IACUC Guidelines: Analgesia

IACUC Guidelines:

Analgesia

Guidelines: The IACUC has provided a set of guidance documents (Policies, Guidelines, and Informational Sheets) for use when planning animal procedures at the University of Iowa. An exception to a Guideline must be described and justified in the Animal Protocol and approved during the normal review process.

Purpose

The purpose of these guidelines is to describe appropriate analgesia regimens for the management of pain in animals used in teaching, research and testing at the University of Iowa.  These guidelines include minimum analgesia recommendations.  Animals should be monitored for an appropriate time period to determine if analgesia provisions are adequate.  Any animal showing evidence of pain should be provided analgesia.  If analgesia cannot be provided due to scientific reasons, the rationale should be described and approved in the Animal Protocol.

Recognition of Pain

Adequate alleviation of pain in laboratory animals requires the training and knowledge to recognize signs of pain which may differ between species. An information sheet titled “Pain Recognition in Laboratory Animals” is provided for reference, and veterinary consultation is available for personnel training and advice on pain recognition in unique models.

Pre-Emptive Use of Analgesic Agents

Pre-emptive analgesia should be provided whenever possible.  Analgesia provisions are most effective at reducing the intensity of painful stimulation when given prior to the painful event.

  • Advantages of pre-emptive use of analgesics:
    • Reduces the intensity of painful stimulation
    • Improves the animal's comfort level after surgery
    • Decreases the amount of anesthesia required to maintain a surgical plane
    • Results in a smoother recovery

Multi-Modal Use of Analgesic Agents

  • Multi-modal analgesia (giving multiple drugs with different mechanisms of action) provides the best analgesia possible
    • e.g., local analgesia + opioid + NSAID (when appropriate)
    • Classes, dosages, routes and frequency of administration are listed in the “Common Analgesic Agents” section of these guidelines

 

 

Minimum Analgesia Requirements

  • Subcutaneous wounding, implantations or procedures without incising through muscle wall:
    • NSAIDS
    • Analgesia should be provided for a minimum of 24 hours post-op
  • Incisions into retro-peritoneal or abdominal cavity or the muscle wall:
    • NSAIDS and/or Opioids
    • Analgesia should be provided for a minimum of 48 hours post-op
  • Incisions into thoracic cavity through the muscle wall:
    • Opioids
    • Analgesia should be provided for a minimum of 48 hours post-op
  • Craniotomy
    • NSAIDS and/or Opioids
    • Analgesia should be provided for a minimum of 48 hours post-op

 

 

Local Anesthesia Along Intended Incisions (Line Blocks)

 

Formulary: Rats and Mice

Local Anesthetic

Dose

Application

Notes

Lidocaine

Dilute to 0.5%, do not exceed 7mg/kg total dose; Incisional line block

Inject locally before surgical incision

Faster onset than bupivacaine (2-3 minutes after injection) but short (<1hour) duration of action

Bupivacaine

Dilute to .25%, do not exceed 8mg/kg total dose; incisional line block

Inject locally before surgical incision

Slower onset than lidocaine (20+ minutes) but longer (4-8 hour) duration of action

0.5% Lidocaine/0.25% Bupivacaine mixture

See formulation below; do not exceed maximum doses

Inject locally before surgical incision

Best option – rapid action of lidocaine with prolonged action of bupivacaine

 

 

 

Dilutions:

 

  • Lidocaine

Dilute the 2% (20 mg/ml) Lidocaine 1:4 to get final concentration of 0.5% (5 mg/ml)

  • Example: 0.5 mL of 2% lidocaine + 1.5 mL sterile saline
  • Label with drug, concentration, and expiration date
  • See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

 

  • Bupivacaine

Dilute the 0.5% (5 mg/ml) Bupivacaine 1:2 to get final concentration of 0.25%

  • Example: 0.5 mL of 0.5% bupivacaine + 0.5 mL sterile saline
  • Label with drug, concentration, and expiration date
  • See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

 

 

  • 50/50 Mixture of Lidocaine/Bupivacaine

Dilute 2% (20 mg/ml) Lidocaine 1:4 and 0.5% (5mg/mL) Bupivacaine 1:2 in the same vial

  • Example: 0.5 mL 2% lidocaine + 1 mL 0.5% bupivacaine + 0.5 mL sterile saline
  • Label with drug, concentration, and expiration date
  • See “IACUC Guidelines: Use of Drugs and Chemicals in Laboratory Animals” for further details (proper handling, expiration guidance, etc.)

