Vasopressors - Know Your Concentrations

This is the first in a new series of ""Bedside Tutorials in Critical Care" that reflects issues that we dynamically come across while doing rounds in the ICU.
A critically ill patient arrives in the ICU – transferred from another hospital – there is a baffle of pumps attached – each one delivering a different inotrope or vasopressor. The pumps are programmed in ml per hour. You need to change the patient over to your own pumps – how do you know whether the dose that you deliver is the same as what the patient is currently receiving – is there an argument to standardize the dilution and dosage of commonly used vasopressors? I believe there is.

Vasopressors are very widely used drugs in critical illness - norepinephrine (noradrenaline) is the most widely prescribed catecholamine, used in most types of shock and considered the standard of care vasopressor in septic shock. Epinephrine, these days may be added as an inotrope or used in neurogenic or anaphylactic shock. Vasopressin is used to restore vascular tone as a form of hormone replacement therapy.

Norepinephrine and Epinephrine concentration and dosing is extremely confusing. Many ICUs dose these agents in micrograms (mcg) per minute. This translates to ml/hour - often the bedside practitioner has not made the conversion. Consequently, when asked "how much norepinephrine the patient is on?" the response may be 5 or 10ml per hour. This is unsatisfactory, as, based on weight, there may be a tremendous variability in the dose received. Moreover the concentration of norepinephrine varies widely. In our hospital we have been required to use a pre-diluted formula of 4mg in 50ml (delivered by syringe driver) resulting in a concentration of 80mcg/ml. Conversely, epinephrine needs to be drawn up, using 1mg ampoules, usually 3mg in 50ml or 60mcg/ml (conveniently this works out as 1mcg/min/ml. Peripherally infused norepinephrine is constructed by placing 4mg in 250ml, leading to a concentration of 16mcg/ml.

Alternatively, norepinephrine may be diluted 16mg in 250ml to yield 64mic/ml. When a patient is transferred from another hospital or another country, it may be really difficult to translate the dilution and concentration used there to match up dosage. And that is important - escalating doses of pressors are suggestive of failure of source control, but 10ml/hour is twice to dose delivered to a 50kg person than a 100kg person. And at what dose do you start vasopressin?

Consequently, I strongly recommend that you use mcg/kg/minute as your dosing strategy for both norepinephrine and epinephrine. The starting dose is 0.01-0.03mcg/kg/min and it is titrated upwards to achieve a mean arterial pressure of 65mmHg. Once the dose has exceeded 0.25mic/kg/min, the patient should receive vaspressin 0.03 international units per minute. If 40iu is diluted in 50ml, to deliver 0.03 iu/min, the infusion should run at 2.3ml/hour.
Description
00:00 Introduction
01:14 Titrating Norepinephrine (noradrenaline)
02:08 Translating ml/hour to mcg/min
05:38 Translating ml/hour to mcg/kg/min (50ml syringe dilutions)
10:00 250ml Dilutions of Norepinephrine (noradrenaline)
12:21 Peripheral Administration of Norepinephrine (noradrenaline)
14:15 Titrating Epinephrine (adrenaline)
16:51 Vasopressin
19:08 Review
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