Chapter 016, Rabbit Neoplasia (American College of Laboratory Animal Medicine)
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The time that it takes until an animal is fully recovered from anesthesia will vary depending on the anesthetic agent, the type and duration of the surgery, and the physiological imbalances induced by the surgery or anesthesia. During this period the animal must be closely e.
Furthermore, since in rodents hypothermia and dehydration are two of the most common complications that are encountered, it is very important to provide supplemental heat and fluids. The response of animals to pain, and hence any clinical or behavioral signs of pain, will vary depending on the animal species and the surgical procedure. The best way to identify signs of pain is to closely observe the appearance and behavior of the animal prior to surgery, and note any changes after surgery.
The following are a number of signs associated with persistent pain. Sedatives and tranquilizers are generally used in animals to produce a psychological calming to facilitate handling, however, an important fact to remember is that analgesia is not produced.
They are most often used as pre-anesthetic agents to reduce fear and anxiety and facilitate handling. When used as pre-anesthetic agents the amount of general anesthetic agent needed is decreased. Upon painful stimulation, arousal may occur and thus, these drugs should be used with caution on animals that are intractable or overtly aggressive.
Loud noises may also cause arousal and unpredictable behavior. High doses may cause ataxia, cardiovascular and respiratory depression and hypotension without necessarily producing greater sedation. Depression may be even more pronounced in combination with a general anesthetic. The physiological state of the animal prior to administration of tranquilizers may markedly affect the degree of sedation achieved. Animals that are overtly aggressive, intractable and excited may not become manageable except with very high, respiratory-depressing doses. Inhalant anesthetics provide a relatively rapid onset and recovery.
UCSB Office of Research - Laboratory Animal Anesthesia and Analgesia
The high degree of control over anesthetic depth and the relative constant response over a wide variety of species are advantages. However, specialized equipment and constant monitoring of the patient are required with use of inhalant anesthetics. The depth and duration of effect in inhalation anesthesia can be controlled by the anesthesiologist through the manipulation of anesthetic concentration and pulmonary ventilation.
Differences in anesthetic solubility determine the rate at which the anesthetic concentration increases in the arterial blood. As highly soluble agents require more time to attain a significant concentration in the blood, they result in a more prolonged induction and recovery. The reverse is true for the highly insoluble agents which are therefore more controllable as their blood concentration can be rapidly changed; however, for this reason they are more hazardous.
Use of inhalant agents requires the following special equipment: Numerous simple apparatuses have been devised and reported in the literature and are commercially available for use in small laboratory animals for these purposes. Regardless of the system, proper scavenging of waste anesthetic gas is required to avoid personnel exposure. In general, experimental and surgical procedures that cause pain in humans should be expected to cause pain in laboratory animals. However, uncertainty exists regarding the degree to which the psychological interpretive component of pain might be a determinant of postoperative discomfort or suffering in animals.
In determining which procedures require postoperative analgesia and which analgesic agents may be useful, several factors should be considered. Postoperative analgesia is desirable for all surgical procedures involving penetration deeper than skin and subcutaneous tissues. The following categorical examples may be useful to investigators in determining the necessity for supplementary postoperative analgesia in procedures involving experimental or instructional use of animals:.
Local anestheticsare are used to produce desensitization and analgesia of the skin, local tissues, or regional structures. These agents may be used topically, by local infiltration, infiltration around a major nerve, or epidurally. They block the generation and transmission of nerve impulses by interfering with nerve cell membrane permeability.
These agents may be combined with a vasoconstrictor such as epinephrine to increase the intensity and the duration of analgesia. They must not be injected intravenously.
Circadian rhythm, 43 , 48 , 49 , , Phototoxic retinopathy, 48 , The stock solution should be stored in a refrigerator protected from light i. Local anestheticsare are used to produce desensitization and analgesia of the skin, local tissues, or regional structures. Desirable effects Safe and effective in most mammalian species No significant respiratory or cardiovascular depression or change in hepatic or renal function Increased sedation and analgesia in combination with alphaadrenergic agonist xylazine Many reflexes left intact:
The use of these agents is becoming more common in laboratory animal medicine. They are frequently infiltrated along incision lines to produce local anesthesia. This practice frequently reduces dosage requirements for the primary anesthetic agent and postoperative analgesic, minimizing adverse effects these agents may cause. Adverse side effects of local anesthetics are rare, but one must use caution when administering them to small rodents. This document is a compilation of anesthesia and analgesia guidelines prepared and revised by numerous laboratory animal veterinarians.
