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Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been well described in surgical patients. Large-volume resuscitation is thought to be a risk factor for IAH/ACS in this group. However, little is known of the incidence of IAH/ACS in critically ill medical patients. The authors aim to ascertain the incidence of ACS in critically ill medical patients receiving large-volume resuscitation. Over an 8-month study period, the authors performed a prospective cohort study of medical intensive care unit (ICU) patients with a minimum net positive fluid balance of 5 L within the preceding 24 hours. The primary outcome of interest is the development of ACS, defined as an intra-abdominal pressure (IAP) ≥20 mm Hg associated with new organ dysfunction. IAP was measured by transducing bladder pressure and was recorded along with fluid balance at enrollment and every 12 hours thereafter up to 96 hours. The setting is a medical ICU at a major university hospital. Of the 468 medical ICU admissions screened, 40 (8.5%) were identified who met the 24-hour fluid balance inclusion criterion. Upon enrollment, this cohort had a mean Acute Physiology And Chronic Health Evaluation II score of 23 and a median positive fluid balance of 6.9 L. Thirty-four of the 40 study patients (85%) had intra-abdominal hypertension (IAP ≥12 mm Hg). During the study period, 13 of the 40 (33%) patients developed IAP ≥20 mm Hg and 10 (25%) met the criteria for ACS. None underwent laparotomy. ACS is frequently found in critically ill medical patients receiving large-volume resuscitation. The clinical significance of this finding remains unclear. However, routine monitoring of IAP should be considered in medical patients with a 5-L net positive fluid balance in 24 hours. Future studies are warranted to evaluate clinical outcomes of medical patients with ACS and risk factors for its development.