Anesthesia and Analgesia in Research Animals

Federal guidelines, the Animal Welfare Act (AWA)  and the Public Health Service Research Extension Act and the Guide for the Care and Use of Laboratory Animals (The Guide), require that procedures involving animals be conducted in a manner that avoids or minimizes discomfort, pain or distress. The Guide states:

The proper use of anesthetics, analgesics, and tranquilizers in research animals is an ethical and scientific imperative.   The selection of the most appropriate analgesic or anesthetic should reflect professional judgment as to which best meet clinical and humane requirements without compromising the scientific aspects of the research protocol”.

If a painful procedure must be conducted without the use of an anesthetic, analgesic, or tranquilizer – because such use would defeat the purpose of an experiment – the procedure must be approved by the committee [IACUC] and supervised directly by the responsible investigator. Muscle relaxants or paralytic drugs (e.g., succinylcholine or other curariform drugs) are not anesthetics. They must not be used alone for surgical restraint, although they can be used in conjunction with drugs known to produce adequate analgesia.

The following sections provide detailed information regarding the IACUC recommendations for the use of analgesics and anesthetics as well recommendations for acceptable agents and dose ranges.

1)    Overview

2)    Species-specific considerations

3)    Commonly used anesthetics and analgesics

4)    Species-specific anesthesia-analgesia formularies:


• Cat
• Chinchilla
• Ferret
• Gerbil
• Hamster
• Mouse
• Nonhuman primates
• Rabbit
• Rat
• Swine

1.    OVERVIEW: STANDARD OF CARE IN ANIMAL PAIN MANAGEMENT

Animal anesthesia, analgesia and pain management are crucial components of research involving animal subjects. The standard of care at Boston University is to prevent animal pain as far as possible and to treat animal pain whenever diagnosed. Exceptions to these principals are permitted only in the minority of protocols approved by the Institutional Animal Care and Use Committee (IACUC) is USDA Category E with adequate scientific justification.

Multi-modal anesthetic and analgesic regimens combine drugs from a variety of classes. They are designed to maximize the desired effects while minimizing those undesirable side effects that occur with over-reliance on a single agent.

Animals must be acclimated to their surroundings for several days prior to major procedures.  In all instances, animals must have been released from quarantine, or the acclimatization period as established by Boston University Animal Science Center (BU ASC) must be completed.

1.1.  The ideal anesthetic/analgesic regimen

The ideal anesthetic/analgesic regimen must balance several goals. It will:

  • Provide pre-emptive analgesia so that animal pain is already being treated as the general anesthetic is wearing off, to prevent sensitization (“ramp-up”) of pain sensory mechanisms, and to lower the overall amount of general anesthetic required for the procedure.
  • Provide a pre-procedural tranquilizer as appropriate for the species.
  • Include the administration of an anticholinergic to protect cardiovascular function during anesthesia.
  • Be precisely titratable to assure that animals receive adequate anesthesia to block pain sensation, to produce unconsciousness, and to produce immobility without experiencing hemodynamic instability or life-threatening anesthetic overdoses.
  • Not interfere with the study that the animals are on.
  • Not result in excessive undesirable post-operative side-effects.
  • Not cause pain or distress on induction or recovery.
  • Be compatible with available equipment and available medications.

Pre-emptive analgesia

To meet the first goal, BU ASC and IACUC advocate pre-emptive analgesia, using one or more of three drug classes 30 minutes prior to the start of surgery, or, if that is not practical, as soon as possible after the animal has been induced. The three classes of injectable drugs are:

  • opioid analgesics (such as buprenorphine or morphine);
  • non-steroidal anti-inflammatory drugs (such as carprofen, meloxicam, ibuprofen);
  • local/regional anesthetics (lidocaine, bupivacaine, proparacaine).

Pre-emptive use enhances pain management during the immediate post-surgical period. The disadvantages of this approach are that they add a pre-anesthetic injection that may be distressful to the animals.  To avoid this issue, it is acceptable to administer the pre-emptive analgesia as soon as the animal has been induced.  By the time the animal is aseptically prepared and moved to the operating table or area (in the case of rodents) and the surgeon makes the first incision, the pre-emptive analgesic, if administered intravenously (IV) or intraperitoneally (IP), will have had time to take effect.  Other possible drawbacks with the administration of pre-emptive analgesia is that anesthesia will be deepened and anesthetic doses may need to be reduced, anesthesia recovery may be delayed, and that some are Controlled Substances requiring special storage and records keeping.

Administration of a tranquilizer prior to induction

This may be considered when working with anxious or fractious animals, notably cats.  The administration of acepromazine together with an anticholinergic 30 minutes before induction may significantly reduce stress to both the the animal and the handler.  The animal should be kept in a quiet room while the medication takes effect.

Administration of an anticholinergic prior to or at the same time as induction of anesthesia

Atropine or glycopyrrolate is routinely administered to large animals undergoing general anesthesia.  Atropine is acceptable but glycopyrrolate is recommended due to the fact that it has a longer half life and fewer side effects than atropine.  The anticholinergic may be administered before induction to anesthesia but it is commonly administered at the same time as the animal is induced.  Atropine or glycopyrrolate prevent bradycardia and cardiac arrhythmias which are especially prone to occur if xylazine is part of the general anesthetic regimen; however, an anticholinergic is strongly recommended to be administered when isoflurane anesthesia is used as well.  While anticholinergics are not required or usually used in rodents, if there are any problems with the general anesthesia of using ketamine and an α2 agonist such as xylazine or medetomidine, it is strongly recommended, especially for longer procedures.

Be precisely titratable

Volatile anesthetics (isoflurane, sevoflurane) delivered via a precision vaporizer best meet this goal. Adjusting the inhaled percentage of anesthetic gas to deepen anesthesia is far safer than repeated redosing of injected drugs. Volatile anesthetics are easier to decrease as well, even compared to drugs for which there is an injectable antagonist or reversal agent. A major shortcoming of the inhalant anesthetic agents is the lack of residual analgesia once the vaporizer has been turned off.

The investigator should determine the best option for a particular study and include it in their proposal to the IACUC. Veterinary consultation is required when planning any potentially painful study.

1.2 Ophthalmic Ointment

Sterile ophthalmic ointment must be used anytime animals are anesthetized, to prevent corneal trauma.  If ketamine alone is used, as is common practice for chemical restraint of nonhuman primates, and the procedure is short, less than 30 minutes, then ophthalmic ointment may be omitted.  In all other cases it must be used.

1.3.  Preanesthesia fasting

Most animal species are routinely fasted overnight prior to undergoing anesthesia and surgery.  Food deprivation is done to prevent the vomiting and aspiration of gastric contents when anesthesia is induced.   In a laboratory animal setting, where staff may leave at 5 pm and the surgery may be scheduled for 9 am the next day, overnight fasting may be equivalent to 16 hours or longer.  The recommended time interval is at least 12 hours.  Feed deprivation is not recommended in rats and mice for two reasons:  First, because of their gastric anatomy, mice and rats are not able to vomit, thus making it unnecessary to withhold food.  Secondly, since mice and rats are nocturnal eaters, removing food overnight means that in effect the animal may not have eaten anything during the previous 24 hours.  Rabbits also do not vomit and are usually fed overnight prior to anesthesia and surgery; however, in some studies it may be advisable to fast them overnight.
IT IS NOT NECESSARY OR ADVISABLE TO WITHHOLD WATER BEFORE ANESTHESIA AND SURGERY IN ANY SPECIES.  IF WATER IS WITHHELD, IT SHOULD BE LIMITED TO ONE (1) HOUR.
Any deviations from these procedures must be stated in the protocol and approved by the IACUC.

1.4  Drug dosages and frequencies of administration

Drugs must be listed in the protocol with approximate dose ranges (e.g. 2.0-3.5 mg/kg) and routes of administration.  These are starting points which must be titrated up or down for the individual animal, or for the particular application (procedures conducted, animal age, health status and strain differences). When laboratory experience finds that recommended dose ranges are consistently too high or too low for the particular application, the veterinarian should be informed, and a protocol modification submitted to the Institutional Animal Care and Use Committee.

Anesthetics are always titrated to effect. It is not acceptable to conduct surgical procedures unless the animal is fully anesthetized.

Analgesic doses and frequencies are more difficult to gauge. Caution is required for overnight pain management. Most analgesics administered at 5 pm will not still be effective at 8 am the next morning. Newer, longer-lasting non-steroidal anti-inflammatory analgesics may have longer durations of action than available opioids; they are frequently co-administered with an opioid to combine potency of effect with duration of action. Another option for management of postoperative pain after major surgical procedures is the use of fentanyl patches.  These are applied to a shaved area of the skin usually on the back of the animal under where a bandage will be placed.  Morphine is administered pre-emptively and 4 hours and 8 hours later.  The fentanyl patch is fully active after 12 hours and lasts for approximately 72 hours, providing 3 days of post-operative pain relief.

1.5  Safe and effective animal anesthesia

Plans for intra- and post-operative monitoring must be included in the IACUC protocol application, and then practiced as written and according to IACUC guidelines.

Supplemental administration of warmed fluids (lactated ringers solution or isotonic saline) and maintenance of body temperature will improve anesthetic safety for the animals.

  1. 2.    Species-specific consideration

In general, smaller animals have higher metabolic rates and frequently require higher doses at more frequent intervals to achieve the desired effect. Species, strain and age differences often overshadow this general principle however. It is always best to start with a drug regimen developed in the species, age and strain with which the Principal Investigator is working, rather than extrapolate from one species to another. Also, when starting to use a new species or strain of animal, it is safer to administer the lower end of the dose range of parenteral anesthetics and analgesics.  More can then be administered as needed.  Safety and efficacy should thus be demonstrated in a pilot group of animals before a large-scale study is initiated.

2.1.  Mice

Dilution of injected drugs allows more precise dosing, may make some drugs less irritating when injected, and may facilitate absorption, but also may shorten the shelf-life of the compound.  Aseptic technique must be observed as mixtures (cocktails) are prepared; this includes wiping the cover of each vial or bottle with 70% ethanol or isopropanol, diluting with sterile water or sterile saline and not reusing needles used for dilution or administration.  Only new, sterile needles must be used for withdrawing aliquots from the cocktail.  Diluted drugs must be labeled with the contents and concentration of the dilution, the preparer’s name or initials, and dated, then discarded after 1 month, at the expiration date of any of the components, or as indicated by the manufacturer.

Isoflurane is encouraged as the first choice anesthetic in mice. It should be delivered as a known percentage (1-3% for maintenance; up to 5% for induction) in oxygen from a precision vaporizer or nose cone. See: Inhalant Anesthetics

Anesthetic monitoring of small rodents includes testing of rear foot reflexes before any incision is made, and continual observation of respiratory pattern, mucous membrane color and responsiveness to manipulations throughout the procedure. It is recommended that rectal temperature and heart rate are monitored electronically if possible during long or involved procedures.  Monitor the rodent continually, documenting findings every 15 minutes on the Rodent Surgical Record and note the following:

Toe pinch method:  The toe pinch method to evaluate depth of anesthesia is useful but not enough in itself.  One must use two fingers and give the toe/foot a good squeeze.  If there is no withdrawal reaction, the animal is judged deep enough to commence surgery.  Remember that after this has been done the fingers are not sterile anymore.  A sterile gauze pad may be used to protect the sterile gloves.  Alternatively, a hemostat may be used to squeeze toe/foot.  In this case, one must be careful not to squeeze too hard.  Remember that after the hemostat has been used to squeeze toe, it is not sterile anymore and must not be used for surgery.

