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

- Rogue Medic

Shortage of Lifesaving Drugs Reaches Epic Proportions

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.

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.

“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.


Image credit.

“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?

“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.

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.


Image credit.

Footnotes:

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

[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

.

Propofol and the Michael Jackson Effect


ResearchBlogging.org
Also posted over at Paramedicine 101 (now at EMS Blogs) and at Research Blogging. Go check out the excellent material at these sites.

One contributing site introduced propofol into its ED 22 months after it began entering patients into the registry. This timing permitted a natural experiment to examine the impact of the use of this drug on physician preferences and patient outcomes in patients undergoing procedural sedation at this site. After the introduction of propofol, all previously available procedural sedation agents remained in the ED formulary and no endorsement for use of propofol over existing medication options was presented to the EPs.[1]

You should already know the questions I am going to raise – The Michael Jackson Drug? Where did they put all of the dead bodies?

You should also know the response – What dead bodies?

Why do we allow one unusual, dramatically publicized case affect our expectations? Because we don’t stop and think for ourselves.

Minor complications are probably what killed Michael Jackson. Minor complications that should easily have been treated by any First Responder, or any Patient Care Technician, or and Nurse’s Aide in a nursing home. Minor complications that would have resulted in a great big YAWN from anyone with any experience managing airways.

Airway obstruction: responds to repositioning

Anyone who has taken CPR and even vaguely remembers the “Head tilt, chin lift,” method of opening the airway could treat this. No big deal.

or

Hypoxia: responsive to oxygen

Anyone monitoring the patient’s pulse oximetry could have noticed this and delivered some oxygen to bring the patient’s oxygen saturation back up to the normal range.

This requires only three things –

1. Pulse oximetry measuring equipment.

2. Oxygen (with a means of delivering the oxygen to the patient).

3. A clue.

All of these are part of the minimum equipment that should be present for the use of propofol.

None of these appear to have been present.

Part of the problem with the safety of propofol is that it is deceptive. So many of the complications resolve on their own, that some people will become complacent and not be prepared to deal with the complications, not even the minor complications. Then these minor complications become major life threatening/life ending complications.

How many times did Dr. Conrad Murray administer propofol (and other sedatives) to Michael Jackson, but get away with it because the complications resolved on their own?

Many hospitals only permit anesthesia to administer propofol. The other drugs on this list are much less commonly restricted to just anesthesia. Yet, this most restricted drug, too dangerous for anyone outside of anesthesia, appears to be the safest.

Minor complications dropped from 5.8% to 1.7% when propofol use went from zero percent of procedural sedations to 40% of procedural sedations.

Propofol went from being the least commonly used drug (never used) to the most commonly used drug and the minor complication rate decreased by almost a factor of 3 1/2.

During that period there was an even greater decrease in major complications – from 3.6% they decreased to only 1.0%. This is a decrease by greater than a factor of 3 1/2.

I understand the concern about the ability of people to underestimate the potential for complications, but that is true of all of the drugs that anesthesia does not make a big deal about. By limiting access to the safest drug for procedural sedation, the anesthesia departments are harming patients.

Is propofol a hand grenade or a Holy Grail?

Neither, but it depends on the person using it, which is just a variation of what Paracelsus warned us about medication/poison –

All things are poison and nothing is without poison, only the dose permits something not to be poisonous. – Paracelsus.

There are several possible Michael Jackson effects with propofol.

Patients are choosing more dangerous medications when they need strong sedation.

Doctors should be using propofol with more awareness of the potential complications.

The shortage of propofol seems to have ended, perhaps because propofol was being used less often after the death of Michael Jackson.

Teva
Teva Pharmaceuticals has discontinued their propofol injection.

Hospira – 1-877-946-7747
All presentations: ample levels of inventory to support market demand.
Please check with your wholesaler for available inventory.

