Introduction with a clinical conundrum

A 66-year-old man is transferred from an outside hospital due to inability to be liberated from the ventilator. He presented a week earlier with pneumonia and sepsis. He received six liters of fluid initially, and has been running net positive 1-2 liters daily since then (for a total of about 15 liters net positive). Despite receiving this volume he has developed a mild acute kidney injury with a creatinine of 1.7 mg/dL.

On examination he is grossly edematous. He is maintaining a MAP of 60 mm off vasopressors. His urine output is poor at about 20 ml/hr. His intraabdominal pressure is 18 mm. His plateau pressures on the ventilator are elevated. How should this patient be managed?

Abdominal compartment syndrome & intraabdominal hypertension

Very high pressures within the abdomen may cause a compartment syndrome with organ failure. Compression of the inferior vena cava causes reduced venous return and hypotension. Lung compression causes atelectasis and impaired ventilation. Compression of renal veins impairs renal perfusion. Gut hypoperfusion also occurs, causing translocation of bacteria into circulation leading to vasodilatory shock. Untreated, this creates a spiral of multiorgan failure and death.

Intraabdominal hypertension is defined as elevated pressure without overt organ failure (table below). Among critically ill patients, intraabdominal hypertension is much more common than abdominal compartment syndrome. Although moderate intraabdominal hypertension doesn't cause obvious multiorgan failure, it may cause organ injury particularly to the kidneys.

Elevated intraabdominal pressures are common in sepsis

Abdominal hypertension classically occurs in patients with surgical abdominal disease. However, it can also occur in any patient with systemic inflammation undergoing large-volume fluid resuscitation. For example, it is common among medical ICU patients undergoing large-volume fluid resuscitation for sepsis (Ortiz-Diaz 2014). Daugherty 2007 prospectively studied 40 septic medical ICU patients who received >5 liters over 24 hours. 85% had an intraabdominal pressure >12 mm and 33% had a pressure >20 mm.

More recently, Anvari 2015 analyzed abdominal pressures among 53 patients admitted to a medical ICU with at least two risk factors for intraabdominal hypertension (table below). Among these patients, a majority had pressures >12 mm, while 16% had pressures above 20 mm.

Diagnosing abdominal compartment syndrome in sepsis is difficult

Differentiating between abdominal hypertension and abdominal compartment syndrome is generally tricky. Technically the diagnosis of compartment syndrome is made on the basis of higher pressures (at least 20 mm) and new organ failure. However, these two entities exist as a continuum, rather than being fundamentally distinct:

This differentiation becomes nearly impossible in the context of septic shock. The primary defining feature of compartment syndrome is new organ failure. However, patients in septic shock already have organ failure. It's often impossible to know how much of this failure may be caused by elevated intraabdominal pressure.

Consequently, it's hard to make an irrefutable diagnosis of compartment syndrome in septic patients. This may lead to under-recognition and under-treatment of this condition. For example, in the Daugherty study above, 10 patients met diagnostic criteria for abdominal compartment syndrome. However, none underwent laparotomy (one patient was scheduled for surgery but arrested beforehand).

Management: Lowering intraabdominal pressure

Although common, the management of sepsis-associated intraabdominal hypertension is unclear. The following interventions seem sensible:

Avoid additional fluid resuscitation.

Once the acute phase of illness has passed, remove fluid with diuresis or dialysis. Numerous studies have demonstrated that fluid removal reduces intraabdominal pressure (Regli 2015).

Drainage of ascites if significant volumes are present. Placing an indwelling peritoneal catheter may be more effective than paracentesis.

Management of ileus or constipation.

Avoidance of bucking the ventilator (with use of comfortable ventilator settings and treatment of pain/agitation).

Reverse Trendelenberg position? (Might limit transmission of pressure to thorax and avoid abdominal compression that results from elevating the head of the bed).

Orogastric tube suction is generally reserved as a last resort, as this will impair nutrition.

Surgical consultation for possible laparotomy is reasonable in patients with abdominal pressures >20 mm and overt compartment syndrome refractory to medical intervention. However, most patients don't have a sufficiently clear-cut compartment syndrome to merit laparotomy.

