Abdominal Compartment Syndrome: pathophysiology and definitions

As originally described over 80 years ago by Emerson, rising IAP increases intrathoracic pressure through cephalad deviation of the diaphragm [30]. Increased intrathoracic pressure significantly reduces venous return resulting in reduced cardiac output [33, 47‐57]. Such reductions have been demonstrated to occur at an IAP of only 10 mmHg [18, 57]. Hypovolemic patients appear to sustain reductions in cardiac output at lower levels of IAP than do normovolemic patients [50, 53]. Hypervolemic patients demonstrate increased venous return in the presence of mild to moderate elevations in IAP suggesting that volume resuscitation may have a protective effect [53]. Diaphragmatic elevation and increased intrathoracic pressure have also been postulated to cause direct cardiac compression reducing ventricular compliance and contractility [49]. Systemic vascular resistance (afterload) is increased through compression of both the aorta and systemic vasculature and pulmonary vascular resistance through compression of the pulmonary parenchyma [33, 48, 51‐56, 58]. As a result, in the absence of severe IAH, mean arterial pressure typically remains stable despite a decrease in venous return and cardiac output. Such increases in afterload may be poorly tolerated by those with marginal cardiac contractility or inadequate intravascular volume. Preload augmentation through volume administration appears to ameliorate, at least partially, the injurious effects of IAH-induced increases in afterload [18, 33, 48, 53, 56, 58, 59].

Paradoxically, intracardiac filling pressures such as pulmonary artery occlusion ("wedge") pressure (PAOP) and central venous pressure (CVP) typically increase with rising IAP despite the reduced venous return and cardiac output [47‐49, 51, 53, 56, 57, 59‐64]. This apparent deviation from Starling's Law of the heart is due to the fact that both PAOP and CVP are measured relative to atmospheric pressure and are actually the sum of both intravascular pressure and intrathoracic pressure [63, 64]. In the presence of IAH-induced elevations in intrathoracic pressure, PAOP and CVP tend to be erroneously elevated and no longer reflective of true intravascular volume status [47‐49, 57, 59‐61, 63, 64]. Such alterations in PAOP and CVP have been demonstrated with an IAP of only 10 mmHg [57]. Attempts to correct for this measurement error through use of transmural pressures (i.e., PAOP minus intrathoracic pressure) has confirmed that transmural PAOP decreases with rising IAP correctly reflecting the decreased venous return and cardiac preload [59]. Several studies have demonstrated that volumetric parameters, such as right ventricular end-diastolic volume (RVEDV), global end-diastolic volume (GEDV), or stroke volume variation (SVV) are superior predictors of intravascular volume status whose accuracy is unaffected by changes in intrathoracic pressure [63‐66]. When traditional intracardiac filling pressures must be used, transmural pressures may be estimated as follows [63, 64]:

Transmural PAOP = PAOP - 0.5*IAP

Transmural CVP = CVP - 0.5*IAP

IAH also reduces venous return from the lower extremities functionally obstructing inferior vena caval blood flow by two mechanisms. First, inferior vena caval pressure increases significantly in the presence of IAH and has been demonstrated to parallel changes in IAP [18, 33, 53, 56]. Second, cephalad deviation of the diaphragm causes a mechanical narrowing of the vena cava at the diaphragmatic crura further reducing venous return to the heart [54, 67]. Femoral vein pressures are markedly increased and venous blood flow and pulsatility dramatically reduced [68, 69]. The resulting increases in extremity venous hydrostatic pressure promote the formation of peripheral edema. These changes place the patient with IAH at risk for development of deep venous thrombosis [69‐71]. Reduction of IAP restores femoral venous blood flow, but has anecdotally been reported to result in pulmonary embolism [71].

