Approved by Animal Institute Committee: 11/14/01
Albert Einstein College of Medicine (Einstein) follows U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Teaching and the Public Health Service Policy on Humane Care and Use of Laboratory Animals which state:
“Proper use of animals, including the avoidance or minimization of discomfort, distress and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals.”
“Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia, [unless the omission of these agents is justified for scientific reasons in writing by the investigator]. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents.”
“Animals that would otherwise suffer severe or chronic pain or distress that cannot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure.”
Furthermore, to comply with the USDA’s implementation of the Animal Welfare Act, investigators must document in their written protocols, the methods they have used to explore alternatives to procedures that cause more than momentary or slight discomfort, pain, or distress, and they must provide a written plan for dealing with pain, discomfort, or distress when it is encountered.
In interpreting and implementing these policies and regulations, the Animal Institute Committee (AIC) has adopted the following specific policies, which apply to all vertebrate species used by Einstein investigators:
- Surgical Procedures: All surgical procedures are considered to be potentially painful and must be performed under anesthesia. Furthermore, many surgical procedures entail post-operative pain and therefore, require post-operative analgesia.
Procedures That Can Result in Chronic Discomfort or Distress: Analgesic treatment must be considered in case there are signs of discomfort/distress. Omission of analgesic treatment when signs of pain or distress are observed must be scientifically justified.
- Surgical procedures that absolutely require post-operative analgesia include:
Orthopedic procedures (including amputations)
Abdominal procedures involving gastrointestinal tract resection
Other surgical procedures such as craniotomy and laparotomy may require post-operative analgesia if such procedures involve substantial cutting or detachment of muscle tissue.
- Injection of irritants
- Tumorigenicity/metastasis studies
- Spontaneous or experimental diseases that are considered to be painful - arthritis, pancreatitis, peritonitis, etc.
- Prolonged restraint
- While anesthesia is recommended, it is not required for a single incident of tail amputation (biopsy for genotyping) or toe-clipping (for identification) in mice younger than 4 weeks of age. These procedures performed on mice 4 weeks of age or older require topical, local, or general anesthesia (see also AIC Policy 0001). A contingency plan to provide post-operative analgesia to older animals must be in place (see 6 below).
- Blood sampling from the retroorbital sinus or peripheral veins of mice may be performed by experienced individuals with manual restraint alone.
Assessment of Pain, Distress, Discomfort
Pain, discomfort, and distress in humans have a subjective component which makes it difficult to compare pain levels with animals. Furthermore, many laboratory animals, especially prey species such as rodents, have evolved to mask signs of minor to moderate discomfort. Therefore, any outward signs observed in a laboratory animal, probably indicate real discomfort or illness.
- Evaluation of conscious (awake) animals: Many of the signs described below are general indications of illness whose expression varies with species. The context (e.g. immediately post-op) accompanied by obvious injury or lesion (e.g. abscess), as well as response to analgesic therapy, will help interpretation.
Signs that may indicate pain or distress in conscious animals include:
Evaluation of unconscious patients - intraoperative monitoring: All animals undergoing surgical procedures, either survival or non-survival, must be adequately anesthetized. The adequacy of anesthesia must be evaluated periodically during the procedure.
- Piloerection (ruffled fur)
- Unkempt fur (failure to groom)
- Hunched or abnormal posture
- Reluctance to move (spontaneously or in response to stimuli)
- Withdrawal (withdrawn from cagemates, hiding in corner, or in nest)
- Protection (withdrawal/avoidance in response to palpation of the affected area or part
- Bruxism (teeth grinding)
- Vocalization (spontaneous or in response to palpation of the affected area or part)
- Decreased appetite, reduced fecal output, weight loss, loss of body condition
- Dehydration, decreased urine output
- Excessive attention to the affected area or part (licking, biting, scratching)
- Abnormal gait
- Persistent struggling during restraint
Signs of an inadequate level of anesthesia include:
- Responses to toe pinch (withdrawal reflex)
- Responses to corneal or palpebral stimulus (touch) - blink response
- Increased respiratory rate, heart rate, and/or blood pressure - usually as level of anesthesia is reduced, these will increase as a sign of pain
- Response to surgical manipulation
- If the animal is responsive, the investigator must stop the procedure immediately and adjust the anesthetic level.
