Search

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates., Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo., Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation., Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days., Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL., Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen., Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

Background: Acute kidney injury (AKI) is a serious clinical condition in critically ill children and is associated with worse outcomes. A few pediatric studies focused on the risk factors of AKI. We aimed to identify the incidence, risk factors, and outcomes of AKI in the pediatric intensive care unit (PICU)., Patients and Methods: All the patients admitted to PICU over a period of 20 months were included. We compared both groups the risk factors between AKI and non-AKI., Results: A total of 63 patients (17.5%) of the 360 patients developed AKI during PICU stay. The presence of comorbidity, diagnosis of sepsis, increased PRISM III score, and positive renal angina index were found to be risk factors for AKI on admission. Thrombocytopenia, multiple organ failure syndrome, the requirement of mechanical ventilation, use of inotropic drugs, intravenous iodinated contrast media, and exposure to an increased number of nephrotoxic drugs were independent risk factors during the hospital stay. The patients with AKI had a lower renal function on discharge and had worse overall survival., Conclusions: AKI is prevalent and multifactorial in critically sick children. The risk factors of AKI may be present on admission and during the hospital stay. AKI is related to prolonged mechanical ventilation days, longer PICU stays, and a higher mortality rate. Based on the presented results early prediction of AKI and consequent modification of nephrotoxic medication may generate positive effects on the outcome of critically ill children., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objectives: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction., Design: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3)., Setting: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting., Patients: Ninety-six adult septic and critically ill nonseptic patients were enrolled., Interventions: None., Measurements and Main Results: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation., Conclusions: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness., Competing Interests: Dr. Halstead is a speaker for Swedish Orphan Biovitrum pharmaceuticals and lectures specifically about the disease process and therapeutic strategies for hemophagocytic lymphohistiocytosis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose of Review: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome., Recent Findings: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice., (© 2023. The Author(s).)

Background: Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA)., Methods: This was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels., Results: Of 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC., Conclusions: The addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction., (© 2021. The Author(s).)

Predictions of mortality may help in the selection of patients who benefit from intensive care. Endothelial dysfunction is partially responsible for many of the organic dysfunctions in critical illness. Reactive hyperaemia is a vascular response of the endothelium that can be measured by peripheral arterial tonometry (RH-PAT). We aimed to assess if reactive hyperaemia is affected by critical illness and if it correlates with outcomes. Prospective study with a cohort of consecutive patients admitted to an Intensive Care Unit. RH-PAT was accessed on admission and on the 7th day after admission. Early and late survivors were compared to non-survivors. The effect of RH-PAT variation on late mortality was studied by a logistic regression model. The association between RH-PAT and severity scores and biomarkers of organic dysfunction was investigated by multivariate analysis. 86 patients were enrolled. Mean ln(RHI) on admission was 0.580 and was significantly lower in patients with higher severity scores (p < 0.01) and early non-survivors (0.388; p = 0.027). The model for prediction of early-mortality estimated that each 0.1 decrease in ln(RHI) increased the odds for mortality by 13%. In 39 patients, a 2nd RH-PAT measurement was performed on the 7th day. The variation of ln(RHI) was significantly different between non-survivors and survivors (- 24.2% vs. 63.9%, p = 0.026). Ln(RHI) was significantly lower in patients with renal and cardiovascular dysfunction (p < 0.01). RH-PAT is correlated with disease severity and seems to be an independent marker of early mortality, cardiovascular and renal dysfunctions. RH-PAT variation predicts late mortality. There appears to be an RH-PAT impairment in the acute phase of severe diseases that may be reversible and associated with better outcomes., (© 2020. Springer Nature B.V.)

Objectives: Determine whether the Heart Rate Variability Dysfunction score, a novel age-normalized measure of autonomic nervous system dysregulation, is associated with the development of new or progressive multiple organ dysfunction syndrome or death in critically ill children., Design, Setting, and Patients: This was a retrospective, observational cohort study from 2012 to 2018. Patients admitted to the PICU with at least 12 hours of continuous heart rate data available from bedside monitors during the first 24 hours of admission were included in the analysis., Interventions: None., Measurements and Main Results: Heart rate variability was measured using the integer heart rate variability, which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The Heart Rate Variability Dysfunction score was derived from age-normalized values of integer heart rate variability and transformed, so that higher scores were indicative of lower integer heart rate variability and a proxy for worsening autonomic nervous system dysregulation. Heart Rate Variability Dysfunction score performance as a predictor of new or progressive multiple organ dysfunction syndrome and 28-day mortality were determined using the area under the receiver operating characteristic curve. Of the 7,223 patients who met inclusion criteria, 346 patients (4.8%) developed new or progressive multiple organ dysfunction syndrome, and 103 (1.4%) died by day 28. For every one-point increase in the median Heart Rate Variability Dysfunction score in the first 24 hours of admission, there was a 25% increase in the odds of new or progressive multiple organ dysfunction syndrome and a 51% increase in the odds of mortality. The median Heart Rate Variability Dysfunction score in the first 24 hours had an area under the receiver operating characteristic curve to discriminate new or progressive multiple organ dysfunction syndrome of 0.67 and to discriminate mortality of 0.80. These results were reproducible in a temporal validation cohort., Conclusions: The Heart Rate Variability Dysfunction score, an age-adjusted proxy for autonomic nervous system dysregulation derived from bedside monitor data is independently associated with new or progressive multiple organ dysfunction syndrome and mortality in PICU patients. The Heart Rate Variability Dysfunction score could potentially be used as a single continuous physiologic biomarker or as part of a multivariable prediction model to increase awareness of at-risk patients and augment clinical decision-making., Competing Interests: Dr. Badke’s institution received funding from Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Musculoskeletal injuries are common following trauma and variables that are associated with late femur fracture fixation are important to perioperative management. Furthermore, the association of late fracture fixation and multiple organ failure (MOF) is not well defined., Methods: We performed a retrospective cohort investigation from 2 academic trauma centers., Inclusion Criteria: age 18-89 years, injury severity score (ISS) >15, femoral shaft fracture requiring operative fixation, and admission to the intensive care unit >2 days. Admission physiology variables and abbreviated injury scale (AIS) scores were obtained. Lactate was collected as a marker of shock and was described as admission lactate (LacAdm) and as 24-hour time-weighted lactate (LacTW24h), which reflects an area under the curve and is considered a marker for the overall depth of shock. The primary aim was to evaluate clinical variables associated with late femur fracture fixation (defined as ≥24 hours after admission). A multivariable logistic regression model tested variables associated with late fixation and is reported by odds ratio (OR) with 95% confidence interval (CI). The secondary aim evaluated the association between late fixation and MOF, defined by the Denver MOF score. The summation of scores (on a scale from 0 to 3) from the cardiac, pulmonary, hepatic, and renal systems was calculated and MOF was confirmed if the total daily sum of the worst scores from each organ system was >3. We assessed the association between late fixation and MOF using a Cox proportional hazards model adjusted for confounding variables by inverse probability weighting (a propensity score method). A P value <.05 was considered statistically significant., Results: One hundred sixty of 279 (57.3%) patients received early fixation and 119 of 279 (42.7%) received late fixation. LacTW24h (OR = 1.66 per 1 mmol/L increase, 95% CI, 1.24-2.21; P < .001) and ISS (OR = 1.07 per 1-point increase, 95% CI, 1.03-1.10; P < .001) were associated with higher odds of late fixation. Late fixation was associated with a 3-fold increase in the odds of MOF (hazard ratio [HR] = 3.21, 95% CI, 1.48-7.00; P < .01)., Conclusions: In a cohort of multisystem trauma patients with femur fractures, greater injury severity and depth of shock, as measured by LacTW24h, were associated with late operative fixation. Late fixation was also associated with MOF. Strategies to reduce the burden of MOF in this population require further investigation.