 

Maximum Volumes

Weight of Mouse

Maximum Volume Diluted Lidocaine (0.5%) or Mixture

   Do not exceed:

Maximum Volume Diluted Bupivicaine (0.25%)

    Do not exceed:

25g

0.03ml

0.08ml

35g

0.05ml

0.11ml

45g

0.06ml

0.14ml

55g

0.07ml

0.17ml

 

Weight of Rat

Maximum Volume Diluted Lidocaine (0.5%)                

Do not exceed:

Maximum Volume Diluted Bupivicaine (0.25%)                          Do not exceed:

250g

0.35ml

0.8ml

350g

0.49ml

1.12ml

250g

0.63ml

1.44ml

550g

0.77ml

1.76ml

 

Line Block Procedure:

  1. Determine maximum dose that can be used depending on weight of animal
  2. Anesthetize the animal, and prepare skin for aseptic surgery
  3. Inject local anesthetic into the subcutaneous space (“line block”) below the planned incision line, while withdrawing needle along incision line

 

Local Anesthetics should be used pre-operatively (before the first incision) and can be used in conjunction with opioid analgesics and/or NSAIDs for controlling moderate to severe pain. Intramuscular and intravenous injection of local anesthetics must be avoided. Systemic toxicity (seizures, heart rhythm disturbances and death) results from overdose or accidental intravenous injection.

 

Common Analgesic Agents

The following is a list of commonly used analgesic agents by species.  This list is not inclusive; other analgesic agents may be listed and used in an Animal Protocol.

Other accepted resources for appropriate analgesics include the following formularies:

  • Plumb’s Veterinary Drug Handbook (Plumb)
  • Anesthesia and Analgesia in Laboratory Animals (ACLAM)
  • Formulary for Laboratory Animals (Hawk)
  • Exotic Animal Formulary (Carpenter & Marion)
  • Swine in the Laboratory (Swindle)
  • Sheep and Goat Medicine (Pew)

Appropriate analgesic drugs and dosage(s) should be determined in consultation with an OAR or IACUC veterinarian.

Mouse:

   

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

See above

NSAID

Flunixin meglumine

2.5 mg/kg SC every 12-24 hours

NSAID

Meloxicam

/Meloxicam-SR*

1-5 mg/kg SC every 24 hours

Opioid

Buprenorphine

0.05-2.5 mg/kg SC or IP every 6-12 hours

Opioid

Buprenorphine SR-LAB (sustained release)**

0.5-2.0 mg/kg SC every 48 hours

Opioid

Butorphanol

0.2-2 mg/kg SC or IP every 2-4 hours

Opioid

Oxymorphone

0.2-0.5 mg/kg SC every 6-12 hours

*Meloxicam-SR is a new product which claims 72 hours of duration in cats and dogs. Independent studies have not demonstrated efficacy beyond 24 hours post-administration in rodents. Use of this product in rodents is under continuing review by OAR veterinarians and requires close monitoring for signs of pain if expected effect is greater than 24 hours.

**Contact OAR Veterinarians for prescription and training

 

   

Rat:

   

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

See above

NSAID

Ketoprofen

5 mg/kg SC or PO every 24 hours

NSAID

Meloxicam
 / Meloxicam-SR*

1-2 mg/kg SC or PO every 24 hours

Opioid

Buprenorphine

0.02-0.5 mg/kg SC, IV or IP every 6-12 hours

Opioid

Buprenorphine SR-LAB (sustained release)**

1.0-1.2 mg/kg SC every 48 hours

Opioid

Butorphanol

0.2-2 mg/kg SC or IP every 2-4 hours

Opioid

Oxymorphone

0.2-0.5 mg/kg SC every 6-12 hours

*Meloxicam-SR is a new product which claims 72 hours of duration in cats and dogs. Independent studies have not demonstrated efficacy beyond 24 hours post-administration in rodents. Use of this product in rodents is under continuing review by OAR veterinarians and requires close monitoring for signs of pain if expected effect is greater than 24 hours.

