Introduction
Despite recent advances in the management of patients, such as early enteral nutrition and withholding surgery until proven infection of pancreatic necrosis, severe acute pancreatitis (SAP) remains a disease with an unpredictable clinical course and significant morbidity and mortality [
1]. Infection still remains the most feared complication, but also the presence of organ dysfunction is increasingly recognized as an important risk factor for mortality in patients with severe disease [
2‐
4].
Intra-abdominal hypertension (IAH) has been recognized as a cause of organ dysfunction in critically ill patients, with respiratory and renal dysfunction often most prominent [
5]. This syndrome, referred to as the abdominal compartment syndrome, has most extensively been described in patients who underwent emergency abdominal surgery or after abdominal trauma, but also in patients with non-abdominal diseases such as burns [
6] and massive fluid resuscitation [
7].
Some recent studies [
8,
9] suggest that IAH is a frequent finding in SAP patients. The clinical relevance of this remains unclear, although Pupelis
et al. [
9] found a relation between elevated intra-abdominal pressure (IAP; above 25 mmHg) and persistent subsequent organ dysfunction. Tao
et al. [
10] described a high incidence of IAH in patients with early SAP, but lack of a definition of IAH and methodological issues make interpretation of these data difficult [
10].
The levels at which elevated IAP can cause organ dysfunction are lower than in the study by Pupelis
et al. Values of as low as 15 mmHg may result in clinically significant organ damage [
11‐
13], but clinical significance of this lower threshold in patients with SAP remains to be determined.
The aim of this analysis was to study patient factors associated with the development of IAH. Furthermore, we studied the incidence of organ failure in patients with SAP and IAH, and the association of the presence of IAH and outcome.
Materials and methods
Patients
We studied all patients admitted because of SAP to the intensive care unit (ICU) of the Ghent University Hospital (Gent, Belgium) between January 2000 and March 2004. SAP was defined according to the criteria described by the International Symposium on Acute Pancreatitis [
14]. Patients names were retrieved from the hospital registry using ICD code 577.0 (acute pancreatitis), and files were reviewed retrospectively. Patients who were referred from other hospitals later than 7 days after the start of SAP were excluded. The study was approved by the local ethical committee.
Preoperative data collected included age, gender, etiology of SAP, C-reactive protein level, Ranson score and Acute Physiology And Chronic Health Evaluation (APACHE) II score [
15] on admission and C-reactive protein at 48 h after admission.
Data acquisition
IAP values were measured every 8 h when IAP was below 15 mmHg, and every 4 h when above 15 mmHg, and were retrieved from the patients file. IAP was measured using the transvesical route, as described by Cheatham
et al. [
16], after instillation of 50 ml of saline in the bladder. IAP measurements were obtained from patients when multiple intra-abdominal fluid collections were present on CT scan on admission, or when there was the clinical suspicion of IAH. These clinical indications included oliguria, hypoxia, abdominal distension, and severe abdominal pain. The incidence of IAH (defined as IAP ≥ 15 mmHg) was recorded, as was the maximal IAP value obtained during ICU stay, and the duration of IAP levels ≥ 15 mmHg.
The occurrence rate of organ dysfunction during ICU stay was recorded and defined as: cardiovascular, hypotension requiring vasoactive medication (epinephrine, norepinephrine, dobutamine at any dose, or dopamine at doses above 2 mcg/kg/min); renal, serum creatinine above 2.0 mg/dl; pulmonary, the need for mechanical ventilation or PaO2/FiO2 ratio < 300. Mortality was defined as in-hospital mortality.
Interventions to alleviate IAH were recorded, as were complications of these interventions. Decompressive laparotomy was considered when rapidly deteriorating, therapy resistant multiple organ dysfunction was present in the first days after admission, and decided on a patient to patient basis.
Statistical analysis
Statistical analysis was performed using SPSS for Windows 11.0.1 ® (SPSS, Chicago, IL, USA). Continuous variables were compared using the Mann Whitney U-test. Categorical data were compared using the Chi-square or Fisher Exact test. Continuous data are expressed as mean (standard deviation) if the data were normally distributed, or median (interquartile range) if the distribution was not normal. Categorical data are reported as n (%). Pearson correlation coefficient between maximal IAP and APACHE II score was calculated. Mean IAP values from day 1 to 7 were compared using the Friedman test. A double sided p-value of less than 0.05 was considered statistically significant.
