Clinical review: Intra-abdominal hypertension: does it influence the physiology of prone ventilation?

Prone ventilation (PV) is a ventilatory strategy that frequently improves oxygenation and lung mechanics in critical illness, yet does not consistently improve survival. While the exact physiologic mechanisms related to these benefits remain unproven, one major theoretical mechanism relates to reducing the abdominal encroachment upon the lungs. Concurrent to this experience is increasing recognition of the ubiquitous role of intra-abdominal hypertension (IAH) in critical illness, of the relationship between IAH and intra-abdominal volume or thus the compliance of the abdominal wall, and of the potential difference in the abdominal influences between the extrapulmonary and pulmonary forms of acute respiratory distress syndrome. The present paper reviews reported data concerning intra-abdominal pressure (IAP) in association with the use of PV to explore the potential influence of IAH. While early authors stressed the importance of gravitationally unloading the abdominal cavity to unencumber the lung bases, this admonition has not been consistently acknowledged when PV has been utilized. Basic data required to understand the role of IAP/IAH in the physiology of PV have generally not been collected and/or reported. No randomized controlled trials or meta-analyses considered IAH in design or outcome. While the act of proning itself has a variable reported effect on IAP, abundant clinical and laboratory data confirm that the thoracoabdominal cavities are intimately linked and that IAH is consistently transmitted across the diaphragm - although the transmission ratio is variable and is possibly related to the compliance of the abdominal wall. Any proning-related intervention that secondarily influences IAP/IAH is likely to greatly influence respiratory mechanics and outcomes. Further study of the role of IAP/IAH in the physiology and outcomes of PV in hypoxemic respiratory failure is thus required. Theories relating inter-relations between prone positioning and the abdominal condition are presented to aid in designing these studies.

Th e World Society of the Abdominal Compartment Syndrome defi nes intra-abdominal hypertension (IAH) as sustained IAP ≥12 mmHg, and defi nes the abdominal compartment syndrome (ACS) as IAP >20 mmHg with new organ failure [29]. IAH is a condition that can complicate virtually any critical condition, greatly infl uences the respiratory system and associates with adverse clinical outcomes [30]. Obesity and high body mass index (BMI) are inter-related characteristics associated with IAH that also impair respiratory mechanics [30,31]. Although the study of PV was initiated in 1974 after Bryan suggested the tech nique as a means of alleviating intrusion of the abdominal contents upon the thoracic volume [32], the role of the abdomen in general, and of IAH in particular, has been largely ignored in subsequent studies. Many pioneers of PV considered it critical to unload or suspend the abdominal cavity while proning. In 1977 Douglas and colleagues predicted that protuberant abdomens which were not suspended adequately would 'have little or no improvement or may even have a deterioration in PaO 2 when turned prone' [33]. We therefore reviewed both the reported experiences and possible infl uence of the abdominal status in PV research.

Materials and methods
Th e MEDLINE, EMBASE, BioMed Central, CINAHL, and Cochrane databases were searched for original research concerning PV, IAP, IAH, and ACS. Bibliographies of all retrieved articles were reviewed to identify additional literature. One reviewer abstracted data from each study related to study type (animal versus clinical), study design (randomized trial, other controlled clinical, or physiologic study), population (setting, numbers), whether body weight was specifi cally positioned over the chest and pelvic bones (thoracopelvic support) and/or whether the abdomen was freely suspended to permit free abdominal movements independent of the bed (suspension), as well as baseline physiologic characteristics.

Data relating prone ventilation and intra-abdominal pressure Animal studies
Only two porcine studies measured IAP during PV; one with normal lungs [34], the other with an oleic-acid lunginjury model [35] (Table 1). Mure and colleagues used an infl atable balloon to distend the abdomen with normal lungs in either supine positioning or PP. Th ey observed greater improvement in gas exchange after PP in the presence of abdominal distension than without [34]. Conversely, Colmenero-Ruiz and colleagues reported no diff erential eff ect on the oxygenation with proning when the abdomen was freely suspended in their normal lung model without IAH [35]. Th ere are no reported animal data concerning injured lungs in the setting of abdominal distension or IAH.

