Future options for (economically) sustainable research in sepsis.

The relentless increase in healthcare costs and the global economic crisis require us to rethink the way research is done. The heterogeneity of patients is a major challenge in designing and coordinating high-quality studies about sepsis. Studies on new treatments and devices, such as polymyxin B hemoperfusion, must be optimized not only for potential benefits for a specific population (i.e. efficacy), but also for their eventual implementation in real-world situations (i.e. effectiveness) and for economic costs (i.e. efficiency). In this regard, theragnosis and newer statistical tools could help us obtain useful information from real-life observational data. In this review, we discuss the basic components required for sustainable research in polymyxin B hemoperfusion.

Cost-effectiveness analysis of polymyxin-B immobilized fiber column and conventional medical therapy in the management of abdominal septic shock in Italy.

INTRODUCTION: Severe abdominal sepsis and septic shock are common problems in intensive care units (ICUs), and carry high mortality. The purpose of this economic analysis was to determine the cost-effectiveness of polymyxin B immobilized fiber column (PMX-F) plus conventional therapy (CT) (PMX-F-CT) versus CT alone for patients with severe sepsis/septic shock of abdominal origin, in the perspective of the Italian hospital. METHODS: This was a retrospective cost-effectiveness analysis (CEA) based on data of clinical efficacy and consumption of resources collected alongside an Italian randomized clinical trial. 64 patients were enrolled following emergency surgery for intra-abdominal infection in 10 tertiary care ICUs from December 2004 to December 2007. Direct medical costs analyzed in the study included the consumption of hospital days, ICU days, catecholamine treatment days, renal replacement therapy days, mechanical ventilation treatment days, and the use of the PMX-F device. Resources were valued using published 2010 tariffs and market values. All-cause hospital mortality was extrapolated to survival as expected life years (LY) per patient/arm: for each survivor, average age-gender-related years of life expectancy were retrieved from national life tables; for deceased patients, only the number of CRF reported survival days was retained. Baseline expected years of survival were weighed by the severity of sepsis, according to individual Acute Physiology and Chronic Health Evaluation (Apache) II scores, showing that age/disease severity were comparable in the two groups before treatment initiation. Life expectancy per patient in each treatment group was thus calculated as the combination of life expectancy from Italian National Statistics Institute life tables and intra-hospital mortality detected in the Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock (EUPHAS) study. After all costs and 3% discounted survival years were calculated per patient per treatment arm, the incremental CEA was run to obtain the incremental cost-effectiveness ratio (ICER). Univariate sensitivity analyses and 2,000 bootstrap replications were run to test the robustness of the study results. RESULTS: Based on the expected survival years (mean discounted PMX-F-CT 9.37 LY/patient, CT 4.92 LY/patient; difference for PMX-F-CT 4.45 LY/patient; mean undiscounted PMX-F-CT 13.92 LY/patient, CT 7.19 LY/patient; difference +6.73 LY/patient), and the expected mean cost (PMX-F-CT mean 59,922 EUR/patient, CT mean 42,712 EUR/patient; difference for PMX-F-CT 17,211 EUR/patient), the mean ICER for PMX- F-CT resulted in 3,864 EUR/life year gained (LYG; ICER 2,558/undiscounted LYG). Results of the base-case CEA were confirmed by all sensitivity analyses, with ICER values always well below commonly accepted value thresholds. CONCLUSION: PMX-F-CT versus CT is a cost-effective intervention for treatment of severe sepsis/septic shock of abdominal origin and could be considered for use in the Italian National Health System hospital setting.

[For which cases should clinicians perform blood purification in the management of acute poisoning? Clinical and pharmacological analyses].

Indications for performing blood purification such as direct hemoperfusion (DHP), hemodialysis (HD) and hemodiafiltration (HDF) in patients with acute poisoning were retrospectively analyzed. Although a quick improvement in consciousness level was achieved by an intensive treatment with DHP for three hours in 27 patients suffering from acute tranquilizer poisoning, a slow but safe recovery was surely obtained in another 111 cases who received general supportive care. The medical costs of patients treated by DHP were 2.07 times greater than those of cases treated by general supportive care. Plasma and urine concentrations of theophylline could be obtained simultaneously during the treatment by DHP. The excretion rate of DHP at 1, 2, 3 and 6 hours after starting DHP ranged from 99.4% to 96.0%. At the end of DHP, the clinical findings markedly improved and sufficient elimination from the body could be obtained. The rebound phenomenon was observed after three hours DHP in one case of acute anilin poisoning and the patient died of fatal fulminant hepatic failure at 9th hospital day. In this case, further DHP was needed. DHP is presently becoming less prevalent due to concerns over such issues as rapid metabolism and elimination efficacy in acute organophosphate and aconitine poisoning. In a case of 23-year old female who took a potentially fatal dose of 100 g of acetaminophen, blood purification was not performed and oral N acetylcysteine antidotal therapy was quite effective in order to prevent hepatic injury. The serum acetaminophen concentration was 287 microg/ml on her admission and the value fell to 28.8 microg/ml after 35 hours. These results indicate that blood purification is not always necessary because of it's poor elimination efficacy in some kinds poisoning. Nevertheless, in severe cases it was quite an effective and useful extracorporeal elimination technique for both improvement of clinical outcome and clearance of poisons. Although it is difficult to draw a definitive conclusion from this study, it is suggested that a rapid and prudent decision should be made as to perform blood purification.

[Economic effectiveness of extracorporeal methods of treating surgical patients]. / Ekonomicheskaia éffektivnost' ékstrakorporal'nykh metodov lecheniia khirurgicheskikh bol'nykh.

On the basis of the analysis of the results of treatment of 125 patients of the surgical profile, who were at critical state because of acute renal and hepatic failure, the high cost effectiveness of the extracorporeal methods of detoxication is shown.