Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, 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. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed 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 potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Optimized venous return with a self-expanding cannula: from computational fluid dynamics to clinical application.

The Smart canula concept allows for collapsed cannula insertion, and self-expansion within a vein of the body. (A) Computational fluid dynamics, and (B) bovine experiments (76+/-3.8 kg) were performed for comparative analyses, prior to (C) the first clinical application. For an 18F access, a given flow of 4 l/min (A) resulted in a pressure drop of 49 mmHg for smart cannula versus 140 mmHg for control. The corresponding Reynolds numbers are 680 versus 1170, respectively. (B) For an access of 28F, the maximal flow for smart cannula was 5.8+/-0.5 l/min versus 4.0+/-0.1 l/min for standard (P<0.0001), for 24F 5.5+/-0.6 l/min versus 3.2+/-0.4 l/min (P<0.0001), and for 20F 4.1+/-0.3 l/min versus 1.6+/-0.3 l/min (P<0.0001). The flow obtained with the smart cannula was 270+/-45% (20F), 172+/-26% (24F), and 134+/-13% (28F) of standard (one-way ANOVA, P=0.014). (C) First clinical application (1.42 m2) with a smart cannula showed 3.55 l/min (100% predicted) without additional fluids. All three assessment steps confirm the superior performance of the smart cannula design.

Prise en charge de l'ulcère de jambe d'origine veineuse [Management of venous leg ulcers].

Leg ulcers are a major health and economic problem especially in elderly. More than 70% are associated with venous disease. Compressive therapy is the most effective treatment but bandages are often poorly tolerated and well trained nurses are required to apply them effectively. In recent years, the VAC system (vacuum assisted closure) has profoundly changed the wound healing approach. The objective is now to regenerate the tissues and not to replace them with skin grafts which give uncertain results. The other important challenge is to prevent recurrences. New pharmacologic treatments acting on microcirculation and hemostasis would probably appear in the near future opening new therapeutic perspectives.

Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Prevalence and clinical importance of mesenteric venous thrombosis in the Swiss Inflammatory Bowel Disease Cohort

OBJECTIVE: The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS: Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS: The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION: MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Platelet count and outcome in patients with acute venous thromboembolism.

The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.

Validation of a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism.

BACKGROUND: The only available score to assess the risk for fatal bleeding in patients with venous thromboembolism (VTE) has not been validated yet. METHODS: We used the RIETE database to validate the risk-score for fatal bleeding within the first 3 months of anticoagulation in a new cohort of patients recruited after the end of the former study. Accuracy was measured using the ROC curve analysis. RESULTS: As of December 2011, 39,284 patients were recruited in RIETE. Of these, 15,206 had not been included in the former study, and were considered to validate the score. Within the first 3 months of anticoagulation, 52 patients (0.34%; 95% CI: 0.27-0.45) died of bleeding. Patients with a risk score of <1.5 points (64.1% of the cohort) had a 0.10% rate of fatal bleeding, those with a score of 1.5-4.0 (33.6%) a rate of 0.72%, and those with a score of >4 points had a rate of 1.44%. The c-statistic for fatal bleeding was 0.775 (95% CI 0.720-0.830). The score performed better for predicting gastrointestinal (c-statistic, 0.869; 95% CI: 0.810-0.928) than intracranial (c-statistic, 0.687; 95% CI: 0.568-0.806) fatal bleeding. The score value with highest combined sensitivity and specificity was 1.75. The risk for fatal bleeding was significantly increased (odds ratio: 7.6; 95% CI 3.7-16.2) above this cut-off value. CONCLUSIONS: The accuracy of the score in this validation cohort was similar to the accuracy found in the index study. Interestingly, it performed better for predicting gastrointestinal than intracranial fatal bleeding.

