Resuscitation with hypertonic saline following cardiac surgery
To modulate the risks of volume overload with isotonic crystalloid solutions, resuscitation with hypertonic saline (HS) is of increased clinical interest in the perioperative setting [21, 74]. HS has been used for over 30 years in the treatment of hypovolemic and septic shock, burn injuries, hyponatremia and increased intercranial pressure [74-76]. Due to a higher tonicity relative to human plasma, HS creates an osmotic gradient that promotes fluid to shift from the extracellular space to the intravascular space [74]. This relative increase in intravascular volume serves to increase preload [60, 74, 76, 77]. Thus, when compared to equivalent volumes of NS, resuscitation with HS results in a more profound increase in MAP, CO and stroke volume in those who are critically ill [74, 78].
Beyond its hemodynamic effects, resuscitation with HS may also have an impact on systemic inflammation [76]. HS has been found to blunt neutrophil activity, cytokine production, and pro-inflammatory markers (e.g. IL-G and TNF-alpha) all while upregulating the activity of anti-inflammatory markers, such as IL-10 [76]. This is of particular significance in patients undergoing cardiac surgery, given the degree of systemic inflammation and complement activation that occurs during extracorporeal circulation [76].
To investigate this further, Yousefshahi et al. conducted a randomized, double-blinded clinical trial comparing inflammatory markers predictive of AKI in individuals given HS compared to NS prior to their CABG procedure (n=40). Inflammatory markers of interest (neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C) were measured before cardiac surgery, 24 hours and 48 hours post-CABG [79]. While investigators did not find a statistically significant decrease in NGAL or cystatin C in those given HS compared to NS (p=0.792 and p=0.874, respectively) [79], other analyses have demonstrated increased urinary output independent of diuretic usage and less weight gain post-CABG in those given HS compared to NS [74, 80].
To further investigate HS as a resuscitation fluid in patients following elective cardiac surgery, Pfortmueller et al. recently published a study protocol for a single-center, prospective randomized controlled clinical trial comparing post-operative FBT with HS to NS in patients post-CABG[21] The primary objective of The Hypertonic Saline for Fluid resuscitation after cardiac surgery (HERACLES) trial is to determine if resuscitation with HS results in less total fluid volume administered when compared to NS [21] The HERCULES trial further aims to investigate whether the use of HS results in a difference in post-operative weight gain, cumulative vasopressor use, or urinary output when compared to NS after cardiac surgery [21]. Exploratory outcomes described in the HERCULES protocol also includes comparing
ICU and hospital mortality, duration of ventilator dependence, and need for renal replacement therapy between study groups [21]. While results from the HERCULES trial are pending, this robust study highlights the paucity of literature currently available describing the use of HS for resuscitation in those following revascularization procedures [21].