Informational

Anesthesia and Analgesia Drug Descriptions

Unit for Laboratory Animal Medicine
Jun 15, 2017 12:00 am
  • Glossary Definitions

    Hypnosis

    Artificially induced sleep induced by central nervous system (CNS) depression.

    Local Analgesia

    A loss of sensation in a restricted body area creating a local area of analgesia.

    Sedation

    Central depression causing stupor where the animal is unaware of its surroundings but still responsive to painful procedures.

  • Anesthetic Inhalants

    1. Inhalation Agents

    Inhalation agents enable the anesthetist to precisely control the depth of anesthesia. They are the drugs of choice for procedures lasting longer than 30 minutes or for major surgical procedures. They can be delivered by mask, endotracheal tube, or in a secure container. Endotracheal tubes are the safest and preferred method.  In larger species, it is preferable to induce anesthesia using an injectable agent and then maintain anesthesia using an inhalational agent.  The provision of effective gas scavenging is also essential.

    1. Isoflurane (Recommended)
      1. The most commonly used inhalation agent for all species. Some advantages of this agent are its short onset of action and recovery times. It does not sensitize the heart to catecholamine induced arrhythmias and it produces less myocardial depression than some other inhalation agents.
    2. Nitrous Oxide(NO2)
      1. Nitrous oxide causes limited cardiovascular, limited respiratory system depression, and minimal toxicity. However, it is not a potent anesthetic and cannot be used alone to anesthetize healthy animals. NO2 can be used to enhance the effects of other inhalants when used in combination.  Following the cessation of prolonged nitrous oxide administration, 100% oxygen should be administered to prevent diffusion hypoxia.
    3. Sevoflurane
      1. Inhalation anesthetic similar to isoflurane.  Sevoflurane is better tolerated than other inhalational agents.  Sevoflurane has a very low blood/gas partition coefficient (0.6) allowing very rapid anesthesia induction and recovery. Because of the extremely rapid recovery associated with sevoflurane, use caution (and appropriate sedation) during the recovery phase. Sevoflurane can react with carbon dioxide absorbents to produce "compound A", a nephrotoxin, unless an oxygen flow rate of at least 1 liter per minute is used.
  • Anesthetic & Sedative Injectables

    1. Anticholinergics

    Anticholinergics are parasympatholytic drugs especially affecting the cardiovascular and gastrointestinal systems. They are given pre-surgically to reduce bronchial and salivary secretions. These drugs are commonly used to treat bradycardia secondary to other anesthetics such as opioids. Anticholinergics can cause sinus tachycardia complicating previous cardiovascular disease and should be avoided in conjunction with ketamine as infarcts have been described. These drugs can also reduce tone of the esophageal sphincter leading to increased incidences of reflux and esophagitis.

    1. Atropine
      1. Atropine is rapidly absorbed with intramuscular administration and cardiovascular changes can be seen within 5 minutes. The duration of action is typically 45 minutes to an hour. Atropine is not recommended for animals with glaucoma or suspected increased intraocular pressure due to its ability to block drainage from the anterior chamber.  Avoid the use of atropine if the heart rate is already elevated. Atropine is rapidly metabolized in some strains of rabbits so its effects may be unpredictable in this species.  Atropine can be administered SC, IM, and IV; but IM and IV are more reliable in uptake timing.
    2. Glycopyrrolate
      1. The onset of action of Glycopyrrolate is similar to Atropine; however, the duration is longer at 4 hours and it does not cross the blood-brain barrier. Glycopyrrolate is a safer alternative for patients with increased intraocular pressure and has less sinus tachycardia associated with it. Glycopyrrolate can also be given SC, IM, and IV.

    2. Barbiturates

    Barbiturates cause depression of CNS by acting directly on neurons similar to inhibitory transmitter GABA. All barbiturates are controlled substances. Anesthetic doses cause respiratory depression and cardiac depression. A significant fall in blood pressure can be seen. The termination of effect seen from barbiturates at anesthetic does is determined by physical redistribution. If a barbiturate is given perivascularly, tissue necrosis and sloughing can occur.

    1. Methohexital
      1. Methohexital is an ultra-short action and half of the estimated dose should be injected quickly with the rest administered to effect due to increased likelihood of respiratory arrest. Recovery is quick but animals may be prone to muscle spasms and violent excitement.  This agent is now rarely used as an anesthetic.
    2. Pentobarbital
      1. Pentobarbital is an injectable general anesthetic agent that for the most part has been replaced by the inhalation agents. It provides excellent muscle relaxation and analgesia sufficient for major surgical procedures. Pentobarbital does have some significant disadvantages. Severe respiratory depression occurs at high doses and depth of anesthesia is very difficult to control. Recovery from pentobarbital anesthesia can be very prolonged. This drug is generally not recommended for painful surgeries due to poor analgesic activity.  It can be useful for neurosurgical procedures, imaging studies such as MRI, or non-survival procedures.

