General
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.
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.
- Infiltration or infusion- injection beneath the skin and other tissue layers along the site of an incision before or after a procedure
- Field block, ring block- injection into soft tissues distant from the actual incision in a pattern that intersects the nerve supplying the surgical site
- Nerve conduction block- infusion of a small amount of drug or directly adjacent to the sheath of a nerve supplying the surgical site
- Regional or spinal anesthesia- injection into the vertebral canal, epidurally or into the sub-arachnoid space. To avoid systemic toxicity, care must always be taken not to inject local anesthetics into blood vessels.
- Topical local anesthetics, such as lidocaine jelly, may be useful for some surgical wounds.
- Proparicaine may be used as a local anesthetic during retroorbital blood collection from mice. One drop on the eye, wait 10-15 minutes before performing the procedure.
An interesting use of local anesthetics is for amphibian and fish anesthesia. Tricaine and benzocaine can be added to water at a dose of from 25-100 mg/L, depending on the depth of anesthesia required. When the fish loses equilibrium (floats belly up) or an amphibian becomes inactive, it can be handled. For longer procedures, intermittent supplementation of anesthetic treated water to the gills or skin may be required. The animal is recovered in fresh water.
Phenothiazine and Buterophenone Sedatives
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.
Benzodiazapines
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 analgesic in 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.
The barbiturates are an acid ring molecule with various ring substitutes that imbue the drug with different properties. Barbiturates are also considered narcotics.
- Phenobarbital is the longest-acting of the barbiturates. Its use is limited primarily to sedation or as an anticonvulsant.
- Pentobarbital is a short-acting oxybarbiturate. It is usually used as a sole anesthetic agent, or is supplemented with an analgesic.When given intravenously, about 50-75% of the calculated dose is administered. Within several minutes the animal will lose consciousness, although it may experience a brief period of excitement. When the jaw muscle tone is relaxed, the animal should be intubated. If given intraperitoneally, usually the entire dose of pentobarbital is given and surgery can be performed when the animal no longer reacts to a toe pinch. Anesthesia from pentobarbital can last from 45-120 min, depending on the dose given. Additional drug can be supplemented as needed, being careful not to overdose as described below under "Precautions".
- Thiopental and Thiamylal are thiobarbiturates that are considered ultra-short acting. Similar to these is methohexital which is an oxybarbiturate. Because of the extremely short duration of activity (up to 10 min with methohexital, up to 15-20 min with thiopental or thiamylal) of these drugs, they are usually used as an intravenous anesthetic induction agent to allow intubation prior to use of inhalant anesthesia. Use is similar to that described for pentobarbital. However, when low doses are given IV, there may only be several minutes of anesthesia before the animal begins to waken. This is desirable as an induction agent. If higher doses are give for longer effect, care must be taken not to overdose as described below under "Precautions". Longer anesthesia may be seen when these drugs are used intraperitoneally in rodents.
- Effects and Side Effects In general the barbiturates cause generalized central nervous system depression, which can be dosed to provide sedation or general anesthesia. The drugs also have an anticonvulsant effect. Analgesia provided by the barbiturates is poor and a relatively deep plane of anesthesia is required for surgery, unless used in combination with analgesics. The barbiturates have significant cardiopulmonary depression, with apnea and hypotension commonly seen. Anesthetic death is common in animals that are not receiving supportive care. The barbiturates induce hepatic microsomal enzymes and may increase the metabolic rate of other drugs. Tolerance to the barbiturates develops with repeated use and doses may have to be adjusted accordingly.
- Precautions
- Barbiturates are poorly water soluble and are only available in intravenous preparations, although they are frequently administered intraperitoneally to smaller animals with limited venous access. Because of their acidic properties, barbiturates can be irritating when administered intraperitoneal, or if any leak from the intravenous injection site. Perivascular barbiturates can result in significant tissue necrosis and skin sloughing. If any barbiturate leaks (a visible swelling is seen during injection), the best thing to do is to infuse the area with sterile saline at several times the volume of the original leak. Some people recommend mixing the saline with 2% lidocaine to prevent pain and subsequent self-trauma.
- The barbiturates redistribute rapidly into all body tissues, including fat. Redistribution is one way that the drug is eliminated from the blood and obese animals may require higher doses of barbiturates to induce anesthesia. However, once the fat becomes saturated with the drug, metabolism becomes the primary means of elimination. Because metabolism is much slower, a common problem in administering barbiturates is overdosing with prolonged anesthetic recoveries (up to several days). Because of this problem it is best to titrate the dose carefully rather than administer large boluses. For obese animals, alternative anesthetics might be considered, although to a greater or lesser extent, most anesthetics share this problem when administered to obese animals. Prolonged anesthetic recovery can also be a problem when barbiturates are used in older animals or other animals with compromised hepatic and renal function which decreases metabolism of the drugs.
- Barbiturates are also controlled substances and their use requires special record keeping.
- Despite these disadvantages, the barbiturates are perhaps the most commonly used anesthetics in laboratory animals. Overall, they are a relatively easy to use anesthetic.
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.
Other Anesthetics
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). 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.
One disadvantage of the NSAIDs (or any other analgesics) when given to the animal for oral self-administration (e.g. in drinking water, juice, treat food, etc) is that the physiological disturbances caused by an anesthetic episode may significantly decrease an animal’s willingness to eat or drink during the immediate post-procedural period. This effect is independent of the level of invasiveness of any surgical procedure. To alleviate pain from surgical procedures, some form of parenteral analgesia should be given prior to anesthetic recovery and should be continued for a minimum of 12-24 hours after the animal has regained consciousness.
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.