Pulmonary Transit of Echocontrast Agents During Mechanical Ventilation: A Clinical Transthoracic Echocardiographic Study Federico Bilotta, M.D., Ph.D., ∗ Luciano Agati, M.D.,† Laura Fiorani, M.D.,‡ Mariapina Madonna, M.D.,† Giovanni Pinto, M.D.,‡ and Giovanni Rosa, M.D. ∗ ∗ Department of Anesthesiology, Intensive Care and Pain Medicine, and †Department of Cardiology, University of Rome “La Sapienza,” Rome, Italy, and † ‡ Ospedale S Andrea, Rome, Italy In this study, we investigated whether the ultrasound contrast agents Levovist  or Sono Vue  injected intravenously during mechanical ventilation effectively pass through the pulmonary circulation. With echocardiography, we measured the time for the contrast to pass through the lungs; and the intensity of right and left ventricular cavity opacification at four time points: during spontaneous breathing (baseline), 5 minutes after the beginning of mechanical ventilation, and 5 minutes and 30 min- utes after extubation. Forty patients undergoing elective peripheral neurosurgical procedures were prospectively and randomly enrolled: 20 patients received intravenous Levovist(r) 1 g and 20 patients received intravenous Sono Vue  1 mL, at the four pre-defined time points. After intravenous injection, both Levovist  and Sono Vue  effectively passed through the lungs and opacified the right and left ventricular cavities, at the four time points. Pulmonary transit times were similar and constant for the two contrast agents tested: 6 ± 2 seconds at baseline, 5 ± 2 seconds during mechanical ventilation, 7 ± 2 seconds at 5 minutes and 6 ± 2 seconds at 30 minutes after extubation with Levovist  ; and 6 ± 4 seconds at baseline, 6 ± 3 seconds during mechanical ventilation, 6 ± 2 seconds at 5 minutes and 7 ± 3 seconds at 30 minutes after extubation with Sono Vue  . In all patients, each of the four contrast in- jections achieved high-grade right and left ventricular chamber opacification. In conclusion, both the ultrasound contrast agents tested in this study, Levovist  and Sono Vue  , after intravenous injection pass through the pulmonary circulation during mechanical ventilation. Ultrasound contrast agents with these characteristics are suitable for intraoperative organ perfusion studies, with intravenous injection. (ECHOCARDIOGRAPHY, Volume 22, May 2005) ultrasound contrast agents, Levovist  , Sono Vue  , intraoperative organ perfusion, neuroanesthesia After intravenous injection in spontaneously breathing patients and anesthetized dogs, ul- trasound contrast agents opacify the right ven- tricle, pass through the lungs, opacify the left ventricle and reliably depict systemic organ per- fusion patterns, 1–5 and visualize tumor perfu- sion. 6 Intraoperative organ-perfusion studies with ultrasound contrast agents have so far been limited to intraarterial and intraaortic in- jection. 7,8 In an earlier study, we found that This work was funded in part with departmental research funds, no corporate sponsorship has been received. Pro- fessor Luciano Agati is recipient of a research grant from Bracco Research, SA, Geneva, Switzerland. ∗ Address for correspondence and reprint requests: Federico Bilotta, M.D., Ph.D., Viale Somalia 81, 00199, Rome, Italy. Fax: +39-06-860-82-73; E-mail: bilotta@tiscali.it ultrasound contrast agents based on sonicated albumin microbubbles failed to transit the pul- monary circulation during mechanical ventila- tion in humans. 9 Whether an ultrasound con- trast agent passes the lungs during mechanical ventilation depends on many factors, including biochemical interactions with blood gasses, in- travascular pressure, and shell stability. 10 Me- chanical ventilation alters the physiology of the pulmonary microcirculation, by increasing in- trathoracic pressure and pulmonary vascular resistance. 11 Levovist  (Schering AG, Berlin, Germany) is a suspension of air-filled ultra- sound contrast microbubbles with a galactose and palmitic acid agent shell, used for organ perfusion studies with intravenous injection in spontaneously breathing patients. 4,6 Sono Vue  (Bracco Research, SA, Geneva, Switzerland) is a suspension of microbubbles (mean diameter Vol. 22, No. 5, 2005 ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech. 1