Neuromuscular Blocking Agents

Policy

The use of neuromuscular blocking agents will only be approved for research procedures where scientific justification is provided for paralysis of the animal and chemical relief from pain and/or distress is provided. Therefore, proposed use will be reviewed on a case-by-case basis. Neuromuscular blocking drugs may not be used alone to provide restraint and immobilization, and may only be used in conjunction with drugs that produce surgical anesthesia, and hence, unawareness of the paralytic state. Due to the inherent difficulties in assessing the level of surgical anesthesia in paralyzed animals, the use of these drugs will be approved only if it is clearly established that (1) neuromuscular blockers are essential for the proposed procedure, and (2) that the investigator is able to monitor the animals appropriately for signs of pain and distress.

Guidelines

The Chancellor’s Animal Research Committee (ARC) has adopted the following guidelines for the review of protocols that include the use of neuromuscular blocking agents:

1. Veterinary Oversight
   Prior to using neuromuscular blocking drugs in a procedure, investigators must demonstrate to a DLAM veterinarian that the anesthetic technique is sufficient to prevent pain and distress associated with the procedure in the absence of the neuromuscular blocking agent, confirming that escape behavior does not occur.
   
   
2. Use of General Anesthesia
   A surgical plane of anesthesia must be induced and the animal intubated prior to administration of the neuromuscular blocking drug; furthermore, unless described in an approved protocol, a surgical plane of anesthesia must be maintained during the entire time that the neuromuscular blocking drug is present and active in vivo. Neuromuscular blockers must not be administered until after the initiation of the procedure to ensure that the depth of anesthesia is adequate and the animal does not feel pain. Use of neuromuscular blocking agents should be confined solely to that phase of the procedure for which they are indicated. Neuromuscular blocking agents must not be used as a matter of convenience or to substitute for poor control of anesthesia.

   Nitrous oxide alone is not an anesthetic and cannot provide a surgical plane of anesthesia; therefore, it must not be used alone with neuromuscular blocking agents during surgical procedures.

   The use of a pre-operative analgesic is recommended in addition to the general anesthetic during surgical procedures where neuromuscular blockers are being used.

   Controlled ventilation must be initiated prior to administration of the neuromuscular blocking drug.

3. Monitoring for Pain and Distress
   During the period of paralysis, signs of reaction to pain and distress must be continuously monitored as appropriate to the species (e.g., heart rate, blood pressure). If these parameters increase by 20% or more without other explanation, pain/distress may be assumed to be present, and the anesthetic level should be deepened. Baseline measurements must be established at the initiation of anesthesia for comparison. If a surgical procedure is being performed, baseline measurements should be made at the initiation of the surgery (skin incision) to determine that the depth of anesthesia is adequate. Electroencephalographic (EEG) monitoring may also be helpful. As normal EEG appearance differs with different types of anesthetics, and confirmation of an anesthetized state may not always be possible based on EEG, the investigator should be thoroughly familiar with the expected EEG pattern for the particular anesthetic used.

   Physiological parameters (e.g., core temperature, blood gases, and fluid and electrolyte balance) must be maintained within normal levels for the species during the period of paralysis.

For more information on this topic

1. Drummond, J. C., M. M. Todd, and L. J. Saidman. 1996. Use of neuromuscular blocking drugs in scientific investigations involving animal subjects: The benefit of the doubt goes to the animal. Anesthesiology 85:697-699.
2. Guide for the Care and Use of Laboratory Animals. National Research Council. 2010. Washington, D.C.: National Academy Press.
3. Hammond, P. 1978. Inadequacy of nitrous oxide/oxygen mixtures for maintaining anaesthesia in cats: satisfactory alternatives. Pain 5:143-151.
4. Mahmoudi, N. W., D. J. Cole, and H. M. Shapiro. 1989. Insufficient anesthetic potency of nitrous oxide in the rat. Anesthesiology 70:345-349.
5. Marsch, S. C. U. and W. Studer. 1999. Guidelines to the use of laboratory animals: what about neuromuscular blocking agents? Cardiovascular Research 42:565-566.
6. Gordon B. Drummond. Reporting ethical matters in The Journal of Physiology: standards and advice. February 1, (2009). The Journal of Physiology, 587, 713-719.
7. Richard Fish (Editor), Marilyn Brown (Editor), Peggy J. Danneman (Editor), Alicia Karas (Editor). (2008). Anesthesia and Analgesia in Laboratory Animals, second edition. pp 266-268.
8. Edmund Jooste, M.B., ChB., Yi Zhang, M.D., Charles W. Emala, M.D. (2007). Neuromuscular Blocking Agents’ Differential Bronchoconstrictive Potential in Guinea Pig Airways. The American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Anesthesiology; 106:763–72.

Approved 1/90; Revised 7/9/01, 4/26/04, 4/12/10, 11/4/24; Updated 1/18/11