Guidelines for theUse of Analgesics and Tranquilizers in Laboratory Animal3
Barbiturates
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. [UniversityControlled Substances Policy]
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.
Don't forget to follow the University Controlled Substances Policy
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). 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.
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