Intra‐abdominal Hypertension: An Important Consideration for Diuretic Resistance in Acute Decompensated Heart Failure

ABSTRACT

Fluid accumulation is the hallmark of heart failure decompensation. Fluid overload and congestion are associated with recurrent hospitalizations, poor quality of life, and increased mortality in heart failure. Despite the use of high‐dose intravenous loop diuretic therapy, acutely decompensated heart failure patients may develop diuretic resistance. Diuretic refractoriness can be a result of elevated intra‐abdominal pressure (IAP) in acutely decompensated heart failure. Increased renal venous and interstitial pressures in patients with elevated IAP may lead to renal impairment and diuretic resistance. Routine approaches such as sequential nephron blockade with a combination of loop and thiazide or thiazide‐like diuretics, continuous diuretic infusion, and ultrafiltration may not be sufficient. Presented here is a case illustrating the importance of recognizing intra‐abdominal hypertension in patients with diuretic resistance. Lowering IAP improves renal perfusion, renal filtration, and diuresis. When elevated, IAP is an easily reversible cause of diuretic resistance. Additionally, abdominal perfusion pressure can be used to guide therapy to reverse end‐organ damage and avoid permanent renal replacement therapy.

Case Presentation

A 72‐year‐old, morbidly obese Caucasian male with known biventricular systolic failure, chronic kidney disease, and paroxysmal atrial fibrillation was hospitalized for acute decompensated heart failure (ADHF). Physical examination revealed bilateral pulmonary crackles and significant peripheral edema. Abdomen was obese, with parietal‐wall edema and abundant ascites. Admission serum creatinine was 3.7 mg/dL (baseline, 1.8 mg/dL), N‐terminal pro‐brain natriuretic peptide was 33 500 pg/mL, and serum albumin was 2.5 g/dL. The patient did not respond to 2 intravenous (IV) 80‐mg boluses of furosemide. The second bolus was preceded by 2.5 mg of metolazone 30 minutes prior. Bedside right‐heart catheterization showed a pulmonary capillary wedge pressure of 20 mm Hg and mixed venous oxygen content of 44% (Table 1). The patient did not respond to a continuous infusion of bumetanide and dobutamine. Conventionally, this patient would likely have been started on ultrafiltration (UF) therapy as per guidelines.1, 2 As his abdomen was distended, we obtained the intra‐abdominal pressure (IAP), which was found to be elevated (19 mm Hg). An ultrasound‐guided paracentesis was performed, and 8 liters of clear amber fluid was removed with simultaneous infusion of 25% albumin (5 g/L removed). No hypotension was observed. The serum ascites albumin gradient was <1.1 and leukocyte count was 215 cells/μL. There was a brisk diuresis after abdominal paracentesis (>8L over 48 hours). Intravenous bumetanide and dobutamine were discontinued. Serum creatinine improved from a peak value of 4.5 mg/dL (preparacentesis) to 2.5 mg/dL on discharge. Follow‐up creatinine was 2.0 mg/dL a week later. The patient elected hospice care and died 3 weeks later.

Table 1.

Hemodynamic Parameters on Admission and After Paracentesis

Hemodynamic Parameters	Preparacentesis	48 Hours Postparacentesis	Normal Values
RA	23 mm Hg	7 mm Hg	5–7 mm Hg
RV	48/17 mm Hg		15–30/1–5 mm Hg
PA	50/25 mm Hg (33 mm Hg)	35/6 mm Hg (16 mm Hg)	15–30/4–10 mm Hg; mean <20 mm Hg
PA O2 saturation	44%	50%	60%–80%
PCWP	20 mm Hg	7 mm Hg	<12 mm Hg
Cardiac output	6.2 L/min	6.8 L/min	4–8 L/min
Cardiac index	2.6 L/min/m2	3.0 L/min/m2	2.6–4.2 L/m2
PVR	1.8 WU	1.3 WU	<3 WU
Hg	6.8 g/dL	7.0 g/dL	13.5–17.5 g/dL

Abbreviations: Hg, hemoglobin; O₂, Oxygen; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle; WU, Wood units.

In summary, relief of increased IAP with abdominal paracentesis clearly triggered abundant diuresis in a patient who did not respond to IV loop diuretic therapy and inotropic support.

Diuretic Resistance in Acute Decompensated Heart Failure

Fluid accumulation is the hallmark of ADHF. Congestion is associated with recurrent hospitalizations, poor quality of life, and increased mortality in heart failure.3 Inadequate fluid removal leads to recurrent hospitalization with high readmission (24%–31%)4 and mortality rates.4 Despite the use of high‐dose IV loop diuretic therapy, ADHF patients may develop diuretic resistance. Diuretic refractoriness has been attributed to (1) the competition of organic anions with receptor sites for tubular transporters; (2) the “braking phenomenon” in fluid contraction that leads to neurohormonal activation, resulting in reduced solute delivery in the proximal tubule and enhanced solute reabsorption in the distal tubule; and (3) the rebound phenomenon, where infrequent dosing of diuretics result in periods of subtherapeutic diuretic concentrations when enhanced sodium retention takes place.5, 6, 7 Furthermore, in ADHF patients, a rise in IAP increases renal venous pressure, thereby reducing the transrenal perfusion gradient and renal perfusion. Elevated IAP also causes increased renal interstitial pressure that opposes net filtration pressure. Both increased renal venous and interstitial pressures contribute to renal impairment and diuretic resistance.5 Routinely used approaches such as sequential nephron blockade with a combination of loop and thiazide or thiazide‐like diuretics, continuous diuretic infusion, and UF may not remedy the issue at hand. In contrast, lowering IAP will improve renal perfusion, renal filtration, and diuresis.

