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New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

ABSTRACT: OBJECTIVES:To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. DESIGN:Secondary analysis of a prospective, cross-sectional, point prevalence study. SETTING:International, multicenter PICUs. PATIENTS:Pediatric patients with severe sepsis identified on five separate days over a 1-year period. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). CONCLUSIONS:Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

SUBMITTER: Lin JC

PROVIDER: S-EPMC7261134 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

Lin John C JC Spinella Philip C PC Fitzgerald Julie C JC Tucci Marisa M Bush Jenny L JL Nadkarni Vinay M VM Thomas Neal J NJ Weiss Scott L SL

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20170101 1

<h4>Objectives</h4>To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis.<h4>Design</h4>Secondary analysis of a prospective, cross-sectional, point prevalence study.<h4>Setting</h4>International, multicenter PICUs.<h4>Patients</h4>Pediatric patients with severe sepsis identified on five separate days over a 1-year period.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>Of 567 patients from 1 ...[more]

PMID: 28060151

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Project description:IntroductionSepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain.MethodsWe conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.ResultsA total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.ConclusionsWe found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.

Project description:Objective: To evaluate serial ferritin levels measured in the initial 72 h of admission as a biomarker for new and progressive multi organ dysfunction syndrome (NPMODS) and mortality (unfavorable outcomes) in critically ill children with sepsis due to tropical infections. Material and Methods: In this prospective observational study from a tertiary care teaching hospital in India, children 3 month to 12 years with a diagnosis of acute febrile illness and any two features suggesting tropical infections [cytopenia (platelet count <1,00,000/cu.mm, total leucocyte count <4,000/cu.mm), hepatomegaly and/or splenomegaly, lymphadenopathy, systemic signs (rash, edema), respiratory distress, and encephalopathy not accounted by localized infection] were eligible for inclusion. Children with known or suspected disorder of iron metabolism were excluded. Primary outcome was to determine the association of serial ferritin levels with mortality and NPMODS. Secondary outcomes included estimation of the prevalence of hyperferritinemia and comparison of risk prediction scores with serial ferritin measurement in predicting unfavorable outcomes. Measurements and Main Results: In the 202 children enrolled, diagnosis could be established in 133 (65.8%) children. Scrub typhus and dengue were the most common infections. Median (IQR) ferritin measured at admission (n = 183) and on day 3 (n = 120) of hospital stay were 798 (378, 3,205) μg/L and 429 (213,680) μg/L, respectively. Majority (n = 180, 89.1%) had MODS at admission defined as per International pediatric sepsis consensus conference. NPMODS occurred in 47 (23.3%) children of whom 37 (18.3%) died. Children with three or less organ dysfunctions had lower mortality. Neither admission ferritin values nor the percentage change over 72 h was different between children with favorable and unfavorable outcomes. Pediatric Risk of Mortality (PRISM-III) and daily Pediatric Logistic Organ Dysfunction score (dPELOD2 score) were significantly different in those with unfavorable outcomes. Admission ferritin levels and percentage change in 72 h had poor discriminatory power for mortality with AUC of 0.53 (0.53, 0.67) and 0.50 (0.50, 0.64), respectively. dPELOD2 had the best discriminatory power for mortality with AUC of 0.89 (0.89, 0.95). Conclusions: Serial ferritin estimation predicted neither organ dysfunction nor mortality in pediatric sepsis with tropical infections. dPELOD-2 and PRISM-III predicted unfavorable outcomes better than ferritin. The current diagnostic criteria for MODS overestimated organ dysfunctions in tropical infections and hence may need modification with further validation in this epidemiological cohort.

Project description:ObjectivesTo evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis.DesignRetrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764).SettingOne hundred and four pediatric centers in 18 countries.SubjectsChildren with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384).InterventionsNone.Measurements and main resultsPoor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9.ConclusionsIn this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an individual's clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.

