Chapter 4: Indirect Portal Pressure Measurement and Carbon Dioxide Wedged Hepatic Portography

Historically, portal pressures were directly measured through surgical, percutaneous transhepatic, or transjugular catheterization of the portal vein. Given the invasive nature and associated procedural risks, direct portal pressure measurement was rarely performed. Publications in 1951 by Myers and Taylor and separately by Friedman and Weiner described occlusive hepatic venous catheterization in humans, cats, and dogs.1–3 Advancing the catheter to the terminus of the hepatic venule transduces the sinusoidal pressure, which is termed the wedged hepatic venous pressure (WHVP), and is an indirect reflection of the portal venous pressure. However, because the WHVP can be spuriously elevated due to increased intraabdominal pressure, for example from ascites, the free hepatic venous pressure (FHVP) is also measured by retracting the catheter into a nonocclusive position within the vein. Subtracting the FHVP from the WHVP results in the hepatic venous pressure gradient (HVPG), which is not subject to intraabdominal pressure changes. In the forthcoming sections, technical considerations and prognostic implications are discussed.

Comparison of End-Hole and Balloon Catheters for HVPG Measurement

Indirect portal pressure can be measured by advancing any variety of end-hole catheters into a wedged position within a hepatic vein ( Fig. 4.1; Fig. 4.2). Functionally, the pressure measurements represent only a small area in the liver with smaller veins representing smaller areas of liver, and increased potential for discrepancy. Repeating measurements requires the end-hole catheter to be removed and then repositioned into the same vein. Moreover, an end-hole catheter may be subject to kinking or partial obstruction resulting in spurious values. In 1979, Barth and Udoff reported on the use of balloon catheters for indirect portal pressure measurement.⁴ Balloon catheters can occlude larger hepatic venous branches, allowing measurement of pressures across more sinusoids ( Fig. 4.3; Fig. 4.4). Repeat measurements are performed by deflating and inflating the balloon, providing reproducible measurements from the same area more easily.

Fig. 4.1 Wedged end-hole catheter: Fluoroscopic image with an end-hole catheter in a wedged position. Iodinated contrast was hand injected to blush the hepatic parenchyma (arrowhead) with reflux across the hepatic sinusoids, opacifying portal radicals (arrows).

Fig. 4.2 Magnification wedged end-hole catheter. Magnification fluoroscopic image with an end-hole catheter in a wedged position. Iodinated contrast was hand injected to blush the hepatic parenchyma (arrowhead) with reflux across the hepatic sinusoids, opacifying portal radicals (arrows).

Fig. 4.3 Confirmation of balloon occlusion. Fluoroscopic image with the balloon inflated. After the wedged hepatic measurement was recorded and before deflating the balloon, contrast is injected to confirm that the balloon was occluding the hepatic vein.

Several studies have compared the reliability and reproducibility of indirect portal pressure measurements between end-hole and balloon catheters spanning over 40 years. Thalheimer and associates performed a meta-analysis of 11 studies on 320 patients over 44 years and ultimately found that wedged hepatic venous pressure did indeed reflect the portal venous pressure.5 It is notable that 7 of the 11 studies used an end-hole catheter and that the 3 most recent studies were with the balloon technique.

The most recent studies comparing balloon with end-hole catheters for the measurement of HVPG were performed by Zipprich et al in 2010, Maleux et al in 2011, and Smith et al in 2011.^6–8 Zipprich et al compared the two methods head to head and noted that the assessment of the WHVP was the most striking weakness of the end-hole catheter. Moreover, they note the heterogeneity of liver disease and the possibility of sampling variability covering smaller areas of the liver and inherent peripheral positioning of the end-hole catheter to measure a WHVP as weaknesses of the technique. The balloon catheter produced more consistent results that were more closely correlated with the portal pressure.⁶ Maleux et al compared end-hole catheter measurements with balloon catheter measurements and noted that both corresponded well with a direct portal measurement. However, in this publication the agreement with direct portal pressure was “clearly much better” with the balloon catheter and there was more variability with the end-hole catheter measurements.⁷ Smith et al noted significant overall differences between the two techniques, particularly in patients with fibrosis.⁸ Overall differences in the HVPG were small. Collectively, these studies comprise nearly 300 patients and generally found improved accuracy, reproducibility, and reliability with occlusion balloon catheters versus end-hole catheters for the measurement of WHVP.

Fig. 4.4 Confirmation of balloon occlusion, a second example: Fluoroscopic image with a balloon occlusion catheter in a wedged position. Iodinated contrast was hand injected to confirm stasis in the hepatic vein. Care is taken not to reflux across the hepatic sinusoids.

