Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

If your Versed (midazolam) isn’t working, maybe it’s Zofran (ondansetron)

 
If you were giving a lot more midazolam (Versed) by intramuscular injection to stop a seizure and the seizure just would not stop, or got worse, maybe you were giving ondansetron (Zofran).

If you were giving a lot more midazolam by injection to sedate a patient and the sedation just wasn’t having its usual effect, maybe you were giving ondansetron. While rare, there can be very serious side effects from too much ondansetron.
 

Dose-dependent serious cardiac arrhythmias may be observed with higher dosages of ondansetron in those patients with certain pre-existing cardiac conditions. Patients may also be at risk for serotonin syndrome. Serotonin syndrome is associated with increased serotonergic activity in the central nervous system. Most reports of serotonin syndrome have been associated with concomitant use of certain drugs, some commonly used during surgery, such as fentanyl. Some of the reported cases of serotonin syndrome were fatal.[1]

 

How do you recognize serotonin syndrome?
 

Serotonin syndrome (SS) is a group of symptoms that may occur following use of certain serotonergic medications or drugs. [1] The degree of symptoms can range from mild to severe.[2] Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea.[1][2] Body temperature can increase to greater than 41.1 °C (106.0 °F).[2] Complications may include seizures and extensive muscle breakdown.[2] [2]

 

2 mg of midazolam is much too low a dose to try to stop a seizure, unless it is the only packaging you have and you are giving 5 intramuscular injections at a time. The best response to prehospital treatment of seizures was by giving 10 mg of intramuscular midazolam to adults (over 40 kg) and 5 mg of intramuscular midazolam to children (under 40 kg).

Maybe you think that is too much midazolam. The highest quality and largest pre-hospital study does not support using lower doses.
 

Our data are consistent with the finding that endotracheal intubation is more commonly a sequela of continued seizures than it is an adverse effect of sedation from benzodiazepines.11 [3]

 

There are other uses for midazolam, so you should be aware of the possibility that what you think is midazolam is really ondansetron.

Are the syringes labeled incorrectly for the contents?
 

Fresenius Kabi USA is voluntarily recalling Lot 6400048 of Midazolam Injection, USP, 2 mg/2 mL packaged in a 2 mL prefilled single-use glass syringe to the hospital/user level. The product mislabeled as Midazolam Injection,
USP, 2 mg/2 mL contains syringes containing and labeled as Ondansetron Injection, USP, 4 mg/2 mL.
[1]

 

Based on that, the syringes should be correctly labeled as ondansetron, but they are in blister packs labeled as containing midazolam or they are in boxes of blister packs listed as containing midazolam or both or something else.

If you use this packaging of midazolam, check the lot number, the syringe, and any other labels to make sure that they all agree.

What if you need some ondansetron pre-filled syringes?

Send them back anyway. Maybe only some of the syringes are labeled correctly.

What do the syringes look like?
 


 

What does the ondansetron syringe look like? This one is with a blister pack.
 


 

There are other possibilities for mislabeling that could be much more harmful, so read the syringe before you push anything by any manufacturer.
 


 

That probably would not be as harmful as it seems, because it would be pushed slowly, so it might be metabolized as quickly as it is pushed. The ones below would still be expected to produce a much greater respiratory depression than even an extreme midazolam respiratory depression.
 


 

Footnotes:

[1] Fresenius Kabi Issues Voluntary Nationwide Recall of Midazolam Injection, USP, 2 mg/2 mL Due to Reports of Blister Packages Containing Syringes of Ondansetron Injection, USP, 4 mg/2 mL
For Immediate Release
November 3, 2017
Voluntary Recall
Recall announcement

[2] Serotonin syndrome
Wikipedia
Article

[3] Intramuscular versus intravenous therapy for prehospital status epilepticus.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators.
N Engl J Med. 2012 Feb 16;366(7):591-600.
PMID: 22335736 [PubMed – in process]

Free Full Text from N Engl J Med.