**Contact OAR Veterinarians for prescription and training

 

 

Rabbit:

   

 

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

Line block, consult with vet staff

NSAID

Carprofen

1-2.2 mg/kg PO every 12 hours

NSAID

Flunixin meglumine

1-2 mg/kg SC or IM every 12-24 hours

NSAID

Ketoprofen

3 mg/kg SC every 24 hours

NSAID

Meloxicam

0.2-0.6 mg/kg SC or PO every 24 hours

Opioid

Buprenorphine

0.01-0.05 mg/kg SC, IM or IV every 6-12 hours

Opioid

Buprenorphine SR  (sustained release)**

0.1-0.3 mg/kg SC every 48-72 hours

Opioid

Butorphanol

0.1-1 mg/kg SC, IM or IV every 4-6 hours

Opioid

Oxymorphone

0.05-0.2 mg/kg SC or IM every 8-12hours

**Contact OAR Veterinarians for prescription and training

 

Pig:

   

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

Line block, consult with vet staff

NSAID

Carprofen

2-3 mg/kg IM, SC or PO every 24 hours

NSAID

Flunixin meglumine

1-4 mg/kg IM or SC every 12-24 hours

NSAID

Ketoprofen

1-3 mg/kg IM, SC or PO every 24 hours

NSAID

Meloxicam

0.4 mg/kg SC every 24 hours

NSAID

Phenylbutazone

4-8 mg/kg PO every 12 hours

Opioid

Buprenorphine

0.005-0.1 mg/kg IM, SC or IV every 8-12 hours

0.005-0.01 recommended for augmenting anesthetia; 0.01-0.1 recommended for post-operative pain control

Opioid

Buprenorphine SR (sustained release)**

0.12-0.2 mg/kg SC every 48-72 hours

Opioid

Butorphanol

0.1-0.3 mg/kg IM, SC or IV every 8-12 hours

Opioid

Oxymorphone

0.15 mg/kg IM or SC every 4 hours

**Contact OAR Veterinarians for prescription and training

 

Sheep:

   

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

Line block, consult with vet staff

NSAID

Carprofen

4 mg/kg SC every 24 hours

NSAID

Flunixin meglumine

1-2 mg/kg IM, IV or PO every 12-24 hours

Opioid

Ketoprofen

2-3 mg/kg IM, IV or PO every 24 hours

Opioid

Phenylbutazone

2-6 mg/kg IV or PO every 12 hours

Opioid

Buprenorphine SR  (sustained release)**

0.05-0.3 mg/kg SC or IM every 48-72 hours

Opioid

Buprenorphine

0.005-0.01 mg/kg IM every 4-6 hours

Opioid

Butorphanol

0.5 mg/kg SC every 2-3 hours

**Contact OAR Veterinarians for prescription and training

 

Ferret:

   

Class

Agent

Dose/Route/Frequency

Local

Bupivacaine 0.25%

Lidocaine 0.5%

Line block, consult with vet staff

NSAID

Carprofen

1 mg/kg PO every 12-24 hours

NSAID

Flunixin meglumine

0.3-2 mg/kg SC every 12-24 hours

NSAID

Ketoprofen

1 mg/kg PO, SC or IM every 24 hours

Opioid

Buprenorphine

0.01-0.03 mg/kg SC, IM or IV every 8-12 hours

Opioid

Butorphanol

0.05-0.5 mg/kg SC, IM or IV every 8-12 hours

Opioid

Oxymorphone

0.05-0.2 mg/kg SC, IM or IV every 8-12 hours

 

 

 

 

Non-pharmacologic methods of pain management

When pharmacological intervention (i.e. analgesic agents) is not possible or in addition to pharmacological intervention, these methods can be employed to decrease pain:

  • Skilled surgeon (reduce unintentional surgical trauma)
  • Acclimation of animals prior to surgery
  • Enhance environment to minimize stress (soft bedding, easy food access, soft food, warm temperature, decrease human traffic, decrease noise)
  • Fluid therapy to sustain hydration

Last Reviewed by Committee 9/12/18