APP – 1-888-386-1300
ALL Diprivan and Propofol presentations are sufficiently stocked at wholesalers and distributors nationwide.
Diprivan 1% (20mL, 50mL, and 100mL)
Generic Propofol 1% (20mL, 50mL, and 100mL)
Novaplus Propofol 1% (20mL, 50mL, and 100mL)
Please check with your wholesalers and distribution centers for available inventory.
[2]

If you have not been able to get propofol for your ED (Emergency Department) because of supply issues, that should not be a problem any more.

If you have not been able to get propofol for your ED because of inappropriate restrictions by anesthesia, this study should help to clearly demonstrate that emergency physicians working in community emergency departments are able to use propofol safely. Emergency physicians are safer using propofol than the more conventional medicines – etomidate, fentanyl, and midazolam.

The lesson most people seem to have learned is that propofol is dangerous.

The reality is that propofol may be the safest drug for procedural sedation.

There is also a discussion about this problem of inappropriate restriction of propofol to only anesthesia at Emergency Physicians Monthly –

CMS and Deep Sedation: A Win for Emergency Medicine
by Kevin Klauer, DO, EJD on January 31, 2011
Article

Also see Steve Whitehead’s explanation of the cause of death – BLS Before ALS.

Footnotes:

[1] Impact of addition of propofol to ED formulary.
Senula G, Sacchetti A, Moore S, Cortese T.
Am J Emerg Med. 2010 Oct;28(8):880-3. Epub 2010 Feb 25.
PMID: 20887909 [PubMed – indexed for MEDLINE]

[2] Propofol Injection (updated 10/11/2011)
FDA
Current Drug Shortages

Senula, G., Sacchetti, A., Moore, S., & Cortese, T. (2010). Impact of addition of propofol to ED formulary The American Journal of Emergency Medicine, 28 (8), 880-883 DOI: 10.1016/j.ajem.2009.04.035

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Stressful Drug Shortage Update


The FDA (Food and Drug Administration) reports that their lorazepam (Ativan) injection drug shortage has been updated.[1]

Baxter’s 20 mg/10 ml vials are available, but have the potential for a bit more of a dose than most patients might require.

Baxter’s 2 mg/1 ml vials are on back order until the end of April, as long as things go as planned.

Bedford’s 2 mg/1 ml vials and 20 mg/10 ml vials are on such long term back order, that the company cannot estimate a release date.

Hospira’s 2 mg/1 ml vials, 20 mg/10 ml vials, and 2 mg/1 ml syringes are anticipated to be released in mid to late April, 2011.

The FDA does not provide any information about when Hospira’s 4 mg/1 ml vials and 4 mg/1 ml syringes will be available. The ASHP (American Society of Health System Pharmacists) has different information about the availability of some of the Hospira lorazepam preparations.

Hospira has all injectable lorazepam presentations on back order. The company estimates a release date of mid-April, 2011 for the 2 mg/mL 1 mL and 10 mL vials. The company estimates a release date of late-April, 2011 for the 2 mg/mL 1 mL Carpuject syringes, and the 4 mg/mL 1 mL and 10 mL vials. The 2 mg/mL 1 mL iSecure syringes and the 4 mg/mL 1 mL Carpuject syringes were voluntarily suspended until 2012 to allow increased production of other lorazepam presentations.3 [2]

During this shortage, use alternative injectable benzodiazepines.
There are no direct dosage conversions between the benzodiazepines because each has a distinct pharmacokinetic profile that dictates the agent’s therapeutic use and dosing. The Table compares the pharmacokinetics of injectable benzodiazepines.
[2]

There is no Table provided on this page. There are four related drug shortages listed on the page, but none are benzodiazepines, but both midazolam and diazepam are listed by ASHP as current drug shortages.

The most practical substitute for emergency treatment with lorazepam is midazolam. There are no reported midazolam shortages from the FDA, but the ASHP does list midazolam as a current drug shortage and has 13 updates going back to August of 2010.