Management: Defending the abdominal perfusion pressure

In the context of elevated intraabdominal pressure, the perfusion pressure for organs in the abdomen (e.g. the kidneys) may be calculated as follows:

Abdominal Perfusion Pressure = MAP – (Abdominal compartment pressure)

This is analogous to the cerebral perfusion pressure:

Cerebral Perfusion Pressure = MAP – (Intracranial pressure)

The abdominal perfusion pressure may be more important than the abdominal compartment pressure. Observational studies have found that an abdominal perfusion pressure below 60 mm may predict death better than either lactate or urine output (Cheatham 2000). A logical approach may be to increase the MAP goal, in order to defend the abdominal perfusion pressure:

Target MAP > (Abdominal compartment pressure) + 60 mm

In patients with a normal intraabdominal pressure (~5 mm), this yields the usual MAP target of above 65 mm. However, for patients with intraabdominal hypertension (e.g., pressure of 15-20 mm), it would suggest a slightly higher MAP target (>75-80 mm). The SENSIPAM trial proved that targeting higher MAPs is reasonably safe and potentially effective. It’s possible that patients with intraabdominal hypertension may represent a subset of patients who could benefit from a slightly higher MAP goal.

The practice of adjusting a MAP goal based in abdominal compartment pressure is often advocated, but remains untested. Pending investigation, this seems like a reasonable intervention based on general physiologic principles (similar to increasing MAP targets for patients with elevated intracranial pressure).

Dangers of unrecognized intraabdominal hypertension

Early recognition of abdominal hypertension may facilitate effective management based on simple interventions. Alternatively, unrecognized intraabdominal hypertension may lead to a misguided and ineffective resuscitative strategy. For example, undiagnosed intraabdominal hypertension might cause clinicians to accept an inadequate MAP.

Unrecognized intraabdominal hypertension may also lead to over-resuscitation. For example:

Intraabdominal hypertension may compress the inferior vena cava, producing an ultrasound image suggesting hypovolemia.

Abdominal compartment syndrome is associated with lactic acidosis.

Intraabdominal hypertension increases pulse-pressure variation, probably due to poor thoracic compliance with exaggerated swings in intrathoracic pressure during ventilation (Regli 2015).

A small inferior vena cava, persistently elevated lactate, and high pulse-pressure variation could prompt the clinician to administer more fluid. However, this would only worsen the situation by causing more tissue edema and higher abdominal pressures.

Over-resuscitation and intraabdominal hypertension

A growing body of literature suggests that volume overload in critically illness is harmful. For example, Paul Marik just published a study relating the volume of fluid received by septic patients during the first hospital day to mortality (Marik 2017). Receipt of >5 liters of fluid correlated with increased mortality:

Intraabdominal hypertension may be an important mechanism whereby over-resuscitation causes harm:

Large-volume resuscitation is the most important cause of intraabdominal hypertension among patients without primary abdominal pathology. For example, investigators have found linear relationships between fluid volume and intraabdominal pressure among CABG and burn patients (figure below). Conversely, fluid removal reduces intraabdominal pressure.

Animal and human data show that intraabdominal hypertension causes organ injury. Several studies have found intraabdominal pressures to be an independent risk factor for mortality (Ortiz-Diaz 2014).

Numerous studies prove that intraabdominal hypertension is common in critically ill patients who receive large-volume resuscitation.

If intraabdominal hypertension is an important mediator of harm from volume overload, this would have important clinical implications. For example, serial measurement of intraabdominal pressure could detect that the patient is developing intraabdominal hypertension (an indication to stop giving fluid).

One common misconception is that if a patient doesn't have pulmonary edema, then it is safe to give additional fluid. Unfortunately, life isn't this simple. Even in the absence of pulmonary congestion, dangerous abdominal congestion may be occurring. Pulmonary congestion relates to left ventricle function (elevation of pulmonary capillary wedge pressure), whereas intraabdominal congestion relates to right ventricle function (elevation of central venous pressure). Therefore, it is possible for a patient with impaired right ventricular function to develop severe intraabdominal congestion despite having dry lungs.

