Objectives: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality. Design: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not. Studies: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists. Main outcome measures: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure. Results: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0.006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P Conclusions: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.

/pdf/reduction-of-postoperative-mortality-and-morbidity-with-1uuz7uqkyl.pdf

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.

Biomarkers can be useful for identifying or ruling out sepsis, identifying patients who may benefit from specific therapies or assessing the response to therapy. We used an electronic search of the PubMed database using the key words "sepsis" and "biomarker" to identify clinical and experimental studies which evaluated a biomarker in sepsis. The search retrieved 3370 references covering 178 different biomarkers. Many biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been tested clinically, primarily as prognostic markers in sepsis; relatively few have been used for diagnosis. None has sufficient specificity or sensitivity to be routinely employed in clinical practice. PCT and CRP have been most widely used, but even these have limited ability to distinguish sepsis from other inflammatory conditions or to predict outcome.

/pdf/sepsis-biomarkers-a-review-4665vgzfzb.pdf

Sepsis biomarkers: a review

Hyaluronan fragments: an information-rich system.

Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included. We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

/pdf/biomarkers-of-sepsis-time-for-a-reappraisal-1os8yb6o8k.pdf

Biomarkers of sepsis: time for a reappraisal

Hyaluronan catabolism: a new metabolic pathway

Hyaluronan (hyaluronic acid) is normally rapidly cleared from the circulation by the endothelial cells in the liver sinuoids, which make up part of the reticulo-endothelial system (RES). An impaired RES function in severe infection and sepsis might therefore lead to elevated hyaluronan plasma levels. Thus, plasma concentrations of hyaluronan were analysed in 44 patients with severe infection at onset of disease and twice during the following 2-3 days. The patients were divided with respect to severity of disease; no septic shock (n = 29), group 1), septic shock survivors (n = 7, group 2), and septic shock non-survivors (n = 8, group 3). Patients in group 1 showed significantly higher values of plasma hyaluronan on day 1 (p less than 0.05) compared with controls. There was no significant difference on the following two sampling occasions. Patients with septic shock (groups 2 and 3) showed higher values than both controls (p less than 0.001) and patients with severe infection without septic shock (group 1, p less than 0.001) at all three sampling occasions. Non-survivors of septic shock (group 3) had significantly higher values than survivors (group 2), (p less than 0.01-0.05). Septic shock, and especially fatal septic shock, thus appears to be associated with elevated plasma hyaluronan concentrations. Possible mechanisms might be an increased release of the polysaccharide from the interstitial space to the bloodstream, or a decreased rate of clearance by liver endothelial cells. This question demands further study.

Elevated levels of plasma hyaluronan in septicaemia

Plasma fibronectin may be of critical importance for the septic patient through its proposed function as the major opsonin for macrophage clearance of circulating, noncellular debris. As a rule, critically ill, septic patients are depleted of fibronectin. In earlier uncontrolled studies, infusion of fibronectin-rich cryoprecipitate had resulted in improved renal and pulmonary functions and changes in peripheral hemodynamics. In this controlled study, 32 septic ICU patients (mean initial fibronectin level = 60% of normal) received cryoprecipitate or control infusions. Although the fibronectin level was significantly elevated to the normal range in the cryoprecipitate group, no effects were seen in hemodynamics, oxygen metabolism, or lung and kidney functions. Our results indicate that this form of fibronectin therapy does not influence the impaired organ function in septic shock.

Cryoprecipitate infusion fails to improve organ function in septic shock.

Background and methods Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver. Increased plasma hyaluronan concentrations have been found in patients with sepsis. We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis. Results Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 [SEM] to mean maximum concentrations of 964 +/- 255 micrograms/L [p less than .01]) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L). A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01). Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs. 285 +/- 43 micrograms/L [p less than .05]). Conclusions Experimental sepsis is associated with an increase in serum hyaluronan values. The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause. An association between high hyaluronan values and nonsurvival in sepsis is possible.

Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.

All of the eight contributions on the question of the theoretical basis of therapeutic use of cryoprecipitates as a source of fibronectin make the cardinal point that clinical efficacy of fibronectin has not been established in well-designed and controlled clinical trials. Accordingly, the Forum contributors do not support the therapeutic use of cryoprecipitates as a source of fibronectin, and the Editors are of the same opinion. It appears that such use should be confined to experimental protocols, that fibronectin should be preferentially prepared from plasma not suitable for Factor VIII production, and that caution should be exercised by avoiding use of fibronectin preparations that have not been heated to inactivate contaminating viruses. The last precaution leads us to prefer purified concentrates of fibronectin which can be heattreated prior to experimental use to assess the clinical efficacy of this interesting glycoprotein. Bern, March 1985

What Is the Theoretical Basis for the Therapeutic Use of Cryoprecipitates as a Source of Fibronectin

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate.

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