Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill as causes of significant morbidity and mortality. Over the last decades, IAH has been shown to be an important predictor of adverse outcomes in critical patients. The variety of previous definitions has led to confusion and difficulty in comparing one study to another [1]. The prevalence of IAH has recently been estimated between 32% and 65% in both medical and surgical intensive care units [2] [3].

Abdominal compartment syndrome refers to organ dysfunction caused by intra-abdominal hypertension. When intra-abdominal pressure rises, perfusion of internal organs is declined leading to tissue hypoxia. If undetected or untreated, multi-organ failure occurs and patient mortality may ensue [4].

It may be under-recognized because it primarily affects patients who are already severely ill and whose organ failure may be incorrectly contributed to progression of the underlying disease.

Since treatment can improve organ dysfunction, it is important to detect early in the appropriate clinical situation.

In 1947, Bradley and Bradley published a study of the effects of elevated IAP on kidneys in humans [5]. Since that time, many studies have been conducted to evaluate the renal manifestations of IAH/ACS, mainly in surgical patients. Critically, ill medical patients have been also the field of study in the last two decades. However, physicians in many countries are still not aware of this condition.

The world society of abdominal compartment syndrome (WSACS) has published a consensus statement including definitions and recommendations for the screening and management of IAH and ACS [6]. According to the WSACS, ACS is defined as sustained intra-abdominal pressure (IAP) of >20 mmHg with the presence of an attributable organ dysfunction. It is very important to differentiate between ACS from its predecessor, intra-abdominal hypertension. In the absence of any underlying disease, the average intra-abdominal pressure ranges from 5 to 7 mmHg with a normal upper limit of 12 mmHg. Thus, IAH is defined as sustained IAP greater than 12 mmHg.

Following this consensus, the goal of this study was to determine the incidence and prognosis of IAH in higher risk critically ill medical patients.

The study was conducted in ICU at Makassed General Hospital in Beirut. The study included an informed consent from the patients on admission (or their family if necessary) to participate and publish the results. All medical patients admitted to the ICU during a four-month period and expected to stay >24 h were prospectively enrolled. Exclusion criteria were ICU stay less than 24 h, age <18 years, pregnancy, contraindication for intravesical pressure measurement (pelvic fracture, gross hematuria, or neurogenic bladder), and bladder surgery.

Demographic data
Gender, body mass index (BMI) expressed as kg/m² [7], age, cumulative fluid balance, length of ICU and hospital stay, incidence of acute kidney injury (AKI), and hospital mortality were considered in collecting the patient's data.

Organ dysfunction
On admission, APACHE II (Acute Physiology and Chronic Health Evaluation II), APACHE III (Acute Physiology and Chronic Health Evaluation III)and SOFA (Sequential Organ Failure Assessment) scores were recorded [8] [9].

Risk factors for IAH
Patients were screened for categorized risk factors (CRF) of IAH on admission based on four categories from the WSACS algorithm (Table 1). Patients who present any risk factor (RF) of at least two different categories, on admission or during the ICU stay, were considered to have a high risk of developing IAH, and IAP was measured daily. IAP was not measured in the low risk group as our study aim to evaluate the incidence of IAH/ACS in the high risk group. IAP is classified into 3 grades according to the staging criteria by WSACS (I, 12-15; II, 16-20; III, 21-25; IV, ≥25 mmHg) [1].

Intra-abdominal pressure measurement
Intra-abdominal pressure was measured intravesically using a Foley catheter according to the revised closed system repeated measurements technique description of Malbrain and Sugrue [10] [11][12].

Measurements of IAP were recorded every 24 h in patients with ≥2 CRF until resolution of IAH, death, or discharge from the ICU.

IAP measurements according to WSACS [1] [4]:

1. Expressed in mmHg (1 mmHg = 1.36 cm H2O)
2. Measured at end-expiration
3. Performed in the supine position
4. Zeroed at the iliac crest in the mid-axillary line
5. Performed with an instillation volume of no greater than 50 ml of saline
6. Measured 30-60 seconds after instillation to allow for bladder detrusor muscle relaxation
7. Measured in the absence of active abdominal muscle

AKI definition and staging
Acute kidney injury was defined according to the latest KDIGO definition 2012 [13]:

• Increase in SCr by ≥ 0.3 mg/dl within 48 hours; or
• Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
• Urine volume < 0.5 ml/kg/h for 6 hours.

The severity of AKI was based on the definition of KDIGO 2012 [13] and classified into three stages according to increment of creatinine and/or drop in urine output (Table 2).