.

Drug Shortages Affecting EMS


 

The most recent FDA (Food and Drug Administration) listing of drug shortages, editing out the many cancer drugs, and other non-EMS drugs, includes the following:
 

Generic Name or Active Ingredient                                                 Status
 

Albuterol Sulfate Inhalation Solution (0.5%)         Resolved

This is important, but one way of dealing with a nebulized albuterol shortage is to alternate albuterol with nebulized saline. this prevents giving too much albuterol to the patient who is maintaining a reasonable oxygen saturation and keeping the airway humidified.
 

Atropine Sulfate Injection         Currently in Shortage

We should be accumulating atropine, since we no longer use atropine for asystole. Atropine maintains its strength, even when stored for extended periods, so we should only discard atropine when there is contamination.
 

Calcium Chloride Injection, USP         Currently in Shortage

Calcium (chloride or gluconate) appears to be the best drug for hyperkalemia. We are fortunate in EMS to not have to deal with sodium polystyrene (Kayexalate), which is just a means of creating the appearance of clostridium difficlie. Senna glycoside (ex-lax) can be just as effective at causing diarrhea and anything that causes diarrhea will cause some removal of potassium.
 

Calcium Gluconate Injection         Currently in Shortage

See above.
 

Cromolyn Sodium Inhalation Solution, USP         Currently in Shortage
 

Dexamethasone Sodium Phosphate Injection         Resolved
 

Dextrose 50% Injection         Currently in Shortage

We should be using 10% dextrose, rather than 50%, but we are slow to learn from our mistakes.

Comment on 10% Dextrose vs 50% Dextrose.
 

Epinephrine Injection, 0.1 mg/mL         Currently in Shortage

Maybe we will be using less epinephrine after the results of the Paramedic2 trial are published. I expect that some patients will be shown to benefit from epinephrine in cardiac arrest. I hope that the results will help us to identify which patients benefit from epinephrine in cardiac arrest and which patients have worse outcomes because of receiving epinephrine in cardiac arrest. I don’t really expect these answers, because we seem to be trying to avoid asking appropriate questions about drug treatment.
 

Epinephrine Injection, 1 mg/mL         Resolved
 

Fentanyl Citrate (Sublimaze) Injection         Currently in Shortage

There are other drugs that are effective for pain management. Hydromorphone (Dilaudid) can be used safely by EMS.
 

Labetalol Hydrochloride Injection         Currently in Shortage
 

Lidocaine Hydrochloride (Xylocaine) Injection         Currently in Shortage

EMS should have disposed of our supplies of lidocaine and amiodarone following the ALPS and PROCAMIO.

Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’

The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia
 

Lidocaine Hydrochloride (Xylocaine) Injection with Epinephrine         Currently in Shortage

This is more for wilderness EMS, than urban.
 

Methylprednisolone Sodium Succinate for Injection, USP         Currently in Shortage

This is an important drug for reactive airway conditions.
 

Nitrous Oxide, Gas         Currently in Shortage

A lot of people are uncomfortable with the idea of using nitrous oxide, but it is safe – as long as there is good circulation of fresh air.
 

Pantoprazole (Protonix) Powder for Injection         Currently in Shortage

This is usually not the part of allergic reaction that EMS treats, but it can be helpful.
 

Potassium Chloride Injection         Currently in Shortage

Not generally prehospital EMS, but interfacility.
 

Procainamide Hydrochloride Injection, USP         Currently in Shortage

This is an antiarrhythmic drug that actually works, but we tend to avoid it out of a lack of understanding and a lack of familiarity with the evidence.
 

Promethazine (Phenergan) Injection         Currently in Shortage
 

Ranitidine Injection, USP         Currently in Shortage
 

Rocuronium Bromide Injection         Currently in Shortage

Succinylcholine may end up as a shortage because of the rocuronium shortage.
 

