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Acute lower extremity compartment syndrome (ALECS) is a devastating complication that often presents silently in critically injured patients; therefore, we developed a protocol to screen high-risk patients.This prospective observational study included all Shock Trauma intensive care unit patients who met specific high-risk criteria including pulmonary artery catheter-directed shock resuscitation, open or closed tibial shaft fracture, major vascular injury below the aortic bifurcation, abdominal compartment syndrome, or pelvic or lower extremity crush injury. Patients were screened at admission and every 4 hours thereafter for the first 48 hours of admission. Screening included physical examination (PE) and anterior or deep posterior calf compartment pressure measurements when PE was suspicious or unreliable. A positive screening, defined as a ΔP <30 mm Hg (where ΔP is the difference between the diastolic blood pressure and the compartment pressure), mandated a four-compartment fasciotomy.During a 6-month period, the incidence of ALECS in screened patients was surprisingly high at 20% (9 patients). With diligent screening, it was diagnosed early in the patient's Shock Trauma intensive care unit course. These were patients with severe injuries with an Injury Severity Score of 32.0 ± 12.5 who exhibited significant volume depletion, with a base deficit of 12.9 ± 5.9 mEq/L and a lactate level of 13.0 ± 5.2 mmol/L, requiring large volume resuscitation. Although aggressive fasciotomy resulted in no limb loss, ALECS was associated with an exceedingly high mortality rate at 67%.ALECS is an important clinical entity in critically injured patients with trauma associated with significant mortality. Aggressive screening may provide some diagnostic insight to those at risk.