Temporal patterns of organ dysfunction after severe trauma.

BACKGROUND: Understanding temporal patterns of organ dysfunction (OD) may aid early recognition of complications after trauma and assist timing and modality of treatment strategies. Our aim was to analyse and characterise temporal patterns of OD in intensive care unit-admitted trauma patients. METHODS: We used group-based trajectory modelling to identify temporal trajectories of OD after trauma. Modelling was based on the joint development of all six subdomains comprising the sequential organ failure assessment score measured daily during the first two weeks post trauma. Further, the time for trajectories to stabilise and transition to final group assignments were evaluated. RESULTS: Six-hundred and sixty patients were included in the final model. Median age was 40 years, and median ISS was 26 (IQR 17-38). We identified five distinct trajectories of OD. Group 1, mild OD (n = 300), median ISS of 20 (IQR 14-27), had an early resolution of OD and a low mortality. Group 2, moderate OD (n = 135), and group 3, severe OD (n = 87), were fairly similar in admission characteristics and initial OD but differed in subsequent OD trajectories, the latter experiencing an extended course and higher mortality. In group 3, 56% of the patients developed sepsis as compared with 19% in group 2. Group 4, extreme OD (n = 40), received most blood transfusions, had the highest proportion of shock at admission and a median ISS of 41 (IQR 29-50). They experienced significant and sustained OD affecting all organ systems and a 28-day mortality of 30%. Group 5, traumatic brain injury with OD (n = 98), had the highest mortality of 35% and the shortest time to death for non-survivors, median 3.5 (IQR 2.4-4.8) days. Groups 1 and 5 reached their final group assignment early, > 80% of the patients within 48 h. In contrast, groups 2 and 3 had a prolonged time to final group assignment. CONCLUSIONS: We identified five distinct trajectories of OD after severe trauma during the first two weeks post-trauma. Our findings underline the heterogeneous course after trauma and describe some potentially important clinical insights that are suggested by the groupings and temporal trajectories.

The initial validation of a novel outcome measure in severe burns- the Persistent Organ Dysfunction +Death: Results from a multicenter evaluation.

INTRODUCTION: A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency. METHODS: This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care. RESULTS: In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used. CONCLUSIONS: POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted. STUDY TYPE: Prospective cohort study, level of evidence: II.

Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis.

BACKGROUND: Severe critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test the hypothesis that hydrocortisone will be differentially associated with clinical outcomes in children with or without immunoparalysis. METHODS: Children with severe sepsis/septic shock underwent blood sampling within 48 h of sepsis onset. Immune function was measured by quantifying whole blood ex vivo LPS-induced TNFα production capacity, with a TNFα response < 200 pg/ml being diagnostic of immunoparalysis. The primary outcome measure was number of days in 14 with MODS. Univariate and multivariable negative binomial regression models were used to examine associations between hydrocortisone use, immune function, and duration of MODS. RESULTS: One hundred two children were enrolled (age 75 [6-160] months, 60% male). Thirty-one subjects received hydrocortisone and were more likely to be older (106 [52-184] vs 38 [3-153] months, p = 0.04), to have baseline immunocompromise (32 vs 8%, p = 0.006), to have higher PRISM III (13 [8-18] vs 7 [5-13], p = 0.0003) and vasoactive inotrope scores (20 [10-35] vs 10 [3-15], p = 0.0002) scores, and to have more MODS days (3 [1-9] vs 1 [0-3], p = 0.002). Thirty-three subjects had immunoparalysis (TNFα response 78 [52-141] vs 641 [418-1047] pg/ml, p < 0.0001). Hydrocortisone use was associated with longer duration of MODS in children with immunoparalysis after adjusting for covariables (aRR 3.7 [1.8-7.9], p = 0.0006) whereas no association with MODS duration was seen in children without immunoparalysis (aRR 1.2 [0.6-2.3], p = 0.67). CONCLUSION: Hydrocortisone use was independently associated with longer duration of MODS in septic children with immunoparalysis but not in those with more robust immune function. Prospective clinical trials using a priori immunophenotyping are needed to understand optimal hydrocortisone strategies in this population.

Derivation and Validation of Novel Phenotypes of Multiple Organ Dysfunction Syndrome in Critically Ill Children.

