BioMed Research International: Critical Care The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Self-Rated Health as a Predictor of Death after Two Years: The Importance of Physical and Mental Wellbeing Postintensive Care Mon, 21 Aug 2017 00:00:00 +0000 Introduction. The objective of this study is, among half-year intensive care survivors, to determine whether self-assessment of health can predict two-year mortality. Methods. The study is a prospective cohort study based on the Procalcitonin and Survival Study trial. Half-year survivors from this 1200-patient multicenter intensive care trial were sent the SF-36 questionnaire. We used both a simple one-item question and multiple questions summarized as a Physical Component Summary (PCS) and a Mental Component Summary (MCS) score. The responders were followed for vital status 730 days after inclusion. Answers were dichotomized into a low-risk and a high-risk group and hazard ratios (HR) with 95% confidence interval (CI) were calculated by Cox proportional hazard analyses. Conclusion. We found that self-rated health measured by a single question was a strong independent predictor of two-year all-cause mortality (HR: 1.8; 95% CI: 1.1–3.0). The multi-item component scores of the SF-36 also predicted two-year mortality (PCS: HR: 2.9; 95% CI 1.7–5.0) (MCS: HR: 1.9; 95% CI 1.1–3.4). These results suggest that self-rated health questions could help in identifying patients at excess risk. Randomized controlled trials are needed to test whether our findings represent causality. Marie Vejen, Jakob B. Bjorner, Morten H. Bestle, Anne Lindhardt, and Jens U. Jensen Copyright © 2017 Marie Vejen et al. All rights reserved. Low Molecular Weight Heparin Nebulization Attenuates Acute Lung Injury Mon, 15 May 2017 00:00:00 +0000 Background. As acute lung injury (ALI) caused high mortality rate, it is important to explore the protection and treatment of ALI. The aim of the current study is to evaluate the effect of low molecular weight heparin (LMWH) nebulization on attenuating acute lung injury and the associated mechanism. Methods. The arterial blood gas, total protein content in bronchoalveolar lavage fluid, lung wet/dry weight ratio, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and Akt phosphorylation were evaluated after the ALI rabbits were treated with or without LMWH nebulization. Results. PaO2 was increased and lung wet/dry weight ratio as well as total protein content in BALF was decreased after LMWH nebulization. After the application of LMWH nebulization therapy, the SOD and GSH-Px activity was rebounded and the increase of MDA content was significantly inhibited. The Akt protein phosphorylation level was decreased after LMWH nebulization therapy. Conclusions. LMWH nebulization treatment can relieve the traumatic ALI in rabbits and inhibit oxidative stress possibly by suppressing the Akt phosphorylation. Nianlin Xie, Menglei Huan, Feng Tian, Zhongping Gu, and Xiaofei Li Copyright © 2017 Nianlin Xie et al. All rights reserved. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis Mon, 15 May 2017 00:00:00 +0000 Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis”) translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis. Quentin Maestraggi, Benjamin Lebas, Raphaël Clere-Jehl, Pierre-Olivier Ludes, Thiên-Nga Chamaraux-Tran, Francis Schneider, Pierre Diemunsch, Bernard Geny, and Julien Pottecher Copyright © 2017 Quentin Maestraggi et al. All rights reserved. Risk Factors for the Mortality of Pneumocystis jirovecii Pneumonia in Non-HIV Patients Who Required Mechanical Ventilation: A Retrospective Case Series Study Mon, 08 May 2017 00:00:00 +0000 Background. The risk factors for the mortality rate of Pneumocystis jirovecii pneumonia (PCP) who required mechanical ventilation (MV) remained unknown. Methods. A retrospective chart review was performed of all PCP patients admitted to our intensive care unit and treated for acute hypoxemic respiratory failure to assess the risk factors for the high mortality. Results. Twenty patients without human immunodeficiency virus infection required mechanical ventilation; 19 received noninvasive ventilation; and 11 were intubated. PEEP was incrementally increased and titrated to maintain FIO2 as low as possible. No mandatory ventilation was used. Sixteen patients (80%) survived. Pneumothorax developed in one patient with rheumatoid arthritis (RA). Median PEEP level in the first 5 days was 10.0 cmH2O and not associated with death. Multivariate analysis showed the association of incidence of interstitial lung disease and increase in serum KL-6 with 90-day mortality. Conclusions. We found MV strategies to prevent pneumothorax including liberal use of noninvasive ventilation, and PEEP titration and disuse of mandatory ventilation may improve mortality in this setting. Underlying disease of interstitial lung disease was a risk factor and KL-6 may be a useful predictor associated with mortality in patients with RA. These findings will need to be validated in larger studies. Toru Kotani, Shinshu Katayama, Yuya Miyazaki, Satoshi Fukuda, Yoko Sato, and Koichi Ohsugi Copyright © 2017 Toru Kotani et al. All rights reserved. Advanced Age as a Predictor of Survival and Weaning in Venoarterial Extracorporeal Oxygenation: A Retrospective Observational Study Thu, 06 Apr 2017 00:00:00 +0000 Background. In most reports on ECMO treatment, advanced age is classified as a contraindication to VA ECMO. We attempted to investigate whether advanced age would be a main risk factor deciding VA ECMO application and performing VA ECMO support. We determined whether advanced age should be regarded as an absolute or relative contraindication to VA ECMO and could affect weaning and survival rates of VA ECMO patients. Methods. VA ECMO was performed on 135 adult patients with primary cardiogenic shock between January 2010 and December 2014. Successful weaning was defined as weaning from ECMO followed by survival for more than 48 hours. Results. Among the 135 patients, 35 survived and were discharged uneventfully, and the remaining 100 did not survive. There were significant differences in survival between age groups, and older age showed a lower survival rate with statistical significance (P = .01). By multivariate logistic regression analysis, age was not significantly associated with in-hospital mortality (P = .83) and was not significantly associated with VA ECMO weaning (P = .11). Conclusions. Advanced age is an undeniable risk factor for VA ECMO; however, patients of advanced age should not be excluded from the chance of recovery after VA ECMO treatment. WooSurng Lee, YoHan Kim, HyunHee Choi, HyoungSoo Kim, SunHee Lee, HeeSung Lee, HyunKeun Chee, JunSeok Kim, JaeJoon Hwang, SongAm Lee, YongHun Kim, SeongJoon Cho, SeMin Ryu, and SungMin Park Copyright © 2017 WooSurng Lee et al. All rights reserved. Hepatotoxicity of Antimycotics Used for Invasive Fungal Infections: In Vitro Results Tue, 04 Apr 2017 06:47:20 +0000 Purpose. Drug-induced liver injury (DILI) is the most common cause of liver injury and a serious clinical problem; antimycotics are involved in approximately 3% of all DILI cases. The hepatotoxicity of many drugs, including the antimycotics, is poorly screened in human models. Methods. In a standardized assay the cytotoxicity on hepatocytes of different concentrations (max, 5x max, and 10x max) of the antimycotics used for systemic infections was tested. Anidulafungin (ANI), liposomal amphotericerin B (L-AmB), caspofungin (CASPO), fluconazole (FLUCO), and voriconazole (VORI) were incubated with HepG2/C3A cells. After incubation, the viability of cells (XTT test, LDH release, trypan blue staining), the synthesis of albumin, the cytochrome 1A2 activity, and the cell death (DNA fragmentation) were determined. Kruskal-Wallis and Mann–Whitney tests were used for statistical analyses. Results. L-AmB, ANI, and CASPO showed a mild hepatotoxicity in the max concentrations. Higher concentrations of anidulafungin led to a severe impairment of hepatocyte viability and function. The azoles FLUCO and VORI had a higher hepatotoxic potential in all concentrations. Conclusion. Antimycotics, especially azoles, used for systemic infections should be given with caution in patient with liver insufficiency or liver failure or high risk for this; therefore, therapeutic drug monitoring should be used. Further studies with this approach are encouraged. Sandra Doß, Heike Potschka, Fanny Doß, Steffen Mitzner, and Martin Sauer Copyright © 2017 Sandra Doß et al. All rights reserved. Patients Admitted to Three Spanish Intensive Care Units for Poisoning: Type of Poisoning, Mortality, and Functioning of Prognostic Scores Commonly Used Tue, 28 Mar 2017 00:00:00 +0000 Objectives. To evaluate the gravity and mortality of those patients admitted to the intensive care unit for poisoning. Also, the applicability and predicted capacity of prognostic scales most frequently used in ICU must be evaluated. Methods. Multicentre study between 2008 and 2013 on all patients admitted for poisoning. Results. The results are from 119 patients. The causes of poisoning were medication, 92 patients (77.3%), caustics, 11 (9.2%), and alcohol, 20 (16,8%). 78.3% attempted suicides. Mean age was 44.42 ± 13.85 years. 72.5% had a Glasgow Coma Scale (GCS) ≤8 points. The ICU mortality was 5.9% and the hospital mortality was 6.7%. The mortality from caustic poisoning was 54.5%, and it was 1.9% for noncaustic poisoning (). After adjusting for SAPS-3 (OR: 1.19 (1.02–1.39)) the mortality of patients who had ingested caustics was far higher than the rest (OR: 560.34 (11.64–26973.83)). There was considerable discrepancy between mortality predicted by SAPS-3 (26.8%) and observed (6.7%) (Hosmer-Lemeshow test: ; ). The APACHE-II (7,57%) and APACHE-III (8,15%) were no discrepancies. Conclusions. Admission to ICU for poisoning is rare in our country. Medication is the most frequent cause, but mortality of caustic poisoning is higher. APACHE-II and APACHE-III provide adequate predictions about mortality, while SAPS-3 tends to overestimate. María Esther Banderas-Bravo, Maria Dolores Arias-Verdú, Ines Macías-Guarasa, Eduardo Aguilar-Alonso, Encarnación Castillo-Lorente, Lucia Pérez-Costillas, Raquel Gutierrez-Rodriguez, Guillermo Quesada-García, and Ricardo Rivera-Fernández Copyright © 2017 María Esther Banderas-Bravo et al. All rights reserved. Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin Domain-Containing 3 Inflammasome in Polymicrobial Sepsis Mon, 27 Mar 2017 00:00:00 +0000 Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed. Compared with CLP group, the CLP + GIK group had milder histological damage, lower levels of cytokines in the serum and ileum tissue samples, and lower UCP2 expression, whereas the CLP + GK group had no such effects. Moreover, the CLP + GIK group exhibited decreased epithelial permeability of the ileum and increased expression of zonula occludens-1, occludin, and claudin-1 in the ileum. The findings demonstrated that the UCP2 and NLR family-pyrin domain-containing 3/caspase 1/interleukin 1β signaling pathway may be involved in intestinal barrier injury and that GIK treatment decreased intestinal barrier permeability. Thus, GIK may be a useful treatment for intestinal barrier injury during sepsis. Jun-liang Zhang, Yi-ting Chen, Guang-dao Chen, Tao Wang, Ju-xin Zhang, and Qi-yi Zeng Copyright © 2017 Jun-liang Zhang et al. All rights reserved. Prospective Multicentre Study on the Epidemiology and Current Therapeutic Management of Severe Bronchiolitis in Spain Wed, 22 Mar 2017 10:13:28 +0000 Objective. To determine the epidemiology and therapeutic management of patients with severe acute bronchiolitis (AB) admitted to paediatric intensive care units (PICUs) in Spain. Design. Descriptive, prospective, multicentre study. Setting. Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission to any of the participating PICUs over 1 year. Interventions. Both epidemiological variables and medical treatment received were recorded. Results. A total of 262 patients were recruited; 143 were male (54.6%), with median age of 1 month (0–23). Median stay in the PICU was 7 days (1–46). Sixty patients (23%) received no nebuliser treatment, while the rest received a combination of inhalation therapies. One-quarter of patients (24.8%) received corticosteroids and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and noninvasive ventilation (NIV) was used in 75.6%. Endotracheal intubation was required in 24.4% of patients. Younger age, antibiotic therapy, and invasive mechanical ventilation (IMV) were risk factors that significantly increased the stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised bronchodilator treatment and corticosteroid therapy. Despite NIV being widely used in this condition, intubation was required in one-quarter of cases. Younger age, antibiotic therapy, and IMV were associated with a longer stay in the PICU. Jose C. Flores-González, Juan Mayordomo-Colunga, Iolanda Jordan, Alicia Miras-Veiga, Cristina Montero-Valladares, Marta Olmedilla-Jodar, Andrés J. Alcaraz-Romero, Miren Eizmendi-Bereciartua, Francisco Fernández-Carrión, Carmen Santiago-Gutierrez, Esther Aleo-Luján, Sonia Pérez-Quesada, Cristina Yun-Castilla, Carmen Martín, Álvaro Navarro-Mingorance, and Concha Goñi-Orayen Copyright © 2017 Jose C. Flores-González et al. All rights reserved. Intra-Abdominal Hypertension Causes Bacterial Growth in Lungs: An Animal Study Sun, 05 Mar 2017 10:14:28 +0000 To study the effect of intra-abdominal hypertension (IAH) on the frequency of pneumonia with an experimental study, thirteen Sprague-Dawley rats were included. Eight out of thirteen animals were randomly assigned to receive 10 ml of benzalkonium chloride 0.2% (megacolon group) and five animals received 10 ml NaCl 0.9% (controls). Animals were anaesthetized by intramuscular delivery of ketamine. The incidence of positivity for bacteria lung tissue cultures and mesenteric lymph node cultures was assessed at the 21st day after animals’ sacrification, or before in case of death. All megacolon group animals presented progressive increase of the abdomen and increased IAP (≥10 mmHg) whereas the frequency of their evacuations was almost eliminated. Controls presented normal evacuations, no sign of abdominal distention, and normal IAP. In megacolon group animals, there was evidence of significant amount of bacteria in lung cultures. In contrast, no bacteria were found in control animals. Eleni Papakrivou, Demosthenes Makris, Efstratios Manoulakas, Magda Mitroudi, Konstantinos Tepetes, Konstantinos Papazoglou, and Epaminondas Zakynthinos Copyright © 2017 Eleni Papakrivou et al. All rights reserved. Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process Sun, 05 Feb 2017 06:52:28 +0000 Inappropriate mechanical ventilation (MV) can result in ventilator-induced lung injury (VILI). Probing mechanisms of VILI and searching for effective methods are current areas of research focus on VILI. The present study aimed to probe into mechanisms of endothelial microparticles (EMPs) in VILI and the protective effects of Tetramethylpyrazine (TMP) against VILI. In this study, C57BL/6 and TLR4KO mouse MV models were used to explore the function of EMPs associated with p21 activated kinases-4 (PAK-4) in VILI. Both the C57BL/6 and TLR4 KO groups were subdivided into a mechanical ventilation (MV) group, a TMP + MV group, and a control group. After four hours of high tidal volume (20 ml/kg) MV, the degree of lung injury and the protective effects of TMP were assessed. VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level. The intercellular junction protein of β-catenin was also decreased accompanied by a thickening alveolar wall, increased lung W/D values, and neutrophil infiltration. TMP alleviated VILI via decreasing circulating EMPs, stabilizing intercellular junctions, and alleviating neutrophil infiltration. Shuming Pan, Aihua Fei, Lihong Jing, Xiangyu Zhang, and Chengjin Gao Copyright © 2017 Shuming Pan et al. All rights reserved. Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis? Wed, 01 Feb 2017 00:00:00 +0000 Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01–50 ng/mL procalcitonin for  h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey’s test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis () and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all ). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients. Martin Sauer, Sandra Doß, Johannes Ehler, Thomas Mencke, and Nana-Maria Wagner Copyright © 2017 Martin Sauer et al. All rights reserved. Is Hydrogen Breath Test with Lactulose Feasible for Measuring Gastrocecal Transit in Critically Ill Children? Pilot Study about Modification of the Technique Thu, 26 Jan 2017 13:11:20 +0000 Introduction. Gastrocecal transit time (GCTT) can be measured by exhaled hydrogen after lactulose intake (lactulose-eH2 test). The objectives were to assess whether it is possible to carry out this test in critically ill children with and without mechanical ventilation (MV) and to analyze whether the results are consistent with clinical findings. Methods. Patients admitted to the Pediatric Intensive Care Unit (PICU) for more than 3 days were included. Those with gastrointestinal disease prior to admission were excluded. A modified technique to obtain eH2 from the ventilator tubes was performed. Results. Sixteen patients (37.5% boys) with a median age of 19 (5–86.5) months were included. Five patients (31.2%) were breathing spontaneously but lactulose-eH2 test could not be performed while it could be performed successfully in the 11 patients with MV. Seven patients (63.3%) did not show an eH2 peak. The other 4 showed a median time of 130 min (78.7–278.7 min) from lactulose intake to a 10 ppm eH2 peak. Children with an eH2 peak had intestinal movements earlier [6.5 (1.5–38.5) versus 44 (24–72) hours ]. Conclusion. Although the designed adaption is useful for collecting breath samples, lactulose-eH2 test may not be useful for measuring GCTT in critically ill children. J. López, C. Sánchez, S. N. Fernández, R. González, M. J. Solana, J. Urbano, M. Tolín, and J. López-Herce Copyright © 2017 J. López et al. All rights reserved. Organ Donation and Elective Ventilation: A Necessary Strategy Sun, 15 Jan 2017 12:39:34 +0000 Organ transplantation is the sole treatment to improve or save the life of patients with final-stage organ failure. The shortage of available organs for transplantation constitutes a universal problem, estimating that 10% of patients on waiting lists die. Brain death is an undesirable result; nevertheless, it has beneficial side-effects since it is the most frequent source of organs for transplantation. However, this phenomenon is relatively uncommon and has a limited potential. One of the options that focuses on increasing organ donation is to admit patients with catastrophic brain injuries (with a high probability of brain death and nontreatable) to the Intensive Care Unit, with the only purpose of donation. To perform elective nontherapeutic ventilation (ENTV), a patient’s anticipated willingness to donate organs and/or explicit acceptance by his/her relatives is required. This process should focus exclusively on those patients with catastrophic brain injuries and imminent risk of death which, due to its acute damage, are not considered treatable. This article defends ENTV as an effective strategy to improve donation rate, analyzing its ethical and legal basis. Dolores Escudero, Jesus Otero, Begoña Menéndez de León, and Marcos Perez-Basterrechea Copyright © 2017 Dolores Escudero et al. All rights reserved. Accuracy of Cardiac Output by Nine Different Pulse Contour Algorithms in Cardiac Surgery Patients: A Comparison with Transpulmonary Thermodilution Wed, 28 Dec 2016 06:50:12 +0000 Objective. Today, there exist several different pulse contour algorithms for calculation of cardiac output (CO). The aim of the present study was to compare the accuracy of nine different pulse contour algorithms with transpulmonary thermodilution before and after cardiopulmonary bypass (CPB). Methods. Thirty patients scheduled for elective coronary surgery were studied before and after CPB. A passive leg raising maneuver was also performed. Measurements included CO obtained by transpulmonary thermodilution () and by nine pulse contour algorithms (). Calibration of pulse contour algorithms was performed by esophageal Doppler ultrasound after induction of anesthesia and 15 min after CPB. Correlations, Bland-Altman analysis, four-quadrant, and polar analysis were also calculated. Results. There was only a poor correlation between and during passive leg raising and in the period before and after CPB. Percentage error exceeded the required 30% limit. Four-quadrant and polar analysis revealed poor trending ability for most algorithms before and after CPB. The Liljestrand-Zander algorithm revealed the best reliability. Conclusions. Estimation of CO by nine different pulse contour algorithms revealed poor accuracy compared with transpulmonary thermodilution. Furthermore, the less-invasive algorithms showed an insufficient capability for trending hemodynamic changes before and after CPB. The Liljestrand-Zander algorithm demonstrated the highest reliability. This trial is registered with NCT02438228 ( Ole Broch, Berthold Bein, Matthias Gruenewald, Sarah Masing, Katharina Huenges, Assad Haneya, Markus Steinfath, and Jochen Renner Copyright © 2016 Ole Broch et al. All rights reserved. Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis Sun, 18 Dec 2016 13:36:19 +0000 Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway. Gui-Jun Wang, Yue Wang, Yong-Sheng Teng, Fa-Lv Sun, Hong Xiang, Jian-Jun Liu, Shi-Lin Xia, Gui-Xin Zhang, Hai-Long Chen, and Dong Shang Copyright © 2016 Gui-Jun Wang et al. All rights reserved. Pulmonary Infection Is an Independent Risk Factor for Long-Term Mortality and Quality of Life for Sepsis Patients Mon, 05 Dec 2016 11:23:02 +0000 Background. Long-term outcomes (mortality and health-related quality of life) of sepsis have risen as important indicators for health care. Pulmonary infection and abdominal infection are the leading causes of sepsis. However, few researches about long-term outcomes focused on the origin of sepsis. Here we aim to study the clinical differences between pulmonary-sepsis and abdominal-sepsis and to investigate whether different infection foci were associated with long-term outcomes. Methods. Patients who survived after hospital discharge were followed up by telephone interview. Quality of life (QoL) was assessed using the EuroQol 5-dimension (EQ5D) questionnaire. Results. Four hundred and eighty-three sepsis patients were included, 272 (56.3%) had pulmonary-sepsis, and 180 (37.3%) had abdominal-sepsis. The overall ICU and one-year mortality rates of the cohort were 17.8% and 36.1%, respectively. Compared with abdominal-sepsis, pulmonary-sepsis patients had older age, higher APACHE II, higher ICU mortality (31.7% versus 12.6%), and one-year mortality (45.4% versus 24.4%), together with worse QoL. Age, septic shock, acute renal failure, fungus infection, anion gap, and pulmonary infection were predictors for one-year mortality and pulmonary infection was a risk factor for poor QoL. Conclusions. Pulmonary-sepsis showed worse outcome than abdominal-sepsis. Pulmonary infection is a risk factor for one-year mortality and QoL after sepsis. Xiao-Li He, Xue-Lian Liao, Zhi-Chao Xie, Li Han, Xiao-Lei Yang, and Yan Kang Copyright © 2016 Xiao-Li He et al. All rights reserved. Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome Thu, 01 Dec 2016 13:42:42 +0000 Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH) treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS) (not acute kidney injury, AKI) with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group () and a non-ECVVH group (). Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, extravascular lung water index (EVLWI), and E-selectin level were not significantly different between groups (all ). Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all ) at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU) were shorter in ECVVH group (all ), but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI), treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU. Jian-biao Meng, Zhi-zhen Lai, Xiu-juan Xu, Chun-lian Ji, Ma-hong Hu, and Geng Zhang Copyright © 2016 Jian-biao Meng et al. All rights reserved. Satisfaction Domains Differ between the Patient and Their Family in Adult Intensive Care Units Thu, 01 Dec 2016 13:35:46 +0000 Background. Patients’ and family’s satisfaction data from the Asian intensive care units (ICUs) is lacking. Objective. Domains between patient and family satisfaction and contribution of each domain to the general satisfaction were studied. Method. Over 3 months, adult patients across 4 ICUs staying for more than 48 hours with abbreviated mental test score of 7 or above and able to understand English and immediate family members were surveyed by separate validated satisfaction questionnaires. Results. Two hundred patients and 194 families were included in the final analysis. Significant difference in the satisfaction scores was observed between the ICUs. Patients were most and least satisfied in the communication (4.2 out of 5) and decision-making (2.9 out of 5) domains, respectively. Families were most and least satisfied in the relationship with doctors (3.9 out of 5) and family’s involvement domains (3.3 out of 5), respectively. Domains contributing most to the general satisfaction were the illness management domain for patients (β coefficient = 0.44) and characteristics of doctors and nurses domain for family (β coefficient = 0.45). Discussion. In an Asian ICU community, patients and families differ in their expectations and valuations of health care processes. Health care providers have difficult tasks in attending to these different domains. Amartya Mukhopadhyay, Ge Song, Pei Zhen Sim, Kit Cheng Ting, Jeffrey Kwang Sui Yoo, Qing Li Wang, Raudhah Binte Haji Mohamad Mascuri, Venetia Hui Ling Ong, Jason Phua, and Yanika Kowitlawakul Copyright © 2016 Amartya Mukhopadhyay et al. All rights reserved. Evaluation of Bone Metabolism in Critically Ill Patients Using CTx and PINP Tue, 29 Nov 2016 06:46:41 +0000 Background. Prolonged immobilization, nutritional and vitamin D deficiency, and specific drug administration may lead to significant bone resorption. Methods and Patients. We prospectively evaluated critically ill patients admitted to the ICU for at least 10 days. Demographics, APACHE II, SOFA scores, length of stay (LOS), and drug administration were recorded. Blood collections were performed at baseline and on a weekly basis for five consecutive weeks. Serum levels of PINP, β-CTx, iPTH, and 25(OH)vitamin D were measured at each time-point. Results. We enrolled 28 patients of mean age 67.4 ± 2.3 years, mean APACHE II 22.2 ± 0.9, SOFA 10.1 ± 0.6, and LOS 31.6 ± 5.7 days. Nineteen patients were receiving low molecular weight heparin, 17 nor-epinephrine and low dose hydrocortisone, 18 transfusions, and 3 phenytoin. 25(OH)vitamin D serum levels were very low in all patients at all time-points; iPTH serum levels were increased at baseline tending to normalize on 5th week; β-CTx serum levels were significantly increased compared to baseline on 2nd week (peak values), whereas PINP levels were increased significantly after the 4th week. Conclusions. Our data show that critically ill patients had a pattern of hypovitaminosis D, increased iPTH, hypocalcaemia, and BTMs compatible with altered bone metabolism. Alexandra Gavala, Konstantinos Makris, Anna Korompeli, and Pavlos Myrianthefs Copyright © 2016 Alexandra Gavala et al. All rights reserved. Impact of WHO Hand Hygiene Improvement Program Implementation: A Quasi-Experimental Trial Wed, 23 Nov 2016 13:28:28 +0000 Objectives. As affirmed by the World Health Organization (WHO), hand hygiene is the most powerful preventive measure against healthcare-associated infections (HCAIs) and, thus, it has become one of the five key elements of patient safety program. The aim is to assess the effect of implementation of the WHO’s Multimodal Hand Hygiene Improvement Strategy among healthcare workers of a tertiary teaching hospital in a developing country. Methods. Hand hygiene compliance was assessed among healthcare workers, according to five defined moments for hand hygiene of the WHO, before and after implementation of the WHO’s Multimodal Hand Hygiene Improvement Strategy in fourteen wards of a tertiary teaching hospital in Shiraz, Iran. We used direct observation method and documented the results in WHO hand hygiene observation forms. Results. There was a significant change in compliance before and after implementation of WHO’s Multimodal HH Improvement Strategy (29.8% and 70.98%, resp.). Conclusions. Implementing WHO hand hygiene program can significantly improve hand hygiene compliance among nurses. Farinaz Farhoudi, Anahita Sanaei Dashti, Minoo Hoshangi Davani, Nadiyeh Ghalebi, Golnar Sajadi, and Raziyeh Taghizadeh Copyright © 2016 Farinaz Farhoudi et al. All rights reserved. The Role of Targeted Temperature Management in Adult Patients Resuscitated from Nonshockable Cardiac Arrests: An Updated Systematic Review and Meta-Analysis Tue, 25 Oct 2016 15:52:21 +0000 Routine targeted temperature management is recommended for comatose adult patients with return of spontaneous circulation after cardiac arrest. However, the role of targeted temperature management in patients resuscitated from nonshockable cardiac arrests remains uncertain. We conducted an updated systematic review and meta-analysis to evaluate the effects of targeted temperature management in this population. Medline, EMBASE, and Cochrane databases were systematically reviewed for studies published between January 2005 and March 2016, in which targeted temperature management was compared with standard care or normothermia for adult patients resuscitated from nonshockable cardiac arrests. A total of 25 trials that included 5715 patients were identified from 10985 relevant papers. Pooled data showed that targeted temperature management not only associated with improved short-term survival (RR = 1.42, 95% CI: 1.28–1.57) and neurological function (RR = 1.63, 