Anesthesiology 2007; 107:75– 81 Copyright © 2007, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep Jo ¨ rg Krebs, D.V.M., Ph.D.,* Stephen J. Ferguson, Ph.D.,† Katja Nuss, D.V.M.,‡ Boris Leskosek,§ Simon P. Hoerstrup, M.D., Ph.D., Ben G. Goss, Ph.D.,# Nikolaus Aebli, M.D., Ph.D.** Background: Sudden, intraoperative cardiovascular deterio- ration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anes- thetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Se- lective pulmonary vasodilation may be an appropriate prophy- lactic or therapeutic measure. The effect of sildenafil (phospho- diesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated. Methods: Bone cement (polymethylmethacrylate) was in- jected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals re- ceived a bolus injection (0.7 mg/kg) of sildenafil, with contin- uous infusion (0.2 mg · kg 1 ·h 1 ) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat. Results: Fat embolism was associated with a transient in- crease (21  7mmHg) in pulmonary arterial pressure. A tran- sient decrease in arterial blood pressure and temporary in- creases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1). Conclusions: Administration of sildenafil prevented the acute cardiovascular complications after bone marrow fat embolism in sheep. EMBOLIZATION of bone marrow fat during orthopedic surgery can lead to intraoperative cardiovascular deteri- oration. Incidences have been observed during total hip 1 and knee 2 arthroplasty and intramedullary nailing for stabilization of fractured long bones. 3 More recently, fat embolism has also been reported during instrumented spine surgery 4 and augmentation of fractured osteopo- rotic vertebrae with bone cement (vertebroplasty). 5,6 Fat embolization occurs in almost all patients undergoing major orthopedic surgery; however, not every patient shows clinical signs. Cardiovascular changes after pul- monary fat embolization are characterized by an increase in pulmonary arterial pressure, systemic arterial hypo- tension, and a decrease in cardiac output, hypoxemia, and arrhythmia. 7,8 Cardiovascular deterioration is often transient but may be fulminant, resulting in cardiac ar- rest and even death. 5,6,9 The number of orthopedic in- terventions provoking fat embolization is increasing, and therefore, the risk of intraoperative cardiovascular emer- gencies is also increasing. Prevention and correction of cardiovascular deteriora- tion after fat embolization during orthopedic surgery are therefore gaining importance. Modifications of surgical techniques, such as drilling vent holes, 1,10 lavage of the bone marrow cavity, 11 or using different orthopedic tools, 12 have aimed at reducing the embolic load and thus the risk of severe cardiovascular deterioration. An- esthetic management consists of maintaining arterial blood pressure and cardiac output. 13,14 However, this may be challenging in the presence of increased right ventricular afterload and decreased left ventricular pre- load. Different authors have reported that the character- istic increase in pulmonary arterial pressure during fat embolism is a result of pulmonary vasoconstriction, rather than mechanical blockage. 7,8 Pharmacologic vaso- dilation of the pulmonary vasculature may therefore be an appropriate measure for preventing or alleviating cardiovascular deterioration after fat embolization. Ad- ministration of sildenafil, a type 5 phosphodiesterase inhibitor, caused selective pulmonary vasodilation 15 and alleviated pulmonary arterial hypertension after experi- mental embolism induced by injecting microspheres. 16 However, embolization of microspheres does not ade- quately reproduce the pathophysiologic complexity of bone marrow fat embolization after an orthopedic inter- vention. Therefore, the use of sildenafil for preventing or alle- viating pulmonary hypertension after bone marrow fat embolization was investigated using a clinically relevant animal model (vertebroplasty in sheep). * Postdoctoral Researcher, † Assistant Professor, MEM Research Center, Insti- tute for Surgical Technology and Biomechanics, Medical Faculty, University of Bern, Bern, Switzerland. ‡ Postdoctoral Researcher, Musculoskeletal Research Unit, § Technician,  Professor, Department of Surgical Research and Clinic for Cardiovascular Surgery, University of Zu ¨rich, Zu ¨rich, Switzerland. # Research Director, AO Spine Research Centre, Queensland University of Technology, Brisbane, Australia. ** Associate Professor, Department for Orthopaedic Sur- gery, Swiss Paraplegic Centre, Nottwil, Switzerland; School of Medicine, Griffith University, Queensland, Australia. Received from the MEM Research Center, Institute for Surgical Technology and Biomechanics, Medical Faculty, University of Bern, Bern, Switzerland. Sub- mitted for publication October 6, 2006. Accepted for publication March 16, 2007. Supported by the Wesley Foundation, Brisbane, Australia; the Foundation of the Association for Osteosynthesis (AO Foundation), Davos, Switzerland; the Spine Society of the Association for Osteosynthesis (AOSpine), Du ¨bendorf, Swit- zerland (SRN 02/105); and the National Center of Competence in Research, Computer Aided Surgery and Image Guided Medical Interventions (NCCR Co-Me) of the Swiss National Science Foundation, Bern, Switzerland. Pfizer AG (Zu ¨rich, Switzerland) provided sildenafil and Tecres Medical (Verona, Italy) provided bone cement. Address correspondence to Dr. Krebs: MEM Research Center, Institute for Surgical Technology and Biomechanics, Medical Faculty, University of Bern, Stauffacherstr. 78, 3014 Bern, Switzerland. jorg.krebs@MEMcenter.unibe.ch. In- formation on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. ANESTHESIOLOGY’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue. Anesthesiology, V 107, No 1, Jul 2007 75