Flávia Ribeiro Machado

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

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 key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The authors were advised to follow the principles of the Grading of Recommendations 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 as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Results:Key recommendations and suggestions, listed by category, include: early quantitative 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 a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ⩽ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ⩽ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”‘ adrenal insufficiency (2C). Conclusions:Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Sepsis: a roadmap for future research

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.

TLR2, TLR4, CD14, CD11B, and CD11c expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock

ABSTRACT Bacterial recognition and induced cellular activation are fundamental for the host control of infection, yet the limit between protective and harmful response is still inexact. Forty-one patients were enrolled in this study: 14 with sepsis, 12 with severe sepsis, and 15 with septic shock. Seventeen healthy volunteers (HV) were included as control. The expression of TLR2, TLR4, CD14, CD11b, and CD11c was analyzed on monocytes surface in whole blood. sCD14 was measured in serum, and TNF-&agr;, IL-6, and IL-10 cytokine levels were measured in PBMC supernatants after LPS, IL-1&bgr;, and TNF-&agr; stimuli by ELISA. An increase in sCD14 and a decreased mCD14 were found in patients as compared with HV (P < 0.001). However, no differences in the expression of TLR2, TLR4, and CD11c were found among the groups. A trend toward differential expression of CD11b was observed, with higher values found in patients with sepsis as compared with HV. A negative regulation of the inflammatory cytokine production was observed in patients with severe sepsis and shock septic in relation to sepsis and HV, regardless of the stimulus. No significant difference in IL-10 production was found among the groups. In this study, we show that the inflammatory response is associated with the continuum of clinical manifestations of sepsis, with a strong inflammatory response in the early phase (sepsis) and a refractory picture in the late phases (severe sepsis and septic shock). Correlation between cell surface receptors and cytokine production after IL-1&bgr; and TNF-&agr; stimuli and the observation of a single and same standard response with the different stimulus suggest a pattern of immunology response that is not dependent only on the expression of the evaluated receptors and that is likely to have a regulation in the intracellular signaling pathways.

A Multicentre, Prospective Study to Evaluate Costs of Septic Patients in Brazilian Intensive Care Units

BackgroundSepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable.ObjectivesTo assess the standard direct costs of sepsis management in Brazilian intensive care units (ICUs) and to disclose factors that could affect those costs.MethodsThis multicentre observational cohort study was conducted in adult septic patients admitted to 21 mixed ICUs of private and public hospitals in Brazil from 1 October 2003 to 30 March 2004. Complete data for all patients admitted to the ICUs were obtained until their discharge or death. We collected only direct healthcare-related costs, defined as all costs related to the ICU stay.Enrolled patients were assessed daily in terms of cost-related expenditures such as hospital fees, operating room fees, gas therapy, physiotherapy, blood components transfusion, medications, renal replacement therapy, laboratory analysis and imaging. Standard unit costs (year 2006 values) were based on the Brazilian Medical Association (AMB) price index for medical procedures and the BRASINDICE price index for medications, solutions and hospital consumables. Medical resource utilization was also assessed daily using the Therapeutic Intervention Scoring System (TISS-28). Indirect costs were not included.ResultsWith a mean (standard deviation [SD]) age of 61.1 ± 19.2 years, 524 septic patients from 21 centres were included in this study. The overall hospital mortality rate was 43.8%, the mean Acute Physiology And Chronic Health Evaluation II (APACHE II) score was 22.3 ± 5.4, and the mean Sequential Organ Failure Assessment (SOFA) score at ICU admission was 7.5 ± 3.9.The median total cost of sepsis was

Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis

US9632 (interquartile range [IQR] 4583–18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost per patient was

Recognizing Sepsis as a Global Health Priority — A WHO Resolution

US934 (IQR 735–1170; 95% CI 897, 963). The median daily ICU cost per patient was significantly higher in non-survivors than in survivors, i.e.

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

US1094 (IQR 888–1341; 95% CI 1058, 1157) and

International study on microcirculatory shock occurrence in acutely ill patients

US826 (IQR 668–982; 95% CI 786, 854), respectively (p < 0.001). For patients admitted to public and private hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1, respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively (p = 0.006). Patients admitted to public and private hospitals had a similar length of stay of 10 (IQR 5–19) days versus 9 (IQR 4–16) days (p = 0.091), and the median total direct costs for public (

Generation of nitric oxide and reactive oxygen species by neutrophils and monocytes from septic patients and association with outcomes.

US9773; IQR 4643–19 221; 95% CI 8503, 10 818) versus private (

Positive fluid balance as a prognostic factor for mortality and acute kidney injury in severe sepsis and septic shock

US9490; IQR 4305–17 034; 95% CI 7610, 11 292) hospitals did not differ significantly (p = 0.37).ConclusionsThe present study provides the first economic analysis of direct costs of sepsis in Brazilian ICUs and reveals that the cost of sepsis treatment is high. Despite similar ICU management, there was a significant difference regarding patient outcome between private and public hospitals. Finally, the median daily costs of non-survivor patients were higher than survivors during ICU stay.