How Bad are the Drug Shortages

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I rant a bit about the misuse of many of these drugs, but there are a lot of drugs used in EMS on the current drug shortage list.

There is a lot written about the drug shortages, but what drugs are affected right now? I copied a list of what drugs are currently experiencing shortages as of today from the FDA (Food and Drug Administration).^[1], ^[2]

What about EMS drugs?

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Alfentanil Injection (Alfenta, Rapifen) – An opioid that may be used in some EMS systems as a substitute for fentanyl. Or another reason for EMS to use ketamine.^[7]

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Atracurium besylate (Tracrium) – A paralytic used in RSI (Rapid Sequence Induction/Intubation).

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Atropine Sulfate Injection – Amphastar lists no delays, but other manufacturers list manufacturing delays and an increase in product demand. One manufacturer temporarily suspended production in April 2011.

The FDA search shows that there were drug shortages updates for atropine on 12/11/2008, 4/07/2009, and 9/30/2011 (the current shortage?), but all of the cached pages are the most recent, so the original information is not there.^[3]

Following concerns about possible terrorist attacks using poisons that may be treated with atropine, the long term stability of atropine, and the continuing lack of evidence of benefit of atropine in treating cardiac arrest.^[4]

How much did each of those contribute to another magic treatment biting the dust?

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Caffeine, anhydrous (125 mg/mL) and Sodium benzoate (125 mg/mL) (Starbucks, Dunkin’ Donuts) – OK, that is not the kind of caffeine they are referring to. There might be true rebellion among EMS and hospital personnel if caffeine were not available.

What does that tell us about sleep deprivation, medicine, and the need for naps on the job?

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Calcium Chloride Injection – If we are treating emergency hyperkalemia (which I recently saw written as hyperpotassiumemia :oops:) with anything other than calcium chloride as the first line drug, we are not providing good patient care.^[5]

But calcium is dangerous!!

The danger of calcium is just another EMS myth.

What is dangerous is using much less effective treatments, such as sodium bicarbonate.

What is even more dangerous is using harmful, but ineffective treatments, such as sodium polystyrene sulfonate (Kayexalate)

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Calcium Gluconate – A less concentrated form of calcium, that is safer in IV (IntraVenous) lines of questionable patency, not that this is the biggest concern in treating peri-arrest patients. IO (IntraOsseous) works for calcium chloride.^[6]

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Desmopressin Injection (DDAVP, Stimate, Minirin) – Similar to vasopressin.

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Dexamethasone Injection (Decadron) – Methylprednisolone (Medrol, Solu-Medrol) is a good alternative that is not listed as a current drug shortage.

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Diazepam Injection (Valium, Diastat) – The common alternative benzodiazepine sedatives (lorazepam [Ativan] and midazolam [Versed]) are also listed as current drug shortages.

Maybe this is a good reason to start carrying ketamine.^[7]

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Digoxin Injection – An inotrope alternative to catecholamines. The only inotrope not supposed to raise heart rate or myocardial oxygen demand at therapeutic levels. On the other hand, there is debate about whether digoxin improves outcomes.^[8], ^[9]

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Diltiazem Injection (Cardizem) – Verapamil (Calan, Isoptin, and Verelan) is the common alternative calcium channel blocker that should be used in the place of diltiazem for A Fib (Atrial Fibrillation) or SVT (SupraVentricular Tachycardia).

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Diphenhydramine Hydrochloride Injection (Benadryl) – A medication to treat dystonic reactions. For dystonia, it can be replaced by benztropine (Cogentin). The more common use of diphenhydramine is as an antihistamine, such as after IM (IntraMuscular) epinephrine for anaphylaxis. It may sedate and decrease itching, but do not expect diphenhydramine to reverse anaphylaxis.

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An example of dystonia. Image credit.

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Etomidate Injection (New!!) (Amidate) – Etomidate is commonly used for pseudo-RSI or DFI (Drug Facilitated Intubation). In Pennsylvania, we have a dose of 0.3 mg/kg, that is often restricted even more by some medical command doctors out of an apparent fear of giving a dose that might be effective. Should they want to give orders for more, the maximum dose listed in the protocol is 30 mg. The medical command doctor can order more, but few seem to realize that this is not a restriction on what they can order. Etomidate is only supposed to be used with a paralytic for RSI, but is expected to be both sedative and paralytic, when EMS uses it in Pennsylvania. 😳

Why use a not-very-effective drug at a dose that is not expected to be effective?

