Advantages of injectable anaesthesia
- Multiple animals can be anaesthetised at the same time (provided you can monitor them effectively).
- Injectable anaesthetics do not require the use of specialist equipment, but it is important to be able to deliver oxygen as all of these agents cause respiratory depression.
Disadvantages of injectable anaesthesia:
- Once the anaesthetic has been administered the dose cannot be changed.
- There is individual variability in the response to a given dose of anaesthetic.
- Since the dose of anaesthetic needed by individual animals varies, the best way to give these agents is by intravenous injection. This is the preferred route for administering injectable anaesthetics as it allows the dose to be adjusted to match the particular animals requirements. Unfortunately it can be technically difficult to use this route in small rodents, so most injectable anaesthetics are given by intraperitoneal or subcutaneous injection in these species.
Commonly used injectable anaesthetic agents
There are many available injectable anaesthetic agents. These include:
- Ketamine (in combination with a sedative)
- Hypnorm (with midazolam or diazepam)
- Propofol
- Alphaxalone
- Pentobarbital
The most commonly used anaesthetic are:
Ketamine (in combination with a sedative)
Ketamine, when used alone, does not produce surgical anaesthesia in most animal species. In cats and non-human primates, sufficient analgesia for minor surgical procedures can be produced, but it is better combined with other agents such as acepromazine, midazolam or diazepam. When used in this way, ketamine produces light to moderate surgical anaesthesia in many species. In small rodents the effects of these combinations are less predictable than in larger species, and usually only light planes of anaesthesia, insufficient even for minor surgery, are produced.
In contrast, administration of ketamine in combination with medetomidine or xylazine results in surgical anaesthesia in most mammals and many species of birds. Its effects are slightly less uniform in guinea pigs, and some individuals may not become sufficiently deeply anaesthetised for major surgery. In these circumstances, it is preferable to deepen anaesthesia using an inhalational agent, or to provide additional analgesia using local anaesthesia.
Ketamine combined with medetomidine or xylazine also has less predictable results in pigs, and the combination should be evaluated in the particular strain used. In all species, anaesthesia can be partially reversed by administration of atipamezole.
Fentanyl/fluanisone (“Hypnorm”)
“Hypnorm”, when administered alone, produces sedation and sufficient analgesia for superficial surgery in most small mammals. The degree of muscle relaxation is generally poor, and the high doses needed for more major surgery produce marked respiratory depression. Combining this regimen with a benzodiazepine (midazolam or diazepam) produces surgical anaesthesia with only moderate respiratory depression. The combination has the advantage that it can be partially reversed with a mixed opioid agonist/antagonist such as butorphanol or a partial agonist such as buprenorphine. This reverses the respiratory depression caused by the fentanyl, but maintains post-operative analgesia. The benzodiazepine antagonist can be used to further speed recovery, but repeated doses are needed to avoid resedation.
In small rodents, a mixture of midazolam and “Hypnorm” can be given as a single intraperitoneal injection. In rabbits it is preferable to give the “Hypnorm” first, by intramuscular injection. The midazolam or diazepam can then be administered intravenously to effect as described above.
Although the use of
Other Opioid Combinations
Because of their potent analgesic action, short-acting opioids such as fentanyl and alfentanil can be used in combination with a variety of compounds to produce balanced anaesthesia. Mixtures of fentanyl or alfentanil and a benzodiazepine produce effective surgical anaesthesia in dogs and pigs, and they can be added to anaesthetics in which analgesia would otherwise be inadequate (e.g. alphaxalone or propofol). The use of opioids often enables the production of profound analgesia, without major effects on the cardiovascular system, although bradycardia can be produced if the drugs are given rapidly. Opioid-induced bradycardia can rapidly be reversed with atropine, without affecting the analgesia produced by these drugs. Severe respiratory depression can occur when using high doses of opioids, although this can be overcome by the use of intermittent positive pressure ventilation (IPPV).