Sodium Bicarbonate Injection, USP         Currently in Shortage

After calcium, sodium bicarbonate can be effective for hyperkalemia. Flush the line. Even better, use a different line for these incompatible medications.

We should not be wasting sodium bicarbonate in cardiac arrest patients, since it is not going to do anything to make things better, but it will make it more difficult to get sodium bicarbonate for the patients who can actually benefit.
 

Sodium Chloride 0.9% Injection Bags         Currently in Shortage

Do we really need to start as many IV (IntraVenous) lines with a drip?
 

Sodium Chloride 23.4% Injection         Currently in Shortage

Also effective for hyperkalemia, since it is the sodium that moves the potassium, not any myth of alkalinizing the patient.

.

FDA bans useless, possibly dangerous, antibacterial soap ingredients

antiseptic soaps safe - qm - WSJ and FDA logo
 

As of September 6, 2017, The FDA (Food and Drug Administration) will ban manufacturers from selling antiseptic soaps over the counter to consumers because the manufacturers could not provide evidence that they work and that they are safe. The list of ingredients is in the footnotes.[1],[2]

In 2013, the FDA gave manufacturers a deadline to provide information about the products they sell to consumers. After decades of use, the manufacturers finally needed to provide evidence that the ingredients in their products are GRAS/GRAE. What does GRAS/GRAE mean?

GRAS = Generally Recognized As Safe
GRAE = Generally Recognized As Effective
GRAS/GRAE = Generally Recognized As Safe and Effective

As a consumer, do we want to spend our money on something that is not safe, is not effective, or is both unsafe and is ineffective?

Does the absence of evidence prove that the ingredients are unsafe or that they are ineffective? No.

The failure to provide evidence shows one of the following –

A. The manufacturers cannot show that the ingredients are safe.
B. The manufacturers cannot show that the ingredients are effective.
C. The manufacturers cannot show that the ingredients are safe and effective.

Those three are the most obvious possibilities, but there are several more possibilities. For example –

D. The manufacturers don’t care enough to find out if the ingredients are safe or effective.

Is it a business decision that the amount of money to be made in this multi-billion dollar market is not worth the amount of money that would be lost, but would any money be lost? Is the failure to provide evidence essentially an admission that the antibacterial soaps are just a marketing gimmick? Have the manufacturers avoided providing evidence? No.

Is there an absence of information? No. There is plenty of evidence, but the evidence does not show benefit or safety.
 

Both sides in the debate have submitted reams of evidence to the FDA supporting their stance, offering up conflicting studies that make it a challenge for the average consumer to make informed decisions.[3]

 

The more conspiratorial would add some other possibilities –

E. The manufacturers can show that the ingredients are not safe.
F. The manufacturers can show that the ingredients are not effective.
G. The manufacturers can show that the ingredients are not safe and not effective.

These are not impossible, but should we assume that manufacturers are intentionally and maliciously marketing dangerous and useless products? Hanlon’s razor addresses this –

Never attribute to malice that which is adequately explained by stupidity.

Stupidity does not appear to be the right word for this situation. There is another version of Hanlon’s razor that seems to be written just for the those who think that a lack of evidence of harm is the same as safety and efficacy.

Don’t assume bad intentions over neglect and misunderstanding.
 

How different is this from medical treatments that have no evidence of efficacy or safety? We stopped using backboards to stabilize the spine, atropine for cardiac arrest, furosemide for CHF, . . . , and we may no longer be able to justify using amiodarone.

Footnotes:

[1] FDA issues final rule on safety and effectiveness of antibacterial soaps – Rule removes triclosan and triclocarban from over-the-counter antibacterial hand and body washes
FDA (Food and Drug Administration)
For Immediate Release
September 2, 2016
FDA News Release

[2] Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use
A Rule by the Food and Drug Administration on 09/06/2016
Final rule.

What ingredients are banned?