Objectives: To determine clinician accuracy in the identification and prediction of multiple organ dysfunction syndrome., Design: Prospective cohort study., Setting: University of Michigan's C.S. Mott Children's Hospital PICU., Patients: Patients admitted to the PICU with an anticipated PICU length of stay greater than 48 hours., Interventions: None., Measurements and Main Results: For each patient, the clinical team (attending, fellow, resident/nurse practitioner) was surveyed regarding existing and anticipated organ dysfunction. The primary outcomes were clinicians' accuracy at identifying multiple organ dysfunction syndrome and predicting new or progressive multiple organ dysfunction syndrome, compared to the objective assessment of multiple organ dysfunction syndrome using Proulx criteria. We also measured sensitivity, specificity, negative and positive predictive values, and negative and positive likelihood ratios of clinician assessments. We tested for differences in accuracy by clinician type using chi-square tests. Clinicians rated their confidence in prediction on a 5-point Likert scale. There were 476 eligible PICU admissions, for whom 1,218 surveys were completed. Multiple organ dysfunction syndrome was present in 89 patients (18.7%) at enrollment, and new or progressive multiple organ dysfunction syndrome occurred in 39 (8.2%). Clinicians correctly identified multiple organ dysfunction syndrome with 79.9% accuracy and predicted additional organ dysfunction with 82.6% accuracy. However, the positive and negative likelihood ratios for new or progressive multiple organ dysfunction syndrome prediction were 3.0 and 0.7, respectively, indicating a weak relationship between the clinician prediction and development of new or progressive multiple organ dysfunction syndrome. The positive predictive value of new or progressive multiple organ dysfunction syndrome prediction was just 22.1%. We found no differences in accuracy by clinician type for either identification of multiple organ dysfunction syndrome (80.2% vs 78.2% vs 81.0%; p = 0.57) or prediction of new or progressive multiple organ dysfunction syndrome (84.8% vs 82.8% vs 80.3%; p = 0.26) for attendings, fellows, and residents/nurse practitioners, respectively. There was a weak correlation between the confidence and accuracy of prediction (pairwise correlation coefficient, 0.26; p < 0.001)., Conclusions: PICU clinicians correctly identified multiple organ dysfunction syndrome and predicted new or progressive multiple organ dysfunction syndrome with 80% accuracy. However, only 8% of patients developed new or progressive multiple organ dysfunction syndrome, so accuracy was largely due to true negative predictions. The positive predictive value for new or progressive multiple organ dysfunction syndrome prediction was just 22%. Accuracy did not differ by clinician type, but was correlated with self-rated confidence and was higher for negative predictions.

Background: Vitamin D deficiency is common in intensive care unit (ICU) patients (50 - 82%) and is associated with multi-organ dysfunction. Vitamin D deficiency alters pathways of glutamine metabolism in critical illness, but the impact of vitamin D status on glutamine levels is poorly characterised., Objectives: To assess the prevalence of vitamin D deficiency and its association with organ dysfunction and glutamine levels in a South African (SA) ICU., Methods: Records of 103 adult patients admitted to the Wits Donald Gordon Medical Centre ICU, Johannesburg, SA were retrospectively reviewed. 25-hydroxyvitamin D (25(OH)D) and glutamine levels were measured on admission. The association between admission vitamin D levels and glutamine levels, illness severity scores, organ support and outcomes was examined., Results: On ICU admission, 66% (68/103) of patients were vitamin D deficient (&lt;20 ng/mL) (95% confidence interval (CI) 56 - 75). Vitamin D deficiency was significantly associated with mechanical ventilation (40% v. 14%) (p=0.013) and a higher median sequential organ failure assessment (SOFA) score on admission (6 (interquartile range (IQR) 3 - 8) v. 4 (IQR 2 - 6)) (p=0.047) and on day 7 (5 (IQR 2 - 10) v. 2 (IQR 1 - 4)) (p=0.017). Median admission serum glutamine levels were 481 μmol/L, with 38% deficient (&lt;420 μmol/L) (95% CI 28 - 48). Vitamin D deficiency status on admission was not significantly associated with median admission glutamine levels (p=0.66)., Conclusions: Vitamin D deficiency is common in ICU patients in SA. Deficient patients were more severely ill and required more respiratory support. No significant relationship between deficiency and median glutamine levels was noted.

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.

