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Guidelines for the Use of Anesthetics, Analgesics and Tranquilizers in Laboratory Animals
Curariform skeletal muscle relaxants or neuromuscular blockers (e.g. succinylcholine, decamethonium, curare, gallamine, pancuronium) are not anesthetics and have no analgesic effects. They may only be used in conjunction with general anesthetics. Normally, artificial respiration must be provided. Physiologic monitoring methods must also be used to assess anesthetic depth, as normal reflex methods will not be reliable.
It is important to realize that anesthesia is not a simple thing. It has profound effects on an animal's physiology because of the generalized central nervous system effects as well as specific effects on all other body systems. Thus, while anesthesia is necessary to prevent pain or distress in research animals, it must not be ventured into lightly. It is important to learn about the drugs you will be using and about the physiology of the animal you will be monitoring. Specific anesthetic drugs and their use are detailed below. All drug dosages are listed in RAR's formulary.
The Guide for the Care and Use of Laboratory Animals and the Institutional Animal Care and Use Committee Guidebook require that animals under anesthesia be carefully monitored to insure adequate depth of anesthesia, animal homeostasis, timely attention to problems, and support during anesthetic recovery. Monitoring includes, but is not limited to, checking anesthetic depth and physiological parameters (minimum: heart rate and respiratory rate) on a regular basis (minimum every 10 minutes).
Record keeping is an essential component of peri-operative care. For major surgical procedures on non-rodent mammals, an intra-operative anesthetic record must be kept and included with the surgeonís report as part of the animalís records. In addition to the above requirements, the record should include all drugs administered to the animal, noting the dose, time, and route of administration. These records should be available to RAR and any other personnel providing post-operative care. Although it is not required, RAR strongly encourages the use of an intra-operative rodent anesthetic record during surgical procedures.
The required monitoring will vary according to the species and the complexity of the procedure, but should include:
The following are suggestions from the American College of Veterinary Anesthesiology for monitoring anesthetized animals:
GeneralInjectable Anesthetics, Analgesics and Sedatives
Some of the drugs listed here do not possess all three criteria for an anesthetic and must be used in combinations to achieve full anesthesia or may be administered individually for restraint, sedation or analgesia. Dosages for specific animals are linked from RAR's formulary. Often injectable drugs are used in combinations. These drugs tend to have synergistic effects. Mixing them can significantly reduce the dosage needed for any individual drug.
As with inhalation anesthesia, injectables are given to effect. Dosages listed are guidelines. Effects may vary among individuals. If a drug is scheduled by the Controlled Substances Act of 1970, licenses are required to purchase them, and written records must be kept of their use. University policy outlines these requirements. Anesthetic drugs that have exceeded their expiration date may not be used, even for terminal procedures
Injectable anesthetics are, in general, metabolized by the liver and excreted by the kidneys. Animals with liver or kidney disease should not be anesthetized with these agents. Inhalation anesthetics are safer for use in sick or debilitated animals, because there is minimal metabolism, the amount of anesthetic administered can be controlled and one can cease administration as the situation dictates. Injectable anesthetics offer the advantage of requiring less expensive equipment.
The generic and brand names of local anesthetics often have the suffix "caine". Common local anesthetics are procaine (Novacaine), bupivicaine, lidocaine (Xylocaine) and proparicaine. Considerable experience and skill are necessary in the administration of local anesthetics to animals, and aseptic techniques must be employed. Some animals must be sedated before local anesthetics are injected.
Local anesthetics may be administered by several techniques. Anesthetic effects are seen within 15 minutes of administration and may last from 45 minutes to several hours, depending on the drug used.
These sedatives include acepromazine, chlorpromazine, droperidol (Innovar-Vet) and azaperone (Stresnil). These drugs have excellent sedative properties, as well as muscle relaxation, antiemetic and antiarrhythmogenic effects. They have no analgesic activity, but when administered with other anesthetics can potentiate their effect. Acepromazine is the most commonly used. It is recommended as a sole sedative in dogs and as an anesthetic premedication to improve both induction and recovery (it is long acting) in all species. Droperidol is usually only available in combination with the narcotic, fentanyl (Innovar-vet) and has been associated with aggressive behavior in dogs.
Disadvantages of these sedatives are that they are alpha adrenergic blockers and cause peripheral vasodilation which can lead to hypothermia. They may have prolonged activity in sight hounds. Acepromazine and chlorpromazine decrease seizure threshold, and are contraindicated in animals with CNS lesions. Because these sedatives lack analgesic activity it is important to realize that any painful stimulation of the animal may cause it to emerge rapidly from the sedated state.
