By Kris T. Kruse-Elliott, DVM, PhD, DACVAA • Dechra Veterinary Products

Successful procedural sedation that optimizes drug and dose selection specific to the patient results in a better experience for both patients and staff. Most hospitals carry a limited number of injectable drugs for sedation in dogs. With appropriate selection of drugs and drug combinations, you should be able to create the depth of sedation needed for the patient and the procedure. Familiarity with the drugs you have allows you to be creative in application while maintaining safety and effectiveness. In the discussion and examples below, we’ll discuss simple variations on the intramuscular use of the common sedation drugs acepromazine, alpha-2 agonists, and butorphanol that yield the range of sedation from mild to moderate to deep and a few pros and cons of each drug.

Sedation encompasses a spectrum from the awake patient to the fully anesthetized patient. The need for mild, moderate or deep sedation depends on patient and procedure. Planning for sedation is no different than planning for general anesthesia – know your patient history, do a thorough physical exam, and perform indicated diagnostics. The line between heavy sedation and general anesthesia is quite blurry and many deeply sedated patients are very near to being anesthetized. All sedated patients deserve monitoring of cardiorespiratory function similar to an anesthetized patient and supplemental oxygen whenever possible. This is especially true when the plan is to deeply sedate a patient. Your sedation plan should also include how you will manage recovery and discharge following procedural sedation.

Acepromazine and alpha-2 agonists are commonly used sedatives. These are used as the sole agent, or for greater effect, they may be combined with an opioid and/or ketamine. Acepromazine is an old drug providing relatively predictable sedation that is synergistic when it is combined with opioids. However, it may not be adequate in fractious or overly anxious patients, has a slower onset of action and a long (4-6 hour) duration of action, and is not reversible. The duration of action and potential for inadequate sedation tend to limit acepromazine to situations where only mild sedation is needed.

Alpha-2 agonists (medetomidine and dexmedetomidine) offer a consistent and reliable combination of sedation, anxiolysis, and analgesia. The ability to reverse alpha-2 agonists may help allow for a more predictable duration of sedation. Cardiovascular side effects of alpha-2 agonists limits their use to healthy, exercise-tolerant patients. The initial hypertension and reflex bradycardia keeps many from fully adopting alpha-2 agonists. Alpha-2 agonist induced hypertension is dose-related and greater with IV administration. Elevating the heart rate with an anticholinergic in a hypertensive patient places additional stress on the myocardium and is not recommended. After 30-45 minutes bradycardia often remains with normal or low blood pressure, at which point an anticholinergic may be administered. While effective for sedation, anxiolysis, and analgesia, it is unfortunate that alpha-2 side effects are a deterrent to use in appropriate patients.

Recently, a new alpha-2 formulation, Zenalpha® (medetomidine and vatinoxan hydrochlorides), has become available. Zenalpha® is a combination of the peripherally acting alpha-2 antagonist, vatinoxan with medetomidine. Addition of vatinoxan reduces hypertension and bradycardia while maintaining the desirable sedation qualities of medetomidine. For those who are not comfortable with the usual alpha-2 agonist-induced cardiovascular side effects, it is worth exploring this new drug combination. Quick onset of action and recovery make this combination particularly useful for short procedural sedation. Zenalpha® is for use in dogs only and is not intended for use in cats. Zenalpha® should not be administered in the presence of pre-existing hypotension, hypoxia or bradycardia.

When building a sedation plan with acepromazine or an alpha-2 agonist determine if you are aiming for mild, moderate, or deep sedation and then add appropriate drugs from there. For mild sedation, think acepromazine (0.01-0.02 mg/kg) either alone or in combination with an opioid. Butorphanol (0.2-0.4 mg/kg) is a common and effective addition to acepromazine for mild sedation. The goal is mild central nervous system depression with reduced anxiety and excitement.