95% CI: 1.39–1.91) but also associated with improved long-term survival (RR = 1.64, 95% CI: 1.27–2.12) and neurological recovery (RR = 1.42, 95% CI: 1.07–1.90) in observational cohort studies. However, more frequent infectious complications were reported in hypothermia-treated patients (RR = 1.46, 95% CI: 1.26–1.70) and the quality of the evidence ranged from moderate to very low. Lijuan Song, Liang Wei, Lei Zhang, Yubao Lu, Kaifa Wang, and Yongqin Li Copyright © 2016 Lijuan Song et al. All rights reserved. Sepsis: Diagnostic and Therapeutic Challenges Mon, 17 Oct 2016 11:54:38 +0000 Zsolt Molnár, Evangelos J. Giamarellos-Bourboulis, Anand Kumar, and Axel Nierhaus Copyright © 2016 Zsolt Molnár et al. All rights reserved. Acute Kidney Injury Classified by Serum Creatinine and Urine Output in Critically Ill Cancer Patients Mon, 10 Oct 2016 05:51:55 +0000 Acute kidney injury (AKI) is common in critically ill patients and is associated with higher mortality. Cancer patients are at an increased risk of AKI. Our objective was to determine the incidence of AKI in our critically ill cancer patients, using the criteria of serum creatinine (SCr) and urine output (UO) proposed by the Kidney Disease: Improving Global Outcomes (KDIGO). Methods. We performed a retrospective cohort analysis of a prospectively collected database at the intensive care unit (ICU) of the Instituto Nacional de Cancerología from January 2013 to March 2015. Results. We classified AKI according to the KDIGO definition. We included 389 patients; using the SCr criterion, 192 (49.4%) had AKI; using the UO criterion, 219 (56.3%) had AKI. Using both criteria, we diagnosed AKI in 69.4% of patients. All stages were independently associated with six-month mortality; stage 1 HR was 2.04 (95% CI 1.14–3.68, ), stage 2 HR was 2.73 (95% CI 1.53–4.88, ), and stage 3 HR was 4.5 (95% CI 2.25–8.02, ). Patients who fulfilled both criteria had a higher mortality compared with patients who fulfilled just one criterion (HR 3.56, 95% CI 2.03–6.24, ). Conclusion. We diagnosed AKI in 69.4% of patients. All AKI stages were associated with higher risk of death at six months, even for patients who fulfilled just one AKI criterion. Bertha M. Córdova-Sánchez, Ángel Herrera-Gómez, and Silvio A. Ñamendys-Silva Copyright © 2016 Bertha M. Córdova-Sánchez et al. All rights reserved. The Role of Obesity in Sepsis Outcome among Critically Ill Patients: A Retrospective Cohort Analysis Thu, 29 Sep 2016 05:45:00 +0000 Background. The objective of this study was to assess the correlation between sepsis, obesity, and mortality of patients admitted to an Intensive Care Unit (ICU). Subjects and Methods. Data of all patients admitted to the ICU of a tertiary hospital during a 28-month period were retrospectively analyzed and included in the study. Results. Of 834 patients included, 163 (19.5%) were obese, while 25 (3.0%) were morbidly obese. Number of comorbidities (), bloodstream infection (), and carbapenemase-producing Klebsiella pneumoniae colonization during ICU stay () were significantly associated with obesity, while nonobese patients suffered more frequently from spontaneous intracranial hemorrhage (). Total ICU mortality was 22.5%. Increased mortality among obese ICU patients was observed. Sepsis was the main condition of admission for which obese patients had statistically lower survival than normal weight subjects (76.3% versus 43.7%; ). Mortality of septic patients upon admission was independently associated with SOFA score upon ICU admission (), obesity (), pneumonia (), and development of septic shock (). Conclusions. Our study revealed that sepsis upon ICU admission is adversely influenced by obesity but further studies are needed in order to assess the role of obesity in sepsis outcome. Matthaios Papadimitriou-Olivgeris, Diamanto Aretha, Anastasia Zotou, Kyriaki Koutsileou, Aikaterini Zbouki, Aikaterini Lefkaditi, Christina Sklavou, Markos Marangos, and Fotini Fligou Copyright © 2016 Matthaios Papadimitriou-Olivgeris et al. All rights reserved. Advanced Hemodynamic Management in Patients with Septic Shock Wed, 14 Sep 2016 07:01:31 +0000 In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies. Bernd Saugel, Wolfgang Huber, Axel Nierhaus, Stefan Kluge, Daniel A. Reuter, and Julia Y. Wagner Copyright © 2016 Bernd Saugel et al. All rights reserved. The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis Tue, 06 Sep 2016 14:18:59 +0000 Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures. Lukas Martin, Patrick Koczera, Elisabeth Zechendorf, and Tobias Schuerholz Copyright © 2016 Lukas Martin et al. All rights reserved. The Effect of Esmolol on Tissue Perfusion and Clinical Prognosis of Patients with Severe Sepsis: A Prospective Cohort Study Mon, 29 Aug 2016 06:18:26 +0000 Purpose. This study was aimed at investigating the effect of esmolol on tissue perfusion and the clinical prognosis of patients with severe sepsis. Materials and Methods. One hundred fifty-one patients with severe sepsis were selected and divided into the esmolol group () or the control group (), who received conventional antiseptic shock treatment. The esmolol group received a continuous infusion of esmolol via a central venous catheter, and their heart rate (HR) was maintained at 70–100 bpm over 72 hours. Results. The HR of all patients reached the target level within 72 hours of treatment for both groups. The effect of esmolol on PvaCO2 was only significant at 48 hours (). ScvO2 increased in the esmolol group and decreased in the control group (). Lac showed a linear downward trend over the treatment time, but the reduction was more significant in the control group at 48 hours () between the two groups. Kaplan-Meier analysis showed a significantly shorter duration of mechanical ventilation in the esmolol group than in the control group (). Conclusions. Esmolol reduced the duration of mechanical ventilation in patients with severe sepsis, with no significant effect on circulatory function or tissue perfusion. Xiuling Shang, Kaiyu Wang, Jingqing Xu, Shurong Gong, Yong Ye, Kaihua Chen, Fayang Lian, Wei Chen, and Rongguo Yu Copyright © 2016 Xiuling Shang et al. All rights reserved. Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments Tue, 28 Jun 2016 15:24:43 +0000 Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged. Martin Sauer, Jens Altrichter, Cristof Haubner, Annette Pertschy, Thomas Wild, Fanny Doß, Thomas Mencke, Maren Thomsen, Johannes Ehler, Jörg Henschel, Sandra Doß, Stephanie Koch, Georg Richter, Gabriele Nöldge-Schomburg, and Steffen R. Mitzner Copyright © 2016 Martin Sauer et al. All rights reserved. L-Malate’s Plasma and Excretion Profile in the Treatment of Moderate and Severe Hemorrhagic Shock in Rats Wed, 15 Jun 2016 13:19:30 +0000 Introduction. Malate is a standard component in fluid therapy within a wide range of medical applications. To date, there are insufficient data regarding its plasma distribution, renal excretion, and metabolism after infusion. This study aimed to investigate these three aspects in a rat model of moderate and severe hemorrhagic shock (HS). Methods. Male Wistar rats were subjected to HS by dropping the mean arterial blood pressure to 25–30 mmHg (severe) and 40–45 mmHg (moderate), respectively, for 60 minutes. Subsequently, reperfusion with Ringer-saline or a malate containing crystalloid solution (7 mM, 13.6 mM, and 21 mM, resp.) was performed within 30 minutes, followed by an observation period of 150 minutes. Results. In the present experiments, malate rapidly disappeared from the blood, while only 5% of the infused malate was renally excreted. In the resuscitation interval the urinary citrate and succinate amounts significantly increased compared to control. Conclusion. Malate’s half-life is between 30 and 60 minutes in both, moderate and severe HS. Thus, even under traumatic conditions malate seems to be subjected to rapid metabolism with participation of the kidneys. Indra N. Waack, Stephan Himmen, Friederike Mueller, Ricarda Rohrig, Friederike Roehrborn, Johanna K. Teloh, and Herbert de Groot Copyright © 2016 Indra N. Waack et al. All rights reserved. Venovenous Extracorporeal Membrane Oxygenation in Intractable Pulmonary Insufficiency: Practical Issues and Future Directions Tue, 05 Apr 2016 07:37:31 +0000 Venovenous extracorporeal membrane oxygenation (vv-ECMO) is a highly invasive method for organ support that is gaining in popularity due to recent technical advances and its successful application in the recent H1N1 epidemic. Although running a vv-ECMO program is potentially feasible for many hospitals, there are many theoretical concepts and practical issues that merit attention and require expertise. In this review, we focus on indications for vv-ECMO, components of the circuit, and management of patients on vv-ECMO. Concepts regarding oxygenation and decarboxylation and how they can be influenced are discussed. Day-to-day management, weaning, and most frequent complications are covered in light of the recent literature. T. S. R. Delnoij, R. Driessen, A. S. Sharma, E. A. Bouman, U. Strauch, and P. M. Roekaerts Copyright © 2016 T. S. R. Delnoij et al. All rights reserved. The Complex Relationship of Extracorporeal Membrane Oxygenation and Acute Kidney Injury: Causation or Association? Wed, 24 Feb 2016 13:05:54 +0000 Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass (CPB) circuit capable of providing prolonged cardiorespiratory support. Recent advancement in ECMO technology has resulted in increased utilisation and clinical application. It can be used as a bridge-to-recovery, bridge-to-bridge, bridge-to-transplant, or bridge-to-decision. ECMO can restitute physiology in critically ill patients, which may minimise the risk of progressive multiorgan dysfunction. Alternatively, iatrogenic complications of ECMO clearly contribute to worse outcomes. These factors affect the risk : benefit ratio of ECMO which ultimately influence commencement/timing of ECMO. The complex interplay of pre-ECMO, ECMO, and post-ECMO pathophysiological processes are responsible for the substantial increased incidence of ECMO-associated acute kidney injury (EAKI). The development of EAKI significantly contributes to morbidity and mortality; however, there is a lack of evidence defining a potential benefit or causative link between ECMO and AKI. This area warrants investigation as further research will delineate the mechanisms involved and subsequent strategies to minimise the risk of EAKI. This review summarizes the current literature of ECMO and AKI, considers the possible benefits and risks of ECMO on renal function, outlines the related pathophysiology, highlights relevant investigative tools, and ultimately suggests an approach for future research into this under investigated area of critical care. Daniel J. Kilburn, Kiran Shekar, and John F. Fraser Copyright © 2016 Daniel J. Kilburn et al. All rights reserved. Current Applications for the Use of Extracorporeal Carbon Dioxide Removal in Critically Ill Patients Thu, 04 Feb 2016 06:43:04 +0000 Mechanical ventilation in patients with respiratory failure has been associated with secondary lung injury, termed ventilator-induced lung injury. Extracorporeal venovenous carbon dioxide removal (ECCO2R) appears to be a feasible means to facilitate more protective mechanical ventilation or potentially avoid mechanical ventilation in select patient groups. With this expanding role of ECCO2R, we aim to describe the technology and the main indications of ECCO2R. Luigi Camporota and Nicholas Barrett Copyright © 2016 Luigi Camporota and Nicholas Barrett. All rights reserved. Method Based on the β-Lactamase PenPC Fluorescent Labeled for β-Lactam Antibiotic Quantification in Human Plasma Sun, 24 Jan 2016 11:49:38 +0000 Recently, Wong et al. have successfully developed a fluorescent biosensor based on the PenPC β-lactamase which changes its intrinsic fluorescence in presence of β-lactam antibiotics (BLAs). Here, we studied systematically this correlation among the fluorescence change of the biosensor and the concentration of different BLAs aimed at developing a novel method for estimating the concentration of a wide range of BLAs. This method showed high precision and specificity and very low interference from clinically relevant samples. We were able to monitor the pharmacokinetics of meropenem in healthy volunteers as well as in an ill animal model too, indicating that the implemented method could be suitable for clinical practice. Max Andresen, Kwok-Yin Wong, Yun-Chung Leung, Wai-Ting Wong, Pak-Ho Chan, Max Andresen-Vasquez, Leyla Alegria, Camila Silva, Pablo Tapia, Patricio Downey, and Dagoberto Soto Copyright © 2016 Max Andresen et al. All rights reserved. Research Advances in Critical Care: Targeting Patients’ Physiological and Psychological Outcomes Mon, 26 Oct 2015 09:09:06 +0000 Elizabeth Papathanassoglou, Ged Williams, and Julie Benbenishty Copyright © 2015 Elizabeth Papathanassoglou et al. All rights reserved. An Integrative Literature Review of Organisational Factors Associated with Admission and Discharge Delays in Critical Care Mon, 19 Oct 2015 08:16:43 +0000 The literature shows that delayed admission to the intensive care unit (ICU) and discharge delays from the ICU are associated with increased adverse events and higher costs. Identifying factors related to delays will provide information to practice improvements, which contribute to better patient outcomes. The aim of this integrative review was to explore the incidence of patients’ admission and discharge delays in critical care and to identify organisational factors associated with these delays. Seven studies were included. The major findings are as follows: (1) explanatory research about discharge delays is scarce and one study on admission delays was found, (2) delays are a common problem mostly due to organisational factors, occurring in 38% of admissions and 22–67% of discharges, and (3) redesigning care processes by improving information management and coordination between units and interdisciplinary teams could reduce discharge delays. In conclusion, patient outcomes can be improved through efficient and safe care processes. More exploratory research is needed to identify factors that contribute to admission and discharge delays to provide evidence for clinical practice improvements. Shortening delays requires an interdisciplinary and multifaceted approach to the whole patient flow process. Conclusions should be made with caution due to the limited number of articles included in this review. Laura-Maria Peltonen, Louise McCallum, Eriikka Siirala, Marjaana Haataja, Heljä Lundgrén-Laine, Sanna Salanterä, and Frances Lin Copyright © 2015 Laura-Maria Peltonen et al. All rights reserved. The Impact of Pain Assessment on Critically Ill Patients’ Outcomes: A Systematic Review Mon, 19 Oct 2015 08:12:11 +0000 In critically ill patients, pain is a major problem. Efficient pain management depends on a systematic, comprehensive assessment of pain. We aimed to review and synthesize current evidence on the impact of a systematic approach to pain assessment on critically ill patients’ outcomes. A systematic review