We acknowledge their contribution below:.
Laboratory Animal Anesthesia and Analgesia Dr. Manuel Garcia, Campus Veterinarian January ; revised April , December , June Table of Contents To facilitate navigation through this large document, each of the following sections has been hyperlinked.
Describe the drugs or techniques that will be used to ameliorate pain or distress, or provide scientific justification why these drugs or techniques would adversely affect the procedures, results, or interpretation of the results and therefore withholding them is necessary. Pain alleviating drugs or techniques should be withheld only for the necessary period of time. Management of Anesthesia General The most important factor in carrying out a successful anesthetic protocol is to start with a healthy, well-conditioned animal.
Fasting A period of fast sufficient to empty the stomach should be implemented prior to anesthesia to help prevent regurgitation and aspiration of gastric contents. Handling the Patient The animal should always be handled gently and calmly. Observations to make include: Cardiovascular system Heart rate and rhythm Mucous membrane color Capillary refill time Arterial pulse and pressure Body temperature Respiratory System Respiratory rate Depth of breathing Character of breathing Blood gases Hemoglobin oxygen saturation SpO2 Muscle tone Jaw or limb tone Response to painful stimulus toe or tail pinch Eye Position of eye presence or absence of movement Size of pupil Responsiveness of pupil to light Palpebral reflex Corneal reflex Lacrimation In general, the signs of pain perception and light anesthetic depth are: Tachycardia, arrhythmias Pupillary dilation, tearing, globe movement Presence of palpebral reflex Tachypnea or breath holding Movement in response to stimulus Arterial hypertension Coughing, swallowing, phonation The signs of deep anesthesia are: Bradycardia, arrhythmias, cardiac arrest Dry cornea, centrally fixed eyes, dilated pupil Cessation of breathing not breath holding Hypotension If you are ever in doubt about anesthetic depth, it is always better to decrease the rate of anesthetic administration.
It should also be kept in mind that anesthetic depth is influenced by: Drugs pre-medications, anesthetics, neuromuscular blocking agents, etc. Species and strain of animal Respiration and resulting changes in arterial blood gases, e. Circulation may be maintained through proper anesthetic dosing, maintaining proper body temperature, and the use of I.
Respiration is aided with the use of an endotracheal tube which ensures that the airway remains patent and free from obstruction. When spontaneous ventilation is not adequate due to patient positioning, an open thoracic cavity, or use of neuromuscular blocking agents, a mechanical ventilator should be used. Hypothermia will occur during exposure to anesthetic gases and in abdominal or thoracic surgery, particularly in small animals e. This may result in a greatly prolonged anesthetic recovery or even death.
Recovery from Anesthesia Surgery is not successful until the animal has fully recovered from anesthesia without any unintended physical or physiological impairments. The following are recommendations for caring for an animal during the post-anesthetic phase: The animal should be continuously monitored until it is conscious, or can be aroused when handled, and has stable vital signs e. Prevent hypothermia by placing the animal on a clean dry and warm surface.
For example, the animal's cage may be placed on a padded surface supplied with supplemental heat e. Be cautious with supplemental heat sources; hyperthermia can be as detrimental as hypothermia. Replacement fluid therapy is not usually required for most rodent surgeries, because they do not involve prolonger operative times or result in significant blood loss.
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However, fluid therapy can be beneficial and aids in the postoperative recovery of the animal. How much fluid to administer depends on numerous variables, but in most uncomplicated i. As a general rule, animals should not be returned to the animal room until they can stand and move about their cage.
To prevent cannibalism or suffocation, house rodents individually until they can stand and move around. After the animal is returned to the animal room, a member of the investigator's staff or other individual to whom postoperative care has been delegated should monitor the animal at least once a day.
The animal should be observed for signs of pain, and surgical complications, including infection or dehiscence of the surgical site s. Pain assessment guidelines are included below. The Campus Veterinarian should be contacted if there are any unexpected complications. External wound clips or sutures should be removed days after the surgery. Pain Assessment The response of animals to pain, and hence any clinical or behavioral signs of pain, will vary depending on the animal species and the surgical procedure.
Sign Explanation Guarding The animal alters its posture to avoid moving or causing contact to a body part, or to avoid the handling of that body area. Abnormal appearance Different species show different changes in their external appearance, but obvious lack of grooming, changed posture, and a changed profile of the body are all observable signs. Altered behavior Behavior may be depressed; animals may remain immobile, or be reluctant to stand or move even when disturbed. They may also exhibit restlessness e.
