Development Of Multiple Organ Dysfunction Syndrome Research Articles

Multiple organ dysfunction syndrome (MODS) prediction score in multi-trauma patients

BackgroundMultiple organ dysfunction syndrome (MODS) in patients with major trauma remains a frequent and devastating complication in emergency departments and intensive care units. Easily and accurately identifying patients at risk for MODS post-injury, especially in multi-trauma cases, is important. The aim of this study was to develop an instrument to predict the development of MODS in adult multi-trauma patients using clinical and laboratory data available in the first 24 h after trauma. MethodsWe prospectively enrolled adult multi-trauma patients with Injury Severity Score (ISS) ≥16, between 16 and 65 years old, admitted to four academic Level-I trauma centers for 1 year between September 2014 and 2015. Sequential organ failure assessment score was used to determine MODS during hospitalization. A risk score was created from the final regression model consisting of significant variables as MODS predictors. ResultDuring the period of the study, 98 multi-trauma patients were included. The mean age was 35.2 years, and most were male (85.71%). The mean ISS was 23.6, mostly (76.53%) caused by blunt injury mechanism. MODS occurred in 43 patients (43.87%). The prediction risk score consists of Revised Trauma Score (<7.25) and lactate level ≥2.75 mmol/L. This study also verified several independent risk factors for post-multi-trauma MODS such as ISS >25, presence of systemic inflammatory response syndrome, shock grade 2 or more, and white blood cells >12,000. ConclusionWe derived a novel simple and applicable instrument to predict MODS in adults following multi-trauma. The use of this scoring system may allow early identification of trauma patients who are at risk for MODS and result in more aggressive targeted resuscitation and damage control surgery. Trial registrationISCRTN ISRCTN16661943. 09/11/2016 retrospectively registered.

Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients.

BackgroundSevere stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients.MethodsNinety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated.Results33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS.ConclusionsIn acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important.

Effects of insulin combined with ethyl pyruvate on inflammatory response and oxidative stress in multiple-organ dysfunction syndrome rats with severe burns

BackgroundInflammation response and oxidative stress promote the occurrence and development of multiple-organ dysfunction syndrome (MODS). MethodsEighty MODS rats with third-degree burns were divided randomly into 4 groups: insulin, ethyl pyruvate (EP), insulin combined with EP, and control. Blood levels of glucose, alanine aminotransferase (ALT), creatine (CRE), creatine kinase (CK), tumor necrosis factor α (TNF-α), high-mobility group box 1 (HMGB-1), malondialdehyde (MDA), and total antioxidant capacity (TAC) before as well as 1, 3, 5, and 7 days after burns were measured. ResultsBlood levels of ALT, CRE, CK, TNF-α, HMGB-1, and MDA in INS, EP, and INS+EP groups at different time points were significantly lower, and TAC was significantly higher than that in the control group (C) (P<.01). These parameters in the INS+EP group were significantly lower, and TAC was significantly higher than that in INS and EP groups (P<.01). Blood levels of TNF-α, HMGB-1, and TAC in the INS group at different time points after burns were significantly lower, and MDA was significantly higher than that in the EP group (P<.01). ConclusionsInsulin combined with EP can effectively reduce the inflammatory response, oxidative stress, and main organ dysfunctions in MODS rats after severe burns. The therapeutic effect of insulin combined with EP is superior to single-agent treatment. The insulin anti-inflammatory effect is better than that of pyruvic acid ethyl ester, and the ethyl pyruvate antioxidation effect is better than that of insulin. The insulin can treat inflammation, whereas EP can reduce oxidative stress in MODS rats.

Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients.