Importance: Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity and mortality in critically ill children. Objective: To determine whether data-driven phenotypes of MODS based on the trajectories of 6 organ dysfunctions have prognostic and therapeutic relevance in critically ill children. Design, Setting, and Participants: This cohort study included 20 827 pediatric intensive care encounters among 14 285 children admitted to 2 large academic pediatric intensive care units (PICUs) between January 2010 and August 2016. Patients were excluded if they were older than 21 years or had undergone cardiac surgery. The 6 subscores of the pediatric Sequential Organ Failure Assessment (pSOFA) score were calculated for the first 3 days, including the subscores for respiratory, cardiovascular, coagulation, hepatic, neurologic, and renal dysfunctions. MODS was defined as a pSOFA subscore of at least 2 in at least 2 organs. Encounters were split in a 80:20 ratio for derivation and validation, respectively. The trajectories of the 6 subscores were used to derive a set of data-driven phenotypes of MODS using subgraph-augmented nonnegative matrix factorization in the derivation set. Data analysis was conducted from March to October 2019. Exposures: The primary exposure was phenotype membership. In the subset of patients with vasoactive-dependent shock, the interaction between hydrocortisone and phenotype membership and its association with outcomes were examined in a matched cohort. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included persistent MODS on day 7, and vasoactive-free, ventilator-free, and hospital-free days. Regression analysis was used to adjust for age, severity of illness, immunocompromised status, and study site. Results: There were 14 285 patients with 20 827 encounters (median [interquartile range] age 5.2 years [1.5-12.7] years; 11 409 [54.8%; 95% CI, 54.1%-55.5%] male patients). Of these, 5297 encounters (25.4%; 95% CI, 24.8%-26.0%) were with patients who had MODS, of which 5054 (95.4%) met the subgraph count threshold and were included in the analysis. Subgraph augmented nonnegative matrix factorization uncovered 4 data-driven phenotypes of MODS, characterized by a combination of neurologic, respiratory, coagulation, and cardiovascular dysfunction, as follows: phenotype 1, severe, persistent encephalopathy (1019 patients [19.2%]); phenotype 2, moderate, resolving hypoxemia (1828 patients [34.5%]); phenotype 3, severe, persistent hypoxemia and shock (1012 patients [19.1%]); and phenotype 4, moderate, persistent thrombocytopenia and shock (1195 patients [22.6%]). These phenotypes were reproducible in a validation set of encounters, had distinct clinical characteristics, and were independently associated with outcomes. For example, using phenotype 2 as reference, the adjusted hazard ratios (aHRs) for death by 28 days were as follows: phenotype 1, aHR of 3.0 (IQR, 2.1-4.3); phenotype 3, aHR of 2.8 (IQR, 2.0-4.1); and phenotype 4, aHR of 1.8 (IQR, 1.2-2.6). Interaction analysis in a matched cohort of patients with vasoactive-dependent shock revealed that hydrocortisone had differential treatment association with vasoactive-free days across phenotypes. For example, patients in phenotype 3 who received hydrocortisone had more vasoactive-free days than those who did not (23 days vs 18 days; P for interaction < .001), whereas patients in other phenotypes who received hydrocortisone either had no difference or had less vasoactive-free days. Conclusions and Relevance: In this study, data-driven phenotyping in critically ill children with MODS uncovered 4 distinct and reproducible phenotypes with prognostic relevance and possible therapeutic relevance. Further validation and characterization of these phenotypes is warranted.

Temperature-Neutrophils-Multiple Organ Failure Grading for Complicated Intra-Abdominal Infections.

Background: The grading systems for intra-abdominal sepsis (IAS) are not employed commonly in clinical practice because they are too complicated or too specific. We propose to grade IAS with a simple grading system: the TNM system, which is an acronym borrowed from cancer staging, where T indicates Temperature, N indicates Neutrophils, and M indicates Multiple organ failure (MOF). The aim of this prospective observational study is to assess the predictive value of the TNM score on deaths of patients with complicated IAS. Patients and Methods: We considered 147 patients with complicated IAS. Three classes of attribute were chosen: Temperature (T), Neutrophil count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3), and M (M0-M2), they were grouped in stages (0-IV). We analyzed specific variables for their possible relation to death: Age, gender, blood transfusion, causes of IAS, T, N, pre-operative organ failure, immunocompromised status, stage 0, I, II, III, and IV. Odds ratios were calculated in a uni-variable and multi-variable analysis. Results: This was the distribution in classes, based on TNM stages: One patient was in stage 0; 15 patients in stage I; 47 patients in stage II; 56 patients in stage III; 28 patients in stage IV. Death occurred in 45 (30.6%) patients. The N, pre-operative organ failure, immunocompromised status, stage III-IV were potential predictors of post-operative death in uni-variable analysis. Only pre-operative organ failure and stage IV were significant independent predictors of post-operative death in multi-variable analysis. Conclusions: The TNM classification is an easy system that could be considered to define the death risk of patients with IAS and to compare patients with sepsis.