Respiratory pattern:  Anesthesia will cause a distinct slowing of respiratory rate (RR).  The surgeon must evaluate if RR becomes too slow and the anesthesia needs to be lightened and if the depth of respiration becomes too shallow. Increasing RR indicates the need for supplemental anesthesia.

Mucous membranes (MM):   MM are evaluated by the color of the pinnae (ears) and toes.  If these become bluish this is an emergency, indicating that the animal does not have enough oxygen.  Pink is good and red MM usually indicates that the animal is too warm.  This is not likely to occur during surgery but may occur during recovery from anesthesia, especially if a heat lamp is used to keep the animal warm.  In such a case, the animal recovering from anesthesia must be protected and the lamp moved.

Reaction to surgical manipulation:  If the animal makes any kind of move in response to incision or manipulation of organs, surgery must be temporarily stopped and anesthesia supplemented.

Injectable anesthetics are typically administered by the intraperitoneal (IP) route. Injectable analgesics and reversal agents are often administered by the subcutaneous or the IP route. Intramuscular (IM) injections must generally be avoided because of the small muscle mass in this species. Diluting drugs in sterile saline solution will make it easier to accurately measure volume for injection.

Ketamine-xylazine and ketamine-medetomidine combinations produce short-duration surgical anesthesia in larger species, but may be insufficient for major surgical procedures in many strains of mice. An alternative approach is to use a ketamine combination, but then titrate to effect with isoflurane from a precision vaporizer. Partial reversal of the xylazine or medetomidine using yohimbine or atipamezole is possible, and will restore cardiovascular status more quickly. See: Dissociative Anesthetics

Pain control

Mice are nocturnal animals, and are frequently housed in groups of nearly identical animals. These two factors make diagnosis of mild to moderate pain challenging. Weight loss is frequently monitored in animals at risk for ongoing pain. Pre-emptive treatment of pain before signs of pain are obvious is strongly recommended.

See: Mouse Formulary

2.2.  Rats

Dilution of injected drugs allows more precise dosing, but may shorten the shelf-life of the compound.  Aseptic technique must be observed as mixtures (cocktails) are prepared; this includes wiping the cover of each vial or bottle with 70% ethanol or isopropanol, diluting with sterile water or sterile saline and not reusing needles used for dilution or administration.  Only new, sterile needles must be used for withdrawing aliquots from the cocktail.  Diluted drugs must be labeled and dated, then discarded after 1 month, at the expiration date of any of the components, or as indicated by the manufacturer.

Rat anesthesia and analgesia considerations are similar to mouse anesthesia considerations, though some doses vary. In rats, ketamine combinations are more likely to provide adequate surgical anesthesia than in mice, and so may not require supplemental isoflurane. See: Dissociative Anesthetics, Inhalant Anesthetics, and,
Rat Formulary

2.3.  Gerbils
Gerbil anesthesia is similar to rat and mouse anesthesia, though some anesthetic doses differ. Peripheral veins are difficult to access in gerbils, limiting some of the anesthetic options.

2.4.  Hamsters

Hamster anesthesia is similar to rat and mouse anesthesia, though some anesthetic doses differ. Peripheral veins are extremely difficult to access in hamsters, limiting some of the anesthetic options.

2.5.  Guinea Pigs

Guinea pigs can be difficult to anesthetize, especially on a survival basis. Intravenous injection is difficult. Intramuscular injection is acceptable, though animals may self-mutilate at injection sites when they have recovered from anesthesia. Intraperitoneal (IP) administration works well, if the large cecum can be avoided. Guinea pigs may be anesthetized by face mask with volatile anesthetics; endotracheal intubation requires specialized training.

2.6.  Rabbits

Long procedures are best performed using inhalant anesthesia with an endotracheal tube in place. BU ASC and IACUC staff are available to train researchers in this technique. See: Rabbit Formulary

2.7.  Cats

Cats are readily anesthetized using a variety of injectable or inhalant methods.

Initial restraint of a fractious or frightened cat can be a challenge for the researcher’s safety and for the animal’s welfare; choice of technique will depend on the skill level of the researchers as well as the individual cat’s temperament. It is recommended that a tranquilizer such as acepromazine together with ketamine be administered IM or even SC initially to provide chemical restraint.  After this has taken effect an IV catheter may be placed and general anesthesia may be induced.  Alternatively, chamber induction with isoflurane may be considered.  This can be stressful to the cat, and may pose an occupational exposure risk to the workers. Intramuscular or subcutaneous injection of sedatives requires a moderate level of skill, and carries some risk of cat bites and scratches. Training is available, and veterinarians and veterinary technicians can provide direct assistance when necessary.

Non-steroidal anti-inflammatory drugs may be useful, but must be used with extreme caution in cats. Do not exceed recommended doses or frequencies of administration. Acetaminophen is never used in cats. See: Cat Formulary

2.8.  Dogs

Dogs are easily anesthetized with a variety of techniques. Intramuscular injection of ketamine or ketamine combinations are to be avoided, because of the incidence of behavioral disturbances. See: Dog Formulary

2.9.  Nonhuman Primates

Nonhuman primates require specialized handling and restraint to deliver anesthetics without compromising human safety. Ketamine alone or ketamine-diazepam are typically used by intramuscular injection for initial sedation. Once sedated, primates are easily anesthetized with a variety of techniques. Use of palatable oral medications decreases the need for restraint for medication. See: Nonhuman Primates Formulary

2.10.  Swine

Swine are easily anesthetized with a variety of techniques.  However, sedation to achieve endotracheal intubation can be a challenge.  Ketamine-xylazine is a common intramuscular sedative, but requires a large volume of injection. Use of Telazol® or Telazol® combinations can significantly reduce the volume of injection for larger animals.  See: Swine Formulary

2.11.  Frogs and amphibians

Immersion anesthetic (tricaine methanesulfonate, or MS-222) is common, especially for fully aquatic species like Xenopus.  Because MS-222 is an acidic solution that can cause stress, discomfort, and prolonged anesthetic induction time when concentrations are above 0.5 g/L it must be titrated to a normal pH (~7) by adding sodium bicarbonate.  Once a surgical plane of anesthesia has been reached, anesthesia may be supplemented, but not eliminated, by maintaining the animal at 4o C. Post-operative pain management can include local infiltration of bupivacaine.  [See: Local anesthetics]

2.12.  Fish

Immersion anesthetic (Tricaine methanesulfonate, or MS-222) is the most common anesthetic in use with fish.

2.13.   Birds

Small birds may be anesthetized by inhalation anesthetics (such as isoflurane) or injectables. Fasting is not generally required in advance. It is vital to maintain adequate warmth during the anesthetic period.  Birds, because of their flexible neck and trachea, must be placed with neck stretched and linear so that the airway remains open while the animal is under anesthesia.

3.    Commonly used anesthetics and analgesics

Anticholinergics

Anticholinergics are routinely used in human surgery and are strongly recommended for laboratory animals.  The routine administration of atropine or glycopyrrolate before or at the time of induction for general anesthesia will protect cardiac function, and especially prevent bradycardia and cardiac arrhythmias.  Anticholinergics are not routinely used in rodents, but there is no reason to omit them.  Atropine, the older drug, is shorter acting and has more side effects, so glycopyrrolate is the recommended agent.  In rabbits, glycopyrrolate is preferred, because a certain percentage of rabbits have atropinase, which metabolizes atropine making it inactive.

3.1.  Inhalant agents

3.1.1.    Isoflurane and Sevoflurane

The standard inhalant anesthetics for laboratory animal use are either isoflurane or sevoflurane, delivered to effect in concentrations of 1-3% in oxygen (up to 5% for initial induction), using a precision vaporizer.

Advantages: Advantages of inhalant agents include rapid induction and recovery, with the ability to precisely titrate the level of anesthesia.

Disadvantages: Disadvantages include the cost and logistics of using precision vaporizers, occupational exposure concerns, and the risk of fatal over-dosage if an open system is used instead of a precision vaporizer.  In addition, once animals awaken from gas anesthesia, there is no residual analgesic activity.

Pre-emptive analgesia is mandatory with isoflurane and sevoflurane anesthesia.  This is because the moment the animal recovers from anesthesia, which occurs rapidly with gas anesthesia, there is NO pain control, unless it has been administered BEFORE surgery.

Occupational safety is a serious concern. Inhalants must be directly vented out of the room, or (less reliable), adsorbed in f-air charcoal canister filter. Filters must be weighed and replaced before they reach target weight (usually an increase of 50 gm). Office of Environmental Health and Safety (OEHS) can provide assistance in evaluating potential exposures.

3.2.  Nitrous Oxide (N2O)

May be used 50:50 or 60:40 with oxygen as carrier gas for inhalant anesthetics such as Isoflurane. Nitrous oxide is not acceptable as sole anesthetic agent for surgery, but it can be used to lower the required dose of inhalant.  Occupational exposure is potentially dangerous so direct venting is required (charcoal filters do not absorb nitrous oxide).

3.3.  Other inhalant agents

Other agents and techniques may be used for inhalant anesthesia, only when specifically approved by the IACUC in the animal use protocol.

Ether is an irritant and a fire and explosion hazard, and its use is strongly discouraged.  The use of ether must be scientifically justified and then its use reviewed and approved by the IACUC.

Carbon dioxide is a potent anesthetic, but concentrations are difficult to control, making the margin of safety unacceptably low.

3.4.  Dissociative anesthetics

3.4.1.    Ketamine & Tiletamine

Ketamine is a widely used anesthetic in a variety of species. In low doses, ketamine provides chemical restraint with some somatic analgesia (no visceral analgesia). In higher doses, it may provide short-term surgical anesthesia in some species. In most instances, ketamine is used in combination with other injectable agents.  Tiletamine is similar to ketamine; it is primarily used in combination with zolazepam as the drug Telazol.

Advantages of ketamine: Advantages of ketamine are its wide margin of safety in most species and its analgesic action. In combination with other drugs, it
can provide surgical plane of anesthesia for about one half hour.

Disadvantages of ketamine: Disadvantages of ketamine include some irritancy due to low pH, note that ketamine has an acidic pH of about 4 and stings when administered IM.  If injected near the sciatic nerve in the gluteal muscles in rodents and rabbits it may cause neuronal damage evidenced by the animal losing sensation in the hind leg and self-mutilating.

It is not sufficient for anesthesia by itself, but is extensively used in NHP for non-painful procedures where the animal needs to be restrained, such as blood collection, TB testing and physical exams.  The sole use of ketamine in other species is discouraged, as the recovery may be very stressful and agitated. Ketamine is a Class III controlled substance and subject to regulatory requirements governed by the Drug Enforcement Agency (DEA).

