Hey everyone, this is Jessica, and welcome to CritIC!
This video covers one of my favorite topics in critical care medicine:
The pharmacokinetic changes that occur in ICU patients and the implications in clinical practice.
If the pharmacokinetic steps are unfamiliar to you, please watch my introductory series first.
Most of what you'll find in this video is based on the research by professor Jeffrey
Lipman, from Brisbane, Australia.
I highly recommend you listen to his SMACC podcast.
Link in the description.
Now, let's get into the good stuff.
The recommended dose for a drug you prescribe is based on the average adult.
And you probably make a few adjustments based on body weight or renal function.
However, in the ICU, your typical patient isn't the average adult anymore that that
dose was based upon.
ICU patients are frequently hemodynamically unstable requiring vasoactive support, and
they have all sorts of tubes connected to them, like a mechanical ventilator.
These can all influence pharmacokinetics.
For absorption:
Gastrointestinal absorption is decreased in
most ICU patients.
Any type of shock results in reduced gut motility, and thus delayed gastric emptying, as well
as reduced splanchnic blood flow.
The use of vasopressors reduces splanchnic blood flow even more.
Excessive fluid administration could cause bowel edema.
And lastly, the typical ICU patient is being fed through a nasogastric tube, usually 24/7.
You can imagine that the absorption of certain drugs, like levothyroxine, is compromised.
All these factors decrease drug absorption through the gut.
Absorption through subcutaneous injection is compromised by shock or the use of vasopressors,
since they reduce skin perfusion.
So, what does this mean in clinical practice?
You're better off prescribing most of your drugs i.v., at least initially.
For distribution:
In a lot of ICU patients, total body water
is increased through several intertwined processes.
Excessive fluid administration, used for the initial treatment of shock, increases total
body water by filling up not only the intravascular compartment, but also the interstitial space.
This is especially so if the patient can't pee it all out (in severe renal failure) or
if the patient can't keep the fluids in the intravascular compartment, which is the case
in hypoalbuminemia and when the patient experiences capillary leak syndrome.
Capillary leak syndrome is the result of a systemic inflammatory state (like in septic shock)
that leads to vasodilation and increases vascular permeability.
Note that albumin is a negative acute phase protein, meaning it decreases in an inflammatory
state.
So, a septic patient in the ICU has 3 major reasons why they have an increase in total
body water (excessive fluid administration, hypoalbuminemia and capillary leak syndrome).
This is even more so if they have severe renal failure.
Let alone that there are specific conditions in which this is expressed even more.
For example: in severe liver failure, there is ascites due to not only low albumin levels
but also due to increased hydrostatic pressure in the portal system.
Another example is acute pancreatitis, where the patient loses a lot of alkaline fluids
in the abdomen.
So what does this mean in clinical practice?
An increase in total body water means that for hydrophilic drugs, the volume of distribution
is increased.
If we don't take this into account, it will take a lot longer for our drug to reach optimal
serum concentrations.
Thing is that a lot of antibiotics, especially aminoglycosides like gentamicin, glycopeptides
like vancomycin, and serveral beta-lactam antibiotics, are hydrophilic drugs.
So in these patients, we need to administer a loading dose for these drugs, to quote professor Lipman:
"if you care about time to antibiotics".
For clearance:
For hydrophilic drugs, renal clearance is
the most relevant versus hepatic clearance.
Renal failure is common in the ICU.
But did you know some ICU patients develop an increase in renal function and thus clearance?
This is called augmented renal clearance, and it is defined as a 10% increase in normal
renal clearance, so typically renal clearance of around 130-140 ml/min.
Note that a lower serum albumin leads to an increase in free drug concentration.
However, in people with augmented renal clearance, this leads to lower serum concentrations because
more can be renally cleared.
Now who are these patients with augmented renal clearance?
They are the younger, fairly healthy ICU patients, with normal to high cardiac outputs, singular
organ failure (obviously not renal failure), that arrive at the ICU with normal serum creatinine levels.
As increased clearance leads to lower serum levels, this would imply you would need to
increase maintenance dose in these patients.
In summary In ICU patients, absorption is usually decreased,
so to be safe, administer intravenously initially.
Combining the changes that occur in volume of distribution and clearance: for hydrophilic
drugs, which are a lot of commonly used antibiotics, these changes result in a decrease in serum
concentrations.
So beware of possible subtherapeutic levels.
Thank you for watching this video.
I tried to be concise, but a lot more can be said about this topic.
And a lot more research is currently being done.
I've put a few interesting articles in the description if you're interested in more on
this topic.
Please share this video if you liked it, and I'll see you in the next one.