The present study demonstrates that IAP increases to only 12 mmHg for a relatively short duration are associated with metabolic changes in the abdominal wall muscle tissue of patients undergoing laparoscopic surgery. This indicates that anaerobic metabolism, and thereby RAM hypoperfusion, occurs upon very modest increases of IAP.
Several recent studies have shown that an increase in the mean IAP is associated with adverse ICU outcomes [2, 14–16]. However, the time course of IAP-related adverse events in humans is poorly understood. To address this issue, we used microdialysis-aided sample collection from the extravascular space of the RAM. The RAM is surrounded by a tight sheet of fascia, which makes the muscle-fascia compartment relatively noncompliant. Thereby, the pressure in the intra-abdominal cavity is reflected to the muscle tissue and its perfusion. Meier and co-workers used a similar microdialysis approach in a rat model of IAH. They showed that during a 3-h period of IAP at 20 mmHg, the L/P ratio in the RAM tissue increased significantly, indicating ischemia and energy failure. To the best of our knowledge, the present study is the first to make similar observations in humans. Our findings are generally in accordance with previous animal experiments . Notably, metabolic changes in the human RAM tissue were observed at lower levels of IAP than those that were found to cause metabolic changes in rats.
The limitations of our study include its small sample size and microdialysis-related problems, specifically catheter displacement before or during surgery in two patients. The first limitation is expected, given that we are reporting these results as a pilot trial. The latter reflects the limitations of the method per se. Microdialysis is an invasive, relatively expensive and time-consuming procedure. Therefore, this study lacks comparative data from control patients or other anatomical regions of the same patient. Because the insertion of a central venous line was not clinically indicated in these patients, we also did not measure global indices of preload and circulation, which would be required for an in-depth interpretation of the microdialysis data. However, the observed arterial blood pressure and heart rate dynamics do not suggest remarkable alterations in cardiac output during pneumoperitoneum.
The L/P ratio of a tissue reflects its reaction to changing oxygen and glucose supplies , and it is a better marker of cell ischemia than lactate alone . Lactate might also be produced under aerobic conditions , while the L/P ratio is a specific marker of anaerobic conditions. In severe sepsis, the L/P ratio is an independent predictor of 28-day mortality . One possible explanation for this observation is that it may reflect the reduced activity of pyruvate dehydrogenase, which leads to the anaerobic metabolism of pyruvate to lactate and an elevated L/P ratio [19, 21]. During endotoxin shock, the L/P ratio of pre-hepatic venous blood can be increased due to the intestinal uptake of pyruvate .
During ischemia, both the oxygen and the glucose supply to the tissue are compromised. Inadequate delivery combined with increased uptake leads to a marked decrease in the interstitial glucose levels during severe ischemia . We observed a decrease in dialysate glucose levels in our patients, although this trend was not statistically significant. It may be speculated that a moderate increase in IAP due to pneumoperitoneum for laparoscopy is not severe enough to deprive glucose delivery to the RAM tissue in these patients.
Elevated tissue glycerol levels indicate cell membrane damage. Bäckström et al. have demonstrated that mesenteric vein glycerol is an indicator of splanchnic ischemia . We observed no significant changes in RAM glycerol; however, there was a trend toward higher glycerol levels during pneumoperitoneum, which may further support the idea that tissue injury is caused by increased IAP.
IAH has a global impact on the human body. It results in a variable series of pathophysiological consequences, the specifics of which depend on the underlying diagnosis . Although epidemiological studies suggest a threshold of 12 mmHg for the diagnosis of IAH, it is doubtful whether a single IAP level can be universally applied as a critical level for all patients. It remains unclear whether any subclinical effects of IAP may be inferred before detectable organ dysfunction. One good example of a work on this topic is a study by Kirkpatrick et al., who demonstrated that ultrasound measurements of renal blood flow correlate with IAH in pigs . Renal blood flow was impaired prior to a decrease in urine output, an obvious and common symptom of renal dysfunction caused by increased IAP. These results are supported by those of Wauters et al., who showed that IAH is associated with decreased renal blood flow and blood flow redistribution away from the kidney . Olofsson et al. have demonstrated altered intestinal microcirculation in a similar experimental setting with a stepwise increase in IAP by CO2 insufflation . In all of these animal experiments, significant changes were described at markedly high levels of IAP. The results of the present study, in which an increased L/P ratio in the rectus muscle tissue of our patients was observed after only 1 h of moderate IAH, are surprising. However, it remains unclear whether the observed metabolic changes in RAM are directly related to the altered perfusion of intra-abdominal organs, whether they are related to clinical outcome and whether patient treatment should be modified based on these metabolic changes. The results indicate that IAP levels of 12 mmHg are associated with unfavourable metabolic conditions, and they therefore support the recommended IAH grading . The European practice guidelines for pneumoperitoneum in laparoscopic surgery states that IAP levels higher than 12 mmHg should be avoided and that the duration of the procedure must be kept as short as possible .