Multiple organ dysfunction after trauma.

BACKGROUND: The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level. METHODS: Adult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes. RESULTS: Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003). CONCLUSION: Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.

ANTECEDENTES: La naturaleza del síndrome de disfunción orgánica múltiple (Multiple Organ Dysfunction Syndrome, MODS) resultante de un traumatismo está evolucionando a medida que avanzan las prácticas de reanimación y más pacientes sobrevive a las lesiones y pueden recibir cuidados críticos. El objetivo de este estudio fue caracterizar los subtipos actuales MODS en atención crítica de trauma a nivel poblacional. MÉTODOS: Los pacientes adultos ingresados en unidades de cuidados intensivos de trauma se incluyeron en este estudio de prevalencia puntual de 4 semanas. MODS se definió como una puntuación total diaria de la escala de Evaluación de Fallo Orgánico Secuencial (Sequential Organ Failure Assessment, SOFA) > 5. Se utilizó el agrupamiento jerárquico de las puntuaciones SOFA a lo largo del tiempo para determinar los subtipos MODS. RESULTADOS: Se incluyeron 440 pacientes, de los cuales 245 (56%) presentaron MODS. MODS conllevó una alta mortalidad (22% versus 1%, P < 0,001) y 24% de las muertes fueron precoces, durante las primeras 48 horas tras el traumatismo. Se identificaron tres patrones de MODS, estando todos presentes al ingreso. En el tipo 1, MODS se resolvió de forma temprana, con una mediana de tiempo de recuperación de 4 días y una mortalidad del 14%. El tipo 2 presentaba un tiempo de recuperación retardado (mediana 13 días) y una mortalidad del 35%. El tipo 3 presentaba un tiempo de recuperación prolongado (mediana 25 días) y una mortalidad asociada alta del 46%. El análisis multivariable reveló asociaciones clínicas diferentes para cada tipo de MODS, con la administración de cristaloides durante 24 horas fuertemente asociada al tipo 1 (P < 0,001); el traumatismo craneal al tipo 2 (P < 0,01); y la gravedad del shock al ingreso al tipo 3 (P < 0,01). CONCLUSIÓN: Los MODS actuales presentan al menos tres tipos distintos basados en patrones de gravedad y recuperación. La caracterización de los subtipos de MODS y su fisiopatología subyacente puede contribuir a futuras oportunidades de estratificación temprana e intervenciones dirigidas.

Clinical spectrum and outcome of critically ill hospitalized patients with acute febrile illness and new-onset organ dysfunction presenting during monsoon season.

Acute febrile illness (AFI) is one of the commonest indications for hospitalization and can present with varying severity including single or multiple organ dysfunction syndrome (MODS). During monsoon season, there is a spurt of AFI often caused by vector borne diseases leading to substantial morbidity and mortality. Our aim was to determine distribution of etiological causes, differential organ involvement and predictors of mortality in critically ill patients with AFI. It was a hospital based observational study which included patients with AFI with dysfunction of at least one organ system. The study was conducted over 4 months during monsoon season. Admitted patients were included who had been subjected to a standard battery of tests and managed with standard hospital based management protocol. 145 patients were included and etiology of fever was ascertained in 81.4% of patients with the most common single infection being chikungunya (20.7%) followed by dengue (20%) fever. Thrombocytopenia and deranged liver biochemistry each were seen in nearly 75% of the patients. Renal (50.3%) and nervous system (46.2%) dysfunction were the predominant organ failures. 49 patients died (33.8%) which correlated with predicted mortality by APACHE (acute physiological assessment and chronic health evaluation) II score. Independent predictors for mortality were older age (> 55 years) (p = 0.01), acidemia (p = 0.01), altered sensorium (p = 0.02) and coagulopathy (p = 0.048). Sub-group analysis revealed that amongst patients with MODS, hypotension could help differentiate between bacterial and non-bacterial causes (p = 0.01). Critically ill patients with AFI suffer from significant morbidity and mortality. Features like the presence of hypotension in MODS may differentiate between a bacterial cause vis-à-vis viral or protozoal etiology.

Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients.

BACKGROUND: Multiple organ dysfunction is a common cause of morbidity and mortality in intensive care units (ICUs). Original development of the Sequential Organ Failure Assessment (SOFA) score was not to predict outcome, but to describe temporal changes in organ dysfunction in critically ill patients. Organ dysfunction scoring may be a reasonable surrogate outcome in clinical trials but further exploration of the impact of case mix on the temporal sequence of organ dysfunction is required. Our aim was to compare temporal changes in SOFA scores between hospital survivors and non-survivors. METHODS: We performed a population-based observational retrospective cohort study of critically ill patients admitted from January 1, 2004, to December 31, 2013, to 4 multisystem adult intensive care units (ICUs) in Calgary, Canada. The primary outcome was temporal changes in daily SOFA scores during the first 14 days of ICU admission. SOFA scores were modeled between hospital survivors and non-survivors using generalized estimating equations (GEE) and were also stratified by admission SOFA (≤ 11 versus > 11). RESULTS: The cohort consisted of 20,007 patients with at least one SOFA score and was mostly male (58.2%) with a median age of 59 (interquartile range [IQR] 44-72). Median ICU length of stay was 3.5 (IQR 1.7-7.5) days. ICU and hospital mortality were 18.5% and 25.5%, respectively. Temporal change in SOFA scores varied by survival and admission SOFA score in a complicated relationship. Area under the receiver operating characteristic (ROC) curve using admission SOFA as a predictor of hospital mortality was 0.77. The hospital mortality rate was 5.6% for patients with an admission SOFA of 0-2 and 94.4% with an admission SOFA of 20-24. There was an approximately linear increase in hospital mortality for SOFA scores of 3-19 (range 8.7-84.7%). CONCLUSIONS: Examining the clinical course of organ dysfunction in a large non-selective cohort of patients provides insight into the utility of SOFA. We have demonstrated that hospital outcome is associated with both admission SOFA and the temporal rate of change in SOFA after admission. It is necessary to further explore the impact of additional clinical factors on the clinical course of SOFA with large datasets.

Mortality Risk Using a Pediatric Quick Sequential (Sepsis-Related) Organ Failure Assessment Varies With Vital Sign Thresholds.

OBJECTIVES: We evaluated adapting the quick Sequential (Sepsis-Related) Organ Failure Assessment score (fast respiratory rate, altered mental status, low blood pressure) for pediatric use by selecting thresholds from three commonly used definitions: Pediatric Logistic Organ Dysfunction 2, Pediatric Advanced Life Support, and International Pediatric Sepsis Consensus Conference. We examined their respective performance in identifying children who had a discharge diagnosis of infection at high risk of mortality using PICU registry data, with additional focus on the influence of age on performance. DESIGN: Analysis of retrospective data obtained from the Virtual Pediatric Systems PICU database. The performance in predicting observed mortality was assessed for the three candidate approaches using receiver operating characteristics analysis, including age group effects. SETTING: The Virtual Pediatric Systems database contains data on diagnosis, clinical markers, and outcomes in prospectively collected clinical records from 130 participating PICUs in the United States and Canada. PATIENTS: Children who had a discharge diagnosis of infection in a participating PICU between 2009 and 2014, for which all required data were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 40,228 children revealed an overall mortality of 4.22%. Area under the receiver operating characteristics curve (95% CI) was 0.760 (0.749-0.771) for Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation, 0.700 (0.689-0.712) for Pediatric Advanced Life Support, and 0.709 (0.696-0.721) for International Pediatric Sepsis Consensus Conference. When split by age group, the performance of Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation was lowest in the youngest neonates (under 1 wk old), with an area under the receiver operating characteristics curve (95% CI) of 0.724 (0.656-0.791), and in the teenagers (13-18 yr), with an area under the receiver operating characteristics curve of 0.710 (0.682-0.738), yet it still outperformed Pediatric Advanced Life Support and International Pediatric Sepsis Consensus Conference in both groups. CONCLUSIONS: Among critically ill children who had a discharge diagnosis of infection in the PICU, quick Sequential (Sepsis-Related) Organ Failure Assessment score performs best when using the Pediatric Logistic Organ Dysfunction 2 age thresholds with mechanical ventilation, while all definitions performed worse at extremes of pediatric age. Thus, mortality risk varies with vital sign thresholds, and although Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation performed marginally better, it is unlikely to be of use to clinicians. More work is needed to develop a robust and relevant pediatric sepsis risk score.