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Fentanyl Citrate Injection (Sublimaze) – The shortage of both benzodiazepines and opioids are just more reasons for EMS to use ketamine.^[7]

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Furosemide Injection (Lasix) – A drug that EMS should not use. Furosemide is so far down on the list of treatments for CHF (Congestive Heart Failure), that it suggests we have been digging a grave for the patient, if we stay on scene long enough to give furosemide. A worthless EMS treatment.^[10], ^[11] Pennsylvania is ahead of most states in moving furosemide to medical command order only, but the better move is to remove it from EMS use completely.

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Ketorolac Injection (Toradol) – A pain medicine related to aspirin, so not a good idea for trauma, but some people are less worried about interfering with the ability of trauma patients to stop bleeding than they are about the possibility that the 10/10 severe pain patient might stop screaming and, without anyone noticing, stop breathing. 😳

One possible superiority is for calculi (kidney stones and gall stones). Of course, this is just another reason for EMS to use ketamine.^[7]

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Labetalol Hydrochloride Injection (Normodyne, Trandate) – A beta blocker. Beta blockers have been de-emphasized since the CRUSADE trial, but there are still EMS indications in heart attack. Patients with signs of dramatic catcholamine release (they look as if someone gave them epinephrine) except for patients with tachycardia (greater than 110 beats per minute).

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Lorazepam Injection (Ativan) – Not the best, or even the second best, EMS sedative, but one that is preferred by a lot of people. A much better idea is midazolam, because aggressive doses can be given and they should be wearing off at about the time the patient is being transferred to the ED (Emergency Department), so that one-on-one observation of a heavily sedated patient is not required and flumazenil (Romazicon) is not given. Another reason for EMS to use ketamine.^[7]

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Magnesium Sulfate Injection – A safer antiarrhythmic than amiodarone and a treatment for some of the arrhythmias caused by amiodarone, such as torsades des pointes.-

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Mannitol Injection – An osmotic diuretic used in some EMS systems.

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Methylphenidate HCl (Ritalin) – Possibly the second most common EMS drug – after caffeine.

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Metoclopramide injection (Reglan) – Anti-nausea medication.

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Midazolam Injection (Versed) – This used to be my favorite EMS sedative, but this is one more reason for EMS to use ketamine.^[7]

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Morphine Sulfate Injection – For pain management and another reason for EMS to use ketamine.^[7]

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Nalbuphine Injection (Nubain) – A poor substitute for morphine and a pathetic excuse for risk management. Just another reason for EMS to use ketamine.^[7]

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Naltrexone Oral Tablets (New!!) (Depade, ReVia) – With the use of nebulized naloxone, who knows what might be next? As long as we are treating something other than respiratory depression (patients unlikely to be able to use a nebulizer), maybe oral tablets will be next and the longer acting opioid antagonist may appeal to those terrified of any potential for respiratory depression.

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NeoProfen (ibuprofen lysine) Injection – For treatment of PDA (Patent Ductus Arteriosus) in premature babies. Some EMS may use this, but it is more likely to be found in the ED or neonatal ICU.

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Ondansetron Injection 2 mg/mL (Zofran) – One effective antiemetic.

Ondansetron Injection 32 mg/50 mL premixed bags (Zofran) – Same thing, different preparation.

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Oxytocin Injection, USP (synthetic) (Pitocin) – For post-partum hemorrhage that is not otherwise controlled. Massage the fundus and consider direct pressure. Direct pressure is not in EMS protocols, but when the alternative is the death of the patient, do we want to stop the bleeding, or do we want to follow protocols?

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Pancuronium Bromide Injection (Pavulon) – A paralytic used in RSI.

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Phentolamine Mesylate for Injection (Regitine) – For treatment of extravasation of catecholamines (epinephrine, dopamine, dobutamine). Not usually carried by EMS (after all, it only happens in other EMS systems), but used in the ED (even to treat the extravasation of catecholamines from EMS IVs – but only from those other EMS systems). 😎

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Procainamide HCL Injection (Pronestyl) – An antiarrhythmic that is very effective, but it has a lot of side effects – just like the much less effective drugs that are used in its place.

