Supported Research

General Audience Summary

Inflammation is present in all intensive care patients. Leukocytes, white blood cells are important in the inflammatory response. However, when the inflammation is too great, the compensatory mechanisms of the patients are overwhelmed and the patients can then have complications such as acute kidney injury (AKI) or other dysfunctions. The immune system of these patients goes from a period of hyperactivation to a period of immune fatigue associated with immunosuppression leading to infections. Any stimuli can then contribute to overstimulate leukocytes, exacerbating renal and tissue damage, leading to immunological fatigue. Critical care patients, in addition to receiving antibiotics, also receive fluids in the form of crystalloids. Three solutions are available clinically: Normal Saline, Ringer's Lactate and PlasmaLyte. Recently, normal saline, with a higher concentration of chlorine, has been associated with more AKI and other bad kidney events, with no real explanation. However, the impact of fluids on the modulation of inflammation and their role in renal insults and immunosuppression in intensive care patients are unknown. Our hypothesis is that Normal Saline is the solution with the worst inflammatory impact, thus causing more AKI. In order to test our hypothesis, we will study the inflammatory modulation induced by the infusion of each of the solutions in cardiac surgery patients. Furthermore, we will perform experiments on their leukocytes to understand the mechanism by which sodium actives them. We will also evaluate the inflammatory impact and the consequences on renal function of the various crystalloids in a murine model of renal insult: ischemia-reperfusion. The absence of excessive inflammation prior to the surgery at the time of administration in cardiac surgery patient will make it possible to assess any modulation induced by these solutions on the activation of leukocytes and the production of associated inflammatory cytokines. The murine model of renal ischemia by arterial clamping and contralateral nephrectomy will reproduce a clinical condition often found in intensive care patients. Immunological analyzes and with immune stimulation in vitro will be carried out in order to evaluate the inflammatory potential of the fluids in vivo and in vitro. We will assess leukocyte activation by flow cytometry and the measurement of plasma levels of inflammatory proteins varioius techniques. This study will provide further insight into the immunomodulatory impact of clinically used fluids and its role in the increased incidence of AKI as seen with Normal Saline. It will identify the type of crystalloids with the least inflammatory and nephrotoxic potential. These results will lead to a greater understanding of immunological effects in order to allow personalized use of solutions in the clinic.