By now, I wouldn’t be surprised if you were asking yourself, “I thought this was a book about ECMO?” Why are we talking about hemoglobin dissociation, shock recognition, shunt physiology, and lactate clearance?
Hopefully this chapter will put it all together.
We have been building toward a fundamental concept that we will unpack more in this chapter, namely, that everything we do in the intensive care unit (ICU) comes with a cost. There is toxicity associated with interventions, and this toxicity is often dose related.
Let me underscore that one more time, to hopefully make sure we appreciate its implications.
Every intervention in the ICU has a dose-related toxicity – the more we have to dial up support, the more we have to consider the potentially toxic effects of what we are doing ( Fig. 5.1 ).
Let’s return to the oxygen delivery equation:
DO2→CO×Hb×SaO2
We are going to unpack the concept of dose-related toxicity for each component, highlighting the cost of optimizing each component, especially as things start to break down as patients begin to decompensate.
What is meant by dose-related toxicity of ICU interventions?
Let’s say you have a patient who is septic from a urinary tract infection, with Escherichia coli , a gram-negative bacteria, growing in the urine as well as blood cultures. He is placed on vancomycin, an antibiotic with gram-positive coverage but poor gram-negative coverage. When he does not improve, the dose of vancomycin is increased 20-fold.
What is wrong with this story? Why do we all cringe at this plan?
There are two fundamental flaws to this plan:
- 1.
You have to know what you are treating
- 2.
If you are treating the wrong diagnosis, increasing the dose will only expose this patient to toxicity without any benefit
Is this really a fair example?
Let’s entertain another example. In this case, it is a patient who arrives in the ICU with shock due to a pulmonary embolism with primarily right ventricular failure. The team assesses the patient, sees a low blood pressure, high heart rate, and low urine output and gives fluid.
When this doesn’t work, they give another bolus of fluid. And then a third.
After this doesn’t work, they initiate norepinephrine, with no improvement in blood pressure, uptitrating from 0.1 mcg/kg/min to the maximum of 2 mcg/kg/min. After this doesn’t work, the team initiates vasopressin, uptitrated to a maximum rate of 0.04 units/min. After this, with the patient still hypotensive, the team initiates a neosynephrine drip, uptitrating it to a maximum of 200 mcg/kg/min.
What is happening with this patient?
Much like our first patient who was being treated with escalating doses of the wrong antibiotic, this patient was exposed to escalating doses of support that was not helping his underlying condition. Let’s explore why.
In a pulmonary embolism, there is an occlusive thrombus in the pulmonary artery, which can increase right ventricular afterload and lead to right heart failure.
Recall from Chapter 2 that preload has a limited effect on a failing right ventricle. This is due to the various characteristics of the right ventricle – it is less muscular, shortens on a different axis, and this is eventually limited by the pericardium ( Fig. 5.2 ).
Additionally, recall that the failing right ventricle will not only dilate but can actually compress on the left ventricle, as is illustrated here. This can be the unfortunate consequence of excessive fluid bolus in right heart failure ( Fig. 5.3 ).
Next, the team initiates norepinephrine, which has the effect of improving systemic vascular resistance by increasing vasoconstriction, but remember also increases the pulmonary vascular resistance, which will only worsen right ventricular afterload ( Fig. 5.4 ).
Uptitrating norepinephrine and neosynephrine was the equivalent of increasing vancomycin to 20 g – uptitrating a medication that is not improving the clinical situation while only causing more adverse effects.
How do pressors worsen the clinical situation in shock?
One of the most important clinical effects of a mean arterial pressure (MAP) is maintaining a vascular pressure head to allow forward flow of blood and perfusion of peripheral tissues and end organs.
This pressure differential is normally maintained by the higher pressure that exists in the arterial system versus the venous system, which drives blood forward. The lower the MAP, the lower this forward flow and the lower the perfusion of the end organs ( Fig. 5.5 ).
Think of a garden hose that is losing water flow, not allowing you to reach a bush that you are watering. You can put your thumb over the top, which increases the pressure differential and allows you to now reach that bush. However, if the water flow continues to decrease, further occluding the hose with your thumb may allow you to reach the bush, but the overall amount of water that is reaching the bush decreases ( Fig. 5.6 ).
