My Approach to Agitated Saline Contrast Echocardiography in Pediatric PatientsAbstract
Agitated saline contrast is a simple, safe, widely available echocardiography technique. It is particularly useful for evaluating right-to-left shunts and pulmonary vascular abnormalities in the pediatric population. This article presents a practical approach to using this technique in pediatric echocardiography. It reviews the underlying physiological principles, the technical aspects of preparation and image acquisition, and the main clinical applications.
Keywords
Ecocardiography; Contrast Echocardiography; Patent Foramen Ovale; Atrial Septal Defect; Hepatopulmonary Syndrome
My Approach to Agitated Saline Contrast in Pediatric Patients: Clinical Applications. A4C: apical four-chamber view; ASD: atrial septal defect; HPS: hepatopulmonary syndrome; IVC: inferior vena cava; IV: intravenous; LV: left ventricle; PFO: patent foramen ovale; RA: right atrium; PA: pumonary artery.
Resumo
O contraste com solução salina agitada é um método simples, seguro e amplamente disponível na ecocardiografia, sendo particularmente útil na população pediátrica para a investigação de shunts direita-esquerda e alterações vasculares pulmonares. Este artigo apresenta uma abordagem prática para o uso dessa técnica na ecocardiografia pediátrica. São revisados os princípios fisiológicos envolvidos, os aspectos técnicos relacionados ao preparo e à aquisição das imagens, bem como suas principais aplicações clínicas.
Palavras-chave
Ecocardiografia; Ecocardiografia de Contraste; Forame Oval Patente; Comunicação Interatrial; Síndrome Hepatopulmonar
AD: átrio direito; A4C: apical de quatro câmaras; AVP: acesso venoso periférico; CIA: comunicação interatrial; FOP: forame oval patente; MMII: membros inferiores; MSD: membro superior direito; SHP: síndrome hepatopulmonar; VCI: veia cava inferior; VE: ventrículo esquerdo; AE: átrio esquerdo; VD: ventrículo direito; AP: artéria pulmonar.
What is agitated saline contrast?
Agitated saline contrast consists of the intravenous (IV) administration of normal saline that has been vigorously agitated, a process that promotes the formation of microbubbles from gases dissolved in the fluid under hydrostatic pressure. These microbubbles have a mean diameter greater than 9 μm, which prevents their passage through the pulmonary capillary bed under normal physiological conditions.1
After injection, immediate opacification of the right-sided chambers occurs. The microbubbles have a short half-life and dissolve rapidly as they pass through the pulmonary circulation. Therefore, in an intact cardiopulmonary system, they are not observed in the left-sided chambers.
The detection of microbubbles in the left atrium (LA) or left ventricle indicates diversion of blood flow beyond the pulmonary capillary bed, consistent with the presence of an intracardiac or intrapulmonary shunt. Under normal conditions, microbubbles (> 9 μm) do not traverse the pulmonary capillaries and dissolve within the lungs. Thus, any visualization of contrast in the left side of the heart is considered abnormal and indicates deviation from normal capillary flow.
Which echocardiographic view should be used?
For evaluation with agitated saline, the preferred echocardiographic view is the apical four-chamber view, as it provides optimal visualization of the interatrial septum, minimizes shadowing artifacts over the left-sided chambers, and facilitates identification of microbubble passage from the right atrium (RA) to the LA.
If an adequate apical window cannot be obtained, the subcostal four-chamber view is an appropriate alternative, particularly in the pediatric population, in which this window often provides superior image quality.
Image acquisition should begin before the arrival of microbubbles in the RA and be maintained for at least 10-20 heartbeats after opacification of this chamber, allowing proper temporal assessment of contrast appearance in the left-sided chambers. The use of harmonic imaging is recommended to increase diagnostic sensitivity.2 In addition, when feasible, physiological maneuvers such as Valsalva or coughing should be synchronized with contrast arrival in the RA to enhance detection of right-to-left shunts.
How should the solution be prepared?
Preparation requires peripheral IV access in an upper limb (preferably the right one) and a standardized technique to ensure adequate microbubble formation.
The technique consists of vigorous agitation by rapidly transferring the solution between two syringes connected by a three-way stopcock approximately 20 times, promoting appropriate microbubble formation (Central Illustration). Before IV administration, any visibly large air bubbles should be discarded to ensure procedural safety.
Injection should be performed immediately after agitation, as microbubbles have a short half-life.1–3 On echocardiography, the contrast appears as hyperechoic material within the right-sided chambers, allowing dynamic assessment of its distribution and potential passage into the left-sided chambers. Recommended preparation options for pediatric use are described in Table 1.
Materials
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Peripheral IV access (preferably in an upper limb);
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Two 10 mL syringes;
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Three-way stopcock.