Background: Plasma lactate has been used to predict the prognosis of critically ill children, but mortality risk scores appear to be more appealing, particularly in resource-limited countries., Objective: To assess the prognostic utility of lactate compared with the pediatric Sequential Organ Failure Assessment (pSOFA) score among the general pediatric intensive care unit (PICU) population., Methods: This was a prospective observational study including 78 children admitted to a tertiary-level PICU. Plasma lactate was measured upon admission and repeated 24h later. pSOFA score, Pediatric Risk of Mortality, and Pediatric Index of Mortality-2 (PIM2) were calculated. The primary outcome was 30-day mortality., Results: In total, 47.4% of patients had hyperlactatemia at admission. Among these, 20.5% had persistent hyperlactatemia. No significant difference in admission lactate level was found between survivors and nonsurvivors. The 24-h, peak, and average lactate levels were higher among nonsurvivors (P=0.005, 0.035, and 0.019, respectively). The 24-h lactate level and pSOFA score were independent predictors of mortality (adjusted odds ratio and 95% confidence interval=1.12 [1.02-1.23] and 1.80 [1.23-2.64], respectively]. The 24-h lactate level showed positive correlations with pSOFA, PRISM, and PIM2 (Spearman correlation coefficient=0.31, 0.23, 0.43; P=0.006, P=0.047, P<0.001, respectively). The 24-h lactate level had an area under the receiver operating characteristic curve (AUC) of 0.77 (P=0.013) for mortality prediction, while admission, peak, and average lactate level had an AUC of 0.69, 0.69, 0.71 (P=0.086, P=0.035, P=0.019), respectively. PIM2, PRISM, and pSOFA score had an AUC of 0.80, 0.78, 0.82 (P=0.001, P=0.001, and P<0.001), respectively. Combining 24-h lactate level with pSOFA demonstrated superior performance (AUC=0.88)., Conclusion: Both 24-h lactate level and pSOAF are useful for prediction of mortality. Incorporating the 24-h lactate level into the pSOFA Score achieved superior prognostic utility., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The Pediatric Logistic Organ Dysfunction-2 is a validated score that quantifies organ dysfunction severity and requires complex data collection that is time-consuming and subject to errors. We hypothesized that a computer algorithm that automatically collects and calculates the Pediatric Logistic Organ Dysfunction-2 (aPELOD-2) score would be valid, fast and at least as accurate as a manual approach (mPELOD-2)., Design: Retrospective cohort study., Setting: Single center tertiary medical and surgical pediatric critical care unit (Sainte-Justine Hospital, Montreal, Canada)., Patients: Critically ill children participating in four clinical studies between January 2013 and August 2018, a period during which mPELOD-2 data were manually collected., Interventions: None., Measurements and Main Results: The aPELOD-2 was calculated for all consecutive admissions between 2013 and 2018 (n = 5,279) and had a good survival discrimination with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.81-0.88). We also collected data from four single-center studies in which mPELOD-2 was calculated (n = 796, 57% medical, 43% surgical) and compared these measurements to those of the aPELOD-2. For those patients, median age was 15 months (interquartile range, 3-73 mo), median ICU stay was 5 days (interquartile range, 3-9 d), mortality was 3.9% (n = 28). The intraclass correlation coefficient between mPELOD-2 and aPELOD-2 was 0.75 (95% CI, 0.73-0.77). The Bland-Altman showed a bias of 1.9 (95% CI, 1.7-2) and limits of agreement of -3.1 (95% CI, -3.4 to -2.8) to 6.8 (95% CI, 6.5-7.2). The highest agreement (Cohen's Kappa) of the Pediatric Logistic Organ Dysfunction-2 components was noted for lactate level (0.88), invasive ventilation (0.86), and creatinine level (0.82) and the lowest for the Glasgow Coma Scale (0.52). The proportion of patients with multiple organ dysfunction syndrome was higher for aPELOD-2 (78%) than mPELOD-2 (72%; p = 0.002). The aPELOD-2 had a better survival discrimination (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.72-0.90) over mPELOD-2 (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.82; p = 0.01)., Conclusions: We successfully created a freely available automatic algorithm to calculate the Pediatric Logistic Organ Dysfunction-2 score that is less labor intensive and has better survival discrimination than the manual calculation. Use of an automated system could greatly facilitate integration of the Pediatric Logistic Organ Dysfunction-2 score at the bedside and within clinical decision support systems.

Background: Hemophagocytic lymphohistiocytosis (HLH) causes multiple organ dysfunction frequently leading to intensive care unit (ICU) referral and/or death. We report on a series of critically ill adult patients treated with a non-etoposide-based regimen including interleukin 1 antagonist anakinra, intravenous immunoglobulin (IVIG), and/or corticosteroids (CS) for HLH., Methods: Eight adult (≥18 years) ICU patients having received treatment with anakinra ± IVIG ± CS for HLH between March 2014 and March 2016 at a large tertiary care university hospital (Medical University of Vienna, Vienna, Austria) were retrospectively analyzed., Results: Eight patients (median age: 38 years; range: 20-58 years; 4 males and 4 females) received anakinra together with IVIG (n = 7) and/or high-dose CS (n = 5) for suspected reactive HLH (median H-score: 214; range: 171-288). Seven (88%) patients required vasopressors and invasive mechanical ventilation and 6 (75%) patients required renal replacement therapy (median Sequential Organ Failure Assessment [SOFA] score at HLH diagnosis: 9.5; range: 6-14). Six patients showed a significant decline in the SOFA score at 1 and 2 weeks following treatment initiation ( P = .03), and the remainder 2 patients experienced early death. Five patients survived to ICU discharge, 4 of them could further be discharged from hospital (hospital survival rate: 50%). No overt treatment-related toxicity was noted., Conclusion: Anakinra in combination with IVIG and/or CS resulted in a hospital survival rate of 50% in 8 critically ill adult patients with HLH despite a vast degree of organ dysfunction and the need for aggressive ICU treatment. Further research on non-etoposide-based treatment strategies for HLH in critically ill adults is warranted.

Fournier's gangrene is a rare, rapidly progressing, and life-threatening infection associated with necrotizing fasciitis in the perineal, genital, and/or lower abdominal regions. Septic shock and multiple organ dysfunction syndrome due to the condition are even rarer events. We describe the case of a 58-year-old man who visited the emergency department with severely painful swelling in the scrotal, perianal, and lower abdominal regions. Physical examination combined with computed tomography and clinical findings led to the diagnosis of Fournier's gangrene with septic shock and multiple organ dysfunction syndrome. Broad-spectrum antibiotics, fluid resuscitation, sedative administration, and several surgeries that included perineum reconstruction were performed successfully, and the patient fully recovered. Comprehensive, timely treatments are critical for treating Fournier's gangrene.

Objective: The condition of critically ill patients in the emergency department (ED) varies from moment to moment. The aims of this study are to quantify sequential organ failure assessment (SOFA) and changes in SOFA scores over time and determine its prognostic impact., Patients and Methods: This is a prospective observational cohort study. We included 269 patients consecutively admitted to the ICU from the ED over 18 months. The SOFA scores at ED admission (ED-SOFA) and ICU admission (ICU-SOFA) were obtained. Relative changes in SOFA scores were calculated as follows: Δ-SOFA=ICU-SOFA-ED-SOFA. Patients were divided into two groups depending on the Δ-SOFA score: (a) Δ-SOFA=0-1; and (b) Δ-SOFA more than or equal to 2., Results: The median ED-SOFA score was two points (interquartile range: 1-4.5) and the Δ-SOFA score was 2 points (interquartile range: 0-3). The Δ-SOFA score was more powerful (area under the curve: 0.81) than the ED-SOFA score (area under the curve: 0.75) in predicting hospital mortality. Sixteen (6%) patients had a Δ-SOFA score less than 0, 116 (43%) patients had a Δ-SOFA=0-1, and 137 (51%) patients had a Δ-SOFA of at least 2 points. The probability of being alive at hospital discharge was 51 and 86.5% in Δ-SOFA of at least 2 and Δ-SOFA=0-1 groups, respectively (P<0.001). Risk factors for an increase of two or more SOFA points were age, cirrhosis, a diagnosis of sepsis, and a prolonged ED stay., Conclusion: SOFA and changes in the SOFA score over time are potentially useful tools for risk stratification when applied to critically ill patients admitted to ICUs from the ED.