Advantages of Telazol: A low volume of injection is required. Like ketamine combinations, it can occasionally produce short-term anesthesia, though rarely of sufficient depth for surgery. It is more useful as an induction agent prior to general inhalant anesthesia, or for chemical restraint for short non-surgical procedures.

Disadvantages of Telazol: Telazol must be stored under refrigeration once reconstituted. It is not safe for use in rabbits (kidney disease). Telazol is a Class III controlled substance

3.5.  Ketamine combinations

3.5.1.    Ketamine-alpha2-agonists (Xylazine or Medetomidine)

Αlpha-2 agonists are centrally acting anesthetics, with excellent analgesic properties.  At lower doses they induce sedation.  Their most common side effects are bradycardia and cardiac arrhythmia.  When combined with ketamine, these properties are minimized and the combination of ketamine with the α2-agonists xylazine or medetomidine in the same syringe produces a surgical level of anesthesia in many species, notably rodents and rabbits.

In swine the combination of Ketamine-alpha2-agonists is used to restrain the animal prior to induction with isoflurane.

Advantages: Advantages of ketamine-α2-agonist combinations are that they may be combined in one syringe; that they may produce short-term surgical anesthesia with good analgesia, and that recovery can be hastened by reversing the α2-agonist with Atipamezole or Yohimbine.

Disadvantages: Disadvantages of ketamine-α2-agonist combinations are that they will not reliably reach surgical anesthesia in all cases, and that they can cause profound cardiac depression. Xylazine may cause vomiting, especially in cats. Ketamine is a Class III controlled substance

Caution for use: if a ketamine-a2-agonist combination is used for surgery longer than 20 minutes, animals will likely require additional anesthetic. Redosing with ketamine alone rather than the combination is safer, as the cardiovascular depression of α2-agonists is often longer-lasting than the sedation or analgesia produced.

Adding acepromazine to the ketamine-α2-agonist combination may result in deeper and/or longer plane of anesthesia in small rodents, especially rats, and possibly some strains of mice as well.

3.5.2.    Ketamine-benzodiazepines (Midazolam or Diazepam)

Ketamine may be combined with the benzodiazepines Midazolam or Diazepam in the same syringe to produce a deep level of sedation. In most cases, this sedation will require an inhalant agent or other anesthetic to achieve surgical anesthesia. In most applications, Midazolam is preferred, as it can be injected intramuscularly; intramuscular injection of propylene glycol (the carrier in injectable diazepam) can cause painful, sterile abscesses and is discouraged.

Advantages: Advantages of ketamine-benzodiazepine combinations are that they may be combined in one syringe and will produce deep sedation with moderate analgesia as well as amnesia. Recovery from ketamine-midazolam is often smoother than recovery from ketamine alone.

Disadvantages: Disadvantages of ketamine- benzodiazepine combinations are that they will not reliably reach surgical anesthesia in most cases. Diazepam should be restricted to intravenous or intraperitoneal use. Ketamine is a Class III controlled substance while the benzodiazepines are in Class IV.

Pharmacologically, Telazol is a dissociate-benzodiazepine combination.

3.6.  Barbiturates

Though superseded in most applications by newer anesthetics, barbiturates still have their place in the animal laboratory. They are most frequently used in terminal or acute studies, as recovery can be prolonged and unpleasant, especially in larger animals. Barbiturates are often the anesthetic of choice when neuron-physiological recordings are being conducted, such as visual or auditory evoked responses. Concurrent use of an analgesic (opioid or non-steroidal anti-inflammatory drug) is encouraged as it may improve pain relief with barbiturate use, and lower the required dose of barbiturate.

Sodium pentobarbital (Nembutal) and sodium thiopental (Pentothal) are currently the two most commonly used barbiturates. The duration of action of pentobarbital is considerably longer than that of thiopental.

Advantages: Barbiturates do not depress cortical evoked responses to the extent that other anesthetics might. Animals do not feel pain when they are at a surgical plane of anesthesia. Once stable anesthesia has been achieved, it may be longer lasting than with most other injectable agents. Barbiturates are the most common of the injected euthanasia solutions, as they reliably produce unconsciousness before respiratory depression and death.

Disadvantages: Disadvantages of barbiturates include a narrow margin of safety, primarily associated with respiratory depression. Pain sensation is only decreased at surgical planes of unconsciousness, and may even be heightened (hyperalgesia) at subanesthetic doses. Larger animals may experience a distressful anesthetic recovery. Outside of the vein (perivascular, or intraperitoneal) injection of barbiturates can be irritating; barbiturates for IP injection should be diluted to a strength of 6 mg/kg. Barbiturates are Class II controlled substances, except for some Class III euthanasia solutions.

3.7. α2-agonists (Xylazine or Medetomidine)

The α2-agonists (Xylazine or Medetomidine) are hypnotic analgesics with significant pain relief. Used as sole agents, they do not produce sufficient depth of anesthesia for even minor surgical procedures. Combined with Ketamine and possibly supplemented with inhalants or local or topical analgesics [link to local anesthetics later in document], they may be useful during surgery. In some species, medetomidine appears to lead to greater anesthetic depth than does xylazine, and it is more reliably antagonized by atipamezole.

Advantages: α2-agonists are that they produce profound analgesia of short duration, can be combined with ketamine (and in rodents, acepromazine) to produce deeper anesthesia, they are not controlled substances, and they are reversible with IP or subcutaneous atipamezole (yohimbine is sometimes used for xylazine reversal). They are not irritant when injected via intramuscular or intraperitoneal routes.

Disadvantages: Disadvantages in most species include cardiovascular depression (decreased heart rate, decreased cardiac output, and hypotension), which is somewhat controlled by use of atropine or glycopyrrolate. α2-agonists cause a transient hyperglycemia which may have research implications. Xylazine often causes transient nausea and vomiting, especially in cats. Rapid IV administration of reversal agent has produced seizures in some species.

Caution for use: If a ketamine α2-agonist combination is used for surgery longer than 20 minutes, animals will likely require additional anesthetic. Redosing with ketamine rather than the combination is usually safer, as the cardiovascular depression of α2-agonists is often longer-lasting than the sedation or analgesia produced.

3.8       A2 Reversal agents:

Advantages:  Administration of a reversal agent can rescue an animal which is in cardiac distress due to bradycardia or cardiac arrhythmia.  It will also promote quicker recovery from α2 agent anesthesia.

Disadvantages:  If ketamine and alpha2 agent have been used for anesthesia and the alpha2 agonist action is reversed, this may result in agitated recovery from anesthesia due to the ketamine remaining in the system not being softened by the α2-agonist.

3.9       Propofol

Propofol can produce general anesthesia in animals, as a sole agent with continuous infusion for surgery, or as a pre-anesthetic for endotracheal intubation. It is valued for its fast recovery time, even after prolonged administration.

Advantages: Animals recover from propofol in minutes, even after prolonged administration.

Disadvantages: Propofol has minimal analgesia at sub-anesthetic doses. It can be a profound respiratory depression, and may also cause hypotension. Because of its rapid elimination, it must be administered IV, and so is of limited use in small rodents.  Once opened, propofol easily supports microbial growth; therefore unused propofol from an opened ampule should be discarded after use and not stored for future use.

3.10     Tribromoethanol (Avertin)

Avertin has been the standard anesthetic in much mouse transgenic work. It produces short-term (15-20 minutes) surgical anesthesia with good muscle relaxation and moderate respiratory depression. It does not produce significant residual post-procedural analgesia. Unless strongly justified in the animal care and use protocol, use of Avertin is restricted to mice only, for a single survival anesthesia plus terminal/acute use.

Advantages: Advantages of Avertin are that it is easily administered via the intraperitoneal route, produces good short-term surgical anesthesia, and is not a controlled substance.

Disadvantages: Avertin is not commercially available as a pharmaceutical drug, and must be made in the laboratory from the reagents tribromoethanol and amylene hydrate. Avertin can cause peritonitis in mice, and the risk of peritonitis, including fatal peritonitis, increases with each time it is used. Post-procedural analgesia has not been demonstrated, so use of another analgesic is generally required. Though surgical anesthesia is short (15-20 minutes), anesthetic recovery can take 40 minutes, during which time the animal must be continually attended and kept warm.

Cautions for use: Avertin must be carefully prepared in the laboratory under aseptic conditions.  Working dilution of 1.25% is recommended — this is best prepared fresh for use, or stored for no more than one week. Avertin is used only for mice. It is not to be used twice in one animal on a survival basis (if used a second time that use should be terminal/acute). Where possible, IACUC recommends that inhalants replace Avertin.

3.11     Opioids  

Opioid drugs are important components of many surgical anesthesia regimens, and are the most potent available post-procedural analgesics. Drugs in this group vary in their potency as well as their duration of action. Fentanyl, oxymorphone, morphine, buprenorphine and butorphanol are the most commonly used opioids in laboratory animal medicine, though others may be used on occasion. Fentanyl is the most potent of the three μ agonists, but also the shortest acting. Buprenorphine is longer-acting and is good for most post-operative applications. Butorphanol may be more efficacious than buprenorphine for birds and for cats. Buprenorphine and butorphanol are mixed agonist/antagonists at different opioid receptors; they produce a less profound respiratory depression than full agonists, but also have a “ceiling effect” in the degree of analgesia produced with increasing doses.  Administered as a part of the anesthesia regimen as pre-emptive analgesia, they enable the anesthetist to lower the dose of other anesthetics and contribute to the comfort and safety of the patient.

Opioids are most often administered by injection. Oral use is effective, but requires much higher doses because of “first-pass” liver metabolism when absorbed from the gut.

Advantages: Opioids are potent analgesics. Concurrent use with inhalant or barbiturate general anesthesia will lower the required dose of the anesthetic.

Disadvantages: Opioids can suppress respiration (more marked effect in fentanyl than in buprenorphine). Opioids may increase locomotor activity, and may cause pica (abnormal ingestion of non-food items such as bedding) in rats. Alternatively, they may sometimes cause sleepiness and slower recovery from general anesthesia. Fentanyl has a very short duration of action in most animal species and must be administered as an IV drip. Opioids are controlled substancesMorphine, oxymorphone and fentanyl are Schedule IIBuprenorphine and butorphanol are schedule IV.

Cautions for use: Buprenorphine has found favor as the longest-acting opioid analgesic. However, this duration of action is closer to 6 hours in most situations than it is to 12 hours. 12 hours is the absolute maximum dosing interval for use of buprenorphine for post-procedural pain. Pure mu receptor agonists (morphine, fentanyl, and oxymorphone) are not recommended in swine and should be used cautiously if at all in cats.  This is because these drugs may cause excitement in these species.  However, cats and swine do well with kappa receptor agonists (buprenorphine and butorphanol).

3.12     Non-steroidal anti-inflammatory drugs (NSAIDs)

The advent of newer, more potent, more specific anti-inflammatory agents has increased their usefulness in laboratory animal use. Most reduce fever, reduce inflammation, and provide varying degrees of analgesia (acetaminophen does not significantly reduce inflammation).

Advantages: Carprofen, ketoprofen, ketorolac, and meloxicam may have duration of analgesic action up to 24 hours. They may be used concurrently with anesthetics, with opioid analgesics, and with local anesthetic/analgesics. Injectable NSAIDs are useful for accurate dosage and administration to small rodents. Oral flavored analgesics are useful for mild pain in nonhuman primates.

