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As with the death of Michael Jackson, this is not a call you want to be on, because everybody is going to be second-guessing everything that was done, but let’s assume that you are dispatched.

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Law enforcement sources tell TMZ … multiple medicine bottles were found in the Beverly Hills hotel room where Whitney Houston died … but we’re told there were NOT a lot of pills at the scene.^[1]

there were NOT a lot of pills at the scene.

This suggests that a lot of pills were taken, but does not tell us over what time period?

How many pills should have been in the containers if the pills were taken as prescribed?

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Among the pills … ibuprofen (painkiller), Xanax (anti-depressant), Midol (for menstrual cramps), amoxicillin (for treating bacterial infections) … and more.^[1]

Ibuprofen and Midol are sometimes the same thing, but Midol comes in so many different formulations, that you cannot tell without knowing the specific version.^[2] I did not know there were so many different drugs sold under essentially the same name. Besides, I use chocolate to keep my inner woman from PMSing.

The ones that catch my eye are – . . . Xanax … and more.

What is Xanax?

Xanax is the brand name for alprazolam, a benzodiazepine. Other benzodiazepines are drugs we commonly carry – diazepam (Valium), midazolam (Versed), and lorazepam (Ativan). Treatment of benzodiazepine overdose is supportive care (maintain oxygenation and ventilation, and maintain blood pressure). There is a competitive antagonist, flumazenil (Romazicon), but flumazenil does not bring benzodiazepine overdoses back from the dead any more than naloxone (Narcan) brings heroin overdoses back from the dead. The treatment for opioid overdose is also supportive care.

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Absorption
Following oral administration, alprazolam is readily absorbed. Peak concentrations in the plasma occur in 1 to 2 hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay methodology, the mean plasma elimination half-life of alprazolam has been found to be about 11.2 hours (range: 6.3–26.9 hours) in healthy adults.^[3]

11+ hours can be a long time. Xanax XR (eXtended Release) does not appear to prolong the clearance of alprazolam, only the onset. What can affect the rate of elimination of alprazolam?

Metabolism/Elimination
Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4 (CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and α-hydroxyalprazolam.^[3]

A lot of the technical drug information is not important, but the cytochrome P450 metabolism is important in the elimination of a lot of medications

CYP3A4 is a member of the cytochrome P450 superfamily of enzymes. . . . This enzyme is involved in the metabolism of approximately half the drugs that are used today, including acetaminophen, codeine, ciclosporin, diazepam, and erythromycin. . . . Most drugs undergo deactivation by CYP3A4, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYP3A4 to form their active compounds, and many protoxins being toxicated into their toxic forms^[4]

Grapefruit juice can slow down metabolism by about half, so some consumer sites may recommend that people drink grapefruit juice to cut down on the cost of medications. This really is not a great idea, since it may affect other medications. It is something to discuss with a doctor, so that your doctor is aware of things that may interact with the medications you are taking, but doctors should do that anyway.

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One interesting item that does not appear to be related to CYP3A4 metabolism. It makes me wonder about the effect flumazenil might have on smokers. There is no mention of smoking or cigarettes on the flumazenil label.^[5]

Cigarette Smoking
Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers.^[4]

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We’re told some of the pills were old … some issued in 2011 … but some of the bottles were from 2012.^[1]

As long as a month and a half ago? Some people have milk and eggs that are that old, too. The medications should age much better than dairy products.

A prescription for alprazolam is often written as PRN (Pro Re Nata – Latin for according to the circumstances, or to be taken as needed). Alprazolam is an anti-anxiety drug that has addiction potential, just as with other GABA (GammaAminoButyric Acid) agonists (such as benzodiazepines and alcohol).

A PRN prescription that is more than a month old is not a problem. A prescription that is empty too soon is much more likely to be a problem. One problem with PRN prescriptions is that we usually do not know how quickly the patient has been taking them, so we do not know how many should be in the pill bottle. Some people do not want others to know that they are taking medication to manage anxiety (Tony Soprano), so their family may not even know they have a prescription for these medications.