Project description:OBJECTIVES:Limited data exist about the timing and significance of mitochondrial alterations in children with sepsis. We therefore sought to determine if alterations in mitochondrial respiration and content within circulating peripheral blood mononuclear cells were associated with organ dysfunction in pediatric sepsis. DESIGN:Prospective observational study SETTING:: Single academic PICU. PATIENTS:One-hundred sixty-seven children with sepsis/septic shock and 19 PICU controls without sepsis, infection, or organ dysfunction. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Mitochondrial respiration and content were measured in peripheral blood mononuclear cells on days 1-2, 3-5, and 8-14 after sepsis recognition or once for controls. Severity and duration of organ dysfunction were determined using the Pediatric Logistic Organ Dysfunction score and organ failure-free days through day 28. Day 1-2 maximal uncoupled respiration (9.7?±?7.7 vs 13.7?±?4.1 pmol O2/s/10 cells; p = 0.02) and spare respiratory capacity (an index of bioenergetic reserve: 6.2?±?4.3 vs 9.6?±?3.1; p = 0.005) were lower in sepsis than controls. Mitochondrial content, measured by mitochondrial DNA/nuclear DNA, was higher in sepsis on day 1-2 than controls (p = 0.04) and increased in sepsis patients who had improving spare respiratory capacity over time (p = 0.005). Mitochondrial respiration and content were not associated with day 1-2 Pediatric Logistic Organ Dysfunction score, but low spare respiratory capacity was associated with higher Pediatric Logistic Organ Dysfunction score on day 3-5. Persistently low spare respiratory capacity was predictive of residual organ dysfunction on day 14 (area under the receiver operating characteristic, 0.72; 95% CI, 0.61-0.84) and trended toward fewer organ failure-free days although day 28 (? coefficient, -0.64; 95% CI, -1.35 to 0.06; p = 0.08). CONCLUSIONS:Mitochondrial respiration was acutely decreased in peripheral blood mononuclear cells in pediatric sepsis despite an increase in mitochondrial content. Over time, a rise in mitochondrial DNA tracked with improved respiration. Although initial mitochondrial alterations in peripheral blood mononuclear cells were unrelated to organ dysfunction, persistently low respiration was associated with slower recovery from organ dysfunction.

Project description:BackgroundSepsis remains a complex medical problem and a major challenge in healthcare. Diagnostics and outcome predictions are focused on physiological parameters with less consideration given to patients' medical background. Given the aging population, not only are diseases becoming increasingly prevalent but occur more frequently in combinations ("multimorbidity"). We hypothesized the existence of patient subgroups in critical care with distinct multimorbidity states. We further hypothesize that certain multimorbidity states associate with higher rates of organ failure, sepsis, and mortality co-occurring with these clinical problems.MethodsWe analyzed 36,390 patients from the open source Medical Information Mart for Intensive Care III (MIMIC III) dataset. Morbidities were defined based on Elixhauser categories, a well-established scheme distinguishing 30 classes of chronic diseases. We used latent class analysis to identify distinct patient subgroups based on demographics, admission type, and morbidity compositions and compared the prevalence of organ dysfunction, sepsis, and inpatient mortality for each subgroup.ResultsWe identified six clinically distinct multimorbidity subgroups labeled based on their dominant Elixhauser disease classes. The "cardiopulmonary" and "cardiac" subgroups consisted of older patients with a high prevalence of cardiopulmonary conditions and constituted 6.1% and 26.4% of study cohort respectively. The "young" subgroup included 23.5% of the cohort composed of young and healthy patients. The "hepatic/addiction" subgroup, constituting 9.8% of the cohort, consisted of middle-aged patients (mean age of 52.25, 95% CI 51.85-52.65) with the high rates of depression (20.1%), alcohol abuse (47.75%), drug abuse (18.2%), and liver failure (67%). The "complicated diabetics" and "uncomplicated diabetics" subgroups constituted 9.4% and 24.8% of the study cohort respectively. The complicated diabetics subgroup demonstrated higher rates of end-organ complications (88.3% prevalence of renal failure). Rates of organ dysfunction and sepsis ranged 19.6-69% and 12.5-46.7% respectively in the six subgroups. Mortality co-occurring with organ dysfunction and sepsis ranges was 8.4-23.8% and 11.7-27.4% respectively. These adverse outcomes were most prevalent in the hepatic/addiction subgroup.ConclusionWe identify distinct multimorbidity states that associate with relatively higher prevalence of organ dysfunction, sepsis, and co-occurring mortality. The findings promote the incorporation of multimorbidity in healthcare models and the shift away from the current single-disease paradigm in clinical practice, training, and trial design.

Dataset Information

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

Publications

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

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