Discussion
In this cohort of patients admitted to the ICU because of SAP, the incidence of IAH was 51%. When only patients in who IAP monitoring was performed are considered, the incidence reached 78%, but this might be an overestimation as IAP measurement was not performed routinely and was based upon clinical suspicion for IAH. Also, IAH developed early in the course of the disease; in the majority of the patients in whom IAP monitoring was available from the day of admission, IAH developed within 24 h after ICU admission.
Although the difference in IAP during the first week was not significant, there seem to be three time frames early in the course of the disease. At day 1 the IAP was already elevated, and it then increased to the maximal level at day 2 and remained elevated until day four after admission. IAH in patients with SAP seems to be an early event.
Maximal IAP values were well above the 15 mmHg threshold used for the definition of IAH, and were as high as 25 to 40 mmHg in some patients, including the four patients who underwent abdominal decompression for abdominal compartment syndrome. These high values of IAP may be an explanation for the high incidence of organ failure in these patients, as all patients with IAH developed at least one organ failure, and the majority two or more.
SAP patients develop IAH for several reasons. Pancreatic or retroperitoneal inflammation is the most obvious reason in the early course of the disease. Aggressive fluid resuscitation, resulting in generalized and visceral odema in particular, will add to the intra-abdominal volume during the first days of severe disease. Furthermore, paralytic ileus and peripancreatic acute fluid collections can also increase IAP.
From the APACHE II and Ranson scores of the patients, it seems that the more severe the disease, the higher the likelihood to develop IAH. But IAH itself may be an early predictor of severe disease, as elevated IAP seems to occur early in the course of the disease. IAH may even contribute to disease severity in patients with SAP, but the exact role remains to be determined. Elevated IAP causes intestinal hypoperfusion even at levels as low as 8 to 12 mmHg [
12]. In the setting of SAP, pancreatic perfusion may also be affected, and possibly IAH may contribute to the development of pancreatic hypoperfusion and eventually pancreatic necrosis. The observation of increased bacterial translocation in patients with IAH and abdominal compartment syndrome [
17] may also apply to patients with SAP. Animal studies have shown an increased rate of bacterial translocation in acute pancreatitis [
18], but the role of IAH in this remains to be elucidated.
Patients with IAH had necrosis more often and were operated on more often. This resulted in a longer ICU and hospital stay for these patients. Surgical decompression was performed in four patients with IAP levels above 25 mmHg and severe organ dysfunction, but only one patient survived. The three other patients succumbed early after decompression, two patients from hemorrhagic shock and one from further deteriorating multiple organ dysfunction syndrome. The necrosectomy that was performed in the first patient treated with abdominal decompression possibly played a role in the hemorrhagic shock and deterioration early after surgery. Necrosectomy was not applied to subsequent patients who underwent decompression. In the second patient who died of uncontrollable bleeding from the retroperitoneum, the bleeding itself may have played a role in the development of IAH. At laparotomy, there was a large retroperitoneal haematoma, with active bleeding, possibly caused by an eroded vessel or pseudoaneurysm. Due to the profound bleeding, no clear cause could be identified and, unfortunately, the family of the patient refused a post mortem examination.
This experience in our four patients has tempered our initial enthusiasm for decompression in patients with IAH and SAP [
19]. Other authors also reported poor survival rates after surgical decompression in patients with SAP [
8]. Patient selection may, however, bias the results of decompression, as only patients with uncontrollable organ dysfunction have been considered candidates for decompression in our unit, and also the timing of surgical decompression may play a crucial role.
There has been a recent trend towards postponing surgery in patients with SAP because early surgical intervention was associated with an increased mortality rate [
20,
21]. This could also be concluded from our limited number of patients who died shortly after surgery, but it should be considered that the strategy of early intervention in SAP without infection, where the retroperitoneum is debrided, differs substantially from a procedure in which the abdomen is opened, but the retroperitoneum is left untouched. Moreover, in one of the patients that was decompressed and debrided in our study, an uncontrollable haemorrhage from the retroperitoneum occurred, and the patient died a few hours later.
Little can be concluded from this study as to the usefulness of early debridement but, in our experience, the absence of infection, increased age and acute renal failure were associated with an increased mortality in a series of patients who were treated surgically for severe acute pancreatitis; the timing of the surgical intervention itself had no effect on this [
22].
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
JDW and EH conceived and designed the study. Acquisition of a substantial portion of data was done by JDW. Analysis and interpretation of data was performed by JDW, EH and SB. JDW and SB drafted the manuscript. FC, JDC and EH critically revised the manuscript for important intellectual content. EH and SB supplied statistical expertise. FC supervised and was responsible overall for all aspects of the study.