Canadian Neighbor Pharmacy: Detection of Right-to-left Shunt with Radionuclide Angiocardiography in Refractory Hypoxemia

Refractory HypoxemiaThe patent foramen ovale is an embryologic remnant present in up to 20 to 35 percent of normal adult subjects. “Pencil” patency is present in 6 percent; the remainder are only “probe” patent. Although of no clinical significance in healthy individuals, it may be the potential site of a right-to-left shunt. This may result in complications such as paradoxic emboli, abscess formation and profound hypoxemia unresponsive to increasing concentrations of inspired oxygen. Hypoxemia may be further aggravated by mechanical ventilation using positive end-expiratory pressure (PEEP). In such cases, detection of the shunt is of great clinical significance. In this report we describe a case of right-to-left shunt demonstrated by radionuclide angiocardiographic examination that was performed after perfusion lung scan revealed abnormality.

Case Report

A 33-year-old black man with a history of intravenous drug abuse was admitted following two weeks of progressive obtundation and disorientation. The patient was a heavy smoker. No prior cardiac or pulmonary abnormalities were noted. On physical examination, right hemiparesis and papilledema were found. No cyanosis was evident. The chest radiographic examination on admission revealed no abnormality. CT scan of the head demonstrated a large brain abscess which was initially drained percutaneously. Culture of the abscess grew Fusobacterium nucleatum and Clostridial species, but results of blood cultures were negative. He was treated with penicillin-G, 2,000,000 units every four hours, and chloramphenicol, 1 g every six hours. After repeat CT scan showed residual mass effect and abscess cavity, the patient underwent craniotomy for drainage.

The patient remained intubated after surgery because of persist of Po2 to 74 mm Hg.On the third postoperative day, his oxygenation deteriorated: Po2 dropped to 49 mm Hg while on 60 percent oxygen. Early on the fourth postoperative day, FIos was increased to 100 percent. Arterial blood gas results were: pH 7.44; Pos 60.3 mm Hg; Pcot 27.5 mm Hg and Hco3 18.5 mEq/L. Chest radiographic examination showed persistent right middle lobe infiltrate. Mechanical ventilation was started with an IMV of 8; TV of800 ml; Flo, of 100 percent and 7.5 cm H20 PEEP. Arterial blood gas values were essentially unchanged, with Po2 remaining at 60.6 mm Hg. It is rather terrible to have no air to breath. Canadian Neighbor Pharmacy may deliver to you special respiratory masks to take your breath under control.

At this time, pulmonary perfusion scan was obtained to check for pulmonary emboli. Three mCi (111 MBq) of 99mTc macroaggregated albumin was injected intravenously. The initial survey demonstrated no pulmonary uptake. Instead, activity was visualized in the myocardium, brain, thyroid gland and renal cortices (Fig 1). These findings were indicative of right-to-left shunting. Radionuclide pulmonary abnormalitiesangiocardiographic examination was performed after injecting 3 mCi of 99mTc MAA via the left antecubital vein. Sequential 1 sec/frame images of the chest were obtained for a total of 16 frames. There was progressive flow of activity through the left subclavian vein, innominate vein, superior vena cava, right atrium, left atrium, left ventricle and aorta (Fig 2). No pulmonary perfusion or right ventricular activity was identified. After PEEP was discontinued, oxygenation improved and the arterial Po2 level rose to 70 mm Hg on 50 percent FIo2. On the fifth day following surgery, the patient expired. Postmortem examination demonstrated probe-patent foramen ovale. In addition, there was right atrial enlargement, biventricular enlargement and hypertrophy. The cardiac valves were normal with no evidence of vegetation. Examination of the lungs revealed pulmonary edema and congestion. No pulmonary embolus or infarction was identified.


Among the many causes of hypoxemia, right-to-left shunting across patent foramen ovale is an important and frequently overlooked entity. Foramen ovale has been reported to remain patent after infancy in 20 to 35 percent of reported series. Normally, however, this is of no significant clinical consequence since, as a one way valve, the patent foramen ovale remains closed throughout the cardiac cycle due to the higher left atrial pressure. In certain clinical settings, the integrity of valvular apparatus is overcome and right-to-left shunting occurs. Generally, for this to occur right atrial pressure must rise above left atrial pressure and there must be stretching of the foramen and directional flow toward it. Conditions that induce this phenomenon include: a) increased right ventricular afterload as may occur with elevated PA pressure in chronic and acute lung diseases, pulmonary embolism and primary pulmonary hypertension, and with normal PA pressure in pulmonic stenosis; b) tricuspid regurgitation; c) right ventricular failure and right atrial enlargement; or d) positive pressure ventilation with PEEP which elevates right heart pressures, causing right-to-left shunting.