Baxter and Bedford could not provide a reason for the midazolam shortage.
APP has their product on allocation due to increase in demand.
Hospira has changed several NDC numbers. The company cites increased demand as the reason for the shortage.
Wockhardt has discontinued all midazolam injection presentations.
Cura has discontinued manufacturing all products.
The 5 mg/mL presentations are not generally affected by this shortage.
[3]

The 5 mg/mL presentations are not generally affected by this shortage.

This raises the question – What is the purpose of smaller dose containers outside of pediatric treatment areas?

If a patient is in need of some sedation, I find that 5 mg midazolam is usually not enough for even 50 kg (110 pounds) patients. For large patients (100+ kg or 220+ pounds) 5 mg midazolam is like whispering sweet nothings in the patient’s ear. It only works when the proper mood has been set. When the patient is agitated/violent, we should assume that the mood is not working and 5 mg midazolam is not going to be effective unless followed with more doses.

This is important –

The treatment for too aggressive dosing of benzodiazepines is supportive care.

The treatment for not aggressive enough dosing of benzodiazepines can be exacerbation of underlying medical conditions, traumatic injuries to the patient, and/or traumatic injuries to those providing patient care.

Now that CMS (Centers for Medicare & Medicaid Services) is discouraging the use of TASERs on violent patients, we need to consider being much more aggressive in providing large enough doses to violent patients – for everyone’s protection. CMS will not show up to resuscitate the patients who arrest due to following their misguided rules.[4]

APP has available midazolam 1 mg/mL injection 2 mL vials (NDC 63323-0411-12), 5 mL (NDC 63323-0411-25) and 10 mL vials (NDC 63323-0411-10). These products are being allocated due to increased demand.
Hospira has available midazolam 1 mg/mL preservative-free injection 2 mL (NDC 00409-2305-17) and 5 mL (NDC 00409-2305-05) vials, 2 mL (NDC 00409-2305-21) and 5 mL (NDC 00409-2305-50) Novaplus vials, and 2mL iSecure syringes (NDC 00409-2306-12). The 2 mL Carpuject syringes are on back order and the company estimates a release date of mid-May, 2011.
Bedford has available midazolam 1 mg/mL 10 mL vials (NDC 55390-0125-10). The 2 mL and 5 mL vials are on back order and the company cannot estimate a release date.
Baxter has available midazolam as 1 mg/mL 2 mL vials in 25 count packages (NDC 10019-0028-04), 2 mL latex-free vials in 10 count packages (NDC 10019-0028-01), 5 mL multiple-dose vials (NDC 10019-0028-05), and 10 mL multiple-dose vials (NDC 10019-0028-10). Other presentations are on back order and the company cannot estimate a release date.
[3]

ASHP also has diazepam listed as being a drug shortage with updates going back to 2008.

Hospira has available diazepam 5 mg/mL injection in 2 mL iSecure syringes (NDC 00409-1273-05) and 10 mL 10 count vials (NDC 00409-3213-120. The 2 mL Carpuject Luer-Lock syringes are on back order with an estimated release date of early-April, 2011. The 10 mL multiple-dose vials in packages of 5 were discontinued.[5]

ASHP states that Hospira is the sole provider of diazepam injection, but DailyMed currently lists three other civilian manufacturers[6],[7],[8] and one supplier to the military.[9]

Footnotes:

[1] Lorazepam Injection
2 mg/ml

Current Drug Shortages
FDA
4/11/2011
Drug shortage Update

[2] Lorazepam injectable presentations
[08 April 2011]
Drug Shortages: Current Drugs
ASHP
Current Bulletin

[3] Midazolam 1 mg/mL Injections
[04 April 2011]
Drug Shortages: Current Drugs
ASHP
Current Bulletin

[4] Patient Safety Versus Workplace Safety – Stun Gun Debate Illustrates Dueling Federal Mandates
Rogue Medic
Part I
Part II

[5] Diazepam Injection
[01 April 2011]
Drug Shortages: Current Drugs
ASHP
Current Bulletin

[6] Diazepam (diazepam) Injection
[Baxter Healthcare Corporation]

Revised: 02/2006
DailyMed
DailyMed HTML of FDA Label

[7] DIAZEPAM (diazepam) injection
[General Injectables and Vaccines, Inc.]