Fentanyl and medetomidine
Fentanyl and medetomidine can be combined to produce anaesthesia in dogs, rabbits, guinea pigs and rats. The combination is most effective in dogs and rats. In the dog, the drugs are given by intravenous injection, and in the rat, the two compounds are combined and given as a single intraperitoneal injection. The combination reliably produces surgical anaesthesia with good muscle relaxation in some species. Anaesthesia is completely reversible by administering specific antagonists (nalbuphine or butorphanol together with atipamezole). Mild to moderate respiratory depression is produced. In the rat, the relatively large volume for injection is inconvenient for the operator, but does not appear distressing to the animal. In the mouse, the combination can cause urinary retention which may result in rupture of the bladder, and so should not be used in this species.
The rapid and complete reversal of anaesthesia avoids the problems that may be associated with managing animals during the prolonged recovery that can be associated with other injectable anaesthetic techniques. Reversal of the fentanyl component with a mixed opioid agonist/antagonist results in maintenance of post-operative analgesia.
The combination of medetomidine, midazolam, and fentanyl also provides an effective and reversible anaesthetic regimen for rats. Administration of atipamezole, flumazenil and butorphanol
Propofol
When administered intravenously, propofol produces short periods of surgical anaesthesia in most species, and additional doses can be given to prolong the period of anaesthesia, without unduly prolonging recovery. Although it can be used safely in sheep, this species requires unusually high dose rates for induction and maintenance of anaesthesia.
Because of its rapid redistribution and metabolism, propofol is best given by intravenous injection to be effective; otherwise, the rapid redistribution to body tissues that occurs will prevent anaesthetic concentrations being achieved in the brain. Propofol should be administered relatively slowly, as this avoids causing transient apnoea. Typically, the dose needed to produce unconsciousness and sufficient relaxation to allow intubation should be given over 1–2 minutes in small animals (1–10 kg).
Some hypotension can occur following its administration, but this is not generally a concern in healthy individuals. Mean arterial blood pressure is often better maintained than with inhalational agents. The dose of propofol required to maintain anaesthesia can be reduced by concurrent administration of opioids. This balanced anaesthetic technique can be used to provide prolonged periods of anaesthesia, with a relatively mild degree of cardiovascular depression. Respiratory depression is often marked, however, so it is strongly advised that animals are mechanically ventilated. A number of short acting potent opioids can be used, such as fentanyl, alfentanil and sufentanil. At the end of the period of anaesthesia, respiratory depression caused by the opioid can be reversed by administration of a mixed agonist-antagonist opioid such as nalbuphine, butorphanol or buprenorphine.
Alphaxalone
In most species, intravenous administration of this steroid anaesthetic produces surgical anaesthesia, which can be prolonged with additional doses without greatly prolonging recovery times. When given by deep intramuscular injection, alphaxalone produces light anaesthesia, and this route is useful in cats, rabbits and primates. After administration of an initial dose intramuscularly, additional drug is given intravenously to induce surgical anaesthesia. Anaesthesia can then be maintained by further doses or by continuous infusion of the agent. In other species, the high volumes of drug required make intramuscular administration impracticable.
Both alphaxalone and propofol are relatively non-cumulative, unlike the barbiturates, so that recovery following prolonged anaesthesia is relatively rapid. The short duration of action of these agents (approximately 10 minutes after a single dose) means that the depth of anaesthesia can be adjusted easily by changing drug infusion rates.
Since both drugs are rapidly metabolized, they are excellent agents for maintenance of long-term anaesthesia, although moderate hypotension may occur. Continuous intravenous infusion can be used to provide safe and stable anaesthesia in sheep, pigs, primates, cats and rodents, although in larger species economic considerations may limit the use of alphaxalone.
Pentobarbital
Pentobarbital has been the most widely used laboratory animal anaesthetic. Surgical anaesthesia is attained in most small laboratory animals only when dosages close to those that cause respiratory failure have been administered. At these dose rates, severe cardiovascular depression and respiratory depression are produced. Slow intravenous administration of a dose sufficient to produce loss of consciousness, followed by further incremental small doses, usually achieves surgical levels of anaesthesia reasonably safely. Intraperitoneal administration of the calculated dose of drug as a single bolus is often associated with high mortality, not only because the anaesthetic dose is very close to the lethal dose, but because there is also considerable between-strain variation. Pentobarbital is probably best used to provide loss of consciousness and light anaesthesia rather than full surgical anaesthesia, and in most circumstances, safer and more effective agents are available.