Thus, the following active ingredients are not GRAS/GRAE for use as a consumer antiseptic wash:
    *Cloflucarban
    *Fluorosalan
    *Hexachlorophene
    *Hexylresorcinol
    *Iodophors (Iodine-containing ingredients)
○ Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)
○ Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)
○ Nonylphenoxypoly (ethyleneoxy) ethanoliodine
○ Poloxamer—iodine complex
○ Povidone-iodine 5 to 10 percent
○ Undecoylium chloride iodine complex
    *Methylbenzethonium chloride
    *Phenol (greater than 1.5 percent)
    *Phenol (less than 1.5 percent)
    *Secondary amyltricresols
    *Sodium oxychlorosene
    *Tribromsalan
    *Triclocarban
    *Triclosan
    *Triple dye
Accordingly, OTC consumer antiseptic wash drug products containing these active ingredients are misbranded, and are new drugs for which approved new drug applications are required for marketing.

IV. Ingredients Not Generally Recognized as Safe and Effective

[3] Are Antibacterial Soaps Safe? Companies say there’s no cause for alarm, but studies suggest they may be dangerous. Now the FDA is preparing to rule.
Wall Street Journal
By Laura Landro
Updated Feb. 15, 2016 11:01 p.m. ET
Article

.

FDA takes steps to improve reliability of automated external defibrillators


 

Why improve the reliability of AEDs (Automated External Defibrillators)?

AEDs are important, much more important than the epinephrine I wrote about yesterday, because AEDs actually work – at least when the AEDs work as they are supposed to.

AEDs fail much more often than they should.
 

From January 2005 through September 2014, the FDA received approximately 72,000 medical device reports associated with the failure of these devices. Since 2005, manufacturers have conducted 111 recalls, affecting more than two million AEDs. The problems associated with many of these recalls and reports included design and manufacturing issues, such as inadequate control of components purchased from other suppliers.[1]

 

72,000 reports over ten years. In the US, there are about 300,00 cardiac arrests a year where treatment is considered and an AED might be applied. Out of those, how many times is an AED applied? 1/3?

If I use that ballpark number guess, then 72,000 out of 1,000,000 is 0.72%. The reporting of problems that are identified during equipment checks and maintenance should also decrease the rate of failure in the treatment of real patients. Maybe I decrease that guess at a failure rate during cardiac arrest treatment/assessment to 0.5% or 0.1%?

A decrease to 0.1% is one out of every 1,000 uses. Is that a tolerable level of failure for a device that has only two tasks, but has to remain ready to perform those tasks at all times? The two tasks are to differentiate between ventricular fibrillation/ventricular tachycardia and any other cardiac rhythm and to deliver a shock to the patient after ventricular fibrillation or ventricular tachycardia has been identified.
 


Image credit.
 

There are only a few moving parts and the designs may vary from what I describe. The wire that is manually attached to the defibrillator pads. The lids that is opened, turns on the AED, and triggers the voice prompts. The buttons that are pressed to turn on the AEDs not turned on by opening the lid, to analyze the rhythm, and to deliver the shock.

Would Do we accept a similar failure rate from an ambulance, which has many more moving parts?

Do we accept similar failure rates from our personal vehicles, which have many more moving parts?

Do we accept similar failure rates from aircraft, which has many more moving parts?

Yes and no.

We deal with the failures in these vehicles by building in redundancies and paying attention to maintenance, but the result is that the failures rarely cause death, or the lack of resuscitation that could have occurred with a properly functioning AED.
 

For example, NASA management claimed that they had an isty-bitsy teeny-weeny failure rate. They were shown to be wrong in a very dramatic, and deadly, fashion. Twice.
 

If a reasonable launch schedule is to be maintained, engineering often cannot be done fast enough to keep up with the expectations of originally conservative certification criteria designed to guarantee a very safe vehicle. In these situations, subtly, and often with apparently logical arguments, the criteria are altered so that flights may still be certified in time. They therefore fly in a relatively unsafe condition, with a chance of failure of the order of a percent (it is difficult to be more accurate).

