Severe sepsis induces Disseminated Intravascular Coagulation (DIG) and organ dysfunction. 50 % of the septic patients have thrombocytopenia related to thrombin generation, which activates platelets, and inflammatory cytokines ( IL-1,TNF) which activate leucocytes and endothelial cells increasing platelet adhesion. We investigate ex vivo the platelets aggregability, adhesiveness and vascular growth factor release of patients with severe sepsis (n=l 1) and septic shock (n=10) at Day 0, 3 and 7. ADP, collagen and thrombin (TRAP) induced platelet rich plasma aggregation were impaired in all the patients by comparison to 10 normal subjects, even in absence of thrombocytopenia. The slope and the percentage of aggregation were decreased after collagen and TRAP but not ADP. Whole blood flow cylometry confirms the aggregation defect. GPIIbllla activation, stained by PAC-1 expression and fibrinogen- FITC fixation, was significantly reduced spontaneously and after activation by collagen and TRAP. In opposit, P selectin (CD62p) and vWF receptor remain unchanged. Adhesion of septic patient's platelet to endothelial cells is under investigation. aggreg ADP ADP collagen collagen TRAP TRAP slope % aggreg slope % aggreg slope % aggreg normal 37.7 ±3.5 73.3 ±5.7 46.4 ±6.4 83.3 ±5.9 64.6 ±5.9 83.6 ±3.4 sepsis 30.1 ±5.8 61.0±14.l 34.5±3.6 70.6+7.9 40.1+12.6 70.5 ±9.7 pvalue 0.679 0.185 0.001 0.014 0.002 0.015 FCM CD62p PAC-1 fibrinogen meanfluo PBS TRAP PBS TRAP PBS TRAP normal 153 626.75 158 505.75 255.5 766 sepsis 115.6 530.9 120.1 275.6 233.9 309.8 pvalue 0.575 0.263 0.045 0.009 0.084 0.002 VEGF and PDGF mesured in the plasma supernatant after TRAP induced platelet aggregation, was differently regulated with an increased release of VEGF (125.99±99 in control vs 376 ±170 in septic p=0.017) and an inhibition of PDGF (2629±491 vs 1959+478 p=0.033). In conclusion severe sepsis is characterized by an impaired platelet aggregation with concerved adhesion and complex angiogenic regulation.
The characteristics and outcome of acute respiratory distress syndrome (ARDS) may have changed with time. Some studies have reported that mortality is more commonly related to the development of sepsis/multiple organ failure (MOF), and others that it is related to the severity of acute respiratory failure (ARF). The present study evaluates the relative importance of the two phenomena in a large series of patients. The clinical and biological data of all patients who developed ARDS during a 26 month period (January 1993 until February 1995) in our intensive care unit (ICU) were reviewed retrospectively. A total of 129 patients developed ARDS during the study period, representing an incidence of 2.4% of all ICU admissions. The mortality rate was 52%. The primary cause of death was sepsis/MOF (49%), followed by respiratory failure (16%), cardiac failure or arrhythmias (15%), neurological failure (10%), and other causes (8%). The mortality rate was related to age and degree of organ failure. MOF was not always a cause of late death, since half the deaths occurred within 5 days after admission. In addition, mortality was higher in septic than in nonseptic patients, and lower in trauma and surgical than in medical patients. We conclude that sepsis/multiple organ failure is still the most common cause of death in acute respiratory distress syndrome. Improvements in outcome of acute respiratory distress syndrome may depend more on treatment of sepsis and multiple organ failure than on oxygenation measures.
