There are many studies examining the influence of IAH on haemodynamic or on respiratory parameters. However, there are only a few studies investigating the effect of IAP and PEEP on cardio-respiratory parameters [
26‐
28]. To our knowledge, this is the first study to assess the effect of different levels of PEEP in the setting of different levels of IAP on lung volumes assessed by FRC and CO parameters in a healthy pig model.
Effect of IAP and PEEP on FRC, and PaO2
We found that increasing IAP from baseline to grade II IAH decreased FRC and PaO2 levels by approximately 30% and 10%, respectively. There was no further decrease in FRC and PaO2 when IAP was increased from grade II to grade IV IAH. This suggests either a high impedance to further lengthening and cephalic motion of the diaphragm or compensatory lung expansion due to expansion of the rib cage.
Even in the absence of IAH, a healthy patient requiring mechanical ventilation will experience some degree of FRC reduction due to atelectasis [
24]. Although the role of PEEP in acute lung injury and acute respiratory distress syndrome remains controversial, recruitment manoeuvres and high levels of PEEP have been shown to re-open collapsed alveoli and keep the alveoli open [
17,
24]. As expected in this healthy pig lung model, in the absence of IAH, PEEP increased FRC but did not increase the already high PaO
2 levels.
In the presence of IAH, PEEP up to 15 cmH2O only partially reversed the IAP, induced FRC decline in grade II IAH, and did not increase FRC in grade IV IAH. PEEP did not increase PaO2 values in IAH.
The minimal PaO
2 decrease as compared to the relatively larger FRC decrease in the setting of raised IAP can be explained by the FRC not dropping below the closing capacity of healthy lungs and therefore not resulting in atelectasis, shunting and consecutively impaired gas exchange [
24,
29]. In the setting of acute respiratory distress syndrome where the closing capacity is increased, small decreases in FRC reductions may cause marked reductions in PaO
2. However, this would need to be confirmed in further studies.
We chose PEEP levels of 5 to 15 cmH
2O as these represent PEEP levels frequently applied in critical ill patients. The minimal effect of PEEP on reversing the IAH induced FRC reduction can be explained by the reduced estimated trans-pulmonary end-expiratory pressures (PEEP - IAP) which would have approximated 8, -7 and -15 mmHg at PEEP of 15 cmH
2O (11.0 mmHg) and at IAP of 3 mmHg (baseline), 18 mmHg (grade II IAH), and 26 mmHg (grade IV IAH), respectively. Therefore, with regards to improving FRC and PaO
2, PEEP values that are equal or higher than the corresponding IAP value might be necessary to protect against IAH induced FRC and PaO
2 decrease as has previously been suggested [
13]. However, when higher PEEP levels are applied in the setting of IAH, the potential detrimental effect of high PEEP levels on CO and DO
2 should be considered and balanced against the lowest applicable PEEP in order to avoid haemodynamic compromise in this setting [
7].
Effect of IAP and PEEP on CO, DO2, and SvO2
In agreement with other studies [
29,
30], we found that PEEP caused a dose-dependent decrease in stroke volume and CO and DO
2 (Tables
1,
2 and
3, Figures
1 and
2) which can be attributed to a reduction in venous return [
29].
The effect of IAH on CO is controversial with some studies showing a decrease in CO, while other studies do not show a change or even an increase in CO in the presence of IAH [
7,
10‐
12,
31]. This controversy can be explained by IAH having a biphasic and potentially opposing effect on CO which itself may be explained by the dependence of venous return on the level of IAP [
7,
10,
31]. Low levels of IAP have been shown to increase venous return as a result of a redistribution of abdominal blood to the thoracic compartment, thus increasing stroke volume and CO [
10,
31]. However, further increase in IAP overcomes the compensatory effect of blood redistribution from the abdominal compartment to the thoracic compartment decreasing venous return and therefore stroke volume and CO [
10,
31]. In our study, IAH did not significantly reduce stroke volume, CO and DO
2 when low levels of PEEP were applied (5 cmH
2O, 3.7 mmHg). In agreement with other studies [
7,
11,
12], we also found that SVR increased with rising IAP, which may be associated with a reduction in CO and DO
2.
We found that even modest levels of PEEP depressed CO to a greater extent than IAH alone. This finding is supported by greater depression in SvO
2 with PEEP, than with IAP (Figure
4). These findings suggest that PEEP may be detrimental by reducing DO
2 and failing to recruit atelectatic lung. If increased levels of PEEP are indicated in the clinical setting, it might be prudent to assess CO and arterial oxygen saturation before and after increasing the level of PEEP in order to ascertain that the beneficial effect of PEEP with increasing FRC and oxygenation is not offset by a detrimental effect on CO, with a subsequent decrease in DO
2.
