Introduction
Spontaneous microbubbles, or microcavitations, have been reported in patients on mechanical circulatory support, receiving haemodialysis, in high flow lines, requiring positive pressure ventilation, and possessing mechanical valves . Reference Barak and Katz1–Reference Andersen, Johansen, Paulsen, Nygaard and Hasenkam6 A few case reports have also demonstrated microbubbles in the setting of intestinal pathology. Reference Labbe and el Hafiani7–Reference Azzo, Albeer and Cohen10 Such bubbles have been referred to as microbubbles in the literature, historically, and their size is relatively smaller to that of red blood cells. They are visible by ultrasound when there is a number of them due to their unique physical properties and high echogenicity.
Any air in the vasculature raises concern for air embolism, but the risk posed by microbubbles has not been delineated. Some studies have evaluated iatrogenic microbubbles created by agitated saline for echocardiography, with findings from these studies being inconclusive in regards to what the embolism risk associated with agitated saline is. Reference Bassett, Lin, Tran and Sistino11 Some case reports describe transient ischaemic attacks or ischaemic strokes during, or immediately following, an echocardiographic bubble study. Reference Romero, Frey and Schwamm12 As the quality of echocardiographic images improves, we are identifying microbubbles, particularly those idiopathic in nature, more than previously. Although previous reports describing air embolus in the coronary circulation secondary to microbubbles could not be found, this is a theoretic risk that is mentioned in previous reports. Due to uncertainty of the risk associated with microbubbles, care is taken to prevent bubbles whenever possible.
This report presents a case of spontaneous microbubbles noted in a child with unrepaired CHD in whom the microbubbles were felt to have translocated into the vasculature from the gastrointestinal tract in the setting of necrotising enterocolitis.
Case report
A nine-month-old boy with trisomy 18 presented for routine cardiology follow-up and was found to have spontaneous microbubbles throughout heart chambers on echocardiogram. Intracardiac anatomy consisted of a large atrial septal defect, a large ventricular septal defect, and a patent arterial duct. There was bidirectional shunting noted at all levels in the setting of pulmonary hypertension previously confirmed by cardiac catheterisation. The echocardiogram demonstrated spontaneous microbubbles throughout all cardiac chambers and the great vessels. The leftward panel of Figure 1 is a four-chamber echocardiographic image from the time of admission, which demonstrates microbubbles. Video 1 demonstrates the microbubbles in two different echocardiographic cines.
On the left half of the figure is a four-chamber echocardiographic image from the time of admission demonstrating a large ventricular septal defect and microbubbles in both the right and left side of the heart. The right half of the figure is a similar four-chamber echocardiographic image from the time of admissions. Once again, a large ventricular septal defect is noted and an atrial septal defect is noted. There are no microbubbles noted on this echocardiographic image.
Other pertinent medical history for the child included trisomy 18, chronic lung disease, and tracheostomy with need for mechanical ventilation. No recent changes in his ventilator settings had been made recently and the child had no implanted lines or ports.
At the visit, parents reported no significant concerns except that the child had been having diarrhoea for approximately two days. The patient had multiple watery bowel movements during the visit and began having frank hematochezia. With these findings, he was admitted to the paediatric ICU for evaluation and monitoring for perceived risk for air emboli and evaluation of his haematochezia.
Initial evaluation included an otolaryngology evaluation with flexible tracheobronchoscopy demonstrating no tracheoesophageal fistula or mucosal irregularities. CT of the chest and abdomen was then obtained as well. This demonstrated no free air in the abdomen, no intravascular air, no portal venous gas, and no pneumatosis. CT of the abdomen did demonstrate findings consistent with concern for colitis, specifically necrotising enterocolitis. No specific aetiology for necrotising enterocolitis could be identified, and the child didn’t have usually noted risk factors.
He was clinically treated for necrotising enterocolitis with bowel rest and antibiotics. After completing treatment, his feeds were slowly advanced back to home feeds. Microbubbles continued to be noted intermittently on echocardiogram throughout the admission and improved along with the gastrointestinal symptoms. No microbubbles were noted on the discharge echocardiogram on the ninth day of admission. The rightward panel of Figure 1 is a four-chamber echocardiographic image from the time of discharge, which demonstrates no microbubbles.
