Fluid overload, and resulting inadequate blood flow, is a relatively frequent occurrence in critically ill patients and is often a consequence of critical care intervention with intravenous fluid therapy.
Fluid Overload and hemodynamic instability
Despite a common perception that it is benign, fluid overload in the critically ill is independently associated with increased morbidity and mortality. Fluid extravasation into the interstitial space can adversely affect multiple organ systems, with various manifestations ranging from impaired cognition, impaired contractility of the heart, and tissue edema in skin and muscles giving rise to delayed wound healing, pressure ulcers and wound infection. In lungs, fluid overload induces increased extravascular lung water, with increased work of breathing and impaired gas exchanging leading to hypoxemia. A particular serious complication of fluid overload is kidney injury as discussed below.
In general, fluid overload (FO) contributes to delayed recovery at ICU and prolonged length-of-stay at the hospital, and leads to increased health care resource uses and costs.
Acute Kidney Injury
The kidney is a highly vascular and encapsulated organ that is exquisitely sensitive to inadequate (insufficient or excess) blood flow. Intravenous fluid infusion, when exceeding the capacity of lymphatic drainage in the microcirculation, will inevitably cause interstitial edema. In the kidney, interstitial edema will through a cascade of events lead to tissue hypoxia and acute kidney injury (AKI). Such acute kidney injury is characterized by a rapid loss of renal function. Inadequate urine output in AKI can further worsen tissue edema, creating a vicious cycle.
Moreover, the acute injury often progresses into a chronic state, ultimately leading to end-stage renal disease. These patients are considered to be critically ill and require dialysis or renal replacement therapy. AKI exerts direct effects on other organs and systems as well and contributes to multi-organ failure in critically ill patients.
AKI affects over 3 million patients per year with a mortality rate of up to 70%. AKI is directly associated with short- and long-term complications in patients, and the condition is associated with a mortality rate of 40-70%. The mortality of patients with AKI is approximately 1 out of 4.
Diuretics are the most commonly used drugs to treat clinically diagnosed fluid overload. There is however no conclusive evidence that they alter major outcomes such as survival to hospital discharge or time in hospital.
Currently, the only treatment options for AKI are dialysis and supportive care which do not address the underlying causes, do not limit further damage and do not prevent progression. Currently, no drugs are licensed to treat this condition.
Life-threatening kidney damage can be prevented by directly targeting hemodynamic stability of surgery patients.Therefore, novel treatments are needed that provide an effective solution for patients with fluid overload and to prevent severe side-effectss and life-threatening organ failure caused by this condition.
EBI’s Promising Solution
The therapeutics developed by EBI target the vascular permeability directly and thereby present a promising and novel solution for the fast and effective treatment of fluid overload. In addition to directly addressing the cause of disease, EBI’s solution attenuates the immune response and promotes tissue repair, and thus is a first-in-class drug addressing tissue damage and promoting repair.