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.

To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. 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. 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. 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 Pao
 2/Fio
 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 Pao
 2/Fi
 o
 2 180 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). 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.

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Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

https://www.ajol.info/index.php/eaoj/article/download/77829/68247

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

Background Patients with severe traumatic injuries often present with coagulopathy and require massive transfusion. The risk of death from hemorrhagic shock increases in this population. To treat the coagulopathy of trauma, some have suggested early, aggressive correction using a 1:1 ratio of plasma to red blood cell (RBC) units. Methods We performed a retrospective chart review of 246 patients at a US Army combat support hospital, each of who received a massive transfusion (>/=10 units of RBCs in 24 hours). Three groups of patients were constructed according to the plasma to RBC ratio transfused during massive transfusion. Mortality rates and the cause of death were compared among groups. Results For the low ratio group the plasma to RBC median ratio was 1:8 (interquartile range, 0:12-1:5), for the medium ratio group, 1:2.5 (interquartile range, 1:3.0-1:2.3), and for the high ratio group, 1:1.4 (interquartile range, 1:1.7-1:1.2) (p Conclusions In patients with combat-related trauma requiring massive transfusion, a high 1:1.4 plasma to RBC ratio is independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage. For practical purposes, massive transfusion protocols should utilize a 1:1 ratio of plasma to RBCs for all patients who are hypocoagulable with traumatic injuries.

http://www.emergpa.net/wp/wp-content/uploads/2012/05/2007-Borgman-rato-pf-blood-products-transfused.pdf

The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving Massive Transfusions at a Combat Support Hospital

Intraoperatively administered, tranexamic acid (TA) does not reduce bleeding in total hip replacement (THR). Therefore, its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery. We investigated 40 patients undergoing THR in a prospective, randomized, double-blinded study. Twenty patients received TA given in two bolus doses of 10 mg/kg each, the first just before surgical incision and the second 3 h later. In addition, a continuous infusion of TA, 1.0 mg. kg(-1). h(-1) for 10 h, was given after the first bolus dose. The remaining 20 patients formed a control group. Both groups used preoperative autologous blood donation and intraoperative autotransfusion. Intraoperative bleeding was significantly less (P: = 0.001) in the TA group compared with the control group (630 +/- 220 mL vs 850 +/- 260 mL). Postoperative drainage bleeding was correspondingly less (P: = 0.001) (520 +/- 280 vs 920 +/- 410 mL). Up to 10 h postoperatively, plasma D-dimer concentration was halved in the TA group compared with the control group. One patient in each group had an ultrasound-verified late deep vein thrombosis. In conclusion, we found TA, administrated before surgical incision, to be efficient in reducing bleeding during THR. Implications: In a prospective, double-blinded study of 40 patients undergoing total hip replacement, the preoperative administration of tranexamic acid reduced bleeding by 35%, probably by decreasing induced fibrinolysis. Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study. (Less)

Tranexamic acid reduces blood loss in total hip replacement surgery.

Background:Coagulopathy is a contributor to and predictor of death in bleeding patients. Acidosis is known to be a predictor of worse outcome in trauma patients and to be a coexisting factor in coagulopathic patients, but it has not been studied if it is a causal factor in the development of coagulo

Acidosis impairs the coagulation: A thromboelastographic study.

The glycocalyx is a carbohydrate-rich layer that lines the luminal side of the vascular endothelium. Its soluble components exist in a dynamic equilibrium with the bloodstream and play an important role in maintaining endothelial layer integrity. However, the glycocalyx can be easily damaged and is extremely vulnerable to insults from a variety of sources, including inflammation, trauma, haemorrhagic shock, hypovolemia and ischaemia-reperfusion. Damage to the glycocalyx commonly precedes further damage to the vascular endothelium. Preclinical research has identified a number of different factors capable of protecting or regenerating the glycocalyx. Initial investigations suggest that plasma may convey protective and regenerative effects. However, it remains unclear which exact components or properties of plasma are responsible for this protective effect. Studies have reported protective effects for several plasma proteins individually, including antithrombin, orosomucoid and albumin; the latter of which may be of particular interest, due to the high levels of albumin present in plasma. A further possibility is that plasma is simply a better intravascular volume expander than other resuscitation fluids. It has also been proposed that the protective effects are mediated indirectly via plasma resuscitation-induced changes in gene expression. Further work is needed to determine the importance of specific plasma proteins or other factors for glycocalyx protection, particularly in a clinical setting.

/pdf/the-endothelial-glycocalyx-and-its-disruption-protection-and-4gq5gx6jyi.pdf

The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review

The influence of two different concentrations of iv naloxone infusion on the analgesia and adverse effects of epidural morphine were compared in a double-blind, placebo-controlled study. Forty-five patients undergoing gallbladder surgery were provided postoperative analgesia by 4 mg epidural morphine; they then received an iv infusion over a 12-h period consisting of either 5 micrograms X kg-1 X h-1 naloxone, 10 micrograms X kg-1 X h-1 naloxone, or saline. Pain relief was assessed by hourly visual analog scoring (VAS) and by direct questioning of the patient. Requirement of additional analgesia was noted. Respiratory frequency was monitored every 15 min and arterial blood gases were analyzed every 2 h for 24 h. Peak expiratory flow (PEF) was recorded 6 and 24 h postoperatively. Steady-state kinetics of naloxone were determined by a modified radioimmunoassay (RIA) method. All patients had good to excellent postoperative pain relief. Naloxone, 5 micrograms X kg-1 X h-1, did not appear to have any effect on epidural morphine analgesia. However, naloxone infusion at the rate of 10 micrograms X kg-1 X h-1 reduced the duration of analgesia by about 25%, and more frequent injections of epidural morphine were required to give effective analgesia. Complete reversal of analgesia was not seen in any patient. A dose-related stimulatory effect on respiratory frequency was noted in the groups receiving naloxone. PaCO2 values also were better in these groups as compared to values in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Naloxone Infusion on Analgesia and Respiratory Depression Following Epidural Morphine

Low molecular weight heparins (LMWH's) are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.

https://lucris.lub.lu.se/ws/files/3307114/7753794

Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

Ulf Schött

Papers

Tranexamic acid reduces blood loss in total hip replacement surgery.

Acidosis impairs the coagulation: A thromboelastographic study.

The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review

Influence of Naloxone Infusion on Analgesia and Respiratory Depression Following Epidural Morphine

Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.