Disadvantages: NSAIDs may decrease clotting ability, of possible concern following surgery. Gastric upset and even ulceration may occur, especially with prolonged use. Prolonged use carries the risk of kidney or liver disease.

Cautions for use: Cats are particularly susceptible to toxic effects of NSAIDs. Acetaminophen is never administered to cats; other NSAIDs should be used only at the dose and frequency recommended.

Undesired side effects are more likely with increasing duration of usage — for most situations, limit use of NSAIDs to 3-4 days per animal, except under veterinary supervision. Do not use in dehydrated animals, or in animals with kidney or liver dysfunction.

3.13     Local anesthetic/analgesic drugs (lidocaine and bupivacaine)

Local anesthetic/analgesic drugs (lidocaine and bupivacaine) may be useful both during surgery, and post-operatively. They block nerve conduction when applied locally at sufficient concentration. Lidocaine has a fast onset of action, and provides a couple of hours of analgesia. Bupivacaine has a slower onset of action (up to 30 minutes) but provides up to 12 hours of residual analgesia. Both are infiltrated subcutaneously at the surgical site or (especially in larger animals) may be used regionally (epidural, intrathecal, intercostal).

Lidocaine cream (EMLA or ELAMax) is used topically on shaved, intact skin prior to venipuncture, though it requires 30-60 minutes or more of contact with skin to reach full effect. Tricaine methanesulfonate (MS-222) is a related compound used as a general anesthetic for fish and frogs.

Advantages: Intra-operative use can augment the pain relief of general anesthetics, and reduce the need for frequent redosing. Bupivacaine can augment the post-operative analgesic action of opioids and/or NSAIDs. They are not controlled substances. At appropriate doses, they have minimal cardiovascular effect.

Disadvantages: Intramuscular and intravenous injection should both be avoided. Systemic toxicity (including seizures and death) can result from over-dosage (more likely to occur with smaller subjects) and with accidental intravenous injection. Lidocaine may sting when first injected.

3.14     Miscellaneous agents

Urethane, choral hydrate, equithesin, sodium thiamylal, a-chloralose have some specialized use in laboratory animal anesthesia. Their use should be discussed with a veterinarian.

Note that all of the doses listed in the formula tables are approximations and must be titrated to the animal’s strain, age, sex and individual responses. Significant departures from these doses should be discussed with a veterinarian. Doses will also vary depending on what other drugs are being administered concurrently.

All doses are listed as milligrams per kilogram (mg/kg) unless otherwise noted.   Where a dose has not been determined, it is listed as TBD (To Be Determined).

Dilution of injected drugs allows more precise dosing, may make some drugs less irritating when injected, and may facilitate absorption, but also may shorten the shelf-life of the compound.  Aseptic procedures must be observed as mixtures (cocktails) are prepared; this includes wiping the cover of each vial or bottle with 70% ethanol or isopropanol, diluting with sterile water or sterile saline and not reusing needles used for dilution or administration.  Only new, sterile needles must be used for withdrawing aliquots from the cocktail.  Diluted drugs must be labeled with the contents and concentration of the dilution, the preparer’s name or initials, and dated, then discarded after 1 month, at the expiration date of any of the components, or according to the manufacturer’s instructions. 

 CAT FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias
Atropine 0.02-0.05                                                                                                          IM or SC Once at induction
Recommended:Glycopyrrolate 0.01   IM or SC Once   at induction
Inhalation   anesthetics – Must use precision vaporizer.    Survival surgery requires   concurrent pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%   inhalant to effect (up to 5% for induction). Up to 8% for sevoflurane Whenever   general anesthesia is required Survival   surgery requires concurrent pre-emptive analgesia.
Nitrous   oxide (N2O) Up   to 60% with oxygen Whenever   deep sedation or general anesthesia is required Not   acceptable for surgery as sole agent – usually used with inhalant anesthetic   to potentiate effect and lower required dose
Ketamine   combinations   – May sting upon IM injections.  May be   used for pre-anesthesia prior to intubation and induction of isoflurane   anesthesia and for short procedures.
Recommended:KetamineAcepromazine 5-10+0.1-0.2   IM or SCin   same syringe) For   restraint prior to induction of anesthesia as needed Useful   for minor procedures such as placing IV catheter, physical exam or blood   collection
Recommended:
Ketamine-Midazolam
5-10+   0.1-0.2 IM or SC (in same syringe) For   restraint prior to induction of anesthesia as needed May   be useful for restraint.
KetamineXylazine 10+1   IM(in   same syringe) May   be useful for short painful procedures May   not produce surgical-plane anesthesia for major procedures.
Ketamine-Medetomidine 5   – 10+   0.05 – 0.08 IM or SC(in   same syringe) May   be useful for short painful procedures May   not produce surgical-plane anesthesia for major procedures.
Reversal agents for   alpha 2 agonists – Atipamezole   is more specific for medetomidine than for xylazine (as a general rule,   Atipamezole is dosed at the same volume as Medetomidine, though they   are manufactured at different concentrations).
Atipamezole 0.3   – 0.5 SC, IM, IV  Once.    Repeat if needed. To   reverse medetomidine or xylazine
Yohimbine 0.15   IM .  Once.    Repeat if needed. To   reverse xylazine.
Other injectable   anesthetics and tranquilizers
Sodium   pentobarbital (Nembutal) 20   – 30 IV to effect and maintained withintermittent   bolus as neededor
2-20 mg/kg/hr IV continuous infusion after induction
As   needed.  Recommended for terminal/acute   procedures only. Occasionally used on survival basis when cortical evoked   responses are being measured. Preemptive   analgesia strongly recommended.  Consider   supplemental analgesia (opioid or NSAID) for invasive procedures.
Sodium   thiopental (Pentothal) 13   – 26 IV to effect As   induction agent, prior to general anesthesia with pentobarbital or inhalant Does   not confer adequate analgesia for painful procedures.  Very short acting.
Propofol 8-10   to effect IV As   induction agent, prior to general anesthesia with pentobarbital or inhalant Respiratory   depression upon induction is possible.Very   short acting
Acepromazine 0.08   – 0.2 IM or SC1.0   PO Tranquilizer.May   be used by itself or whenever ketamine combinations are used Usually   used in conjunction with anesthetics such as ketamine. Acepromazine confers   no analgesia.
Opioid analgesia – Pure mu receptor   agonists are not recommended  in cats   as they may produce excitation
Recommended:
Buprenorphine
0.005   – 0.01 SC, IM, IV Used   pre-operatively for preemptive analgesia and post-operatively every 6-12 hour For   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAID
Recommended:
Butorphanol
0.2   – 0.6 IM, SC, IV Used   pre-operatively for preemptive analgesia and post-operatively every 4-6 hour Consider   multi-modal analgesia with a NSAID
Reversal agents     for opioids

 

Naloxone 0.05   – 0.1 IV Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia – Note that prolonged use may   cause renal, gastrointestinal, or other problems.  NSAIDs   in cats must be used with caution.
Recommended:
Carprofen
4.0-5.0   SC Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Recommended:
Meloxicam
0.1   – 0.3 PO, IM or SC Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Ketoprofen ~   1.0 – 2.0 IM, IV, SC Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Ketorolac ~0.25 Used   pre-operatively for preemptive analgesia Do   not use more than 2-3 times per animal during any post-surgical period.
Aspirin 1   children’s aspirin (81 mg) PO Every   48 hours Do   not use more than a few times.  Not   recommended for postoperative pain.
Local anesthetic/analgesics (lidocaine and   bupivacaine may be combined in one syringe for rapid onset and long duration   analgesia)
Lidocaine   hydrochloride May   dilute to 0.5 -1% (=10mg/ml). May be mixed in same syringe with bupivacaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive   analgesia Faster   onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine May   dilute to 0.25 – 0.5%, May be mixed in same syringe with lidocaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive analgesia Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

CHINCHILLA FORMULARY

  “TBD” (To Be Determined)  is listed when a drug dose has not been determined.

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias
Atropine 0.02-0.05                                                                                                          IM   or SC Once at induction
Glycopyrrolate 0.01   IM or SC Once   at induction
Inhalation   anesthetics – Must use precision vaporizer.    Survival surgery requires   concurrent pre-emptive analgesia.
Isoflurane or Sevoflurane 1-3%   inhalant to effect (up to 5% for induction). Up to 8% for sevoflurane Whenever   general anesthesia is required Survival   surgery requires concurrent pre-emptive analgesia.
Ketamine   combinations   – May sting upon IM injections.  May be   used for pre-anesthesia prior to intubation and induction of isoflurane   anesthesia and for short procedures.
KetamineAcepromazine 40   (ket) & 0.5 (ace)IM   in same syringe For   restraint prior to induction of anesthesia as needed May   be useful for minor procedures such as placing IV catheter, physical exam or   blood collection
KetamineXylazine 35   – 40+4   – 8 IM(in   same syringe) Re-dose   as needed with ¼ dose of both
Reversal agents for   alpha 2 agonists – Atipamezole   is more specific for medetomidine than for xylazine (as a general rule,   Atipamezole is dosed at the same volume as Medetomidine, though they   are manufactured at different concentrations).
Atipamezole TBDSC,   IM, IV Once.Repeat   if needed. To   reverse medetomidine or xylazine
Yohimbine 2   IP Once.Repeat   as needed To   reverse xylazine.
Other injectable   anesthetics and tranquilizers
Sodium   pentobarbital (Nembutal) 30   – 40 IV or IPto   effect and maintained withintermittent   bolus as neededor
2-20 mg/kg/hr IV continuous infusion after induction
As   needed.  Recommended for terminal/acute   procedures only. Occasionally used on survival basis when cortical evoked   responses are being measured. Preemptive   analgesia strongly recommended.    Consider supplemental analgesia (opioid or NSAID) for invasive   procedures.
Acepromazine 0.5   – 1.0 IM or SC Tranquilizer.May   be used by itself or whenever ketamine combinations are used Usually   used in conjunction with anesthetics such as ketamine. Acepromazine confers   no analgesia.
Opioid analgesia –
Buprenorphine 0.05SC Used   pre-operatively for preemptive analgesia and post-operatively every 8-12 hour For   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAID
Butorphanol 0.2   – 2.0IM,   IP, SC Used   pre-operatively for preemptive analgesia and post-operatively every 6 hours Consider   multi-modal analgesia with a NSAID
Reversal agents     for opioids

 

Naloxone  0.01-0.1 SC, IP,IV, IM Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia – Note that prolonged use may   cause renal, gastrointestinal, or other problems
Carprofen 2.0   – 5.0 SC,PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Meloxicam 0.5   – 1.0 SC, PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Ketoprofen 1.0IM,   SC Used   pre-operatively for preemptive analgesia and post-operatively every 12 – 24   hour for up to 4 days Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Aspirin 100   – 200 PO Every   6- 8 hours
Local   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one syringe   for rapid onset and long duration analgesia)
Lidocaine   hydrochloride May   dilute to 0.5 -1% (=10mg/ml). May be mixed in same syringe with bupivacaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive   analgesia Faster   onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine May   dilute to 0.25 – 0.5%, May be mixed in same syringe with lidocaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive analgesia Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 