Purpose: Despite significant progress, challenges remain in the management of critically ill children, including early identification of infection and organ failure and robust early risk stratification to predict poor outcome. The Biomarkers of Acute Serious Illness in Children study aims to identify genetic and biological pathways underlying the development of critical illness in infections and organ failure and those leading to poor outcome (death or severe disability) in children requiring emergency intensive care., Participants: We recruited a prospective cohort of critically ill children undergoing emergency transport to four paediatric intensive care units (PICUs) in Southeast England between April 2014 and December 2016., Findings to Date: During the study period, 1017 patients were recruited by the regional PICU transport team, and blood and urine samples were obtained at/around first contact with the patient by the transport team. Consent for participation in the study was deferred until after PICU admission and 674 parents/carers were consented. Further samples (blood, urine, stool and throat swabs) were collected after consent. Samples were processed and stored for genomic, transcriptomic, proteomic and metabolomic analyses. Demographic, clinical and laboratory data at first contact, during PICU stay and at discharge, were collected, as were detailed data regarding infectious or non-infectious aetiology. In addition, 115 families have completed 12-month validated follow-up questionnaires to assess quality of life and child behaviour.The first phase of sample analyses (transcriptomic profiling) is currently in progress., Future Plans: Stored samples will be analysed using genomic, proteomic and metabolic profiling. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis of infection, identification of organ failure and risk stratification to predict poor outcome (death/severe disability)., Trial Registration Number: NCT03238040., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Intra-abdominal hypertension is classified as either primary or secondary - primary occurs due to intra-abdominal or retro-peritoneal pathophysiology, whereas secondary results in alterations in capillary fluid dynamics due to factors, such as massive fluid resuscitation and generalised inflammation. The renal and gastro-intestinal effects occur early in the progression of intra-abdominal hypertension, and may lead to poor patient outcomes if not identified. As a direct response to intra-abdominal hypertension, renal function is reduced with remarkable impairment from pressures of around 10 mmHg, oliguria developing at 15 mmHg and anuria developing at 30 mmHg. Intestinal micro-circulation is significantly reduced by up to 50% with intra-abdominal pressures as low as 15 mmHg. Mucosal and submucosal tissue hypo-perfusion causes considerable damage to the intestinal cells, potentially resulting in bacterial translocation, endotoxin release, sepsis and multiple organ failure. The critical care nurse plays an important role in the early identification of intra-abdominal hypertension however, without this essential knowledge base and comprehension of intra-abdominal hypertension, clinical signs and symptoms may go unnoticed or be misinterpreted as signs of other critical illnesses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Importance: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children., Objectives: To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection., Design, Setting, and Participants: This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison., Exposures: Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions., Main Outcomes and Measures: The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection., Results: In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course., Conclusions and Relevance: The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.

Introduction: There are significant unmet requirements for rapid differential diagnosis of infection in patients admitted to intensive care units. Serum levels of interleukin-6 (IL-6), procalcitonin (PCT), presepsin, and C-reactive protein (CRP) are measured in clinical practice; however, their clinical utility in patients with organ dysfunction has not been tested adequately. Thus, we investigated the diagnostic and prognostic value of IL-6, PCT, presepsin, and CRP in critically ill patients who had organ dysfunction with suspicion of infection., Methods: In 100 consecutive critically ill patients with organ dysfunction and suspected infection, serum levels of IL-6, PCT, presepsin, and CRP were measured upon suspicion of infection and serially every other day up to 7 days (cohort 1). The primary outcome variable was the presence of infections. The diagnostic value of IL-6 was further tested in cohort 2 (n = 72, case-control matched). The secondary outcome variables were the sequential organ failure assessment (SOFA) score, serum creatinine levels, and 28-day mortality., Results: Among the four biomarkers, serum IL-6 levels had the highest area under the curve (AUC) value of 0.824 (95% confidence interval [CI] 0.735-0.913) for diagnosing infection in critically ill patients with organ dysfunction and suspected infection in cohort 1 (AUC [95% CI] for the other biomarkers: PCT, 0.813 [0.714-0.911]; CRP, 0.764 [0.645-0.883]; presepsin, 0.681 [0.513-0.849]). In cohort 2, the sensitivity and specificity of IL-6 for diagnosing infection were 0.861 and 0.806, respectively. The presepsin levels were significantly correlated with the SOFA score and serum creatinine levels upon suspicion of infection (r > 0.5), especially serum creatinine levels in the patients without infection (r = 0.789). Serum IL-6 levels were significant predictors of 28-day mortality. The AUC value of serum IL-6 levels for 28-day mortality increased over time; the serum IL-6 levels on Day 7 had the highest AUC value of 0.883 (95% CI, 0.788-0.978) for 28-day mortality., Conclusion: Among serum IL-6, PCT, presepsin, and CRP levels, serum IL-6 levels had the highest diagnostic value for infection. They were also significant predictors of 28-day mortality. Hence, they may improve diagnosis of infection and prediction of 28-day mortality in critically ill patients with organ dysfunction.

The outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients has significantly improved over the past decade. Still, a significant number of patients require intensive care unit (ICU) management because of life-threatening complications. Literature from the 1990s reported extremely poor prognosis for critically ill allo-HSCT patients requiring ICU management. Recent data justify the use of ICU resources in hematologic patients. Yet, allo-HSCT remains an independent variable associated with mortality. However, outcomes in allo-HSCT patients have improved over time and many classic determinants of mortality have become irrelevant. The main actual prognostic factors are the need for mechanical ventilation, the presence of GvHD and the number of organ failures at ICU admission. Recently, the development of reduced-intensity conditioning regimens, early ICU admission and the increased use of noninvasive ventilation, combined with time effect and general advances in hematology, in allo-HSCT procedures and in ICU management have contributed to improve general outcome. A rational policy of ICU admission triage in these patients is very hard to define, as each decision for ICU admission is a case-by-case decision at patient bedside. The collaboration between hematologists and intensivists is crucial in this context.