The pulmonary effects of elevated IAP have been recognized for many years [30, 33, 49, 51, 59, 68, 72‐74]. IAP is transmitted to the thorax both directly and through cephalad deviation of the diaphragm. This significantly increases intrathoracic pressure resulting in extrinsic compression of the pulmonary parenchyma and development of pulmonary dysfunction [18, 47, 48, 57, 59, 68]. Compression of the pulmonary parenchyma appears to begin with an IAP of 16–30 mmHg and is accentuated by the presence of hemorrhagic shock and hypotension [57, 75]. Parenchymal compression results in alveolar atelectasis, decreased oxygen transport across the pulmonary capillary membrane, and an increased intrapulmonary shunt fraction (Qsp/Qt). IAH-induced atelectasis has been demonstrated to cause an increase in the rate of pulmonary infection [76]. Parenchymal compression also reduces pulmonary capillary blood flow leading to decreased carbon dioxide excretion and an increased alveolar dead space (Vd/Vt) [57]. Both peak inspiratory and mean airway pressures are significantly increased and may result in alveolar volutrauma [57, 75]. Spontaneous tidal volumes and dynamic pulmonary compliance are reduced resulting in further ventilation-perfusion mismatching [57, 75]. In combination, these effects lead to the arterial hypoxemia and hypercarbia that, in part, characterize ACS [18, 33, 48, 51, 59, 73].

IAH-induced reductions in renal blood flow and function have been demonstrated in both animal and human models [33, 35, 42, 51, 77]. These changes occur in direct response to increasing IAP with oliguria developing at an IAP of 15 mmHg and anuria at 30 mmHg [32, 33, 42]. Renal artery blood flow has been demonstrated to be preferentially diminished in comparison to both celiac and superior mesenteric artery blood flow [68]. Renal vein pressure and renal vascular resistance are both significantly elevated [35, 42, 48]. All of these changes shunt blood away from the renal cortex and functioning glomeruli leading to impaired glomerular and tubular function and significant reductions in urinary output [32, 33, 35, 41, 42, 48, 49, 51, 73, 77‐80].

Several mechanisms have been proposed as the etiology for IAH-induced renal dysfunction and failure. Harman et al. negated direct ureteral compression as a cause through studies utilizing ureteral stents [42]. Other authors have suggested that direct parenchymal compression and development of a "renal compartment syndrome" results in renal ischemia and subsequent failure [70, 81]. Stone demonstrated in traumatically injured patients that incising the renal capsule could reverse renal failure if performed early and prior to development of severe renal dysfunction [81]. Recent studies suggest that compression of the renal vein likely plays the primary role in the development of renal dysfunction with reduced cardiac output playing a secondary role [32, 33, 48, 81].

IAH decreases glomerular filtration rate causing a rise in both blood urea nitrogen and serum creatinine and a reduction in creatinine clearance [33, 35, 42, 48, 51, 79]. Osmolar clearance is similarly decreased and fractional excretion of sodium increased [79]. Urinary sodium and chloride concentrations decrease and urinary potassium concentrations increase [33]. Plasma renin activity and aldosterone levels increase significantly [33, 48]. Antidiuretic hormone levels have been demonstrated to increase to more than twice basal levels [82]. All of these pathophysiologic changes appear to be potentially reversible if the patient's IAH is recognized and treated appropriately before significant organ dysfunction has developed [32, 48].

Of all the organ systems, the gut appears to be one of the most sensitive to elevations in IAP. Such reductions in mesenteric blood flow may appear with an IAP of only 10 mmHg [83]. Caldwell et al. has demonstrated decreased blood flow to virtually all intra-abdominal and retroperitoneal organs as a result of elevated IAP [56]. The sole exception was adrenal blood flow which appears to be preserved and has been postulated to be a survival mechanism by which to support catecholamine release in the face of ongoing shock [56]. Celiac artery blood flow is reduced by up to 43% and superior mesenteric artery blood flow by as much as 69% in the presence of intra-abdominal pressures of 40 mmHg [68, 83, 84]. The negative effects of IAP on mesenteric perfusion are augmented by the presence of hypovolemia or hemorrhage [8, 50, 68, 83, 85]. Reintam et al. have recently validated a grading system for predicting mortality due to gastrointestinal dysfunction among patients with IAH/ACS [86].

