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This monograph reviews selected topics related to the care of medically challenging patients who present for cardiothoracic surgery. It includes management strategies to optimize neurologic outcome and clinical considerations for patients with coexisting medical conditions, such as carotid disease, hypertension, hyperglycemia, dialysis-dependent renal disease, and pulmonary hypertension. It reviews clinical considerations for patients with heparin-induced thrombocytopenia, pregnant patients requiring cardiac surgery with cardiopulmonary bypass, and obese patients. Coverage includes considerations for selected patient populations requiring thoracic surgery, such as the patient who requires lung isolation but has a difficult airway, the patient with an anterior mediastinal mass, or the patient with an invasive tumor of the vena cava. A discussion of the patient who refuses transfusion addresses the ethical and legal implications and the clinical options available to optimize care.