Background: Real-time automated continuous sampling of electronic medical record data may expeditiously identify patients at risk for death and enable prompt life-saving interventions. We hypothesized that a real-time electronic medical record-based alert could identify hospitalized patients at risk for mortality., Methods: An automated alert was developed and implemented to continuously sample electronic medical record data and trigger when at least 2 of 4 systemic inflammatory response syndrome criteria plus at least one of 14 acute organ dysfunction parameters was detected. The systemic inflammatory response syndrome and organ dysfunction alert was applied in real time to 312,214 patients in 24 hospitals and analyzed in 2 phases: training and validation datasets., Results: In the training phase, 29,317 (18.8%) triggered the alert and 5.2% of such patients died, whereas only 0.2% without the alert died (unadjusted odds ratio 30.1; 95% confidence interval, 26.1-34.5; P < .0001). In the validation phase, the sensitivity, specificity, area under the curve, and positive and negative likelihood ratios for predicting mortality were 0.86, 0.82, 0.84, 4.9, and 0.16, respectively. Multivariate Cox-proportional hazard regression model revealed greater hospital mortality when the alert was triggered (adjusted hazards ratio 4.0; 95% confidence interval, 3.3-4.9; P < .0001). Triggering the alert was associated with additional hospitalization days (+3.0 days) and ventilator days (+1.6 days; P < .0001)., Conclusion: An automated alert system that continuously samples electronic medical record data can be implemented, has excellent test characteristics, and can assist in the real-time identification of hospitalized patients at risk for death., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose of Review: The current review summarizes different aspects of assessment of gastrointestinal function and provides a practical approach to management of adult patients with gastrointestinal dysfunction in the ICU., Recent Findings: Different ways to define gastrointestinal failure have been used in the past. Recently, the term 'acute gastrointestinal injury (AGI)' has been proposed to specifically describe gastrointestinal dysfunction as a part of multiple organ dysfunction syndrome. Possible pathophysiological mechanisms and different aspects in assessment of gastrointestinal function in adult ICU patients are presented. Currently, there is no single marker that could reliably describe gastrointestinal dysfunction. Therefore, monitoring and management is still based on complex assessment of different gastrointestinal symptoms and feeding intolerance, even though this approach includes a large amount of subjectivity. The possible role of biomarkers (citrulline, enterohormones, etc.) and additional parameters like intra-abdominal pressure remains to be clarified., Summary: Defining gastrointestinal failure remains challenging but broad consensus needs to be reached and disseminated soon to allow conduct of interventional studies. A systematic approach to management of gastrointestinal problems is recommended.

Objectives: Prediction models for ICU mortality rely heavily on physiologic variables that may not be available in large retrospective studies. An alternative approach when physiologic variables are absent stratifies mortality risk by acute organ failure classification., Design: Retrospective cohort study., Setting: Two large teaching hospitals in Boston, MA., Subjects: Ninety-two thousand eight hundred eighty-six patients aged 18 years old or older admitted between November 3, 1997, and February 25, 2011, who received critical care., Interventions: None., Measurements and Main Results: The derivation cohort consisted of 35,566 patients from Brigham and Women's Hospital, and the validation cohort comprised 57,320 patients from Massachusetts General Hospital. Acute organ failure was determined for each patient based on International Classification of Diseases, 9th Revision, Clinical Modification code combinations. The main outcome measure was 30-day mortality. A clinical prediction model was created based on a logistic regression model describing the risk of 30-day mortality as a function of age, medical versus surgical patient type, Deyo-Charlson index, sepsis, and type acute organ failure (respiratory, renal, hepatic, hematologic, metabolic, and neurologic) after ICU admission. We computed goodness-of fit statistics and c-statistics as measures of model calibration and 30-day mortality discrimination, respectively. Thirty-day mortality occurred in 5,228 of 35,566 patients (14.7%) assigned to the derivation cohort. The clinical prediction model was predictive for 30-day mortality. The c-statistic for the clinical prediction model was 0.7447 (95% CI, 0.74-0.75) in the derivation cohort and 0.7356 (95% CI, 0.73-0.74) in the validation cohort. For both the derivation and validation cohorts, the Hosmer-Lemeshow chi-square p values indicated good model fit. In a smaller cohort of 444 patients with Acute Physiologic and Chronic Health Evaluation II scores determined, differences in model discrimination of 30-day mortality between the clinical prediction model and Acute Physiologic and Chronic Health Evaluation II were not significant (chi-square=0.76; p=0.38)., Conclusions: An acute organ failure-based clinical prediction model shows good calibration and discrimination for 30-day mortality in the critically ill. The clinical prediction model compares favorably to Acute Physiologic and Chronic Health Evaluation II score in the prediction of 30-day mortality in the critically ill. This score may be useful for severity of illness risk adjustment in observational studies where physiologic data are unavailable.

Introduction: Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI., Methods: A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission., Results: One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI., Conclusions: For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ "11" on ICU day 1 should be considered an indicator of negative short-term outcome.

An immunocompetent young man became critically ill with multi-organ failure due to primary toxoplasmosis. Although treated successfully, he relapsed after 1 y with bilateral toxoplasmic chorioretinitis. Severe disseminated toxoplasmosis rarely occurs in immunocompetent patients and may reflect an increased risk of relapse. Secondary prophylaxis must be considered.

Introduction: C-reactive Protein (CRP) is used next to clinical scoring systems to recognize critically ill patients prone to develop complications on the Intensive Care Unit (ICU). The purpose of this study is to assess the predictive value of CRP as parameter for clinical deterioration and/or clinical decision making as ordering diagnostic procedures or performing (re)interventions. Also, we wanted to determine the value of CRP in early detection of surgical complications in the critically ill general surgical patient in the ICU and its interpretation in adjunct to a clinical scoring system, the Sequential Organ Failure Assessment Score., Materials and Methods: In our prospective observational study, 174 general surgical patients admitted into the Intensive Care Unit were included. We evaluated the Sequential Organ Failure Assessment Score (SOFA) and daily measured the C-reactive protein (CRP) concentrations. All events (diagnostic or therapeutic interventions) and surgical complications were registered. Then the relationship between SOFA score, CRP concentrations, events and complications were studied., Results: Each 10% increase in CRP resulted in a 3.5% increase in the odds of an event (odds ratio 1.035, 95% CI: 1.004-1.068; p = 0.028). However, an increase in CRP levels did not lead to a higher odds of complication (OR 0.983, 95% CI: 0.932-1.036; p = 0.52). When adjusting for the SOFA score the effect of CRP on the probability of a first event remained significant (OR 1.033, 95% CI: 1.001-1.065; p = 0.046), and again did not significantly affect the complication probability (OR 0.980, 95% CI: 0.929-1.035; p = 0.46)., Conclusions: An increase in C-reactive protein is a poor parameter for early detection of complications in the critically ill surgical patient in the ICU by means of diagnostic procedures or therapeutic (re)-interventions.

