Pediatric Severe Sepsis Research Articles

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Introduction: The global burden of pediatric severe sepsis is not well characterized. Understanding sepsis prevalence, therapies used, and outcomes will help identify research priorities and design adequately powered clinical trials. Methods: We performed a point prevalence study with outcome data in 105 PICUs (26 countries, 6 continents). Results are from the first of 5 planned study days. All patients <18 yrs were screened for severe sepsis by 2 criteria: Research (consensus definitions) and Clinical (physician diagnosis). Data are summarized as medians (IQR) and proportions (95% CI). The prevalence of sepsis by each criterion was compared by McNemar's test. Results: Epidemiology: Of 1,244 patients screened, 127 were identified with severe sepsis. Overall prevalence was 10.2% (8.6, 12.0%), but differed by Research (9.2%, [7.6, 10.9]) v. Clinical (5.5% [4.3, 6.9]) criteria, p<0.001. The most common infection sites were respiratory (39%) and bloodstream (19%). Etiology was 28% bacterial, 21% viral, 9% fungal, and 42% culture-negative. Health care-associated infections accounted for 46% of cases with an identified pathogen. Therapy: At the time of the study, 61% of patients were treated with vasoactive infusions, 48% with corticosteroids, 70% with mechanical ventilation, 13% with renal replacement, 2% with ECMO. There was no difference in therapy by Research v. Clinical criteria. Outcome: PICU mortality for severe sepsis was 21% (14, 30%), PICU length of stay was 14 days (5-25), ventilator-free days were 20 (8-27), 80% had new or progressive multi-organ dysfunction, and 13% of survivors had worsening Pediatric Cerebral Performance Category (PCPC). There were no differences in morbidity or mortality by Research v. Clinical criteria. Conclusions: The global point prevalence of severe sepsis was 10.2%; one-third of these patients had worsened PCPC or died. Severe sepsis was less frequently identified by physicians compared to consensus definitions but groups identified by each criterion received comparable therapies and outcomes were similar.

Continuous Renal Replacement Therapy in Pediatric Severe Sepsis: A Propensity Score-Matched Prospective Multicenter Cohort Study in the PICU.

Continuous renal replacement therapy becomes available utilization for pediatric critically ill, but the impact of mortality rate in severe sepsis remains no consistent conclusion. The aim of the study is to assess the effect of continuous renal replacement therapy in pediatric patients with severe sepsis and the impact this therapy may have on their mortality. Propensity score-matched cohort study analyzing data prospectively collected by the PICUs over 2 years (2016-2018). Four PICUs of tertiary university children's hospital in China. The consecutive patients with severe sepsis admitted to study PICUs were enrolled from July 2016 to June 2018. The patients were divided into the continuous renal replacement therapy group and the conventional (noncontinuous renal replacement therapy) group. A total of 324 patients with severe sepsis were enrolled. The hospital mortality rate was 35.6% (64/180) in the continuous renal replacement therapy group and 47.9% (69/144) in the noncontinuous renal replacement therapy group. After propensity score adjustment, the hospital mortality rate was 21.3% (29/136) in the continuous renal replacement therapy group and 32.4% (44/136) in the noncontinuous renal replacement therapy group. In subgroup analysis, the relative risk of dying was 0.447 (95% CI, 0.208-0.961) only in patients complicated by acute respiratory distress syndrome (p = 0.037), but not in patients with shock, acute kidney injury, acute liver dysfunction, encephalopathy, and fluid overload greater than 10%. The mean duration of continuous renal replacement therapy was 45 hours (26-83 hr) with an ultrafiltration rate of 50 mL/kg/hr. The level of interleukin-6 was decreased, and the percent of natural killer cells (%) was improved in the continuous renal replacement therapy group compared with the noncontinuous renal replacement therapy group. Furthermore, continuous renal replacement therapy was an independently significant risk factor for hospital mortality in pediatric patients with severe sepsis, and the interval between continuous renal replacement therapy initiation and PICU admission was an independent risk factor for hospital mortality in patients receiving continuous renal replacement therapy. Continuous renal replacement therapy with an ultrafiltration rate of 50 mL/kg/hr decreases hospital mortality rate in pediatric severe sepsis, especially in patients with acute respiratory distress syndrome.