However, since we used healthy lungs in our pig model, the arterial oxygen saturation was nearly 100% at all IAP and PEEP settings. Therefore, as DO
2 is derived from arterial oxygen saturation, haemoglobin levels, and CO, the effect of PEEP and IAP on DO
2 paralleled the effect observed on CO (Figures
2 and
3). It is important to appreciate that our findings cannot be extrapolated to patients with a failing heart, where preload and afterload are more important limitations on CO, or to patients with diseased lungs.
Grade II IAH blunted the effect of PEEP on stroke volume, CO and DO
2. This was possibly caused by an increase in venous return associated with low levels of IAH as outlined above. Grade IV IAH did not protect against the PEEP-induced reduction in stroke volume and CO, most likely due to a reduced venous return associated with high levels of IAH [
10,
31]. This suggests the existence of IAP levels that are relatively resistant to PEEP induced CO reduction by counteracting the reduction in venous return caused by increasing levels of PEEP.
Limitations
We used pigs in this study because pig models have been used extensively in IAH research and the physiology of this animal is very similar to humans.
However, it is always difficult to transfer animal data into clinical practice, especially when applying higher levels of PEEP in healthy pigs with IAH. Therefore, an extrapolation of our results onto the effects of IAP and PEEP in critically ill patients remains difficult.
We used an inflatable balloon to achieve different levels of IAP as a model of acute IAH [
19]. We chose not to use a pneumoperitoneum using gas inflation as used by some other investigators for two reasons. First, we wanted to eliminate the cardiovascular and respiratory response to hypercapnia when carbon dioxide or air is used when performing pneumoperitoneum [
12]. Second, we wanted to measure the influence of PEEP on IAP and this is difficult to perform in the setting of a pneumoperitoneum due to possible gas leakage.
Ideally, in order to imitate the clinical setting as closely as possible, a fluid based IAH model should be used (haemorrhage, ascites, oedema). However, models using fluid instillation have their own disadvantages mainly due to uncontrollable abdominal fluid absorption with possible change in cardio-respiratory physiology [
36,
37].
To ensure the absence of changes in IAP caused by leakage from the balloon, we assessed the changes in IAP over time. As there were no significant changes in IAP before and after the five-minute stabilization period, we conclude that there was insignificant gas leakage from the intra-abdominal balloon or adaptive abdominal processes.
As we used healthy pigs in our experimental model it is not surprising that we obtained high PaO
2 levels and a near 100% arterial oxygen saturation at all IAP and PEEP settings. We used a porcine mathematical model to calculate oxygen saturation that shows a good agreement with the measured oxygen saturation [
23].
As we did not use an oesophageal catheter to measure pleural pressures, we are unable to give information on chest wall compliance, which is strongly influenced by IAP in the setting of IAH [
33]. Trans-pulmonary pressures have been shown to be useful in titrating the level of PEEP in the setting of acute respiratory distress syndrome [
38]. In the setting of IAH, trans-pulmonary pressures have been recommended not only to help titrate the level of PEEP but also to guide recruitment manoeuvres [
13]. As we limited our recruitment manoeuvres to a maximum of 40 cmH
2O airway pressure and not to maximum trans-pulmonary pressures of 25 cmH
2O we were not able to perform sufficient recruitment in all PEEP and IAP settings, especially at 26 mmHg of IAP. This might explain the absent effect of PEEP in reversing IAP induced FRC decline in the setting of grade IV IAH, respectively. However, we think this reduced influence of PEEP in reversing IAP induced FRC decline is better explained by the relative small estimated trans-pulmonary PEEP (-7 mmHg and -15 mmHg at PEEP of 11 mmHg and IAP of 18 and 26 mmHg, respectively).
We chose four PEEP settings and three IAP settings in our experimental model, as our main focus was to study the effect of PEEP on FRC, CO and DO
2 in the setting of increased IAP. We used PEEP values of 5, 8, 12, and 15 cmH
2O as these PEEP values are frequently applied ventilator settings in critically ill patients. Since it remains unclear what the exact threshold value of IAP is at which a surgical abdominal decompression should be performed, we chose grade II and grade IV IAH because surgical abdominal decompression is currently not recommended for grade II whereas it is recommended for persistent grade III and IV in the presence of a new organ failure [
1,
2].
Another limitation is that we measured the mean IAP instead of the end-expiratory IAP as suggested by the World Society of Abdominal Compartment Syndrome [
1]. As it has been shown that the difference between end-inspiratory and end-expiratory IAP increases in proportion to IAP, our measured mean IAP will underestimate end-expiratory IAP by approximately 1 mmHg at 11 mmHg end-expiratory IAP [
39].