In this paper we present a new expert knowledge based clinical decision support system for prediction of intensive care units outcome based on the physiological measurements collected during the first 48 hours of the patient's admission to the ICU. The developed CDSS algorithm is composed of several stages. First, we categorize the collected data based on the physiological organ that they represent. We then extract clinically relevant features from each data category and then rank these features based on their mutual information with the outcome. Then, we design an artificial neural network to serve as a classifier to detect patients at high risk of critical deterioration. We use the eight-fold cross validation method to test the developed CDSS classifier. The results from the classification show that the newly designed CDSS outperforms the widely used acuity scoring systems, SOFA and SAPS-III. The F-score classification result of our developed algorithms is 42% while the F-score results for SOFA and SAPS-III are 26% and 29% respectively.