Anesthesia Drug Shortages

Shortages of sedatives, analgesics, and anesthetic agents happen with uncomfortable frequency and the COVID-19 pandemic is putting great pressure on supplies of drugs that, in some cases, were already in and out of availability. Providing safe and humane anesthetic care in such times requires flexibility on the part of the provider.

The following post is a summary of ideas put together by a group of veterinary anesthetists for how to deal with shortages of drugs that specifically may be affected by the current healthcare crisis. Many of these strategies will apply to future shortage situations as well - which, unfortunately, almost certainly will occur.

ANESTHESIA & PERIOPERATIVE DRUG SHORTAGES associated with COVID-19

Nancy Brock DVM DACVAA

Rachael Carpenter DVM

Kris Kruse-Elliot DVM PhD DACVAA

Lydia Love DVM DACVAA

Heidi Shafford DVM PhD DACVAA

Check FDA website for updated info on drug shortages: https://www.accessdata.fda.gov/scripts/drugshortages/

❖ Anesthesia & perioperative drugs that may be in short supply

This is how I look when I think about anesthesia drug shortages, especially when it comes to analgesics for our patients.

• Fentanyl, hydromorphone, morphine

• Midazolam, diazepam

• Propofol (but maybe not Propofol-28?)

• Dexmedetomidine (possibly due to raw material shortage)

• Ketamine (veterinary-labeled products may be ok)

• Dopamine, dobutamine, norepinephrine, epinephrine, phenylephrine, vasopressin

• Corticosteroids (injectable)

• Neuromuscular blocking agents

• Albuterol, theophylline, other bronchodilators

• Furosemide

• IV fluids

• Antibiotics

The major issues for veterinary anesthetists will likely be adequate pain management, induction drug choices, and management of blood pressure. Here are some strategies for adjusting to these drug shortages while maintaining patient comfort and safety.

❖ Consider oral sedation/analgesia at home

• Benefits: reduced patient anxiety & decreased anesthetic requirements - ability to avoid full mu opioid agonists for sedation, less inhalant-induced hypotension

• Gabapentin, trazodone, oral-transmucosal acepromazine

Resources

• This NAVAS blog post: https://www.mynavas.org/post/oral-sedatives-and-anxiolytics-for-veterinary-visits

• Pre-Hospital Sedation Options for Cats and Dogs https://vetanesthesiaspecialists.com/for-vets/resources/

• Veterinary Anesthesia Update 3rd Edition: Available on VIN, or as a print version https://www.nancybrockvetservices.com/

❖ Decrease use of full mu agonist opioids

• Avoid using full mu opioids for sedation / premedication

• Reserve current stock of full mu agonist opioids for control of moderate-to-severe pain

• Consider other pharmaceuticals for sedation: acepromazine, dexmedetomidine, medetomidine, butorphanol

• Be ready to substitute one full mu agonist opioid for another

• It is legal to obtain compounded drugs for hospital use from a 503b pharmacy during a shortage situation

• Reserve fentanyl for high risk patients with significant acute pain

• Reduce fentanyl infusion rate & draw up smaller quantities to reduce waste

• Consider micro-dose ketamine boluses or infusion

• Use butorphanol if no/mild pain anticipated or main goal is sedation or premedication

• Buprenorphine may be adequate for moderate pain and, if combined with other analgesics, may be adequate for severe pain in some patients.

• Pain score your patients frequently!

❖ Specific strategies for preserving opioids, especially pure mu agonists

Need sedation - use butorphanol (0.2-0.4 mg/kg IM or IV). Can be part of your premedication protocol, preserves pure mu agonist for intra-op and overlap is not an issue since premed of butorphanol unlikely to last significantly into the surgical period.

Buprenorphine - reasonably good analgesic but not very sedating. IV administration requires 30 min+ to be effective. More about buprenorphine here: https://www.mynavas.org/post/7-things-to-know-about-buprenorphine

Utilize local and regional anesthetic blocks whenever and wherever possible. Not only do they reduce parental analgesic and inhalant requirements, but they provide superior pain management when properly applied.

Easy local anesthetic blocks that usually do not require advanced training or imaging: local infiltration of wound edges, splash blocks, intra-testicular, intraperitoneal, injection into the suspensory ligament, declaw blocks, radius/ulnar/median/musculocutaneous nerve blocks, dental blocks, intravenous regional anesthesia.

Acheivable advanced regional blocks: epidural placement, ultrasound guided blocks such as transversus abdominal plane block, femoral/sciatic, and brachial plexus blocks.

Regional and local anesthesia decreases the need for perioperative opioids, thereby decreasing some of the side effects of opioids including sedation, reduced GI transit, and worries about the prescription of controlled drugs.