    3. Dissociatives

    Dissociatives work by disrupting signals from the brain responsible for conscious functions. This produces a cataleptoid state in which the swallowing reflex remains intact and the eyes remain open. Generally, it is recommended to use a sedative or muscle relaxant concurrently to counteract skeletal muscle hypertonia.

    1. Ketamine
      1. Ketamine is a very common agent used for chemical restraint of a wide range of animals. It has a wide margin of safety and can be used alone or in combination with other drugs. If used alone, Ketamine produces immobility and some analgesia. The analgesia is more effective for somatic pain than visceral. It can also cause muscle contractions, tremors, and excess salivation. It can be used effectively for chemical restraint and short non-invasive procedures. Laryngeal, pharyngeal, and corneal reflexes will be preserved.   Consequently, ketamine used alone is insufficient for endotracheal intubation, complete immobilization, or performing surgical procedures. Seizures can occur in animals predisposed to epilepsy or other seizure disorders.  Salivary secretions are increased and airway obstruction remains a significant hazard. In all species, it may be necessary to use atropine or glycopyrrolate together with ketamine to reduce these otherwise excessive bronchial and salivary secretions.  
    2. Ketamine/Xylazine
      1. This combination is highly recommended for short term well balanced anesthesia. The xylazine prevents muscle contractions seen with ketamine and complete immobilization with a moderate amount of analgesia is provided. If longer anesthetic time is required, additional administration of ketamine at 1/3 original dose can be used. Additional doses of xylazine should be avoided due to the hypotensive affects. Side effects of the combination include bradycardia and hypotension.
    3. Telazol® (Tiletamine-Zolazepam)
      1. Telazol® is a combination of the dissociative tiletamine and the benzodiazepine zolazepam. Due to the combination of benzodiazepine with the dissociative, seizures are rarely seen with Telazol®. Telazol® can be used for endotracheal intubation and minor surgical procedures. Hypothermia will result when used to induce general anesthesia. Telazol® only provides very mild somatic analgesia and cannot be used alone to provide pain relief for procedures that cause moderate to severe pain. The zolazepam portion of the combined drug can be reversed with the benzodiazepine antagonist flumazenil.

    4. Steroid Anesthetics

    1. Alfaxan® (Alphaxalone)
      1. This drug produces smooth induction of anesthesia following IV administration. Administration of repeated doses has little effect on recovery time. The agent is non-irritant, and accidental extravascular injection does not appear to be associated with any adverse effects. The drug is rapidly metabolized and an excellent agent for maintenance of long-term anesthesia, although moderate hypotension may occur. Although structurally related to the steroid hormones, alphaxalone has no significant endocrine effects.

    5. Misc. Injectables

    1. Tricaine Methanesulphone (MS222)
      1. Tricaine is used for induction and maintenance of anesthesia of a wide range of fish species. It is administered as a solution, by immersion; the concentration used determines the depth of anesthesia. The anesthetic solution should be buffered before use, using sodium bicarbonate.

    6. Local Anesthetics

    Local Anesthetics block sodium channels and block nerve conduction interrupting transmission in sensory tracts. They can be used for specific tissue infiltration, nerve blocks or as an epidural to reduce pain detection during surgery. Under certain circumstances, local anesthetics can be used to perform surgery on a local area in a conscious patient. When used in combination with a vasoconstrictor such as epinephrine, a prolonged anesthetic activity and increased intensity can be achieved. The epinephrine delays vascular absorption reducing potential toxicity due to higher blood concentrations. A maximum allowable dose must be calculated prior to use for each animal to prevent lethal overdose toxicities affecting the CNS and cardiovascular systems.

    Aspiration of the syringe to assure the needle is not in a vessel is very important, as intravenous injection of lidocaine or bupivacaine can result in non-resuscitatable cardiac arrest and death.

    1. Bupivicaine
      1. Bupivicaine has a slower onset of action when compared to lidocaine at 20-30 minutes. However, it has a longer duration of action of up to 4-5 hours. Pre-emptive use is excellent for pain prevention. The application must be administered 30 minutes before the procedure begins.
    2. Lidocaine
      1. Lidocaine has a fairly rapid onset at 10-15 minutes but has a shorter duration of action at 1-1.5 hours.
    3. 50:50 mixtures of Lidocaine and Bupivicaine
      1. Can provide a quicker onset of action coupled with a longer duration.

