Animal health, conditioning & stress

The well-being of the animal and validity of the study are enhanced by proper management before the operative procedure.

Animal health status
The health status of animals should be assessed before undergoing a surgical procedure. Evaluation of blood, urine, and feces can be helpful, depending on the animal species and health history of the animal or colony. Health assessments are usually conducted during a quarantine period when the animals are kept separate from conditioned animals. The quarantine period of random source animals is generally a few weeks duration, in part since these animals may need to be immunized against common infectious diseases. Purpose bred animals also require quarantine, but the period is much shorter.

Conditioning
It is important that animals be provided a period of adaptation prior to undergoing surgical procedures. This allows the animal's physiologic and metabolic systems to stabilize to a new environment thereby minimizing risk of complications; this period also minimizes the effects of uncontrolled environmental influences on the results obtained from the experimental protocol.

Animal stress
Investigators and research staff should be familiar with the normal behavior of the species and recognize abnormal behaviors. Since distress can alter experimental results, efforts should be targeted to reduce stresses associated with survival surgery, prolonged studies, confinement, and chronic pain.

Antimicrobial prophylaxis
might be indicated prophylactically for certain surgical procedures or when known breaks in sterility occur, but should not be used as a substitute for proper aseptic techniques. Please consult the veterinarian about using antimicrobials for each individual animal.

Principles of Anesthetic Management
Prevention of perceived pain during surgery is the primary function of anesthesia. Anesthesia also enables humane restraint, improves safety, and increases technical efficiency. Although many factors affect choice of a particular anesthetic drug or technique, the greatest concern must be the well-being of the animal. A general rule of thumb is “aim only for the degree of restraint and anesthesia required” - more may not be better and often is associated with a greater potential for adverse effects.

Criteria for choosing anesthetic agents

• knowledge of the procedure and duration
• compatibility of the anesthetic with experimental design
• actions and properties of the anesthetic agent(s)
• biological characteristics of the selected species
• prior experience with the anesthetic in the species
• available equipment, personnel and facilities.

Anesthetic & Analgesia Definitions

• anesthetic - a drug which causes a reversible loss of conscious awareness and sensation, including pain.
• analgesic - a drug which causes an absence of pain in response to stimulation which would normally be painful; often, what is actually achieved following administration of an analgesic is hypoalgesia, or diminished pain in response to a stimulus.
• sedative - a drug which produces a state of decreased motor activity, mental calmness, and drowsiness; does not imply analgesia, although most sedatives will increase the pain tolerance threshold by reducing anxiety and fear.
• neuromuscular blocking agent (paralytic agent) - a drug which blocks transmission at the neuromuscular junction; these drugs lack anesthetic and analgesic properties. It is illegal to use a neuromuscular blocking agent for painful procedures, unless anesthetics or analgesic drugs are used in conjunction.

General Anesthesia provides overall insensitivity and unconsciousness. Basic elements of general anesthesia include:

• unconsciousness
• amnesia (loss of memory of pain or distress)
• analgesia
• muscle relaxation
• diminished motor response to noxious stimuli
• reversibility

Two main delivery systems are used in veterinary medicine, inhalation and injection; a brief review of common drugs follows:

Inhalation anesthetics
are gaseous or volatile agents administered via the respiratory tract. Inhalation anesthetics, when properly administered allow one to control and regulate anesthetic depth. Disadvantages include need for specialized delivery equipment and potential toxicosis to personnel chronically exposed to anesthetic vapors. Endotracheal intubation facilitates effective and safe delivery of inhalation anesthetics. A waste gas scavenging system should be used to minimize exposure to personnel. Examples include: ether, halothane, methoxyflurane, and isoflurane.

Injectable anesthetics
can serve as the sole anesthetic agent, be used to induce anesthesia before inhalation anesthesia, or supplement regional anesthesia. To minimize the chance of drug overdose and to reduce drug-related tissue damage, drugs used for smaller (<4 kg) laboratory animals may need to be diluted.

• Hypnotic/sedative drugs are widely used for inducing or managing general anesthesia. They induce a dose-dependent spectrum of CNS depression, from sleep to deep general anesthesia. Higher doses may cause medullary paralysis, respiratory arrest and death. Examples include: pentobarbital, sodium thiamylal, sodium thiopental and chloral hydrate.
• alpha 2-Adrenergic receptor agonists have tranquilizing, sedative, and potent analgesic properties. Examples include: xylazine (trade name Rompum).
• Dissociative drugs induce anesthesia, have short duration of action, a wide safety margin, and cause minimal cardiopulmonary depression. To decrease undesirable actions such as muscle hypertonus and emergence delirium, they may be used in combination with hypnotics, tranquilizers, or alpha 2-adrenergic agonists. Examples include: ketamine and tiletamine which is often in combination with the tranquilizer, zolazepam.
• Muscle relaxants are predominantly central or peripheral acting. The peripheral acting muscle relaxants are devoid of sedative and analgesic properties. These drugs, when used during surgery, must be administered only in conjunction with general anesthetics. The investigator must remain aware that the animal is unable to respond with purposeful movement to noxious stimulation and the animal must be closely monitored (e.g. heart rate, arterial blood pressure) to ensure adequate general anesthesia. Examples include: succinylcholine and dimethyl tubocurarine.

