The Rule of Six in Infusion Part 2 - The Pros and Cons

For the last one week, there has been some interesting discussion in my group on the use of the rule of six for infusion. I have previously written a blog post on this.

According to an article (click here to access), the rule of six is not optimal for patient safety - which I sincerely agree.

Some of the points raised in that article:

1. the rule of 6 is not followed consistently. Some practitioners use it; others don’t. Those who don't maybe confused by the infusion prepared by another managing team (usually the previous team). For example, if the A&E team follow the rule of six, and the ICU team does not, this may cause confusion; and therefore the next team may discard the previously prepared solutions. For that matter, I think it is vital that whoever prepare the infusion, should label properly x mg in 100 ml, y ml/Hr = y mcg/kg/min

2. Pediatric drug solutions that have been prepared using the rule of 6 can result in fluid overload when dose adjustments are necessary. For example, if a dopamine infusion rate were increased from 5 mcg/kg/minute to 10 mcg/kg/minute, a small infant would receive 10 ml/hour, or the daily fluid requirement with this solution alone. This is a perfectly valid point and I would be very cautious in applying the rule of six in such a case.

Nevertheless, most of these errors highlighted are human errors, not the errors with the rule of six itself. These has been highlighted in an article in Medscape that I linked in my previous post.

In essence, the rule of six is a mathematical principle just like Kinetic Energy = 1/2 mv sq. Being a mathematical principle means it is independent of the weight, the types of drugs, and the dosages. And when something is a mathematical formula, it means you can prove it from first principle. You just need to prove it once, convinced about it and can start using it.

Some have advocated to do direct calculation for each infusion. For example,

for IV Dopamine infusion

with an estimated weight = 70kg

and to run at 10mcg/kg/min

therefore, 200mg (or 200,000mcg) dopamine diluted in 50ml NS

50ml NS: 200,000mcg dopamine

1ml NS=200,000/50 = 4000mcg dopamine

(10mcg * 70 * 60)/4000

= 42,000/4000=10.5ml/hr

So we run the dopamine 10.5ml/hr

For a 70-kg man, 200 mg dopamine in 50 ml, if you want 10 mcg/kg/min, you need to give 10.5ml/hr.

If using rule of six, we need to give 210 mg in 50 ml if we want to run 10 ml/hr in order to achieve 10mcg/kg/min.

If we don't want to waste another ampoule of 200 mg just to obtain the extra 10mg, we will just use one ampoule.

So how much are we actually giving if we infuse 10 ml/hr in a 200 mg in 50 ml solution?

Let's calculate backwards:

200 mg in 50 ml

so 1 ml means 4 mg

10 ml means 40 mg

10 ml in 1 hour or 60 min, which means every one min, the dose is (40/60) mg.

1 mg = 1000 mcg

and the weight is 70 kg, so the actually dose given is actually (40/60*1/70*1000) mcg/kg/min, that is, 9.5 mcg/kg/min

9.5 mcg/kg/min vs 10 mcg/kg/min?? Is there a huge difference here?

So, rather than saying that we start 10 mcg/kg/min, we can start 9.5 mcg/kg/min and we titrate accordingly. There is no need to be rigid here.

Furthermore, how sure are you in the first place the weight is actually precisely 70 kg? Maybe the weight is only 60 kg.

In other words, the 10.5 ml/hr obtained from direct calculation is more accurate than 10 ml/hr from the rule of six (if and only if) the patient's weight is precisely 70 kg.

In the rule of six, we either give (6*BW) mg in 100 cc, that is, (6*70) = 420 mg in 100ml OR 210 mg in 50 ml, or we give an estimate of 200 mg in 50 ml. It is not practical to break another 200 mg ampoule just to extract that 10 mg.

But as mentioned, that is actually not a big problem especially in adults because of 2 reasons:

1. We can always adjust the sliding scale and titrate according to patient's requirement. If BP is still low, titrate up; if BP improved, taper down.
2. The weight 70 kg is often an estimated weight only unless you actually put the patient on weighing machine.

Similarly,

• for noradrenaline, we are assuming Wt ~ 65 or 130 kg, because noradrenalines come in 4-mg ampoule (if 65 kg, 4 mg in 50cc means 1 ml/hr = 0.02 mcg/kg/min, if 130 kg means, 4 mg in 50cc, 1 ml/hr = 0.01 mcg/kg/min)
• for dobutamine, we are assuming Wt ~ 80 kg because dobutamine comes in 250-mg ampoules.

But if you were to do direct calculation, then you will have to re-calculate every time you change:

• the dosage
• the weight of the patient
• the type of medications

How about now if we want to run 15 mcg/kg/min for the same 50 kg patient for dopamine? Or IV noradrenaline infusion for 80 kg on 1 mcg/kg/min?

Let's put it this way: if I have the time to calculate one by one, then by all means, I will do the direct calculation. I will do the direct calculation if I only one patient to manage. It is also more accurate if the weight is precisely known.

Furthermore, I know my mathematical skills cannot be trusted in times of emergency when the infusion is needed within minutes! I might calculate wrongly, I might get confused or I might miss the decimal points, in which case, I might give 10 times or 100 times more than needed (which I believe this is more dangerous than not giving the optimal dosing when applying rule of six).

Bottom line, whether you do direct calculation or the rule of six, you still need to be vigilant and cannot be careless. You should doubly check again to make sure you have done the right calculation.