General results of the study cohort
During the study period, 88 patients were admitted to the ICU. All of the patients had ICU stay >24 hours, no one had had contraindications for intravesical pressure measurement or bladder surgery, 1 patient was <18. All patients who were admitted to ICU were screened for categorized risk factors of intra-abdominal hypertension. Not all patients admitted to ICU were included for IAP measurements. Only high risk patients with two or more than two categorized risk factors were included. Algorithm of general results of the study cohort is shown in Figure 1. Twenty-one patients had <2 CRF on admission and during all the ICU stay, so IAP was not followed-up. The remaining 66 patients, the high risk group, presented with ≥ 2 CRF on admission, so IAP was measured daily.

In the high risk group, 41 (62.1%) developed IAH. Of this group, 16 (39%) patients developed Grade 1 IAH, 23 (56.1%) patients had Grade 2 and only two patients developed Grade 3 IAH. The main diagnosis on admission is given in Table 3 with predominance of pulmonary diseases and septic shock.

General characteristics of the study cohort
Table 4 shows the general characteristics of participants. Different variables were studied including age, sex, IAH severity (Grade 1, 2 and 3), AKI or ESRD, critical care severity scores (APACHE II, APACHE III, SOFA score), BMI>30, CFB, mechanical ventilation, length of stay and mortality rate.

Incidence of AKI in pts with different grades of IAH
Patients with IAH (41 out of total number of patients 66 with CRF) had higher incidence of AKI (24 patients; 58.5%). Of the total AKI patients in this group, 15 patients (62.5%) were diagnosed with AKI (AKI on top of chronic kidney disease) upon presentation and nine patients (37.5%) develop AKI during hospitalization. Figure 2 shows the distribution of renal impairment in the form of AKI in patients with IAH. Higher incidence of AKI was among patients with IAH Grade 2 (55.2%), Grade 1 (37.90%) and Grade 3 (6.09%).

Mortality rates in patients with different grades of IAH
Mortality rate with significantly higher in patients with IAH Grade 2 (62.50%), 29.20% in patients with IAH Grade 1 and 8.30% with Grade 3 Figure 3.

Comparative analysis between IAH versus no IAH in patients with ≥ 2 CRF
In Table 5, we compared patients who developed IAH with ≥2 CRF (n=41) with those who did not (n=25). Severity scores among patients with IAH were higher with statistical significance (p-value for SOFA score 0.002, for APACHE II p-value < 0.0001, for APACHE III p-value <0.0001). Mortality rate was also higher in patients with IAH (p-value <0.0001). Decline in kidney function in the form of AKI, or AKI on top of chronic was also noted to be higher in patients with IAH with significant p-value =0.008. Other variables like BMI>30, LOS, positive cumulative fluid balance were studied among both groups but showed no statistical significance.

Comparative analysis between survivors and non survivors
Non-survivors had higher incidence of renal impairment in the form of AKI, and AKI on top of chronic with statistical significance. Non-survivors had higher critical care severity scores with significant p-value as given in Table 6. Patients with Grade 2 IAH had higher mortality rate comparing to other grades.

Multivariate analysis: predictive and prognostic models
Predictive model for IAH development in the high risk group (66 patients with ≥2 CRF)

APACHE II on admission (odds ratio (OR) 0.832, 95% confidence interval (CI), 0.722–0.958), mortality occurrence (OR, 4.777; 95% (CI), 1.099–20.763) were independent predictors of IAH development. Mechanical ventilation as one out of 2 CRF was not shown to be statistically significant for IAH Table 7.

Predictive model of mortality in the high risk group
IAH development was independent predictor of mortality (OR, 5.382; 95% CI, 1.218–23.781). SOFA score was also shown to be independent predictor for mortality (OR, 0.613; 95% CI, 0.450–0.835).

In our prospective epidemiologic study, we performed assessment of IAH in critically ill medical patients, according to the updated consensus definitions and clinical practice guidelines from the WSACS 2013 (screening, IAP measurement, definitions, and classification recommendations).

In our study, we found several significant findings:

• Significant number of patients with ≥2 CRF developed IAH on admission or during hospitalization stay,
• IAH at intensive care admission or during hospitalization stay was independent risk factor for mortality,
• Decline in renal function (AKI) was more common in patients with IAH, mainly IAH
  Grade 2, and mortality rate among this group was higher,
• Critical care severity scores (SOFA, APACHE II, APACHE III) were higher in patients with IAH,
• Mortality rate was significantly higher in patients with higher critical care severity scores,
• Other variables like sex, age, LOS, and BMI>30 were not shown to be statistically significant in patients with IAH.

The results of our study support the importance of screening for risk factors of IAH as recommended by the WSACS, as early detection and management of IAH may improve outcomes in this high risk group of patients.