In addition to reducing arterial blood flow, IAP compresses thin walled mesenteric veins promoting venous hypertension and intestinal edema. Visceral swelling further increases IAP initiating a vicious cycle which results in worsening malperfusion, bowel ischemia, decreased intramucosal pH, feeding intolerance, systemic metabolic acidosis, and significantly increased patient mortality [8, 13, 50, 86, 87]. Intestinal mucosal perfusion is diminished by levels of IAP as low as 20 mmHg as demonstrated using gastric or colonic tonometry and by laser flow probe [8, 50, 84, 87]. Sugrue et al. found that patients with IAH were over 11 times more likely to have abnormal gastric intramucosal pH measurements than were those without IAH [87]. Djavani et al have recently reported a similar significant correlation between abnormal colonic intramucosal pH and IAH [85]. They have further confirmed a high risk of colonic ischemia in post-abdominal aortic aneurysmectomy patients with IAP > 20 mmHg [88]. Malperfusion of the gut as a result of elevated IAP has been speculated as a possible mechanism for loss of the mucosal barrier and subsequent development of bacterial translocation, sepsis, and multiple system organ failure [84, 89, 90]. Gargiulo et al. demonstrated bacterial translocation to mesenteric lymph nodes in the presence of hemorrhage and an IAP of only 10 mmHg [90].

Hepatic artery, hepatic vein, and portal vein blood flow are all reduced by the presence of IAH [50, 52, 54, 77, 91]. Hepatic artery flow is directly affected by decreases in cardiac output. Hepatic and portal venous flow are diminished as a result of both extrinsic compression of the liver as well as anatomic narrowing of the hepatic veins as they pass through the diaphragm [67]. Increased hepatic vein pressures have been demonstrated to result in increased azygos vein blood flow suggesting a compensatory increase in gastroesophageal collateral blood flow in response to hepatic venous congestion [54]. On a microscopic level, hepatic microcirculatory blood flow is decreased resulting in a reduction in hepatic mitochondrial function and production of energy substrates [50, 91]. Lactic acid clearance by the liver appears to be compromised potentially confounding its use as a marker of resuscitation adequacy [92]. Of particular importance is that these changes have been documented with IAP elevations of only 10 mmHg and in the presence of both normal cardiac output and mean arterial blood pressure [50].

Cerebral perfusion and function are also directly affected by the presence of IAH. According to the Monroe-Kellie doctrine, the brain consists of four discrete compartments: parenchymal, vascular, osseous, and cerebrospinal fluid. An increase in the pressure within one compartment results in a reciprocal increase in the pressure within each of the other non-osseous compartments. Whereas chronic, slowly developing increases in intracranial pressure (ICP) may allow time for compensation, the acute increases in ICP characteristic of both traumatic injury and acute illness commonly result in rapidly escalating intracranial pressures. Elevations in intra-abdominal and intrathoracic pressure may also directly impact the pressures within the cranium. Coughing, defecating, emesis, and other common causes of increased intra-abdominal and intrathoracic pressure are well known to transiently increase ICP [48, 93, 94]. IAH can induce similar increases in ICP, but these elevations are sustained as long as the IAH is present and can result in significant reductions in cerebral perfusion pressure (CPP) [47, 48, 61, 94‐96]. The mechanism by which IAH causes elevations in ICP has long been a subject of debate [47, 48, 94, 97, 98]. Proposed mechanisms have included decreased lumbar venous plexus blood flow (leading to increased CSF pressure), increased PaCO₂ (resulting in increased cerebral blood flow), and decreased cerebral venous outflow [47, 48, 94, 97, 98]. Luce et al. in a series of animal experiments and Bloomfield et al. in clinical studies involving humans have confirmed that increased intrathoracic pressure impairs venous return from the cranium and decreases cerebral venous blood flow [48, 97]. This increases intracranial venous blood volume in a manner similar to that encountered with the use of both PEEP and military anti-shock trousers [97‐99]. Intracerebral venous pooling can markedly worsen pre-existing cerebral perfusion abnormalities due to trauma, chronic intracranial hypertension, or other causes of decreased cerebral compliance [96, 98]. Sugerman et al. have demonstrated that normal cerebral compliance appears to be protective against intrathoracic pressure-induced increases in ICP [96]. Decreased pulmonary compliance as a result of severe pulmonary dysfunction, as occurs in IAH, also appears to have a protective effect on ICP [61, 95]. Hypovolemia, on the other hand, may worsen already marginal cerebral perfusion [79, 95].