    7. Neuromuscular Blocking Agents

    Neuromuscular Blocking Agents are used as an adjunct to general anesthesia for the procedures requiring minimal movement, including ophthalmic studies. Neuromuscular blocking agents produce a level of enhanced muscle relaxation that cannot be achieved with anesthesia alone. Because these agents do not render the animal unconscious and therefore able to perceive pain, extreme care must be taken to ensure that a proper level of anesthesia and analgesia are achieved prior to administering a neuromuscular blocking agent. Parameters such as heart rate and blood pressure should be monitored throughout the procedure to make sure that adequate anesthesia and analgesia are maintained. It is essential that all animals receiving neuromuscular blocking agents be placed on Intermittent Positive Pressure Ventilation (IPPV). In addition, a peripheral nerve stimulator is attached to the tibial or peroneal nerve of the hindlimb or ulnar nerve of the forelimb can be used to assess the inhibitors such as edrophonium, neostigmine, and pyridostigmine.

    1. Atracurium
      1. A short acting nondepolarizing NMBA with an onset of action around 5 minutes and duration of action approximately 30 minutes. Hepatic metabolism and renal excretion are not necessary so it can be administered safely in animals with hepatic or renal compromise. Continuous intravenous infusion can be used to maintain and repeated doses are not cumulative. Administration should be done slowly to prevent histamine release and secondary hypotension and tachycardia.
    2. Vecuronium
      1. Unlike atracurium, vecuronium does not induce tachycardia or histamine release. The onset of action and duration of action are similar to atracurium. Hepatic metabolism and renal excretion are required for this drug and animals with renal insufficiency may experience a prolonged duration of action.
    3. Pancuronium
      1. Pancuronium has an onset of action of 5 minutes and duration of action of 40-60 minutes. Most of the drug is excreted by the kidneys and the rest by hepatic metabolism. Animals with renal or hepatic insufficiency will have prolonged effects.

    8. Nonbarbiturates

    Nonbarbiturates are often used for short periods of anesthesia that provide rapid recovery. They are often used in combination with pre-anesthetics and analgesics to provide sufficient pain relief. Nonbarbiturates induce a hypnotic state.

    1. a-Chloralose
      1. A long-lasting (8-10 hours) hypnotic most often used for terminal procedures due to a prolonged recovery and involuntary excitement. Induction and recovery can be very prolonged and anesthetic state may not be sufficient for surgical procedures. Due to the prolonged onset, a second induction agent, such as isoflurane, may be used. Chloralose is useful in cardiovascular studies because there is minimal cardiovascular depression.
    2. Chloral Hydrate
      1. A hypnotic that depresses the cerebrum causing depression of reflex excitability. It is considered a poor anesthetic and amounts required to produce anesthetic states are similar to minimum lethal doses. Hypotension and depressed respiration can be seen. It may be administered orally, IV, or IP; however, gastric mucosa irritation and vomiting will occur if not diluted in water.
    3. Propofol
      1. A highly lipophilic anesthetic providing very rapid induction and smooth rapid recovery. When used for anesthesia, a constant rate infusion or rapid bolus series must be used to maintain an anesthetic state. There is a high incidence of apnea resulting in cyanosis when propofol is given too rapidly. It is recommended to titrate the dose to effect by giving 25% of the calculated dose every 30 seconds until unconsciousness is achieved.
      2. Propofol is supplied in two formulations, the original macroemulsion which is a single dose vial (SDV) and a microemulsion which is a multiple dose vial (MDV). Due to the lipophilic state, SDV propofol can encourage bacterial growth, therefore the unused SDV propofol must be discarded within 6 hours after opening. The MDV propofol must be discarded 28 days after opening.
    4. Tribromoethanol
      1. A hypnotic with very short acting anesthetic effects in rats and mice. Duration is only 15-20 minutes and should only be considered for short procedures. Intraperitoneal administration can cause peritonitis and adhesions after repeated dosing. No analgesic effect is seen and a secondary analgesic is recommended. When not stored in proper conditions, toxic byproducts can be produced leading to hepatotoxicity or nephrotoxicity.

