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. 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 h 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 h of the 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 h 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 (1B); 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 is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (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 Pa
o
2
/Fi
o
2
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 h) for patients
with
early ARDS and a Pa
o
2
/F
i
o
2
<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 h 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 h 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 5–10 min (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.
Emergency department (ED) overcrowding is a serious issue worldwide.
This study was done to evaluate the degree of overcrowding in local “teaching hospitals” in Beijing, and to ascertain the apparent ...root causes for the pervasive degree of overcrowding in these EDs.
This is a multicenter cross-sectional study. The studied population included all ED patients from 18 metropolitan teaching hospital EDs in Beijing for calendar years 2013 and 2014. Patient characteristics, and the primary reasons that these patients sought care in these EDs, are described.
The total numbers of annual emergency visits were 1,554,387 and 1,615,571 in 2013 and 2014, respectively. High acuity cases accounted for 4.6% and 5.5% of the total annual emergency visits in 2013 and 2014, respectively. The percentage of patients placed into “Observation” beds, which were created to accommodate patients deemed to have problems too complex to be treated in an inpatient bed, or to accommodate patients simply needing chronic care, was 11.9% and 13.1% in 2013 and 2014, respectively. The ED-boarded patients accounted for 2.71% and 2.6% of the total annual emergency visits in 2013 and 2014, respectively. The average waiting time to admit the ED-boarded patients was 37.1 h and 36.2 h in 2013 and 2014, respectively. Respiratory symptoms were the most common presenting complaints, and an upper respiratory infection was the most common ED diagnosis. Patients who had pneumonia or various manifestations of end-stage diseases, such as advanced dementia or multiple organ dysfunction, were the most common characteristics of patients who had stays in “Observation” units.
One principal reason for ED crowding in Beijing lies in the large numbers of patients who persist in the expectation of receiving ongoing care in the ED for minor illnesses. However, as is true in many nations, one of the other most important root causes of ED crowding is “access block,” the inability to promptly move patients deemed by emergency physicians to need inpatient care to an inpatient bed for that care. However, in our system, another challenge, not widely described as a contributor to crowding in other nations, is that doctors assigned to inpatient services have been empowered to refuse to admit patients perceived to have overly “complex” needs. Further, patients with multisystem illnesses or end-stage status, who need ongoing chronic care to manage activities of daily living, have begun to populate Beijing EDs in increasing numbers. This is an issue with various root causes.
A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients ...admitted to an intensivecare unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (⩾0.40 endotoxin activity EA units) or high (⩾0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.
Sepsis with acute organ dysfunction (severe sepsis) is common, frequently fatal, and associated with a significant national health/economic burden. In addition to standard care, investigators have ...focused on interrupting the inflammatory and anti-inflammatory cascade associated with this disease. Unfortunately, despite promising preclinical results, interventions directed at the inflammatory elements have not reduced the morbidity and mortality associated with this disease. Inflammation and coagulation are tightly linked. In fact, sepsis-associated coagulopathy is almost universal in patients with severe sepsis. Preclinical observations indicate that antithrombotic-targeted therapy has the potential to reduce morbidity and mortality in patients with this disease. Treatment with recombinant human activated protein C (drotrecogin α activated) was the first antithrombotic-targeted therapy to significantly reduce 28-day all-cause mortality in patients with severe sepsis. The pathophysiological and clinical significance of this evidence and the relationship of coagulation to inflammation are discussed, as are positive and negative results of clinical trials of antithrombotic therapy.
To assess neuropathology in individuals with restless legs syndrome (RLS).
A standard neuropathologic evaluation was performed on seven brains from individuals who had been diagnosed with RLS. The ...substantia nigra was examined in greater detail for iron staining and with immunohistochemistry for tyrosine hydroxylase and proteins involved in iron management. Five age-matched individuals with no neurologic history served as controls.
There were no histopathologic abnormalities unique to the RLS brains. Tyrosine hydroxylase staining in the major dopaminergic regions appeared normal in the RLS brains. Iron staining and H-ferritin staining was markedly decreased in the RLS substantia nigra. Although H-ferritin was minimally detected in the RLS brain, L-ferritin staining was strong. However, the cells staining for L-ferritin in RLS brains were morphologically distinct from those in the control brains. Transferrin receptor staining on neuromelanin-containing cells was decreased in the RLS brains compared to normal, whereas transferrin staining in these cells was increased.
