serum K(+), Na(+), Ca(2+), BUN values were not significantly changed during bypass. Compared to the pre-bypass stage, pH was decreased in the post-bypass stage (P < 0.05), serum lactic acid value was increased in the bypass and post-bypass stage (P < 0.05), active clotting time was increased in the bypass stage (P < 0.05), serum creatinine value was increased on first postoperative day (P < 0.05). CONCLUSIONS: Venovenous bypass could improve hemodynamic and metabolic stability in the anhepatic phase, but it also could increase operation duration, liver ischemic time and cost.