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Prochlorperazine Injection (Compazine) – Another anti-nause medication. This is also one of the drugs that may cause dystonic reactions.

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Promethazine Injection (Phenergan) – Still another anti-nause medication. Another drug that may cause dystonic reactions.

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Vasopressin Injection (Pitressin) – An alternative to epinephrine as a pressor to treat cardiac arrest, even though there is no evidence of improved survival. Also goes by the name “pit,” so that it can be easily confused with Pitocin (“pit”) used in OB/GYN.

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Vecuronium Injection (Norcuron) – A paralytic used in RSI.

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That is it for the drugs that are used in some EMS systems. Fortunately, a lot can be replaced by ketamine, or their use can be reduced by the use of ketamine. Pain management, sedation, RSI, excited delirium, DSI (Delayed Sequence Intubation), et cetera. One long list of reasons for EMS to use ketamine.^[7]

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Also see Stressful Drug Shortage Update.

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Footnotes:

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^[1] Current Drug Shortages
Drug Shortages
FDA
02/15/2012
Drug shortage Update

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^[2] List of medications from FDA drug shortages update on 02/15/2012

Acetylcysteine Inhalation Solution

Alcohol Dehydrated (Ethanol > 98%)

Alfentanil Injection

Amikacin Injection

Amino Acid Products (New!!)

Aminocaproic Acid

Ammonium Chloride Injection

Ammonium Molybdate Injection

Ammonul (sodium phenylacetate and sodium benzoate) Injection 10%/10%

Amphetamine Mixed Salts, ER Capsules

Amphetamine Mixed Salts Immediate-Release Tablets

Anadrol-50 tablets (Oxymetholone Tablets)

Aquasol A

Atracurium besylate

Atropine Sulfate Injection

Avalide (irbesartan and hydrochlorothiazide)Tablets

Bleomycin Injection

Bupivacaine Hydrochloride Injection

Buprenorphine Injection

Butorphanol Injection

Caffeine, anhydrous (125 mg/mL) and Sodium benzoate (125 mg/mL)

Calcitriol 1 mcg/mL Injection

Calcium Chloride Injection

Calcium Gluconate

Cerezyme (imiglucerase for injection)

Chromic Chloride Injection

Cisplatin injection 1 mg/mL solution

Corticorelin Ovine Triflutate (New!!)

Cosyntropin Injection

Cyanocobalamin injection

Daunorubicin hydrochloride solution for injection

Desmopressin Injection

Dexamethasone Injection

Dexrazoxane Injection

Dextroamphetamine Tablets

Diazepam Injection

Digoxin Injection

Diltiazem Injection

Diphenhydramine Hydrochloride Injection

Doxorubicin (adriamycin) lyophilized powder

Doxorubicin Liposomal (Doxil) Injection

Doxorubicin Solution for Injection

Ethiodol (ETHIODIZED OIL) ampules

Etomidate Injection (New!!)

Etoposide solution for injection

Fabrazyme (agalsidase beta)

Fentanyl Citrate Injection

Fluorouracil Injection

Foscarnet Sodium Injection

Fosphenytoin Sodium Injection

Furosemide Injection

Haloperidol Decanoate Injection

Indigo Carmine Injection

Insulin glulisine [rDNA origin] injection) solution for injection (Apidra SoloStar)

Intravenous Fat Emulsion

Isoniazid Tablets

Ketorolac Injection

Labetalol Hydrochloride Injection

L-cysteine hydrochloride

Leucovorin Calcium Lyophilized Powder for Injection

Leuprolide Injection

Levaquin Injection

Levofloxacin Injection

Levoleucovorin (Fusilev) 50 mg single use vials

Lorazepam Injection

Magnesium Sulfate Injection

Mannitol Injection

Mesna 100 mg/mL Injection

Methotrexate Injection

Methylphenidate HCl

Methyldopate Injection

Metoclopramide injection

Mexiletine Capsules (150mg, 200mg, and 250mg)

Midazolam Injection

Mitomycin Powder for Injection

Morphine Sulfate Injection

Multi-Vitamin Infusion (Adult and pediatric)

Mustargen (mechlorethamine HCl) injection

Nalbuphine Injection

Naltrexone Oral Tablets (New!!)