FERRET FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents bradycardia   and cardiac arrhythmias
Atropine 0.05                                                                                                          IM or SC Once at induction
Recommended:Glycopyrrolate 0.01   IM or SC Once   at induction
Inhalation   anesthetics – Must use precision vaporizer.    Survival surgery requires   concurrent pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%   inhalant to effect (up to 5% for induction). Up to 8% for sevoflurane Whenever   general anesthesia is required Survival   surgery requires concurrent pre-emptive analgesia.
Ketamine   combinations   – May sting upon IM injections.  May be   used for pre-anesthesia prior to intubation and induction of isoflurane   anesthesia and for short procedures.
KetamineAcepromazine 20   – 35+0.2-0.35   IM or SC

in   same syringe)

For   restraint prior to induction of anesthesia as needed May   be useful for minor procedures such as placing IV catheter, physical exam or   blood collection
KetamineXylazine 20   – 40+2   – 4 IM(in   same syringe) Re-dose   as needed with ¼ dose of both
Ketamine-Medetomidine 4   – 8+   0.08 – 0.1 IM or SC(in   same syringe) May   be useful for short painful procedures May   not produce surgical-plane anesthesia for major procedures.
Reversal agents for   alpha 2 agonists – Atipamezole   is more specific for medetomidine than for xylazine (as a general rule,   Atipamezole is dosed at the same volume as Medetomidine, though they   are manufactured at different concentrations).
Atipamezole 0.4   IM Once.Repeat   if needed. To   reverse medetomidine or xylazine
Yohimbine 0.5   IM Once.Repeat   if needed. To   reverse xylazine.
Other injectable   anesthetics and tranquilizers
Sodium   pentobarbital (Nembutal). 30   – 40 IV to effect and maintained withintermittent   bolus as neededor
2-20 mg/kg/hr IV continuous infusion after induction
As   needed.  Recommended for terminal/acute   procedures only. Occasionally used on survival basis when cortical evoked   responses are being measured. Preemptive   analgesia strongly recommended.    Consider supplemental analgesia (opioid or NSAID) for invasive   procedures.
Propofol 5   – 8 to effect IV As   induction agent, prior to general anesthesia with pentobarbital or inhalant Respiratory   depression upon induction is possible.Very   short acting
Acepromazine 0.2   – 0.5 IM or SC Tranquilizer.May   be used by itself or whenever ketamine combinations are used Usually   used in conjunction with anesthetics such as ketamine. Acepromazine confers   no analgesia.
Opioid analgesia –
Buprenorphine 0.01   – 0.03 SC, IM, IV Used   pre-operatively for preemptive analgesia and post-operatively every 6-12 hour For   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAID
Butorphanol 0.05   – 0.1 IM, SC, IV Used   pre-operatively for preemptive analgesia and post-operatively every 4-6 hour Consider   multi-modal analgesia with a NSAID
Reversal agents     for opioids

 

Naloxone 0.04   – 1.0 IV, IM, SC Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia – Note that prolonged use may   cause renal, gastrointestinal, or other problems
Carprofen 1.0PO Used   pre-operatively for preemptive analgesia and post-operatively every 12 – 24   hour for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Meloxicam 0.2SC,   IM, PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days. Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Ketoprofen 1.0IM,   PO, SC Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Aspirin 0.5   – 22 PO Every   8 – 24 hours
Local   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)
Lidocaine   hydrochloride 1.0   – 2.0 SCMay   dilute to 0.5 -1% (=10mg/ml). May be mixed in same syringe with bupivacaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive   analgesia Faster   onset than bupivacaine but short  duration of action (15-30 minutes)
Bupivacaine 1.0   – 1.5 SCMay   dilute to 0.25 – 0.5%, May be mixed in same syringe with lidocaine.
SC or intra-incisional
Use   locally before making surgical incision to provide pre-emptive analgesia Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 


GERBIL FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias.
Atropine 0.04   IP, SC, or                                                                                                          IM Once at induction
Recommended:Glycopyrrolate 0.01-0.02IM   or SC Once   at induction
Inhalation   anesthetics   – Best administered using a precision vaporizer but may also be administered   via nose cone containing small amount of anesthetic.  Survival   surgery requires concurrent pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%   inhalant to effect (up to 5% for induction). Up to 8% for Sevoflurane Whenever   general anesthesia is required Induction   is commonly performed in an induction box.Survival   surgery requires concurrent pre-emptive analgesia.
NOT recommendedEther To   effect (cannot determine percentage) Whenever   general anesthesia is required Strongly   discouraged because of flammability and distress to animals. Used for short   procedures requiring anesthesia.
Carbon   dioxide To   effect (cannot determine percentage) Once,   at time of euthanasia May   be used for fast terminal procedure such as cardiac blood collection followed   by euthanasia
Ketamine   combinations   – These dose combinations vary depending upon the type of procedure and the   age/strain of the animal.  Higher ketamine   dose with lower xylazine dose are used for less invasive procedures and for   very young/very old or critical patients.    In general, higher doses of xylazine with concomitant lowering of the   ketamine dose are used for more invasive procedures.
Recommended:
Ketamine-Xylazine
50+   2(all   IP in same syringe) As   needed Does   not provide surgical level of anesthesia for major procedures.  If redosing, administer ¼ dose of the   mixture. May be partially reversed with Atipamezole or Yohimbine
Ketamine-Medetomidine 75-90+   0.5(all   IP in same syringe) As   needed May   not produce surgical-plane anesthesia for major procedures. If redosing, use   ketamine alone. May be partially reversed with Atipamezole
Ketamine-Diazepam 50+   5(all   IP in same syringe) As   needed Does   not produce surgical-plane anesthesia for major procedures, but may be useful   for restraint.
Reversal agents to   alpha 2 agents.  Atipamezole is more specific for medetomidine than   for xylazine (as a general rule, Atipamezole is dosed at the same volume   as Medetomidine, though they are manufactured at different concentrations).
Atipamezole 1.0   – 2.0 IP, SC,  IM Once.  Repeat if needed To   reverse medetomidine or xylazine
Yohimbine 1.0   – 2.0 SC or IP Once.  Repeat if needed.  For   reversal of xylazine effects
Other injectable   anesthetics
Sodium   pentobarbital (Nembutal) 60   – 80 IP Recommended   for terminal/acute procedures only, with booster doses as needed. High   mortality with doses higher than 80mg/kg. Consider   supplemental analgesia (opioid or NSAID) for invasive procedures, especially   when used on a survival basis.  Very   long acting with a long recovery period.    Keep animal warm.
Tribromoethanol   (Avertin) 250-300mg/kg May   be used once for survival procedure (boosted as necessary during procedure)   and once for terminal/acute procedure Use   fresh solution (<1 week of age).    See recipe below.
AVERTIN   recipe
66.66% stock solution
Dissolve 1 g 2, 2, 2-tribromoethanol in 0.5 g amylene hydrate.Store   wrapped in foil (light sensitive solution, ok to use brown glass bottle), at   -20 o C.  Date and label   bottle.  Stock solution can be kept for   up to one year.1.25%   working solution (12.5 mg/ml)
Take 0.5 ml concentrate and mix with 39.5 ml sterile saline.  Adjust to pH 7.

Recommended   to be used the same day it is prepared.    If it must be stored, it should be kept frozen at -20 o C, in   a foil wrapped container or brown bottle.    Use the frozen aliquots after it is thawed the same day; discard   frozen aliquots after 2 months.  Date   and label all bottles.

 

Opioid analgesia
Recommended:
Buprenorphine
0.1   – 0.2 SC, IP, Used   pre-operatively for preemptive analgesia and post-operatively every 8 hours Major   procedures require more frequent dosing than 12 hour intervals. Consider   multi-modal analgesia with an NSAID
Recommended:
Butorphanol
1.0   – 5.0 SC, IP Used   pre-operatively for preemptive analgesia and post-operatively every 4 hours Consider   multi-modal analgesia with a NSAID.    Shorter acting than buprenorphine
Morphine 2   – 5 SC, IP Every   2 -4 hours As   pre-emptive analgesia and post-procedural analgesic for very painful   procedures
Reversal agents     for opioids

 

Naloxone 0.01   -0.1 IP, IM Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia.    Note that prolonged use may cause renal, gastrointestinal or other   problems
Recommended:
Carprofen
4-5   SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose:  27 ug/ml = 5 mg/kg/day.  Carprofen is light sensitive –use dark   bottles.
Recommended:
MeloxicamMetacam®
0.5   – 1.0 SC, PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose: 1.7 ug/ml (0.3 mg/kg/day).  Use   injectable form of meloxicam to prepare drinking water:  Meloxicam suspension does not dissolve well   in water.
Recommended:
Ketoprofen
2   – 5 SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Flunixin   meglubinBanamine® 2.5   SC For   supplemental postop analgesiaEvery   12 – 24 hours for no more than 3 days Make   sure animal is well-hydrated.
Local   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)
Lidocaine   hydrochloride Dilute   to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Faster   onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine Dilute   to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 

HAMSTER FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias.
Atropine 0.04   IP, SC, or                                                                                                          IM Once at induction
Recommended:Glycopyrrolate 0.01-0.02IM   or SC Once   at induction
Inhalation   anesthetics   – Best administered using a precision vaporizer but may also be administered   via nose cone containing small amount of anesthetic.  Survival   surgery requires concurrent pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%   inhalant to effect (up to 5% for induction). Up to 8% for Sevoflurane Whenever   general anesthesia is required Induction   is commonly performed in an induction box.Survival   surgery requires concurrent pre-emptive analgesia.
NOT recommendedEther To   effect (cannot determine percentage) Whenever   general anesthesia is required Strongly   discouraged because of flammability and distress to animals. Used for short   procedures requiring anesthesia.
Carbon   dioxide To   effect (cannot determine percentage) Once,   at time of euthanasia May   be used for fast terminal procedure such as cardiac blood collection followed   by euthanasia
Ketamine   combinations   – These dose combinations vary depending upon the type of procedure and the   age/strain of the animal.  Higher   ketamine dose with lower xylazine dose are used for less invasive procedures   and for very young/very old or critical patients.  In general, higher doses of xylazine with   concomitant lowering of the ketamine dose are used for more invasive   procedures.
Recommended:
Ketamine-Xylazine
200+   10(all   IP in same syringe) As   needed Surgical   level of anesthesia for major procedures.    If redosing, administer ¼ dose of the mixture. May be partially   reversed with Atipamezole or Yohimbine
Ketamine-Medetomidine 100+   0.25(all   IP in same syringe) As   needed May   not produce surgical-plane anesthesia for major procedures. If redosing, use   ketamine alone. May be partially reversed with Atipamezole
Ketamine-Diazepam 70+   2(all   IP in same syringe) As   needed Does   not produce surgical-plane anesthesia for major procedures, but may be useful   for restraint.
Reversal agents to   alpha 2 agents.  Atipamezole is more specific for medetomidine than   for xylazine (as a general rule, Atipamezole is dosed at the same volume   as Medetomidine, though they are manufactured at different concentrations).
Atipamezole 1.0   – 2.0 IP, SC,  IM Once.  Repeat if needed To   reverse medetomidine or xylazine
Yohimbine 1.0   – 2.0 SC or IP Once.  Repeat if needed.  For   reversal of xylazine effects
Other injectable   anesthetics
Sodium   pentobarbital (Nembutal) 50   – 90 IP Recommended   for terminal/acute procedures only, with booster doses as needed. High risk   of mortality in this species. Consider   supplemental analgesia (opioid or NSAID) for invasive procedures, especially   when used on a survival basis.  Very   long acting with a long recovery period.    Keep animal warm.
Opioid analgesia
Recommended:
Buprenorphine
0.5   SC, IP, Used   pre-operatively for preemptive analgesia and post-operatively every 8 hours Major   procedures require more frequent dosing than 12 hour intervals. Consider   multi-modal analgesia with an NSAID
Recommended:
Butorphanol
1.0   – 5.0 SC, IP Used   pre-operatively for preemptive analgesia and post-operatively every 4 hours Consider   multi-modal analgesia with a NSAID.    Shorter acting than buprenorphine
Morphine 2   – 5 SC, IP Every   2 -4 hours As   pre-emptive analgesia and post-procedural analgesic for very painful   procedures
Reversal agents     for opioids

