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].