Moderate levels of sedation are required for procedures like radiographs, ultrasound, and aspirates of superficial masses and usually requires more than just acepromazine and butorphanol. Beyond mild sedation, alpha-2 agonists become the foundation of procedural sedation protocols. You may accomplish moderate procedural sedation with just dexmedetomidine (2-10 mcg/kg) or Zenalpha® (see package insert for dosing) alone. For more anxious or active dogs, consider adding an opioid to your sedation plan for improved quality of sedation as a more multimodal approach to both sedation and analgesia. As you move to moderate levels of sedation it is important to monitor cardiorespiratory function and provide supplemental oxygen via facemask until the patient is recovered.

Deep sedation is often needed to accomplish longer procedures or those that may be more painful or stimulating but does approach general anesthesia. Monitoring cardiorespiratory function and supplemental oxygen are critically important when using deep sedation levels since these patients are closer to the cardiorespiratory depression observed with general anesthesia. Occasionally, deep sedation is also required for relatively simple and non-invasive procedures in very fractious dogs where staff safety would otherwise be compromised. In that scenario, monitoring closely is particularly important given that a physical exam was likely not accomplished due to the behavioral challenges. To accomplish deep sedation, you will build on the moderate sedation protocol by increasing the dose of dexmedetomidine to 10 mcg/kg with the higher butorphanol dose of 0.4 mg/kg but also consider if that will be adequate for the patient and procedure. You may need to add ketamine at 2-5 mg/kg to this combination in particularly challenging patients and it is best to make that determination at the start as opposed to chasing sedation in your patient. Also, keep in mind that with this combination of drugs, you are now bordering on general anesthesia, and if you find you can intubate, then you absolutely should intubate!

Successful procedural sedation occurs when you optimize drug and dose selection to match the patient and procedure. You don’t need an entire catalog of drugs, but you should have certain options available that can be readily modified to meet the occasion. Acepromazine, alpha-2 agonists, an opioid, and perhaps ketamine are enough to allow flexible planning and options. Become familiar with the drugs you choose to use and how you can alter the dose and combine them to get the level of sedation you need. As always, familiarity with the drugs means you generally know what to expect for side effects and can more safely and effectively accomplish the procedure. 

Select references for further reading:

• Murrell JC and Hellebrekers LJ. Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Veterinary Anaesthesia and Analgesia, 2005:117-127.
• Lemke KA. Perioperative use of selective alpha-2 agonists and antagonists in small animals. Canadian Veterinary Journal, 2004:475-480.
• Joerger FB, Wieser ML, Steblaj B et al. Evaluation of cardiovascular effect of intramuscular medetomidine and a medetomidine-vatinoxan combination in beagle dogs: a randomized blinded crossover laboratory study. Veterinary Anaesthesia and Analgesia, 2023:397-407.

Zenalpha® Important Safety Information

As with all drugs, side effects may occur. For use in dogs only. Not intended for use in cats. Not for use in humans. Avoid skin, eye or mucosal contact. In case of accidental oral intake or self-injection, seek medical advice immediately and show the package insert to the physician. DO NOT DRIVE as sedation, loss of consciousness, and changes in blood pressure may occur. People with cardiovascular disease and pregnant women should exercise special caution to avoid exposure. Uterine contractions and decreased fetal blood pressure may occur after accidental systemic exposure. As with all alpha-2 adrenoceptor agonists, onset of sedation may be delayed or may be inadequate in some dogs. Do not use Zenalpha in dogs with cardiac disease, respiratory disorders, shock, severe debilitation, that have hypoglycemia or are at risk of developing hypoglycemia, or are stressed due to extreme heat, cold or fatigue. Zenalpha should not be administered in the presence of pre-existing hypotension, hypoxia or bradycardia. Due to the pronounced cardiovascular effects of alpha-2 adrenoceptor agonists, only clinically healthy dogs (American Society of Anesthesiologists [ASA] classes I and II) should be administered Zenalpha. Dogs should be monitored frequently during sedation for changes in heart rate, blood pressure, respiratory rate and body temperature. Tachycardia may occur in some dogs after recovery from sedation. The following adverse reactions have been reported: diarrhea, muscle tremors and colitis. Refer to the prescribing information for complete details or visit www.dechra-us.com.

Zenalpha is a registered trademark of Dechra Limited; all rights reserved.