 

Naloxone 0.01   -0.1 IP, IM Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia.    Note that prolonged use may cause renal, gastrointestinal or other   problems
Recommended:
Carprofen
4-5   SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose:  27 ug/ml = 5 mg/kg/day.  Carprofen is light sensitive –use dark   bottles.
Recommended:
MeloxicamMetacam®
0.5   – 1.0 SC, PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose: 1.7 ug/ml (0.3 mg/kg/day).  Use   injectable form of meloxicam to prepare drinking water:  Meloxicam suspension does not dissolve well   in water.
Recommended:
Ketoprofen
 5 SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Flunixin   meglubinBanamine® 2.5   SC For   supplemental postop analgesiaEvery   12 – 24 hours for no more than 3 days Make   sure animal is well-hydrated.
Local   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)
Lidocaine   hydrochloride Dilute   to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Faster   onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine Dilute   to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 

MOUSE FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias.  Not   commonly used in mice
Atropine 0.02-0.05                                                                                                          IM or SC Once at induction
Recommended:Glycopyrrolate 0.01-0.02IM   or SC Once   at induction
Inhalation   anesthetics   – Best administered using a precision vaporizer but may also be administered   via nose cone containing small amount of anesthetic.  Survival   surgery requires concurrent pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%   inhalant to effect (up to 5% for induction). Up to 8% for Sevoflurane Whenever   general anesthesia is required Induction   is commonly performed in an induction box.Survival   surgery requires concurrent pre-emptive analgesia.
NOT recommendedEther To   effect (cannot determine percentage) Whenever   general anesthesia is required Strongly   discouraged because of flammability and distress to animals. Used for short   procedures requiring anesthesia.
Carbon   dioxide To   effect (cannot determine percentage) Once,   at time of euthanasia May   be used for fast terminal procedure such as cardiac blood collection followed   by euthanasia
Ketamine   combinations   – These dose combinations vary depending upon the type of procedure and the   age/strain of the animal.  Higher   ketamine dose with lower xylazine dose are used for less invasive procedures   and for very young/very old or critical patients.  In general, higher doses of xylazine with   concomitant lowering of the ketamine dose are used for more invasive   procedures.  See cocktail recipe at the   end of table.
Recommended:
Ketamine-Xylazine
50   – 100+   10-15(all   IP in same syringe) As   needed Provides   surgical level anesthesia.  If   redosing, administer ¼ dose of the mixture. May be partially reversed with   Atipamezole or Yohimbine
Recommended:Ketamine-Xylazine-Acepromazine   50 – 75+10   – 15+2.0(all   IP in same syringe) As   needed  Provides surgical level anesthesia.  Acepromazine extends the anesthesia time   for long surgical procedures.  If   redosing, use ketamine/xylazine ¼ dose. May be partially reversed with   Atipamezole or Yohimbine
Ketamine-Medetomidine 50-75+   0.5 -1(all   IP in same syringe) As   needed May   not produce surgical-plane anesthesia for major procedures. If redosing, use   ketamine alone. May be partially reversed with Atipamezole
Ketamine-Midazolam 80-100+   4-5(all   IP in same syringe) As   needed Does   not produce surgical-plane anesthesia for major procedures, but may be useful   for restraint.
                                                 Mouse  cocktails  Ketamine/xylazine/acepromazine   Dosing IP    To administer 

Ketamine          65 mg/kg

Xylazine           13 mg/kg

Acepromazine 2.0 mg/kg

 

Mouse   body weight        Volume   cocktail

20   g                                 0.13   ml

25   g                                 0.16   ml

30   g                                 0.20   ml

35   g                                 0.23   ml

To prepare cocktail

Ketamine (100 mg/ml)       1.0 ml

Xylazine     (20 mg/ml)         1.0 ml

Acepromazine (10 mg/ml) 0.3 ml

Sterile water or saline        7.7 ml

Cocktail                             10.0 ml

 

This cocktail is useful for longer   more invasive surgical procedures in mice.    It provides anesthesia for 45 -60 minutes.  If the acepromazine is eliminated, the   anesthesia will be shorter and the recovery faster.

 

Reversal agents to   alpha 2 agents.  Atipamezole is more specific for medetomidine than   for xylazine (as a general rule, Atipamezole is dosed at the same volume   as Medetomidine, though they are manufactured at different concentrations).
Atipamezole 1.0   – 2.0 IP, IM, IV, SC Once.  Repeat if needed To   reverse medetomidine or xylazine
Yohimbine 1.0   – 2.0 SC or IP Once.  Repeat if needed.  For   reversal of xylazine effects
Other injectable   anesthetics
Sodium   pentobarbital (Nembutal) 50   – 90 IP Recommended   for terminal/acute procedures only, with booster doses as needed. May be   appropriate for some survival procedures such as brain surgery Consider   supplemental analgesia (opioid or NSAID) for invasive procedures, especially   when used on a survival basis.  Very   long acting with a long recovery period.    Keep animal warm.
Tribromoethanol   (Avertin) 0.2   ml/10 g200   – 240 mg/kg IP May   be used once for survival procedure (boosted as necessary during procedure)   and once for terminal/acute procedure Use   fresh solution (<1 week of age).    See recipe below.
AVERTIN   recipe
66.66% stock solution
Dissolve 1 g 2, 2, 2-tribromoethanol in 0.5 g amylene hydrate.Store   wrapped in foil (light sensitive solution, ok to use brown glass bottle), at   -20 o C.  Date and label   bottle.  Stock solution can be kept for   up to one year.1.25%   working solution 12.5 mg/ml)
Take 0.5 ml concentrate and mix with 39.5 ml sterile saline.  Adjust to pH 7.

Recommended   to be used the same day it is prepared.    If it must be stored, it should be kept frozen at -20 o C, in   a foil wrapped container or brown bottle.    Use the frozen aliquots after it is thawed the same day; discard   frozen aliquots after 2 months.  Date   and label all bottles.

 

Dosing 200 -240   mg/kg

Mouse   body weight        Volume working   solution

20   g                                   0.32-0.38 ml

25   g                                 0.40   – 0.48 ml

30   g                                 0.48   – 0.58 ml

35   g                                 0.56   – 0.68 ml

 

Propofol 20   – 30 IV As   needed/to effect Only   useful IV, so therefore limited usefulness in mice. Respiratory depression   upon induction is possible.
Opioid analgesia
Recommended:
Buprenorphine
0.05   – 0.5 SC, IP, IV Used   pre-operatively for preemptive analgesia and post-operatively every 6-8 hour For   major procedures, requires more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with an NSAID
Recommended:
Butorphanol
0.5   – 5.0 SC, IP, IV Used   pre-operatively for preemptive analgesia and post-operatively every 1 – 4   hours Consider   multi-modal analgesia with a NSAID.    Shorter acting than buprenorphine
Morphine 5   – 10 IP Every   2 -4 hours As   pre-emptive analgesia and post-procedural analgesic for very painful   procedures
Reversal agents     for opioids

 

Naloxone 0.01   -0.05 IV, IM Once   as needed to reverse respiratory depression Note   that reversal will also remove the analgesic effect of the opioid
Non-steroidal   anti-inflammatory drugs (NSAID) analgesia.    Note that prolonged use may cause renal, gastrointestinal or other   problems
Recommended:
Carprofen
4-5   SC, PO Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose:  27 ug/ml = 5 mg/kg/day.  Carprofen is light sensitive –use dark   bottles.
Recommended:
MeloxicamMetacam®
1.0   – 5.0 SC, PO Used   pre-operatively for preemptive analgesia and post-operatively every 24 hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose: 1.7 ug/ml (0.3 mg/kg/day).  Use   injectable form of meloxicam to prepare drinking water:  Meloxicam suspension does not dissolve well   in water.
Recommended:
Ketoprofen
2   – 5 SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Ketorolac 5   – 7.5 oral or SC Used   pre-operatively for preemptive analgesia and post-operatively every 12-24   hour Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.
Flunixin   meglubinBanamine® 1.0   – 2.0 SC For   supplemental postop analgesiaEvery   12 – 24 hours for no more than 3 days Useful   for treating hyperthermia
Local anesthetic/analgesics (lidocaine and   bupivacaine may be combined in one syringe for rapid onset and long duration   analgesia)
Lidocaine   hydrochloride Dilute   to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Faster   onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine Dilute   to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisional Use   locally before making surgical incision Slower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 


NONHUMAN PRIMATE FORMULARY

DRUG     NAME DOSE     (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents     bradycardia and cardiac arrhythmias
Atropine 0.02-0.05                                                                                                            IM or SC Once at induction
Recommended:

Glycopyrrolate

0.01     IM or SC Once     at induction
Inhalation     anesthetics     – Must use precision vaporizer.  Survival surgery requires concurrent     pre-emptive analgesia.
Recommended:
Isoflurane or Sevoflurane
1-3%     inhalant to effect (up to 5% for induction). Up to 8% for Sevoflurane Whenever     general anesthesia is required Survival     surgery requires concurrent pre-emptive analgesia.
Nitrous     oxide (N2O) Up     to 60% with oxygen Whenever     deep sedation or general anesthesia is required Not     acceptable for surgery as sole agent – may be used with inhalant anesthetic     to potentiate effect and lower required dose
Ketamine     combinations     – May sting on IM injection
Recommended:Ketamine     alone 5     – 20 IM, SC As     needed.Administer     as pre-anesthetic, or as sole sedative/restraint.  Add ¼ – ½ dose as needed Ketamine     alone is recommended for NHP only.      Used for restraint for short procedures, including blood collection,     Tb testing, physical exam and prior to induction of gas anesthesia
Recommended:
Ketamine-Midazolam
5     -20+     0.05-0.2 IM, SC(in     same syringe) As     needed May     not produce surgical-plane anesthesia for major procedures, but useful for     restraint.
Ketamine-Medetomidine(Rhesus) 5     – 10+     0.1 IM or SC(in     same syringe) As     needed Will     not produce surgical plane of anesthesia for major procedures. If redosing,     use ketamine alone
Ketamine     – Xylazine 3     – 10+     0.15 – 0.6IM or SC(in     same syringe) As     needed Will     not produce surgical plane of anesthesia for major procedures. If redosing,     use ketamine alone.
Reversal agents     for alpha 2 agonists– Atipamezole is more specific for medetomidine than     for xylazine (as a general rule Atipamezole is dosed at the same volume as     Medetomidine, though they are manufactured at different concentrations).
Atipamezole ~     1.0 subcutaneous or IV Once.Repeat     as needed. To     reverse medetomidine or xylazine
Yohimbine 0.1     IV (slowly), IM Once.Repeat     as needed. To     reverse xylazine.
Other injectable     anesthetics and tranquilizers
Sodium     pentobarbital (Nembutal) 15     – 30 IV to effect and maintained withintermittent     bolus as neededor
2-20 mg/kg/hr IV continuous infusion after induction
Recommended     for terminal/acute procedures only. Occasionally used on survival basis     when cortical evoked responses are being measured. Preemptive     analgesia strongly recommended.      Consider supplemental analgesia (opioid or NSAID) for invasive     procedures.
Propofol 2.5     – 5.0 IV boluses. 0.3 – 0.4 mg/kg/hr continuous infusion As     induction agent, prior to general anesthesia with pentobarbital or     inhalant, or as sole agent on continuous infusion. Respiratory     depression/apnea upon induction is possible. Requirement for IV     administration usually means that ketamine must be used first.
Opioid analgesia
Recommended:
Buprenorphine
0.01     – 0.03 SC Used     pre-operatively for preemptive analgesia and post-operatively every 6-12     hour For     major procedures, require more frequent dosing than 12 hour intervals.     Consider multi-modal analgesia with a NSAID
Morphine 0.5     – 2.0 IM. SC or IV Every     2 -4 hours As     pre-emptive analgesia and post-procedural analgesic for very painful     procedures
Fentanyl     patch Patch/B.Wt.25     µg/hr in <7 kg50     µg/hr in 7–18kg  Place     patch 24 hours in advance of surgery and maintain for up to 3 days.Alternatively,     place at induction, premedicate with morphine, adm. morphine at 4 and 8     hrs. When     severe post-surgical pain is anticipated.
Reversal agents     for opioids
Naloxone 0.01     – 0.05 IV, IM Once     as needed to reverse  respiratory     depression Note     that reversal will also remove the analgesic effect of the opioid
Non-steroidal     anti-inflammatory drugs analgesia (NSAID) – Note that prolonged use may     cause renal, gastrointestinal, or other problems
Recommended:
Carprofen
2     – 4 SC or PO Used     pre-operatively for preemptive analgesia and post-operatively every 24 hour     for up to 4 days. Depending     on the procedure, may be used as sole analgesic, or as multi-modal     analgesia with buprenorphine.
Recommended:
Meloxicam
0.1     – 0.3 PO or SC Used     pre-operatively for preemptive analgesia and post-operatively every 24 hour     for up to 7 days. Depending     on the procedure, may be used as sole analgesic, or as multi-modal     analgesia with buprenorphine.
Ketorolac 0     0.5 – 1.0 SC or IM Used     pre-operatively for preemptive analgesia and post-operatively every 8 -12     hour for up to 4 days. Animal     must be well-hydrated. Use as multi-modal analgesia with buprenorphine.
Flunixin     meglubinBanamine® 1.0     – 2.0 IM only For     supplemental postop analgesiaEvery     12 – 24 hours for no more than 3 days Useful     for treating hyperthermia
Local     anesthetic/analgesics (lidocaine and bupivacaine may be combined in one     syringe for rapid onset and long duration analgesia)
Lidocaine     hydrochloride May     dilute to 0.5 -1% (=10mg/ml). May be mixed in same syringe with     bupivacaine.
SC or intra-incisional
Use     locally before making surgical incision Faster     onset than bupivacaine but short (<1 hour) duration of action
Bupivacaine 1.0mg/kgMay     dilute to 0.25 – 0.5%, May be mixed in same syringe with lidocaine.
SC or intra-incisional
Use     locally before making surgical incision Slower     onset than lidocaine but longer (~ 4-8 hour) duration of action

 


RABBIT FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias
Atropine 0.02-0.05                                                                                                          IM or SC Once   at induction.  May need to administer   booster dose. Not   recommend in this species. Some rabbits have atropinase and atropine is   quickly metabolized
Recommended:

Glycopyrrolate0.01   IM or SCOnce   at induction.

May   need to administer booster dose. Inhalation   anesthetics   – Must use precision vaporizer. Survival   surgery requires concurrent pre-emptive analgesia.  Mask or chamber induction without injected   pre-medication may result in breath-holding and injury.Recommended:
Isoflurane or Sevoflurane1-3%   inhalant to effect (up to 5% for induction). Up to 8% for SevofluraneWhenever   general anesthesia is requiredSurvival   surgery requires concurrent pre-emptive analgesia.Nitrous   oxide (N2O)Up   to 60% with oxygenWhenever   deep sedation or general anesthesia is requiredNot   acceptable for surgery as sole agent – usually used with inhalant anesthetic   to potentiate effect and lower required doseKetamine   combinations   – May sting on IM injection. May be used for pre-anesthesia prior to   intubation and induction of isoflurane anesthesia or as general anesthesia.Recommended:
Ketamine-Xylazine   35 – 50

+   5 -10 IM or SC (in same syringe.

Or   with xylazine adm. 10-20 minutes in advance) only if pre-medicated with an   anticholinergicAs   needed.

If   redosing use ¼ dose of each.May   not produce surgical-plane anesthesia for major procedures.  May be partially reversed with Atipamezole   or Yohimbine.Recommended:

Ketamine-Xylazine-Acepromazine   35-50

+   5 -10

+   0.75 – 1.0 IM or SC (in same syringe)As   needed.

If   redosing use ¼ dose each of ketamine and xylazine only.May   not produce surgical-plane anesthesia for major procedures. May be partially   reversed with Atipamezole or Yohimbine.Ketamine-Medetomidine   35 – 50

+   0.25 -0.5 IM or SC (in same syringe, or with medetomidine adm. 10-20 minutes   in advance) only if pre-medicated with an anticholinergicAs   needed.

If   redosing use ¼ dose of each.May   not produce surgical-plane anesthesia for major procedures. May be partially   reversed with Atipamezole.Ketamine-Midazolam 35 – 50

+2   – 5 IM or SC

(in   same syringe)As   neededMay   be useful for restraint for performing short, not painful procedures.Reversal agents for   alpha 2 agents – Atipamezole   is more specific for medetomidine   than for xylazine (as a general rule, Atipamezole is dosed at the same volume   as Medetomidine, though they are manufactured at different concentrations)Atipamezole0.1   – 1.0 SC, IM, IVOnce.

Repeat   as needed.To   reverse medetomidine or xylazineYohimbine0.2   – 2.0 IV or SCOnce.

Repeat   as needed. For   reversal of xylazine effectsOther injectable   anestheticsSodium   pentobarbital (Nembutal)20   – 50 IV to effect and maintained with

intermittent   bolus as needed

or
2-20 mg/kg/hr IV continuous infusion after inductionRecommended   for terminal/acute procedures only, with booster doses as neededConsider   supplemental analgesia (opioid or NSAID) for invasive procedures. Rabbits   have a very narrow window of safety for pentobarbital.                     Apnea is common at   anesthetic doses.Propofol12-26   IVAs   needed.  Very short acting unless   administered as a an IV drip.Only   useful IV, so therefore limited usefulness. Respiratory depression upon   induction is possible.Opioid analgesiaRecommended:
Buprenorphine0.01   – 0.1 SC or IPUsed   pre-operatively for preemptive analgesia and post-operatively every 6-12 hourFor   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAIDButorphanol0.1   – 0.5 IM, IV, SCEvery   4 – 6 hoursUseful   for minor, short proceduresMorphine0.5   -5 IV or IMEvery   2-4 hours for 8 hoursWhen   fentanyl patch is placed at inductionFentanyl   patchPatch   /B.Wt.

25   µg/hr

Place   patch 24 hours in advance of surgery and maintain for up to 3 days.

Alternatively,   place at induction, premedicate with morphine, adm. morphine at 4 and 8   hrs.When   severe post-surgical pain is anticipated. Best placed on the back at   induction and covered by a  bandage   after surgery

Reversal agents     for opioids

 

Naloxone0.01   -0.02 IV, IMOnce   as needed to reverse respiratory depressionNote   that reversal will also remove the analgesic effect of the opioid

 

Non-steroidal   anti-inflammatory drugs for analgesia (NSAID) — Note that   prolonged use may cause renal, gastrointestinal, or other problems.  Used pre-operatively for preemptive   analgesia and post-operatively for postoperative analgesia.  Depending on the procedure, may be used as   sole analgesic, or as multi-modal analgesia with buprenorphine.
DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Recommended:
Carprofen
1.0   – 2.2 PO Every   12 hours

Meloxicam0.1   – 0.3 PO, IM or SCAdm.   pre-op, then every 24 hours Flunixin   meglubin

Banamine®1.0   – 2.0 SC, PO, IMFor   supplemental postop analgesia

Every   24 hours for no more than 3 daysUseful   for treating hyperthermiaKetoprofen2   – 5 SC, IMAdm.   pre-op, then every 12-24 hour Local   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)DRUG   NAMEDOSE   (mg/kg) & ROUTEFREQUENCYNOTESLidocaine   hydrochlorideDilute   to 0.5%, do not exceed 0.4ml/kg total dose, SC or intra-incisionalUse   locally before making surgical incisionFaster   onset than bupivacaine but short (<1 hour) duration of actionBupivacaineDilute   to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisionalUse   locally before making surgical incisionSlower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 


RAT FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias .  Not   commonly used in rats.
Atropine 0.02-0.05                                                                                                          IM or SC Once at induction
Recommended:

Glycopyrrolate0.01-   0.02 IM or SCOnce   at induction Inhalation   anesthetics   – Best administered using a precision vaporizer but may also be administered   via nose cone containing small amount of anesthetic.  Survival   surgery requires concurrent pre-emptive analgesia.Recommended:
Isoflurane or Sevoflurane1-3%   inhalant to effect (up to 5% for induction). Up to 8% for SevofluraneWhenever   general anesthesia is requiredSurvival   surgery requires concurrent pre-emptive analgesia.NOT recommended

EtherTo   effect (cannot determine percentage)Whenever   general anesthesia is requiredStrongly   discouraged because of flammability and distress to animals. Used for short   procedures requiring anesthesia.Carbon   dioxideTo   effect (cannot determine percentage)Once,   at time of euthanasiaMay   be used for fast terminal procedure such as cardiac blood collection followed   by euthanasiaKetamine   combinations   – These dose combinations vary depending upon the type of procedure and the   age/strain of the animal.  Higher   ketamine dose with lower xylazine dose are used for less invasive procedures   and for very young/very old or critical patients.  In general, higher doses of xylazine with   concomitant lowering of the ketamine dose are used for more invasive   procedures.  See cocktail recipe at the   end of table.Ketamine-Medetomidine40   – 80

+   ~0.5-1 IP

(in   same syringe)As   neededMay   not produce surgical-plane anesthesia for major procedures. If redosing, use  ¼ dose of cocktail.Recommended:
Ketamine-Xylazine40   – 80

+   5-10 IP

(in   same syringe)As   neededMay   not produce surgical-plane anesthesia for major procedures, though more   reliable than in mice. If redosing, use1/4 dose of cocktail. May be partially   reversed with Atipamezole or YohimbineKetamine-Xylazine-Acepromazine40-80   + 5-10 + 1  (in same syringe)Once,   to induce anesthesia.  Repeat ¼ dose as   neededMay   not produce surgical-plane anesthesia for major procedures. If redosing, use1/4   dose of cocktail. May be partially reversed with Atipamezole or YohimbineKetamine-Midazolam75-100   + 4-5 IP (in same syringe)As   neededMay   not produce surgical-plane anesthesia for major procedures, but may be useful   for restraint.Rat cocktails

     1)    Ketamine/xylazine                            Dosing /100 g IP

 

0.2 ml          0.3 ml              0.4 ml

Ketamine (100 mg/ml) 6.0 ml                40 mg/kg      60   mg/kg          80 mg/kg

Xylazine (20 mg/ml)    3.75 ml                5 mg/kg      7.5   mg/kg         10 mg/kg

Sterile water or saline 20.25 ml

Cocktail                     = 30.0 ml

 

The lower dose provides light anesthesia   for short non-painful or minimally painful procedures.

