Thread by @SaraJPharmD

Just read a uniquely eloquent perspective that should inform volume resuscitation, especially in septic patients.

Allow me to discuss some key points in my first #tweetorial.

doi: 10.1111/AAS.13533
onlinelibrary.wiley.com/doi/abs/10.111…

First, which of these most closely resembles what you currently feel is the ideal DOSE and RATE of initial crystalloid fluids in #septic shock?

This piece is in tune with one of my biggest pharmacist mantras- "fluids are drugs and should be treated as such." But it also dives deep into everyone's LEAST favorite property of drugs- KINETICS 🤓

Like drugs, each fluid has a volume of distribution (Vd), peak concentration (Cp), half-life (t1/2), etc. Unlike pharmacokinetics, fluid kinetics are based on the central (Vc) and peripheral (Vt) compartments' ability to expand, thus exerting their clinical & deleterious effects.

So what do the kinetics of crystalloids look like? Here's the volume expansion from 1.5L of LR infused over 45min in healthy/awake people at different MAPs. Note how much goes into the plasma (Vc) vs. the interstitium (Vt), and for how long it stays there.

Distribution half-life is about 8 minutes, which means the fluid you're infusing won't be done distributing into the interstitium (where we DON'T want it) until around 30mins after the infusion ends.

::Sidebar/shameless foreshadowing: that's why 30mins is basically the time-to-intubation after 30mL/kg is complete in inappropriate patients...::

The total DOSE (I.e. volume) has a lot to do with how much of your fluid stays in the plasma. This is because the interstitial matrix is "gel-like" and requires a certain amt of force exerted against it from volume expansion before it lets the fluid out.

This means that more fluid INFUSED does NOT = more fluid in the PLASMA.
Small volumes, I.e. 2-5mL/kg over 15-30mins, don't expand the plasma volume too fast (don't disrupt the interstitial matrix) + are rapidly excreted so ➡ make great volume expanders! ☑

The fluid infusion RATE also has a lot to do with how much of your dose (volume) stays put in the plasma.
FASTER infusion rates ➡ FASTER distribution into the interstitium + SLOWER re-distribution back into the plasma (the lymphatic system can't keep up).

To visualize these points, just look at how different the kinetics are for crystalloid - acetated Ringer's in this example - infused at 1200mL/hr (red) vs. 6000mL/hr (green).

Lastly, recall that SEPSIS / distributive shock is characterized by arrested re-distribution, meaning all that fluid going into the interstitium ISN'T coming back. This is how we get peripheral edema, intravascular hypovolemia, and ⬇cardiac output.

At this point, you should be asking yourself - "why do we treat septic shock by slamming in piles of crystalloid?" 🤔

Please share widely so that all may ponder this question and stop the madness.

Now which of these most closely approximates what you feel is the ideal DOSE and RATE of initial crystalloid fluids for septic shock?

Obviously there's not one right/clear answer in real life, and I am NOT recommending any of these as the right answer in all your patients, but you get the idea. All drugs should be dosed sensibly and monitored for effect. I like the last one as a starting point best, personally.

Now if only #SEP1 agreed with me...

Thank you for joining me today!

#FOAMed #EmergencyMedicine #EmergencyMedicinePharmacy #fluidresuscitation #volumekinetics #EmergencyMedPharmacy #EMedPharmacy

Excellent article by Dr. Robert G. Hahn in Sweden. Anyone know if he's on Twitter?

Also @iamahawkins we should be friends 👋 I commend your publication on #fluidstewardship 👏