Although commonly overlooked, the abdominal wall is also subject to the effects of elevated IAP. Visceral edema, abdominal packs, and free intraperitoneal fluid all distend the abdomen and reduce abdominal wall compliance [67, 100]. Abdominal wall edema secondary to shock and fluid resuscitation also decreases abdominal compliance. Previous pregnancy, morbid obesity, cirrhosis, and other conditions associated with increased abdominal wall compliance all appear to be protective, to an extent, against the development of IAH [87, 96]. Diebel et al. have demonstrated that IAH dramatically reduces abdominal wall blood flow [101]. Rectus sheath blood flow decreases to 58% of baseline at an IAP of only 10 mmHg and to 20% of baseline at 40 mmHg [101]. These findings may explain the impaired wound healing, high rate of fascial dehiscence, and predilection to development of necrotizing fasciitis identified in patients whose abdomens are closed under tension [70, 101].

The abdomen may be considered as a closed box with walls that are either rigid (costal arch, spine, and pelvis) or flexible (abdominal wall and diaphragm). The compliance of these walls and the volume of the organs contained within determine the pressure within the abdomen at any given time [102‐104] IAP is defined as the steady-state pressure concealed within the abdominal cavity, increasing with inspiration (diaphragmatic contraction) and decreasing with expiration (diaphragmatic relaxation). IAP is directly affected by the volume of the solid organs or hollow viscera (which may be either empty or filled with air, liquid or fecal matter), the presence of ascites, blood or other space-occupying lesions (such as tumors or a gravid uterus), and the presence of conditions that limit expansion of the abdominal wall (such as burn eschars or third-space edema) [19].

Analogous to the widely utilized concept of cerebral perfusion pressure, abdominal perfusion pressure (APP), defined as MAP minus IAP, has been demonstrated to be an accurate predictor of visceral perfusion and an endpoint for resuscitation [64, 105, 106]. APP, by considering both arterial inflow (MAP) and restrictions to venous outflow (IAP), is statistically superior to either parameter alone in predicting patient survival from IAH and ACS [64, 105, 106]. APP is also superior to other common resuscitation endpoints such as arterial pH, base deficit, arterial lactate, and hourly urinary output. Failure to maintain an APP of at least 60 mmHg by day 3 of critical illness has been demonstrated to predict survival from IAH and ACS [64, 105, 106]. APP thus figures prominently in the resuscitation strategy recommended by the WSACS.

As described above, oliguria is one of the first visible signs of IAH. Inadequate renal perfusion pressure and renal filtration gradient (FG) have been proposed as key factors in the development of IAP-induced renal failure [107, 108]. The FG is the mechanical force across the glomerulus and equals the difference between the glomerular filtration pressure (GFP) and the proximal tubular pressure (PTP). In the presence of IAH, GFP may be approximated as MAP minus IAP (or APP) while PTP may be assumed to equal IAP. The FG is thus defined as MAP minus two times the IAP, illustrating that changes in IAP have a greater impact upon renal function and urine production than do changes in MAP.

The sensitivity of both clinical judgement and physical examination have been demonstrated to be very poor in predicting a patient's IAP [109, 110]. Early, serial IAP measurements are therefore essential to both diagnosing the presence of IAH as well as guiding resuscitative therapy [111]. While a variety of methods for IAP measurement have been described, intravesicular or "bladder" pressure has achieved the most widespread adoption worldwide due to its simplicity, minimal cost, and low risk of complications [103, 112‐115]. Several key points must be considered to ensure accurate and reproducible IAP measurements. Early IAH studies utilized water manometers to determine IAP with results reported in cm H₂O while subsequent studies using electronic pressure transducers reported IAP in mmHg (1 mmHg = 1.36 cm H₂O). This led to confusion and difficulty in comparing studies. A point of further confusion has been the appropriate zero reference point for the abdomen. Changes in body position (i.e., supine, prone, head of bed elevated) can have a significant impact upon the measured IAP. While head of bed elevation is now commonly performed to reduce the incidence of ventilator-associated pneumonia, the clinical studies that determined the threshold IAP values that lead to organ dysfunction were determined in the supine position. Further, the presence of both abdominal and bladder detrusor muscle contractions have been demonstrated to impact the accuracy of IAP measurements. Perhaps the greatest point of contention has been the proper priming-volume to be instilled into the bladder to ensure a conductive fluid column between bladder wall and transducer. Large instillation volumes, as commonly utilized in years past, have been demonstrated to result in artificial increases in IAP that could lead to inappropriate therapy. In an attempt to address these issues and ensure both the accuracy and reproducibility of IAP measurements, the WSACS has recommended that IAP be expressed in mmHg and measured at end-expiration in the complete supine position after ensuring that abdominal muscle contractions are absent and with the transducer zeroed at the level of the mid-axillary line [20]. Further, IAP should be measured via the bladder with a maximal instillation volume of 25 mL of sterile saline [20].

