Search

Objective: To test the hypothesis that early RBC transfusion is associated with duration of organ dysfunction in critically ill septic children., Design: Secondary analysis of a single-center prospective observational study. Multivariable negative binomial regression was used to determine relationships between RBC transfusion within 48 hours of sepsis onset and number of days in 14 with organ dysfunction, or with multiple organ dysfunction syndrome., Setting: A PICU at a quaternary care children's hospital., Patients: Children less than 18 years old with severe sepsis/septic shock by consensus criteria were included. Patients with RBC transfusion prior to sepsis onset and those on extracorporeal membrane oxygenation support within 48 hours of sepsis onset were excluded., Interventions: None., Measurements and Main Results: Ninety-four patients were included. Median age was 6 years (0-13 yr); 61% were male. Seventy-eight percentage had septic shock, and 41 (44%) were transfused RBC within 48 hours of sepsis onset (early RBC transfusion). On multivariable analyses, early RBC transfusion was independently associated with 44% greater organ dysfunction days (adjusted relative risk, 1.44 [1.04-2.]; p = 0.03), although risk differed by severity of illness (interaction p = 0.004) and by shock severity (interaction p = 0.04 for Vasoactive Inotrope Score and 0.03 for shock index). Relative risks for multiple organ dysfunction syndrome days varied by shock severity (interaction p = 0.008 for Vasoactive Inotrope Score and 0.01 for shock index). Risks associated with early RBC transfusion were highest for the children with the lowest shock severities., Conclusions: In agreement with previous studies, early RBC transfusion was independently associated with longer duration of organ dysfunction. Ours is among the first studies to document different transfusion-associated risks based on clinically available measures of shock severity, demonstrating greater transfusion-associated risks in children with less severe shock. Larger multicenter studies to verify these interaction effects are essential to plan much-needed RBC transfusion trials for critically ill septic children.

Purpose of Review: Sepsis remains one of the greatest global healthcare burdens, with an estimated greater mortality rate from sepsis in Africa. The increasing global financial, social, and political strain of the twenty-first century has created new challenges when trying to tackle this problem. We aim to compare the differences in the management of sepsis in three countries (Australia, the UK, and South Africa) that face distinctly different challenges. Recent Findings: The Surviving Sepsis Guidelines attempted to provide a good standard of care with bundles to help initiate early appropriate treatment. These bundles of care appear to improve outcomes when implemented early; however, data from Africa is lacking. There are several barriers to the implementation of guidelines, and resource-limited environments face additional challenges of staff shortages, lack of equipment and medication, and clinical pressure with increased strain capacity. Summary: Australia, the UK, and South Africa have both shared and different obstacles when addressing the burden of sepsis. Solutions for the African environment may differ from more well-resourced environments, and global cooperation and innovation will be necessary to tackle sepsis across these continents. There is an urgent need for data from the African continent to understand the burden of sepsis and to help plan and strategize potential solutions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic performance of the Pediatric Index of Mortality 2 (PIM2), ferritin, lactate, C-reactive protein (CRP), and leukocytes, alone and in combination, in pediatric patients with sepsis admitted to the pediatric intensive care unit (PICU). Methods: A retrospective study was conducted in a PICU in Brazil. All patients aged 6 months to 18 years admitted with a diagnosis of sepsis were eligible for inclusion. Those with ferritin and C-reactive protein measured within 48 h and lactate and leukocytes within 24 h of admission were included in the prognostic performance analysis. Results: Of 350 eligible patients with sepsis, 294 had undergone all measurements required for analysis and were included in the study. PIM2, ferritin, lactate, and CRP had good discriminatory power for mortality, with PIM2 and ferritin being superior to CRP. The cutoff values for PIM2 (> 14%), ferritin (> 135 ng/mL), lactate (> 1.7 mmol/L), and CRP (> 6.7 mg/mL) were associated with mortality. The combination of ferritin, lactate, and CRP had a positive predictive value of 43% for mortality, similar to that of PIM2 alone (38.6%). The combined use of the three biomarkers plus PIM2 increased the positive predictive value to 76% and accuracy to 0.945. Conclusions: PIM2, ferritin, lactate, and CRP alone showed good prognostic performance for mortality in pediatric patients older than 6 months with sepsis. When combined, they were able to predict death in three-fourths of the patients with sepsis. Total leukocyte count was not useful as a prognostic marker. [ABSTRACT FROM AUTHOR]