    9. Sedatives

    Sedatives cause a state of central depression with drowsiness. While in this state, animals are not aware of its surroundings; however, they are still responsive to painful stimuli. There are several classes of sedatives and behavioral responses can vary between the classes and for different species. Phenothiazines and a2-agonists are effective in dogs and cats but not so in swine. Benzodiazepines are effective in ferrets, rabbits, and swine but not reliable in cats and young dogs. Reference the species-specific anesthesia and analgesia guidelines for correct use and dosing.

    1. Benzodiazepines: Can be reversed with benzodiazepine antagonist Flumazenil. Enhance binding of inhibitory neurotransmitter GABA.
      1. Diazepam (Valium®) is the most widely used benzodiazepine. It is insoluble and should not be mixed with other drugs. Diazepam is not a reliable sedative but is a good muscle relaxant and anticonvulsant in most species. The intramuscular route is very irritating and poorly absorbed. The intravascular route should be given slowly to avoid cardiotoxic and thrombophlebitis effects.
      2. Midazolam produces excellent sedation and muscle relaxation in small mammals such as ferrets and rabbits as well as in swine and birds. Unlike diazepam midazolam is absorbed well IM and is not irritating. Administration of midazolam produces minimal cardiopulmonary effects.
    2. Phenothiazines: Block dopamine receptors to decrease spontaneous motor activity.
      1. Acepromazine is a very widely used sedative in animals and provides sedation at low doses. Acepromazine produces some muscle relaxation but provides no pain relief. Side effects include vasodilation and hypotension. It should not be given with drugs that lower the seizure threshold.
    3. a2-Agonists: Reversible with selective antagonists.
      1. Dexmedetomidine has selectivity for alpha receptors nearly 1000 times that of xylazine. Can produce a decrease in respiratory rate and heart rate secondary to hypertension. Prolonged use can create hypotension after primary hypertension. If severe adverse reactions are observed, can be reversed with atipamezole.
      2. Xylazine is often used in combination with Ketamine to counteract the muscular hypertonicity often seen as a side effect. Xylazine also has very wide ranging dosing requirements for each species and care must be taken when using with ruminants due to the very potent activity seen. Decreased heart rate and respiratory rate can be seen with xylazine and the myocardium is sensitized to epinephrine induce arrhythmias. The bradycardia is a normal physiologic response to induced hypertension. Xylazine is reversible with atipamezole or yohimbine.
  • Analgesics

    1. NSAIDS (Nonsteroidal Anti-Inflammatory Drugs)

    NSAIDS (Nonsteroidal Anti-Inflammatory Drugs) work by inhibiting cyclooxygenase activity and subsequently preventing prostaglandin synthesis. NSAIDs are effective for pain induced by inflammation; however, they are not sufficient alone to relieve severe and acute pain, which includes postoperative pain. Prolonged NSAID use can cause gastric ulceration and renal disease so ULAM veterinary consultation is recommended in instances NSAID use is needed over 3 days. Also, NSAIDs should never be given in conjunction with steroids because severe adverse reactions can result, including severe gastric erosion.

    1. Carprofen (Rimadyl®)
      1. Carprofen differs from other NSAIDs in that it is a weak inhibitor of cyclooxygenase activity and exerts only a weak influence on prostaglandin E2. This suggests a spinal or central mechanism of action may be responsible for the strong analgesic effects. Carprofen can provide effective post-surgical pain relief.  Studies have shown minimal to no antithrombin activity. Carprofen is available in oral and injectable form and can be dosed in 12 or 24 hour increments.
    2. Flunixin Meglumine (Banamine®)
      1. Banamine is most often used in large animals such as horses and ruminants. It is not FDA approved for use in dogs in the United States.  The most significant problem reported has been nephrotoxicity when administered with a nephrotoxic agent or when renal blood flow was likely compromised. More recently developed NSAIDs should be used when practicable.
    3. Ketoprofen (Orudis®, Oruvail®)
      1. Ketoprofen is an inhibitor of both COX-1 and COX-2 so adverse effects can be more problematic. It should not be used in animals with a high risk of hemorrhage. Ketoprofen can provide excellent analgesia for even severe pain and is available for IV, IM or SQ injection.
    4. Meloxicam (Metacam®)
      1. Meloxicam has a COX-2 specific mechanism of action and is consider a safer NSAID. More common adverse reactions involve the gastrointestinal tract. It is effective against mild to moderate pain, and the palatable oral preparation makes it particularly useful when additional doses of drugs are required.  Studies have shown minimal to no antithrombin activity. Meloxicam can be dosed every 12 or 24 hours and is available in oral and injectable forms.
    5. Phenybutazone (Butazolidin®m "Bute")
      1. Phenybutazone is approved for ruminants, horses and dogs. However, Phenybutazone is not recommended for dogs due to the availability of safer NSAIDs for this species. In ruminants, it has a prolonged duration of action and can be dosed every 24 to 48 hours.