The benzodiazapines include diazepam (Valium), midazolam (Versed) and zolazepam (Telazol). These drugs are anti-anxiety and anticonvulsant drugs with good muscle relaxation. They have minimal cardiovascular and respiratory effects. Sedation is minimal in most species, except for swine and nonhuman primates. The primary use of these drugs in anesthesia is in combination with other drugs. Ketamine-diazepam, midazolam-narcotic, and tiletamine-zolazepam (Telazol) combinations can be very useful for induction of general anesthesia and for short procedures. These drugs are regulated by the Controlled Substances Act and require special record keeping.
The thiazine derivatives include xylazine and medetomidine. These two drugs are very similar. They are alpha-2 adrenergic agonists. They cause CNS depression resulting in sedation, emesis and mild analgesia. They also cause hypotension, second degee atrio-ventricular block and bradycardia. Occasionally, aggressive behavior changes have been seen in dogs. They are very useful in combination with other drugs, like ketamine for anesthesia in rodents and swine. They are best avoided in dogs, cats and nonhuman primates, primarily because their significant side-effects can be avoided by using other drugs. They can be used alone for minor procedures in ruminants. It is important to note that the dose for these drugs in ruminants is 1/10 that used in other species. The effects of the thiazine derivatives can be reversed with yohimbine or atapimazole. Use of these drugs with the reversal agent shortens anesthetic recovery and greatly expands the safety and utility of these drugs. Xylazine is a potent analgesicin frogs appropriate for relief of post-surgical pain.
The opiates, sometimes referred to as narcotics,are a large class of drugs that exert their effects on the opiate receptors in the central nervous system. Depending on the receptors a drug is active against, and the type of action it has on the receptor, the effects of narcotics can be primarily analgesic, as with buprenorphine (Buprenex), pentazocine (Talwin) and nalbuphine (Nubain), or a mixture of analgesia and euphoria with sedation as with butorphanol (Torbugesic), fentanyl (Innovar-Vet), morphine, meperidine (Demerol) or oxymorphone. Opiates have little effect on the myocardium. However, there can be significant respiratory depression, as well as other side-effects such as nausea and vomiting, delayed gastric emptying, hypotension, and bradycardia. Some species may develop hyperexcitability if given certain opiates. These side-effects are seen more with the mixed effect opiates than the pure analgesics. Naloxone is a opiate antagonist that can be used to reverse the effects of other narcotics. Other opiates, like buprenorphine, nalbuphine and nalorphine, have mixed agonist-antagonist effects and may interfere with the effects of concurrently administered narcotics. All opiates are controlled substances and their use requires special record keeping. These drugs can be given alone as a post-procedural analgesic or in combination with other agents to provide balanced anesthesia, restraint with analgesia for minor procedures, or can be used to decrease the dose of an anesthetic that is needed to provide a surgical plane of anesthesia.
Don't forget to follow the University Controlled Substances Policy
The barbiturates are an acid ring molecule with various ring substitutes that imbue the drug with different properties. Barbiturates are also considered narcotics.
The dissociative anesthetics include ketamine (Vetalar, Ketaset) and tiletamine (Telazol). These drugs are easy to use and have a wide margin of safety for most laboratory species. They are cyclohexamine compounds, chemically related to piperazine and phencyclidine (PCP). The dissociative anesthetics uncouple sensory, motor, integrative, memory and emotional activities in the brain, providing there is a functional cerebral cortex. The state induced by high doses of ketamine is best described as catalepsy and is not accompanied by central nervous system depression. There is depression of respiratory function, but cardiovascular function is maintained. Muscle relaxation is very poor.
Ketamine and Telazol are supplied in a solution of 100 mg/ml. Telazol is a 50-50 mixture of tiletamine and zolezepam, a benzodiazepine. These drugs can be injected intramuscularly, intraperitoneally or intravenously; however, the subcutaneous route is discouraged. IP and IM injections of the dissociative anesthetics can be painful, as the drug is very acidic. Induction time for IM administration is three to five minutes; peak effect lasts about 20 min in most laboratory species. IP induction times are longer than with IM administration and recovery may be prolonged. Because the volumes needed are very small, in small animals there is no real advantage to IP injection and IM injection should be used whenever possible. Induction time following IV administration is rapid with only about 10 min of anesthesia provided. Approximately 1/2 of the dose should be given when dosing IV. The drug can be supplemented as needed.
The swallowing reflex is often preserved in animals receiving dissociative anesthetics. This may help prevent aspiration pneumonia if the animal regurgitates. However, this is not 100% and fasting and intubation are still recommended when using these anesthetics. The animal's eyes will usually remain open and the corneas should be protected with a layer of ophthalmic petrolatum or other suitable ointment. These drugs have poor analgesic activity, especially for visceral pain, and should be used in conjunction with an analgesic for abdominal, intracranial, orthopedic, ophthalmic or thoracic surgery.