Consider using liposomal bupivacaine (Nocita®). Off-label use is possible in a wide variety of soft tissue and orthopedic procedures.

A great lecture about Nocita is available to VIN members here: https://www.vin.com/vinmembers/rounds?id=9602144

Consider placing local anesthetic wound (soaker) catheters.

Leverage anti-inflammatory medications whenever possible. NSAIDs - Onsior® (robenacoxib), meloxicam, carprofen available as injectable. Ensure patient is hydrated and cardiovascularly stable. Galliprant®and even oral steroids could be considered in some patients for their anti-inflammatory effects.

❖ Use veterinary-labeled versions of induction agents.

Veterinary labeled products including PropoFlo-28®, PropoFlo®, and ketamine labeled for cats and horses cannot currently be used legally in humans. The raw materials may be pressured eventually however.

❖ Replace propofol

Alfaxalone is not currently labeled for use in humans.

• More detailed information about alfaxalone here: https://www.mynavas.org/post/should-i-be-using-alfaxalone

• Smooth IV induction with alfaxalone is very similar to propofol.

• Cardiovascular & respiratory depression often of shorter duration and less noticeable

• Duration of alfaxalone is short but noticeably longer than propofol

• Alfaxalone can be used in cats, dogs, young, old, ill and pregnant patients, also exotics

• Top-up doses of alfaxalone during anesthesia okay

• Routes of administration for alfaxalone include IV, IM, SC (IM & SC are off-label in US)

• Alfaxalone can be used to enhance IM/SC sedation

• Alfaxalone does not replace dexmedetomidine; can replace ketamine in sedation protocols

• Link to alfaxalone quick reference: https://vetanesthesiaspecialists.com/for-vets/resources/

• Alfaxalone is a more expensive but great alternative to propofol. For the most part, you can look at alfaxalone as “clear” propofol. In the average premedicated patient the dose is 1-2 mg/kg depending on sedation level. Occasionally you will need more.

• Notable differences – occasional tachycardia, increased airway secretions may be observed, somewhat rough and vocal recoveries for short anesthetic procedures (under 45 min or so). If we get into the situation of limited propofol or propofol-28 supply, then we should be reserving propofol for quick/short procedures given the slightly better recovery quality in that situation.

• While ketamine remains an available induction drug, it isn’t recommended without coadministration of a benzodiazepine, and the cardiorespiratry effect of ketamine are quite different from propofol. Also, ketamine may go into shortage as well, so we should reserve it for use as a co-induction drug (for example: ketamine with propofol or alfaxalone) and as an analgesic infusion.

• Teletamine/zolazepam is a veterinary-only labeled product that can be used much like ketamine/diazepam

Remember Telazol? Did you know there's a generic version?

❖ Reserve benzodiazepines for seizure patients and sick/older patients

• Midazolam is crucial for use in our seizure patients as either bolus or infusion. When it comes to anesthesia, while it does reduce the dose of our induction agents, it is not particularly sedating in the vast majority of patients we anesthetize. Indeed, younger more healthy patients will often have a paradoxical excitement reaction to midazolam (or diazepam). For sicker and older patients, it can be useful as part of a neuroleptanalgesic protocol that minimizes the more cardiovascularly depressant drugs like propofol or alfaxalone.

• Diazepam can be used for seizure patients. However, if diazepam is needed for infusion, it should be administered through a central line due to vascular irritation and extravasation concerns.

❖ Replace dexmedetomidine with medetomidine

Dexmedetomidine currently available, but if not:

Medetomidine is the racemic mix version and still available (MWI has it and there are other sources). Dosing is approximately double what we use for dexmedetomidine.

❖ If ketamine becomes unavailable:

• The only real substitute for ketamine is Telazol (Tiletamine and Zolazepam) which is generally not an optimal drug for use in the majority of veterinary patients because of higher expense, inability to use as an analgesic infusion, longer duration of action and poor quality of recovery.

❖ Reduce reliance on pressors & inotropes

• Anesthetic hypotension is almost always inhalant-induced dose-dependent vasodilation & cardiovascular depression

• Reduce inhalant requirements! especially for patients at risk of low blood pressure

• Pre- & intra-operative analgesia & sedation

• Balanced anesthetic techniques

• Support normal heart rate & rhythm

• Save pressors & inotropes for the patients that really need them; dilute in a syringe; gain experience with ephedrine as this medication is typically veterinary-only

• Resources for treatment of hypotension: Veterinary Anesthesia Update online

• https://www.mynavas.org/post/a-quick-guide-to-hypotension-during-anesthesia

❖ Veterinarians may receive direct requests for medications and supplies

• Some requests come from the veterinary medical board & local/state/regional health departments; other requests may come from a hospital representative

• Trust but verify