Human studies Eff ect of proning on intra-abdominal pressure in humans
Eight studies measured IAP during PV in critically ill patients, and another study concerned obese patients during elective surgery (Table 2). Two studies unloaded the abdomen [36,37] while fi ve did not [38][39][40][41][42], and one study did not report on abdominal unloading [43]. Finally, one study randomized abdominal suspension [44].
Several authors reported that the PP raises IAP in certain situations [38][39][40]. Michelet and colleagues found that while gas exchange increased with either method, IAP signifi cantly increased on the conventional mattresses from normal to grade II IAH [40]. Although not presented numerically, graphical analysis suggests that IAP increased from approximately 7 to 15 mmHg on a conventional mattress and from 8 to 12 mmHg on an aircushioned mattress during PP [40]. None of these patients had IAH prior to proning and all had pulmonary ALI/ARDS. Hering and colleagues reported two studies in which mixed pulmonary and extrapulmonary ALI patients who were proned on air-cushioned beds without suspension had mean IAP rises on average from 10 to 11 mmHg up to 13 to 14 mmHg [38,39]. Kiefer and colleagues studied 25 patients (BMI and suspension not reported) requiring MV, and found that the mean IAP was not signifi cantly aff ected by proning [43]. Pelosi and colleagues measured IAP in 10 patients with ALI before and after PP with abdominal suspension, and noted that the mean IAP rose nonsignifi cantly from 11.4 to 14.8 mmHg [36].
Chiumello and colleagues conducted the only ran domized trial comparing abdominal suspension versus no suspension during PV. Th ey studied 11 patients with mixed pulmonary and extrapulmonary ARDS [44]. Th ey found an improve ment in respiratory function with PV and an increase in IAP when turned to prone regardless of suspension or not [44]. Most recently, in 10 patients with pulmonary ARDS and initial IAP constituting grade II IAH (14.5 mmHg), Fletcher reported a small but statistically signifi cant fall after proning [42].

Reported consequences of prone positioning induced intraabdominal pressure changes in humans
Despite reports of statistically signifi cant changes in IAP, consistent clinical eff ects have not been seen with these modest IAP changes [45]. Michelet and colleagues examined a number of parameters after proning [40]. Th ey studied the disappearance rate of indocyanine green as a surrogate for splanchnic perfusion. While extravascular lung water and intrathoracic blood volume were unmodifi ed, the disappearance rate of indocyanine green was signifi cantly diff erent after proning on the conventional mattress; however, changes in the disappearance rate of indocyanine green were not correlated with IAP changes [40]. Similarly, Kiefer and colleagues found that MV in PP may be associated with increased gastricmucosal gradients of the partial pressure of carbon dioxide. Although there were major inter-individual variations, the mucosal pH gradient also increased in nine out of 11 patients in whom IAP increased [43]. Hering and colleagues found that while the renal fraction of cardiac output decreased and renal vascular resistance increased, there were no other important physiological changes and no diff erences in hepatic function or gastric mucosal carbon dioxide tension compared with the supine position [39].
As an aggregate, none of these studies involved a population with severe IAH, and only two studies (25%) reported BMI data. Not considering the eff ect of IAP as a potential consequence of PV needs to be interpreted in light of the fact that IAP changes of as little as 3 mmHg  after proning were associated with increased gastric mucosal-arterial gradients of partial pressure of carbon dioxide [43]. Further, the eff ects of even modest IAH in critical illness may be subtle in the setting of multiple organ failure [46], and pressures as low as 10 mmHg may have signifi cant end organ eff ects [47].

Abdominal considerations in randomized studies of prone ventilation for ALI/ARDS
Th e fi rst large randomized controlled trial (RCT) of prone ventilation for ALI/ARDS was reported by Gattinoni and colleagues in 2001 [4]. Th is trial was followed by nine others in rapid succession, with the largest completed in 2009 [9][10][11][12][13][14]45,48,49], in addition to studies examining PV with concurrent additional therapies or related res piratory techniques [9,50,51] (Table 3). Six meta-analyses were subsequently published [7,8,[17][18][19]52]. Nine out of 10 RCTs studying ALI/ARDS distinguished or provided descriptions to allow classi fi cation into pulmonary and extrapulmonary groups, although only one meta-analysis considered this factor (Table 3). No study considered IAP or BMI in the design. In terms of the proning technique, one RCT reported free suspension, four trials reported specifi cally not, and fi ve trials did not discuss suspension.
No meta-analysis considered abdominal suspension.