By Kris T. Kruse-Elliott, DVM, PhD, DACVAA • Dechra Veterinary Products

Successful procedural sedation that optimizes drug and dose selection specific to the patient results in a better experience for both patients and staff. Most hospitals carry a limited number of injectable drugs for sedation in dogs. With appropriate selection of drugs and drug combinations, you should be able to create the depth of sedation needed for the patient and the procedure. Familiarity with the drugs you have allows you to be creative in application while maintaining safety and effectiveness. In the discussion and examples below, we’ll discuss simple variations on the intramuscular use of the common sedation drugs acepromazine, alpha-2 agonists, and butorphanol that yield the range of sedation from mild to moderate to deep and a few pros and cons of each drug.

Sedation encompasses a spectrum from the awake patient to the fully anesthetized patient. The need for mild, moderate or deep sedation depends on patient and procedure. Planning for sedation is no different than planning for general anesthesia – know your patient history, do a thorough physical exam, and perform indicated diagnostics. The line between heavy sedation and general anesthesia is quite blurry and many deeply sedated patients are very near to being anesthetized. All sedated patients deserve monitoring of cardiorespiratory function similar to an anesthetized patient and supplemental oxygen whenever possible. This is especially true when the plan is to deeply sedate a patient. Your sedation plan should also include how you will manage recovery and discharge following procedural sedation.

Acepromazine and alpha-2 agonists are commonly used sedatives. These are used as the sole agent, or for greater effect, they may be combined with an opioid and/or ketamine. Acepromazine is an old drug providing relatively predictable sedation that is synergistic when it is combined with opioids. However, it may not be adequate in fractious or overly anxious patients, has a slower onset of action and a long (4-6 hour) duration of action, and is not reversible. The duration of action and potential for inadequate sedation tend to limit acepromazine to situations where only mild sedation is needed.

Alpha-2 agonists (medetomidine and dexmedetomidine) offer a consistent and reliable combination of sedation, anxiolysis, and analgesia. The ability to reverse alpha-2 agonists may help allow for a more predictable duration of sedation. Cardiovascular side effects of alpha-2 agonists limits their use to healthy, exercise-tolerant patients. The initial hypertension and reflex bradycardia keeps many from fully adopting alpha-2 agonists. Alpha-2 agonist induced hypertension is dose-related and greater with IV administration. Elevating the heart rate with an anticholinergic in a hypertensive patient places additional stress on the myocardium and is not recommended. After 30-45 minutes bradycardia often remains with normal or low blood pressure, at which point an anticholinergic may be administered. While effective for sedation, anxiolysis, and analgesia, it is unfortunate that alpha-2 side effects are a deterrent to use in appropriate patients.

Recently, a new alpha-2 formulation, Zenalpha® (medetomidine and vatinoxan hydrochlorides), has become available. Zenalpha® is a combination of the peripherally acting alpha-2 antagonist, vatinoxan with medetomidine. Addition of vatinoxan reduces hypertension and bradycardia while maintaining the desirable sedation qualities of medetomidine. For those who are not comfortable with the usual alpha-2 agonist-induced cardiovascular side effects, it is worth exploring this new drug combination. Quick onset of action and recovery make this combination particularly useful for short procedural sedation. Zenalpha® is for use in dogs only and is not intended for use in cats. Zenalpha® should not be administered in the presence of pre-existing hypotension, hypoxia or bradycardia.

When building a sedation plan with acepromazine or an alpha-2 agonist determine if you are aiming for mild, moderate, or deep sedation and then add appropriate drugs from there. For mild sedation, think acepromazine (0.01-0.02 mg/kg) either alone or in combination with an opioid. Butorphanol (0.2-0.4 mg/kg) is a common and effective addition to acepromazine for mild sedation. The goal is mild central nervous system depression with reduced anxiety and excitement.