Monitoring, Evaluation and Treatment
- Responsibility: Even though Einstein and the AIC are responsible from a regulatory perspective for ensuring that all animals used on campus receive adequate and timely veterinary care, each investigator and his or her staff bear primary responsibility for monitoring, evaluating, and treating their animals. In most cases, AIC veterinary staff can help investigators make an assessment of animals that are exhibiting signs of discomfort or distress. However, it is not possible for the veterinary staff to monitor all animals at appropriate time intervals to detect the onset of problems. Therefore, the AIC requires that investigators check their animals regularly as indicated in the protocol. The protocol must also have a written contingency (treatment) plan for dealing with discomfort and distress.
- Frequency of monitoring: All animals owned by an investigator must be examined by the principal investigator or his/her staff at least once per week, even when no experiments have been performed. When animals are on an experiment or are otherwise likely to develop clinical disease which may cause pain, discomfort or distress, the investigator or his/her staff should check animals at least 3 times a week, or as often as specified in the approved protocol. Animals that have developed clinical signs must be evaluated daily and in some cases more frequently. Unless there is strong scientific justification, the AIC does not permit animals to experience unrelieved pain or distress longer than 12 hours (see below).
Surgical Recovery and Post-Operative Period
All animals undergoing surgery must be monitored continuously during the surgery and subsequent recovery period, until they are ambulatory. For animals that do not automatically receive an analgesic during the recovery period, an evaluation of pain and distress must be made once the animal is awake, before it is returned to the animal facility. The AIC requires that each animal then be checked again within 12 hours and at least once daily thereafter for at least 2 additional days to reevaluate pain and wound healing. Animals that show signs of pain or distress must be monitored at least once daily until they return to normal behavior. More frequent or extended monitoring may be required, as specified in the approved protocol.
Treatments and Interventions
Investigators must have a plan for treatment / intervention described in their approved protocols. The AIC expects one of the following interventions to be made within 12 hours of detecting pain/distress:
- Continue to monitor for up to 12 hours, at which time if signs of pain/distress have not subsided, the animal is euthanized.
- Upon detection of signs of pain/distress, administer analgesic medication. Reevaluate at the time the next analgesic dose is recommended, but not more than 12 hours later. Thus if the recommended dosing interval is every 6 hours, the animals must be reevaluated within 6 hours. Reevaluation includes a decision to either discontinue analgesia, euthanize the animal, continue the same dose, or to adjust the dose. This plan must be followed for the period of time specified in the protocol, after which if the animal is still in pain or distress, it is euthanized.
- Analgesic medication can be scheduled to be given routinely for a specific number of treatments during the post-procedural period (fixed plan). The efficacy of the treatment must still be monitored, and any deviations in the prescribed dose or schedule must be justified and documented. This may include reducing the dose, if the animal appears to be free of pain/distress, to reduce the occurrence of potential undesirable side effects. A final evaluation of the animal’s condition must be made one dosage period after the final treatment.
Record Keeping and Documentation
To demonstrate compliance with regulatory requirements for adequate monitoring, assessment, and treatment of animals during the operative and post-operative period, or at other times when animals may be experiencing pain or distress, such activities must be documented. The written plan, as approved in the animal use protocol, must be followed explicitly.
- For USDA-regulated species (all mammals except laboratory rats and laboratory mice), individual animal records must be maintained on forms provided by the Institute for Animal Studies (IAS) and kept with the animals until euthanasia. The records must then be returned to the IAS; copies may be made for the investigator’s own files. The minimum information includes: date, species, animal ID, name of procedure, anesthetic dose and route, an evaluation of anesthetic level prior to starting the procedure, and written statement about level of anesthesia periodically (e.g. every 15 minutes) throughout surgery, including objective monitoring data such as RR or HR, if any. This record should also include reasons for giving supplemental anesthesia or other drugs. Finally, a statement about the animal’s condition following recovery and an assessment of the need, if any, for post-operative intervention should be provided. Notes must be initialed and dated.
Word for word compliance with the written plan provided in the protocol is demanded by the USDA. The AIC recommends that a copy of the approved protocol be maintained with the laboratory’s animal records so that research personnel can cross-check. Decisions to deviate from the written/approved plan must be documented and explained in the animal record.
- For laboratory rats and mice and all other non-USDA regulated species, records to be kept will depend on the procedure, as specified in the approved protocol. They may be documented as group records for a cohort of animals undergoing the same procedure without complication. Records may be maintained in laboratory notebooks, but must be kept available in the laboratory for inspection by AIC personnel or site visitors / inspectors from regulatory agencies at any time.
Anesthetics, Analgesics, Sedatives
A list of recommended agents and doses for each species is available in the IAS office, and may also be downloaded from the AIC/IAS website at /forms_and_documents_to_download.htm Investigators may also consult with the IAS veterinary staff for advice