Copyright © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. <zdoi;10.1097/ALN.0000000000001133> Anesthesiology, V 125 • No 1 168 July 2016 I N the past few decades, a number of studies have evalu- ated the relationship between hospital volume and patient outcomes in varieties of medical and surgical conditions. 1–4 Several studies have also evaluated the volume–outcome rela- tionship in critically ill patients. 5–7 Sepsis is a leading cause of death among critically ill patients in the United States, which puts an enormous strain on the healthcare system and is becoming a pressing public health crisis. 8 In the past decades, the incidence of sepsis has rapidly increased worldwide, 9–12 while the mortality from sepsis has steadily decreased over time despite the absence of novel therapeutics. 13,14 Early rec- ognition, treatment, and advances in processes of care mainly contribute to the declining mortality. 15 Te number of sep- tic patients treated in a hospital (i.e., annualized case volume or hospital volume), refecting experience, may also partly be associated with this decline. However, the relationship between annualized case volume and mortality in patients with sepsis has not been fully understood. Previous studies have evaluated the relationship between annualized case volume and mortality in patients with sep- sis but have shown inconsistent results. 16–25 Terefore, we performed this meta-analysis with the following objectives: (1) to examine the relationship between annualized case What We Already Know about This Topic • Much evidence suggests that hospitals with higher volumes of septic patients have better outcomes in sepsis. What This Article Tells Us That Is New • A dose–response meta-analysis (10 studies, 3.4 million pa- tients, 0.83 million deaths) demonstrated a consistent dose– response relationship with lower mortality in higher volume hospitals with up to 400 cases (intensive care unit, emergency department) per year; above this level, the outcomes pla- teaued. The fndings were consistent across subgroups and may help plan optimal centralization of care. Copyright © 2016, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2016; 125:168-79 ABSTRACT Background: Te relationship between annualized case volume and mortality in patients with sepsis is not fully understood. Te authors performed a dose–response meta-analysis to assess the efect of annualized case volume on mortality among patients with sepsis in the intensive care unit, emergency department, or hospital, hypothesizing that higher annualized case volume may lead to lower mortality. Methods: Te authors searched PubMed and Embase through July 2015 to identify observational studies that examined the relationship between annualized case volume and mortality in sepsis. Te predefned outcome was mortality. Odds ratios with 95% CIs were pooled using a random-efects model. Results: Ten studies involving 3,495,921 participants and 834,009 deaths were included. Te pooled estimate suggested that annualized case volume was inversely associated with mortality (odds ratio, 0.76; 95% CI, 0.65 to 0.89; P = 0.001), with high heterogeneity (I 2 = 96.6%). Te relationship was consistent in most subgroup analyses and robust in sensitivity analysis. Dose–response analysis identifed a nonlinear relationship between annualized case volume and mortality (P for nonlinearity less than 0.001). Conclusions: Tis meta-analysis confrmed the study hypothesis and provided strong evidence for an inverse and a nonlinear dose–response relationship between annualized case volume and mortality in patients with sepsis. Variations in cutof values of category for annualized case volume across studies may mainly result in the overall heterogeneity. Future studies should uncover the mechanism of volume–mortality relationship and standardize the cutof values of category for annualized case volume in patients with sepsis. (ANESTHESIOLOGY 2016; 125:168-79) Drs. W.-J. Gu and Wu contributed equally as first authors. Submitted for publication October 22, 2015. Accepted for publication March 14, 2016. From the Department of Anesthesiology, Drum Tower Hospital, Medical College of Nanjing University, Nanjing, China (W.-J.G., J.Z., Z.-L.M., X.-P.G.); Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China (X.-D.W.); Department of Science and Education, First People’s Hospital of Changde City, Changde, China (Q.Z.); and Department of Anesthesiology, General Hospital of Jinan Military Command, Jinan, China (F.W.). Relationship between Annualized Case Volume and Mortality in Sepsis A Dose–Response Meta-analysis Wan-Jie Gu, M.D., Xiang-Dong Wu, M.D., Quan Zhou, M.D., Juan Zhang, M.D., Fei Wang, M.D., Ph.D., Zheng-Liang Ma, M.D., Ph.D., Xiao-Ping Gu, M.D., Ph.D.