info:eu-repo/semantics/published
We do not believe that randomized controlled trials (RCTs) have shown similar outcomes with a restrictive transfusion strategy compared to a liberal one—this is true only at first sight.1–3 Indeed, a deeper analysis of these trials indicates that the reality might not be so straightforward. Just to take the latest study on blood transfusions after cardiac surgery,3 in which the conclusion based on the primary outcome was that a restrictive transfusion threshold was not superior to a liberal threshold, there were actually more deaths in the restrictive than in the liberal threshold group (4.2 vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P = 0.045).Importantly, in these large RCTs, it is more than likely that there were patients in each arm who experienced benefit and others who were harmed. In other words, there will have been some patients who received a transfusion simply because they were randomized to the high threshold group, although in normal practice a transfusion would not have been considered; similarly, some patients at higher risk who would normally have been transfused will have received no transfusion because they were randomized to the low threshold group. This concept was highlighted by an analysis of the data from the landmark Canadian Transfusion Requirements in Critical Care study by Deans et al.,4 showing that 30-day mortality rates were different and opposite in the liberal compared with the restrictive arm depending on the presence (21 vs. 26%) or absence (25 vs. 16%) of ischemic heart disease (P = 0.03).The need for erythrocyte transfusion and the benefit/risk ratio vary according to individual patient characteristics, including age and comorbidities, so large-scale RCTs in heterogeneous groups of patients may not be the most appropriate tool to investigate these issues; smaller RCTs in carefully defined patient groups may provide more useful information.5 Observational studies including a sufficient number of covariates have also indicated that blood transfusions can be associated with better outcomes in critically ill patients.6–8Our results9 clearly show that a liberal strategy of erythrocyte transfusion, in comparison with a restrictive one, reduced mortality and major complications in our population of surgical cancer patients. We focused on cancer patients undergoing major abdominal surgery during their ICU stay because there is good evidence that transfusions are most beneficial in the sickest patients,4,10 and the majority of postoperative complications happen in the ICU setting.1–3 Our RCT included well-balanced groups in terms of baseline demographic data and preoperative characteristics. As Dr. Waters and colleagues will know, calculations of P values should not be used to compare baseline data11 and are avoided in the leading journals.3 The intervention was clearly different in the two groups. The proportion of patients who received a transfusion was about 50% lower in the restrictive group than in the liberal one, both during the ICU stay and during the hospital stay. The restrictive group received a total of 88 erythrocyte units and the liberal group 134 units. The average hemoglobin concentration was higher in the liberal strategy group than in the restrictive strategy group before transfusion (7.9 ± 0.5 vs. 6.8 ± 0.5 g/dl; P < 0.001) and during the ICU stay. As a result, the restrictive group was exposed to more postoperative severe anemia than the liberal group, which may explain their higher rates of complications.Drs. Sharifpour, Hall, and von Heymann comment that our results were different from those of the Transfusion Requirements in Septic Shock trial.2 However, there are some clear differences between our study and the Transfusion Requirements in Septic Shock trial, in which patients were already in septic shock with marked organ failure (median Sequential Organ Failure Assessment score of 10 in both groups). This was not the case in our study. At that stage of septic shock, few interventions have been shown to improve outcome.We agree with Dr. Xue et al. that low serum albumin concentration is a common finding in patients with cancer and has been associated with poor outcome in surgical patients in previous studies. We reported the serum albumin concentration of patients, along with other laboratory and clinical data, to describe our population. We do not believe that intraoperative adverse events and different reasons for admission could have influenced our results. As mentioned above, prerandomization characteristics were well balanced between groups, including intraoperative factors, such as type of anesthesia, duration of surgery, and rates of erythrocyte transfusion. We agree with Dr. Xue et al. that in clinical practice we also consider clinical variables to guide our transfusion decisions, but this potential limitation was also present in the other studies on this subject. In addition, physicians in the trial could decide to give a blood transfusion out of protocol in life-threatening situations.We agree with Drs. Hall and Sharifpour that there is still a shortage of robust evidence from large RCTs that leukodepleted blood and shorter duration of blood storage can improve outcomes in surgical patients. As mentioned in the article, we agree with Dr. Sharifpour that despite the apparent benefits of a liberal strategy of erythrocyte transfusion in cancer patients undergoing abdominal surgery on short-term outcomes, the effects of this therapy on long-term outcomes such as cancer recurrence are not known.As pointed out by von Heymann et al., anemia may represent a heavy burden in oncologic patients with severe comorbidities and a substantial postoperative risk. Our RCT clearly showed that in a well-balanced population of cancer patients, a restrictive strategy of postoperative transfusion was associated with worse outcomes after abdominal surgery. This specific group of patients may not adapt well to anemia, presenting a higher incidence of complications, including 30-day cardiovascular events and mortality. Our results are in agreement with other data reported in the literature.The authors declare no competing interests.
SCOPUS: ar.j
Severe sepsis is a common occurrence in critically ill patients and a major cause of morbidity and mortality in this population. Management relies on the early identification and treatment of the underlying causative infection, adequate and rapid hemodynamic resuscitation, support of associated organ failure and modulation of the immune response with drotrecogin alfa (activated) when it is not contraindicated, and corticosteroids in severe septic shock. We will review current approaches to each of these categories.
