(Stroke. 2000;31:2266-l.)
© 2000 American Heart Association, Inc.
Letters to the Editor |
Continuous Infusion Versus Bolus Injection Of Ultrasound Contrast Agents in Vascular Doppler Flow Imaging
Division of Neurology, Department of Medicine
Department of Medicine, Division of Neurology, Vascular Laboratory, Scripps Clinic, La Jolla, California
Key Words: • contrast media • carotid artery diseases • ultrasonography, Doppler, duplex
To the Editor:
The recent report from Germany by Droste et al1 in this journal reinforces the benefits of echocontrast-enhanced transcranial Doppler imaging of the collateral circulation with use of the echocontrast agent Levovist (Schering AG). Their results, showing that ultrasound contrast improved imaging resolution and diagnostic confidence, parallel our American experience with this same ultrasound contrast agent in a similar clinical application.2 We note with interest the investigators’ mention of using a new type of administration for this echocontrast agent (namely, continuous infusion by means of a pump), whereas our early clinical trial experience with Levovist has been limited to intravenous bolus injection. Medline searching revealed that several European centers have now reported experience with the continuous infusion of ultrasound contrast during Doppler studies of the intracranial,3 4 5 6 carotid and peripheral,7 8 9 and coronary arteries.10 11
A comparative evaluation of the advantages of continuous infusion and bolus injection in transcranial Doppler applications would be timely to standardize ultrasound contrast delivery parameters for broad general usage. Such a study could also incorporate analysis of the influence of total dose and the time-intensity curve on side effect profiles. Because continuous infusion appears to be clinically effective in transcranial Doppler indications, it may be prudent to adopt this method of administration over bolus injection for the additional theoretical benefit of avoiding steep concentration gradients and acute microbubble loading in the entire vasculature. Albrecht et al7 compared both modes of administration in the setting of peripheral vascular Doppler imaging in 6 healthy volunteers with the Doppler gain set to a low level to simulate suboptimal scanning conditions. This pilot investigation demonstrated that continuous infusion yielded a steady-state concentration of the echocontrast agent and greater examination time at optimal enhancement, avoided bloom and possibly other artifacts, and reduced the need to alter Doppler system settings. Continuous infusion also permitted the sonographer to titrate echocontrast enhancement tailored for the individual patient and vessel under examination with the additional benefit of being more "dose effective," ie, required a lower overall microbubble burden in the patient in order to achieve the desired diagnostic result.
We would be interested in the viewpoints of our European counterparts, Droste et al, who have reported separately their transcranial Doppler experiences with the bolus injection method.12 13 14 The use of ultrasound contrast has ramifications beyond the technical specifications of Doppler examinations. In the United States the demand for access to vascular ultrasonography, including transcranial Doppler, has moved beyond the finite number of academic investigator-sonographer laboratories into widespread application by nonvascular specialty practitioners. In this context, there exists the possibility that a majority of patients with clinical indications for transcranial Doppler studies may exhibit "suboptimal" imaging characteristics relative to the sonographer’s level of expertise. Therefore, another important purpose and benefit of ultrasound contrast agents may ultimately become its use to enhance access to quality care in vascular ultrasonography by reducing operator dependency and enabling sonographers throughout a spectrum of expertise to achieve clearly visible, standardized, and dependable results.
References
1.
Droste DW, Jürgens R, Weber S, Tietje R,
Ringelstein EB. Benefit of echocontrast-enhanced
transcranial color-coded duplex ultrasound in the
assessment of intracranial collateral pathways. Stroke.. 2000;31:920–923.
2.
Otis S, Rush M, Boyajian R. Contrast-enhanced
transcranial imaging: results of an American phase-two
study. Stroke.. 1995;26:203–209.
3.
Postert T, Braun B, Meves S, Köster O, Przuntek
H, Weber S, Büttner T. Contrast-enhanced transcranial
color-coded sonography in acute hemispheric brain infarction.
Stroke.. 1999;30:1819–1826.
4. Postert T, Braun B, Pfundtner N, Sprengelmeyer R, Meves S, Przuntek H, Büttner T. Echo contrast-enhanced three-dimensional power Doppler of intracranial arteries. Ultrasound Med Biol.. 1998;24:953–962.[Medline] [Order article via Infotrieve]
5.
Klötzsch C, Bozzato A, Lammers G, Mull M,
Lennartz B, Noth J. Three-dimensional transcranial
color-coded sonography of cerebral aneurysms.
Stroke.. 1999;30:2285–2290.
6.
Uggowitzer MM, Kugler C, Riccabona M, Klein GE, Leber
K, Simbrunner J, Quehenberger F. Cerebral arteriovenous
malformations: diagnostic value of echo-enhanced
transcranial Doppler sonography compared with
angiography. AJNR Am J Neuroradiol.. 1999;20:101–106.
7.
Albrecht T, Urbank A, Mahler M, Bauer A, Dore CJ,
Blomley MJ, Cosgrove DO, Schlief R. Prolongation and optimization of
Doppler enhancement with a microbubble US contrast agent by using
continuous infusion: preliminary experience. Radiology.. 1998;207:339–347.
8.
