Acta Anaesthesiol Scand 2007; 51: 1107–1114 Printed in Singapore. All rights reserved # 2007 The Authors Journal compilation # 2007 Acta Anaesthesiol Scand ACTA ANAESTHESIOLOGICA SCANDINAVICA doi: 10.1111/j.1399-6576.2007.01369.x Plasma levels of endothelin-1 after a pulmonary embolism of bone marrow fat J. KREBS 1 , S. J. FERGUSON 1 , K. NUSS 2 , B. LESKOSEK 3 , S. P. HOERSTRUP 3 , B. G. GOSS 4 , S. SHAW 5 and NIKOLAUS AEBLI 6,7 1 MEM Research Center, Institute for Surgical Technology and Biomechanics, Medical Faculty, University of Bern, Bern, 2 Musculoskeletal Research Unit and 3 Department of Surgical Research and Clinic for Cardiovascular Surgery, University of Zu ¨ rich, Zu ¨ rich Switzerland, 4 AO Spine Research Center, Queensland University of Technology, Brisbane, Australia, 5 Department for Clinical Research, Vasoactive Peptide Group, University of Bern, Bern, 6 Department for Orthopaedic Surgery, Swiss Paraplegic Center, Nottwil, Switzerland and 7 School of Medicine, Griffith University, Queensland, Australia Background: During orthopedic surgery, embolization of bone marrow fat can lead to potentially fatal, intra-operative cardio- vascular deterioration. Vasoactive mediators may also be released from the bone marrow and contribute to these changes. Increased plasma levels of endothelin-1 (ET-1) have been observed after pulmonary air and thrombo-embolism. The role of ET-1 in the development of acute cardiovascular deterioration as a result of bone marrow fat embolization during vertebroplasty was there- fore investigated. Methods: Bone cement was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continu- ously until 60 min after the last injection. Cardiac output, arterial and mixed venous blood gas parameters and plasma ET-1 concentrations were measured at selected time points. Post- mortem, lung biopsies were taken for analysis of intravascular fat. Results: Cement injections resulted in a sudden (within 1 min) and severe increase in pulmonary arterial pressure (>100%). Plasma concentrations of ET-1 started to increase after the second injection, but no significant changes were observed. Intravascular fat and bone marrow cells were present in all lung lobes. Conclusion: Cement injections into vertebral bodies elicited fat embolism resulting in subsequent cardiovascular changes that were characterized by an increase in pulmonary arterial pressure. Cardiovascular complications as a result of bone marrow fat embolism should thus be considered in patients undergoing vertebroplasty. No significant changes in ET-1 plasma values were observed. Thus, ET-1 did not contribute to the acute cardiovascular changes after fat embolism. Accepted for publication 3 May 2007 Key words: Endothelin-1; fat embolism; vertebroplasty; car- diovascular changes; pulmonary hypertension; vasoactive mediators; sheep. # 2007 The Authors Journal compilation # 2007 Acta Anaesthesiol Scand I NTRA-oPERATIVE cardiovascular deterioration as a result of pulmonary embolization of bone mar- row fat is a potentially fatal complication during total hip and knee arthroplasty (1, 2), intramedullary nail- ing for stabilization of fractured long bones (3), instrumented spine surgery (4, 5) and augmentation of fractured osteoporotic vertebrae with bone cement (vertebroplasty) (6, 7). Although cardiovascular deterioration is often transient and may pass unno- ticed, it can be fulminant, resulting in intra-operative cardiac arrest and even death (6–9). Deterioration occurs within a few minutes of embolization and is characterized by an increase in pulmonary arterial pressure, systemic arterial hypotension, decrease in cardiac output and hypoxemia (10, 11). The manage- ment of these complications has aimed at maintain- ing arterial blood pressure and cardiac output (12, 13). However, this may be challenging in the presence of increased right ventricular after-load. Aggressive volume support will deteriorate right ventricular overload and vasoconstrictive as well as positive inotropic drugs may not be effective. A better understanding of the pathophysiology of cardiovascular deterioration after bone marrow fat embolism would assist in devising effective countermeasures. After an embolism, pulmonary hypertension may be the result of pulmonary vasoconstriction elicited by vasoactive mediators that are released from the bone marrow cavity or as a result of lung injury (14, 15). The endothelin (ET) system consists of a group of vasoactive peptides of which ET-1 is the predominant isoform. Endothelin-1 is mainly synthe- sized in vascular endothelium and is the most potent 1107