Official management, on the other hand, claims to believe the probability of failure is a thousand times less. One reason for this may be an attempt to assure the government of NASA perfection and success in order to ensure the supply of funds. The other may be that they sincerely believed it to be true, demonstrating an almost incredible lack of communication between themselves and their working engineers.

. . . .

For a successful technology, reality must take precedence over public relations, for nature cannot be fooled.[2]

 

We need to understand what the actual failure rates are. We also need to work on the failure rate that comes from operator error.

The reason people are able to lie to us with statistics (statistics do not lie, but statistics can be used by liars) is that we choose to remain ignorant of the appropriate use of statistics. We ask to be lied to.
 

What is an acceptable failure rate? It isn’t zero, because a zero failure rate is a lie.

Footnotes:

[1] FDA takes steps to improve reliability of automated external defibrillators
January 28, 2015
Food and Drug Administration
FDA News Release

[2] Volume 2: Appendix F – Personal Observations on Reliability of Shuttle
Report of the Presidential Commission on the Space Shuttle Challenger Accident (Also known as The Rogers Commission Report)
by R. P. Feynman
Conclusions
NASA report

.

The FDA Gives Us Recalls and Label Changes for EMS Week


Image credit.
 

The FDA (Food and Drug Administration) has been busy with recalls and label changes this past week for EMS week.
 

Labetalol Hydrochloride Injection, USP, 100 mg/20 mL (5 mg/mL) 20 mL Multidose Vial, NDC 0409-2267-20, Lot 36-225-DD, Expiration 12/01/2015.[1]

 

This is worse than the usual particulate matter. Since this is often used to lower the blood pressure of patients with bad things happening in the brain or the heart, a bit of particulate matter could be the coup de grâce.
 

The embedded particulate was identified as stainless steel and the floating particulate as iron oxide. To date, Hospira has not received reports of any adverse events associated with this issue for this lot. Hospira has attributed the embedded particulate to a supplier’s glass defect.[1]

 
 


Image at DailyMed.
 

Dobutamine is another medication with a recall that is given to some of our less stable patients.
 

In general, injected particulate matter may result acutely in local inflammation, phlebitis, and/or low level allergic response through mechanical disruption of tissue or immune response to the particulate. Small capillaries may become obstructed.[2]

 

Dobutamine is supposed to improve circulation through small capillaries. 😳
 
 


 

Suppose you would like to ventilate a patient with a BVM (Bag Valve Mask) resuscitator (with the mask or connected to an endotracheal tube, a tracheostomy tube, and LMA, a King airway, . . . ). Some of them might not work properly.
 

voluntary medical device removal of a limited number of Ventlab™ Resuscitator Bags after becoming aware of complaints regarding a sticking duckbill valve that resulted in the resuscitation bags delivering no air through the patient valve, to the patient. The valves may stick due to incomplete curing during the manufacturing process. Resuscitation bags affected may not function properly and may result in a delay of treatment and life threatening health consequences that include hypoxia and hypoventilation.[3]

 

A sticking duckbill valve?

At 25 seconds of this video, there is a good view of the duckbill valve from the patient end.
 

[youtube]z0pX-gHfe6Y[/youtube]
 

There has been one report of injury requiring medical intervention due to the lack of a functional resuscitation bag and 31 reports of a delay in oxygenation due to the requirement to utilize a 2nd or 3rd device. The FDA has been notified of this voluntary action by Ventlab, LLC.[3]

 

If you are using injectable risperidone (Risperdal), watch out for anaphylaxis. It is rare, but it can make a bad situation worse and you probably were not injecting risperidone because the patient is being helpful.
 

6.8 Postmarketing Experience [for Risperdal Consta ]

  • added: Very rarely, cases of anaphylactic reaction after injection with RISPERDAL CONSTA have been reported during postmarketing experience in patients who have previously tolerated oral risperidone.[4]
  •  
     

    One of the new anticoagulants does not appear to increase the rate of stroke or heart attack (compared to warfarin [Coumadin]). Yay!