Six subphenotypes in septic shock: Latent class analysis of the PROWESS Shock study.

PURPOSE: Septic shock is a highly heterogeneous condition which is part of the challenge in its diagnosis and treatment. In this study we aim to identify clinically relevant subphenotypes of septic shock using a novel statistic al approach. METHODS: Baseline patient data from a large global clinical trial of septic shock (n = 1696) was analysed using latent class analysis (LCA). This approach allowed investigators to identify subgroups in a heterogeneous population by estimating a categorical latent variable that detects relatively homogeneous subgroups within a complex phenomenon. RESULTS: LCA identified six different, clinically meaningful subphenotypes of septic shock each with a typical profile: (1) "Uncomplicated Septic Shock, (2) "Pneumonia with adult respiratory distress syndrome (ARDS)", (3) "Postoperative Abdominal", (4) "Severe Septic Shock", (5): "Pneumonia with ARDS and multiple organ dysfunction syndrome (MODS)", (6) "Late Septic Shock". The 6-class solution showed high entropy approaching 1 (i.e., 0.92), indicating there was excellent separation between estimated classes. CONCLUSIONS: LCA appears to be an applicable statistical tool in analysing a heterogenous clinical cohort of septic shock. The results may lead to a better understanding of septic shock complexity and form a basis for considering targeted therapies and selecting patients for future clinical trials.

Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome.

INTRODUCTION: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. METHODS: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. RESULTS: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. CONCLUSION: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

Tadalafil: protective action against the development of multiple organ failure syndrome

Abstract Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

[A retrospective clinical study of sixty-three cases with persistent inflammation immunosuppression and catabolism syndrome].

Objective: To study the clinical characteristics and prognosis of patients with persistent inflammation immunosuppression and catabolism syndrome (PICS) in ICU. Methods: A total of 126 patients admitted to ICU (ICU stay of more than 10 days, age≥18 years) between January 2014 to December 2014 were retrospectively studied.Data were collected from electronic medical records including demographics, underlying disease, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) score, Sequential Organ Failure Assessment (SOFA) score, laboratory parameters, ICU acquired infections and clinical outcome. Results: The overall incidence of PICS in ICU patients (ICU stay of more than 10 days) was 50.0%(63/126). There were no significant differences in baseline data such as gender, age, APACHEⅡscore, SOFA score and underlying diseases between the two groups(all P>0.05). Compared with the non-PICS group, there were more patients with gastrointestinal perforation in the PICS group (P=0.042), however, the medical or surgical admission did not differ between the two groups(P>0.05). During the stay in ICU, the PICS group showed a higher risk of developing acquired infections compared with the non-PICS group[PICS 63.5%(40/63) vs non-PICS 23.8%(15/63); P<0.001]. The infections were more caused by Candida in the PICS group than the non-PICS group [PICS 22.4%(11/49) vs non-PICS 2/17; P=0.003]. Moreover, the PICS group experienced longer stay in ICU[PICS(31.6±28.8) days vs non-PICS (20.4±11.3) days; P=0.0046] and higher ICU mortality [PICS 28.6%(18/63) vs non-PICS 6.3%(4/63), P=0.001]. Conclusion: PICS is a common manifestation of patients who stay in ICU more than 10 days, which is associated with high risk of ICU acquired infections, prolonged length of stay and high mortality.

[Acute-on-chronic liver failure - new Definition of a complex clinical picture]. / Akut-auf-chronisches Leberversagen: Neue Definition eines komplexen Krankheitsbildes.

Acute-on-chronic liver failure (ACLF) is characterized by a sudden onset of decompensation in patients with preexisting liver disease followed by subsequent organ failure and high short-term mortality. ACLF is extremely heterogeneous in terms of predisposing stage of liver disease, precipitating events, and the course of organ failure and has been defined differently by different medical associations in the East and in the West. A recent consensus working definition is the basis for further research in order to understand underlying pathophysiological mechanisms, to establish diagnostic and prognostic biomarkers, and to implement risk-adapted treatment strategies.

[Actual problems of the pathology of sepsis: 25 years in search of a consensus]. / Aktual'nye problemy patologii sepsisa: 25 let v poiskakh konsensusa.

