In general, smaller animals have higher metabolic rates and frequently require higher doses of anesthetics and analgesics at more frequent intervals to achieve the desired effect.
Species, strain and age differences often overshadow this general principle however. It is always best to start with a drug regimen developed in the species, age and strain with which the Principal Investigator is working, rather than extrapolate from one species or strain to another.
Mice
Isoflurane is recommended as the first choice anesthetic in mice. It should be delivered at a known percentage (1-3% for maintenance; up to 5% for induction) in oxygen from a precision vaporizer.
Anesthetic monitoring of small rodents includes testing of rear foot reflexes before any incision is made, and continual observation of respiratory pattern, mucous membrane color, and responsiveness to manipulations and rear foot reflexes throughout the procedure. Rectal temperature and heart rate should be monitored electronically during long or involved procedures.
Injectable anesthetics are typically administered by intraperitoneal route. Injectable analgesics and reversal agents are often administered by the subcutaneous route. Intramuscular injections must generally be avoided because of the small muscle mass. Diluting drugs in sterile water or saline solution will make it easier to accurately measure volume for injection. It may also make some drugs less irritating when injected. Dilution may decrease shelf-life; the standard is to discard drugs within one month of dilution. Vials containing sterile, diluted drugs must be labeled with the contents and the expiration date.
Ketamine/alpha-2 agonist combinations produce short-duration surgical anesthesia in larger species, but are frequently insufficient for major surgical procedures in many strains of mice. An excellent approach is to use a ketamine combination, but then titrate to effect with isoflurane from a precision vaporizer. Safety and efficacy should be demonstrated in a pilot group of animals before a large-scale study is initiated. Partial reversal of the xylazine or medetomidine using yohimbine or atipamezole is possible, and will restore cardiovascular status more quickly.
Mice are nocturnal animals and are frequently housed in groups of nearly identical animals. These two factors make diagnosis of mild to moderate pain challenging. Weight loss is an important parameter to monitor in animals at risk for on-going pain. Pre-emptive treatment of pain, before signs of pain are apparent, is recommended.
Isoflurane provides no post-operative pain relief. If used for surgery, concurrent and follow-up use of buprenorphine and/or a non-steroidal anti-inflammatory will be necessary. The veterinary staff recommends injecting the analgesic 30 minutes prior to the start of surgery.
Rats
Rat anesthesia and analgesia considerations are similar to those described for the mouse, though some doses vary. In rats, ketamine combinations are more likely to provide adequate surgical anesthesia than in mice and so may not require supplemental isoflurane.
Hamsters
Hamster anesthesia is similar to rat and mouse anesthesia, though some anesthetic doses differ. Peripheral veins are extremely difficult to access in hamsters, limiting some of the anesthetic options.
Guinea Pigs
Guinea pigs can be difficult to anesthetize, especially on a survival basis. Intravenous injection is difficult. Intramuscular injection is acceptable for non-survival procedures only as animals may self-mutilate at injection sites if they have recovered from anesthesia. Intraperitoneal (IP) administration works well, if the large cecum can be avoided. Guinea pigs may be anesthetized by face mask with gas anesthetics; endotracheal intubation requires specialized training. The toe-pinch withdrawal reflex is less reliable as an indicator of surgical anesethesia in this species and instead the ear pinch (“flick”) response is used instead.
Formulary for Mice
Local anesthetics/analgesics
Lidocaine hydrochloride (2%)
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Dilute to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisional
Use locally before making surgical incision
Faster onset than bupivicaine but short (<1 hour) duration of action
Bupivicaine (0.5%) (Marcaine)
(Recommended)
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Dilute to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisional
Use locally before making surgical incision
Slower onset than lidocaine but longer (~ 4-8 hour) duration of action
Ketamine combinations
Ketamine-Medetomidine
(Recommended)
75-150 mg/kg + ~0.5-1 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedures. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole. Causes hyperglycemia and diuresis.
Ketamine-Xylazine
75-150 mg/kg + 16-20 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedure. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole or Yohimbine. Causes hyperglycemia and diuresis.
Ketamine-Xylazine-Acepromazine
(Recommended)
75-100 mg/kg + 16-20 mg/kg + 3 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedures. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole or Yohimbine. Causes hyperglycemia and diuresis.
Ketamine-Midazolam
75-100 mg/kg + 4-5 mg/kg IP
(in same syringe)
Will not produce surgical-plane anesthesia for major procedures, but may be useful for restraint.
Other injectable anesthetics
Sodium pentobarbital
(Nembutal)
50-90 mg/kg IP
Recommended for terminal/acute procedures only, with booster doses as needed. May occasionally be appropriate for survival procedures. Dilute to 6 mg/ml for use.
Consider supplemental analgesia (opioid or NSAID) for invasive procedures, especially when used on a survival basis.
Tribromoethanol
(avertin)
125-250 mg/kg IP
Not approved for recovery anesthesia
Causes peritonitis, hepatotoxicity and/or ileus.
Opiod Analgesia
Buprenorphine
(Recommended)
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0.01 - 0.05 mg/kg SC or IP
Used pre-operatively for preemptive analgesia and post-operatively every 6-12 hour
For major procedures, require more frequent dosing than 12 hour intervals. Consider multi-modal analgesia with a NSAID. High doses of buprenorphine may lead to pica behavior in rats.
Non-steroidal anti-inflammatory analgesia
Note that prolonged use may cause renal, gastrointestinal, or other problems. Avoid using longer than 2 to 3 days.
Carprofen
5 mg/kg SC or orally
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Meloxicam
(Recommended)
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1 -2 mg/kg SC or orally
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Ketoprofen
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5 mg/kg SC
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Inhalation Anesthetics
Isoflurane or Halothane
(Recommended)
1-3% inhalant to effect (up to 5% for induction).