Discussion
Small studies in selected patients without IAH have demonstrated modest elevations in IAP without marked physiologic eff ects after proning. Despite the increasing recognition of the importance of thoracoabdominal interactions, no animal or clinical study has specifi cally addressed these interactions in a population with either IAH or obesity. Th e evidence as to whether proning itself induces important changes in IAP therefore remains inconsistent and is unhelpful to guide clinical practice. Th e use of PV in ALI/ARDS appears to be decreasing, presumably due to the inability of RCTs to demonstrate a survival advantage using a technique that requires great logistical input and has signifi cant side eff ects [19,52,53]. Although a number of methodological reasons have been previously discussed [19], we suggest an additional factor to be considered when interpreting previous clinical and physiological studies on PV: the role of the thoraco abdominal cavity as a complete entity, and the lack of appreciation for the relationship between IAP and intra-abdominal volume (IAV) refl ecting abdominal com pliance (Cab).

Physiology of prone ventilation
Achieving improved gas exchange through proning has been variably attributed to improvements in gradients of transpulmonary pressures from chest wall mechanics, in homogeneity of lung infl ation, in recruitment of the dorsal lung relative to ventral derecruitment, in increases of end-expiratory lung volumes, in redirection of the compressive forces of the heart weight, in better secretion clearance, or in interactions of all the above [16,18,33,36,37,44,50,54]. No matter what the exact mechanism is, however, the presence of atelectasis and lung recruitability is the simplest reason for the PV value [55].

Pulmonary versus extrapulmonary ALI/ARDS and the abdomen
Extrapulmonary and pulmonary subtypes of ALI/ARDS have been reported to diff er greatly in their respiratory mechanics, in their response to positive end-expiratory pressure (PEEP), in lung recruitment, and in prone positioning [21,[24][25][26]. Gattinoni and colleagues demonstrated signifi cant IAP diff erences with either pulmonary or extrapulmonary ALI/ARDS -with mean values of 8.5 mmHg versus 22 mmHg, respectively -and changes in chest wall elastance [24]. Extrapulmonary ALI/ARDS from condi tions frequently associated with IAH, such as intra-abdominal sepsis or trauma, were thus considered cases that would most benefi t from PV. Protti and colleagues discussed prone responders using a wet sponge model in which the greater the lung weight, the greater the collapse and the greater the recruitment poten tial [3]. Heavier lungs were associated with decreases in carbon dioxide that were associated with increased recruita bility [3]. Since the juxtadiaphragmaticdependent regions frequently com pressed in ALI/ARDS appeared less amenable to recruitment using higher PEEP, which may simply over distend aerated nondependent lung regions [56,57], PV off ers a potential recruitment tech nique that focuses on the most gravitationally at-risk lung regions. Animal models have clearly illustrated diff ering pathology between extrapulmonary and intrapulmonary ALI/ARDS [27,58,59], as well as generally greater responsive ness to recruitment maneuvers in extra pul monary ALI/ARDS [26,28]. Th e critically ill human is much more complex, however, and investigators have not consistently con fi rmed greater lung recruitability within these subgroups of the ALI/ARDS population, or even to consistently subtype accurately [60,61]. Missing data continue to be the chest wall mechanics, abdominal status, and IAP [60]. We question whether the diffi culty in accurately cate gor iz ing ALI/ARDS into two subgroups in order to predict prone responsiveness is necessary, and whether simply considering the abdominal status with easily measured parameters such as IAP might guide the clinician better. Th is is congruous with the opinion of Talmor and colleagues, who recently noted markedly improved respiratory parameters in ALI/ARDS patients with PEEP selected based on esophageal pressures [62]. Th ey suggested that disappointing results utilizing algorithmic PEEP adjustments may relate to the lack of recognition of elevated pleural or IAP [62]. We therefore question whether the etiology of ALI/ARDS is critical or whether, instead, the relative changes in lung and chest wall mechanics including IAP should be the focus for future subtyping of ALI/ARDS. In reference to PV, however, this hypothesis has not been tested to date, as no prospective RCTs evaluating PV have considered measuring, report ing, or stratifying by either IAP or BMI.