Main indications in pediatric echocardiography
a) Investigation of intracardiac shunts
Agitated saline is widely used in pediatric echocardiography for the investigation and characterization of intracardiac shunts, particularly patent foramen ovale (Figure 1) and atrial septal defects, including coronary sinus-type defects (Figure 2).2
The key technical criterion for diagnosing an intracardiac shunt is the early appearance of microbubbles in the left-sided chambers, typically within the first 3 heartbeats after RA opacification. In sedated patients, brief abdominal compression may be applied to increase the sensitivity of the test.
Transesophageal echocardiography demonstrating opacification of the RA after infusion of agitated saline contrast via peripheral IV access, with early passage of microbubbles into the LA through a PFO. IV: intravenous; LA: left atrium; PFO: patent foramen ovale; RA: right atrium.
Transesophageal echocardiography in the four-chamber view after infusion of agitated saline contrast via peripheral IV access in the left upper limb, demonstrating opacification of the coronary sinus, the LSVC, and the LV, secondary to the presence of a coronary sinus-type ASD. ASD: atrial septal defect; LA: left atrium; LSVC: left superior vena cava; LV: left ventricle; RA: right atrium; RV: right ventricle.
This technique also assists in the characterization of venous anomalies, such as persistent left superior vena cava (SVC), unroofed coronary sinus, and arteriovenous fistulas.4,5
b) Hepatopulmonary syndrome (HPS) in pediatrics
HPS in pediatric patients occurs in the context of liver disease or portal hypertension and is characterized by intrapulmonary vascular dilation, partly mediated by increased nitric oxide production. This process leads to the formation of pulmonary microfistulas and disruption of the ventilation-perfusion relationship, allowing poorly oxygenated blood to enter the systemic circulation.
Diagnosis is based on the triad of underlying liver disease, evidence of intrapulmonary vascular dilation on echocardiography, and an increased alveolar-arterial gradient on arterial blood gas analysis. Clinically, it presents predominantly with hypoxemia of variable severity.6,7
On echocardiography, a delayed appearance of microbubbles in the left-sided chambers (> 3 heartbeats) is observed (Figure 3). This pattern differentiates HPS from intracardiac shunts, in which contrast appears early.7
Transthoracic echocardiography in the apical four-chamber view demonstrating delayed appearance of microbubbles (> 3 heartbeats) in the left-sided chambers after infusion of agitated saline via peripheral IV access. IV: intravenous.
c) Arteriovenous fistulas after Glenn/Fontan procedures
Following Glenn/Fontan surgeries, the development of pulmonary arteriovenous fistulas is related to the hemodynamic alterations inherent to single-ventricle physiology. The absence of pulsatile pulmonary flow, exclusion of hepatic flow with consequent deprivation of the so-called "hepatic factor," and chronically elevated central venous pressure promote endothelial dysfunction and pulmonary vascular remodeling, favoring microfistula formation.2,8
Clinically, these patients may present with persistent or progressive cyanosis. On agitated saline echocardiography, the characteristic finding is delayed appearance of microbubbles in the left-sided chambers, consistent with an intrapulmonary shunt pattern (Figure 4).
Transesophageal echocardiography in a patient following extracardiac Fontan surgery. The arrow indicates the RSPV, where microbubbles are observed after injection of agitated saline via peripheral IV access, which suggests the presence of pulmonary microfistulas. IV: intravenous; RA: right atrium; RSPV: right superior pulmonary vein.
The origin of the shunt determines the site of contrast injection9:
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Upper limb access (cephalic or basilic veins) allows evaluation of SVC drainage into the pulmonary arteries and is useful for detecting pulmonary arteriovenous fistulas in cases of uneven flow distribution;
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Lower limb access (saphenous or femoral veins) is mandatory to assess the distribution of the hepatic factor. Early appearance of microbubbles in the left-sided chambers after injection via the inferior vena cava confirms the presence of an intrapulmonary shunt.
d) Pericardiocentesis
Agitated saline injection can be used during pericardiocentesis to confirm, under echocardiographic guidance, correct positioning of the needle or catheter within the pericardial space, particularly when the aspirate is bloody or there is uncertainty regarding instrument location.
The appearance of microbubbles in the pericardial space after the injection of 3–5 mL of agitated saline allows differentiation between the pericardial space and the cardiac chambers, as shown in Figure 5, reducing the risk of inadvertent puncture of intracardiac structures.10
Transthoracic echocardiography with infusion of agitated saline into the pericardial space to confirm correct needle positioning during puncture.
Classification
Severity grading: 9
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Grade 1: sparse microbubbles in the LA (< 5 bubbles per frame);
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Grade 2: 5-25 microbubbles in the LA;
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Grade 3: > 25 microbubbles without complete cavity opacification;
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Grade 4: dense LA opacification, similar to right-sided chambers, with contrast visible in the systemic ventricle and aorta.
