Fluid Management: Essentials for Pharmacists
Here's the scene. I'm a new PGY1 resident. I'm still a little nervous with the whole "residency" thing. I'm on my first rotation, covering is an IMC unit (which has patients less sick than an ICU, but more sick than a regular medicine floor). It's still early in the residency, and I'm already tired. Rounds start at 9am, but I arrived hours before to work up my patients. And I woke up hours before that because I hadn't yet lost my motivation for exercise and general health and wellness.
Rounds begin, and I learn that we have a patient that will be transferred to the chemo floor later that day. She has a primary CNS lymphoma and they are treating with high dose methotrexate. While waiting for a bed, the resident explains that we are going to pre-hydrate her with bicarbonate. This will alkalinize the urine, which will help the patient clear the ridiculous dose of methotrexate (about 17 GRAMS) she'll be getting later.
Then the resident asks. "We want to give her 150 mEq of bicarb per liter until she gets transferred. Do I just order that to go in normal saline?"
And I freeze.
I don't remember really talking about fluids at all during pharmacy school. I have no idea what 3 amps of bicarb can go into. It was in that moment that I perfected the classic "I'm not sure, but let me look it up really quick" routine.
I went on to see that fluid management is one of the most common interventions encountered in a hospital system. Even in retail (ahem: community) pharmacy, there are opportunities to make a difference in the fluid status of your CHF, liver failure, and pregnant patients.
So although fluid management may not be the "sexiest" topic for pharmacists you'll be doing yourself (and your patients) a favor by having an understanding of what's going on in the wonderful world of fluids.
And, if the suspense is killing you: Putting 3 amps of bicarb in NS creates a hypertonic solution. Typically, you will use either D5W or sterile water if you're adding that much bicarb.
Fluid Management: A Math Fantasy
Let's start with a breakdown of fluid distribution in the body. About 60% of total body fluid lives inside of cells (intracellular). The remaining 40% is outside of cells (extracellular).
The 40% that is our extracellular fluid, is broken down a little further. Surprisingly, only 25% of this fluid is intravascular fluid.
Intravascular (IV) fluid is what most people think of when they say "body fluid." It's the blood in your arteries and veins. It supplies oxygen and nutrients to the body. It's what trauma victims "bleed out." In total, it's roughly about 3 liters.
What about the remaining 75% of the extracellular fluid? This fluid is called interstitial fluid. What the crap is that? It's fluid that is said to "bathe" your cells. It lives in-between and surrounding your cells. If you're struggling to visualize this (you're not the only one), just think of it as everything that is not inside of a cell or in the blood stream.
This all can be easily demonstrated with some flowcharts:
Got it? Good. Moving on then.
This 60/40 split of intra/extracellular fluid is created and driven by oncotic pressure. Remember in 7th grade biology class when you learned about diffusion and osmosis? How an equilibrium is naturally created as water diffuses from a low concentration of solute to a high concentration?
Like the membraned beaker of 7th grade bio, so are the cells of your body. The lipid bi-layer cell membrane does a pretty good impression of the semi-permeable membrane in the image above. Most solutes (Na, K, Ca, Mg, etc...) cannot freely pass into or out of your cells. However, water can and does pass freely. And it does this based on the rules governed by oncotic pressure. Water "creates" an equilibrium based on solute concentration inside and outside of your cells.
All of that is well and good, but how do we actually use fluids for therapy.
For starters, IV fluids are broken down into two major branches: Crystalloids and Colloids. We'll start with crystalloids.
Crystalloids are a mixture of water and solute. They include all concentrations of sodium chloride, dextrose, and also lactated ringers (LR). We'll get more into this in a bit, but 0.9% NaCl and 5% Dextrose in water are isotonic with physiologic fluid. We often abbreviate them as normal saline (NS) or D5W respectively.
Another quick tidbit; the lactate in LR is metabolized by the body to bicarbonate; which can raise serum pH levels. This may make it preferred in a patient with acidosis, while steering you away in a patient with alkalosis. However, in most patients, either NS or LR are fine for first line fluid therapy.
When you give NS or LR to a patient, it distributes evenly throughout the extracellular fluid. Remember; solutes like Na or Cl cannot freely cross into cells so the fluid stays entirely in the extracellular compartment. Referring back to our diagram, 25% of the fluid will stay in the IV space, and the remaining 75% will go to the interstitial space. Put another way, if you give a patient a liter of NS, 750 ml will go to the interstitial space and 250 ml will stay in the blood vessels.
This rule does not apply to dextrose!
Although a crystalloid, fluids with dextrose are a different beast. Dextrose is a sugar (carbohydrate), which means your body can metabolize it. Actually, dextrose is just the configuration of glucose that your body uses for energy. For those who remember biochemistry, D-glucose = Dextrose.
The end product of carbohydrate metabolism is water and carbon dioxide. In the body, the carbon dioxide leaves when you exhale and the water sticks around. Therefore, in terms of fluid administration, giving dextrose results in giving free water. The patient will also get about 17 kcal / 100 ml of D5W, so there is a caloric component to consider.
Important disclaimer: The body may convert D5W into free water, but it is isotonic when administered. With few exceptions, all fluids should be isotonic when injected into the IV space. Do not under any circumstances inject water directly into a patient. Hypotonic fluids can very quickly kill your patient when administered IV. Do you remember the image that always followed the above image of the beaker in your biology text book?