of published studies (CINAHL, PUBMED, SCOPUS, EMBASE, and COCHRANE databases) with predetermined eligibility criteria was undertaken. Methodological quality was assessed by the EPHPP quality assessment tool. A total of 10 eligible studies were identified. Due to big heterogeneity, quantitative synthesis was not feasible. Most studies indicated the frequency, duration of pain assessment, and types of pain assessment tools. Methodological quality assessment yielded “strong” ratings for 5/10 and “weak” ratings for 3/10 studies. Implementation of systematic approaches to pain assessment appears to associate with more frequent documented reports of pain and more efficient decisions for pain management. There was evidence of favorable effects on pain intensity, duration of mechanical ventilation, length of ICU stay, mortality, adverse events, and complications. This systematic review demonstrates a link between systematic pain assessment and outcome in critical illness. However, the current level of evidence is insufficient to draw firm conclusions. More high quality randomized clinical studies are needed. Evanthia Georgiou, Maria Hadjibalassi, Ekaterini Lambrinou, Panayiota Andreou, and Elizabeth D. E. Papathanassoglou Copyright © 2015 Evanthia Georgiou et al. All rights reserved. Defining the Role of Dexmedetomidine in the Prevention of Delirium in the Intensive Care Unit Mon, 19 Oct 2015 08:06:49 +0000 Dexmedetomidine is a highly selective agonist used as a sedative agent. It also provides anxiolysis and sympatholysis without significant respiratory compromise or delirium. We conducted a systematic review to examine whether sedation of patients in the intensive care unit (ICU) with dexmedetomidine was associated with a lower incidence of delirium as compared to other nondexmedetomidine sedation strategies. A search of PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews yielded only three trials from 1966 through April 2015 that met our predefined inclusion criteria and assessed dexmedetomidine and outcomes of delirium as their primary endpoint. The studies varied in regard to population, comparator sedation regimen, delirium outcome measure, and dexmedetomidine dosing. All trials are limited by design issues that limit our ability definitively to conclude that dexmedetomidine prevents delirium. Evidence does suggest that dexmedetomidine may allow for avoidance of deep sedation and use of benzodiazepines, factors both observed to increase the risk for developing delirium. Our assessment of currently published literature highlights the need for ongoing research to better delineate the role of dexmedetomidine for delirium prevention. S. Nelson, A. J. Muzyk, M. H. Bucklin, S. Brudney, and J. P. Gagliardi Copyright © 2015 S. Nelson et al. All rights reserved. Auditing of Monitoring and Respiratory Support Equipment in a Level III-C Neonatal Intensive Care Unit Mon, 19 Oct 2015 07:46:30 +0000 Background. Random safety audits (RSAs) are a safety tool but have not been widely used in hospitals. Objectives. To determine the frequency of proper use of equipment safety mechanisms in relation to monitoring and mechanical ventilation by performing RSAs. The study also determined whether factors related to the patient, time period, or characteristics of the area of admission influenced how the device safety systems were used. Methods. A prospective observational study was conducted in a level III-C Neonatal Intensive Care Unit (NICU) during 2012. 87 days were randomly selected. Appropriate overall use was defined when all evaluated variables were correctly programmed in the audited device. Results. A total of 383 monitor and ventilator audits were performed. The Kappa coefficient of interobserver agreement was 0.93. The rate of appropriate overall use of the monitors and respiratory support equipment was 33.68%. Significant differences were found with improved usage during weekends, OR 1.85 (1.12–3.06, ), and during the late shift (3 pm to 10 pm), OR 1.59 (1.03–2.4, ). Conclusions. Equipment safety systems of monitors and ventilators are not properly used. To improve patient safety, we should identify which alarms are really needed and where the difficulties lie for the correct alarm programming. Elena Bergon-Sendin, Carmen Perez-Grande, David Lora-Pablos, Javier De la Cruz Bertolo, María Teresa Moral-Pumarega, Gerardo Bustos-Lozano, and Carmen Rosa Pallas-Alonso Copyright © 2015 Elena Bergon-Sendin et al. All rights reserved. Is It Time to Beta Block the Septic Patient? Sun, 18 Oct 2015 12:00:10 +0000 Beta blockers are some of the most studied drugs in the pharmacopoeia. They are already widely used in medicine for treating hypertension, chronic heart failure, tachyarrhythmias, and tremor. Whilst their use in the immediate perioperative patient has been questioned, the use of esmolol in the patients with established septic shock has been recently reported to have favourable outcomes. In this paper, we review the role of the adrenergic system in sepsis and the evidence for the use of beta stimulation and beta blockers from animal models to critically ill patients. Philip Pemberton, Tonny Veenith, Catherine Snelson, and Tony Whitehouse Copyright © 2015 Philip Pemberton et al. All rights reserved. Symptoms of Posttraumatic Stress after Intensive Care Delirium Sun, 18 Oct 2015 11:41:43 +0000 Introduction. Long-term psychological consequences of critical illness are receiving more attention in recent years. The aim of our study was to assess the correlation of ICU-delirium and symptoms of posttraumatic stress disorder (PTSD) anxiety and depression after ICU-discharge in a Danish cohort. Methods. A prospective observational cohort study assessing the incidence of delirium in the ICU. Psychometrics were screened by validated tools in structured telephone interviews after 2 months () and 6 months () after ICU-discharge. Results. Delirium was detected in 54% of patients in the ICU and symptoms of PTSD in 8% (2 months) and 6% (6 months) after ICU-discharge. Recall of ICU stay was present in 93%. Associations between ICU-delirium and post-discharge PTSD-symptoms were weak and insignificant. Memories of delusions were significantly associated with anxiety after two months. Remaining associations between types of ICU-memories and prevalence of post-discharge symptoms of PTSD, anxiety, and depression were insignificant after adjusting for age. Incidence of ICU-delirium was unaffected by preadmission use of psychotropic drugs. Prevalence of PTSD-symptoms was unaffected by use of antipsychotics and sedation in the ICU. Conclusion. ICU-delirium did not increase the risk of PTSD-symptoms at 2 and 6 months after ICU discharge. Helle Svenningsen, Ingrid Egerod, Doris Christensen, Else Kirstine Tønnesen, Morten Frydenberg, and Poul Videbech Copyright © 2015 Helle Svenningsen et al. All rights reserved. Basic Competence of Intensive Care Unit Nurses: Cross-Sectional Survey Study Sun, 18 Oct 2015 09:12:44 +0000 Critical care patients benefit from the attention of nursing personnel with a high competence level. The aim of the study was to describe and evaluate the self-assessed basic competence of intensive care unit nurses and related factors. A cross-sectional survey design was used. A basic competence scale (Intensive and Critical Care Nursing Competence Scale version 1, Likert scale 1–5, 1 = poor and 5 = excellent) was employed among Finnish intensive care unit nurses (). Intensive care unit nurses’ self-assessed basic competence was good (mean 4.19, SD 0.40). The attitude and value base of basic competence was excellent whereas experience base was the poorest compared to the knowledge base and skill base of intensive and critical care nursing. The strongest factor explaining nurses’ basic competence was their experience of autonomy in nursing care ( value 60.85, β 0.11, SE 0.01, and ). Clinical competence was self-rated as good. Nurses gave their highest competence self-ratings for ICU patient care according to the principles of nursing care. The ICU nurses also self-rated their professional competence as good. Collaboration was self-rated as the best competence. In basic and continuing education and professional self-development discussions it is meaningful to consider and find solutions for how to improve nurses’ experienced autonomy in nursing. Riitta-Liisa Lakanmaa, Tarja Suominen, Marita Ritmala-Castrén, Tero Vahlberg, and Helena Leino-Kilpi Copyright © 2015 Riitta-Liisa Lakanmaa et al. All rights reserved. Glutamine May Repress the Weak LPS and Enhance the Strong Heat Shock Induction of Monocyte and Lymphocyte HSP72 Proteins but May Not Modulate the HSP72 mRNA in Patients with Sepsis or Trauma Tue, 13 Oct 2015 17:10:03 +0000 Objective. We assessed the lipopolysaccharide (LPS) or heat shock (HS) induction of heat shock protein-72 (HSP72) in peripheral blood mononuclear cells (PBMCs) of patients with severe sepsis (SS) or trauma-related systemic inflammatory response syndrome (SIRS), compared to healthy individuals (H); we also investigated any pre- or posttreatment modulating glutamine (Gln) effect. Methods. SS (11), SIRS (10), and H (19) PBMCs were incubated with 1 μg/mL LPS or 43°HS. Gln 10 mM was either added 1 h before or 1 h after induction or was not added at all. We measured monocyte (m), lymphocyte (l), mRNA HSP72, HSP72 polymorphisms, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and cortisol levels. Results. Baseline lHSP72 was higher in SS , and mHSP72 in SIRS , compared to H. Only HS induced l/mHSP72/mRNA HSP72; LPS induced IL-6, IL-8, IL-10, and MCP-1. Induced mRNA was related to l/mHSP72, and was related negatively to cytokines. Intracellular l/mHSP72/HSP72 mRNA was related to serum ILs, not being influenced by cortisol, illness severity, and HSP72 polymorphisms. Gln did not induce mRNA in any group but modified l/mHSP72 after LPS/HS induction unpredictably. Conclusions. HSP72 mRNA and l/mHSP72 are higher among critically ill patients, further induced by HS, not by LPS. HSP72 proteins and HSP72 mRNA are related to serum ILs and are negatively related to supernatant cytokines, not being influenced by HSP72 polymorphisms, cortisol, or illness severity. Gln may depress l/mHSP72 after LPS exposure and enhance them after HS induction, but it may not affect early induced HSP72 mRNA. Efrossini Briassouli, Marianna Tzanoudaki, Dimitris Goukos, Christina Routsi, Serafim Nanas, Kostas Vardas, Kleovoulos Apostolou, Maria Kanariou, George Daikos, and George Briassoulis Copyright © 2015 Efrossini Briassouli et al. All rights reserved. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest Thu, 08 Oct 2015 14:00:45 +0000 Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. Tao Yu, Zhengfei Yang, Heng Li, Youde Ding, Zitong Huang, and Yongqin Li Copyright © 2015 Tao Yu et al. All rights reserved. Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy Thu, 01 Oct 2015 16:08:03 +0000 Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care. Peter Stehle and Katharina S. Kuhn Copyright © 2015 Peter Stehle and Katharina S. Kuhn. All rights reserved. Functional Outcomes: One Year after a Cardiac Arrest Thu, 03 Sep 2015 09:05:23 +0000 Objective. The study aim was to characterize the time-course of recovery in impairments, activity limitations, participation restrictions, disability, and quality of life during the first year after cardiac arrest. Secondarily, the study described the associations between the instruments used to measure each of these domains. Methods. Measures of global disability (Cerebral Performance Category, CPC, Modified Rankin Scale, mRS), quality of life, activity limitations, participation restrictions, and affective and cognitive impairments were administered to 29 participants 1, 6, and 12 months after cardiac arrest. Results. Global measures of disability indicated recovery between one month and one year after cardiac arrest (mean CPC: 2.1 versus 1.69,  ; mean mRS: 2.55 versus 1.83, ). While global measures of disability were moderately associated with participation, they were poorly associated with other measures. The cohort endorsed depressive symptomatology throughout the year but did not have detectable cognitive impairment. Conclusions. Recovery from cardiac arrest is multifaceted and recovery continues for months depending upon the measures being used. Measures of global disability, reintegration into the community, and quality of life yield different information. Future clinical trials should include a combination of measures to yield the most complete representation of recovery after cardiac arrest. Ketki D. Raina, Jon C. Rittenberger, Margo B. Holm, and Clifton W. Callaway Copyright © 2015 Ketki D. Raina et al. All rights reserved. Myocardial Dysfunction and Shock after Cardiac Arrest Wed, 02 Sep 2015 12:03:02 +0000 Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. Jacob C. Jentzer, Meshe D. Chonde, and Cameron Dezfulian Copyright © 2015 Jacob C. Jentzer et al. All rights reserved. Predict Defibrillation Outcome Using Stepping Increment of Poincare Plot for Out-of-Hospital Ventricular Fibrillation Cardiac Arrest Wed, 02 Sep 2015 07:20:41 +0000 Early cardiopulmonary resuscitation together with early defibrillation is a key point in the chain of survival for cardiac arrest. Optimizing the timing of defibrillation by predicting the possibility of successful electric shock can guide treatments between defibrillation and cardiopulmonary resuscitation and improve the rate of restoration of spontaneous circulation. Numerous methods have been proposed for predicting defibrillation success based on quantification of the ventricular fibrillation waveform during past decades. To date, however, no analytical technique has been widely accepted for clinical application. In the present study, we investigate whether median stepping increment that is calculated from the Euclidean distance of consecutive points in Poincare plot could be used to predict the likelihood of successful defibrillation. Electrocardiographic recordings of out-of-hospital cardiac arrest patients were obtained from the external defibrillators. The performance of the proposed method was evaluated by receiver operating characteristic curve and compared with the results of other established features. The results indicated that median stepping increment has comparable performance to the established methods in predicting the likelihood of successful defibrillation. Yushun Gong, Yubao Lu, Lei Zhang, Hehua Zhang, and Yongqin Li Copyright © 2015 Yushun Gong et al. All rights reserved. