sepsis affects more than 750,000 patients each year in the united states ; it is the 10th leading cause of death and one of the leading causes for admission to the intensive care unit [ 1 - 4 ] . the estimated mortality from sepsis is 2030% , meaning that approximately 500,000 patients survive their septic episode annually in the united states alone . are they able to resume their lives and regular activities , or does sepsis have far - reaching effects that extend beyond the hospitalization ? ten years ago , quartin and colleagues were the first to show that sepsis has long - lasting effects and increases the risk of death up to 5 years after hospitalization for the septic episode . mounting evidence has since demonstrated that survivors of sepsis have a higher long - term risk of death and a lower health - related quality of life ( hrqol ) when compared with the general population [ 6 - 8 ] . in 2001 , recombinant human activated protein c ( rhapc ) was shown to significantly reduce the 28-day mortality in patients with severe sepsis . a subgroup analysis demonstrated that patients who were more severely ill , with multiple organ dysfunction or with acute physiology and chronic health evaluation ( apache ) ii scores  25 , accrued the greatest benefit from rhapc , resulting in drug approval focused on these sepsis populations . a subsequent randomized controlled trial that evaluated rhapc use in patients with severe sepsis and a low risk of death ( apache ii score < 25 ) found no survival benefit with rhapc . given the high cost of rhapc , the attendant bleeding risk associated with its use , and the lack of clinical trials confirming its efficacy , there continues to be debate and controversy regarding its appropriate use . with the increasing emphasis on patient - centered outcomes in clinical trials , we are now more frequently assessing short - term and long - term survival and , at least sometimes , hrqol . in assessing long - term outcomes among sepsis survivors from the original rhapc trial , the short - term survival benefit for more severely ill patients ( apache ii scores  25 ) treated with rhapc was also evident at 3 , 6 and 12 months , while there was no difference in survival for those less severely ill patients . in the previous issue of critical care , longo and colleagues evaluated the effect of rhapc on long - term hrqol and resource utilization in patients with severe sepsis . using an observational cohort of 100 patients with severe sepsis ( 36 patients received rhapc and 64 patients received standard care ) who survived to day 28 , the patients ' hrqol was measured using the short form 36 ( sf-36 ) at 3 , 5 and 7 months , and resource utilization was measured using patients ' self - reports recorded in a diary . patients who were treated with rhapc had significantly better physical component scores on the sf-36 throughout the follow - up period , without significant differences in other components of the sf-36 . patients treated with rhapc also had a significantly shorter hospital stay compared with patients in the standard care group , and showed statistically nonsignificant improvements in the rate of return to employment . one of the major limitations of their study is that rhapc was administered in a nonrandomized fashion , meaning the use of rhapc was left to the discretion of the attending physician . unfortunately , we are given little information about what factors the attending physicians considered when deciding to treat patients with rhapc . without the design of a randomized controlled trial , the results are subject to bias and confounding by unmeasured factors . the authors recognize these limitations and demonstrated that the two groups of patients ( rhapc vs. standard care ) were similar in illness severity ( apache ii score ) and had similar numbers of comorbidities . however , patients who received rhapc were significantly younger and more likely to have been admitted through the emergency department . further , there are no data provided about other factors that may have influenced survival and hrqol such as the type or severity of comorbities ( hiv , malignancy ) [ 13 - 15 ] , organ dysfunction , use of vasopressors or need for mechanical ventilation . these unmeasured differences may fully or partially account for the observed differences in long - term hrqol . for example , younger patients with minor comorbidities ( for example , hypertension ) and a better chance of long - term survival may have been more likely to receive rhapc than an elderly patient with metastatic cancer . other limitations include the small sample size and the limited power to detect smaller but meaningful differences in other components of the sf-36 or resource utilization . despite the limitations of the study , longo and colleagues address an important issue  evaluating the long - term effects of a sepsis therapy . their findings suggest that treatment with rhapc may result in improved long - term physical functioning in patients with severe sepsis . the authors hypothesize that rhapc may reduce acute organ dysfunction , thereby diminishing the likelihood of chronic dysfunction and thus improving long - term hrqol . as noted by the authors , this study does not provide conclusive evidence that rhapc improves long - term hrqol , and nor does this study provide any insight into the mechanisms responsible for the improvement in physical functioning . instead , the study offers intriguing preliminary data that should provide the foundation for a larger , more rigorously designed clinical trial examining the long - term effects of rhapc on hrqol . certainly , if rhapc is shown to improve long - term health outcomes , including hrqol , it will open new windows for drug evaluation and provide more evidence to help us determine the optimal use of this controversial medication . apache = acute physiology and chronic health evaluation ; hrqol = health - related quality of life ; rhapc = recombinant human activated protein c ; sf-36 = short form 36 .