Incidence of IAH in high risk group (≥ 2 CRF)
The incidence of IAH in the high risk group was high [41 (62.1%)]. High incidence of IAH had also been reported in literature [11] [14] [15][16][17]. Other studies done on mixed population (surgical and medical) [14] [15], and recent study done on critically ill medical patients [18] showed also high incidence of IAH in high risk group (≥2 CRF).

In contrast to other studies, screening for CRF was done on admission and upon occurrence of any risk factors or any new organ failure. In addition to the previously mentioned, our study assessed exclusively critically ill medical patients according the latest recommendations and clinical practice guidelines by WSACS [6].

Incidence of renal dysfunction in patients with IAH
The study came out with some interesting findings. Higher incidence of AKI was among patients with IAH (24 patients = 58.5%). Upon presentation 15 patients (62.5%) were considered to have AKI or AKI on top of chronic kidney disease, whereas nine patients (37.5%) develop AKI during hospitalization. Furthermore, patients who had no IAH had higher chance not to have AKI (68%). The results obtained in our study were similar to results of other studies that showed that IAH is an under-appreciated cause of acute renal failure [19] and that IAH is an independent cause of postoperative renal impairment [20]. Other articles also supported the same idea about renal dysfunction associated with IAH and ACS [21].

In addition to the significance incidence of AKI in IAH patients, it was also noticed, with statistical significance, the higher mortality rate among patients with AKI (55.6%). Low incidence of AKI and high survival rate in high risk group (56.4%) was noticed.

In conclusion, it is believed now that IAH or even small rises in IAP elevation are under-appreciated causes of AKI, and should be added to the list of causes of acute renal failure. Renal dysfunction in ACS appears to be caused by renal hypoperfusion, due to the raised renal vein pressure and partly to the low cardiac output and high renal vascular resistance [19].

Comparing critical care severity scores in patients with IAH versus non-IAH
Several organ dysfunction scores were taken using measurements obtained at the first day of admission. IAH was significantly associated with higher severity of critical care scores and incidence of organ failure. Concerning APACHE II score, patients with IAH had higher index with mean of (23.56), comparing to (17.92) in non-IAH patients. APACHE III score had similar results with higher index in the IAH group (78.34) versus non-IAH (61.40). SOFA was also taken in the first day of admission/or occurrence of IAH, and showed higher score in the IAH group (10.34) versus (8.24) in the comparison group, with statistical significance in all critical care severity score. On the other hand, illness severity scores were higher in deceased patients with IAH, comparing to the survived group. The mean values were 19.41, 66.67 and 8.33 for APACHE II, APACHE III and SOFA respectively, in the survived group comparing to higher values in the deceased group.

The study showed the higher severity scores in IAH group. As a result, it is becoming clear that IAH is independent risk factor for mortality. However, none of critical care severity indices includes IAP measurement despite all of the recommendations of WSACS.

Development of IAH has been described as an independent predictor of mortality in mixed populations [18]. In another study, IAH was a non-independent predictor of mortality, and this supported the fact that IAH was a marker of mortality in association with other clinical factors.

In our study, IAH was an independent risk factor for mortality in critically ill medical patients.

We found a high rate of resolution of IAH in our medical patients, but non-resolution was an independent predictor of mortality. Treatment of IAH was proposed by the final 2013 WSACS consensus management statements (Table 8), but still not applied in most of the ICU medical patients due to lack of awareness of IAH.

In conclusion, intra-abdominal hypertension (IAH) is a frequent finding in critically ill medical patients, and showed an independent association with mortality and deterioration in kidney function. IAH was significantly associated with more severe organ failures. Intravesical pressure technique is the gold standard method for measurement of IAP. Intra-abdominal hypertension's manifestations are difficult to detect on physical examination. At-risk patient populations should be routinely screened and monitored, and whenever diagnosis in confirmed patients should be managed early and aggressively. Our study highlights the importance of screening and early detection of IAH, as early detection and management may improve outcomes. Specific guidelines and recommendations for the management of patients with IAH/ACS have been published in 2004 and updated in 2013.

Our study generated important findings but unfortunately, there were several limitations.First of all IAP was only measured in high risk patients with ≥2 CRF. Second, measurements of IAP was performed only once daily due to the lack of trained staff. Another limitation is that the study did not identify the significance of subgroups of risk factors in the incidence of IAH and did not analyze each RF of the four categories as predictors of IAH. Additionally, not all patients who had their IAP measured were sedated, which could have caused a falsely elevated IAP. Finally, the study had small sample size, although other international studies had similar numbers of patients.

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