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis Mon, 17 Aug 2015 11:50:28 +0000 Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [] and septic shock []) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (, , , and , resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 ( and , resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients. Sang Hoon Lee, Moo Suk Park, Byung Hoon Park, Won Jai Jung, In Seon Lee, Song Yee Kim, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Se Kyu Kim, Joon Chang, and Kyung Soo Chung Copyright © 2015 Sang Hoon Lee et al. All rights reserved. A Novel Noninvasive Method for Measuring Fatigability of the Quadriceps Muscle in Noncooperating Healthy Subjects Tue, 21 Jul 2015 12:46:55 +0000 Background. Critical illness is associated with muscle weakness leading to long-term functional limitations. Objectives. To assess the reliability of a novel method for evaluating fatigability of the quadriceps muscle in noncooperating healthy subjects. Methods. On two occasions, separated by seven days, nonvoluntary isometric contractions (twitch and tetanic) of the quadriceps femoris muscle evoked by transcutaneous electrical muscle stimulation were recorded in twelve healthy adults. For tetanic contractions, the Fatigue Index (ratio of peak torque values) and the slope of the regression line of peak torque values were primary outcome measures. For twitch contractions, maximum peak torque and rise time were calculated. Relative (intraclass correlation, ICC3.1) and absolute (standard error of measurement, SEM) reliability were assessed and minimum detectable change was calculated using a 95% confidence interval (MDC95%). Results. The Fatigue Index (ICC3.1, 0.84; MDC95%, 0.12) and the slope of the regression line (ICC3.1, 0.99; MDC95%, 0.03) showed substantial relative and absolute reliability during the first 15 and 30 contractions, respectively. Conclusion. This method for assessing fatigability of the quadriceps muscle produces reliable results in healthy subjects and may provide valuable data on quantitative changes in muscle working capacity and treatment effects in patients who are incapable of producing voluntary muscle contractions. Jesper B. Poulsen, Martin H. Rose, Kirsten Møller, Anders Perner, and Bente R. Jensen Copyright © 2015 Jesper B. Poulsen et al. All rights reserved. Automating Quality Metrics in the Era of Electronic Medical Records: Digital Signatures for Ventilator Bundle Compliance Mon, 08 Jun 2015 13:53:11 +0000 Ventilator-associated events (VAEs) are associated with increased risk of poor outcomes, including death. Bundle practices including thromboembolism prophylaxis, stress ulcer prophylaxis, oral care, and daily sedation breaks and spontaneous breathing trials aim to reduce rates of VAEs and are endorsed as quality metrics in the intensive care units. We sought to create electronic search algorithms (digital signatures) to evaluate compliance with ventilator bundle components as the first step in a larger project evaluating the ventilator bundle effect on VAE. We developed digital signatures of bundle compliance using a retrospective cohort of 542 ICU patients from 2010 for derivation and validation and testing of signature accuracy from a cohort of random 100 patients from 2012. Accuracy was evaluated against manual chart review. Overall, digital signatures performed well, with median sensitivity of 100% (range, 94.4%–100%) and median specificity of 100% (range, 100%–99.8%). Automated ascertainment from electronic medical records accurately assesses ventilator bundle compliance and can be used for quality reporting and research in VAE. Haitao Lan, Charat Thongprayoon, Adil Ahmed, Vitaly Herasevich, Priya Sampathkumar, Ognjen Gajic, and John C. O’Horo Copyright © 2015 Haitao Lan et al. All rights reserved. Modeling Fluid Resuscitation by Formulating Infusion Rate and Urine Output in Severe Thermal Burn Adult Patients: A Retrospective Cohort Study Sun, 10 May 2015 12:11:47 +0000 Acute burn injuries are among the most devastating forms of trauma and lead to significant morbidity and mortality. Appropriate fluid resuscitation after severe burn, specifically during the first 48 hours following injury, is considered as the single most important therapeutic intervention in burn treatment. Although many formulas have been developed to estimate the required fluid amount in severe burn patients, many lines of evidence showed that patients still receive far more fluid than formulas recommend. Overresuscitation, which is known as “fluid creep,” has emerged as one of the most important problems during the initial period of burn care. If fluid titration can be personalized and automated during the resuscitation phase, more efficient burn care and outcome will be anticipated. In the present study, a dynamic urine output based infusion rate prediction model was developed and validated during the initial 48 hours in severe thermal burn adult patients. The experimental results demonstrated that the developed dynamic fluid resuscitation model might significantly reduce the total fluid volume by accurately predicting hourly urine output and has the potential to aid fluid administration in severe burn patients. Qizhi Luo, Wei Li, Xin Zou, Yongming Dang, Kaifa Wang, Jun Wu, and Yongqin Li Copyright © 2015 Qizhi Luo et al. All rights reserved. Effects of High Volume Haemodiafiltration on Inflammatory Response Profile and Microcirculation in Patients with Septic Shock Wed, 29 Apr 2015 08:49:27 +0000 Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients. Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients. Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p = 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF. Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved. Kadri Tamme, Liivi Maddison, Rein Kruusat, Hans-Erik Ehrlich, Mirjam Viirelaid, Hartmut Kern, and Joel Starkopf Copyright © 2015 Kadri Tamme et al. All rights reserved. Sepsis: Pathogenesis, Biomarkers, and Treatment Thu, 05 Mar 2015 08:22:14 +0000 Baoli Cheng, Andreas H. Hoeft, Malte Book, Qiang Shu, and Stephen M. Pastores Copyright © 2015 Baoli Cheng et al. All rights reserved. Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis Mon, 02 Mar 2015 11:29:41 +0000 Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies. Xia Fan, Zheng Liu, He Jin, Jun Yan, and Hua-ping Liang Copyright © 2015 Xia Fan et al. All rights reserved. Incidence and Risk Factors of Postoperative Pulmonary Complications in Noncardiac Chinese Patients: A Multicenter Observational Study in University Hospitals Mon, 02 Mar 2015 07:12:55 +0000 Purpose. To assess the incidence of postoperative pulmonary complications (PPCs) in Chinese inpatients, and to develop a brief predictive risk index. Methods. Between August 6, 2012, and August 12, 2012, patients undergoing noncardiac operations in four university hospitals were enrolled. The cohort was divided into two subsamples, cohort 1 to develop a predictive risk index of PPCs and cohort 2 to validate it. Results. 1673 patients were enrolled. PPCs were recorded for 163 patients (9.7%), of whom the hospital length of stay (LOS) was longer (). The mortality was 1.84% in patients with PPCs and 0.07% in those without. Logistic Regression modeling in cohort 1 identified nine independent risk factors, including smoking, respiratory infection in the last month, preoperative antibiotic use, preoperative saturation of peripheral oxygen, surgery site, blood lost, postoperative blood glucose, albumin, and ventilation. The model was validated within cohort 2 with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.86 to 0.94). Conclusions. PPCs are common in noncardiac surgical patients and are associated with prolonged LOS in China. The current study developed a risk index, which can be used to assess individual risk of PPCs and guide individualized perioperative respiratory care. Yue Jin, Guohao Xie, Haihong Wang, Lielie Jin, Jun Li, Baoli Cheng, Kai Zhang, Andreas Hoeft, and Xiangming Fang Copyright © 2015 Yue Jin et al. All rights reserved. Quantitative Analysis of Lung Ultrasonography for the Detection of Community-Acquired Pneumonia: A Pilot Study Wed, 25 Feb 2015 10:51:29 +0000 Background and Objective. Chest X-ray is recommended for routine use in patients with suspected pneumonia, but its use in emergency settings is limited. In this study, the diagnostic performance of a new method for quantitative analysis of lung ultrasonography was compared with bedside chest X-ray and visual lung ultrasonography for detection of community-acquired pneumonia, using thoracic computed tomography as a gold standard. Methods. Thirty-two spontaneously breathing patients with suspected community-acquired pneumonia, undergoing computed tomography examination, were consecutively enrolled. Each hemithorax was evaluated for the presence or absence of abnormalities by chest X-ray and quantitative or visual ultrasonography. Results. Quantitative ultrasonography showed higher sensitivity (93%), specificity (95%), and diagnostic accuracy (94%) than chest X-ray (64%, 80%, and 69%, resp.), visual ultrasonography (68%, 95%, and 77%, resp.), or their combination (77%, 75%, and 77%, resp.). Conclusions. Quantitative lung ultrasonography was considerably more accurate than either chest X-ray or visual ultrasonography in the diagnosis of community-acquired pneumonia and it may represent a useful first-line approach for confirmation of clinical diagnosis in emergency settings. Francesco Corradi, Claudia Brusasco, Alessandro Garlaschi, Francesco Paparo, Lorenzo Ball, Gregorio Santori, Paolo Pelosi, Fiorella Altomonte, Antonella Vezzani, and Vito Brusasco Copyright © 2015 Francesco Corradi et al. All rights reserved. Managing Hypercapnia in Patients with Severe ARDS and Low Respiratory System Compliance: The Role of Esophageal Pressure Monitoring—A Case Cohort Study Wed, 28 Jan 2015 08:20:35 +0000 Purpose. Patients with severe acute respiratory distress syndrome (ARDS) and hypercapnia present a formidable treatment challenge. We examined the use of esophageal balloon for assessment of transpulmonary pressures to guide mechanical ventilation for successful management of severe hypercapnia. Materials and Methods. Patients with severe ARDS and hypercapnia were studied. Esophageal balloon was inserted and mechanical ventilation was guided by assessment of transpulmonary pressures. Positive end expiratory pressure (PEEP) and inspiratory driving pressures were adjusted with the aim of achieving tidal volume of 6 to 8 mL/kg based on ideal body weight (IBW), while not exceeding end inspiratory transpulmonary (EITP) pressure of 25 cm H2O. Results. Six patients with severe ARDS and hypercapnia were studied. Mean PaCO2 on enrollment was  mmHg. One hour after adjustment of PEEP and inspiratory driving pressure guided by transpulmonary pressure, PaCO2 decreased to  mmHg (). Tidal volume was  mL/kg IBW before and increased to  mL/kg IBW after intervention . EITP pressure before intervention was low with a mean of  cm H2O and remained low at  cm H2O () after intervention. Adjustment of PEEP and inspiratory driving pressures did not worsen oxygenation and did not affect cardiac output significantly. Conclusion. The use of esophageal balloon as a guide to mechanical ventilation was able to treat severe hypercapnia in ARDS patients. Arie Soroksky, Julia Kheifets, Zehava Girsh Solomonovich, Emad Tayem, Balmor Gingy Ronen, and Boris Rozhavsky Copyright © 2015 Arie Soroksky et al. All rights reserved. Monitoring the Modifications of the Vitreous Humor Metabolite Profile after Death: An Animal Model Thu, 22 Jan 2015 13:47:56 +0000 We applied a metabolomic approach to monitor the modifications occurring in goat vitreous humor (VH) metabolite composition at different times (0, 6, 12, 18, and 24 hours) after death. The 1H-NMR analysis of the VH samples was performed for the simultaneous determination of several metabolites (i.e., the metabolite profile) representative of the VH status at different times. Spectral data were analyzed by Principal Component Analysis (PCA) and by Orthogonal Projection to Latent Structures (OPLS) regression technique. PCA and OPLS suggested that different spectral regions were involved in time-related changes. The major time-related compositional changes, here detected, were the increase of lactate, hypoxanthine, alanine, total glutathione, choline/phosphocholine, creatine, and myo-inositol and the decrease of glucose and 3-hydroxybutyrate. We attempted a speculative interpretation of the biological mechanisms underlying these changes. These results show that multivariate statistical approach, based on 1H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions. Maria Francesca Rosa, Paola Scano, Antonio Noto, Matteo Nioi, Roberta Sanna, Francesco Paribello, Fabio De-Giorgio, Emanuela Locci, and Ernesto d’Aloja Copyright © 2015 Maria Francesca Rosa et al. All rights reserved. Metabolism of Albumin after Continuous Venovenous Hemofiltration in Patients with Systemic Inflammatory Response Syndrome Wed, 14 Jan 2015 13:41:50 +0000 Background. The systemic inflammatory response syndrome (SIRS) is characterized by a hypercatabolic state induced by inflammatory mediators. Continuous venovenous hemofiltration (CVVH) stabilizes the internal environment but also aggravates loss of amino acids. The effect of CVVH on protein dynamics is largely unknown. We adopted the stable isotopic tracer technology to investigate how CVVH changed serum albumin metabolism. Methods. Twenty SIRS patients were randomized into low- (2000 mL/h) and high- (4000 mL/h) volume CVVH groups according to the rate of replacement fluid. Eight patients with abdominal infection matched for age, sex, and laboratory index served as controls. Consecutive arterial blood samples were drawn during a primed-constant infusion of two stable isotopes to determine the albumin fractional synthesis rate (FSR) and fractional breakdown rate (FBR). Results. Before treatment, there was no significant difference of FSR and FBR among 3 groups. After CVVH, the albumin FSR in high- and low-volume groups was 7.75 ± 1.08% and 7.30 ± 0.89%, respectively, both higher than in the control (5.83 ± 0.94%). There was no significant difference in albumin FBR after treatment. Conclusions. Protein dynamic indicators could reflect protein synthesis and breakdown state directly and effectively. CVVH increased albumin synthesis, while the breakdown rate remained at a high level independently of the CVVH rate. Yu Chen, Jianan Ren, Xiaodong Qin, Guanwei Li, Bo Zhou, Guosheng Gu, Zhiwu Hong, JiYe Aa, and Jieshou Li Copyright © 2015 Yu Chen et al. All rights reserved. The Increase of Intra-Abdominal Pressure Can Affect Intraocular Pressure Wed, 14 Jan 2015 07:18:57 +0000 Objective. This study aims to explore the usage of intraocular pressure measurements as the early indicator of the increase in intra-abdominal pressure. Methods. In this prospective study, 40 patients undergoing elective surgery were included. Patients were divided into four groups of 10 patients. The control group (Group C) was not subjected to laparoscopic intervention. Laparoscopic surgery was, respectively, performed with an intra-abdominal pressure of 9, 12, and 15 mmHg in Groups L (low), M (medium), and H (high pressure). Intraocular pressure was measured binocularly in each patient at three different times (before, during, and end of surgery) using a contact tonometer. Results. Patients’ gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, and operative times were not different among the groups. No complications occurred with either the surgery or measurement of intraocular pressure. Intubation was associated with a severe rise in IOP . An increase in intraocular pressure was seen in groups M and H . Conclusion. Intraocular pressure was increased in the groups with an intra-abdominal pressure of 12 mmHg or more. Measuring the intraocular pressure might be a useful method to estimate the intra-abdominal pressure. This trial is registered with NCT02319213. Ilhan Ece, Celalettin Vatansev, Tevfik Kucukkartallar, Ahmet Tekin, Adil Kartal, and Mehmet Okka Copyright © 2015 Ilhan Ece et al. All rights reserved. The Effect of Bicarbonate Administration via Continuous Venovenous Hemofiltration on Acid-Base Parameters in Ventilated Patients Thu, 08 Jan 2015 13:51:14 +0000 Background. Acute kidney injury (AKI) and metabolic acidosis are common in the intensive care unit. The effect of bicarbonate administration on acid-base parameters is unclear in those receiving continuous venovenous hemofiltration (CVVH) and mechanical ventilatory support. Methods. Metabolic and ventilatory parameters were prospectively examined in 19 ventilated subjects for up to 96 hours following CVVH initiation for AKI at an academic tertiary care center. Mixed linear regression modeling was performed to measure changes in pH, partial pressure of carbon dioxide (pCO2), serum bicarbonate, and base excess over time. Results. During the 96-hour study period, pCO2 levels remained stable overall (initial pCO2 42.0 ± 14.6 versus end-study pCO2 43.8 ± 16.1 mmHg; for interaction with time), for those with initial pCO2 ≤40 mmHg (31.3 ± 5.7 versus 35.0 ± 4.8; ) and for those with initial pCO2 >40 mmHg (52.7 ± 12.8 versus 53.4 ± 19.2; ). pCO2 decreased during the immediate hours following CVVH initiation (42.0 ± 14.6 versus 37.3 ± 12.6 mmHg), though this change was nonsignificant (). Conclusions. We did not detect a significant increase in pCO2 in response to the administration of bicarbonate via CVVH in a ventilated population. Additional studies of larger populations are needed to confirm this finding. Andrew S. Allegretti, Jennifer E. Flythe, Vinod Benda, Emily S. Robinson, and David M. Charytan Copyright © 2015 Andrew S. Allegretti et al. All rights reserved. Risk Factors for Hospital and Long-Term Mortality of Critically Ill Elderly Patients Admitted to an Intensive Care Unit Tue, 16 Dec 2014 06:51:02 +0000 Background. Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. Materials and Methods. Adult patients (, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. Results. 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. Conclusions. Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality. A. Mukhopadhyay, B. C. Tai, K. C. See, W. Y. Ng, T. K. Lim, S. Onsiong, S. Ee, M. J. Chua, P. R. Lee, M. L. Loh, and J Phua Copyright © 2014 A. Mukhopadhyay et al. All rights reserved. Vasopressin in Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Randomized Animal Trials Mon, 01 Sep 2014 12:46:52 +0000 Objective. The latest European guidelines for the management of hemorrhagic shock suggest the use of vasopressors (norepinephrine) in order to restore an adequate mean arterial pressure when fluid resuscitation therapy fails to restore blood pressure. The administration of arginine vasopressin (AVP), or its analogue terlipressin, has been proposed as an alternative treatment in the early stages of hypovolemic shock. Design. A meta-analysis of randomized controlled animal trials. Participants. A total of 433 animals from 15 studies were included. Interventions. The ability of AVP and terlipressin to reduce mortality when compared with fluid resuscitation therapy, other vasopressors (norepinephrine or epinephrine), or placebo was investigated. Measurements and Main Results. Pooled estimates showed that AVP and terlipressin consistently and significantly improve survival in hemorrhagic shock (mortality: 26/174 (15%) in the AVP group versus 164/259 (63%) in the control arms; ; 95% CI 0.05 to 0.15; for effect < 0.001; for heterogeneity = 0.30; ). Conclusions. Results suggest that AVP and terlipressin improve survival in the early phases of animal models of hemorrhagic shock. Vasopressin seems to be more effective than all other treatments, including other vasopressor drugs. These results need to be confirmed by human clinical trials. Andrea Pasquale Cossu, Paolo Mura, Lorenzo Matteo De Giudici, Daniela Puddu, Laura Pasin, Maurizio Evangelista, Theodoros Xanthos, Mario Musu, and Gabriele Finco Copyright © 2014 Andrea Pasquale Cossu et al. All rights reserved. Role of Circulating Lymphocytes in Patients with Sepsis Thu, 28 Aug 2014 00:00:00 +0000 Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed. Raul de Pablo, Jorge Monserrat, Alfredo Prieto, and Melchor Alvarez-Mon Copyright © 2014 Raul de Pablo et al. All rights reserved. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response Wed, 27 Aug 2014 11:38:09 +0000 Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF)-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI. Xuanfei Li, Zheng Liu, He Jin, Xia Fan, Xue Yang, Wanqi Tang, Jun Yan, and Huaping Liang Copyright © 2014 Xuanfei Li et al. All rights reserved. Early Response Roles for Prolactin Cortisol and Circulating and Cellular Levels of Heat Shock Proteins 72 and 90α in Severe Sepsis and SIRS Wed, 27 Aug 2014 00:00:00 +0000 Objective. To evaluate the early heat shock protein (HSP) and hormonal stress response of intensive care unit (ICU) patients with severe sepsis/septic shock (SS) or systemic inflammatory response syndrome (SIRS) compared to healthy subjects (H). Methods. Patients with early (first 48 hrs) SS () or SIRS () admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72) and interleukins. Mean fluorescence intensity (MFI) values for intracellular HSPs (iHSP72, iHSP90α) were measured using 4-colour flow-cytometry. Results. Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (). ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (). SS monocytes expressed lower iHSP72 MFI levels compared to H (). Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (). In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. Conclusion. Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases. K. Vardas, K. Apostolou, E. Briassouli, D. Goukos, K. Psarra, E. Botoula, S. Tsagarakis, E. Magira, C. Routsi, S. Nanas, and G. Briassoulis Copyright © 2014 K. Vardas et al. All rights reserved. Epinephrine Enhances the Response of Macrophages under LPS Stimulation Tue, 26 Aug 2014 10:33:32 +0000 Trauma associated with infection may directly trigger a neuroendocrine reaction in vivo while the hormone epinephrine is known to mediate immune responses to inflammation after injury. However, the role of epinephrine during the earliest stage of trauma still remains unclear. We therefore explored the role of epinephrine on activated macrophages under LPS stimulation in vitro as well as the mechanisms underlying its effect. Dose- and time-dependent effects of epinephrine on macrophage immune function were assessed after LPS activation. We also employed CD14 siRNA interference to investigate whether CD14 played a role in the mechanism underlying the effect of epinephrine on LPS-induced macrophage responses. Our results showed that epinephrine pretreatment (10 ng/mL) significantly promoted immune responses from LPS stimulated macrophages, including phagocytic rate, phagocytic index, TNFα/IL-1β/IL-10 secretion, and CD14 expression (P < 0.05). Moreover, TNFα/IL-1β/IL-10 levels attained their peak value 1 hour after incubation with 10 ng/mL epinephrine (P < 0.05), and CD14 siRNA transfection dramatically decreased phagocytosis and cytokine secretion by LPS-activated macrophages (P < 0.05). We therefore conclude that 10 ng/mL epinephrine enhances immune responses from macrophages under LPS stimulation and that the underlying mechanism may relate to CD14 upregulation on the surface of macrophages. Jianyun Zhou, Jun Yan, Huaping Liang, and Jianxin Jiang Copyright © 2014 Jianyun Zhou et al. All rights reserved. Defensins and Sepsis Tue, 19 Aug 2014 00:00:00 +0000 Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins’ effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis. Guo-Hao Xie, Qi-Xing Chen, Bao-Li Cheng, and Xiang-Ming Fang Copyright © 2014 Guo-Hao Xie et al. All rights reserved. Fluid Resuscitation in Sepsis: Reexamining the Paradigm Mon, 11 Aug 2014 07:26:54 +0000 Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis. Poorna Madhusudan, Bharath Kumar Tirupakuzhi Vijayaraghavan, and Matthew Edward Cove Copyright © 2014 Poorna Madhusudan et al. All rights reserved. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury Wed, 06 Aug 2014 00:00:00 +0000 The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI. Velat Şen, Abdulmenap Güzel, Hadice Selimoğlu Şen, Aydın Ece, Ünal Uluca, Sevda Söker, Erdal Doğan, İbrahim Kaplan, and Engin Deveci Copyright © 2014 Velat Şen et al. All rights reserved. Acinetobacter baumannii Infection in Prior ICU Bed Occupants Is an Independent Risk Factor for Subsequent Cases of Ventilator-Associated Pneumonia Wed, 02 Jul 2014 06:48:51 +0000 Objective. We aimed to evaluate risk factors for ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (AbVAP) in critically ill patients. Methods. This was a prospective observational study conducted in an intensive care unit (ICU) of a district hospital (6 beds). Consecutive patients were eligible for enrolment if they required mechanical ventilation for 48 hours and hospitalization for 72 hours. Clinical, microbiological, and laboratory parameters were assessed as risk factors for AbVAP by univariate and multivariate analysis. Results. 193 patients were included in the study. Overall, VAP incidence was 23.8% and AbVAP, 11.4%. Previous hospitalization of another patient with Acinetobacter baumannii infection was the only independent risk factor for AbVAP (OR (95% CI) 12.016 (2.282–19.521) ). ICU stay versus , the incidence of other infections (OR (95% CI) 9.485 (1.640–10.466) (urinary tract infection, catheter related infection, and bacteremia), or sepsis (OR (95% CI) 10.400 (3.749–10.466) were significantly increased in patients with AbVAP compared to patients without VAP; no difference was found with respect to ICU mortality. Conclusion. ICU admission or the hospitalization of patients infected by Acinetobacter baumannii increases the risk of AbVAP by subsequent patients. Eirini Tsakiridou, Demosthenes Makris, Zoe Daniil, Efstratios Manoulakas, Vasiliki Chatzipantazi, Odysseas Vlachos, Grigorios Xidopoulos, Olympia Charalampidou, and Epaminondas Zakynthinos Copyright © 2014 Eirini Tsakiridou et al. All rights reserved. Role of AMPKα in Skeletal Muscle Glycometabolism Regulation and Adaptation in relation to Sepsis Sun, 29 Jun 2014 08:32:57 +0000 Background. AMP-activated protein kinase (AMPK) and the translocation of glucose transporter 4 (GLUT4) protein always involve disturbance of carbohydrate metabolism. Objective. To determine whether the change of blood glucose in the early stage of septic rat is associated with the alteration of AMPKα protein expression and GLUT4 protein translocation expression. Methods. Animal models of sepsis were induced by tail vein injection of LPS in Wistar rats. The dynamic values of blood glucose within 2 hours after injection of LPS were observed. AMPKα protein and GLUT4 protein translocation in different tissues (such as soleus muscle and extensor digitorum longus) were assessed by western blot. Results. Blood glucose levels appeared to rise at 0.5 h after injection of LPS, arrived the peak value at 1 h, then fell at 1.5 h and 2 h Animals in LPS group experienced the increase of phos-AMPKα protein and GLUT4 protein translocation expression in soleus muscle and extensor digitorum longus. Conclusion. The dynamic change of blood glucose, represented in a form of initiative increase and subsequent decrease in the early stage of sepsis, may be related to glycometabolism disorder in the skeletal muscle, coming down to enhancement of GLUT4 translocation expression promoted by activation of AMPKα. Xia Zheng, Mi Xu, and Qiang Fang Copyright © 2014 Xia Zheng et al. All rights reserved. Admission Cell Free DNA as a Prognostic Factor in Burns: Quantification by Use of a Direct Rapid Fluorometric Technique Sun, 22 Jun 2014 00:00:00 +0000 Background. Despite great advances in the treatment of burn patients, useful prognostic markers are sparse. During the past years there has been increasing interest in circulating plasma cell free DNA as a potential marker for tissue injury. We have developed a rapid direct fluorescent assay for cell free DNA quantification that allows obtaining accurate, fast, and inexpensive measurements. Objective. To use this technique for measuring plasma cell free DNA levels in burn patients and to further explore the use of cell free DNA as a potential marker of patient outcome in burns. Methods. Cell free DNA levels obtained from 14 burn victims within 6 hours of injury and 14 healthy controls were quantified by a direct rapid fluorometric assay. Results. Patient admission cell free DNA levels were significantly elevated compared with that of controls (1797 ± 1523 ng/mL versus 374 ± 245 ng/mL, ). There are statistically significant correlations between cell free DNA admission levels and burn degree (Spearman’s correlation = 0.78, ), total body surface area (Spearman’s correlation = 0.61, ), and total burn volume (Spearman’s correlation = 0.64, ). Conclusions. Admission cell free DNA levels can serve as a prognostic factor in burns and future routine use can be made possible by use of our direct rapid fluorometric assay. Yaron Shoham, Yuval Krieger, Zvi H. Perry, Gad Shaked, Alexander Bogdanov-Berezovsky, Eldad Silberstein, Amiram Sagi, and Amos Douvdevani Copyright © 2014 Yaron Shoham et al. All rights reserved. Intensive Insulin Therapy for Septic Patients: A Meta-Analysis of Randomized Controlled Trials Wed, 18 Jun 2014 06:40:42 +0000 Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality. Methods. We searched PubMed, Embase, the Cochrane Library,, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model. Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], ), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], ), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26], ), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14], ), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11], ), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06], ). Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia. Fang Song, Liu-Jun Zhong, Liang Han, Guo-Hao Xie, Cheng Xiao, Bing Zhao, Yao-Qin Hu, Shu-Yan Wang, Chao-Jin Qin, Yan Zhang, Deng-Ming Lai, Ping Cui, and Xiang-Ming Fang Copyright © 2014 Fang Song et al. All rights reserved. Pediatric Index of Mortality and PIM2 Scores Have Good Calibration in a Large Cohort of Children from a Developing Country Sun, 15 Jun 2014 06:21:56 +0000 Objective. Our objective was to validate the Pediatric Index of Mortality (PIM) and PIM2 scores in a large cohort of children from a developing country. Design. Prospective observational study. Setting. Pediatric intensive care unit of a tertiary care teaching hospital. Patients. All children aged <18 years admitted between June 2011 and July 2013. Measurements and Main Results. We evaluated the discriminative ability and calibration as measured by the area under the receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit (GOF), and standardized mortality ratio (SMR), respectively. Of the 819 children enrolled, 232 (28%) died. The median (IQR) age of the study subjects was 4 years (0.8, 10). The major reasons for ICU admission as well as mortality were sepsis/severe sepsis. The area under ROC curves for PIM and PIM2 was 0.72 (95% CI: 0.67–0.75) and 0.74 (95% CI: 0.70–0.78), respectively. The goodness-of-fit test showed a good calibration across deciles of risk for the two scores with values being >0.05. The SMR (95% CI) was 0.99 (0.85–1.15) and 1 (0.85–1.16) for PIM and PIM2, respectively. The calibration across different age and diagnostic subgroups was also good. Conclusion. PIM and PIM2 scores had good calibration in our setup. Jhuma Sankar, Archana Singh, M. Jeeva Sankar, Sunil Joghee, Shashikant Dewangan, and Nandkishore Dubey Copyright © 2014 Jhuma Sankar et al. All rights reserved. Myeloid-Derived Suppressor Cells in Sepsis Tue, 03 Jun 2014 11:15:32 +0000 Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state of septic shock or acute organ dysfunction. Since sepsis is responsible for nearly 3 million cases per year in China and severe sepsis is a common, expensive fatal condition in America, developing new therapies becomes a significant and worthwhile challenge. Clinical research has shown that sepsis-associated immunosuppression plays a central role in patient mortality, and targeted immune-enhancing therapy may be an effective treatment approach in these patients. As part of the inflammatory response during sepsis, there are elevations in the number of myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that possess immunosuppressive activities via suppressing T-cell proliferation and activation. The role of MDSCs in sepsis remains uncertain. Some believe activated MDSCs are beneficial to the sepsis host by increasing innate immune responses and antimicrobial activities, while others think expansion of MDSCs leads to adaptive immune suppression and secondary infection. Herein, we discuss the complex role of MDSCs in immune regulation during sepsis, as well as the potential to target these cells for therapeutic benefit. Dengming Lai, Chaojin Qin, and Qiang Shu Copyright © 2014 Dengming Lai et al. All rights reserved. Complications of Trauma Patients Admitted to the ICU in Level I Academic Trauma Centers in the United States Tue, 03 Jun 2014 08:26:25 +0000 Background. The aims of this study were to evaluate the complications that occur after trauma and the characteristics of individuals who develop complications, to identify potential risk factors that increase their incidence, and finally to investigate the relationship between complications and mortality. Methods. We did a population-based retrospective study of trauma patients admitted to ICUs of a level I trauma center. Logistic regression analyses were performed to determine independent predictors for complications. Results. Of the 11,064 patients studied, 3,451 trauma patients developed complications (31.2%). Complications occurred significantly more in younger male patients. Length of stay was correlated with the number of complications . The overall death rate did not differ between patients with or without complications. The adjusted odds ratio (OR) of developing complication for patients over age 75 versus young adults was 0.7 . Among males, traumatic central nervous system (CNS) injury was an important predictor for complications (adjusted OR 1.24). Conclusions. Complications after trauma were found to be associated with age, gender, and traumatic CNS injury. Although these are not modifiable factors, they may identify subjects at high risk for the development of complications, allowing for preemptive strategies for prevention. Stefania Mondello, Amy Cantrell, Domenico Italiano, Vincenzo Fodale, Patrizia Mondello, and Darwin Ang Copyright © 2014 Stefania Mondello et al. All rights reserved. Body Mass Index and Comorbidities in Adult Severe Asthmatics Wed, 28 May 2014 06:53:30 +0000 Both severe asthma and obesity are growing health problems. Severe asthma leads to a poor quality of life. The relationship among BMI, comorbidities, and severe asthma control in adults is still unclear. The aim of the study is to better understand the effect of the comorbidities as atopy, type II diabetes, OSAS, gastroesophageal reflux, hypertension, cardiovascular diseases, osteoporosis, infections, and psychological factors with BMI on asthma control in a cohort of adult severe asthmatics. One hundred and two patients were enrolled in a cross-sectional study assessing asthma control, treatments, pulmonary function, inflammatory markers, and comorbidities. Patients were divided into 3 classes according to BMI: normal weight, overweight, and obese. We found that the optimal state of asthma control is lower. whereas the score of Asthma Control Questionnaire, the number of asthma exacerbations during last year, the oral corticosteroids requirement during the previous year, and the LABA treatments are higher in obese than in overweight and normal weight severe asthmatics. The number of subjects with type II diabetes and OSAS are higher among obese and overweight patients than in normal weight asthmatics. In conclusion, BMI represents per se a factor for the deterioration in disease control in severe asthma. Andreina Bruno, Elisabetta Pace, Fabio Cibella, and Pascal Chanez Copyright © 2014 Andreina Bruno et al. All rights reserved. A Simple Method to Detect Recovery of Glomerular Filtration Rate following Acute Kidney Injury Tue, 27 May 2014 09:45:03 +0000 In acute kidney injury (AKI), elevated plasma creatinine is diagnostic of an earlier loss of glomerular filtration rate (GFR) but not of the concomitant GFR. Only subsequent creatinine changes will inform if GFR had already recovered or not. We hypothesized that the creatinine excretion rate to production rate ratio would provide this information. A retrospective analysis of 482 critically ill patients from two intensive care units (ICU) is shown. Plasma creatinine was measured on ICU entry and 12 hours later. Four-hour creatinine excretion rates () were measured on entry. Creatinine production rates were estimated (). The ability of the ratio to predict a decrease in plasma creatinine concentration, identify recovered AKI (≥0.3 mg/dL decrease), and predict AKI (≥0.3 mg/dL increase) was assessed by the area under the receiver operator characteristic curves (AUC). There was a linear relationship between reduced creatinine concentration and (; ). predicted a decrease in creatinine (AUC 0.70 (0.65 to 0.74)), identified recovered AKI (0.75 (0.67 to 0.84)), and predicted AKI (0.80 (0.73 to 0.86)). A ratio of the rates of creatinine excretion to estimated production much less than 1 indicated a concomitant GFR below baseline, whereas a ratio much more than 1 indicated a recovering or recovered GFR. John W. Pickering and John Mellas Copyright © 2014 John W. Pickering and John Mellas. All rights reserved. Development of a Murine Model of Early Sepsis in Diet-Induced Obesity Sun, 25 May 2014 00:00:00 +0000 Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD) induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD) for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue) compared to age matched ad lib (44.1 ± 2.86 U/mg tissue) and diet restricted (63.2 ± 5.60 U/mg tissue) controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly () larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury. Momina Khan, Amanda L. Patrick, Alison E. Fox-Robichaud, and The Canadian Critical Care Translational Biology Group Copyright © 2014 Momina Khan et al. All rights reserved. Cortisol Is an Associated-Risk Factor of Brain Dysfunction in Patients with Severe Sepsis and Septic Shock Mon, 28 Apr 2014 07:40:01 +0000 Objectives. To investigate cortisol levels in brain dysfunction in patients with severe sepsis and septic shock. Methods. In 128 septic and sedated patients, we studied brain dysfunction including delirium and coma by the evaluation of Richmond Agitation Sedation Scale (RASS), the Confusion Method Assessment in the ICU (CAM-ICU) after sedation withdrawal and the measurement of serum S100B biomarker of brain injury. Serum cortisol and S100B were measured within 12 hours after ICU admission and daily over the next four days. Results. Brain dysfunction was observed in 50% (64/128) before but in 84% (107/128) of patients after sedation withdrawal, and was more common in the patients older than 57 years (P = 0.009). Both cortisol (P = 0.007) and S100B levels (P = 0.028) were higher in patients with than patients without brain dysfunction. Cortisol levels were associated with ICU mortality (hazard ratio = 1.17, P = 0.024). Multivariate logistic regression showed that cortisol (odds ratio (OR): 2.34, 95% CI (2.01, 3.22), P = 0.02) and the combination effect of cortisol with age (OR: 1.004, 95% CI (1.002, 1.93), P = 0.038) but not S100B were associated with brain dysfunction. Conclusions. Cortisol was an associated-risk factor of brain dysfunction in patients with severe sepsis and septic shock. Duc Nam Nguyen, Luc Huyghens, Haibo Zhang, Johan Schiettecatte, Johan Smitz, and Jean-Louis Vincent Copyright © 2014 Duc Nam Nguyen et al. All rights reserved. Hydrogen Gas Presents a Promising Therapeutic Strategy for Sepsis Wed, 16 Apr 2014 15:58:08 +0000 Sepsis is characterized by a severe inflammatory response to infection. It remains a major cause of morbidity and mortality in critically ill patients despite developments in monitoring devices, diagnostic tools, and new therapeutic options. Recently, some studies have found that molecular hydrogen is a new therapeutic gas. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis. The mechanisms are associated with the regulation of oxidative stress, inflammatory response, and apoptosis, which might be through NF-κB and Nrf2/HO-1 signaling pathway. In this paper, we summarized the progress of hydrogen treatment in sepsis. Keliang Xie, Lingling Liu, Yonghao Yu, and Guolin Wang Copyright © 2014 Keliang Xie et al. All rights reserved. Optimal Management of the Critically Ill: Anaesthesia, Monitoring, Data Capture, and Point-of-Care Technological Practices in Ovine Models of Critical Care Tue, 25 Mar 2014 12:57:33 +0000 Animal models of critical illness are vital in biomedical research. They provide possibilities for the investigation of pathophysiological processes that may not otherwise be possible in humans. In order to be clinically applicable, the model should simulate the critical care situation realistically, including anaesthesia, monitoring, sampling, utilising appropriate personnel skill mix, and therapeutic interventions. There are limited data documenting the constitution of ideal technologically advanced large animal critical care practices and all the processes of the animal model. In this paper, we describe the procedure of animal preparation, anaesthesia induction and maintenance, physiologic monitoring, data capture, point-of-care technology, and animal aftercare that has been successfully used to study several novel ovine models of critical illness. The relevant investigations are on respiratory failure due to smoke inhalation, transfusion related acute lung injury, endotoxin-induced proteogenomic alterations, haemorrhagic shock, septic shock, brain death, cerebral microcirculation, and artificial heart studies. We have demonstrated the functionality of monitoring practices during anaesthesia required to provide a platform for undertaking systematic investigations in complex ovine models of critical illness. Saul Chemonges, Kiran Shekar, John-Paul Tung, Kimble R. Dunster, Sara Diab, David Platts, Ryan P. Watts, Shaun D. Gregory, Samuel Foley, Gabriela Simonova, Charles McDonald, Rylan Hayes, Judith Bellpart, Daniel Timms, Michelle Chew, Yoke L. Fung, Michael Toon, Marc O. Maybauer, and John F. Fraser Copyright © 2014 Saul Chemonges et al. All rights reserved. Moderate Intra-Abdominal Hypertension Leads to Anaerobic Metabolism in the Rectus Abdominis Muscle Tissue of Critically Ill Patients: A Prospective Observational Study Thu, 13 Mar 2014 13:31:11 +0000 Purpose. We hypothesize that intra-abdominal hypertension (IAH) is associated with the presence of anaerobic metabolism in the abdominal rectus muscle (RAM) tissue of critically ill patients. Methods. We included 10 adult, critically ill patients with intra-abdominal pressure (IAP) above 12 mmHg. Microdialysis catheters (CMA 60) were inserted into the RAM tissue. The samples were collected up to 72 hours after enrollment. Results. The patients’ median (IQR) APACHE II at inclusion was 29 (21–37); 7 patients were in shock. IAP was 14.5 (12.5–17.8) mmHg at baseline and decreased significantly over time, concomitantly with arterial lactate and vasopressors requirements. The tissue lactate-to-pyruvate (L/P) ratio was 49 (36–54) at the beginning of the study and decreased significantly throughout the study. Additionally, the tissue lactate, lactate-to-glucose (L/G) ratio, and glutamate concentrations changed significantly during the study. The correlation analysis showed that lower levels of pyruvate and glycerol were associated with higher MAP and abdominal perfusion pressures (APP) and that higher levels of glutamate were correlated to elevated IAP. Conclusions. Moderate IAH leads to RAM tissue anaerobic metabolism suggestive for hypoperfusion in critically ill patients. Correlation analysis supports the concept of using APP as the primary endpoint of resuscitation in addition to MAP and IAP. Liivi Maddison, Juri Karjagin, Jyrki Tenhunen, Ülle Kirsimägi, and Joel Starkopf Copyright © 2014 Liivi Maddison et al. All rights reserved. A New Device to Automate the Monitoring of Critical Patients’ Urine Output Tue, 28 Jan 2014 08:03:04 +0000 Urine output (UO) is usually measured manually each hour in acutely ill patients. This task consumes a substantial amount of time. Furthermore, in the literature there is evidence that more frequent (minute-by-minute) UO measurement could impact clinical decision making and improve patient outcomes. However, it is not feasible to manually take minute-by-minute UO measurements. A device capable of automatically monitoring UO could save precious time of the healthcare staff and improve patient outcomes through a more precise and continuous monitoring of this parameter. This paper presents a device capable of automatically monitoring UO. It provides minute by minute measures and it can generate alarms that warn of deviations from therapeutic goals. It uses a capacitive sensor for the measurement of the UO collected within a rigid container. When the container is full, it automatically empties without requiring any internal or external power supply or any intervention by the nursing staff. In vitro tests have been conducted to verify the proper operation and accuracy in the measures of the device. These tests confirm the viability of the device to automate the monitoring