Technical differentiation between intracardiac and intrapulmonary shunts
The distinction is based on the timing of microbubble appearance in the left-sided chambers (Table 2).
Conclusion
Agitated saline contrast is a simple, safe, highly useful technique in pediatric echocardiography. It enables the identification and differentiation of intracardiac and intrapulmonary shunts, the characterization of systemic venous anomalies, the assessment of alterations related to single-ventricle physiology, and procedural support, such as image-guided pericardiocentesis.
When applied judiciously and with appropriate monitoring, it improves diagnostic accuracy, enhances procedural safety, and reduces the need for invasive or higher-cost methods, thereby optimizing clinical decision-making.
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Sources of Funding
There were no external funding sources for this study.
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Study Association
This study is not associated with any thesis or dissertation work.
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Ethics Approval and Consent to Participate
This article does not contain any studies with human participants or animals performed by any of the authors.
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Use of Artificial Intelligence
During the preparation of this work, the authors used NotebookLM to create the central figure. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.
Availability of Research Data
The underlying content of the research text is contained within the manuscript.
References
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1 Gupta SK, Shetkar SS, Ramakrishnan S, Kothari SS. Saline Contrast Echocardiography in the Era of Multimodality Imaging--Importance of "Bubbling It Right". Echocardiography. 2015;32(11):1707-19. doi: 10.1111/echo.13035.
» https://doi.org/10.1111/echo.13035 -
2 Lopez L, Saurers DL, Barker PCA, Cohen MS, Colan SD, Dwyer J, et al. Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations from the American Society of Echocardiography. J Am Soc Echocardiogr. 2024;37(2):119-70. doi: 10.1016/j.echo.2023.11.015.
» https://doi.org/10.1016/j.echo.2023.11.015 -
3 Porter TR, Abdelmoneim S, Belcik JT, McCulloch ML, Mulvagh SL, Olson JJ, et al. Guidelines for the Cardiac Sonographer in the Performance of Contrast Echocardiography: A Focused Update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2014;27(8):797-810. doi: 10.1016/j.echo.2014.05.011.
» https://doi.org/10.1016/j.echo.2014.05.011 -
4 Labovitz AJ, Noble VE, Bierig M, Goldstein SA, Jones R, Kort S, et al. Focused Cardiac Ultrasound in the Emergent Setting: A Consensus Statement of the American Society of Echocardiography and American College of Emergency Physicians. J Am Soc Echocardiogr. 2010;23(12):1225-30. doi: 10.1016/j.echo.2010.10.005.
» https://doi.org/10.1016/j.echo.2010.10.005 -
5 Watzinger N, Brussee H, Fruhwald FM, Schumacher M, Zweiker R, Stoschitzky K, et al. Pericardiocentesis Guided by Contrast Echocardiography. Echocardiography. 1998;15(7):635-40. doi: 10.1111/j.1540-8175.1998.tb00661.x.
» https://doi.org/10.1111/j.1540-8175.1998.tb00661.x -
6 Rodríguez-Roisin R, Krowka MJ. Hepatopulmonary Syndrome--A Liver-Induced Lung Vascular Disorder. N Engl J Med. 2008;358(22):2378-87. doi: 10.1056/NEJMra0707185.
» https://doi.org/10.1056/NEJMra0707185 -
7 Brito MM, Seda J Neto, Fonseca EA, Pugliese R, Danesi VB, Candido HL, et al. Outcomes of Liver Transplantation in Pediatric Recipients with Cardiovascular Disease. Pediatr Transplant. 2018;22(1). doi: 10.1111/petr.13081.
» https://doi.org/10.1111/petr.13081 -
8 Bhatt AB, Foster E, Kuehl K, Alpert J, Brabeck S, Crumb S, et al. Congenital Heart Disease in the Older Adult: A Scientific Statement from the American Heart Association. Circulation. 2015;131(21):1884-931. doi: 10.1161/CIR.0000000000000204.
» https://doi.org/10.1161/CIR.0000000000000204 -
9 Rana BS, Thomas MR, Calvert PA, Monaghan MJ, Hildick-Smith D. Echocardiographic Evaluation of Patent Foramen Ovale Prior to Device Closure. JACC Cardiovasc Imaging. 2010;3(7):749-60. doi: 10.1016/j.jcmg.2010.01.007.
» https://doi.org/10.1016/j.jcmg.2010.01.007 -
10 Holmes DR Jr, Nishimura R, Fountain R, Turi ZG. Iatrogenic Pericardial Effusion and Tamponade in the Percutaneous Intracardiac Intervention Era. JACC Cardiovasc Interv. 2009;2(8):705-17. doi: 10.1016/j.jcin.2009.04.019.
» https://doi.org/10.1016/j.jcin.2009.04.019
Edited by
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Editor responsible for the review:
Marcelo Tavares
