Euthanasia Drugs; Administration rates matter

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If euthanasia becomes necessary to relieve suffering, it should be handled with respect and skill. The speed at which euthanasia solution is administered effects two main things; potential pain and active signs of death. For the most part, veterinarians are taught to inject quickly but it turns out this is only correct part of the time. Depending on the presence or absence of pre-euthanasia drugs and where in the body the injection is occurring, a fast injection may lead to adverse events. The Companion Animal Euthanasia Training Academy (CAETA) teaches how to reduce pain and active signs of dying through proper euthanasia drug administration rates.

There are only a few types of euthanasia solutions used in veterinary medicine. Depending on which country you live in, euthanasia practitioners may reach for pentobarbital, embutramide-combo drugs (T61), potassium chloride, or magnesium sulfate. Of these 4, only pentobarbital is allowed to be given when the patient is awake/conscious. The rest require unconsciousness.

The typical rate of administration of pentobarbital (an anesthetic) in awake patients is 1ml per second via an intravenous (IV) injection. This ensures rapid uptake of the drug to the brain where death is facilitated. Administer too slowly and patients may exhibit dysphoria and other negative effects like paddling and vocalization, often seen in stage 2 anesthesia. This is because they are moving too slowly through the 4 stages of anesthesia before death is reached.

Stages of Anesthesia
~Stage 1 – induction, voluntary actions remain
~Stage 2 – involuntary actions
~Stage 3 – surgical depth
~Stage 4 – overdose and death

In pet patients that are heavily sedated with pre-euthanasia drugs like alpha-2 agonists, opioids, benzodiazepines, and phenothiazines, they are not necessarily anesthetized and unconscious, but can be in a very deep state of sleep depending on the dosage given. Anecdotal findings show that administering pentobarbital at the same rate as awake patients of 1ml per second IV leads to increased active signs of death; agonal breathing, opisthotonus stretching, muscle fasciculations, and urination/defecation. Decreasing the rate of pentobarbital injection to 0.1ml per second has shown effectiveness at reducing these signs.

This is presumidley due to the induction of anesthesia by the pentobarbital before overdosing is achieved. When patients receive pre-euthanasia anesthetics such as alfaxalone, ketamine or propofol to place the patient in stage 3 surgical depth of anesthesia before death, active signs of death decrease. In other words, pet patients who are anesthetized either via pre-euthanasia drugs or through slower administration of pentobarbital to pre-sedated patients tend to pass more smoothly.

Quick Tips for IV Pentobarbital Injection Rates
~Awake = 1ml per second
~Under light sedation = 1ml per second
~Under heavy sedation = 0.1ml per second
~Anesthetized = either rate

Pentobarbital can also be given through intraorgan injections in anesthetized or unconscious patients. The heart, liver, and kidneys are common locations in smaller animals due to the high blood perfusion in the organ tissue. While there are no studied administration rates for intraorgan euthanasia injections, CAETA recommends starting with a very small amount (0.1-0.5ml) to test for pain response. If no response is observed, the rest may be given to achieve death. Pentobarbital is a caustic agent leading to potential pain in organ tissue, and why unconsciousness is required before intraorgan injections. Giving too much too quickly to a patient who appears unconscious but is not has led to some significant pain responses like vocalization and writhing in discomfort.

Non-pentobarbital euthanasia solutions such as T61, potassium chloride or magnesium sulfate require very rapid administration rates. The patient must first be rendered unconscious to avoid pain or distress during injections. These solutions are uncommon in companion animal euthanasia in the United States, but during the pentobarbital shortage experienced in 2021, their use briefly increased.

References:

https://www.cliniciansbrief.com/article/euthanasia-protocols

https://www.ncbi.nlm.nih.gov/books/NBK557596/

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Dr. Kathleen Cooney

DVM, CHPV, CPEV, DACAW resident Founder, Senior Director of Education for the Companion Animal Euthanasia Training Academy