of UO. Abraham Otero, Andrey Apalkov, Roemi Fernández, and Manuel Armada Copyright © 2014 Abraham Otero et al. All rights reserved. Heat Shock Protein 72 Expressing Stress in Sepsis: Unbridgeable Gap between Animal and Human Studies—A Hypothetical “Comparative” Study Sun, 12 Jan 2014 00:00:00 +0000 Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical “comparative study” model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies () were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing. George Briassoulis, Efrossini Briassouli, Diana-Michaela Fitrolaki, Ioanna Plati, Kleovoulos Apostolou, Theonymfi Tavladaki, and Anna-Maria Spanaki Copyright © 2014 George Briassoulis et al. All rights reserved. Scope of Nursing Care in Polish Intensive Care Units Tue, 31 Dec 2013 14:13:03 +0000 Introduction. The TISS-28 scale, which may be used for nursing staff scheduling in ICU, does not reflect the complete scope of nursing resulting from varied cultural and organizational conditions of individual systems of health care. Aim. The objective of the study was an attempt to provide an answer to the question what scope of nursing care provided by Polish nurses in ICU does the TISS-28 scale reflect? Material and Methods. The methods of working time measurement were used in the study. For the needs of the study, 252 hours of continuous observation (day-long observation) and 3.697 time-schedule measurements were carried out. Results. The total nursing time was 4125.79 min. (68.76 hours), that is, 60.15% of the total working time of Polish nurses during the period analyzed. Based on the median test, the difference was observed on the level of between the nurses’ workload resulting from performance of activities qualified into the TISS-28 scale and load resulting from performance of interventions within the scopes of care not considered in this scale in Polish ICUs. Conclusions. The original version of the TISS-28 scale does not fully reflect the workload among Polish nurses employed in ICUs. Mariusz Wysokiński, Anna Ksykiewicz-Dorota, and Wiesław Fidecki Copyright © 2013 Mariusz Wysokiński et al. All rights reserved. Risk Factors for the First Episode of Klebsiella pneumoniae Resistant to Carbapenems Infection in Critically Ill Patients: A Prospective Study Wed, 18 Dec 2013 09:47:05 +0000 Objective. To identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients. Design, Setting, and Methods. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for 48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all. Results. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by non MDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin ). Duration of colistin administration prior to KPRC isolation was independently associated with increased frequency of KPRC infection (odds ratio, 1.156 per day; 95% confidence interval, 1.010 to 1.312; ). KPRC patients stayed longer in the ICU and received mechanical ventilation and sedation for longer periods and presented increased mortality (). Conclusion. KPRC infection is an emerging problem which might be more common in patients with previous use of antibiotics and especially colistin. Konstantinos Mantzarlis, Demosthenes Makris, Efstratios Manoulakas, Marios Karvouniaris, and Epaminondas Zakynthinos Copyright © 2013 Konstantinos Mantzarlis et al. All rights reserved. Interpretation of C-Reactive Protein Concentrations in Critically Ill Patients Mon, 28 Oct 2013 15:08:04 +0000 Infection is often difficult to recognize in critically ill patients because of the marked coexisting inflammatory process. Lack of early recognition prevents timely resuscitation and effective antimicrobial therapy, resulting in increased morbidity and mortality. Measurement of a biomarker, such as C-reactive protein (CRP) concentration, in addition to history and physical signs, could facilitate diagnosis. Although frequently measured in clinical practice, few studies have reported on the pathophysiological role of this biomarker and its predictive value in critically ill patients. In this review, we discuss the pathophysiological role of CRP and its potential interpretation in the inflammatory processes observed in critically ill patients. Christophe Lelubre, Sophie Anselin, Karim Zouaoui Boudjeltia, Patrick Biston, and Michaël Piagnerelli Copyright © 2013 Christophe Lelubre et al. All rights reserved. Different Contribution of Splanchnic Organs to Hyperlactatemia in Fecal Peritonitis and Cardiac Tamponade Sun, 20 Oct 2013 15:50:35 +0000 Background. Changes in hepatosplanchnic lactate exchange are likely to contribute to hyperlactatemia in sepsis. We hypothesized that septic and cardiogenic shock have different effects on hepatosplanchnic lactate exchange and its contribution to hyperlactatemia. Materials and Methods. 24 anesthetized pigs were randomized to fecal peritonitis (P), cardiac tamponade (CT), and to controls ( per group). Oxygen transport and lactate exchange were calculated during 24 hours. Results. While hepatic lactate influx increased in P and in CT, hepatic lactate uptake remained unchanged in P and decreased in CT. Hepatic lactate efflux contributed 20% (P) and 33% (CT), respectively, to whole body venous efflux. Despite maintained hepatic arterial blood flow, hepatic oxygen extraction did not increase in CT. Conclusions. Whole body venous lactate efflux is of similar magnitude in hyperdynamic sepsis and in cardiogenic shock. Although jejunal mucosal pCO2 gradients are increased, enhanced lactate production from other tissues is more relevant to the increased arterial lactate. Nevertheless, the liver fails to increase hepatic lactate extraction in response to rising hepatic lactate influx, despite maintained hepatic oxygen consumption. In cardiac tamponade, regional, extrasplanchnic lactate production is accompanied by hepatic failure to increase oxygen extraction and net hepatic lactate output, despite maintained hepatic arterial perfusion. José Gorrasi, Anestis Eleftheriadis, Jukka Takala, Sebastian Brandt, Siamak Djafarzadeh, Lukas E. Bruegger, Hendrik Bracht, and Stephan M. Jakob Copyright © 2013 José Gorrasi et al. All rights reserved. Postoperative Adiponectin Levels in Pediatric Patients Undergoing Open Heart Surgery Wed, 09 Oct 2013 18:14:03 +0000 Background. Adipose tissue is an important endocrine organ that secretes cytokines, including adiponectin, levels of which are negatively correlated with the severity of the inflammatory process. Aim. To assess the time course of adiponectin levels following open heart surgery with cardiopulmonary bypass and its correlation with early postoperative outcomes. Materials and Methods. Blood samples were obtained from 24 children undergoing cardiac surgery and analyzed for adiponectin, C-reactive protein, and other inflammatory markers. Results. Baseline adiponectin levels were negatively correlated with patients’ preoperative weight and age. Postoperative adiponectin levels decreased compared to baseline () and correlated negatively with duration of cardiopulmonary bypass (, ), length of stay in the pediatric intensive care unit (, ), and the inotropic score (, ). Adiponectin levels were positively correlated with sVCAM 1 levels; however, there was no correlation between adiponectin levels and sP selectin, tPA, MCP1, and sCD40. Conclusions. The inflammatory response after open heart surgery with cardiopulmonary bypass is associated with a reduction in adiponectin levels. Prolonged or more complicated surgery induced a more substantial inflammatory process characterized by a significant reduction in adiponectin levels over time and a delayed return to baseline levels. A. Thaler, H. Kanety, T. Avni, D. Mishali, R. Hemi, E. Yissaschar, C. Pariente, G. Paret, and D. Modan-Moses Copyright © 2013 A. Thaler et al. All rights reserved. The Predictive Prognostic Values of Serum TNF-α in Comparison to SOFA Score Monitoring in Critically Ill Patients Thu, 19 Sep 2013 16:51:49 +0000 Background. The use of inflammatory markers to follow up critically ill patients is controversial. The short time frame, the need for frequent and serial measurement of biomarkers, the presence of soluble receptor and their relatively high cost are the major drawbacks. Our study’s objective is to compare the prognostic values of serum TNF-α and SOFA score monitoring in critically ill patients. Patients and Methods. A total of ninety patients were included in the study. Forty-five patients developed septic complication (sepsis group). Forty-five patients were critically ill without evidence of infectious organism (SIRS group). Patients’ data include clinical status, central venous pressure, and laboratory analysis were measured. A serum level of TNF-α and SOFA score were monitored. Results. Monitoring of TNF-α revealed significant elevation of TNF-α at 3rd and 5th days of ICU admission in both groups. Monitoring of SOFA score revealed significant elevation of SOFA scores in both groups throughout their ICU stay, particularly in nonsurvivors. Positive predictive ability of SOFA score was demonstrated in critically ill patients. Conclusion. Transient significant increase in serum levels of TNF-α were detected in septic patients. Persistent elevation of SOFA score was detected in nonsurvivor septic patients. SOFA score is an independent prognostic value in critically ill patients. Ayman Abd Al-Maksoud Yousef and Ghada Abdulmomen Suliman Copyright © 2013 Ayman Abd Al-Maksoud Yousef and Ghada Abdulmomen Suliman. All rights reserved. Compression of the Inferior Vena Cava in Bowel Obstruction Sat, 14 Sep 2013 08:49:14 +0000 Introduction. We investigated whether (a) the inferior vena cava (IVC) is compressed in bowel obstruction and (b) some tracts are more compressed than others. Methods. Two groups of abdominal computed tomography (CT) examinations were collected retrospectively. Group O () scans were positive for bowel obstruction, group C () scans were negative for diseases. IVC anteroposterior and lateral diameters (APD, LAD) were assessed at seven levels. Results. In group C, IVC section had an elliptic shape (APD/LAD: .76 ± .14), the area of which increased gradually from 1.9 (confluence of the iliac veins) to 3.1 cm2/m2 of BSA (confluence of the hepatic veins) with a significant narrowing in the hepatic section. In group O, bowel obstruction caused a compression of IVC (APD/LAD: .54 ± .17). Along its course, IVC section area increased from 1.3 to 2.5 cm2/m2. At ROC curve analysis, an APD/LAD ratio lower than 0.63 above the confluence of the iliac veins discriminated between O and C groups with sensitivity of 74% and specificity of 96%. Conclusions. Bowel obstruction caused a compression of IVC, which involved its entire course except for the terminal section. APD/LAD ratio may be useful to monitor the degree of compression. Alessandro Cina, Roberto Zamparelli, Sara Venturino, Riccardo Gargaruti, Vittorio Semeraro, and Franco Cavaliere Copyright © 2013 Alessandro Cina et al. All rights reserved. Skeletal Muscle Oxygen Saturation (StO2) Measured by Near-Infrared Spectroscopy in the Critically Ill Patients Wed, 21 Aug 2013 11:25:55 +0000 According to current critical care management guidelines, the overall hemodynamic optimization process seeks to restore macrocirculatory oxygenation, pressure, and flow variables. However, there is increasing evidence demonstrating that, despite normalization of these global parameters, microcirculatory and regional perfusion alterations might occur, and persistence of these alterations has been associated with worse prognosis. Such observations have led to great interest in testing new technologies capable of evaluating the microcirculation. Near-infrared spectroscopy (NIRS) measures tissue oxygen saturation (StO2) and has been proposed as a noninvasive system for monitoring regional circulation. The present review aims to summarize the existing evidence on NIRS and its potential clinical utility in different scenarios of critically ill patients. J. Mesquida, G. Gruartmoner, and C. Espinal Copyright © 2013 J. Mesquida et al. All rights reserved. Cardiac Contractile Reserve Parameters Are Related to Prognosis in Septic Shock Wed, 17 Jul 2013 10:07:02 +0000 Introduction. Cardiac reserve could be defined as the spontaneous magnitude from basal to maximal cardiac power under stress conditions. The aim of this study was to evaluate the prognostic value of cardiac reserve parameters in resuscitated septic shock patients. Methods. Seventy patients with septic shock were included in a prospective and observational study. Prior to inclusion, patients were resuscitated to reach a mean arterial pressure of 65–75 mmHg with an euvolemic status. General, hemodynamic, and cardiac reserve-related parameters (cardiac index, double product, and cardiac power index) were collected at inclusion and at day 1. Results. Seventy patients were included with 28-day mortality at 38.5%. Ten of the 70 patients died during the first day. In multivariate analysis, independent predictors of death were SAPS II ≥58 (OR: 3.36 [1.11–10.17]; ), a high double product at inclusion (OR [95% IC]: 1.20 [1.00–1.45] per 103 mmHg·min; ), and at day 1, a decrease in cardiac index (1.30 [1.08–1.56] per 0.5 L/min/m2; ) or cardiac power index (1.84 [1.18–2.87] per 0.1 W/m2, ). Conclusion. In the first 24 hours, parameters related to cardiac reserve, such as double product and cardiac index evolution, provide crucial and easy to achieve hemodynamic physiological information, which may impact the outcome. Antoine Kimmoun, Nicolas Ducrocq, Sébastien Mory, Remi Delfosse, Laura Muller, Pierre Perez, Renaud Fay, and Bruno Levy Copyright © 2013 Antoine Kimmoun et al. All rights reserved. Higher Plasma Pyridoxal Phosphate Is Associated with Increased Antioxidant Enzyme Activities in Critically Ill Surgical Patients Thu, 30 May 2013 12:18:24 +0000 Critically ill patients experience severe stress, inflammation and clinical conditions which may increase the utilization and metabolic turnover of vitamin B-6 and may further increase their oxidative stress and compromise their antioxidant capacity. This study was conducted to examine the relationship between vitamin B-6 status (plasma and erythrocyte PLP) oxidative stress, and antioxidant capacities in critically ill surgical patients. Thirty-seven patients in surgical intensive care unit of Taichung Veterans General Hospital, Taiwan, were enrolled. The levels of plasma and erythrocyte PLP, serum malondialdehyde, total antioxidant capacity, and antioxidant enzyme activities (i.e., superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase) were determined on the 1st and 7th days of admission. Plasma PLP was positively associated with the mean SOD activity level on day 1 (, ), day 7 (, ), and on changes (Δ (day 7 − day 1)) (, ) after adjusting for age, gender, and plasma C-reactive protein concentration. Higher plasma PLP could be an important contributing factor in the elevation of antioxidant enzyme activity in critically ill surgical patients. Chien-Hsiang Cheng, Shih-Chien Huang, Ting-Yu Chiang, Yueching Wong, and Yi-Chia Huang Copyright © 2013 Chien-Hsiang Cheng et al. All rights reserved.