Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Background The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote “best practices” and to improve patient outcomes. Objective 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. Participants Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001–2006). Methods The Pubmed/MEDLINE literature database (1966–2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. Results The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%–3% in previously healthy, and 7%– 10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. Conclusion The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill ≤2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3–6.0 L/min/m2.

We have observed an unexpected increase in mortality coincident with CPOE implementation. Although CPOE technology holds great promise as a tool to reduce human error during health care delivery, our unanticipated finding suggests that when implementing CPOE systems, institutions should continue to evaluate mortality effects, in addition to medication error rates, for children who are dependent on time-sensitive therapies.

Despite extensive research into the etiology and treatment of severe sepsis, little is known about its epidemiology in children. We sought to determine the age- and sex-adjusted incidence, outcome, and associated hospital costs of severe sepsis in United States children using 1995 hospital discharge and population data from seven states (24% of the United States population). Of 1,586,253 hospitalizations in children who were 19 years old or less, 9,675 met International Classification of Diseases, 9th revision, clinical modification-based severe sepsis criteria or 42,364 cases of pediatric severe sepsis per year nationally (0.56 cases per 1,000 population per year). The incidence was the highest in infants (5.16 per 1,000), fell dramatically in older children (0.20 per 1,000 in 10 to 14 year olds), and was 15% higher in boys than in girls (0.60 versus 0.52 per 1,000, p < 0.001). Hospital mortality was 10.3%, or 4,383 deaths nationally (6.2 per 100,000 population). Half of the cases had underlying disease (49.0%), and over one-fifth (22.9%) were low-birth-weight newborns. Respiratory infections (37%) and primary bacteremia (25%) were the most common infections. The mean length of stay and cost were 31 days and $40,600, respectively. Estimated annual total costs were 1.97 billion US dollars nationally. Severe sepsis is a significant health problem in children and is associated with the use of extensive healthcare resources. Infants are at highest risk, especially those with a low birth weight.

Objective To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome (MAS). Despite equivocal results in sepsis trials, anakinra is effective in treating MAS, a similar entity with fever, disseminated intravascular coagulation (DIC), hepatobiliary dysfunction (HBD), cytopenias, and hyperferritinemia. Hence, sepsis patients with MAS features may benefit from IL-1 receptor blockade. Design Re-analysis of de-identified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis (Opal, et. al. Crit Care Med. 1997 Jul;25(7):1115–24). Setting Multi-center study recruiting through 91 centers from 11 countries in Europe and North America. Participants Sepsis patients with MODS and/or shock (original study) were re-grouped based on presence or absence of concurrent HBD and DIC as features of MAS (HBD/DIC group). The “non-HBD/DIC” group included patients with only HBD, only DIC or neither. Intervention Treatment with anakinra or placebo. Main Outcome(s) and Measure(s) 28-day mortality. Statistical analysis descriptive statistics, chi-square, ANOVA, logistic and Cox regression. Results Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent HBD/DIC was noted in 43 patients (5.6% of total, ages 18–75; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-HBD/DIC patients (71.4% vs. 70.8%, p=.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in HBD/DIC patients (65.4% anakinra vs. 35.3% placebo), with HR for death 0.28 (0.11–0.71, p = 0.0071) for the treatment group in Cox regression. Conclusions and Relevance In this subgroup analysis, IL-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent HBD/DIC. A prospective randomized trial using features of MAS for mortality risk stratification should be undertaken to confirm the role of IL-1 blockage.