Normal IAP ranges from sub-atmospheric to zero mmHg [109, 113, 116]. In the typical intensive care unit patient, however, IAP is commonly elevated to a range of 5–7 mmHg while patients with recent abdominal surgery, sepsis, organ failure, or need for volume resuscitation may demonstrate IAPs of 10–20 mmHg [11, 15]. Prolonged elevation in IAP to such levels can result in organ dysfunction and failure while pressures above 25 mmHg are associated with significant potential mortality [65, 80, 105].

Pathological IAP is a continuum ranging from mild IAP elevations without clinically significant adverse effects to substantial increases in IAP with grave consequences to virtually all organ systems in the body. The exact IAP that defines IAH has long been debated. Burch et al. defined an early grading system for IAH (in cm H₂O) as follows: Grade I, 7.5–11 mmHg (10–15 cm H₂0); Grade II, 11–18 mmHg (15–25 cm H₂0); Grade III, 18–25 mmHg (25–35 cm H₂0); and Grade IV, > 25 mmHg (> 35 cm H₂0) [117]. Burch suggested that most patients with Grade III and all patients with Grade IV should undergo abdominal decompression. The deleterious effects of elevated IAP on renal, cardiac, and gastrointestinal function, however, may be witnessed at IAP levels as low as 10–15 mmHg which would be classified as Grade I in the Burch system [11, 44, 87, 104, 118‐124]. In recognition of the pathophysiologic impact of these lower levels of IAP, the WSACS has defined IAH as a sustained or repeated pathologic elevation of IAP ≥ 12 mmHg. The WSACS has also modified the Burch system to increase its clinical sensitivity as follows: Grade I: IAP 12–15 mmHg; Grade II: IAP 16–20 mmHg; Grade III: IAP 21–25 mmHg; and Grade IV: IAP > 25 mmHg [19, 20]. In this scenario, medical intervention is appropriate for any grade of IAH while surgical decompression is typically reserved for Grade IV IAH.

Among the majority of patients, critical IAP appears to be 10–15 mmHg. It is at this pressure that reductions in microcirculatory blood flow occur and the initial signs of organ dysfunction and failure are witnessed. ACS is the natural progression of these pressure-induced end-organ changes and develops if IAH is not recognized and treated in a timely manner. Failure to recognize and appropriately treat ACS is commonly fatal while prevention and/or timely intervention is associated with marked improvements in organ function and patient survival [8, 11, 23, 44, 125‐127].

In contrast to IAH, ACS is not graded, but rather considered an "all or nothing" phenomenon. The WSACS defines ACS as a sustained IAP > 20 mmHg (with or without an APP < 60 mmHg) that is associated with new organ dysfunction or failure (Appendix 1) [19, 20]. ACS may be further classified as either primary, secondary, or recurrent based upon the duration and etiology of the patient's IAH. Primary ACS is characterized by IAH of relatively brief duration occurring as a result of an intra-abdominal etiology such as abdominal trauma, ruptured abdominal aortic aneurysm, hemoperitoneum, acute pancreatitis, secondary peritonitis, retroperitoneal haemorrhage, or liver transplantation. Primary ACS is therefore defined as a condition associated with injury or disease in the abdomino-pelvic region that frequently requires early surgical or interventional radiological intervention. It is most commonly encountered in the traumatically injured or post-operative surgical patient. Secondary ACS is characterized by IAH that develops as a result of an extra-abdominal etiology such as sepsis, capillary leak, major burns, or other conditions requiring massive fluid resuscitation. It is most commonly encountered in the medical or burn patient [43, 104, 128, 129]. Recurrent ACS represents a redevelopment of ACS symptoms following resolution of an earlier episode of either primary or secondary ACS. It is most commonly associated with the development of acute IAH in a patient who is recovering from IAH/ACS and therefore represents a "second-hit" phenomenon. It may occur despite the presence of an open abdomen or as a new ACS episode following definitive closure of the abdominal wall. Recurrent ACS, due to the patient's current or recent critical illness, is associated with significant morbidity and mortality.