RLS may not be rooted in pathologies associated with traditional neurodegenerative processes but may be a functional disorder resulting from impaired iron acquisition by the neuromelanin cells in RLS. The underlying mechanism may be a defect in regulation of the transferrin receptors.
This randomized, controlled trial involving patients with complicated intraabdominal infections and proper source control showed similar outcomes after fixed-duration antimicrobial therapy (4 days) ...and after a longer course (approximately 8 days).
Complicated intraabdominal infection continues to be a common problem worldwide. Approximately 300,000 cases of appendicitis occur each year in the United States,
1
and at least twice that many cases of non-appendiceal infection require management.
2
Morbidity ranges from 5% among patients evaluated in broad observational studies
2
–
4
to close to 50% in some cohorts, such as the elderly or critically ill.
5
,
6
Despite the diversity of specific processes in these infections, the basic tenets of management are similar: resuscitate patients who have the systemic inflammatory response syndrome (SIRS), control the source of contamination, remove most of the infected or necrotic material, . . .
Abstract Background It is well known that poor sepsis outcomes are related to delays in diagnosis and treatment. Objectives The aim of this study was to compare the mortality rate between two groups ...of patients, one group presenting before and one group presenting after implementation of the Surviving Sepsis Campaign (SSC) sepsis performance improvement bundles in the Emergency Department (ED). Methods This was a prospective study. The studied population included severe sepsis and septic shock patients entered in the SSC database who were admitted to the ED between June 2008 and December 2009. Patients were divided into two groups based on when they presented to the ED. Key treatment interventions, admission to the intensive care unit, and in-hospital mortality were compared. In addition, a survey was completed by the treating physicians to identify reasons for failures to comply with indicators. Results One hundred ninety-five (195) patients with severe sepsis and septic shock were enrolled in the study. Mortality was significantly higher at 44.8% in the baseline group (Group 1) compared to 31.6% in the group studied after the SSC protocol was instituted (Group 2) ( p < 0.05). Compliance with all elements of the sepsis resuscitation bundle was 1% in Group 1 and 9% in Group 2 ( p < 0.05). Compliance with all elements of the management bundle was 1% in Group 1 and 12.8% in Group 2. The most frequently reported reasons by physicians for failure to comply with the bundles were: “did not think it was needed” and “unsure of reason.” Conclusion The results revealed a significant drop in mortality after implementing the SSC protocol and sepsis performance improvement bundles in the ED. The barriers to implementing sepsis guidelines are knowledge, attitude, and behavioral barriers.
The objectives of this quality standard are to provide an implementation mechanism that will facilitate the reliable administration of prophylactic antimicrobial agents to patients undergoing ...operative procedures in which such a practice is judged to be beneficial and to provide a guideline that will help local hospital committees formulate policies and set up mechanisms for their implementation. Although standards in the medical literature spell out recommendations for specific procedures, agents, schedules, and doses, other reports document that these standards frequently are not followed in practice.
Septic shock is common and has unacceptably high morbidity, mortality, and associated cost with numerous failed attempts at developing effective therapies. Endotoxin, one of the most potent mediators ...of sepsis, is found in high levels in approximately 50% of patients with septic shock. Polymyxin B (PMX) hemoperfusion has been shown in numerous studies to successfully remove endotoxin and potentially improve outcomes. EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock) is a theragnostic trial (matching blood measurement to treatment capability) of PMX hemoperfusion in patients with septic shock and confirmed endotoxemia as measured by the endotoxin activity assay (EAA).
EUPHRATES is a pivotal regulatory trial that is multi-centered, placebo-controlled and blinded. The trial is being conducted in fifty ICUs in the United States and Canada and is powered to enroll 360 patients. Patients with persistent septic shock despite adequate fluid resuscitation on vasopressors for more than 2 and less than 30 hours are eligible for measurement of the EAA. Those with EAA ≥0.60 are eligible to be randomized to treatment with two sessions of PMX hemoperfusion 24 hours apart. The primary endpoint for the trial is 28-day all-cause mortality.
Unique features of the trial include absence of systemic inflammatory response (SIRS) criteria as a requirement for inclusion, use of the EAA to confirm endotoxemia as a requisite for treatment, and use of a detailed "façade" hemoperfusion event as a blinding mechanism. The outcomes of the second interim analysis included a resizing of the trial to 650 patients and the addition of an exclusion criterion of subjects with multiple organ dysfunction score (MODS) ≤ 9. Results are anticipated in 2016.
Clinicaltrials.gov identifier: NCT01046669. Registered: January 8, 2010.
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