Performing the procedure in a reproducible manner in similar conditions is of paramount importance, particularly if a patient requires repeated measurements to monitor disease progression. Herein is a summary of the technique as published by Groszmann and Wongcharatrawee and reiterated in a separate publication by Groszmann, Vorobioff, and Gao.9,10 Groszmann et al recommend a quartz pressure transducer, which has been calibrated against a known external pressure, and a recorder which can trace the pressure values at a slow recording speed of approximately 1-2 mm/s ( Fig. 4.5).

Using an occlusion balloon catheter and a scale measurement up to 30-40 mm Hg, the transducer should be positioned at the level of the right atrium in the mid-axillary line. The IVC pressure should be recorded; then the catheter can be advanced into the liver for measurement of the FHVP, WHVP, and mean pressure. Of note, the FHVP should be no more than 1 mm Hg greater than the IVC pressure ( Fig. 4.6). Moreover, when performing occlusion measurements, a check for total occlusion is performed at the end of the measurement by injecting contrast. The authors recommend pressure tracings to continue for 45 to 60 seconds, and measurements should be repeated at least three times to ensure reproducibility.

Fig. 4.5 Pressure tracing with free and wedged hepatic venous pressure. Pressure tracing strip shows a baseline pressure of the free hepatic vein. The balloon is inflated (black arrow) revealing a divergence between a wedged hepatic venous pressure (top line) and free hepatic venous pressure (baseline). The difference between the lines (arrowheads) is the hepatic venous pressure gradient. After deflating the balloon (white arrow) the two lines converge.

Generally, benzodiazepine sedatives will not significantly affect the accuracy of hepatic venous pressure measurements, though the patient should be similarly medicated each time if undergoing serial measurements.11 In contradistinction, Reverter et al found that if patients were not awake and under deeper levels of sedation, as would be achieved with propofol and remifentanil, there would be increased variability and uncertainty of the measurements attributable both to a change in the respiratory pattern and the hemodynamic effects of the sedatives.¹²

Fig. 4.6 Right hepatic venogram and free hepatic venous pressure. Fluoroscopic image of the sheath in the right hepatic vein, which is filled with iodinated contrast. The sheath tip is approximately 3 cm from a vertical white line, which demarcates the hepatic venous confluence with the inferior vena cava. Free hepatic venous measurements should be within 1 mm Hg of the IVC pressure.

Indirect portal pressure measurement has added tremendously to the body of knowledge regarding the pathophysiology, treatment, and research regarding portal hypertension. Indirectly measuring the portal pressure not only is diagnostic of portal hypertension, but can help differentiate the underlying etiology. Normal portal pressure ranges between 1 and 5 mm Hg with values above 5 mm Hg reflecting increased resistance through the portal circuit, portal hypertension. The pattern of the acquired pressure measurements (FHVP, WHVP, and HVPG) in conjunction with biopsy can help differentiate portal hypertension into pre-hepatic, intra-hepatic, and post-hepatic etiologies with the large majority, viral hepatides, causing intra-hepatic portal hypertension. For instance, post-hepatic causes typically have elevation of the FHVP and WHVP, but a normal HVPG, while pre-hepatic etiologies will have a normal WHVP despite clinical signs of portal hypertension.13,14

However, the clinical utility of this value transcends strict diagnosis as it can provide important prognostic information in cirrhotics, predict the development of complications of portal hypertension, and monitor therapeutic response in portal hypertensives to support clinical decisions. D’Amico et al systematically reviewed 118 studies to evaluate the natural history and prognostic indicators of survival in cirrhotics, finding that measurement of the portal pressure was predictive of death in 67% of the studies.¹⁵ For the manifestations of portal hypertension such as ascites and varices to develop, the threshold portal pressure of 10 mm Hg must be reached. Above a portal pressure of 12 mm Hg, the risk for variceal hemorrhage exists.^16,17 When diagnosed with portal hypertension, patients are treated with beta-blockers and nitrates to help decrease the portal pressure, thereby decreasing the risk of variceal hemorrhage.¹⁸ Generally, a decrease of the HVPG by 20% is the goal of therapy, and monitoring the response with repeated HVPG measurements will delineate which patients may be nonresponders and warrant more aggressive therapy.^19,20

Wedged CO₂ Portography

Historically, portography was performed either through visceral arteriography, a direct percutaneous transhepatic approach, or through wedged hepatic portography, which forces a contrast medium across the hepatic sinusoids in a retrograde manner (from hepatic venules through the sinusoids and refluxing back into the portal venules). Presently, neither arteriography nor direct percutaneous access is commonly performed for the sole purpose of imaging the portal vein. Refinements in ultrasound technology, MRI, and CT coupled with the wide availability of these exams allow rapid, accurate, and noninvasive assessments of the liver, portal veins, and flow dynamics. However, while wedged CO₂ portography is not considered an essential pre-requisite for TIPS placement, it is routinely performed intraprocedurally prior to TIPS placement to evaluate and localize potential portal venous radicals thereby decreasing needle passes and procedure time.

