This was the first prospective cohort study conducted in a population of critically ill children with onco-hematological diseases following the WSACS 2013 Guideline concerning pediatric-specific recommendations.
The first articles on the incidence of IAH/ACS in pediatric patients were published in 1993. The incidence ranged from 0.6–34% depending on the classification criteria used (IAP measurements of 10, 12, or 15 mmHg), and the study population differed between the studies, with some patients being treated clinically and others surgically [6, 10–14]. In 2006, there was consensus among experts during the Second World Congress on ACS to unify the definitions and pathophysiology of IAH and ACS, and updates were published in 2013 with specific data for pediatric patients [2].
Studies with new classification criteria specific to the pediatric population reported an IAH incidence of 12.6% and a prevalence of 43.9% [15]. Thabet et al. conducted a study in a tertiary and multidisciplinary PICU and reported IAH and ACS incidences of 12,6, and 4%, respectively, which were much lower than those reported in our study (57.4% and 17.7%) [12].
To the best of our knowledge, there has been no published data regarding the incidence of IAH or ACS in children with onco-hematological diseases. The higher incidence of ACS and IAH shown in our study could be explained by the specific features of patients with onco-hematological diseases related to direct or indirect chemotherapy or other immunosuppressive therapy effects. This group of patients also had a greater presence of risk factors such as abdominal surgery, abdominal infection, acidemia, coagulopathy, fluid resuscitation, mechanical ventilation, and abdominal masses.
Previous studies on IAH or ACS in onco-hematology patients were only case reports or isolated cases in multidisciplinary samples. In a descriptive, observational, and retrospective study of 23 children who underwent decompressive laparotomy, they found a case of ACS in a child with Wilms' tumor [16]. Another descriptive, observational, and prospective study of 14 patients with ACS described a case of a 7-year-old boy who survived until his PICU stay and had abdominal Burkitt's lymphoma [6].
Additionally, Egyed et al. (2019) reported a case of an adult with abdominal Burkitt's lymphoma who developed ACS at the time of diagnosis and survived after decompressive laparotomy and chemotherapy [17]. Lode et al. (2019) reported a case of a 10-month-old girl who developed abdominal compression with renal failure, severe bleeding, and tumor lysis syndrome. The diagnosis of an abdominal compartment syndrome (ACS) was established by intragastric pressure (max. 17 cmH2O). Based on the deteriorating clinical condition, the sustained rise of the intraabdominal pressure (IAP) together with the newly developed organ dysfunction it was decided to perform an enterostomy in order to decompress the abdominal cavity. Surgical decompression by enterostomy, local, and systemic bleeding control with platelets and coagulation factors, anti-infective and TLS therapy were effective in stabilizing the patient’s condition. This allowed initiation of the multimodal antineoplastic treatment according to protocol NB 2004 [18].
ACS and IAH are thought to be caused by a variety of pathophysiological mechanisms. A more modern theory suggests that both often result from a two-step process that begins with reperfusion of an ischemic injury and results in a vicious cycle known as “intestinal stress syndrome” or “intestinal permeability syndrome.” The resuscitation phases of different types of shock can cause intestinal reperfusion injuries after ischemia that induce systemic and intestinal inflammatory responses. Pro-inflammatory mediators increase mesenteric and intestinal wall capillary permeability, leading to fluid leakage between the mesentery and intestinal wall, bacterial translocation, and absorption of bacterial endotoxins [19].
The second step is a result of bowel wall edema that increases the IAP, generates compression of the intra-abdominal lymphatic system, and decreases the flow of lymph out of the abdominal cavity [20]. The increase in IAP progressively decreases blood flow to the intestinal mucosa, generating ischemia and further increasing intestinal permeability. Thus, there is an influx of pro-inflammatory mediators into the systemic circulation, which facilitates the worsening of visceral edema and an increase in IAP following the vicious cycle of acute intestinal stress [21]. Bulky fluid resuscitation aggravates this vicious cycle by generating hemodilution, decreasing the oncotic pressure of the intestinal mucosa, and favoring an increase in hydrostatic pressure, further increasing IAP [19].
The increase in pressure in the abdominal cavity is transmitted to the interstitial space and microvascularization, generating a decrease in abdominal perfusion pressure and, consequently, in blood flow to the intracavitary organs, resulting in ischemia, congestion, and edema of the intra-abdominal organs. Visceral edema contributes to an increase in IAP, contributing to the vicious cycle described above and leading to progressive organ dysfunction. When the IAP exceeds the abdominal perfusion pressure, the blood flow to the organs is interrupted, resulting in cell death. Therefore, ischemia and necrosis are the causes and consequences of ACS [22].
The effects of IAP on the respiratory system have also been investigated. Pelosi et al. analyzed the relationship between IAP and chest wall pressure in 58 obese adult patients undergoing general anesthesia. In a healthy patient with an IAP between 0- and 7-mm Hg, these effects did not significantly affect the resistance of the lung wall. However, in a morbidly obese patient with an IAP of approximately 18 mmHg, an increase in the diaphragm and consequently a reduction in lung volume was observed, with a significant increase in the degree of atelectasis in the posterior lung regions [23].
In the cardiovascular system, the effects of an increased IAP are multifactorial and occur via three processes: 1) vascular intra-abdominal compression with venous stasis in the inferior vena cava, generating a reduction in preload; 2) elevation of the diaphragm leading to cardiac compression and an increase in the intrathoracic pressure, which consequently generates a decrease in cardiac contractility, aggravation of the decrease in preload, and a reduction in biventricular diastolic volume leading to a reduction in cardiac output; and 3) intra-abdominal organic compression generating activation of the renin-angiotensin-aldosterone system, thereby promoting an increase in the afterload. These three effects generate a decrease in coronary perfusion secondary to a reduction in cardiac output, increasing myocardial damage and the need for vasoactive drugs, as well as the systemic effects of a decrease in cardiac output, including a reduction in abdominal perfusion pressure [3].
The most significant effect of IAP on the renal system is related to blood flow. Compared with the control group, experimental studies revealed no significant reduction in renal blood flow or glomerular filtration rate in the group with an isolated increase in pressure in the renal parenchyma. Renal parenchymal compression did not increase the serum renin or aldosterone levels; however, an increase in renal parenchyma pressure and renal venous pressure and a decrease in renal blood flow secondary to a decrease in cardiac output was observed. In this model, there was a decrease in the glomerular filtration rate and consequent activation of the renin-angiotensin-aldosterone system, as confirmed by the increase in serum angiotensin II and aldosterone levels. The attempt to correct cardiac output with fluids did not result in the reversal of renal dysfunction, but the reversal of acute ACS did [24].
Moreover, in 2001, Citerio et al. demonstrated that the increase in IAP was transmitted immediately to the thoracic compartment by elevation of the diaphragm and that the increase in pressure in the internal jugular vein was also transmitted to the intracranial cavity [25].
The present study has some limitations. It had a single-center design, and we could not perform sample calculations. In addition, we studied only 54 patients, which may have limited our ability to detect any associations. Finally, this study was observational with a selection bias and confounding factors. Future studies should include a larger sample size and investigate whether early intervention can prevent mortality in this group of patients.
The high incidence, serious consequences caused by IAH/ACS, and high mortality rate substantiate the importance of monitoring IAP in children with onco-hematological diseases who are admitted to the PICU and have risk factors for IAH/ACS.