Survival surgery requires concurrent preemptive analgesia.
Must use precision vaporizer
Formulary for Rats
Local anesthetics/analgesics
Lidocaine hydrochloride (2%)
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Dilute to 0.5%, do not exceed 7 mg/kg total dose, SC or intra-incisional
Use locally before making surgical incision
Faster onset than bupivicaine but short (<1 hour) duration of action
Bupivicaine (0.5%) (Marcaine)
(Recommended)
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Dilute to 0.25%, do not exceed 8 mg/kg total dose, SC or intra-incisional
Use locally before making surgical incision
Slower onset than lidocaine but longer (∼ 4-8 hour) duration of action
Ketamine combinations
Ketamine-Medetomidine
(Recommended)
75-90 mg/kg + 0.5 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedures. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole. Causes hyperglycemia and diuresis.
Ketamine-Xylazine
75-90 mg/kg + 5-10 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedures, though more reliable than in mice. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole or Yohimbine. Causes hyperglycemia and diuresis.
Ketamine-Xylazine-Acepromazine
(Recommended)
75 -90 mg/kg + 5-10 mg/kg + 1–2 mg/kg IP
(in same syringe)
May not produce surgical-plane anesthesia for major procedures. If redosing, use ketamine alone-may lose surgical anesthesia. May be partially reversed with Atipamezole or Yohimbine. Causes hyperglycemia and diuresis.
Ketamine-Midazolam
75-90 mg/kg + 4-5 mg/kg IP
(in same syringe)
Will not produce surgical-plane anesthesia for major procedures, but may be useful for restraint.
Other injectable anesthetics
Sodium pentobarbital
(Nembutal)
40 -60 mg/kg IP
Recommended for terminal/acute procedures only, with booster doses as needed. May occasionally be appropriate for survival procedures
Consider supplemental analgesia (opioid or NSAID) for invasive procedures, especially when used on a survival basis.
Tribromoethanol
(avertin)
125-300 mg/kg IP
Not approved for recovery anesthesia
Causes peritonitis, hepatotoxicity and/or ileus.
Opiod Analgesia
Buprenorphine
(Recommended)
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0.01 - 0.05 mg/kg SC or IP
Used pre-operatively for preemptive analgesia and post-operatively every 6-12 hour
For major procedures, require more frequent dosing than 12 hour intervals. Consider multi-modal analgesia with a NSAID. High doses of buprenorphine may lead to pica behavior in rats.
Non-steroidal anti-inflammatory analgesia
Note that prolonged use may cause renal, gastrointestinal, or other problems. Avoid using longer than 2 to 3 days.
Carprofen
5 mg/kg SC or orally
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Meloxicam
(Recommended)
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1 mg/kg SC or orally
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Ketoprofen
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5 mg/kg SC
Used pre-operatively for preemptive analgesia and post-operatively every 12-24 hour
Depending on the procedure, may be used as sole analgesic, or as multi-modal analgesia with buprenorphine.
Inhalation Anesthetics
Isoflurane or Halothane
(Recommended)
1-3% inhalant to effect (up to 5% for induction).
Survival surgery requires concurrent preemptive analgesia.
Must use precision vaporizer.
Mice and Rats
Reversal Agents
Atipamezole
1-2.5 mg/kg SC or IP
For reversal of Medetomidine or Xylazine effects
More specific for medetomidine than for xylazine (as a general rule, Atipamezole is dosed at the same volume as Medetomidine, though they are manufactured at different concentrations). Note reversal of alpha-2 agonist results in removal of analgesic properties.
Yohimbine
1.0 – 2.0 mg/kg SC or IP
For reversal of xylazine effects
Note reversal of alpha-2 agonist results in removal of analgesic properties.
Examples of potentially painful procedures
Minimal to Mild Pain
Percutaneous vascular catheter implantation
Ear notching
Superficial tumor implantation
Ocular procedures
Multiple injections
Moderate Pain
Minor laparotomy incision
Thyroidectomy
Orchidectomy
C-section
Embryo transfer
Hypophysectomy
Thymectomy
Vascular access port
Osmotic pump implant
Indwelling vascular cannulae
Intracerebral implantation
Moderate to Severe Pain
Major laparotomy/organ incision
Thoracotomy
Heterotopic organ transplantation
Vertebral procedures
Burn procedures
Trauma models
Orthopedic procedures
Cecal ligation and puncture
Drug selection for alleviating pain in rodents
Minimal to Mild Pain
Lidocaine/Bupivacaine
AND
Meloxicam or Carprofen
OR
Buprenorphine
Moderate Pain
Lidocaine/Bupivacaine
AND
Buprenorphine
OR
Meloxicam or Carprofen
Moderate to Severe Pain
Lidocaine/Bupivacaine
AND
Buprenorphine or Morphine
AND
Meloxicam or Carprofen
*Severe pain may be better alleviated by the combination of NSAID and opioid drugs. This multimodal approach allows for action at different points on the pain pathways, and will allow for a lower dosage of both drugs to be given.
For purposes of administering a drug via the drinking water
Rat
Normal* Daily Water Consumption
8-11 ml/100 gm body weight/day
Mouse
Normal* Daily Water Consumption
15 ml/100 gm body weight/day
Hamster
Normal* Daily Water Consumption
30 ml/day
Gerbil
Normal* Daily Water Consumption
4-7 ml/100gm body weight/day
Guinea Pig
Normal* Daily Water Consumption
10 ml/100 gm body weight/day
*Animals that have been subjected to a painful procedure/surgery will not drink the “normal” amount of water for a minimum of 24 hours post-surgery/post-procedure. It is estimated that normal water consumption will be reduced by at least 50%.