Objective: To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence. Study design: Retrospective study of patients > 1 month to < 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3–7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery. Results: Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI. Conclusions: The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. [ABSTRACT FROM AUTHOR]

Objective: To describe patient and hospital characteristics associated with in-hospital mortality, length of stay (LOS), and charges for children with severe sepsis or septic shock who often require specialized organ-supportive technology to enhance outcomes, availability of which might vary across hospitals. Design: Retrospective study among children hospitalized for severe sepsis or septic shock, using the 2012 Kids' Inpatient Database. Multivariate regression methods identified factors associated with mortality, LOS, and charges. Measurements and Main Results: Of an estimated 11 972 hospitalizations for pediatric severe sepsis or septic shock, most hospitalizations (85%) were to urban teaching hospitals. Hospitalizations were more frequent among neonates and older adolescents than other age groups. Mortality was 17%, average LOS was 24 days, and average hospital charges were US$314 950. Higher mortality was associated with neonates, cumulative organ dysfunction, more comorbidities, and cardiopulmonary resuscitation. Longer hospitalization and higher charges were associated with neonates, more comorbidities, higher illness severity, invasive medical technology, and urban hospitals. Conclusions: Efforts to mitigate the substantial in-hospital mortality and resource use observed in pediatric severe sepsis or septic shock should be age-specific and focused on the influence of comorbidities and organ dysfunction on outcomes. Future research should elucidate reasons for higher resource use at urban hospitals. [ABSTRACT FROM AUTHOR]

Critically ill, severely injured and high-risk surgical patients are vulnerable to secondary infections during hospitalization and after hospital discharge. Studies show that the mitochondrial function and oxidative metabolism of monocytes and macrophages are impaired during sepsis. Alternatively, treatment with microbe-derived ligands, such as monophosphoryl lipid A (MPLA), peptidoglycan, or β-glucan, that interact with toll-like receptors and other pattern recognition receptors on leukocytes induces a state of innate immune memory that confers broad-spectrum resistance to infection with common hospital-acquired pathogens. Priming of macrophages with MPLA, CPG oligodeoxynucleotides (CpG ODN), or β-glucan induces a macrophage metabolic phenotype characterized by mitochondrial biogenesis and increased oxidative metabolism in parallel with increased glycolysis, cell size and granularity, augmented phagocytosis, heightened respiratory burst functions, and more effective killing of microbes. The mitochondrion is a bioenergetic organelle that not only contributes to energy supply, biosynthesis, and cellular redox functions but serves as a platform for regulating innate immunological functions such as production of reactive oxygen species (ROS) and regulatory intermediates. This review will define current knowledge of leukocyte metabolic dysfunction during and after sepsis and trauma. We will further discuss therapeutic strategies that target leukocyte mitochondrial function and might have value in preventing or reversing sepsis- and trauma-induced immune dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process.Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate.Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified.Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effect of 'intermittent' central venous oxygen saturation (ScvO2) monitoring with 'continuous' ScvO2 monitoring on shock resolution and mortality in children with septic shock.Methods: Primary outcome was the achievement of therapeutic goals or shock resolution in the first 6 h. We randomly assigned children < 17 years' age with septic shock to 'intermittent ScvO2' or 'continuous ScvO2' groups. All children were subjected to subclavian/internal jugular line insertion and managed as per Surviving Sepsis Campaign Guidelines. To guide resuscitation, we used ScvO2 estimated at other clinical and laboratory parameters were monitored similarly in both groups.Results: We enrolled 75 and 77 children [median (IQR) age: 6 (1.5-10) years] in the 'intermittent' and 'continuous' groups, respectively. Baseline characteristics were comparable between the groups. When compared to the 'continuous' group, fewer children in the 'intermittent' group achieved shock resolution within first 6 h [19% vs. 36%; relative risk (RR) 0.51; 95% CI 0.29-0.89; risk difference - 18.0%; 95% CI - 32.0 to - 4.0]. The lower bound of confidence interval, however, crossed the pre-specified non-inferiority margin. There was no difference in the proportion of children attaining shock resolution within 24 h (63% vs. 69%; RR 0.86; 95% CI 0.68-1.08) or risk of mortality between the groups (47% vs. 43%; RR 1.06; 95% CI 0.74-1.51).Conclusions: Given that a greater proportion of children attained therapeutic end points in the first 6 h, continuous monitoring of ScvO2 should preferably be used to titrate therapy in the first few hours in children with septic shock. In the absence of such facility, intermittent monitoring of ScvO2 can be used to titrate therapy in these children, given the lack of difference in the proportion of patients achieving shock resolution at 24 h or in risk of mortality between the intermittent and continuous groups. [ABSTRACT FROM AUTHOR]