Droste DW, Jürgen R, Nabavi DG, Schuierer G,
Weber S, Ringelstein EB. Echocontrast-enhanced ultrasound of
extracranial internal carotid artery high-grade stenosis and
occlusion. Stroke.. 1999;30:2302–2306.
9. Hosten N, Puls R, Sahimbas O, Balzer J, Urbank A, Felix R. Color Doppler ultrasonography in peripheral artery occlusive disease: continuous application of signal enhancer. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr.. 1998;169:495–498.[Medline] [Order article via Infotrieve]
10. Caiati C, Montaldo C, Zedda N, Bina A, Iliceto S. New noninvasive method for coronary flow reserve assessment: contrast enhanced transthoracic second harmonic echo Doppler. Stroke.. 1999;99:771–778.
11. Bartel T, Müller S, Baumgart D, Mathew BT, Haude M, Erbel R. Improved high-frequency transthoracic flow velocity measurement in the left anterior descending coronary artery after intravenous peripheral injection of levovist. J Am Soc Echocardiogr.. 1999;12:252–256.[Medline] [Order article via Infotrieve]
12.
Nabavi DG, Droste DW,
Kemény V, Schulte-Altedorneburg G, >Weber
S, Ringelstein EB. Potential and limitations of
echocontrast-enhanced ultrasonography in acute stroke patients: a pilot
study. Stroke.. 1998;29:949–954.
13. Droste DW, Nabavi DG, Kemény V, Schulte-Altedorneburg G, Ritter MA, Weber S, Ringelstein EB. Echocontrast enhanced transcranial colour-coded duplex offers improved visualization of the vertebrobasilar system. Acta Neurol Scand.. 1998;98:193–199.[Medline] [Order article via Infotrieve]
14. Nabavi DG, Droste DW, Schulte-Altedorneburg G, Kemény V, Panzica M, Weber S, Ringelstein EB. Diagnostic benefit of echocontrast enhancement for the insufficient transtemporal bone window. J Neuroimaging.. 1999;9:102–107.[Medline] [Order article via Infotrieve]
Response
Department of Neurology, University of Münster, Münster, Germany
Schering AG, Berlin, Germany
We are very grateful for the comments of Drs Boyajian and Otis. As a matter of fact, we started our experience with echocontrast agents by injecting the agent manually as a bolus. This, however, often led to the initial appearance of blooming artifacts and a relatively short enhancing period, both of which resulted in a reduction of the effective examination time to approximately 2- to 3 minutes. Consecutively, we tried the fractionated use 4 g of the echocontrast agent Levovist (Schering AG) in a concentration of 400 mg/mL (ie, 10- to 11 mL). Five mL of the echocontrast was given as a bolus via a cubital vein with use of a butterfly. The next 2.5 mL was added when the effect of the echocontrast was fading, and finally the residual 2.5 mL was injected. This prolonged the investigation time to approximately 4- to 5 minutes and smoothed the agent’s enhancing effect.R1 Eventually, we applied one 4-g vial of the echo-enhancer Levovist (10- to 11 mL suspension) in a concentration of 400 mg/mL, using a specifically configured infusion pump with a continuous infusion rate of 2.5 mL/min. This procedure allowed for an enhancement time of more than 5 minutes, minimized the effect of blooming, and could be performed by 1 investigator without the need to interrupt the investigation and to relocate the vessels.R2 R3 We therefore feel that continuous infusion offers many advantages over the manual (bolus) injection. Other centers in Europe, as mentioned in the letter by Drs Boyajian and Otis, are also increasingly using this method. Infusion rates from 0.5 mL/min up to 2.5 mL/min were reported. We have never observed any major side effects of Levovist, either during manual injection or during continuous infusion. This is in line with a recent post-marketing surveillance by Schering, in which 585 Levovist applications (416 by manual injection, 169 by infusion pump) were monitored. No relevant side effects were observed (unpublished data, S. Weber, MD, Schering AG, 2000). We agree with the statement of Drs Boyajian and Otis that echocontrast agents could enable sonographers throughout a spectrum of expertise to achieve clearly visible, standardized, and reliable results. However, echocontrast cannot replace adequate training of technicians and doctors involved in diagnostic ultrasonography. Echocontrast agents help to further promote this cost-effective, noninvasive, and easy-to-repeat bedside technique by minimizing the number of patients who cannot be investigated because of technical problems.
References
1. Droste DW, Nabavi DG, Kemény V, Schulte-Altedorneburg G, Ritter M, Weber S, Ringelstein EB. Echocontrast enhanced transcranial color-coded duplex offers improved visualization of the vertebrobasilar system in patients with bad examination conditions. Acta Neurol Scand. 1998;98:193–199.
2. Droste DW, Jürgens R, Nabavi DG, Schuierer G, Weber S, Ringelstein EB. Echocontrast-enhanced ultrasound of extracranial internal carotid artery high-grade stenosis and occlusion. Stroke. 1999;30:2302–2306.
3. Droste DW, Jürgens R, Weber S, Tieje R, Ringelstein EB. Benefit of echocontrast-enhanced transcranial color-coded duplex ultrasound in the assessment of intracranial collateral pathways. Stroke. 2000;31:920–923. \.
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