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Whether febrile illnesses in the intensive care unit (ICU) have unique spectrum, etiologies, and outcome has not been determined in liver transplant recipients. We studied 78 consecutive febrile patients over a 4-yr period; 49% (38/78) were in the ICU and 51% (40/78) were in the non-ICU setting. Of febrile patients in the ICU, 87% (33/38) had infection and 13% had non-infectious etiology for fever. Seventy-nine percent (26/33) of the infections associated with fever in the ICU were bacterial, 9% (3/33) were viral, and 9% (3/33) were fungal in etiology. Pneumonia (30%), catheter-related bacteremia (15%), and biliary tree (9%) were the predominant sources of infections associated with fever in the ICU. Bacteremia was documented in 45% of the patients with fever in the ICU. Fifty-three percent (20/38) of the febrile episodes in the ICU occurred during the initial post-transplant stay, and 47% (18/38) during a subsequent readmission. Pneumonia accounted for 41% of all febrile infections during the first 7 d of ICU stay, but only 14% of those after 7 d. Febrile patients in the ICU had higher APACHE II scores (p = 0.001), higher APS scores (p = 0.0001), higher bilirubin (p = 0.001), lower cholesterol (p = 0.019), higher prothrombin time (p = 0.001), were more tachycardiac (p = 0.002), and were more likely to have abnormal blood pressure (p = 0.001) than those in the non-ICU setting. Twenty-three percent of all infections in the ICU were unaccompanied by fever and 9% were accompanied by hypothermia. Mortality at 14 d (24 versus 0%, p = 0.001) and at 30 d (34 versus 5%, p = 0.001) was significantly higher in febrile patients in the ICU, as compared to the patients in the non-ICU setting. These data have implications for diagnostic evaluation and management of critically ill febrile liver transplant recipients.