In other words, with PRN medications, it is difficult to determine if too much has been taken

The acute oral LD50 in rats is 331–2171 mg/kg. Other experiments in animals have indicated that cardiopulmonary collapse can occur following massive intravenous doses of alprazolam (over 195 mg/kg; 975 times the maximum recommended daily human dose of 10 mg/day).^[3]

Prescriptions often come in a pill bottle that contains 100 pills of 0.5 mg, 1 mg, or 2 mg strengths. It is unlikely that a dose of even 200 mg would be enough by itself to kill a person.

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General Treatment of Overdose
Overdosage reports with XANAX Tablets are limited. As in all cases of drug overdosage, respiration, pulse rate, and blood pressure should be monitored. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors. Dialysis is of limited value. As with the management of intentional overdosing with any drug, it should be borne in mind that multiple agents may have been ingested.^[3]

With any potential overdose, always assume that other drugs/poisons have been taken.

We should use the Plus One Rule –

We should assume that there is at least one drug that we do not know about that the patient has taken. If we find out about more medication, wed still should assume that there is something that the patient has taken that we do not know about. The same rule applies to weapons. We should always assume that a violent/potentially violent patient has at least one weapon that we do not know about. Especially after they have been searched by police or prison personnel.

We should not expect antidotes to work the same way in dead patients as they do in living patients.^[6]

General supportive measures should be employed, along with immediate gastric lavage.

Lavage (pumping the stomach) is not something EMS should be doing. Inducing vomiting is a bad idea in a patient who may not be able to protect her airway – even with an endotracheal tube in place.

Intravenous fluids should be administered and an adequate airway maintained. If hypotension occurs, it may be combated by the use of vasopressors.

Always use fluids for hypotension before pressors, unless fluids are contraindicated, or unless a pressor is specifically indicated, even with acute CHF (Congestive Heart Failure).

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Did drugs kill Whitney Houston?

I don’t know, but the drugs listed in this article probably did not kill her.

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Footnotes:

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^[1] Whitney Houston – Few Pills Recovered at Death Scene
TMZ
2/13/2012 7:45 AM PST by TMZ Staff
Article

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^[2] Midol
Wikipedia
Article

As with cough and cold medicine, it is important to read the label to know what you are getting

The “Midol Complete” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Caffeine 60 mg (Stimulant)
Pyrilamine Maleate 15 mg (Antihistamine)

The “Extended Relief” formulation consists of:

Naproxen Sodium 220 mg (NSAID, Pain Reliever/Fever Reducer)

The “Teen” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Pamabrom 25 mg (Diuretic)

The “Liquid Gels” formulation consists of:

Ibuprofen 200 mg (Pain Reliever)

The “PM” formulation consists of:

Acetaminophen 500 mg (Pain Reliever)
Diphenhydramine citrate 38 mg (Sedative antihistamine)

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^[3] XANAX (alprazolam) tablet
[Pharmacia and Upjohn Company]
DailyMed
NLM
FDA label

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^[4] CYP3A4
Wikipedia
Article

Large list of drugs that affect CYO3A4 metabolism.

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^[5] FLUMAZENIL injection, solution
[Baxter Healthcare Corporation]
DailyMed
NLM
FDA label

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^[6] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Rogue Medic
Tue, 01 Nov 2011
Article

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Continuing from Part I.

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A hospital, or ambulance company, should not allow doctors, nurses, or paramedics to give substitute medications without educating them about the medication. Different concentrations. Different dosages. Different side effects. Different drug interactions. Different indications. Different routes of administration. Et cetera. Even for nearly identical drugs.

Likewise, a doctor, nurse, or paramedic should not give any medication without being familiar with the drug – concentrations, dosages, side effects, drug interactions, indications, et cetera.

Gosh, I’ve never given this before. Let’s play with it. It’s not like anything bad could happen.

Do doctors do this?

Do nurses do this?

Do paramedics do this?

Is this the kind of behavior that any hospital wants/accepts from its employees?

Is this the kind of behavior that any ambulance company wants/accepts from its employees?

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“In our mind, that’s just the tip of the iceberg,” Vaida says of the 15 deaths. “No one may be attributing a death because they really aren’t aware that a drug actually caused the death. If someone is notaware of the potency of one medication and gives too much so that the patient goes into respiratory arrest and dies, they may attribute it to the fact that the patient came into the hospital with respiratory problems.”^[1]

Ex-Dr. Conrad Murray is going to prison for similar behavior.