Animals in pain may also show altered social interactions with others in their group. Vocalization An animal may vocalize when approached or handled or when a specific body area is touched or palpated.
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It may also vocalize when moving to avoid being handled. Mutilation Animals may lick, bite, scratch, shake, or rub a painful area. Inappetence Animals in pain frequently stop eating and drinking, or markedly reduce their intake, resulting in rapid weight loss. General Characteristics of the Different Classes of Agents Sedatives and Tranquilizers Sedatives and tranquilizers are generally used in animals to produce a psychological calming to facilitate handling, however, an important fact to remember is that analgesia is not produced.
Reduces the hematocrits of animals Antagonizes apomorphine-induced emesis in the dog May produce cardiac arrhythmias in the dog High doses of chlorpromazine in the cat produce tremors and rigidity. May produce cleft lip and cleft palate in mouse fetuses May produce ocular lesions after prolonged use Benzodiazepines Common agents: Diazepam is also incompatible in solution with other drugs, therefore it should never be mixed in the same syringe with other drugs except ketamine.
Midazolam works well after IM or SQ injection and may be mixed with certain other drugs Alphaadrenergic agonist Common agents: Little to no therapeutic effect in swine In dogs, bloat from aerophagia may develop May precipitate abortion Miscellaneous: Xylazine is a potent sedative and central nervous system depressant. It is used in combination with other agents to produce anesthesia. Its muscle relaxation and analgesic effects are excellent.
It does, however, cause potent cardiovascular depression. Medetomidine and detomidine are newer and more specific central alpha-2 agonists, resulting in longer, more profound sedation and analgesia than xylazine and fewer adverse cardiovascular side effects. Injectable Anesthetic Agents Ketamine, the most common drug in this class, produces a state of chemical restraint and a type of anesthesia characterized by muscle rigidity and an apparent dissociation of the mind from the environment. Depth of anesthesia is dose related. It produces activation of the limbic system and depression of the thalamoneocortical system rather than dose related general CNS depression.
It is rapidly metabolized to norketamine demethylated ketamine in the liver via the hepatic P microsomal system. The metabolites are mainly excreted in both urine and bile. Desirable effects Safe and effective in most mammalian species No significant respiratory or cardiovascular depression or change in hepatic or renal function Increased sedation and analgesia in combination with alphaadrenergic agonist xylazine Many reflexes left intact: Zolazepam is a diazepinone minor tranquilizer.
There are four basic groups of barbiturates which vary according to duration of action after IV administration. Increased incidence of ventricular fibrillation Intra-arterial injection produces arterial wall spasms and may result in gangrene. In rats, pentobarbital blocks release of LH and FSH if administered prior to normal gonadotropin release. Hypothermia due to increased peripheral vasodilation Resistance may develop after repeated use due to increased rate of metabolism by hepatic microsomal enzymes.
Tribromoethanol TBE is an injectable anesthetic that causes generalized CNS depression, including both the respiratory and cardiovascular centers. It is metabolized by the liver, and excreted in the urine as TBE glucoronate. Avertin is no longer available, and is instead prepared from non-pharmaceutical-grade TBE dissolved in tertiary-amyl alcohol. This agent has no application in clinical veterinary medicine, and its continued routine use for rodent anesthesia is controversial, since effective pharmaceutical-grade alternatives are available.
Approval may be granted if there is sufficient scientific necessity, and the PI can demonstrate that the drug will be prepared, stored and used in a manner that ensures it stability, sterility, and efficacy see preparation and handling recommendations below. Desirable effects Produces surgical anesthesia in mice Good muscle relaxation Undesirable effects Inconsistent and variable anesthetic duration Serious adverse effects peritoneal inflammation or death when administered by the IP route, which is the most common route.
Animals receiving TBE should be carefully and closely monitored for several days, and any morbidities or mortalities should be reported to the Campus Veterinarian. The solvent used to prepare the stock solution, tertiary-amyl alcohol, and the stock solution need to be kept away from sources of ignition and stored in an explosion-proof refrigerator TBE causes skin, eye, and respiratory irritation, therefore it should be prepared in a fume hood and research staff preparing the TBE stock solution should wear gloves, respirator, safety glasses and lab coat when handling TBE.
Narrow margin of safety Preparation and Handling Components, 2, 2, 2 Tribromoethanol and tertiary amyl alcohol, are mixed to prepare a stock solution.