Revised: 06/2010
DailyMed
DailyMed HTML of FDA Label

[8] DIAZEPAM injection, solution
[Rebel Distributors Corp]

Revised: 12/2010
DailyMed
DailyMed HTML of FDA Label

[9] DIAZEPAM injection
[U.S. Army Medical Research and Development Command (MCMR-RCQ-HR)]

Revised: 02/2009
DailyMed
DailyMed HTML of FDA Label

.

Drug Shortage Update – Norepinephrine

The FDA (Food and Drug Administration) has advised of another drug shortage. Norepinephrine Bitartrate Injection (Levophed brand, but also the generic version). This adds to the potential entertainment value in ACLS (Advanced Cardiac Life Support) classes.

This may also contribute to problems when treating real patients, so it is a good idea to prepare for the use of alternatives to the drugs that are not available, or those that are not available in the strength/packaging we are familiar with.

Ironically, as far as using norepinephrine for cardiac arrest, the 2010 ACLS guidelines state –

Other Vasopressors
There are no alternative vasopressors (norepinephrine, phenylephrine) with proven survival benefit compared with epinephrine.268,281,282
[1]

Why ironically?

Vasopressors
To date no placebo-controlled trials have shown that administration of any vasopressor agent at any stage during management of VF, pulseless VT, PEA, or asystole increases the rate of neurologically intact survival to hospital discharge. There is evidence, however, that the use of vasopressor agents is associated with an increased rate of ROSC.
[2]

Epinephrine has not been shown to produce any survival benefit, but norepinephrine has not been shown to produce more of a survival benefit than epinephrine.

We could just as easily state –

There are no alternative vasopressors (epinephrine, norepinephrine, phenylephrine) with proven survival benefit compared with Placebo.

For post-cardiac arrest care, the 2010 ACLS guidelines state –

There is no proven benefit or harm associated with administration of routine IV fluids or vasoactive drugs (pressor and inotropic agents) to patients experiencing myocardial dysfunction after ROSC. Although some studies found improved outcome associated with these therapies, the outcome could not be solely ascribed to these specific interventions because they were only one component of standardized treatment protocols (eg, PCI and therapeutic hypothermia).6,11,12,166 Invasive monitoring may be necessary to measure hemodynamic parameters accurately and to determine the most appropriate combination of medications to optimize perfusion.

Fluid administration as well as vasoactive (eg, norepinephrine), inotropic (eg, dobutamine), and inodilator (eg, milrinone) agents should be titrated as needed to optimize blood pressure, cardiac output, and systemic perfusion (Class I, LOE B). Although human studies have not established ideal targets for blood pressure or blood oxygenation,11,12 a mean arterial pressure ≥65 mm Hg and an ScvO2 ≥70% are generally considered reasonable goals.[3]

As with treatment during cardiac arrest, we could state this as –

There are no treatments (fluids, epinephrine, norepinephrine, phenylephrine) with proven survival benefit compared with Benign Neglect.

For norepinephrine in special resuscitation situations, the 2010 ACLS has –

Recently vasopressin has been used successfully in patients with anaphylaxis (with or without cardiac arrest) who did not respond to standard therapy.77–79 Other small case series described successful results with administration of alternative -agonists such as norepinephrine,80 methoxamine,81,82 and metaraminol.83–85 Alternative vasoactive drugs (vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in cardiac arrest secondary to anaphylaxis that does not respond to epinephrine (Class IIb, LOE C). No randomized controlled trials have evaluated epinephrine versus the use of alternative vasoactive drugs for cardiac arrest due to anaphylaxis.[4]

And –

A number of vasopressors and inotropes have been associated with improvement in the treatment of tricyclic-induced hypotension, ie, epinephrine,239,344,345 norepinephrine,345–348 dopamine,348–350 and dobutamine.349[5]

Back to the drug shortage information.