NeoProfen (ibuprofen lysine) Injection

Neupro (rotigotine transdermal system)

Ondansetron Injection 2 mg/mL

Ondansetron Injection 32 mg/50 mL premixed bags

Ontak injection

Opana ER (oxymorphone hydrochloride) Extended-Release Tablets CII (New!!)

Orphenadrine Citrate Injection

Oxsoralen (methoxsalen) 1% topical lotion

Oxytocin Injection, USP (synthetic)

Paclitaxel Injection

Pancuronium Bromide Injection

Phentolamine Mesylate for Injection

Phytonadione Injectable Emulsion (Vitamin K)

Potassium Phosphate

Primaquine Phosphate Tablets

Procainamide HCL Injection

Prochlorperazine Injection

Promethazine Injection

Selenium injection

Sodium Acetate Injection

Sodium Chloride 23.4%

Sodium Phosphate Injection

Sulfamethoxazole 80mg/trimethoprim 16mg/ml injection (SMX/TMP)

Telavancin (Vibativ) Injection

Tetracycline Capsules

Thiotepa for Injection

Thyrogen (thyrotropin alfa) injection 1.1mg/vial

Thyrolar Tablets

Ticlopidine Tablets

Tobramycin Solution for Injection

Vasopressin Injection

Vecuronium Injection

Vinblastine Sulfate Injection

Voltaren gel 1% (Diclofenac Sodium Topical Gel) (New!!)

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^[3] Atropine Sulfate Injection
FDA
FDA Search

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^[4] What Will We Do With All of That Atropine
Rogue Medic
Fri, 22 Oct 2010
Article

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^[5] Management of severe hyperkalemia.
Weisberg LS.
Crit Care Med. 2008 Dec;36(12):3246-51. Review.
PMID: 18936701 [PubMed – indexed for MEDLINE]

Free Full Text PDF

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^[6] Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs.
Orlowski JP, Porembka DT, Gallagher JM, Lockrem JD, VanLente F.
Am J Dis Child. 1990 Jan;144(1):112-7.
PMID: 1688484 [PubMed – indexed for MEDLINE]

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^[7] Is Ketamine an EMS Wonder Drug
Rogue Medic
Sun, 01 Jan 2012
Article

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^[8] Update on digoxin therapy in congestive heart failure.
Haji SA, Movahed A.
Am Fam Physician. 2000 Jul 15;62(2):409-16. Review.
PMID: 10929703 [PubMed – indexed for MEDLINE]

Free Full Text from Am Fam Physician.

For many more years, digitalis continued to be an important part of heart failure management. The detrimental aspects of digoxin therapy were not considered important until excess mortality was reported in survivors of myocardial infarction who received digitalis.^13,14 Uncontrolled observations that the withdrawal of digoxin produced no ill effects also raised concerns about the efficacy of the drug.^15,16

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^[9] The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group.
[No authors listed]
N Engl J Med. 1997 Feb 20;336(8):525-33.
PMID: 9036306 [PubMed – indexed for MEDLINE]

Free Full Text from N Engl J Med.

In conclusion, digoxin had no effect on overall mortality in patients receiving diuretics and angiotensin-converting–enzyme inhibitors, but it did reduce the overall number of hospitalizations and the combined outcome of death or hospitalization attributable to worsening heart failure. In clinical practice, digoxin therapy is likely to affect the frequency of hospitalization, but not survival.

On the other hand, that is not a study of digoxin for emergency use.

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^[10] Prehospital therapy for acute congestive heart failure: state of the art.
Mosesso VN Jr, Dunford J, Blackwell T, Griswell JK.
Prehosp Emerg Care. 2003 Jan-Mar;7(1):13-23. Review.
PMID: 12540139 [PubMed – indexed for MEDLINE]

Free Full Text PDF

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^[11] Modern management of cardiogenic pulmonary edema.
Mattu A, Martinez JP, Kelly BS.
Emerg Med Clin North Am. 2005 Nov;23(4):1105-25. Review.
PMID: 16199340 [PubMed – indexed for MEDLINE]

Free Full Text PDF

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