Moderate levels of sedation are required for procedures like radiographs, ultrasound, and aspirates of superficial masses and usually requires more than just acepromazine and butorphanol. Beyond mild sedation, alpha-2 agonists become the foundation of procedural sedation protocols. You may accomplish moderate procedural sedation with just dexmedetomidine (2-10 mcg/kg) or Zenalpha® (see package insert for dosing) alone. For more anxious or active dogs, consider adding an opioid to your sedation plan for improved quality of sedation as a more multimodal approach to both sedation and analgesia. As you move to moderate levels of sedation it is important to monitor cardiorespiratory function and provide supplemental oxygen via facemask until the patient is recovered.

Deep sedation is often needed to accomplish longer procedures or those that may be more painful or stimulating but does approach general anesthesia. Monitoring cardiorespiratory function and supplemental oxygen are critically important when using deep sedation levels since these patients are closer to the cardiorespiratory depression observed with general anesthesia. Occasionally, deep sedation is also required for relatively simple and non-invasive procedures in very fractious dogs where staff safety would otherwise be compromised. In that scenario, monitoring closely is particularly important given that a physical exam was likely not accomplished due to the behavioral challenges. To accomplish deep sedation, you will build on the moderate sedation protocol by increasing the dose of dexmedetomidine to 10 mcg/kg with the higher butorphanol dose of 0.4 mg/kg but also consider if that will be adequate for the patient and procedure. You may need to add ketamine at 2-5 mg/kg to this combination in particularly challenging patients and it is best to make that determination at the start as opposed to chasing sedation in your patient. Also, keep in mind that with this combination of drugs, you are now bordering on general anesthesia, and if you find you can intubate, then you absolutely should intubate!

Successful procedural sedation occurs when you optimize drug and dose selection to match the patient and procedure. You don’t need an entire catalog of drugs, but you should have certain options available that can be readily modified to meet the occasion. Acepromazine, alpha-2 agonists, an opioid, and perhaps ketamine are enough to allow flexible planning and options. Become familiar with the drugs you choose to use and how you can alter the dose and combine them to get the level of sedation you need. As always, familiarity with the drugs means you generally know what to expect for side effects and can more safely and effectively accomplish the procedure. 

Select references for further reading:

• Murrell JC and Hellebrekers LJ. Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog. Veterinary Anaesthesia and Analgesia, 2005:117-127.
• Lemke KA. Perioperative use of selective alpha-2 agonists and antagonists in small animals. Canadian Veterinary Journal, 2004:475-480.
• Joerger FB, Wieser ML, Steblaj B et al. Evaluation of cardiovascular effect of intramuscular medetomidine and a medetomidine-vatinoxan combination in beagle dogs: a randomized blinded crossover laboratory study. Veterinary Anaesthesia and Analgesia, 2023:397-407.

Zenalpha® Important Safety Information

As with all drugs, side effects may occur. For use in dogs only. Not intended for use in cats. Not for use in humans. Avoid skin, eye or mucosal contact. In case of accidental oral intake or self-injection, seek medical advice immediately and show the package insert to the physician. DO NOT DRIVE as sedation, loss of consciousness, and changes in blood pressure may occur. People with cardiovascular disease and pregnant women should exercise special caution to avoid exposure. Uterine contractions and decreased fetal blood pressure may occur after accidental systemic exposure. As with all alpha-2 adrenoceptor agonists, onset of sedation may be delayed or may be inadequate in some dogs. Do not use Zenalpha in dogs with cardiac disease, respiratory disorders, shock, severe debilitation, that have hypoglycemia or are at risk of developing hypoglycemia, or are stressed due to extreme heat, cold or fatigue. Zenalpha should not be administered in the presence of pre-existing hypotension, hypoxia or bradycardia. Due to the pronounced cardiovascular effects of alpha-2 adrenoceptor agonists, only clinically healthy dogs (American Society of Anesthesiologists [ASA] classes I and II) should be administered Zenalpha. Dogs should be monitored frequently during sedation for changes in heart rate, blood pressure, respiratory rate and body temperature. Tachycardia may occur in some dogs after recovery from sedation. The following adverse reactions have been reported: diarrhea, muscle tremors and colitis. Refer to the prescribing information for complete details or visit www.dechra-us.com.

Zenalpha is a registered trademark of Dechra Limited; all rights reserved.