Bedford attributes the lack of availability to manufacturing delays –

Bedford has Norepinephrine Bitartrate Injection 1 mg/mL 4 mL vials on back order and the company cannot estimate a release date.[6]

Hospira claims that the problem is increased demand –

Levophed (Norepinephrine Bitartrate Injection) 1 mg/mL 4 mL ampules (NDC 0409-1443-04) and 4 mL vials (NDC 0409-3375-04) are on back order, and the company expects continuous deliveries going forward, with recovery estimated to occur in 3Q 2011.[6]

Teva states that they only temporarily discontinued norepinephrine, but that was in June of 2010 –

Teva anticipates having product available again 4th quarter 2011.[6]

There is probably not an increased overall demand for norepinephrine. More likely is that it is a chain of events. Teva stopped manufacture, Bedford has manufacturing delays, and Hospira is trying to make up for the lack of supply from the other drug companies. This seems to be a trend among the drug shortages.


Footnotes:

[1] Other Vasopressors
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Vasopressors
Free Full Text Article with links to Free Full Text PDF download

[2] Vasopressors
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 8: Adult Advanced Cardiovascular Life Support
Part 8.2: Management of Cardiac Arrest
Medications for Arrest Rhythms
Free Full Text Article with links to Free Full Text PDF download

[3] Use of Vasoactive Drugs After Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 9: Post–Cardiac Arrest Care
Vasoactive Drugs for Use in Post–Cardiac Arrest Patients
Free Full Text Article with links to Free Full Text PDF download

[4] Vasopressors
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 12: Cardiac Arrest in Special Situations
Part 12.2: Cardiac Arrest Associated With Anaphylaxis
ACLS Modifications
Free Full Text Article with links to Free Full Text PDF download

[5] Cyclic Antidepressants
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Part 12: Cardiac Arrest in Special Situations
Part 12.7: Cardiac Arrest Associated With Toxic Ingestions
Free Full Text Article with links to Free Full Text PDF download

[6] Norepinephrine Bitartrate Injection
FDA
updated 3/10/2011
Drug Shortage Update
Drug Shortages – norepinephrine

.

FDA Drug Shortages – Calcium Gluconate and Chloride – Part I

The FDA (Food and Drug Administration) issued a new drug shortage for calcium gluconate – this is in addition to the continuing drug shortage for calcium chloride.[1]

The occurrence of a drug shortage for calcium gluconate several months after the drug shortage for calcium chloride (9/09/2010)0 should not come as a surprise. The most common replacement for calcium chloride is going to be calcium gluconate. There will be all of the regular demand for calcium gluconate plus the demand for three times as much calcium gluconate as the amount of calcium chloride that needs to be replaced.

Who are the patients who really need calcium?

2. Hydrofluoric acid exposure. these patients will have major internal problems related to the acid being absorbed through the skin, even where there is no obvious signs of a burn.

1. Hyperkalemia.

Don’t let any inappropriately cautious person tell you not to start treating hyperkalemia with calcium. This is only evidence that the person does not understand hyperkalemia, pharmacology, risk management, something else, or a combination of all of these.

Here is what the AHA (American Heart Association) writes about treating hyperkalemia –

ACLS Modifications in Management of Severe Cardiotoxicity or Cardiac Arrest Due to Hyperkalemia
Treatment of severe hyperkalemia aims at protecting the heart from the effects of hyperkalemia by antagonizing the effect of potassium on excitable cell membranes, forcing potassium into cells to remove it promptly from the circulation, and removing potassium from the body. Therapies that shift potassium will act rapidly but are temporary and thus may need to be repeated. In order of urgency, treatment includes the following:

· Stabilize myocardial cell membrane:

· Calcium chloride (10%): 5 to 10 mL (500 to 1000 mg) IV over 2 to 5 minutes or calcium gluconate (10%): 15 to 30 mL IV over 2 to 5 minutes

· Shift potassium into cells:

· Sodium bicarbonate: 50 mEq IV over 5 minutes
· Glucose plus insulin: mix 25 g (50 mL of D50) glucose and 10 U regular insulin and give IV over 15 to 30 minutes
· Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes

· Promote potassium excretion:

· Diuresis: furosemide 40 to 80 mg IV
· Kayexalate: 15 to 50 g plus sorbitol per oral or per rectum
· Dialysis

When cardiac arrest occurs secondary to hyperkalemia, it may be reasonable to administer adjuvant IV therapy as outlined above for cardiotoxicity in addition to standard ACLS (Class IIb, LOE C).[2]

Bicarb first?

That depends.

Is the patient stable?

Part II will look at specific cases of hyperkalemia.

Footnotes:

[1] New Drug Shortage – Calcium Gluconate
3/03/2011
FDA
Drug Shortage page

[2] ACLS Modifications in Management of Severe Cardiotoxicity or Cardiac Arrest Due to Hyperkalemia
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 12: Cardiac Arrest in Special Situations
Part 12.6: Cardiac Arrest Associated With Life-Threatening Electrolyte Disturbances
Hyperkalemia
Free Full Text from The AHA with links to Free Full Text PDFs

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Drug Shortages Update – IV Nitroglycerin

While I was finishing writing my 3 part Valentine to IV (IntraVenous) nitroglycerin (Corrections of Misleading Charts Comment – Part I, Part II, and Part III.), the FDA (Food and Drug Administration) sent out a notice that there is a shortage of IV NTG.

It breaks my heart.

On the other hand, it is great that people are using IV NTG, even if it is rare for 911 EMS to use IV NTG for hypertensive CHF (Congestive Heart Failure).

Baxter has all premix nitroglycerin in dextrose presentations on back order, the manufacturing delays are short term and the company anticipates having all presentations available by end of February.

Hospira has all premix nitroglycerin in dextrose presentations on back order with no estimated release date at this time.[1]

and –

Luitpold released product on 1/27/11 and have an additional lot scheduled for release at the end of February.[2]

This isn’t due to increased demand, just manufacturing delays. Manufacturing delays do seem to be the trend, lately.[3] I will write more about this in Hospital Pharmacists Scrambling Amid Vast Drug Shortages.

The IV furosemide (Lasix) drug shortage should have been the final nail in the coffin of IV furosemide for CHF, but too many of us still do not seem to understand appropriate treatment of CHF.

Many of us have demonstrated our lack of understanding of acute pulmonary edema by switching to IV bumetanide (Bumex). Wrong move.

Most of these patients are volume depleted, not volume overloaded. Therefore, diuresis will only make things worse. I repeatedly point this out in posts such as More on Lasix in EMS.

But this is EMS, we often resist the opportunity to learn, as long as it seems that everyone else is harming patients the same way, we insist on maintaining this dangerous standard of care.

Footnotes:

[1] Nitroglycerin in Dextrose 5%
FDA
2/10/2011
Drug Shortage Update

[2] Nitroglycerin Solution 5mg/ml 10ml (NDC 00517-4810-25)
FDA
2/10/2011
Drug Shortage Update

[3] Hospital Pharmacists Scrambling Amid Vast Drug Shortages: Emergency Physicians Between Roc and a Hard Place
Annals of Emergency Medicine News
Maryn McKenna (Special Contributor to Annals News & Perspective)
Free Full Text from Annals of Emergency Medicine with link to Free PDF download

.

Corrections of Misleading Charts


Also posted over at Paramedicine 101, which is now at EMS Blogs. Go check out the excellent material there.

Back in September, I wrote Furosemide and Drug Shortages 2. I was just looking at the charts I made and realized that they were not at all helpful at explaining the information.

When I look at my own charts and have trouble figuring out what I was trying to explain, then I have completely failed.

I have edited the charts to do a better job of presenting the information I was trying to make clear.


Click on charts to make them larger.