Background: The mortality of patients suffering from acute decompensated liver disease treated in the intensive care unit (ICU) varies between 50% and 100%. Previously published data suggest that liver-specific score systems are less accurate compared with the ICU-specific scoring systems acute physiology and chronic health evaluation II (APACHE II) and simplified organ failure assessment (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II) were superior to predict outcome compared with the Child-Pugh score., Methods: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. Eighty-seven adult patients with decompensated liver alcoholic cirrhosis were admitted from January 2007 to January 2010., Results: The patients were severely ill with median scores: SAPS II 60, SOFA (day 1) 11, APACHE II 31, and Child-Pugh 12. Receiver operating characteristic curves area under curve was 0.79 for APACHE II, 0.83 for SAPS II, and 0.79 for SOFA (day 1) compared with 0.59 for Child-Pugh. In patients only in need of mechanical ventilation, the 90-day mortality was 76%. If respiratory failure was further complicated by shock treated with vasopressor agents, the 90-day mortality increased to 89%. Ninety-day mortality for patients in need of mechanical ventilation, vasoactive medication, and renal replacement therapy because of acute kidney injury was 93%., Conclusion: APACHE II, SAPS II, and SOFA were better at predicting mortality than the Child-Pugh score. With three or more organ failures, the ICU mortality was > 90%. APACHE II > 30, SAPS II > 60, and SOFA at day 1 > 12 were all associated with a mortality of > 90%. Referral criteria of patients suffering from decompensated alcoholic liver disease should be revised., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: Sepsis is a leading cause of death in critically ill patients, and apoptosis plays a major role in the pathophysiology of sepsis. Elevated levels of circulating nucleosomes released by apoptotic cells have been detected in patients with severe sepsis and septic shock. The aim of this study was to evaluate the diagnostic/prognostic value of circulating nucleosomes in sepsis., Methods: Seventy-four newly admitted patients with an estimated length of stay in the intensive care unit of more than 48 h, were prospectively enrolled as cohort 1. The second independent cohort (cohort 2) consisted of 91 post-surgery patients. Patients receiving chemotherapy, those with AIDS, those on steroid treatment, and those undergoing transplants were excluded. Levels of circulating nucleosomes within 24h of admission in both cohorts, and for cohort 1 also on days 3, 5, and 7 and a last time-point of ICU discharge or at imminent death, were measured and analyzed for their capacity to predict sepsis. The severity of the inflammatory response and organ dysfunction were assessed by cytokine levels and sepsis scores., Results: Nucleosome levels on admission in septic patients were significantly higher than those in non-septic controls in both of the cohorts. The area under the receiver operating characteristic curve for admission nucleosome levels to differentiate septic patients from non-septic patients was 0.70 (95% confidence interval (CI) 0.51-0.88) in cohort 1, 0.66 (95% CI 0.55-0.79) in cohort 2, and 0.67 (95% CI 0.55-0.79) in all of the subjects. After multiple logistic regression analysis, circulating nucleosomes remained as an independent predictor of sepsis. Furthermore, the levels of circulating nucleosomes on admission were significantly correlated with the inflammatory response and organ dysfunction in sepsis. Meanwhile, a trend was observed for admission levels of circulating nucleosomes in non-survivors to be higher than those in survivors., Conclusions: The level of circulating nucleosomes in the serum has a predictive value for sepsis and organ dysfunction and may serve as a candidate biomarker for the diagnosis/prognosis of sepsis. Further studies are warranted to confirm the present findings., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The provision of therapeutic apheresis to children is a technically challenging procedure, requiring trained personnel and an understanding of the disease processes that leads to the need for apheresis. Most apheresis protocols are derived from studies in adult patients, even though most studies are of limited sample size. The focus of this review is to highlight the disease processes commonly treated with therapeutic apheresis in children, and to address the technical considerations pertinent to the provision of safe and effective apheresis in the pediatric setting., (© 2012 Wiley Periodicals, Inc.)

Background: ICU services represent a significant and increasing proportion of medical care. Population-based epidemiologic studies are essential to inform physicians and policymakers about current and future ICU demands. We aimed to determine the incidence of critical care syndromes, organ failures, and life-support interventions in a defined US suburban community with unrestricted access to critical care services., Methods: This population-based observational cohort from January 1 to December 31, 2006, in Olmsted County, Minnesota, included all consecutive critically ill adult residents admitted to the ICU. Main outcomes were incidence of critical care syndromes, life-support interventions, and organ failures as defined by standard criteria. Incidences are reported per 100,000 population (95% CIs) and were age adjusted to the 2006 US population., Results: A total of 1,707 ICU admissions were identified from 1,461 patients. Incidences of critical care syndromes were respiratory failure, 430 (390-470); acute kidney injury, 290 (257-323); severe sepsis, 286 (253-319); all-cause shock, 194 (167-221); acute lung injury, 86 (68-105); all-cause coma, 43 (30-55); and overt disseminated intravascular coagulation, 18 (10-26). Incidence of mechanical ventilation was invasive, 310 (276-344); noninvasive, 180 (154-206); vasopressors and inotropes, 183(155-208). Renal replacement therapy incidence was 96 (77-116). Of the cohort, 1,330 patients (91%) survived to hospital discharge. Short- and long-term survival decreased by the number of failing organs., Conclusions: In a suburban US community with high access to critical care services, cumulative incidences of critical care syndromes and life-support interventions were higher than previously reported. The results of this study have important implications for future planning of critical care delivery.

The aim was to demonstrate the performance of a modified version of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in medical and surgical patients with cancer. We performed an electronic retrospective review of databases. We included adult patients with cancer admitted into a 53-bed ICU over 28 months. We electronically calculated a modified SOFA (mSOFA) score at admission. A majority of the patients were admitted into the surgical ICU. Of 328 nonsurvivors, 85.1 per cent were medical patients and only 14.9 per cent surgical patients. The mean admission mSOFA scores for medical and surgical patients were 4.7 +/- 3.2 and 1.7 +/- 1.9, respectively. The overall area under the curve (AUC) of the mSOFA score was 0.84. The AUCs for medical and surgical patients were 0.72 and 0.78, respectively. Our results demonstrate that electronic assessment of mSOFA score has potential in resource allocation decisions as well as in critical care outreach programs.