    But it does appear to increase the rate of GI bleed (GastroIntestinal bleed) (compared to warfarin [Coumadin]). Remember to pay attention to any signs of changes in bowel habits of signs of anemia in patients taking the newer anticoagulants.
     

    The new study included information from more than 134,000 Medicare patients, 65 years or older, and found that among new users of blood-thinning drugs, Pradaxa was associated with a lower risk of clot-related strokes, bleeding in the brain, and death, than warfarin. The study also found an increased risk of major gastrointestinal bleeding with use of Pradaxa as compared to warfarin. The MI risk was similar for the two drugs.[5]

     
     

    NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) no longer has the following precaution –
     

    PRECAUTIONS
    Drug Interactions

    deleted: “Patients receiving antihypertensive…..concomitantly”
    [6]

     

    That was the good news.

    NTG is still discouraged if a patient is taking a PDE-5 (PhosphoDiEsterase-5) inhibitor.
     

    Footnotes:

    [1] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Labetalol Hydrochloride Injection, USP, 100 MG/20 ML (5MG/ML), 20 ML, Multidose Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [2] Hospira Announces Voluntary Nationwide Recall Of One Lot Of Dobutamine Injection, USP, 250 MG, 20 ML, Single-Dose Fliptop Vial, Due To Visible Particulates
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [3] Ventlab, LLC. Issues a Nationwide Recall of Ventlab Resuscitator Bags Due to Possible Health Risk
    May 16, 2014
    Recalls, Market Withdrawals, & Safety Alerts
    FDA
    Recall

    [4] Risperdal (risperidone) tablets, oral solution, Risperdal M-Tab (risperidone) orally disintegrating tablets, and Risperdal Consta (risperidone) long-acting injection.
    Page Last Updated: 05/16/2014
    Safety information
    FDA
    Label change

    [5] Pradaxa (dabigatran): Drug Safety Communication – Lower Risk for Stroke and Death, but Higher Risk for GI Bleeding Compared to Warfarin
    [Posted 05/13/2014]
    Safety information
    FDA
    Label change

    [6] Nitrostat (nitroglycerin, USP) Sublingual Tablets
    Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

    Page Last Updated: 05/16/2014
    Safety information
    FDA
    Label change

    .

    Homeopathic Product Recalled for Containing Real Medicine


     

    Homeopathic products are supposed to be diluted down to where they contain nothing.

    They definitely are not supposed to contain antibiotics, since antibiotics were not understood when Samuel Hahnemann made up the idea of homeopathy.
     

    FDA has determined that these products have the potential to contain penicillin or derivatives of penicillin, which may be produced during the fermentation process. In patients who are allergic to beta-lactam antibiotics, even at low levels, exposure to penicillin can result in a range of allergic reactions from mild rashes to severe and life-threatening anaphylactic reactions.[1]

     

    The law of similars. Find a poison that produces similar symptoms, preferably not the cause of the illness (not that a homeopath would know) and dilute the poison down to nothing.

    The water (or alcohol) is expected to remember the poison, but forget everything else that has been in the water, and magically cure the illness by doing the opposite of what the poison would do.

    The water is diluted to 1% of what was in it enough times that there should not be any poison left. The homeopath also hits the water a lot to teach the water to remember the poison. This is the magic memory of water.

    The result is nothing.
     


    Image credit.
     

    When blood-letting was a common treatment, this was better than going to a doctor, but still not as good as staying at home and saving your money, because who needs to go buy nothing?

    The idea that the more dilute the solution, the more potent the “medicine” is ridiculous. Somebody would be able to demonstrate the differences in strengths, but homeopathy is just another placebo with just another excuse to scam people.

    At what concentration of nothing does it start to work?

    At what concentration of nothing does it become dangerous?

    Is it still a solution when there is nothing in it?