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Numerous stock solutions are described in the literature. The concentration of TBE in tertiary-amyl alcohol in the pharmaceutical-grade Avertin was The stock solution should be stored in a refrigerator protected from light i. GMAs, 28 , Caloric management, 31 , 57 , Carcass disposal, 20 , 73 - 74 , , Cattle, 62 - 63 , 64 , - , - Cedar shavings, 69 , Ceilings, 56 , 81 , Centers for Disease Control and Prevention, 19 , 21 , , , Cercopithecine herpes v irus 1 , Chickens, 48 , Chimpanzees, xviii , Chlorines and chloramines, 72 , 78 - 79 , 80 , 85 , Circadian rhythm, 43 , 48 , 49 , , Cleaning agents, 18 , 71 , Clothing and footwear, 20 , 21 , Cold storage and refrigeration, 66 , 73 , , Cold stress, 43 , 44 , Construction guidelines, - Containment of hazardous materials, 21 , - Corridors, 86 , , , , , Cryopreservation, 76 , Desiccation stress, 45 , Disaster planning, 35 , 74 - Disease control, 23 , 72 , 81 , , , , - , , - , Disease susceptibility, 19 , Diurnal cycles, 48 , Doors, , , , , , , , Drafts, 46 , Drainage, 54 , , , , , , Ecdysis molting , 45 , Electric power, , , , , , Enclosures see Cages and caging; Primary enclosures; Secondary enclosures.
IACUC review, 26 , 27 - Engineering standards, 6 , 7. Entrapment, accidental, 51 , Ethical considerations, xiii , xvii , 4 - 5 , AV responsibility, , , Exotic, wild, and zoo animals, 2 , 18 , 32 , 44 , 84 , , - , - Experimental design and statistics, recommended reading, - Experimental endpoints, 27 - 28 , , Field studies, 18 , 32 , Flaky skin, 45 , Floors, - Genetics, recommended reading, - Gerbils, 43 , 44 , Gnotobiotic animals, 52 , 70 , Goats, 49 , 62 , , , , Guinea pigs, 44 , 51 , 57 , 71 n.
Hamsters, 44 , 57 , 64 , 68 , 71 n. Hazard identification and risk assessment, 18 - Hazardous agents, 20 - Heat stress, 43 , Heating and air-conditioning, - Helicobacter spp, , Herpes v irus , 23 , Horses and ponies, 63 , Humane endpoints, xvii , 5 , 12 , 27 - 28 , 29 , , , - Hygiene, personal, 18 , 19 , Identification of animals, 75 , Imaging facilities, - Immunodeficient animals, 21 , 28 , 66 , Inspection of facilities and equipment, Institutional official, 13 - 14 , 17 , 23 , 24 , 25 , 30 , International Air Transport Association, Irradiation facilities, - Laboratory Animal Welfare and Training Exchange, Lymphocytic choriomeningitis virus, Macacine herpes v irus , 23 , Macaques, 23 , Management of animals see Behavioral and social management; Husbandry; Population management.
Laboratory Animal Medicine - 3rd Edition - ISBN: , View all volumes in this series: American College of Laboratory Animal Medicine. Purchase The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents - 1st Edition. American College of Laboratory Animal Medicine; The Laboratory Rabbit, . Rabbits. Chapter 6. The Domestic Rabbit,. Introduction and Background Chapter Rabbit Neoplasia. Introduction. Neoplasms of Oryctolagus cuniculus.
GMAs, 28 , 68 , - Mouse hepatitis virus, , National Institutes of Health, 19 , Neuromuscular blocking agents, - Non-pharmaceutical-grade chemicals or substances, 31 - Other animals, recommended reading, - Owl monkeys Aotus tri v irgatus , Pedigree management, 55 , 76 , Performance standard, defined, 6 - 7. Pest control, 74 , 87 , Pesticides, 65 , Photoperiod, 47 , 48 , 81 , , Phototoxic retinopathy, 48 , Physical hazards, 18 , HVAC, xviii , 46 - 47 , - Pigeons, 60 , , Pilot studies, 26 , Poikilothermic animals, 41 , 44 , 55 , 80 , 82 , Poultry, 44 , 48 , Practice standard, 7 , Primary enclosures, 42 , 43 , 44 - 45 , 46 , 50 - 52 , 72 , 77 , Principal investigator, 5 , 16 , 18 , 27 , 28 , 32 , , Procedural habituation and training, 29 , 64 - Procurement of animals, - IACUC review, 26 - Quail, 60 , ,