We performed a retrospective cohort study to document the progression of organ dysfunction in 182 critically ill adult patients who subsequently met criteria for brain stem death (BSD). Patients were admitted to intensive care units (ICUs) of Mayo Medical Center, Rochester, MN, between January 1996 and December 2006. Daily sequential organ failure assessment (SOFA) scores were used to assess the degree of organ dysfunction. Serial SOFA scores were analyzed using analysis of variance (ANOVA). Mean (standard deviation, SD) SOFA score on the first ICU day was 8.9 (3.2). SOFA scores did not significantly change over the course of ICU stay. 67.6% of patients donated one or more organs after BSD was declared. The median time from ICU admission to declaration of BSD was 18.8 h (interquartile range 10.3-45.0), and in those who donated organs, the time from declaration of BSD to organ retrieval was 11.8 h (9.5-17.6). The fact that mean SOFA scores did not change significantly over time, even after BSD occurred, has implications for the timing of retrieval of organs for transplantation.

The aims of this study were to determine whether standard base excess (SBE) is a useful diagnostic tool for metabolic acidosis, whether metabolic acidosis is clinically relevant in daily evaluation of critically ill patients, and to identify the most robust acid-base determinants of SBE. Thirty-one critically ill patients were enrolled. Arterial blood samples were drawn at admission and 24 h later. SBE, as calculated by Van Slyke's (SBE VS) or Wooten's (SBE W) equations, accurately diagnosed metabolic acidosis (AUC = 0.867, 95%CI = 0.690-1.043 and AUC = 0.817, 95%CI = 0.634-0.999, respectively). SBE VS was weakly correlated with total SOFA (r = -0.454, P < 0.001) and was similar to SBE W (r = -0.482, P < 0.001). All acid-base variables were categorized as SBE VS <-2 mEq/L or SBE VS <-5 mEq/L. SBE VS <-2 mEq/L was better able to identify strong ion gap acidosis than SBE VS <-5 mEq/L; there were no significant differences regarding other variables. To demonstrate unmeasured anions, anion gap (AG) corrected for albumin (AG A) was superior to AG corrected for albumin and phosphate (AG A+P) when strong ion gap was used as the standard method. Mathematical modeling showed that albumin level, apparent strong ion difference, AG A, and lactate concentration explained SBE VS variations with an R(2) = 0.954. SBE VS with a cut-off value of <-2 mEq/L was the best tool to diagnose clinically relevant metabolic acidosis. To analyze the components of SBE VS shifts at the bedside, AG A, apparent strong ion difference, albumin level, and lactate concentration are easily measurable variables that best represent the partitioning of acid-base derangements.

Objective: To evaluate whether hypoalbuminemia on admission is a predictor of adverse outcome in critically ill children., Design: Retrospective medical record review., Setting: A 14-bed medical and surgical pediatric intensive care unit (PICU)., Participants: All patients admitted to the PICU from January 1, 1998, through December 31, 2000, under the care of the PICU team or trauma service and whose albumin level was measured were potential subjects. One hundred fifty-five patients were divided into 4 groups on the basis of age and appropriate albumin level for that age group. The groups of hypoalbuminemic patients were combined (hypoalbuminemia group) and compared with the combined group of patients with albumin levels above the reference cutoff (normal albumin level group)., Exposure: Serum albumin level., Main Outcome Measures: Length of PICU and hospital stays, receipt and length of ventilatory support, survival, pediatric risk of mortality score, mortality risk, and number of organ failures., Results: Controlling for mortality risk, the hypoalbuminemia group had a longer average stay in the PICU (8.08 vs 4.41 days; 95% confidence interval [CI] for difference, 1.02-6.32) and the hospital (11.36 vs 6.63 days; 95% CI for difference, 1.31-8.16) than did the normal albumin level group. The hypoalbuminemia group had a lower survival rate (odds ratio, 0.10; 95% CI, 0.02-0.46) and a higher number of organ failures (1.38 vs 0.65; 95% CI for difference, 0.40-1.04)., Conclusion: Admission hypoalbuminemia is a significant marker of morbidity and mortality in critically ill children.

The ability to accurately adjust for the severity of illness in outcome studies of critically ill patients is essential. Previous studies have showed that Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score can predict hospital mortality of critically ill patients. The effects of combining these two scores to predict hospital mortality of critically ill patients has not been evaluated. This cohort study evaluated the performance of combining the APACHE II score with SOFA score in predicting hospital mortality of critically ill patients. A total of 1311 consecutive adult patients admitted to a tertiary 22-bed multidisciplinary intensive care unit (ICU) in Western Australia were considered. The APACHE II, Admission SOFA, Delta SOFA and maximum SOFA score were all related to hospital survival in the univariate analyses. Combining Max SOFA (area under receiver operating characteristic curve 0.875 vs. 0.858, P = 0.014; Nagelkerke R2: 0.411 vs. 0.371; Brier Score: 0.086 vs. 0.090) or Delta SOFA score (area under receiver operating characteristic curve 0.874 vs. 0.858, P = 0.003; Nagelkerke R2: 0.412 vs. 0.371; Brier Score: 0.086 vs. 0.090) with the APACHE II score improved the discrimination and overall performance of the predictions when compared with using the APACHE II score alone, especially in the emergency ICU admissions. Combining Max SOFA or Delta SOFA score with the APACHE II score may improve the accuracy of risk adjustment in outcome studies of critically ill patients.

The critical care community has been using severity and organ failure assessment tools for over 2 decades. The major adult severity assessment models are Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score, and Mortality Probability Model. All three recent versions of these models perform well in predicting hospital mortality. Sequential Organ Failure Assessment score is the most used tool for assessment of multiple organ failure. These tools have been used extensively in clinical research involving critically ill patients and for benchmarking and the measurement of performance improvement. Their roles as clinical decision support tools at the bedside await future studies because of their unknown or poor performance at the individual patient level.

Objective: To compare the validity of the Multiple Organ Dysfunction Score (MODS), Sequential Organ Failure Assessment (SOFA), and Logistic Organ Dysfunction Score (LOD) for predicting ICU mortality of Thai critically ill patients., Material and Method: A retrospective study was made of prospective data collected between the 1st July 2004 and 31st March 2006 at Songklanagarind Hospital., Results: One thousand seven hundred and eighty two patients were enrolled in the present study. Two hundred and ninety three (16.4%) deaths were recorded in the ICU. The areas under the Receiver Operating Curves (A UC) for the prediction of ICU mortality the results were 0.861 for MODS, 0.879 for SOFA and 0.880 for LOD. The AUC of SOFA and LOD showed a statistical significance higher than the MODS score (p = 0.014 and p = 0.042, respectively). Of all the models, the neurological failure score showed the best correlation with ICU mortality., Conclusion: All three organ dysfunction scores satisfactorily predicted ICU mortality. The LOD and neurological failure had the best correlation with ICU outcome.