     

    Hover text –

    Dear editors of Homeopathy Monthly: I have two small corrections for your July issue. One, it’s spelled “echinacea”, and two, homeopathic medicines are no better than placebos and your entire magazine is a sham.[2]

     

    One of the problems with dealing with a fraud is the inability to tell the difference between incompetence and intentional fraud.

    Homeopath X is a true believer. He believes that homeopathy works, but is too incompetent to keep real medicine out of his nothing.

    Homeopath XX is willing to sell anything that pays. He knows that homeopathy is nonsense, but wants to add real medicine to make it seem that the water is having some sort of effect beyond a placebo effect. He adds real medicine after the dilution for that effect. This is not rare.

    Homeopaths claim that their medicines are safe and that real medicines are dangerous, so why add medicine?

    Since homeopathy is all lies, should we believe anything a homeopath says?

    If you dilute a lie enough times, does it become truth?

    We have enough problems with believing in magic with real medicines without adding the problems of homeopathy, where there is nothing real except fraud.

    Footnotes:

    [1] Pleo Homeopathic Drug Products by Terra-Medica: Recall – Potential for Undeclared Penicillin – Includes Pleo-FORT, Pleo-QUENT, Pleo-NOT, Pleo-STOLO, Pleo-NOTA-QUENT, and Pleo-EX
    Posted 03/20/2014
    FDA
    Safety Alert

    [2] dilution
    xkcd
    Comic

    .

    Etomidate Recall

     

    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]

     


    Image credits.
     


     

    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.

    .

    A Recalled AED is Better Than No AED


     
    Cardiac arrest. CPR in progress. Do not use the AED, because it has been recalled!

    Wrong.
     


     

    HeartStart automated external defibrillators from Philips Healthcare have been recalled.

    What does the FDA (Food and Drug Administration) mean by recall?

    Well, why was the recall issued?
     

    Certain HeartStart automated external defibrillator (AED) devices made by Philips Medical Systems, a division of Philips Healthcare, may be unable to deliver needed defibrillator shock in a cardiac emergency situation, the U.S. Food and Drug Administration said today in a new safety communication for users of these previously recalled devices.[1]

     

    A shock might not be delivered.

    What does the FDA recommend?
     

    “The FDA advises keeping all recalled HeartStart AEDs in service until you obtain a replacement from Philips Healthcare or another AED manufacturer, even if the device indicates it has detected an error during a self-test,” said Steve Silverman, director of the Office of Compliance in the FDA’s Center for Devices and Radiological Health.[1]

     

    Do not take these AEDs out of service service until a replacement is present.

    Why?

    What about the lawyers?

    But it’s defective!

    Thinking is dangerous!
     

    “Despite current manufacturing and performance problems, the FDA considers the benefits of attempting to use an AED in a cardiac arrest emergency greater than the risk of not attempting to use the defibrillator.”[1]

     

    The benefit is greater than the risk.

    There is risk with everything.

    Anyone who tells you otherwise is selling something.

    There is not benefit with everything.

    Since the detection of an error during the self-test does not guarantee that the AED will not deliver a shock when needed, removing the AED without a replacement is more dangerous than leaving the AED in service.

    These recalled AEDs are better than no AED.
     

    Of course, if needed for use in an emergency, make every attempt to clear the error and use the device normally, as described in the Owner’s Manual.[2]

     

    The manufacturer and the FDA agree that, in the case of these AEDs, something is better than nothing.

    Are we really going to make a dead patient more dead by using a defective AED?

    Footnotes:

    [1] FDA issues safety communication on HeartStart automated external defibrillators from Philips Healthcare
    FDA News Release
    For Immediate Release: Dec. 3, 2013
    Media Inquiries: Jennifer Rodriguez, 301-796-8232, jennifer.rodriguez@fda.hhs.gov
    Consumer Inquiries: 888-INFO-FDA
    News Release

    [2] Philips HeartStart FRx and OnSite (HS1) automated external defibrillators (AEDs)
    Phillips Healthcare
    Maintenance Advisory

    .