In search of a consensus the authors give current materials on the pathobiology of sepsis, which concerns the definitions, classification, etiology, pathogenesis, and diagnosis of the disease on the basis of their own experience and the data available in the literature. The sepsis problem that is one of the most controversial and complex ones in pathobiology and medical practice has undergone a great very important 25-year stage of development to culminate in the adoption of clinical Sepsis-3 Consensus. International experts have proposed a new definition of sepsis, with an emphasis on the life-threatening condition and the presence of organ dysfunction that can be regarded as an analogous to organ damage. Systemic inflammatory response remains an essential sign of sepsis, but is not strictly specific. Instead of its previous four forms of sepsis, two forms of the disease (sepsis proper and septic shock) have been identified. The Consensus-proposed Sepsis-3 criteria for diagnosing sepsis continue to remain predominantly clinical laboratory ones, confirming the need for further clinicopathological and experimental morphological comparisons in order to achieve a complete understanding of the problem of sepsis between clinicians and pathologists.

Toma de medición intraabdominal a personas en estado crítico, por el profesional de enfermería / Taking measurement intraabdominal people in critical condition, by the nursing professional", "_e": "n

El aumento de la presión dentro de la cavidad abdominal se asocia a múltiples alteraciones fisiopatológicas, con una importante repercusión en aparatos y sistemas originando disfunción orgánica múltiple, lo que conlleva a un incremento en la morbimortalidad en pacientes en estado crítico, la medición de presión intraabdominal es un procedimiento que se está realizando con mayor frecuencia en las Unidades de Cuidados Intensivos, en donde los profesionales de enfermería tienen un papel muy importante en la toma e identificación de posibles complicaciones que ponen en riesgo la vida del paciente. La siguiente revisión tiene la finalidad de difundir el conocimiento y dar a conocer la importancia e intervenciones de enfermería en la medición de la presión intraabdominal.

The increase in the pressure inside the abdominal cavity is associated with multiple pathophysiological changes, with a significant impact in systems causing multiple organic dysfunction, leading to increased the morbidity and mortality in critically ill patients, the measurement of intra-abdominal pressure is a procedure that is being performed more frequently in the intensive care units, where nurses have an important role in taking and identifying possible complications that endanger the patient’s life. The following review has the purpose of disseminate knowledge and explain the importance and the nursing interventions in measuring intra-abdominal pressure.

20 Years On: Is It Time to Redefine the Systemic Inflammatory Response to Cardiothoracic Surgery?

The "systemic inflammatory response" has never been defined from a cardiothoracic surgery perspective, but borrowed its definition from the critical care field at a landmark 1992 definition conference on sepsis. It is unclear why the diagnostic criteria for the Systemic Inflammatory Response Syndrome (SIRS) were adopted in isolation, ignoring other potentially more useful definitions for Severe Septic Shock or Secondary Multiple Organ Dysfunction Syndrome. The 1992 SIRS definition for sepsis has since been updated at a conference in 2001 advocating PIRO (Predisposition, Infection, host Response, Organ dysfunction) as a hypothetical model to better link sepsis with clinical outcome. PIRO is readily adaptable to cardiothoracic surgery and provides the precedent and road map for how to update a definition. The need is obvious since the current definition of SIRS is widely disregarded in heart surgery: a dwindling proportion (14%) of articles on the systemic inflammatory response even mention SIRS and 0% monitored SIRS criteria in the past decade in an evidence-based review of anti-inflammatory interventions. The name "inflammatory response" is also problematic; it is too narrow and might be replaced with host response (the R in PIRO) to better convey the wide spectrum of host defensive pathways activated during heart surgery (i.e., complement, coagulation, fibrinolysis, kinins, cytokines, proteases, hemolysis, oxidative stiess). A variant on PIRO could allow these elements of the host Response (R) to be anchored within the context of Premorbid conditions (P) and the inevitable Insult (I) from surgery, to better link risk exposures to Organ dysfunction (O) in heart surgery. The precedent of PIRO suggests the following steps will be required to redefine the systemic inflammatory response: 1) buy-in from the leading societies for cardiothoracic surgery, anesthesia, and perfusion on the need for a re-definition conference, 2) assigning relative risk scores to different premorbid exposures, operative insults, and host response factors on clinical outcome, 3) validation of the risk model in a prospective cohort, and 4) development of algorithms or "apps" to facilitate rapid diagnosis and staging of care at bedside.