Trends in the Epidemiology of Pediatric Severe Sepsis*

In the past decade, guidelines have been developed for the early detection and management of severe sepsis in children and neonates. However, severe sepsis continues to be a significant U.S. healthcare problem, accounting for over 720,000 annual hospitalizations. Large-scale epidemiologic studies of severe sepsis continue to be limited, particularly in children. We present data from 1995, 2000, and 2005 in seven U.S. states, examining how case mix, outcome, and resource use for pediatric severe sepsis have changed over time. We constructed a database including all acute-care hospitalizations for children in the seven states. For each case, we extracted data on demographic characteristics; the principal diagnosis, up to six secondary diagnoses, and six procedures as classified by the International Classification of Diseases, 9th Revision, Clinical Modification codes; and in-hospital fatality. We identified patients with severe sepsis using International Classification of Diseases, 9th Revision, Clinical Modification codes for both infection and acute organ failure. Retrospective observational cohort dataset from seven U.S. states from 1995, 2000, and 2005. Children in the U.S. 0-19 years old. None. In 2005, 17,542 children were hospitalized with severe sepsis in the seven states; there was an 81% increase in pediatric severe sepsis cases since 1995 and a 45% increase since 2000. This corresponded to an increase in prevalence from 0.56 to 0.89 cases per 1,000 pediatric population. Between 1995 and 2005, the prevalence of severe sepsis in newborns more than doubled, from 4.5 to 9.7 cases per 1,000 births. The most common infecting organisms in all 3 years were Staphylococcus species. From 1995 to 2005, the case-fatality rate decreased from 10.3% to 8.9%. Case fatality associated with Staphylococcus aureus increased, whereas fatality associated with Streptococcus pneumoniae decreased by 75%. Nationally, there were 75,255 pediatric hospitalizations in 2005 involving severe sepsis, with an associated cost of $4.8 billion. Between 1995 and 2005, the prevalence of severe sepsis in U.S. children steadily rose, due to a significant increase in the prevalence of severe sepsis in newborns.

National estimates of emergency department visits for pediatric severe sepsis in the United States

Objective. We sought to determine the characteristics of children presenting to United States (US) Emergency Departments (ED) with severe sepsis.Study design. Cross-sectional analysis using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Using triage vital signs and ED diagnoses (defined by the International Classification of Diseases, Ninth Revision codes), we identified children <18 years old presenting with both infection (triage fever or ICD-9 infection) and organ dysfunction (triage hypotension or ICD-9 organ dysfunction).Results. Of 28.2 million pediatric patients presenting to US EDs each year, severe sepsis was present in 95,055 (0.34%; 95% CI: 0.29–0.39%). Fever and respiratory infection were the most common indicators of an infection. Hypotension and respiratory failure were the most common indicators of organ dysfunction. Most severe sepsis occurred in children ages 31 days–1 year old (32.1%). Most visits for pediatric severe sepsis occurred during winter months (37.4%), and only 11.1% of patients arrived at the ED by ambulance. Over half of severe sepsis cases were self-pay or insured by Medicaid. A large portion (44.1%) of pediatric severe sepsis ED visits occurred in the South census region. ED length of stay was over 3 h, and 16.5% were admitted to the hospital.Conclusion. Nearly 100,000 children annually present to US EDs with severe sepsis. The findings of this study highlight the unique characteristics of children treated in the ED for severe sepsis.

Interpretation of the international guidelines for management of severe sepsis and septic shock, 2012

The 2012 version of international guidelines for management of severe sepsis and septic shock got re-revised on the basis of the 2008 version.For pediatric severe sepsis, the 2012 version enforces initial resuscitation; develops detailed anti-infection measures; stresses isotonic crystalloid fluid resuscitation and the use of albumin, hetastarch is no longer recommended; reduces the value of early use of dopamine, and clears the use of corticosteroids indications and the use of blood products; mechanical ventilation is recommended to use lung protective ventilation strategy; standardizes sedation and analgesia applications; clears the level of blood glucose control; others include blood purification, nutrition, stress ulcer prevention recommendations. Key words: Severe sepsis; Septic shock; Guideline; Children,

Surviving Sepsis Campaign

Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

Management of children with sepsis and septic shock: a survey among pediatric intensivists of the Réseau Mère-Enfant de la Francophonie