Continuous central venous oxygen saturation (ScvO SB 2 sb ) monitoring became standard of care in adult septic shock following Rivers' 2001 study on goal-directed therapy [[1]]. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. 10.1186/s13054-018-2052-7 11 Samransamruajkit R, Limprayoon K, Lertbunrian R, Uppala R, Samathakanee C, Jetanachai P, Thamsiri N. The utilization of the surviving sepsis campaign care bundles in the treatment of pediatric patients with severe sepsis or septic shock in a resource-limited environment: a prospective multicenter trial. [Extracted from the article]

Background: Sepsis is a common condition affecting the lives of infants and children worldwide. Although implementation of the surviving sepsis campaign (SSC) care bundles was once believed to be effective in reducing sepsis mortality rates, the approach has recently been questioned. Methods: The study was a prospective, interventional, multicenter trial. Infants and children aged 1 month to 15 years in seven different large academic centers in Thailand who had been diagnosed with severe sepsis or septic shock. They were given treatment based on the SSC care bundles. Results: A total of 519 children with severe sepsis or septic shock were enrolled in the study. Among these, 188 were assigned to the intervention group and 331 were recruited to the historical case–control group. There were no significant differences in the baseline clinical characteristics. The intervention group was administered a significantly higher fluid bolus than was the control group (28.3 ± 17.2 cc/kg vs. 17.7 ± 10.6 cc/kg; P = 0.02) with early vasopressor used (1.5 ± 0.7 h) compared to control group (7.4 ± 2.4 h, P < 0.05). More importantly, our sepsis mortality reduced significantly from 37% ± 20.7% during the preintervention period to 19.4% ± 14.3% during the postintervention period (P < 0.001). Conclusion: Our study demonstrated a significant reduction in sepsis mortality after the implementation of the SSC care bundles. Early diagnosis of the disease, optimum hemodynamic resuscitation, and timely antibiotic administration are the key elements of sepsis management. [ABSTRACT FROM AUTHOR]

Objectives The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). Methods This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Results Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively. Conclusions The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities. [ABSTRACT FROM AUTHOR]

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

Background: The identification of sepsis in children varies depending on the definition used. Our purpose was to compare clinical data and outcome of atypical sepsis, manifested as having sepsis but not fulfilling the criteria of systemic inflammatory response syndrome (SIRS-negative sepsis, SNS), in children based on the modified Angus criteria with those of sepsis (S) and severe sepsis (SS) based on the international consensus criteria.Methods: Pediatric departments in 11 regional city and county referral hospitals with emergency and intensive care settings in Huai'an serving for 843,000 children participated in a parallel multicenter prospective survey. Clinical data registry was used to recruit those who fulfilled the diagnostic criteria for pediatric sepsis from all admissions (n = 27,836) from 28 days to 15 years old, from September 1, 2010 to August 31, 2011.Results: A total of 1606 children met the criteria for pediatric sepsis and were divided into three groups: S, (n = 1377), SS (n = 153, including 32 septic shock), based on the consensus definition criteria, and SNS (n = 76) based on the modified Angus criteria. Most deaths (38/54, 70.3%) occurred within three days of admission. The SNS mainly occurred in infants and was associated with cardiopulmonary and neurologic dysfunction without satisfying the SIRS criteria.Conclusions: SNS differed from SS in that it predominantly affected infants and manifested with cardiopulmonary and neurologic dysfunction. There were no laboratory variables which were useful in identification of SNS, or predicting response to therapy or outcome. [ABSTRACT FROM AUTHOR]

Background and purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc. This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals. [ABSTRACT FROM AUTHOR]