Patient fatalities aside, let's remember that water can pass into and out of cells freely. This means that unlike NS or LR, when you administer D5W it distributes evenly among total body fluid (not just the extracellular fluid like NS or LR). So it follows the 60/40 distribution of intra/extracellular. And then the 40% that stays in the extracellular compartment will follow the same 75/25 interstitial/IV distribution that NS or LR demonstrates.
Using real numbers again, if you administer a liter of D5W, 600 ml (60%) will go inside the cells. The remaining 400 ml (40%) will stay in the extracellular compartment. Of this fluid, 300 ml (75%) will become interstitial fluid and only 100 ml (25%) will stay in the intravascular space.
This is one of the reasons why we generally avoid giving D5W for volume depletion. It's just not as effective as NS or LR at replenishing IV fluid. Additionally, there is a (small) risk of hyperglycemia in some patients because you're administering what amounts to sugar water.
The "classic" colloid is albumin, but also included are packed Red Blood Cells (RBCs), dextran (a glucose polymer) and hydroxyethyl starch (hetastarch). It is somewhat unlikely that you'll see a lot of dextran and hetastarch in your day-to-day practice. They both are associated with a pretty significant risk of hypersensitivity, kidney injury, and coagulopathy (read: bleeding). It's not that they're never used; you're just considerably more likely to see albumin and packed RBCs.
Colloids are large molecules. Large molecules aren't usually able to cross the capillary membrane. What this means is that when you give a colloid, the entire dose stays within the IV space. So if you were to theoretically bolus a liter of 5% albumin, you will get one liter of IV volume expansion. (Editor's note: This is rarely going to be a good clinical decision).
5% albumin is isotonic with physiologic fluid. Albumin also comes in a 25% solution. Thinking of our poor, shriveling red blood cells in the picture above; why would we give a hypertonic 25% solution? When the goal is to withdraw fluid. In patients with severe burns or liver failure, fluid can accumulate in the interstitial space. This is referred to as "third spacing."
Giving 25% albumin will draw this fluid out of the interstitial space and into the IV space. Note that the fluid is staying in the extracellar compartment--it's just "shifting" from the interstitial to the blood stream. This is useful because now we can give a diuretic (eg. furosemide) and the patient can urinate the fluid out.
Alternatively, a paracentesis can be performed. With paracentesis, a doctor literally sticks a syringe in the area with the fluid and sucks up the excess. Often a sample of this fluid will be cultured to make sure nothing silly or untoward is growing in it.
Lo' Fluid, Mo' Problems: Treating Volume Depletion
Let me preface this section by saying that it is very common for patients to "automatically" get put on IV fluid when they are admitted to the hospital. Fluids are a part of many computerized initiation order sets and it isn't unheard of for them to get added to a med list without anyone thinking twice about it.
I say this just so you keep an eye out during your practice. As a pharmacist, it's easy to overlook normal saline as a "drug," but if you see a patient getting high doses of Lasix at the same time they have a bag of NS running it's probably worth at least a question.
Most of the time when we talk about volume depletion we are speaking specifically about the IV compartment. Even though this is only about 10% of our total body fluid, the vascular fluid (plasma) is responsible for getting blood (read: oxygen and nutrients) to all of the vital organs.
Volume depletion causes hypoperfusion; where the organs do not get enough oxygen. The end result of hypoperfusion is heart attacks, acute kidney injury (AKI), and lots of sadness. Common causes of volume depletion are trauma (where blood is lost directly) and septic shock (where "leaky" capillaries cause fluid to shift from the IV to the interstitial space).
To treat volume depletion, we bolus 500 - 1000 ml of fluid and re-evaluate. Specifically, we're looking at blood pressure, urine output, dizziness, heart rate, and the BUN:SCr ratio. Improvement in these markers tell us that the patient is responsive to fluid.
If the patient is responsive, we'll keep giving fluid boluses as long as symptoms improve and we get the above markers to normal limits. It is preferred (though not required) to give fluid boluses through a central line because of the relatively large amount of fluid being administered per unit time. Most of the time, unless a central line is already in place they're administered peripherally.
So, which fluid should you choose? There have been numerous studies on this, and it's generally accepted that there is no difference in efficacy between crystalloids and colloids for most patients. However, colloids are a lot more expensive than crystalloids, and have more potential adverse effects--so you'll likely use crystalloids first.
Remembering that you need a lot more D5W to get the same intravascular volume expansion than NS or LR---you'll preferentially use NS or LR for fluid resuscitation.
Colloids may be tried in patients not responsive to crystalloids, or with some other compelling indication (a trauma patient would probably benefit from packed RBCs).
Regarding maintenance fluids--there is really just one very important rule. This is one of the few rules that I would say is pretty close to "universal" in medicine, so memorize it well. If the patient is able to tolerate oral therapy, then use oral therapy. You will see incarnations of this rule all over the place.
Always favor enteral nutrition over parenteral. Give PO drugs instead of IV. There are exceptions to every rule, but for the most part you should use the GI tract if it is functioning and tolerable for the patient. For fluids, give oral hydration if you can.
If a patient requires IV hydration, there are several formulas to calculate daily fluid requirements. That's a bit beyond the scope here (hasn't this article dragged on enough already?).
A fairly accepted estimate for adults is 30 ml/kg/day.
Total body fluid is split up as 60% intracellular and 40% extracellular
Crystalloids include NS, LR, and D5W. They are usually the preferred first line agents to treat volume depletion
Colloids include albumin and packed RBCs. They are not usually considered first line therapy for volume depletion due to cost and risk of adverse effects
Never inject sterile water into a patient. Seriously, just don't do it