BackgroundPediatric sepsis represents an important cause of mortality in pediatric intensive care units (PICU). Although adherence to published guidelines for the management of severe sepsis patients is known to lower mortality, actual adherence to these recommendations is low. The aim of this study was to describe the initial management of pediatric patients with severe sepsis, as well as to describe the main barriers to the adherence to current guidelines on management of these patients.MethodsA survey using a case scenario to assess the management of a child with severe sepsis was designed and sent out to all PICU medical directors of the 20 institutions member of the “Réseau Mère- Enfant de la Francophonie”. Participants were asked to describe in detail the usual management of these patients in their institution with regard to investigations, fluid and catecholamine management, intubation, and specific treatments. Participants were also asked to identify the main barriers to the application of the Surviving Sepsis Campaign guidelines in their center.ResultsTwelve PICU medical directors answered the survey. Only two elements of the severe sepsis bundles had a low stated compliance rate: “maintain adequate central venous pressure” and “glycemic control” had a stated compliance of 8% and 25% respectively. All other elements of the bundles had a reported compliance of over 90%. Furthermore, the most important barriers to the adherence to Surviving Sepsis Campaign guidelines were the unavailability of continuous central venous oxygen saturation (ScvO2) monitoring and the absence of a locally written protocol.ConclusionsIn this survey, pediatric intensivists reported high adherence to the current recommendations in the management of pediatric severe sepsis regarding antibiotic administration, rapid fluid resuscitation, and administration of catecholamines and steroids, if needed. Technical difficulties in obtaining continuous ScvO2 monitoring and absence of a locally written protocol were the main barriers to the uniform application of current guidelines. We believe that the development of locally written protocols and of specialized teams could add to the achievement of the goal that every child in sepsis should be treated according to the latest evidence to heighten his chances of survival.

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Introduction: Severe sepsis in children causes over 4,000 deaths & costs nearly $2B annually (Goldstein, 2005). Additionally, there exists significant variability in the recognition, evaluation & management of sepsis (Carcillo, 2006). 1st generation definitions & criteria for pediatric SIRS, sepsis(S), severe sepsis (SS), & septic shock (SSh) [2005 Sepsis] were published. SS was further parsed into cardiovascular (CV), respiratory (Resp) & Other (Oth). In 2009, an update further delineated pediatric practice parameters. As guidelines continue to be developed, the need for iterative derivation & validation is necessary to optimize efficiency. Hypothesis: We hypothesized that the efficacy of sepsis evaluation in the Pediatric Intensive Care Unit (PICU) can be quantified using the 2005 sepsis criteria. Methods: We reviewed all PICU admissions < 18 yrs old from Jul-Dec 2011 with length of stay > 3 days. Each SIRS event was analyzed independently. The 2005 criteria were used to define SIRS, S, & SS. Additionally, we defined Clinical Sepsis (CS) as treatment with IV antibiotics for > 2days. Multiple organ system failure (MOSF) was identified when 2+ SS domains were satisfied. Results: There were 384 evaluations in 150 patients & SIRS was identified in 239 (62%). SIRS eventuated in S & SS in 109(28%) & 140(37%) cases, respectively. Of the 140 cases of SS, CV, Resp & Oth accounted for 49%, 41%, & 10%, respectively. MOSF occurred in 47% of SS cases. CS occurred in 22% of evaluations. Of the 109 evaluations that met sepsis criteria, 56(51%) were treated for 2+ days. In contrast, 83 evaluations were treated for CS, 56 (67%) met sepsis criteria. Finally, WBC abnormality (vs temperature, HR & RR) was associated with the highest AUC-ROC (SEM) when S 0.68(0.027), MOSF 0.723(0.034) & CS 0.591(0.031) were outcomes. Conclusions: There is significant incoherence between the guidelines & clinical practice. Half of the evaluations meeting criteria were not treated. Conversely, one-third of those clinically treated did not meet criteria. Further efforts are underway to optimize the predictive value of the guidelines to treat those most at risk & minimize wasteful evaluations in PICU patients with non-infectious SIRS.

Biomarker response to drotrecogin alfa (activated) in children with severe sepsis

REsearching severe Sepsis and Organ dysfunction in children: A gLobal perspective (RESOLVE), a phase III trial of drotrecogin alfa (activated) in pediatric severe sepsis, examined biomarker changes in inflammation and coagulation. This report describes biomarker profiles in early severe sepsis and the pharmacodynamic assessment of drotrecogin alfa (activated) in RESOLVE. Serial measurements of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tissue necrosis factor-α, procalcitonin, D-dimer, and thrombin-antithrombin complex were performed at baseline and daily over the first five study days. Protein C levels were performed at baseline and at the end of the 96-hr study drug infusion. Analysis of variance-based log-transformed data compared the treatment groups for each measured variable. : One hundred four pediatric intensive care units in 18 countries. Four hundred seventy-seven children between 38 wks corrected gestational age and 17 yrs with sepsis-induced cardiovascular and respiratory dysfunction. Drotrecogin alfa (activated). Pharmacodynamic activity of drotrecogin alfa (activated) compared with placebo was observed with reduction of D-dimer on day 1 (p < .01) and thrombin-antithrombin complex on days 1-4 (p < .05). There were no significant changes by treatment in multiple cytokines or procalcitonin. In the overall population, a median protein C difference was not observed (p > .05) with drotrecogin alfa (activated) administration compared with placebo, although a difference (median percentage change from baseline) in favor of drotrecogin alfa (activated) was observed in patients >1 yr old (p = .0449). While children in the RESOLVE trial were similar to adults in that they showed a relationship between severity of coagulation and inflammation abnormalities and mortality, their pharmacodynamic response to drotrecogin alfa (activated) differed with respect to changes in protein C activity and systemic inflammation.