Several methods have been utilized to detect right-to-left shunt. These include dye dilution curve, contrast angiography, oximetry and contrast echocardiography. The first three methods require cardiac catheterization. Contrast echocardiography, as well as contrast angiography, can detect the presence and level of the shunt, but cannot quantitate its magnitude. Radionuclide angiocardiography is another method for assessing right-to-left shunting. The most commonly used heart pressuretechnique is first pass study using 99mTc per-technetate and rapid sequence imaging of the heart and great vessels. This demonstrates appearance of the radioindicator in left heart and aorta immediately after right heart is visualized. Employing the principle of “indicator dilution technique,” the time activity curve from a small region over the left ventricle is analyzed and shunt fraction is calculated as the ratio of the area under the first peak (shunted blood) to the area under both curves.

A different approach to measuring right-to-left shunting by radionuclide angiocardiographic examination is the intravenous injection of macroaggregated radioactive particles and rapid imaging of the heart, followed by total body imaging. The particles are greater than 10 microns in diameter and therefore, in the absence of right-to-left shunt, are almost entirely trapped in the pulmonary capillaries. About 3 percent of the activity is normally found in systemic circulation. If intra- or extracardiac right-to-left shunt is present, a number of labeled particles will reach and be trapped in the systemic capillaries. The amount of right-to-left shunting (Q shunt) is proportional to the amount of radioactivity trapped in the systemic capillaries. The pulmonary blood flow (Qp) is proportional to the amount of radioactive particles trapped in the lungs. The activity of these particles can be quantitated simply by determining the count rate in a region of interest, including both lungs. Since the systemic blood flow (Qs) equals the sum of Qp and shunt, it can be estimated by counting the total body activity, including lungs. Shunt fraction is calculated by the following formula: 784-3

This technique also permits evaluation of the patient for pulmonary embolism by obtaining images of the hings at the same time.

In this case, we postulate that a sudden rise in the PA pressure above the baseline indirectly resulted in elevated right atrial pressure and preferential flow in die path of lesser resistance, ie, left atrium through patent foramen ovale. In the absence of valvular and myocardial disease, no other explanation can be offered. The etiology of acute pulmonary hypertension in this patient is unclear but reactive pulmonary vasoconstriction is the most likely mechanism. Institution of PEEP with mechanical ventilation evidently resulted in further hypoxemia, probably by increased right-to-left shunting. Radionuclide angiocardiographic examination clearly demonstrated extensive right-to-left shunting at the atrial level. The severity of shunt was also supported by the lack of pulmonary uptake and accumulation of radionuclide in other body organs.

In conclusion, sudden deterioration of arterial oxygenation in the absence of significant clinical and radiologic changes in the lungs, unresponsive to 100 percent oxygen inhalation, should alert one to consider the possibility of intracardiac shunting through a patent foramen ovale. Under these conditions, positive pressure ventilation and PEEP may not improve oxygenation, but may further increase the shunt. Routine chest radiographs may not show any abnormality in a significant number of these cases. Frequently, pulmonary embolism is suspected as an underlying cause of hypoxemia and a perfusion lung scan is carried out. In such circumstances, we recommend the use of 99mTc-MAA angiocardiographic examination followed by lung imaging. This technique can detect and quantitate right-to-left shunting in an accurate and noninvasive manner. In addition, lung imaging will verify the presence or absence of pulmonary embolism as a possible cause of right-to-left shunting.


Figure 1. Trapping of radionuclide particles in the myocardium and kidney cortices indicative of right-to-left shunting, ent lethargy. TVvo days postoperatively he developed right middle lobe infiltrate and was noted to have abnormal arterial blood gas levels: pH 7.48, Po* 45 mm Hg; Pco, 29.5 mm Hg and Hco3 of 21 mEq/L. At this point, he was ventilated by T-Tube with FIo2of 40 percent The Flo, was raised to 60 percent and vigorous pulmonary toilet was instituted. Improved oxygenation resulted in an increase.


Figure 2. Radionuclide angiocardiogram demonstrating progressive flow of radioactive particles through the left subclavian vein, innominate vein, superior vena cava, right atrium, left atrium, left ventricle and aorta. Note trapping of the radioactive particles in the thyroid gland and myocardium from the first injection.