BackgroundEarly survival following severe injury has been improved with refined resuscitation strategies. Multiple organ dysfunction syndrome (MODS) is common among this fragile group of patients leading to prolonged hospital stay and late mortality. MODS after trauma is widely attributed to dysregulated inflammation but the precise mechanics of this response and its influence on organ injury are incompletely understood. This study was conducted to investigate the relationship between early lymphocyte responses and the development of MODS during admission.MethodsDuring a 24-month period, trauma patients were recruited from an urban major trauma centre to an ongoing, observational cohort study. Admission blood samples were obtained within 2 h of injury and before in-hospital intervention, including blood transfusion. The study population was predominantly male with a blunt mechanism of injury. Lymphocyte subset populations including T helper, cytotoxic T cells, NK cells and γδ T cells were identified using flow cytometry. Early cytokine release and lymphocyte count during the first 7 days of admission were also examined.ResultsThis study demonstrated that trauma patients who developed MODS had an increased population of NK dim cells (MODS vs no MODS: 22 % vs 13 %, p < 0.01) and reduced γδ-low T cells (MODS vs no MODS: 0.02 (0.01–0.03) vs 0.09 (0.06–0.12) × 10^9/L, p < 0.01) at admission. Critically injured patients who developed MODS (n = 27) had higher interferon gamma (IFN-γ) concentrations at admission, compared with patients of matched injury severity and shock (n = 60) who did not develop MODS (MODS vs no MODS: 4.1 (1.8–9.0) vs 1.0 (0.6–1.8) pg/ml, p = 0.01). Lymphopenia was observed within 24 h of injury and was persistent in those who developed MODS. Patients with a lymphocyte count of 0.5 × 109/L or less at 48 h, had a 45 % mortality rate.ConclusionsThis study provides evidence of lymphocyte activation within 2 h of injury, as demonstrated by increased NK dim cells, reduced γδ-low T lymphocytes and high blood IFN-γ concentration. These changes are associated with the development of MODS and lymphopenia. The study reveals new opportunities for investigation to characterise the cellular response to trauma and examine its influence on recovery.

Characteristics of CD4+CD25+Foxp3+ regulatory T cells in patients with multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome (MODS) is a systemic inflammation. The aim of the present study was to evaluate the role of CD4+CD25+Foxp3+ regulatory T cells (Treg) in patients with MODS and to determine the association between Treg cells and serum cytokine levels. The percentage of Treg in 42 MODS patients and 10 healthy subjects was evaluated using flow cytometry. Serum levels of cytokines were measured using an enzyme-linked immunosorbent assay. The percentage of Treg cells was significantly elevated in patients with MODS on Day 1 (P<0.05). At Day 7, the percentage of Treg cells in MODS patients was reduced, but remained higher in comparison with the control group (P<0.05). The CD4+/CD8+ ratio and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10 and IL-1β were significantly enhanced in patients with MODS by Day 1. TNF-α, IL-2, IL-4 and IL-10 levels were gradually reduced to normal by Day 7, whereas the IL-6, IL-8 and IL-1β levels remained higher compared with the healthy subjects (P<0.001). The present results demonstrated an elevated percentage of CD4+CD25+Foxp3+ Treg cells in patients with MODS. Therefore, the proinflammatory cytokines TNF-α, IL-2, IL-6, IL-8 may promote MODS development, whereas the anti-inflammatory cytokines IL-4 and IL-10 may protect against MODS.

HLA-DR expression on monocytes is decreased in polytraumatized patients

BackgroundSepsis, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) remain the most frequent causes of complications and death in severely injured patients. A main reason for the development of these syndromes is a post-traumatic dysregulation of the immune system. Several studies in intensive care unit (ICU) patients could detect a pivotal role of HLA-DR expression on monocytes. So far, its importance for development of SIRS, sepsis or MODS in the severely injured patient is not clear.MethodsTherefore, we have analysed HLA-DR expression on monocytes from severely injured patients (ISS > 16) during the post-traumatic course, which was on the day of trauma, as well as on days 3, 7 and 14 post trauma. Clinical data were analysed and the HLA-DR expression levels of patients who developed post-traumatic sepsis, SIRS or MODS were compared to those with a more favourable outcome. Young and healthy volunteers as well as patients undergoing prosthetic hip replacement after trauma were enrolled as control groups. HLA-DR molecules on monocytes were marked with PE-conjugated antibodies and the mean fluorescence intensity (MFI) was analysed via flow cytometry.Results24 severely injured patients (mean age 34 ± 2.7 years) mainly after high energy motor vehicle accidents as well as 8 controls (total hip replacement) and 9 healthy volunteers (mean age 26.2 ± 1.2 years) were enrolled. A total of eight patients suffered from sepsis (33.3 %) (six males, two females) and 17 patients suffered from SIRS (70.9 %) (10 males, 7 females). MODS was present in five patients (20.8 %), three male and two female patients. In four of these five patients the MODS developed subsequent to sepsis. HLA-DR expression significantly decreased after trauma and slowly returned to normal after 14 days, irrespective of the complications developed.ConclusionIn conclusion, post-traumatic HLA-DR expression on monocytes is significantly reduced after multiple trauma and it is back to normal on day 14. No significant changes in HLA-DR expression on monocytes from severely injured patients suffering from SIRS, MODS or sepsis compared to those who did not have complications could be detected. Nevertheless, HLA-DR expression on monocytes may be used to identify the immunological pro- or anti-inflammatory phase the patient is going through.

Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P < 0.05). There were 39 patients (32%) with mortality during follow-up at 12 months, 10 patients (8%) with MODS on day 1, and 37 patients (30%) on day 7. The area under the receiver operating characteristic curve showed that high NGAL could predict mortality (0.6385) during intensive care unit stay. After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of mortality and MODS (hazard ratios, 2.128 [95% confidence interval, 1.078-4.203; P = 0.030] and 1.896 [95% confidence interval, 1.012-3.552; P = 0.046], respectively). High plasma NGAL independently predicts mortality and MODS in severe sepsis and septic shock.

Potential biomarker panel for predicting organ dysfunction and acute coagulopathy in a polytrauma porcine model.

Traumatic injury remains a major cause of morbidity and mortality worldwide, and patients who survived the initial insult are susceptible to an overwhelming inflammatory dysfunction that will lead to acute coagulopathy of trauma (ACOT) and subsequently multiple organ dysfunction syndrome (MODS). Multiple organ dysfunction syndrome-related scoring systems, although they measure organ dysfunction, present clinical markers, and single-cytokine estimates are unable to predict accurately the events of MODS in the clinical setting to aid risk stratification. In this study, a pig model comprising the lethal triad of trauma was used to determine prognostic patterns of early circulating trauma markers so as to predict the development of MODS and ACOT. We measured early expression of several biomarkers (neutrophil gelatinase-associated protein, high-mobility group box 1, C-reactive protein, tumor necrosis factor-α, heart-type fatty acid binding protein, and D-dimers) and clinical parameters for various organ injuries and abnormalities (creatinine, creatine kinase myocardial band, aspartate aminotransferase, and maximum clot firmness) at later time points. The strength of association between the early expression of several biomarkers to the development of MODS and ACOT in polytraumatized pigs was tested using the Spearman correlation coefficient. These biomarkers were found useful to predict the onset of renal, cardiac, hepatic, and hemostatic abnormalities. The findings show that these biomarkers could help to identify, guide, and streamline damage control surgery and earlier intervention to reverse the detrimental outcomes of MODS and ACOT.

Correlation of lactate/albumin ratio level to organ failure and mortality in severe sepsis and septic shock

BackgroundThis study examines the clinical utility of the increased lactate/albumin ratio as an indicator of multiple-organ dysfunction syndrome (MODS) and mortality in severe sepsis and septic shock. MethodsWe designed a prospective cohort study in an intensive care unit, and 54 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between lactate/albumin ratio and the development of MODS and mortality. These associations were determined by the Mann-Whitney test, multiple logistic regression, plotting the receiver operating characteristic curve and Spearman test. ResultsLactate/albumin ratio level was higher in MODS patients on day 1 (median [interquartile range, or IQR], 2.295 [1.818-3.065]; n = 30, P < .0001) than in those without (median [IQR], 1.550 (1.428-1.685); n = 24), and on day 2, (median [IQR], 1.810 [1.377-2.448]; n = 26, P = .0022) it was higher than in those without (median [IQR], 1.172 (1.129-1.382); n = 23) on day 2. We found that lactate/albumin ratio was an independent predictor of the development of MODS (odds ratio, 5.5; P = .033; 95% confidence interval, 1.1-26.1) during intensive care unit stay. The area under the receiver operating characteristic curve showed that lactate/albumin ratio could predict MODS (0.8458) and mortality (0.8449). Furthermore, the higher the Acute Physiology and Chronic Health Evaluation II score, the more lactate/albumin ratio was discovered on day 1 (r = 0.5315, P < .0001) and day 2 (r = 0.5408, P < .0001), whereas the lower partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, the more lactate/albumin ratio was illustrated on day 1 (r = −0.5143, P < .0001) and day 2 (r = −0.5420, P < .0001). ConclusionsIncreased lactate/albumin ratio correlates with the development of MODS and mortality in patients with severe sepsis and septic shock.

Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial cells during simulated shock and resuscitation.

Circulatory shock and resuscitation are associated with systemic hemodynamic changes, which may contribute to the development of MODS (multiple organ dysfunction syndrome). In this study, we used an in vitro flow system to simulate the consecutive changes in blood flow as occurring during hemorrhagic shock and resuscitation in vivo. We examined the kinetic responses of different endothelial genes in human umbilical vein endothelial cells preconditioned to 20 dyne/cm unidirectional laminar shear stress for 48 h to flow cessation and abrupt reflow, respectively, as well as the effect of flow cessation and reflow on tumor necrosis factor-α (TNF-α)-induced endothelial proinflammatory activation. Endothelial CD31 and VE-cadherin were not affected by the changes in flow in the absence or presence of TNF-α. The messenger RNA levels of proinflammatory molecules E-selectin, VCAM-1 (vascular cell adhesion molecule 1), and IL-8 (interleukin 8) were significantly induced by flow cessation respectively acute reflow, whereas ICAM-1 (intercellular adhesion molecule 1) was downregulated on flow cessation and induced by subsequent acute reflow. Flow cessation also affected the Ang/Tie2 (Angiopoietin/Tie2 receptor tyrosine kinase) system by downregulating Tie2 and inducing its endothelial ligand Ang2, an effect that was further extended on acute reflow. Furthermore, the induction of proinflammatory adhesion molecules by TNF-α under flow cessation was significantly enhanced on subsequent acute reflow. This study demonstrated that flow alterations per se during shock and resuscitation contribute to endothelial activation and that these alterations interact with proinflammatory factors coexisting in vivo such as TNF-α. The abrupt reflow-related enhancement of cytokine-induced endothelial proinflammatory activation supports the concept that sudden regain of flow during resuscitation has an aggravating effect on endothelial activation, which may play a significant role in vascular dysfunction and consequent organ injury. This study implies that the improvement of resuscitation strategies and the pharmacological interference with proinflammatory signaling cascades at the right time of resuscitation of shock patients may be beneficial to regain and/or maintain organ function in patients after circulatory shock.

High plasma levels of high mobility group box 1 is associated with the risk of sepsis in severe blunt chest trauma patients: a prospective cohort study.

BackgroundHigh mobility group box 1 (HMGB1) is a late mediator of systemic inflammation. Extracellular HMGB1 play a central pathogenic role in critical illness. The purpose of the study was to investigate the association between plasma HMGB1 concentrations and the risk of poor outcomes in patients with severe blunt chest trauma.MethodsThe plasma concentrations of HMGB1 in patients with severe blunt chest trauma (AIS ≥ 3) were measured by a quantitative enzyme-linked immunosorbent assay at four time points during seven days after admission, and the dynamic release patterns were monitored. The biomarker levels were compared between patients with sepsis and non-sepsis, and between patients with multiple organ dysfunction syndrome (MODS) and non-MODS. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The short-form 36 was used to evaluate the quality of life of patients at 12 months after injury.ResultsPlasma HMGB1 levels were significantly higher both in sepsis and MODS group on post-trauma day 3, 5, and 7 compared with the non-sepsis and non-MODS groups, respectively. Multivariate analysis showed that HMGB1 levels and ISS were independent risk factors for sepsis and MODS in patients with severe blunt chest trauma.ConclusionsPlasma HMGB1 levels were significantly elevated in patients with severe blunt chest trauma. HMGB1 levels were associated with the risk of poor outcome in patients with severe blunt chest trauma. Daily HMGB1 levels measurements is a potential useful tool in the early identification of post-trauma complications. Further studies are needed to determine whether HMGB1 intervention could prevent the development of sepsis and MODS in patients with severe blunt chest trauma.

NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome.

Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91(phox-/y) (NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation.

Endocan is useful biomarker of survival and severity in sepsis

IntroductionCoagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. Materials and methods60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann–Whitney U test. Categorical variables were compared using chi-square test. ResultsConcentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure. ConclusionsResults of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores.

Dysfunction of peroxisomes as one of the possible causes of multiple organ dysfunction syndrome development

Dysfunction of peroxisomes as one of the possible causes of multiple organ dysfunction syndrome development

Extracellular ATP drives systemic inflammation, tissue damage and mortality

Systemic inflammatory response syndromes (SIRS) may be caused by both infectious and sterile insults, such as trauma, ischemia-reperfusion or burns. They are characterized by early excessive inflammatory cytokine production and the endogenous release of several toxic and damaging molecules. These are necessary to fight and resolve the cause of SIRS, but often end up progressively damaging cells and tissues, leading to life-threatening multiple organ dysfunction syndrome (MODS). As inflammasome-dependent cytokines such as interleukin-1β are critically involved in the development of MODS and death in SIRS, and ATP is an essential activator of inflammasomes in vitro, we decided to analyze the ability of ATP removal to prevent excessive tissue damage and mortality in a murine LPS-induced inflammation model. Our results indeed indicate an important pro-inflammatory role for extracellular ATP. However, the effect of ATP is not restricted to inflammasome activation at all. Removing extracellular ATP with systemic apyrase treatment not only prevented IL-1β accumulation but also the production of inflammasome-independent cytokines such as TNF and IL-10. In addition, ATP removal also prevented systemic evidence of cellular disintegration, mitochondrial damage, apoptosis, intestinal barrier disruption and even mortality. Although blocking ATP receptors with the broad-spectrum P2 purinergic receptor antagonist suramin imitated certain beneficial effects of apyrase treatment, it could not prevent morbidity or mortality at all. We conclude that removal of systemic extracellular ATP could be a valuable strategy to dampen systemic inflammatory damage and toxicity in SIRS.

Dysfunction of peroxisomes as one of the possible causes of multiple organ dysfunction syndrome development

This study demonstrates that low level of plasmalogens (Pls) is an important marker of peroxisomal dysfunction. The primary- OH group in glycerol Pls was not substituted by the acyl group (fatty acid) as in diacylphospholipids but by the aldehydogenic alkenyl group (fatty aldehyde) found in the form of vinyl ether [1]. It is known that there is disruption of several organ systems in diseases connected with peroxisomal dysfunction, as in the case of multiple organ failure.

High plasma levels of high mobility group box 1 is associated with the risk of sepsis in severe blunt chest trauma patients: a prospective cohort study

BackgroundHigh mobility group box 1 (HMGB1) is a late mediator of systemic inflammation. Extracellular HMGB1 play a central pathogenic role in critical illness. The purpose of the study was to investigate the association between plasma HMGB1 concentrations and the risk of poor outcomes in patients with severe blunt chest trauma.MethodsThe plasma concentrations of HMGB1 in patients with severe blunt chest trauma (AIS ≥ 3) were measured by a quantitative enzyme-linked immunosorbent assay at four time points during seven days after admission, and the dynamic release patterns were monitored. The biomarker levels were compared between patients with sepsis and non-sepsis, and between patients with multiple organ dysfunction syndrome (MODS) and non-MODS. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The short-form 36 was used to evaluate the quality of life of patients at 12 months after injury.ResultsPlasma HMGB1 levels were significantly higher both in sepsis and MODS group on post-trauma day 3, 5, and 7 compared with the non-sepsis and non-MODS groups, respectively. Multivariate analysis showed that HMGB1 levels and ISS were independent risk factors for sepsis and MODS in patients with severe blunt chest trauma.ConclusionsPlasma HMGB1 levels were significantly elevated in patients with severe blunt chest trauma. HMGB1 levels were associated with the risk of poor outcome in patients with severe blunt chest trauma. Daily HMGB1 levels measurements is a potential useful tool in the early identification of post-trauma complications. Further studies are needed to determine whether HMGB1 intervention could prevent the development of sepsis and MODS in patients with severe blunt chest trauma.