How can any administrator claim that Conrad Murray behavior is to be expected from their employees, but not end up being investigated.

If I give a medication and the patient stops breathing, I should still be able to ventilate and oxygenate the patient. The same is true for any first responder, or basic EMT.

If the problem is respiratory depression

and the result is death,

is the problem the drugs,

the people giving the drugs,

or the oversight of the people giving the drugs?

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Why hire people who can tell the difference between one and 100?

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How is a death, under these circumstances, any different from the death of Michael Jackson under similar circumstances?

What are the circumstances of these deaths?

So far, 15 deaths attributed to the drug shortage have occurred nationwide, an Associated Press study found.^[1]

One code-blue patient in an undisclosed city died because the preloaded emergency syringe epinephrine wasn’t available.^[2]

In cardiac arrest, epinephrine, does NOT save lives.

Epinephrine does help to just get a pulse back, but that is not saving a life. If just getting a pulse back were saving a life, then we would not have large awards to the families of patients who went in to the hospital without impairment, but came out with just a pulse. That would be considered a good outcome.

If the doctors, nurses, and medics do not know what medications they are using, they should not proceed until they do know what they are doing.

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Footnotes:

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^[1] Shortage of Lifesaving Drugs Reaches Epic Proportions
Beverly Ford Source: Telegram & Gazette (Worchester, MA)
December 21, 2011
EMS World
Article

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^[2] Oklahoma EMS Face Drug Shortage
by Sonya Colberg
The Oklahoman
Monday, October 4, 2010
Article at JEMS.com

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Continuing from Shortage of Lifesaving Drugs Reaches Epic Proportions.

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It’s how to provide the best patientcare while at the same time preventing medical mix-ups when administering drug substitutes, many of which have different potencies than their more commonly used counterparts. Fentanyl, for example, which isused as a substitute for morphine, is 10 times stronger than the opiate. A wrong dose, hospital officials worry, could cause death.^[1]

Fentanyl is 100 times as potent per mg (not 10 times), but the packaging is generally single dose packaging. A syringe of fentanyl with 100 mcg is roughly the same strength as a syringe of morphine that contains 10 mg. I would need to get 99 more syringes of fentanyl to give the same dose in milligrams.

In what hospital is this not going to require a trip to the pharmacy? What ambulance company carries 10 mg fentanyl (10,000 mcg fentanyl) on any ambulance?

This 10 mg of morphine -

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Image credit.

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Is not the same as this 10 mg of fentanyl –

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Image credit. Click on images to make them larger.

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Hold on. That isn’t 10 mg fentanyl. We need more –

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We still need more –

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We aren’t there yet –

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Just a teensy-weensy bit more –

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There is more than a subtle difference between the one syringe and the 100 syringes. If you missed it, go back and look again. Can you tell the difference between 100 syringes and 1 syringe? Are you sure?

Have carpal tunnel symptoms developed from repeatedly pushing the plunger on these syringes? Is each syringe being followed by a flush? If 2 ml fentanyl is followed by a 10 ml flush, that is 1,200 ml for what should have been 1 ml of morphine. The syringes are the same size, although the fentanyl syringes contain 2 ml each and the morphine syringes contain 1 ml each.

There may be other concentrations available, but 50 mcg/ml is the most common concentration of fentanyl. The variation in concentrations is much more common with morphine. The 10 mg/ml concentration is what I carry, which is 10 mg in one 1 ml syringe (as pictured). Everyone should check the concentration at least once before giving any medication.

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To be continued in Part II.
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Footnotes:

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^[1] Shortage of Lifesaving Drugs Reaches Epic Proportions
Beverly Ford Source: Telegram & Gazette (Worchester, MA)
December 21, 2011
EMS World
Article

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I did not come up with the title – Shortage of Lifesaving Drugs Reaches Epic Proportions – that was the title of the article I am criticizing, but not for any lack of hyperbole.