Intraabdominal hypertension and chronic sepsis

Following initial recovery from sepsis, many patients develop a persistent state of renal failure, volume overload, and endothelial failure (“chronic sepsis“). This may be a common cause of chronic critical illness following septic shock, an intractable and morbid condition.

It is likely that abdominal hypertension is a significant player in chronic sepsis. As discussed earlier, volume overload increases intraabdominal pressure. One of the earliest consequences of intraabdominal hypertension is oliguric renal failure (Patel 2016). This may create a vicious cycle leading to intractable volume overload and worsening renal failure:

Renoresuscitation refers to sepsis resuscitation with an emphasis on preserving renal function and fluid balance, in efforts to avoid chronic sepsis. It is possible that early recognition and management of abdominal hypertension could play a useful role in this resuscitative strategy.

Implications for sepsis guidelines

The 2016 Surviving Sepsis Guidelines recommend that all patients receive 30 cc/kg fluid within three hours. Although this seems reasonable in most patients, it may not apply to all patients because it ignores individual patients' physiology.

Another problem with these guidelines is that they focus on avoiding under-resuscitation, while ignoring over-resuscitation. It's possible that over-resuscitation is even more dangerous than under-resuscitation. Traditionally, it was believed that application of vasopressors before adequate volume resuscitation (“pressors with an empty tank”) would cause unopposed vasoconstriction and poor cardiac output. However, we now appreciate that vasopressors actually cause venoconstriction which increases preload. Thus, the concept that patients must receive large-volume fluid resuscitation before vasopressors is wrong.

If the guidelines are going to specify a mandatory minimum fluid volume (30 cc/kg), they should attempt to achieve balance by also suggesting a maximum fluid balance. For example, it could be recommended that clinicians should pay close attention to the patient's inputs and outputs, with avoidance of running the patient severely volume positive (e.g. >80 cc/kg net positive).

Polycompartment syndrome

This post has focused on the renal implications of intraabdominal hypertension, but some other consequences bear mention. Intraabdominal hypertension is closely linked with elevated intrathoracic pressures (Rastogi 2014). In severe cases, elevated intraabdominal and intrathoracic pressures may lead to increased intracranial pressure, a phenomenon termed polycompartment syndrome.

To illustrate the relevance of this physiology, below is a mind-blowing lecture by Thomas Scalea exploring this from the perspective of intracranial pressure (spoiler alert: he treated a young woman with refractory ICP elevation by using ECMO to decompress her thorax):

Resolution of the case

How should we manage our patient with massive volume overload, intraabdominal hypertension, and soft blood pressure? This is a bit of a paradox:

In order to recover from intraabdominal hypertension, he requires fluid removal.

Intraabdominal hypertension and elevated intrathoracic pressure both impair preload, making it doubtful whether he could tolerate diuresis. His blood pressure is already tenuous.

To manage this physiology, the following interventions were used simultaneously (a “squeeze and diurese” strategy).

Vasopressin was initiated, titrated to achieve an abdominal perfusion pressure >60 mm. In his case, this involved targeting MAP >78 mm.

He was aggressively diuresed with a combination of indapamide and furosemide.

Over the next few days he diuresed about 10 liters. Meanwhile, his kidney injury resolved. His pulmonary function improved and he was liberated from the ventilator.

Intraabdominal hypertension is common among septic patients receiving large-volume resuscitation, but usually overlooked.

Intraabdominal hypertension may cause occult organ injury (especially kidney injury), even in the absence of frank abdominal compartment syndrome.

Diagnosing intraabdominal hypertension may identify patients at risk from further fluid administration. Such patients may benefit instead from volume removal.

Abdominal perfusion pressure is equal to the abdominal pressure subtracted from the MAP, analogous to cerebral perfusion pressure. Maintaining an abdominal perfusion pressure >60 mm might be beneficial.

The best approach to intraabdominal hypertension is prevention, by using a conservative fluid resuscitation strategy.

Related

Addendum: After posting this, Dr. Manu Malbrain (@Manu_Malbrain) made some suggestions regarding additional references to add. Here they are, with his comments:

Image credit: Kidney