The absence of a beneficial treatment effect, coupled with an increased incidence of serious bleeding complications, indicates that DrotAA should not be used in patients with severe sepsis who are at low risk for death, such as those with single-organ failure or an APACHE II score less than 25.

Increasing evidence has demonstrated that aggressive crystalloid-based resuscitation strategies are associated with cardiac and pulmonary complications, gastrointestinal dysmotility, coagulation disturbances, and immunological and inflammatory mediator dysfunction. As large volumes of fluids are administered, imbalances in intracellular and extracellular osmolarity occur. Disturbances in cell volume disrupt numerous regulatory mechanisms responsible for keeping the inflammatory cascade under control. Several authors have demonstrated the detrimental effects of large, crystalloid-based resuscitation strategies on pulmonary complications in specific surgical populations. Additionally, fluid-restrictive strategies have been associated with a decreased frequency of and shorter time to recovery from acute respiratory distress syndrome and trends toward shorter lengths of stay and lower mortality. Early resuscitation of hemorrhagic shock with predominately saline-based regimens has been associated with cardiac dysfunction and lower cardiac output, as well as higher mortality. Numerous investigators have evaluated potential risk factors for developing abdominal compartment syndrome and have universally noted the excessive use of crystalloids as the primary determinant. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation. Future resuscitation research is likely to focus on improvements in fluid composition and adjuncts to administration of large volume of fluid.