Abdominal morphology
Abdominal morphology intuitively plays a central role in a technique involving positioning the critically ill patient upon their abdomen. Treating the abdomen as a limited elastic body [63] illustrates how initial modest volume increases may be accommodated with modest pressure increases, but further increases beyond a pressurevolume curve infl ection point will be associated with IAH [45,64] (Figure 1). Initial work supports the contention that the amplitude of IAP oscillation with ventilation may infer the abdominal compliance [64,65]. Essentially, a stiff er abdomen may be indicated by greater fl uctuations and higher peaks from physical compression than more compliant abdomens. Cab may thus at least partially explain the variability in abdominothoracic pressure transmission ratios [66,67]. Identifying the degree of stiff ness or lack thereof may therefore help identify patients at risk for adverse eff ects of IAH in general, and from prone abdominal compression in particular.

Technique: thoracopelvic supports to suspend the abdomen
Th oracopelvic supports are any support specifi cally used to direct the prone patient's body weight upon the chest and pelvic bones, to suspend and thereby unencumber the abdomen. Healthy volunteers who simulated patients had signifi cantly increased contact pressures at the chest and pelvic locations during PP [44] Th is positioning decreases chest wall movements and reduces thoracoabdominal compliance (increasing stiff ness or elastance). We believe that thoracopelvic support are required for at least three reasons in many if not all patients undergoing PV for respiratory reasons: to redistribute ventilatory gasses towards the now dependent ventral and diaphrag matic regions where minimal atelectasis and collapse are present [34,36]; to avoid compressing a noncompliant distended abdomen, especially if IAH is present; and to potentially unload an abdomen off the lungs with suffi cient Cab to allow this, as will be explained.

Gravitational abdominal unloading
Supine positioning compresses the dependent lung bases with collapse and reduces lung volumes in normal patients (Figure 2a), and is worse with obesity or severe IAH [68,69] (Figure 2b). Th e end-expiratory lung volume may be less than one-half after the induction of anes thesia in obese patients [69], and the degree of atelectasis correlates with body weight [68]. When gravity is removed from supine pigs in parabolic fl ight, tidal volumes with constant ventilation signifi cantly increase with both normal IAP and IAH, presumably as the abdominal weight is eff ectively removed [70] (Figure 2c). While treating critically ill patients in weightlessness is impractical, prone ventilation largely accomplishes the same eff ect.
In certain studies, PV increased the end-expiratory lung volume and the forced residual capacity coincident with increased chest wall elastance when the abdomen was suspended [37,71]. While there has been no study in severe IAH or overt ACS, data describing obese patientswho may be considered a surrogate -do exist. Pelosi and   colleagues investigated patients undergoing surgical procedures in PP and ensuring free abdominal movements and gravita tional unloading [36,37,71]. With such attention there were marked increases in the oxygenation and forced residual capacity of patients in PP versus supine position ing (1.9 l versus 2.9 l) with a normal BMI of 23.2 [71], and an increase of 0.89 to 1.98 l in those with an obese BMI of 34.6 [37]. Especially in obese patients, decreased chest wall compliance in PP was off set by increased lung compliance [37]. Th ey hypothesized that increases in forced residual capacity were due to reductions in cephalad diaphragmatic pressures from abdominal visceral unloading or reopening of atelectatic segments [37,71]. While it might be predicted that such lower lung unloading would be associated with a decreased IAP, these measurements were not made and the prediction remains speculation.
Although IAP was not a focus, these studies provide the best guidance regarding proning with IAH, as obesity is well linked to chronic IAH, which compresses the lungs and decreases forced residual capacity [72]. We therefore speculate that, in general, the greater the abdominal distension (larger IAV), the higher the BMIand that the higher the IAP, the more important it is to ensure that the visceral abdominal mass is subjected to downwards gravitational forces rather than allowing IAV to be compressed up into the thorax, inducing atelectasis and reducing lung volumes.