Incidence and risk factors for mortality in paediatric severe sepsis: results from the national paediatric intensive care registry in Japan

To assess the incidence, background, outcome and risk factors for death of severe sepsis in Japanese paediatric intensive care units (PICUs). A data analysis of a prospective, multicentre, 3-year case registry from nine medical-surgical Japanese PICUs. Children with severe sepsis, aged 0-15 years, who were consecutively admitted to the participating PICUs from 1 January 2007 to 31 December 2009 were enrolled. The incidence, background, causative pathogens or infective foci, outcome and risk factors for death caused by severe sepsis were analysed. One hundred forty-one cases were registered. After the exclusion of 14 patients because of incomplete data or inappropriate entry, 127 patients were eligible for the analysis. There were 60 boys and 67 girls, aged 23 [5-68] (median [IQR]) months and weighed 10 [5.5-16.5] kg. The incidence was 1.4 % of total PICU admissions. Sepsis was community-acquired in 35 %, PICU-acquired in 37 % and acquired in hospital general wards in 28 %. Methicillin-resistant Staphylococcus aureus was the most frequent pathogen. The crude 28-day mortality was 18.9 %, comparable to the mean PIM-2 predicted mortality (17.7 %). The mortality rate in patients with shock was significantly increased to 28 % compared to those without shock (5 %). The presences of existing haematological disorders (OR 8.97, 95 % CI, 1.56-51.60) and shock (OR 5.35, 1.04-27.44) were significant factors associated with mortality by multivariate analysis. The mortality from severe sepsis/septic shock in Japanese PICUs was ~19 %. Haematological disorders and presence of shock were associated with death.

Adjunctive corticosteroid therapy in pediatric severe sepsis: Observations from the RESOLVE study*

To assess whether corticosteroids, used as adjunctive therapy for pediatric severe sepsis, is associated with improved outcomes. Retrospective cohort study examining the clinical database derived from the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective, F1K-MC-EVBP) trial of activated protein C for pediatric severe sepsis. A total of 104 pediatric centers in 18 countries from which data were originally gathered. Children with severe sepsis (n = 477), requiring both vasoactive-inotropic infusions and mechanical ventilation. Within this cohort, 193 children received corticosteroids during their septic episode and 284 did not. None. Baseline summary characteristics demonstrated that children receiving or not receiving corticosteroids had similar demographics and disease severity as indicated by age, gender, mean Pediatric Risk of Mortality scores, and mean number of organ dysfunctions. Use of adjunctive corticosteroids increased during the F1K-MC-EVBP trial. Indications for corticosteroid prescription were therapeutic (89%, mostly shock) and prophylactic (13%). All cause 28-day mortality among children receiving and not receiving corticosteroids was 15.1% and 18.8%, respectively, p = .30. There was no difference in mean vasoactive-inotropic infusion days between the corticosteroid and no corticosteroid groups, 4.5 days vs. 4.3 days, respectively, p = .59. Similarly there was no difference in mean ventilator days between the corticosteroid and no corticosteroid groups, 8.3 days vs. 7.7 days, respectively, p = .38. Children with severe sepsis who received adjunctive corticosteroid therapy exhibited similar illness severity compared with those who did not. No definitive improvement in outcomes can be attributable to adjunctive corticosteroid therapy in the largest pediatric sepsis trial conducted to date.

Adjunctive corticosteroid therapy in pediatric severe sepsis: Many unsolved questions*

Adjunctive corticosteroid therapy in pediatric severe sepsis: Many unsolved questions*

EARLY GOAL-DIRECTED THERAPY IN TREATMENT OF PEDIATRIC SEPTIC SHOCK

In the whole world, around 29,000 children younger than 5 years die every day, and sepsis is the most common cause of death. Whereas in adult patients vasomotor paralysis represents the predominant cause of mortality, death in pediatric sepsis is associated with severe hypovolemia and low cardiac output. The purpose of this article was to review the recent evidence on early treatment of pediatric severe sepsis and septic shock. Although current American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines represent best practice, stronger evidences are lacking to confirm the components of these recommendations. Retrospective studies showed, at the same time, the positive effects arising from the utilization of American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines and the existing barriers to its implementation. And one randomized control trial paralleled the results observed in adult patients and revealed that early goal-directed therapy in children is one of the few therapeutic interventions that proved to be beneficial in septic shock treatment. Early goal-directed therapy in pediatric septic shock is a successful method to optimize and parameterize treatment, but there is still a long way to turn septic shock resuscitation simpler and more widely spread.