    2. Opioids

    Opioids create an analgesic state by inhibiting pain pathways centrally rather than peripherally like NSAIDs. They decrease perception of pain by acting in the mesolimbic system and midbrain. Collectively they also induce a mild state of CNS depression along with varying degrees of hypothermia, decreased heart rate, and respiratory depression. Excitatory effects can happen but are uncommon and can be prevented by administering with a sedative. Opioids can cause vomiting in some animal species, notably in non-human primates and dogs. Apart from causing vomiting, opioids may delay gastric emptying, increase intestinal peristalsis and cause spasm of the biliary tract. These effects may preclude the use of opioids in certain experimental procedures, but generally, the effects are of minimal clinical significance.  Opioids are commonly used in combination with other pre-anesthetic agents such as Ketamine and Xylazine to produce a well-balanced induction combination. In the event of severe reactions, accidental overdose or prolonged recovery, opioids can be reversed by using Naloxone. However, Naloxone's effects are shorter in duration than many opioids' so close monitoring of the patient is needed.

    1. Buprenorphine
      1. Different from other opioids in that it is a partial agonist of µ receptors. This causes a delay in activity and should be initiated prior to painful stimulation as it can take 1 hour to fully reach peak effects after IM administration. Although it is a partial agonist, the affinity for the receptors is quite high and reversal with Naloxone is not as effective as with other opioids.  Buprenorphine has been reported to cause pica (eating of bedding) in rats.  Buprenorphine is considered an excellent analgesic for mild to moderate pain and is highly recommended. However, severely painful procedures such as invasive orthopedic procedures or thoracotomies should have secondary analgesics.
    2. Butorphanol
      1. Butorphanol is labeled an agonist of K receptors and an antagonist of µ receptors. The duration of action is very short at 1 hour and is administered IM, SQ or IV. It is considered good for mild to moderate pain and can induce mild sedation. It is often used in combination with sedatives to produce pain relief and good sedation for short minimally painful procedures. Butorphanol can cause a dramatic decrease in heart rate so monitoring parameters should be established before use.
    3. Fentanyl
      1. Also a µ agonist with a more rapid onset and decrease duration time than morphine. Peak analgesia is usually achieved in 5 minutes and lasts 30 minutes. There is excellent cardiovascular stability and fentanyl but bradycardia can be seen with IV bolus and anticholinergics can be used in correct it. Fentanyl is a good choice for severely painful procedures but must be administered as a continuous rate infusion IV or in the form of a transdermal patch. The patch may have varying drug concentrations depending on the species. It is highly recommended exam gloves be worn while handling the patch and to label the patch and/or site with the date and time of application.
    4. Morphine
      1. A full agonist at the µ, K and d receptors. Because of this, morphine is considered one of the most effective analgesics for even severe pain. It is inexpensive and can be administered SQ, IM, IV or as an epidural. Duration of action is only 3-4 hours unless given in the epidural space, which increases the duration to 12 to 24 hours. There is a dose dependent sedation associated with morphine and side effects include decreased heart rate, decreased respiratory rate and nausea. If administering as a preanesthetic cocktail, care must be taken to ensure there is not any aspiration of stomach contents due to the patient vomiting from nausea.
    5. Oxymorphone
      1. Also a full agonist at µ receptors and is similar in efficacy to morphine. The duration of action if longer at 6-8 hours and can be administered IM or SQ. It is less likely to cause vomiting but will increase panting. There is also a dose dependent sedation and decrease heart rate seen with Oxymorphone.
    6. Tramadol
      1. Codeine analog with weak µ receptor activity. Along with its opioid activity, it also affects central catecholamine pathways. This makes it effective for acute or chronic pain of moderately severe intensity including neuropathic pain and osteoarthritis. Tramadol should not be used in animals on studies using monoamineoxidase inhibitors or in animals with seizure histories.
  • References

    1. William J. Tranquilli, John C. Thermon, and Kurt A. Grimm. Lumb & Jones' Veterinary Anesthesia and Analgesia, 4th ed. (Wiley-Blackwell, 2007).
    2. Donald C. Plumb, Plumb's Veterinary Drug Handbook, Desk Edition, 5th ed. (Wiley-Blackwell, 2005).
Questions?

If you have questions or comments about this document, contact ULAM Veterinary Staff (ULAM-vets@umich.edu or 734-936-1696).