Characteristics of Carbon Dioxide

Carbon dioxide is colorless, odorless, widely available, inexpensive, and safe. One of the important features of CO₂ as a gas contrast is that it is highly soluble and does not readily create long-lasting “air-locks,” or rather, “gas-locks” in the studied area. Initially, CO₂ use as a venous contrast agent was described in the 1950s for the evaluation of pericardial effusion and since then it has been applied to many various interventional procedures including peripheral arterial disease, intra-abdominal hemorrhage, venous disease, abdominal aortic aneurysm repair, and TIPS placement among other procedures.21,22 Cho studied the effects of various intravenous CO₂ volumes on cardiopulmonary parameters and confirmed that a single dose up to 1.6 cc/kg resulted in no adverse consequence, though caution should be exercised in patients with pulmonary hypertension. Because CO₂ is continuously produced and exhaled, the small volumes needed for imaging can be repeatedly injected every 30 seconds to 60 seconds. Moreover, as an endogenously produced substance, CO₂ poses no risk of allergy, hepatotoxicity, or nephrotoxicity. This is of particular importance when considering that many patients with vascular or liver disease may be susceptible to contrast induced nephrotoxicity either from impaired renal function or depletion of their intravascular volume.²³

Key characteristics of CO₂ gas compared with other contrast agents include its buoyancy, low viscosity, and high solubility. Although CO₂ rapidly dissolves in blood and is quickly cleared, it does not mix with blood in the same manner as iodinated contrast would. Instead, because CO₂ is buoyant, it remains in the anti-dependent position, floating anterior to blood in a supine patient. With digital subtraction techniques, this displacement of blood decreases the intravascular density and results in a negative contrast image. Taken together with low viscosity and high solubility, these properties allow rapid reflux of large volumes across the hepatic sinusoids. Any extravasation of CO₂ is cleared quickly, and because it is a negative contrast agent, any residual CO₂ does not create a parenchymal stain which may obscure wires or catheters.²⁴ However, because CO₂ is buoyant and is of low viscosity and thus can reflux readily, CO₂ portography is not reflective of portal hemodynamics (for example, whether the portal flow is petal or fugal).

Preparation and Use of CO₂

Several delivery systems exist for CO₂ injection ranging from simple syringe hand injection, automatic and mechanical injectors, to prepackaged carbon dioxide kits from multiple vendors. Two technical challenges in the handling and delivery of this gas are present: air contamination and “explosive delivery” during hand injection.^22,25,26 In serial publications, Hawkins and Caridi described the essential components of a modified plastic bag system with an O-ring, syringe, stopcocks and connectors, and medical grade CO₂ cylinder.^27,28 This system allows controlled delivery and decreases potential contamination with room air. The plastic bag is purged three times through the O-ring filter with medical grade CO₂ and will subsequently serve as the CO₂ reservoir. The reservoir is connected with a three-way stopcock and connectors to a 50-mL syringe and connector tubing. CO₂ from the reservoir is used to fill the syringe and purge the air out of the tubing, which is attached to a second three-way stopcock and then connected to the angiographic catheter. At the second three-way stopcock, it is crucial to elicit a small amount of back bleeding from the catheter and then to purge the blood from the catheter with CO₂. This step functions to minimize the “explosive delivery” or “sudden give” that is noted when CO₂ hand injection is performed. If the catheter is full of fluid, a forceful injection of CO₂ is required to clear the fluid because CO₂ is compressible. Upon clearing the catheter, the “sudden give” is felt as there is a rapid expansion of the CO₂ and “explosive delivery” is realized. Priming the catheter as described allows for controlled, direct, and gentle injections of CO₂.^22,25 Digital subtraction angiography is performed at three to four frames per second. Stacking of images and inversion imaging is also used to increase the sensitivity and specificity of CO₂ imaging²⁴ ( Fig. 4.7; Fig. 4.8).

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