Nauseating Evidence Part 2/3 (Metoclopramide)


"Metoclopa...propa....ah &%%^...Reglan!"

I do not routinely see programs carrying metoclopramide for pre-hospital management of nausea/vomiting. My friction in grabbing this drug for routine treatment of nausea and vomting is probably contributed to:

1.It is not in my primary med bag.

2.Unfamiliarity.

3.Dystonic reactions look like something from the exorcist...(irrational fear)

Metoclopromide

Metoclopramide is a dopamine2 (D2) receptor antagonist with some partial serotonin receptor (5-HT3) effects. In part one of this series we discussed the chemoreceptor trigger zone. The CTZ sat just outside the blood brain barrier and was sensitive to passing chemicals such as cytotoxins, opioids, and serotonin released from the enterochromaffin cells of gastric pits within the stomach.

There are some interesting characteristics of metoclopramide.

1. Only FDA approved medication to treat gastric-paresis.

2. Relaxes pyloric sphincter while increasing lower esophageal sphincter tone (LEST).

3. Increased gastrointestinal motility (so like don't give them aspirin for chest pain, and then metoclopramide for nausea).

What's the ideal dose?

I typically see patients get a single 10 mg dose at my program (because thats all we carry;). It was interesting to see in this RCT of ondansetron, metoclopramide, and placebo, that they were receiving 20 mg in the metoclopramide arm. So I did a little digging to figure out what the ideal dose is. I was unable to find a study comparing various dosing regimens (let me know if you find one). I did find though recommendations by the FDA to deliver no more than 20mg in a single dose or 60mg within a 24 hour period. There does not appear to be any change in symptom relief or peak concentration time between 10 and 20mg. There was however prolonged duration of effects such as increased lower esophageal pressure (LESP) (5mg = 45 minutes vs 20mg = 2-3 hours). For my 20 minute helicopter ride.. 10 mg seems like the goldilocks number.

How common is Tardive Dyskinesia?

Statistically it has been said to have a prevalence of somewhere in between 1-10% . However a review article (A.O.RAO, et al, 2009) found these cases of metoclopramide induced tardive dyskinesia (TD) to be less than 1%. It is well documented that these cases are from prolonged use, or administration with additional medications with TD warnings.

So I feel pretty good that my dose of 10 mg isn't going to turn them into Gene Simmons over the course of the transport.

What about dat Q-T Doh?!

There was an interesting study of 10 healthy adult male volunteers who were entered into a double blind, placebo-controlled, cross over study. They were being evaluated for Q-T Dynamicity (combination of heart rate (R-R) & and depolarization (Q-T) between placebo and 10mg of metoclopramide. Yah... super low N and blah blah blah... I still find this %&*# interesting.

There was an increase in the QT/RR slope with the metoclopramide arm. You can see that the placebo group maintained a linear relationship in juxtapose with before and after. When you look at the metoclopramide arm, there is an interesting finding. The Q-T interval was actually longer before the drug was administered. However higher peak levels were seen in relationship to heart rate with the drug. These were healthy volunteers and thus no arrhythmias or intolerance to the effects were noted. It does however tingle my spidey-senses that this could potentially be a problem in someone who already is at risk for arrhythmias, or receiving multiple doses.

So when should I pull this bad boy out?

My friend Salim Rezaie from Rebel EM sent me a study after reading the first blog a week ago on ondansetron. This paper was a fantastic review on palliative care in the emergency department, but the reason he sent it to me was a chart that listed different causes of nausea, and the ideal agent to treat it. Super cool! (Sal's da man)

Because of metoclopramide's prokinetic properties, it is recommended for patients with GI distention or gastric reflux. just like ondansetron, it has no effect on motion sickness. So reach for the diphenhydramine for your next in-flight nauseated patient. It is worth mentioning that you should avoid giving metoclopramide to patients with GI bleed. For some reason kicking their stomach into warp speed with a bleeding ulcer is a bad idea.

Can't I just make them sniff an alcohol prep?

References are hyperlinked within the blog