Health insurance status and outcomes of critically ill obstetric patients: A prospective cohort study in Argentina

PurposeIn Argentina, uninsured patients receive public health care, and the insured receive private health care. Our aim was to compare different outcomes between critically ill obstetric patients from both sectors. MethodsThis is a prospective cohort, including pregnant/postpartum patients requiring admission to 1 intensive care unit in the public sector (uninsured) and 1 in the private (insured) from January 1, 2008, to September 30, 2011. ResultsA total of 151 patients were included in the study. In uninsured (n = 63) vs insured (n = 88) patients, Acute Physiology and Chronic Evaluation II (APACHE II) and Sequential Organ Failure Assessment scores were 11 ± 6.5 vs 8 ± 4 and 3 (2-7) vs 1 (0-2), respectively, and 84% vs 100% received prenatal care (P = .001 for all). Multiple organ dysfunction syndrome (MODS) was present in 32 (54%) uninsured vs 9 (10%) insured patients (P = .001), and acute respiratory distress syndrome developed in 18 (30.5%) of 59 vs 2(2%) of 88 (P = .001). Neonatal survival was 80% vs 96% (P = .003). Variables independently associated with the development of MODS were APACHE II (odds ratio, 1.30 [1.13-1.49]), referral from another hospital (odds ratio, 11.43 [1.86-70.20]), lack of health insurance (odds ratio 6.75 [2.17-20.09]), and shock (odds ratio 4.82 [1.54-15.06]). Three patients died, all uninsured. ConclusionsUninsured critically ill obstetric patients (public sector) were more severely ill on admission and experienced worse outcomes than insured patients (private sector). Variables independently associated with MODS were APACHE II, shock, referral from another hospital, and lack of insurance.

Multiple Organ Dysfunction Syndrome

Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%.

The value of PCT, CRP, TNF-α and free DNA in predicting the development of MODS in patients with multiple trauma

Objective To explore the value of peripheral blood serum levels of PCT,CRP,TNF-α and free DNA of cells in predicting the development of MODS in patients with multiple trauma.Methods Complete detail clinical data of 54 casualties with multiple trauma admitted within 24 hours after accident from January 2011 through January 2012 were collected for retrospective study.The patients were divided into MODS group and non-MODS group according the criteria set forth by the Chinese Society of Critical Care and Emergency Medicine in 1995 national conference.The data of two groups are comparable,and data of another 20 healthy subjects undertaking routine annual physical examination were taken as control.The peripheral blood levels of PCT,CRP,TNF-α and free DNA of patients of two groups were determined 1 d,2 d,3 d,and 5 days after admission.Then the results were analyzed and compared between groups.Results Compared with non MODS group,the levels of PCT,CRP,free DNA of cells in MODS group were significantly higher (P ＜ 0.05),but there was no deference in TNF-α between MODS group and non-MODS group (P ＞ 0.05).When the relative risks of increased PCT (PCT≥6 mg/L),increased CRP (CRP≥ 130 mg/L)、and increased free DNA of cells (free DNA ≥ 10 0005/L) were analyzed,the presence of these 3 biomarkers with high levels occurred at the same time was the most accurate way to predicts MODS in 6.00 relative risk (RR),and the positive predictive value was 100％.Conclusions PCT,CRP,free DNA of cells could be the predictors of MODS in patients with severe multiple trauma,and the presence of high levels of these three biomarkers appearing together had high sensitivity and specificity for prediction. Key words: Multiple trauma; Procalcitonin (PCT) ; C-reactive protein (CRP) ; Tumor necrosis factor (TNF-α); Cell free DNA; Multiple organ dysfunction syndrome (MODS); Predictive value; Statistically significant