Readmission and Late Mortality After Pediatric Severe Sepsis

Pediatric severe sepsis remains a significant health problem with hospital mortality up to 10%. However, there is little information about later health outcomes or needs of survivors. Therefore, our goal was to evaluate the rates of and risk factors for rehospitalization and late mortality among survivors of pediatric severe sepsis. This was a population-based retrospective cohort study of survivors of pediatric severe sepsis (age 1 month to 18 years) in Washington State over the years 1990-2004. The sentinel admission was linked to subsequent death or episodes of hospitalization. The main outcome measures were readmission and/or late death after surviving an initial hospitalization with severe sepsis. Risk factors for readmission or death were identified by using a multivariate extended Cox model. Overall, 7183 children were admitted with severe sepsis, 6.8% of whom died during the sentinel admission or within 28 days of discharge, whereas an additional 6.5% died subsequently. Almost half (47%) of the survivors were readmitted at least once (median: 3) after a median of 3 months, and the majority of these readmissions were emergent. Sentinel admission factors independently associated with both adverse outcomes were neurologic or hematologic organ dysfunction, government-based insurance, as well as several coexisting health conditions. In addition, age less than 1 year at the time of sepsis and bloodstream and cardiovascular infections were highly associated with subsequent readmission. Late death occurred with similar frequency as early death associated with hospitalization with severe sepsis. Almost half of the pediatric patients suffering from an episode of severe sepsis had at least 1 subsequent hospitalization, two thirds of which were emergent or urgent. These data suggest that late outcomes after an episode of severe sepsis are poor and call for the evaluation of interventions designed to reduce later morbidity and mortality.

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

ObjectiveTo provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004.DesignModified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding.MethodsWe used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations.ResultsKey recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D).Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).ConclusionThere was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

A Retrospective Cohort Study of Prognostic Factors Associated with Outcome in Pediatric Severe Sepsis: What is the Role of Steroids?

A Retrospective Cohort Study of Prognostic Factors Associated with Outcome in Pediatric Severe Sepsis: What is the Role of Steroids?

A Retrospective Cohort Study of Prognostic Factors Associated with Outcome in Pediatric Severe Sepsis: What is the Role of Steroids?

A Retrospective Cohort Study of Prognostic Factors Associated with Outcome in Pediatric Severe Sepsis: What is the Role of Steroids?

A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: What is the role of steroids?*

Systemic corticosteroids remain controversial in the treatment of pediatric patients with severe sepsis. Recent studies in septic adults have shown decreased mortality with the use of hydrocortisone in patients with relative adrenal insufficiency. We conducted this large retrospective cohort study to further characterize severe sepsis in infants and children and correlates of outcome, including the use of steroids. Retrospective cohort study. The Pediatric Health Information System (PHIS), an administrative database of the Child Health Corporation of America (CHCA), was queried for inpatients 0-17 yrs of age with severe sepsis (defined here as an International Classification of Disease 9th edition code for infection with use of simultaneous mechanical ventilation and vasoactive infusions) from 2001 to 2002. In addition to demographic information, use of systemic corticosteroids (hydrocortisone, methylprednisolone, or dexamethasone) concurrent with the ventilatory and vasoactive support was collected. Data from PHIS. None. Patients (n = 6693) were identified at 27 PHIS-participating CHCA member hospitals. Overall mortality was 24%; univariate predictors of death included use of steroids (odds ratio [OR], 1.9; 95% confidence interval (CI), 1.7, 2.2), older age (e.g., 13-17 yrs vs. neonates; OR, 1.6; 95% CI, 1.3, 2.0), a hematologic-oncologic diagnosis (OR, 5.87; 95% CI, 4.19, 8.23), and moderate vs. high case volume (OR, 1.25; 95% CI, 1.09, 1.44). Age, hematologic-oncologic diagnosis, case volume, and use of steroids remained independent predictors of mortality in multivariable analysis. From this administrative database analysis, there is no evidence that steroids are associated with improved outcome in critically ill infants and children with sepsis. Although steroids may be given preferentially to more severely ill children, their use was associated with increased mortality. Clinicians should maintain equipoise on this topic pending prospective randomized clinical trials.