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To examine which patient characteristics increase the risk for intensive care unit readmission and assess the association of readmission with case-mix adjusted mortality and resource use.Retrospective cohort study.Ninety-seven intensive and cardiac care units at 35 hospitals in the United States.A total of 229,375 initial intensive care unit admissions during 2001 through 2009 who met inclusion criteria.None.For patients who were discharged alive and candidates for readmission, we compared the characteristics of those with and without a readmission. A multivariable logistic regression analysis was used to identify potential patient-level characteristics that increase the risk for subsequent readmission. We also evaluated case-mix adjusted outcomes by comparing observed and predicted values of mortality and length of stay for patients with and without intensive care unit readmission. Among 229,375 first admissions that met inclusion criteria, 13,980 (6.1%) were eventually readmitted. Risk factors associated with the highest multivariate odds ratio for unit readmission included location before intensive care unit admission, age, comorbid conditions, diagnosis, intensive care unit length of stay, physiologic abnormalities at intensive care discharge, and discharge to a step-down unit. After adjustment for risk factors, patients who were readmitted had a four-fold greater probability of hospital mortality and a 2.5-fold increase in hospital stay compared to patients without readmission.Intensive care readmission is associated with patient factors that reflect a greater severity and complexity of illness, resulting in a higher risk for hospital mortality and a longer hospital stay. To improve patient safety, physicians should consider these risk factors when making intensive care discharge decisions. Because intensive care unit readmission correlates with more complex and severe illness, readmission rates require case-mix adjustment before they can be properly interpreted as quality measures.