Etomidate, sold as generic etomidate (not the brand name Amidate, although at least one site is erroneously reporting that Amidate is being recalled), is being recalled by the manufacturer.
All of the products bear a Pfizer label.[1]
Above are the images from the FDA (Food and Drug Administration) label for the lot numbers affected. Unless the package design has changed, this is what the packages should look like.
due to the potential for small black particles, identified as paper shipper labels, to be present in individual vials; the potential for missing lot number and/or expiry date on the outer carton, and the potential for illegible/missing lot number and expiry on individual vials.[1]
No adverse events have been reported, yet, according to the manufacturer, but injecting a medication that is suspected of having contaminants very bad patient care.
For example –
Intravenous administration of particles may lead to impairment of microcirculation, phlebitis, infection, embolism and subsequent infarction.[1]
Here are the lot numbers to look for. If the lot number is not legible, then it is included in the recall. If the expiration date is not legible, then it is included in the recall.
Remember that giving etomidate does not relieve pain, it only sedates, so we need to give something for pain if we are doing something that causes pain. Intubation is the most common example.
the immediate recovery period will usually be shortened in adult patients by the intravenous administration of approximately 0.1 mg of intravenous fentanyl, one or two minutes before induction of anesthesia, probably because less etomidate is generally required under these circumstances (consult the package insert for fentanyl before using).[2]
Etomidate is a hypnotic drug without analgesic activity.[1]
The dose is 0.3 mg/kg, so there is no maximum dose because of weight. If there is a maximum dose permitted by protocol, consider using a medication that does not have an inappropriate limit.
The patients most likely to present problems with intubation are the heaviest patients. These are the patients most likely to be inappropriately prevented from getting an effective dose by a bad protocol.
If the maximum dose is 30 mg, then no patient over 100 kg (220 pounds) will receive an appropriate dose if you follow the protocol limit. That is not a very big patient. How difficult should we make airway management in order to appease medical directors? We used to be giving 2 mg of morphine with extreme caution because of the same inappropriate fantasy of caution.
OVERDOSAGE
Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by a fall in blood pressure. No adverse cardiovascular or respiratory effects attributable to etomidate overdose have been reported.[2]
Not from too large a dose?
Not from an appropriate dose that is more than 30 mg, or more than 40 mg, or more than 50 mg, or more than 60 mg, or . . . ?
The LD50 of etomidate administered intravenously to rats is 20.4 mg/kg.[2]
The LD50 is the dose expected to kill about half of those receiving the dose. A little bit larger dose would probably kill more than half, while a little bit smaller dose would probably kill less than half.
This is the dose that gives the patient about a 50/50 chance of survival/death. A Schrödinger dose.
Not 20.4 mg.
20.4 mg/kg, so there is a lot of flexibility in dosing, even in humans.
The dose for induction of anesthesia in adult patients and in children above the age of ten (10) years will vary between 0.2 and 0.6 mg/kg of body weight, and it must be individualized in each case. The usual dose for induction in these patients is 0.3 mg/kg, injected over a period of 30 to 60 seconds.[2]
Anywhere from 20 mg to 60 mg for a 100 kg patients would be an appropriate dose, according to the FDA, but the usual dose would be 30 mg.
Anywhere from 40 mg to 120 mg for a 200 kg patients would be an appropriate dose, according to the FDA, but the usual dose would be 60 mg.
One way to limit the dose of etomidate and decrease the amount of time etomidate is affect the patient is to give fentantl before the etomidate, according to the FDA.
Make sure that intubation is followed by continuous sedation and pain management.[3]
We need to better understand pharmacology for our patients’ sake.
–
Footnotes:
–
[1] Agila Specialties Private Limited Initiates Voluntary Nationwide Recall of 10 Lots of Etomidate Injection 2 mg/mL – 10 mL and 20 mL due to the Presence of Particulate Matter and/or Illegible and Missing Lot Number and/or Expiry Date
FDA
February 19, 2014
Page Last Updated: 02/19/2014
Recall — Firm Press Release
–
[2] ETOMIDATE injection
[Pfizer Laboratories Div Pfizer Inc.]
DailyMed
FDA label
–
[3] Pain and Terror as Effective Pressors
EMCrit
Dr. Scott Weingart
May 16, 2011
Podcast page.
.
The 30 or 40mg max dose seen in many protocols exists because etomidate can cause hemodynamic depression in large doses.
The lower end of the dose range for etomidate is 150 or 200 mcg/kg according to most references; Sota Omoigui’s lists 100 mcg/kg as an acceptable dose. 200 mcg/kg is a commonly used dose for elective ECT’s, and is the same per-kg dose that a 150kg patient would have gotten had he received a bolus dose of 30mg of etomidate. And that doesn’t even take into account the fact that larger patients actually require a smaller per-kg bolus dose of the highly lipid-soluble drugs, since they have a smaller volume of distribution per kg. Some have proposed basing bolus doses on lean body weight or even having separate (lower per kg) dose ranges for heavier patients for this reason.
I do not support arbitrary upper limits for weight-based doses either, but I’m not sure you can call a limit that is in place in order to prevent hemodynamic compromise “arbitrary”, and it is unlikely that many are being underdosed with etomidate.