The middle dose provides anesthesia for   30-45 minutes of surgery.

The upper dose provides deep anesthesia for   terminal procedures, for example perfusion.

 

 

2)    Ketamine/xylazine/acepromazine   Dosing/100 g IP

 

0.3 ml

Ketamine (100 mg/ml)       6.0 ml                               60 mg/kg

Xylazine     (20 mg/ml)        3.75 ml                             7.5 mg/kg

Acepromazine (10 mg/ml) 1.0 ml                               1.0 mg/kg

Sterile water or saline      19.25 ml

Cocktail                             30.0 ml

 

This cocktail is useful for longer   more invasive surgical procedures.  It   provides

anesthesia for 45 -60 minutes.

 

Reversal agents – Atipamezole is   more specific for medetomidine than for xylazine (as a general rule,   Atipamezole is dosed at the same volume as Medetomidine, though they   are manufactured at different concentrations)Atipamezole0.1   – 1.0 SC, IPOnce.

Repeat   as needed.Any   time medetomidine or xylazine has been usedYohimbine1.0   – 2.0 SC or IPOnce.

Repeat   as needed. For   reversal of xylazine effectsOther injectable   anestheticsSodium   pentobarbital (Nembutal)30   – 50 IPRecommended   for terminal/acute procedures only, with booster doses as needed. May be   appropriate for some survival procedures such as brain surgeryConsider   supplemental analgesia (opioid or NSAID) for invasive procedures, especially   when used on a survival basis.  Very   long acting with a long recovery period.    Keep animal warm.Propofol12-26   IVAs   neededOnly   useful IV, so therefore limited usefulness in mice. Respiratory depression   upon induction is possible.Opioid analgesiaRecommended:
Buprenorphine0.025   – 0.075 SC, IP, IVUsed   pre-operatively for preemptive analgesia and post-operatively every 6-12 hourFor   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAID. High doses of buprenorphine may   lead to pica behavior in rats.Butorphanol0.05   – 2.0 SCEvery   4 – 6 hoursUseful   for short, minor proceduresMorphine2   –5 IPEvery   2 -4 hoursAs   pre-emptive analgesia and post-procedural analgesic for very painful   procedures

Reversal agents     for opioids

 

Naloxone0.01   -0.1 IV, IMOnce   as needed to reverse respiratory depressionNote   that reversal will also remove the analgesic effect of the opioidNon-steroidal   anti-inflammatory analgesia (NSAID) Note that prolonged use may cause renal,   gastrointestinal, or other problemsRecommended:
Carprofen4-5   SCUsed   pre-operatively for preemptive analgesia and post-operatively every 12-24   hourDepending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Recommended:
Meloxicam

Metacam®1.0   – 2.0 SC, PO, IPUsed   pre-operatively for preemptive analgesia and post-operatively every 12-24   hourDepending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.  Drinking water   dose: 10.89ug/ml (1.0 mg/kg/day).  Use   injectable form of meloxicam to prepare drinking water:  Meloxicam suspension does not dissolve well   in water.Recommended:
Ketoprofen2   – 5 SCUsed   pre-operatively for preemptive analgesia and post-operatively every 12-24   hourDepending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Ketorolac05   – 7.5 oral or SCUsed   pre-operatively for preemptive analgesia and post-operatively every 12-24   hourDepending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Flunixin   meglubin

Banamine®1.0   – 2.0 SC, IMFor   supplemental postop analgesia

Every   24 hours for no more than 3 daysUseful   for treating hyperthermiaLocal   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)Lidocaine   hydrochlorideDilute   to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisionalUse   locally before making surgical incisionFaster   onset than bupivacaine but short (<1 hour) duration of actionBupivacaineDilute   to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisionalUse   locally before making surgical incisionSlower   onset than lidocaine but longer (~ 4-8 hour) duration of action

 


SWINE FORMULARY

DRUG   NAME DOSE   (mg/kg) & ROUTE FREQUENCY NOTES
Anticholinergics – Prevents   bradycardia and cardiac arrhythmias
Atropine 0.04IM   or SC Once at induction
Recommended:

Glycopyrrolate0.01   IM or SCOnce   at induction Inhalation   anesthetics   – Must use precision vaporizer.  Survival surgery requires concurrent   pre-emptive analgesia.Recommended:
Isoflurane or

Sevoflurane1-3%   inhalant to effect (up to 5% for induction). Up to 8% for SevofluraneWhenever   general anesthesia is requiredMask   induction is possible with small pigs.

 

Survival   surgery requires concurrent pre-emptive analgesia.Nitrous   oxide (N2O)Up   to 60% with oxygenWhenever   deep sedation or general anesthesia is requiredNot   acceptable for surgery as sole agent – usually used with inhalant anesthetic   to potentiate effect and lower required doseKetamine and/or   Telazol®) combinations – May sting on IM injection – Frequently used for   pre-anesthesia prior to intubation and induction of isoflurane anesthesiaKetamine-Acepromazine33   +

1.1   IM, SC

(in   same syringe)

For   sedation and pre-anesthesiaCan   result in large volumesRecommended:
Ketamine-Xylazine–20   +

2 IM

(in   same syringe)Prior   to general anesthesiaCan   result in large volumes – consider using Telazol® or Telazol® combination as   alternativeRecommended:
Telazol® alone (a combination of tiletamine and zolazepam – when   reconstituted with 5 ml sterile water, a vial contains 50 mg/ml of each drug.   Dose listed is based on 100mg/ml of combined active ingredients)6   – 8 IM

=.06   – .08 ml/kgFor   sedation or pre-anesthesiaNote   that Telazol® must be stored refrigerated once reconstituted.Telazol®-Ketamine-Xylazine   (TKX)~   0.025 ml of cocktail per kg IMFor   sedation or pre-anesthesiaNote   that Telazol® must be stored refrigerated once reconstituted.
To mix: reconstitute Telazol® with ‘large animal xylazine (100mg/ml) instead   of water; add 5 ml ketamine (concentration of 100mg/ml) Telazol® – Xylazine4.0   (Telazol) +

2.0   (xylazine)

IM,   SCFor   sedation or pre-anesthesiaNote   that Telazol® must be stored refrigerated once reconstituted. Reconstitute   Telazol with 5ml of sterile water.    Withdraw appropriate dosage and mix in syringe with animal’s dose of   Xylazine.    Reversal agents – Atipamezole is more   specific for medetomidine than for xylazine (as a general rule, Atipamezole   is dosed at the same volume as Medetomidine, though they are   manufactured at different concentrations.Atipamezole0.25   – 1.0 IV, IM SCAny   time medetomidine or xylazine has been used Yohimbine0.125   – 0.3 IV

0.2   IVOnce.

Repeat   as needed.To   reverse xylazineOther injectable   anesthetics and tranquilizersSodium   pentobarbital (Nembutal)20   – 30 IV to effect and maintained with

intermittent   bolus as needed

or
2-20 mg/kg/hr IV continuous infusion after inductionRecommended   for terminal/acute procedures only, with booster doses as needed.Preemptive   analgesia strongly recommended.    Consider supplemental analgesia (opioid or NSAID) for invasive   procedures.Propofol16   – 22 IVAs   induction agent, prior to general anesthesia with pentobarbital or inhalantRespiratory   depression upon induction is possible.Acepromazine0.08   – 0.2 IM or SCMay   be used whenever ketamine combinations are usedUsually   only used in conjunction with anesthetics such as ketamine. Acepromazine is a   tranquilizer and does not confer analgesia.Opioid analgesia – Pure mu receptor   agonists are not recommended  in swine   as they may produce excitationRecommended:
Buprenorphine0.005   – 0.05 SCUsed   pre-operatively for preemptive analgesia and post-operatively every 6-12 hourFor   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAIDButorphanol0.1   – 0.5 SCUsed   pre-operatively for preemptive analgesia and post-operatively every 4-6 hourFor   major procedures, require more frequent dosing than 12 hour intervals.   Consider multi-modal analgesia with a NSAID

Reversal agents     for opioids

 

NaloxoneTBDOnce   as needed to reverse respiratory depressionNote   that reversal will also remove the analgesic effect of the opioidNon-steroidal   anti-inflammatory drugs (NSAID) analgesia-   Note that prolonged use may cause renal, gastrointestinal, or other   problems.Carprofen2   – 4 SC or POUsed   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days.Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Recommended:

Meloxicam0.2   – 0.4 PO, IM or SCUsed   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days.Depending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Ketoprofen~   1.0 – 2.0 SCUsed   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 daysDepending   on the procedure, may be used as sole analgesic, or as multi-modal analgesia   with buprenorphine.Ketorolac1.0   – 5 SCUsed   pre-operatively for preemptive analgesia and post-operatively every 24 hour   for up to 4 days.Use   as multi-modal analgesia with buprenorphine.Recommended:

Flunixin   meglubin

Banamine®2.0   – 2.2 SC, IVFor   supplemental postop analgesia

Every   12 – 24 hours for no more than 3 daysUseful   for treating hyperthermiaLocal   anesthetic/analgesics (lidocaine and bupivacaine may be combined in one   syringe for rapid onset and long duration analgesia)Lidocaine   hydrochloride4   mg/kg

Dilute   to 0.5 -1% (=10mg/ml). May be mixed in same syringe with bupivacaine.
SC or intra-incisionalUse   locally before making surgical incisionFaster   onset than bupivacaine but short (<1 hour) duration of actionBupivacaineDilute   to 0.25 – 0.5%, May be mixed in same syringe with lidocaine.
SC or intra-incisionalUse   locally before making surgical incisionSlower   onset than lidocaine but longer (~ 4-8 hour) duration of action

BU IACUC approved August 2008, revised January 28, 2014