This study compared the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score with two organ failure scores in predicting hospital mortality of critically ill patients. A total of 1311 consecutive adult patients in a tertiary 22-bed multidisciplinary intensive care unit (ICU) in Western Australia were considered. The APACHE II score had a better calibration and discrimination than the Max Sequential Organ Failure Score (Max SOFA) (area under receiver operating characteristic (ROC) curve 0.858 vs 0.829), Admission SOFA (area under ROC 0.858 vs 0.791), and the first day or cumulative 5-day Royal Perth Hospital Intensive Care Unit (RPHICU) organ failure score (area under ROC 0.858 vs 0.822 and 0.819, respectively) in predicting hospital mortality. The APACHE II score predicted hospital mortality of critically ill patients better than the SOFA and RPHICU organ failure scores in our ICU.

Background: Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with post-cardiotomy cardiogenic shock or life-threatening respiratory failure. Acute renal failure following ECMO support has an extremely elevated mortality rate. This study examined the outcomes of patients treated with ECMO and characterized the association between mortality and RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage renal failure) classification., Methods: This retrospective study analysed the medical records of 46 critically ill patients-most had post-cardiotomy cardiogenic shock-treated by ECMO. Sixteen patients (34.8%) were treated with both ECMO and continuous renal replacement therapies., Results: The overall mortality rate was 65.2% (30/46). A progressive and significant increase (chi(2) for trend, P < 0.001) was observed for mortality based on RIFLE classification severity. The Hosmer and Lemeshow goodness-of-fit test demonstrated that the RIFLE category has a good fit. By applying the area under the receiver operating characteristic curve (AUROC), the RIFLE classification tool had good discriminative power (AUROC 0.868 +/- 0.068, P < 0.001). Cumulative survival rates at 6 months follow-up following hospital discharge differed significantly (P < 0.05) for non-ARF vs RIFLE-I and RIFLE-F, and RIFLE-R vs RIFLE-F., Conclusion: This investigation confirms that the prognosis for critically ill patients supported by ECMO is grave. The RIFLE category is a simple, reproducible and easily applied evaluation tool with good prognostic capability that might generate objective information for patient families and physicians and supplements the clinical judgment of prognosis.

Objective: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions., Design: Multiple-center, prospective epidemiologic study., Setting: Fourteen intensive care units in six countries., Patients: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period., Interventions: None., Measurements and Main Results: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension., Conclusions: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.

ICU-acquired limb and respiratory muscle weakness is a common, serious ICU syndrome, increasing in frequency with prolonged ICU stay and sepsis. A systematic approach facilitates precise localization of the problem within central or peripheral nervous system. Most cases relate to critical illness polyneuropathy or myopathy or a combination of both (critical illness neuromyopathy). Within the latter entity, the relative contribution of neuropathy versus myopathy varies considerably among affected patients. Muscle enzyme testing, electromyography-nerve conduction and muscle biopsy are valuable investigative tests. Nerve biopsy is less commonly needed, but is useful when vascultis is suspected.

The study on risk level reduction in specialized surgical clinics with the use of mathematical modeling for optimization medical-diagnostics tactics has been conducted by the author. 215 patients have been observed. The carried out analysis reflects FR of surgical operations as follows: general condition of the patients, severity of surgical pathology, complexity of surgical aggression. The modeling is designed using computer data processing and the system of Cartesian. Number risk assessment enabled to analyze surgical operation outcomes and optimize treatment-and-diagnostics tactics, reduce in number of operated patients in grave condition.

Cardiac troponin I (cTnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). Recent studies have shown that cTnI levels can also be elevated in patients without ACS, such as in sepsis and trauma patients, and that this is associated with an adverse prognosis. We have evaluated the clinical implications and prognostic significance of serum cTnI levels in noncardiac critically ill patients in a prospective observational study in a general medical intensive care unit at a tertiary-level hospital. A total of 108 consecutive patients without ACS or other cardiac disease was enrolled. Serum cTnI levels were measured on admission using enzyme-linked immunoabsorbant assay kits. Clinical laboratory parameters and outcome were compared between patients with elevated and normal cTnI levels. The prognostic significance of cTnI levels and the Acute Physiology And Chronic Health Evaluation (APACHE) II score was also analyzed. Forty-nine patients (45%) had elevated cTnI levels and 59 (55%) had normal levels. Compared with patients with normal cTnI levels, patients with elevated levels had a higher incidence of new failure of two or more organs, had a lower left ventricular ejection fraction during admission, were more likely to be associated with bacteremia, and had a higher intensive care unit mortality; they also had a significantly shorter survival over a 180-day follow up, before and after stratification by the APACHE II score. Multiple organ failure was the leading cause of mortality in patients with elevated cTnI levels. By multivariate analysis, elevated cTnI levels, a high APACHE II score, and underlying cancer were the three most important independent predictors for a shorter survival. Combination analysis showed a shorter survival in patients with a high APACHE II score plus elevated cTnI levels than in patients with a high APACHE II score or elevated cTnI levels alone. In conclusion, elevated serum cTnI levels is a risk factor for multiple organ failure and mortality in noncardiac critically ill patients, and the cTnI levels and APACHE II score have an additive effect in outcome prediction.

Objective: To identify potential future means of monitoring injury and repair in critical illness., Design: Review of the literature., Results: Critically ill patients are monitored extensively and intensively by such means as hemodynamics, laboratory values, and radiologic studies. In general, however, the goal of monitoring has been to measure the degree of injury and to prevent further injury, rather than to measure repair. Measures of repair have been limited to phenotypic end points such as return of organ function, as measured by blood chemistry. In this article, I examine how it may be possible in the future to monitor the progress of repair using genomic and proteomic biomarkers. These types of monitors would enable clinicians to control the healing environment using real time, rapid biomarkers, and sophisticated techniques to target therapy to the patient's current inflammatory state, taking into account the genetic makeup of the patient and his or her likely response to a given drug., Conclusions: The rapidly evolving sciences of genomics, proteomics, computational biology, and complex system theory can be used a) to model critical illness; b) to model adaptive and maladaptive responses to critical illness; c) to tailor treatments to create an ideal inflammatory environment for repair and regeneration, taking into account the individual genetic contribution; and d) to monitor the progress of repair. The major obstacles to reaching these goals are technological, and experience suggests that they will be overcome.