“It’s a perfect storm of conditions with a rapidly consolidating marketplace, a health care system that is trying to control costs, an issue with raw materials and a marketplace that doesn’t have a good redundancy system in place to handle things when a plant shuts down,” says Allen Vaida, executive vice president of the Institute for Safe Medication Practices. “No question about it. It’s a national crisis.”^[1]

In EMS, we are worried about a shortage of drugs, when we should see this as an opportunity to improve patient care.

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Among the drugs Fox found that were in short supply during 2011 were injectable versions of calcium gluconate, used by first responders to regulate heart rhythm in patients suffering cardiac arrest; succinylcholine, a muscle relaxer used to intubate patients; naloxone hydrochloride, which reverses drug overdoses; and propofol, an anestheticused in emergency surgery better known for causing the death of singer Michael Jackson. Most of those medications are older generic injectables that are widely used in emergency situations. Some of those shortages, among them propofol and succinylcholine, have since been resolved but others continually crop up, creating a gap in emergency drug stockpiles.^[1]

calcium gluconate, used by first responders to regulate heart rhythm in patients suffering cardiac arrest

It could be, but that does not make sense. ACLS (Advanced Cardiac Life Support) discourages the routine use of calcium, but in true emergencies we should be using calcium chloride, rather than the slow infusion of calcium gluconate.

Routine administration of calcium for treatment of in-hospital and out-of-hospital cardiac arrest is not recommended (Class III, LOE B).^[2]

naloxone hydrochloride, which reverses drug overdoses

Naloxone is only indicated for life-threatening respiratory depression due to an opioid overdose. However, a response to naloxone is definitely not diagnostic for an opioid overdose.

Suppose that EMS has no naloxone (Narcan), so what? The essential treatment for opioid overdose, and for benzodiazepine overdose, is just supportive care.

and propofol, an anesthetic used in emergency surgery better known for causing the death of singer Michael Jackson.

Propofol did not cause the death of Michael Jackson. The lack of airway management by Dr. Conrad Murray killed Michael Jackson. Opening his airway, and maybe some painful stimulus, would have kept Michael Jackson alive.

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“Gray market” suppliers, usually small wholesalers or individuals who closely monitor and react to pharmaceutical trends, are scooping up medications as soon as a shortage becomes apparent then selling back the products to drug distributors, other wholesalers or hospitals at inflated prices that can sometimes top more than 1,000 percent of a drug’s original cost.^[1]

What is the original cost used for these calculations? Is it the cost to the manufacturer? The list price? The wholesale price to hospitals? The cost per dose to the patient? Why use percentages? Do most people realize that 1,000% as much means ten times as much.

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Image credit.

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“We’re not getting any complaints regarding any infringement on care because of the shortages,” she says. “That doesn’t guarantee it isn’t happening, but we usually see that fairly quickly when there seems to be an uptick in problems. What I surmise is that providers are doing what they are supposed to do under the circumstances.”^[1]

Is it possible for people to actually do what they are supposed to do?

If we are not doing what we are supposed to be doing, why not?

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“Patient access to innovative treatments is the cornerstone of our industry. That is why the critically important issue of drug shortages demands our collective attention to ensure patients can access themedicines they need in the most expeditious manner possible,” says John Castellani, chief executive officer and president of The Pharmaceutical Research and Manufacturers of America, a trade group comprised of pharmaceutical research and biotechnology companies.^[1]

No.

“Patient access to innovative safe and effective treatments is the cornerstone of our industry.

Safe and effective are essential. Innovative is desirable, but not essential.

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Dr. Conrad Murray killed Michael Jackson with incompetence, not with any drug. Is blaming deaths on a drug shortage any different from blaming deaths on a drug?

To be continued in Is the Drug Shortage an Excuse for Incompetence – Part I on 01/06/2012.

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Image credit.

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Footnotes:

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^[1] Shortage of Lifesaving Drugs Reaches Epic Proportions
Beverly Ford Source: Telegram & Gazette (Worchester, MA)
December 21, 2011
EMS World
Article

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^[2] Interventions Not Recommended for Routine Use During Cardiac Arrest
Part 8: Adult Advanced Cardiovascular Life Support
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 8.2: Management of Cardiac Arrest
Free Full Text Article with links to Free Full Text PDF download

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