Correlates of Intra‐abdominal Hypertension

Intra‐abdominal hypertension (IAH) is defined as a sustained pathologic rise in IAP ≥12 mm Hg.8 Intra‐abdominal hypertension may progress to abdominal compartment syndrome (ACS) when IAP is >20 mm Hg. Once considered a postsurgical condition, IAH and ACS are now thought to increase morbidity and mortality in patients receiving medical intensive care with a reported prevalence of 50% and 8%, respectively.8 The level of IAP that results in organ dysfunction is variable, depending on preexisting organ dysfunction, peripheral circulation, and cardiac function. A sustained IAP ≥12 mm Hg may affect the splanchnic microcirculatory flow by reducing net abdominal perfusion pressure (APP), and IAP of >15 mm Hg may cause organ dysfunction.9, 10 Abdominal perfusion pressure is the difference between mean arterial pressure and intra‐abdominal pressure (APP = MAP − IAP). An APP of >60 mm Hg is associated with improved survival, whereas an APP of <50 mm Hg is associated with increased mortality.11

Intra‐abdominal Hypertension in Acute Decompensated Heart Failure

Intra‐abdominal hypertension may be overlooked as a cause of organ dysfunction in ADHF. It has been reported to be elevated in up to 60% of ADHF in the absence of overt abdominal symptoms.12 Splanchnic and interstitial congestion may cause elevated IAP in the absence of ascites in ADHF.13

Factors contributing to decreased abdominal wall compliance, ascites, and capillary leak can increase IAP in ADHF.14 Elevated IAP decreases venous return (preload reduction) and impedes arterial outflow (afterload augmentation). Diaphragmatic elevation increases intrathoracic pressure and reduces ventricular compliance, contributing to decreased cardiac output.15 In addition, increased intrathoracic pressure compresses the pulmonary parenchyma, decreasing pulmonary and chest wall compliance. This results in decreased diffusing capacity of the lung for carbon monoxide, intrapulmonary shunt, hypoxia, and ventilation perfusion mismatch.15 Transmitted pressure from the abdominal cavity may result in spurious elevation of cardiac filling pressures, making preload assessment difficult.15, 16 The elevated values misrepresent the true intravascular volume and may lead to inappropriate use of diuretics.15, 16

Renal‐vein compression and increased renal parenchymal pressure may lead to decreased net filtration. Systemic hypotension and low cardiac output may aggravate the impact of elevated IAP on renal impairment. In turn, this heightens activity of the renin‐angiotensin‐aldosterone axis and vasopressin activity,17 leading to a downward spiral of fluid retention and worsening of IAH.

In the periphery, IAH/ACS reduces venous return from the lower extremities by impeding inferior vena cava flow.15, 18 Increased lower‐limb venous pressure leads to expansion of peripheral edema and increased risk for deep‐venous thrombosis.19, 20, 21, 22

Measurement of Intra‐abdominal Pressure

Physical assessment has a modest sensitivity (<60%) in identifying IAH and ACS.23 In most instances, IAP cannot be directly measured with an intraperitoneal catheter. Intra‐abdominal pressure is routinely assessed as bladder pressure using a urinary catheter attached to a pressure‐monitoring system.9 Normal IAP ranges from 5 to 7 mm Hg; however, IAP may be higher in patients with obesity or in an upright position. Intra‐abdominal pressure increases with inspiration and decreases with expiration during spontaneous breathing. In mechanically ventilated patients, IAP may be elevated due to reduced lung compliance or when positive end‐expiratory pressure is >15 mm Hg. The degree to which positive end‐expiratory pressure affects IAP has not been thoroughly investigated. Measurement of IAP should be performed in the supine position at end‐expiration, with the transducer placed at the mid‐axillary level. The presence of bladder injury, surgical repair, or bladder pathology precludes IAP measurement. Furthermore, neurogenic or contracted bladder conditions may result in inaccurate readings.

Management of Intra‐abdominal Pressure

Fluid removal is the major aim of therapy in ADHF. When IV loop diuretic therapy fails, measuring IAP is an inexpensive and minimally invasive procedure that excludes a cause of diuretic resistance. If IAH/ACS is identified, lowering IAP by mobilization of third space fluid can be achieved through a combination of diuretics, vasodilator, and/or inotropes. However, abundant ascites can be managed with ultrasound‐ or computer tomography–guided fluid removal, as it was in our patient.24 If >5L of ascites is removed, albumin infusion (6–8 g/L removed) is recommended to reduce the incidence of hypotension, hyponatremia, and mortality.25, 26 In certain patients, UF may be appropriate (Figure 1). The goal of therapy is to achieve APP >60 mm Hg, which portends a favorable outcome.11

Figure 1.

Management of ADHF with clinical fluid overload. Abbreviations: ADHF, acute decompensated heart failure; CO, cardiac output; CT, computed tomography; CVP, central venous pressure; IAP, intra‐abdominal pressure; PCWP, pulmonary capillary wedge pressure; SBP, systolic blood pressure; USG, ultrasonography.

In summary, the present case illustrates the importance of recognizing IAH in patients with diuretic resistance. Measurement of IAP is a simple and minimally invasive procedure. When elevated, IAP is an easily reversible cause of diuretic resistance. Additionally, APP can be used to guide therapy to reverse end‐organ damage and avoid permanent renal replacement therapy.