Local and Regional Anesthesia
is used most often in large animals, such as horses, cattle or sheep. Localized insensitivity in awake or mildly sedated animals can result from topical application or injection of appropriate anesthetics in the region of the surgical incision (local anesthesia); injection in proximity to nerve trunks (nerve block); or injection into the subarachnoid or epidural spaces (regional anesthesia).

Local and regional anesthesia advantages include:

• the cost of drugs and equipment is low
• the need for special post-anesthetic care is minimal
• avoids undesirable complications that accompany unconsciousness and recumbency:
  • regurgitation and aspiration of gastric contents
  • inefficient respiratory gas exchange
  • traumatic complications associated with recovery
  • myopathy (particularly in large, heavy animals)

Local and regional anesthesia disadvantages Include:

• some degree of animal cooperation is necessary
• the anesthetic period is relatively short
• tissue damage has been associated with injection of large volumes of anesthetic agents
• rapid absorption or inadvertent intravascular injections of large quantities of anesthetic agents can cause life-threatening reactions.

Analgesic drugs
used to reduce pain are initiated pre-emptively during the surgical period and continued well into the postoperative recovery period. It is often erroneously presumed that an animal is not in pain, when there is no obvious change in behavior. Pain can be difficult to detect because of individual and species variation. "Typical" signs of pain include guarding the painful area, vocalization, licking, biting, self mutilation, signs of depression, grinding of teeth, restlessness, lack of mobility, failure to groom, abnormal posture, changes in sleep patterns, and failure to eat or drink. Pain can be assumed to have been present if administration of analgesics causes these signs to disappear.

Consultation with the attending veterinarian is recommended since there is tremendous variation between species as to their response to analgesic drugs. Limited animal studies have been conducted and for many species there will be widely different published dosage schedules. Never extrapolate from human data, please consult with the veterinarian.

Guidelines for the administration of analgesics

• Medical and veterinary reports suggest analgesics are most effective when administered prior to the painful stimulus, before the surgical incision and tissue manipulation.
• Analgesic drugs must be given at the proper initial dose and subsequent doses must be given according to schedule.
• Federal law requires pain relief according to the same guidelines for a human patient undergoing a similar procedure.

In addition to the care which must be taken when choosing the proper dosage and schedule for a particular species, different analgesics are indicated for different types of pain:

• Nonsteroidal anti-inflammatory agents (NSAID) are effective against pain associated with inflammation, acute pain associated with soft tissue injury, burns, and pain associated with bone injuries or disease. However, severe pain in any of these categories may be best treated with NSAID's in combination with potent opioid agonists. Examples include: banamine, ibuprofen.
• Opioid agonists are effective against most visceral and somatic pain; although generally not as effective as NSAID's against bone pain, they may be used in conjunction with NSAIDs to treat severe bone pain. Examples include: morphine, meperidine.
• Opioid agonist-antagonists are effective against mild to moderate visceral and somatic pain. Examples include: buprenorphine, butorphanol.
• Neurogenic pain is pain which arises from damaged nerves or from amputation. This pain is difficult to treat and rarely responds well to any of the drugs listed above. More likely to be effective: tricyclic antidepressants such as amitriptyline, anticonvulsants such as carbamazepine, or antiarrhythmics such as lidocaine.

Management of Drugs
Drugs which are considered by the U.S. Department of Justice, Drug Enforcement Agency (DEA) to be controlled substances must be stored in a locked cabinet in a secured area (e.g. behind two locked doors). Controlled substances must never be left unattended since the potential for theft and misuse of these drugs is high. In the past, the DEA allowed some latitude in research facilities and did not closely observe who exactly administered these drugs to the research animal. This is no longer true. Therefore, each investigator with a DEA license must personally supervise the administration of these drugs. In addition, OVR may no longer transfer controlled drugs to research staff.

All drugs, whether or not they are DEA regulated, must be properly labeled and included on the label must be the expiration date. Expiration dates should be checked periodically, at least once every three months, and expired drugs immediately discarded. It is a violation to use expired drugs on animals involved in research procedures (there are a few limited occasions wherein expired drugs may be used for terminal, non-survival procedures). University Animal Care staff will discard any drug they observe to be improperly labeled, or in use after the expiration date has passed. At the minimum the label on a drug shall include:

• name of drug and concentration
• expiration date (also the mixing date if a combination)
• name of Investigator (if the drug is not owned by OVR)
• specific storage requirements (e.g. refrigerate)