During the admission, there were no concerns for air embolus. There were no changes in cardiac function by echocardiography and no electrocardiographic evidence of cardiac ischaemia. There were also no changes to baseline neurologic status or concerns for stroke during the admission. Hepatic and renal enzymes remained within normal limits. There was no evidence of significant inflammatory response as c-reactive protein and procalcitonin both remained normal. There was no coagulopathy.
Interestingly, a sparse number of microbubbles were noted six months later on a routine outpatient echocardiogram. At this point, there were no overtly concerning gastrointestinal symptoms except for increased stool frequency. The child was not admitted for this and the patients watched him closely at home. The microbubbles were no longer appreciated on a follow-up echocardiogram a few weeks later.
The patient is still alive 16 months later and remains at neurologic baseline with no concerns for air embolus. He has significant neurodevelopmental delays but has not demonstrated any regression. He is closely followed by physical and occupational therapy and has made slow progress. From a cardiac standpoint, his pulmonary hypertension has remained stable and he is tolerating significant weans in diuretic requirement and tolerated weans in his ventilator settings and the fraction of inspired oxygen to room air. This had led to low concern for air emboli causing injury to the pulmonary vascular bed.
Discussion
We present a unique case of a child with unrepaired CHD who was found to have idiopathic microbubbles in his circulation, believed to have translocated from his gastrointestinal system in the setting of necrotising enterocolitis. Evaluation for airway and gastrointestinal-related aetiologies was done. Only after a diagnosis of necrotising enterocolitis made by CT and other sources of microbubbles were eliminated was the aetiology of translocation settled upon.
It was hypothesised that the microbubbles were translocated through the intestinal mucosa secondary to the enterocolitis-induced inflammation. Further supporting this hypothesis, medical management of the enterocolitis resulted in resolution of the microbubbles. No signs or symptoms of air emboli were appreciated throughout this admission. The patient’s neurological status remained stable, although it is important to note that the neurologic status of the patient was already limited but did not deteriorate in any way during the admission and subsequent follow-up, and if anything, has shown improvement. Cardiac function remained normal as well.
Previous studies have demonstrated a similar finding of circulating microbubbles in the setting of intestinal pathology. Reference Labbe and el Hafiani7–Reference Azzo, Albeer and Cohen10 It is likely that, in most of these cases, microbubbles entered the portal circulation due to loss of intestinal mucosal integrity secondary to enterocolitis. Reference Sebastia, Quiroga, Espin, Boye, Alvarez-Castells and Armengol13,Reference McElvanna, Campbell and Diamond14 In the patient described here, the intracardiac lesions allowed for the microbubbles to then pass into the arterial circulation from the venous circulation. A previous case report in a newborn with unrepaired atrioventricular septal defect hypothesised that perhaps their patient had a patient venous duct but there was no evidence of this by previous cardiac catheterisation, echocardiography, or CT to demonstrate this in the currently presented patient. Reference Abraham, Sachdeva, Vyas and Thomas Collins9
Of note is that in the currently presented patient microbubbles entered the arterial circulation but there were no clinical sequelae of air embolus anywhere. No change was noted in neurologic status, cardiac function, hepatic function, renal function, or coagulation. The gastrointestinal symptoms also improved and with this so did the burden of microbubbles. Previous case reports have noted a temporal association of transient ischaemic attacks and ischaemic strokes with echocardiographic bubble studies. It is interesting to note, however, that in this current case, there was no evidence of air emboli even with a large burden of microbubbles in the systemic circulation. No evidence of air emboli was noted in the previous report by Abraham and colleagues in a child with intracardiac shunts. Reference Abraham, Sachdeva, Vyas and Thomas Collins9 This has been postulated to be due to the small size of such bubbles, which renders such bubbles smaller than capillaries, thus allowing them to circulate through the capillaries without causing obstruction. Additionally, microbubbles are generally composed of gases such as nitrogen that rapidly dissolve, which may occur faster in the higher pressure arterial circulation.
This case report highlights two major points: firstly, that intestinal pathology can lead to microbubbles that can be noted on echocardiography; and secondly, that microbubbles in the systemic circulation may not lead to drastic clinical sequelae by causing air embolism. This case report is unique in that it demonstrates the presence of microbubbles in an older child with unrepaired CHD than previously reported and represents one of the few case reports in patients of any age in whom microbubbles entered the circulation due to intestinal pathology.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S104795112500143X.