An integrated theory of abdominal pressure and morphology in relation to prone positioning
We hypothesize that whether IAP increases or decreases in relation to PV may be a function of how tight the abdomen is and whether it is compressed or decompressed by the act of proning. If an abdomen is obese or distended, placing the full body weight face down would intuitively lead to compression of the contents against the rigid dorsal abdominal wall. Th is compresses the lung bases and induces atelectasis, as seen under general anesthesia -especially after muscle relaxant administration [37]. In the critically ill patient with normal IAP, the abdomen is not compressed when proned even if unsuspended and typically only benefi cial physiologic eff ects of proning are seen (Figure 3a). When the patient has a large abdomen (that is, large IAV) that protrudes beyond the ribcage when standing upright or when supine), then clinicians should consider the risk that the IAP will rise if the abdomen is unsuspended -thus compressing the lung bases (Figure 3b). With a smaller IAV, this compressing eff ect will be minimal or absent (Figure 3a). In some cases, however, IAP may be acceptable when compliance is high -as might occur with chronic increases in IAV such as pregnancy or gradually accumu lated ascites, wherein the abdomen will be splashed out if unsupported (Figure 3c). While formal elasticity was not calculated, Abu-Rafea and colleagues showed that the parity of women undergoing laparoscopy positively correlated with a need for greater volumes of insuffl ated gas to reach target pressures [73]. Conversely, if the same IAV was contained within a noncompliant abdomen, refl ecting many cases of acute IAH, and the contents were compressed by body weight, then IAP would predictably increase greatly.
Acute rises in IAP typical with IAH/ACS will typically be associated with decreased abdominal compliance. To avoid further embarrassing injured lungs in these patients, therefore, we believe abdominal suspension is required for those patients with acute IAH -to possibly unload the abdomen off the juxtadiaphragmatic lung regions, but to certainly avoid compressing the abdomen and worsening IAH. Whether the former improvements occur with suspension, however, probably depends on the Cab. Akin to Figure 3a, if IAP is normal then proning with or without suspension will not markedly aff ect the IAP [44] (Figure 3d). Further, in a theoretical patient with very low compliance and moderate IAH, proning will not unload the lung bases even when the abdomen is suspended (Figure 3e). Alternatively, when compliance is high and the abdomen is suspended, the abdominal contents would be decompressed away from the juxtadiaphrag matic lung and additional benefi ts will be observed ( Figure 3f ). Whether simple interventions such as percu taneous drainage of intraperitoneal fl uid [74] could increase the Cab in cases of acute IAH, and could increase the eff ects of proning, remains speculative but deserves further study. Investigators attempting to truly understand the merits of PV should thus consider IAP and related parameters (Table 4).

Conclusions
Th e chest and abdomen are inexorably linked and must be considered as a single unit. Many critical illnesses culminate in abdominal distension that -along with obesity -often induces IAH, with adverse eff ects through out the body but particularly in the lungs. Despite the eff ort devoted to studies of PV, the potentially confounding issues of IAH have been largely neglected. Even the act of PP appears to have the potential to either exacerbate or ameliorate IAH, depending on the technique, yet these details are often lacking in reports. Th e authors speculate that utilizing a proning technique that unloads the abdomen in ALI/ARDS populations with prominent lung atelectasis complicated/induced by IAH/obesity may be optimal to test the true merits of PV. Th is hypothesis, however, will need to await confi rmation or refutation in a prospective study. Currently, however, clinicians should remain cognizant of the fact thatdepending on the mechanics used -proning activities have the potential to induce IAH, which can defi nitely adversely infl uence the respiratory outcomes.

Competing interests
MLNGM has consulted for and has stock ownership with Pulsion Medical Systems, has received patent support from Pulsion Medical Systems, and has also received royalties from Holtech Medical. The remaining authors state that they have no competing interests.