When looking at the problems with the use of furosemide (Lasix), one import point to remember is that the authors only looked at the primary diagnosis. This is an important shortcoming of the study.

How many of the patients had a secondary diagnosis of CHF?

We don’t know.

It should be noted that seven patients without an ED diagnosis of CHF received ED furosemide and 43 patients received ED nitro with only eight of those having a primary diagnosis of ACS. This data put the accuracy of the primary ED final diagnosis as a reference standard into question,[1]

Another problem is that the authors seem to think that nitro is only for ACS (Acute Coronary Syndromes – essentially heart attacks). NTG (NiTroGlycerin) is the most effective medication for hypertensive CHF.

Only 43 out of 60 patients with a primary diagnosis of CHF received NTG – this needs to be studied.

Were these 17 patients not treated with NTG because they were hypotensive?

In the ED, it is much safer to give normotensive CHF patients NTG, because of IV (IntraVenous) NTG. EMS is usually limited to SL (SubLingual) NTG.

SL NTG is not what is best for patients, unless we feel that it is important to treat patients with NTG before starting an IV.

If we have IV access, we should be giving NTG the safer and more titratable way – IV NTG. (This sentence added 11:50 02/07/11)

This chart was just to show how little difference it would make to add in the patients who did not have a diagnosis.

This chart compares the deaths between the patients treated with furosemide by EMS and receiving a primary diagnosis of CHF and those not receiving a primary diagnosis of CHF.

Due to the shortcomings of this study, it should be replicated with the secondary diagnoses included. This is essential.

Footnotes:

[1] Correlation of paramedic administration of furosemide with emergency physician diagnosis of congestive heart failure
Thomas Dobson, Jan Jensen, Saleema Karim, and Andrew Travers.
Journal of Emergency Primary Health Care
Vol.7, Issue 3, 2009
Free Full Text . . . . . . . Free Full Text PDF

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Do Drug Shortages Really Impact EMS? – Answer 4



Here is part 4 of the details from the points I raised in commenting on the discussion of the drug shortages and the way these affect EMS. Do Drug Shortages Really Impact EMS? – EMS Office Hours and followed by Do Drug Shortages Really Impact EMS? – Answer 1, then by Do Drug Shortages Really Impact EMS? – Answer 2, and that is followed by Do Drug Shortages Really Impact EMS? – Answer 3. This is broken up by answer. There are many points covered for a podcast that lasts less than 40 minutes. Do Drug Shortages Really Impact EMS?

4. Should CPAP (Continuous Positive Airway Pressure) be ALS (Advanced Life Support) only?

Somebody mentioned that CPAP is seen as invasive.

No. CPAP is not invasive.

CPAP falls into the category of NIPPV (Non-Invasive Positive Pressure Ventilation). CPAP has been used safely many places by BLS (Basic Life Support) personnel.

CPAP is a safe and effective BLS treatment for heart failure.

What if we think that medical command permission should be required for BLS to use CPAP?

If that is the case, then we should give CPAP to BLS personnel, train the basic EMTs to use CPAP, even require our magic phone call. Then, after we realize that there was never any good reason to prevent basic EMTs from using CPAP and we realize that the magic phone call is doing nothing to improve safety, but is probably only discouraging appropriate use of CPAP, then we can eliminate the magical medical command phone call ritual.

CPAP should be used aggressively for heart failure by everyone.

If anyone disagrees, please provide some evidence of harm.

Treatments for CHF –

Lasix (furosemide)? Does not decrease the need for intubation, does not improve survival, does not help, but can harm CHF patients and can harm patients with other medical conditions (e.g. pneumonia) mistaken for CHF.

High Dose NTG? Decreases the need for intubation, but is ALS.

ACE Inhibitors? Decrease the need for intubation, but are ALS.

CPAP? Decreases the need for intubation and is BLS. Possibly the best and safest treatment for CHF.

Why would anyone want to do something as dangerous as give Lasix, when there is something as simple and as safe as CPAP available?

I will write about the evidence for CPAP in another post.

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