Temporary caval stenting improves venous drainage during cardiopulmonary bypass

OBJECTIVES: Assess the benefit of temporary caval stenting for remote venous drainage during cardiopulmonary bypass (CPB). METHODS: Temporary caval stenting was realized in bovine experiments (65+/-6 kg) by the means of self-expanding (18F for insertion, 36F in situ) venous cannulas (Smartcanula LLC, Lausanne, Switzerland) with various lengths: 43 cm, 53 cm, 63 cm vs. a standard 28F wire armed cannula in trans-jugular fashion. Maximal blood flows were assessed for 20, 25 and 30 mmHg of driving pressure with a motorized table height adjustment system. In addition, the inferior caval diameters (just above its bifurcation) were measured in real time with intra-vascular ultrasound (IVUS). RESULTS: Venous drainage (flow in l/min) at 20 mmHg, 25 mmHg, and 30 mmHg drainage load was 3.5+/-0.5, 3.7+/-0.7 and 4.0+/-0.6 for the 28F standard vs. 4.1+/-0.7, 4.0+/-1.3 and 3.9+/-1.1 for the 36F smart 43 cm, vs. 5.0+/-0.7, 5.3+/-1.3 and 5.4+/-1.4 for the 36F smart 53 cm, vs. 5.2+/-0.5*, 5.6+/-1.1* and 5.8+/-1.0* for the 36F smart 63 cm. The inferior vena caval diameters at 30 mmHg were 13.5+/-4.8 mm for 28F standard, 11.1+/-3.6 for 36F smart 43 cm, 11.3+/-3.2 for 36F 53 cm, and 17.0+/-0.1* for 36F 63 cm (*P<0.05 for 28F standard vs. 36F smart 63 cm long) CONCLUSIONS: The 43 cm self-expanding 36F smartcanula outperforms the 28F standard wire armed cannula at low drainage pressures and without augmentation. Temporary caval stenting with long self-expanding venous cannulas provides even better drainage (+51%).

Outcome of long-axis percutaneous sacroplasty as first-line treatment of sacral insufficiency fractures : P219

Purpose: To assess the clinical outcome of patients who were subjected to long-axis sacroplasty as first line treatment for sacral insufficiency fractures. Methods and materials: Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of PMMA was delivered along the path of each sacral fracture. For each individual patient, the VAS pain score before sacroplasty and at 1, 4, 24, and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post interventional patient mobility before and after sacroplasty was also recorded. Results: The mean pre-procedure VAS score was 8 ± 1.9. This has rapidly declined in the first week after the procedure (mean 4 ± 1.5) followed by gradual decrease along the rest of follow-up period at 4 weeks (mean 3 ± 1.2), 24 weeks (mean 2 ± 1.3), and 48 weeks (mean 1.3 ± 1.4), respectively. Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas, 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%) (narcotic) and 10/19 53% (non-narcotic). Seven (37%) patients did not address post-procedure analgesic use. The evolution of post interventional mobility was favourable in the study group since they revealed a significant improvement in their mobility point scale. Conclusion: Long-axis percutaneous sacroplasty is a suitable minimally invasive treatment option for patients who present with sacral insufficiency fractures. Future studies with larger patient number are warranted to grasp any potential limitations of this therapeutic approach.

New bench test for venous cannula performance assessment.

Cannula design is of prime importance for venous drainage during cardiopulmonary bypass (CPB). To evaluate cannulas intended for CPB, an in vitro circuit was set up with silicone tubing between the test cannula encased in a movable preload reservoir and another static reservoir. The pressure-drop (DeltaP) value (P-drainage - P-preload) was measured using Millar pressure transducers. Flow rate (Q) was measured using an ultrasound flowmeter. Data display and data recording were controlled using a LabView application, custom made particularly for our experiments. Our results demonstrated that DeltaP, Q, and cannula resistance (DeltaP/Q) values were significantly decreased when the cannula diameter was increased for Smart and Medtronic cannulas. Smartcanula showed 36% and 43% less resistance compared to Medtronic venous and Medtronic femoral cannulas, respectively. The cannula shape (straight- or curved-tips) did not affect the DLP cannula resistance. Out of five cannulas tested, the Smartcanula outperforms the other commercially available cannulas. The mean (DeltaP/Q) values were 3.3 +/- 0.08, 4.07 +/- 0.08, 5.58 +/- 0.10, 5.74 +/- 0.15, and 6.45 +/- 0.15 for Smart, Medtronic, Edwards, Sarns, and Gambro cannulas, respectively (two-way ANOVA, p < 0.0001). In conclusion, the present assay allows discrimination between different forms of cannula with high or low lumen resistance.