Don't forget to follow the University Controlled Substances Policy
Propofol- is a sedative/hypnotic that can be used for induction or maintenance of general anesthesia. Analgesic effect is poor and addition of an analgesic to the anesthetic regimen is necesssary for surgery. The drug comes as an emulsion that must be mixed and used within several days. The advantages of propofol are that it has rapid induction and recovery times. It can be easily titrated and given to effect for prolonged periods without resulting in prolonged recovery. The disadvantages are that it must be given intravenously, it is expensive, it may result in apnea and it can cause bradycardia and hypotension.
Alpha Chloralose- or chloral hydrate is a mild hypnotic drug that does not produce complete anesthesia because of its poor analgesic properties. Chloral hydrate is shorter acting (1-2 h) than alpha chloralose (8-10 h). The primary advantage of these drugs is the minimal cardiopulmonary depression seen at the normal doses (high doses can cause severe respiratory depression). The disadvantage is that they can only be used alone for non-painful procedures. In addition, the drugs are very irritating to the GI tract, causing adynamic ileus if given IP and ulcers if given orally. Therefore IV use is the only route recommended. These drugs should not be used if any other alternative is available.
Tribromoethanol-is a short-acting anesthetic used in rodents for surgeries. The drug has rapid induction and recovery (15 min of surgical anesthesia and up to 90 min for complete recovery). The effect on animals is reported to be quite variable. Tribromoethanol was commonly used in the past but its use is now discouraged. Abdominal adhesions caused by IP administration have been reported to cause high post-procedural mortality, however, other studies have not demonstrated this. Tribromoethanol is not available commercially and must be prepared. Sterile preparation procedures are essential. The drug must be stored in the dark at 4°C to prevent degradation. Avertin Guidelines.
Urethane- is a long-acting (8-10h) anesthetic with minimal cardiopulmonary depression. The drug is used for long procedures in rodents. However, it is carcinogenic and is only allowed to be used with special justification and only for terminal (acute) procedures.
Analgesics are pain relievers most often given after a surgery. Narcotic analgesics have already been described above. Nonsteroidal antiiflammatory drugs (NSAIDs) may also be used for their analgesic effect. The NSAIDs consist of drugs like aspirin, ketoprofen, acetaminophen, flunixin and ketorolac. There are a large number of these drugs available, however, relatively few are used in animals. NSAIDs are, in general, less potent analgesics than are the narcotics. However, in specific instances they can have similar activity.
The advantages of the NSAIDs are that they do not cause sedation nor are they addictive as are the narcotic analgesics. There are no special recordkeeping requirements. In addition, they are more effective against pain caused by inflammation, such as is seen with tissue repair, orthopedic surgery, infection and injury.
The NSAIDs have several side-effects related to their pronounced anti-prostaglandin (anti-cyclooxygenase and in some cases lipooxygenase) activity. This is peripheral with most drugs, but is primarily central with acetaminophen. These effects can alter immune function, platelet function and can cause gastrointestinal ulceration. In addition, the NSAIDs all have the potential to cause nephro- and hepatotoxicity. This is variable among species. Cats, in particular, are sensitive to the NSAIDs. Acetaminophen is contraindicated is cats due to risk of methemoglobinemia.
Acetaminophen- mild analgesic, antipyretic, no effect on platelet function/bleeding time
Aspirin- mild analgesic, antipyretic, antiinflammatory, affects platelet function/bleeding time
Carprofen is a nonsteroidal antiinflammatory drug with antiinflammatory and analgesic effects and lower risk for toxicity in animals than other NSAIDS.
Flunixin meglumine (Banamine)- potent analgesic, antiinflammatory, antipyretic. Has potential for GI ulceration, hepato- and nephrotoxicity.
Ketoprofen- moderate potency analgesic, antiinflammatory, antipyretic. Has potential for GI ulceration, hepato- and nephrotoxicity, affects platelet function/bleeding time.
Ketorolac (Toradol)- potent analgesic, antiinflammatory, antipyretic. Has potential for hepato- and nephrotoxicity, less potential for GI ulceration than other NSAIDs, affects platelet function/bleeding time.
In general, by mixing anesthetic and analgesic drugs, the dose required for each individual drug is reduced, sometimes quite dramatically. Start at the low end of the dose range listed; you can always give more if needed! Drugs not listed below can be mixed using the same concepts, mix a sedative or hypnotic with an analgesic. Do not mix drugs in the syringe until you have determined that they are compatible when mixed. If in doubt administer separately. Determining expiration dates for mixed/diluted anesthetic or pain relieving drugs: In the absence of empirical evidence, expiration dates of diluted or mixed drugs will be determined as follows:
Determining expiration dates for mixed/diluted anesthetic or pain relieving drugs: In the absence of empirical evidence, expiration dates of diluted or mixed drugs will be determined as follows: