For part 3 we will continue to look at the physiology of intravascular volume. Anytime we give crystalloids we are trying to ensure intravascular volume. But what keeps it in the intravascular space? The Starling equation shows the relationship between the intravascular oncotic and hydrostatic pressure versus the interstitial oncotic and hydrostatic pressure and how it will determine whether fluid stays in the intravascular space.
What is missing from this equation is osmolarity. Oncotic pressure contributes to osmolarity as discussed in part 2, but how does osmolarity contribute to intravascular volume?
Figure 1: Driving Forces for Extracellular Fluid Movement
The electrolytes completely dissociate into ions and are major contributors to the osmolarity of the interstitial and intravascular space. In fact, 95% of the osmolarity in the intravascular space is electrolytes. The reason that they do not contribute to the Starling equation is that electrolytes can cross the capillary membrane and, between diffusion and osmosis, the osmolarity equilibrates between the two spaces making the net movement due to electrolytes zero.
The van ‘t Hoff equation shows what determines the osmotic pressure
Osmotic pressure = π = iMRT
i = number of ions a solute will form when dissolved in water (van’t Hoff factor)
M = Molar concentration of the solution (mol/L)
R = Ideal gas constant (0.08206 L atm/mol K)
T = Temperature in Kelvin (K)
Again, since the electrolytes can diffuse across to the interstitial space, they normally do not participate much and the main determinate for keeping fluid in the intravascular space is oncotic pressure.
So why is osmotic pressure shown in figure 1?
The reason that osmotic pressure is represented in the forces for fluid movement is to represent opportunities for clinical intervention. This post is more about clinical opportunities for intervention more than most because physiologically electrolytes do not do much at baseline. But clinically, the osmolarity can be changed and used for resuscitation.
The logical next step in keeping volume intravascularly is giving hypertonic solutions. This is when a solution is given where the osmolarity is higher than the serum osmolarity. hypertonic solutions will change the equilibrium and, through osmosis, will drive fluid from the interstitial space to the intravascular space.
Figure 2: Osmosis
https://en.wikipedia.org/wiki/Osmosis
The change in electrolyte concentration will also cause fluid movement out of the intracellular space as well.
Hypovolemic shock:
In hypovolemic shock, there is decreased intravascular volume and the patient is overall hypovolemic. Hypertonic fluid can lead to shrinkage of the cells which is why it is not typically given for hypovolemic shock. It has been studied in hemorrhagic shock to increase BP acutely in the profoundly hypotensive. But isotonic volume in form of crystalloid or blood is still needed until the total body fluid is returned to normal.
Distributive shock:
Distributive shock, on the other hand, is due to vasodilatation and intravascular fluid leaking into the interstitial space. Crystalloid is given to replace the volume that leaked into the interstitial space and to fill the volume needed from the vasodilation. These patients are actually not volume depleted; they are volume shifted. This means the patients have the fluid, it is just in the wrong place. These are the patients that benefit from hypertonic resuscitation. I will go into why treating fluid shift with fluid leads to complications in more detail in a future post.
Hypertonic resuscitation:
This is not a new idea, although it may be new to some people, and has been used in different solutions for over a decade. Using 0.9% as a baseline concentration, the hypertonic solutions are based on percentages. The two most common hypertonic solutions are 3% hypertonic saline and 4.2% sodium bicarbonate. This is because of ease of use with prepackaged 3% saline and the 4.2% bicarbonate is because of the BICAR-ICU trial.
What is the evidence?
There are papers that show some trends towards mortality, but the larger papers and systematic reviews have not really shown a mortality benefit. Mortality benefit is not the goal for me when using hypertonic solutions. The goal is to ensure intravascular volume to shorten the time in shock and reduce the total volume needed, which has been shown to worsen outcomes. If hypertonic fluid can reach hemodynamic goals with less fluid given and reduce vasopressor requirements it will help with organ perfusion. By reversing shock faster with less fluid it will reduce late organ dysfunction from over-resuscitation with crystalloid. Vasopressin was not to lessen norepinephrine doses in the VASST trial and is used in most ICUs in septic shock patients despite not showing a mortality benefit. So treat hypertonic the same way.
Hypertonic saline in sepsis meta-analysis:
Hypertonic saline does not reduce mortality but did reduce the volume of fluid needed to reach MAP goals and reversal of shock.
BICAR-ICU:
4.2% sodium bicarbonate was used as boluses for acidotic septic shock patients. Overall it did not improve mortality, but in patients with acute kidney injury, it did improve mortality and reduce organ failure and renal replacement therapy requirements.
HERACLES
Hypertonic saline was studied post-cardiac surgery hypotension due to vasoplegia which is similar to septic shock. The overall fluid balance in the ICU stay was lower in the hypertonic saline group 296 ml vs. 1137 ml, but again no change in mortality.
Summary:
When I am trying to resuscitate a patient with distributive shock, I am supporting them until the underlying cause can be reversed. While treating the underlying cause, the support is trying to insure intravascular volume and vascular tone. Ensuring oncotic pressure and using hypertonic fluids are two ways to keep fluid intravascularly while not overloading them.
Infusion instructions:
I use 5 amps of sodium bicarbonate in 250mL of D5W, which will make a 4.2% solution. I give this at 75mL/hr for 7 hours as a 1-time dose. This usually will reverse shock or dramatically reduce vasopressor requirements. I will use this if Na – Cl is < 38, which is most of the time. If Na – Cl is >38 I will use 500mL of 3% saline at the same rate at a 1-time dose.
The reason I do it is as an infusion over 7 hours is to keep the osmotic gradient constantly. I feel that boluses help in the short term, but then they equilibrate.
I will monitor Na levels but they do not change much with such a low amount. I will check potassium and calcium levels when using bicarbonate because they were shown to decrease somewhat in the BICAR-ICU trial.
It is time to use physiology to treat septic shock!
References:
· Orbegozo D, Vincent JL, Creteur J, Su F. Hypertonic Saline in Human Sepsis: A Systematic Review of Randomized Controlled Trials. Anesth Analg. 2019;128(6):1175-1184. doi:10.1213/ANE.0000000000003955
· Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial [published correction appears in Lancet. 2018 Dec 8;392(10163):2440]. Lancet. 2018;392(10141):31-40. doi:10.1016/S0140-6736(18)31080-8
· Pfortmueller CA, Kindler M, Schenk N, et al. Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial. Intensive Care Med. 2020;46(9):1683-1695. doi:10.1007/s00134-020-06132-0