Pentobarbital is no longer commercially available as an anaesthetic in a number of countries; however, the agent can be purchased from specialist suppliers (e.g. Sigma) if needed for specific research projects. It has relatively low solubility, and commercial preparations may include propylene glycol or other solubilising agents. Aqueous solutions of 50 mg/ml can be prepared from pentobarbital powder.
Like other barbiturates, pentobarbital solution has a very high pH, so intraperitoneal injection can cause pain. When used as a euthanasia agent, the addition of a local anaesthetic can prevent pain on intraperitoneal injection.
Suggested dose rates of commonly used injectable anaesthetics for small mammals are given in the tables below. More extensive information is available in Flecknell, 2016.
Mouse
Table: Anaesthetic Dose Rates in the Mouse| Drug | Dose rate | Effect | Duration of | Sleep time |
|---|---|---|---|---|
| anaesthesia | (minutes) | |||
| (minutes) | ||||
| Alphachoralose | 100–120 mg/kg ip | Light anaesthesia | 300–420 | Non-recovery only |
| Alphaxalone | 10 mg/kg iv | Surgical anaesthesia | 5 | 10 |
| Fentanyl/fluanisone (Hypnorm) + diazepam | 0.4 ml/kg ip + 5 mg/kg ip | Surgical anaesthesia | 30–40 | 120–240 |
| Fentanyl/fluanisone | 10.0 ml/kg ip * | Surgical anaesthesia | 30–40 | 120–240 |
| (Hypnorm)/midazolam | ||||
| Ketamine + dexmedetomidine | 75 mg/kg + 1.0 mg/kg ip | Surgical anaesthesia | 20–30 | 60–120 |
| Ketamine + medetomidine | 75 mg/kg + 1.0 mg/kg ip | Surgical anaesthesia | 20–30 | 60–120 |
| Ketamine + xylazine | 80–100 mg/kg + 10 mg/kg ip | Surgical anaesthesia | 20–30 | 60–120 |
| Ketamine + xylazine + acepromazine | 80–100 mg/kg + 10 mg/kg ip + | Surgical anaesthesia | 30–40 | 60–120 |
| 3 mg/kg ip | ||||
| Medetomidine-Midazolam-Fentanyl | 0.5 mg/kg + 5 mg/kg + 0.05 mg/kg | Light-Medium Surgical anaesthesia | 40-50 | Reverse with atipamezole, flumazenil, butorphanol (2.5 mg/kg+ 0.5 mg/kg + 2 mg/kg) |
| Pentobarbital | 40–50 mg/kg ip | Immobilisation/anaesthesia | 20–40 | 120–180 |
| Propofol | 26 mg/kg iv | Surgical anaesthesia | 5–10 | 10–15 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
| Dose in millilitres per kilogram of a mixture of one part ‘Hypnorm’ plus two parts water for injection, and one part midazolam (5 mg/ml initial concentration). | ||||
Rat
Table: Anaesthetic Dose Rates in the Rat| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Alphaxalone | 10 mg/kg iv | Surgical anaesthesia | 5 | 10 |
| Alpha-chloralose | 55–65 mg/kg ip | Light anaesthesia | 480–600 | Non-recovery only |
| Fentanyl/fluanisone + diazepam | 0.6 ml/kg ip + 2.5 mg/kg ip | Surgical anaesthesia | 20–40 | 120–240 |
| Fentanyl/fluanisone/ | 2.7 ml/kg ip† | Surgical anaesthesia | 30–40 | 120–240 |
| midazolam | ||||
| Fentanyl + medetomidine | 300 ug/kg + 300 ug/kg ip | Surgical anaesthesia | 60–70 | 240–360 |
| Ketamine + dexmedetomidine | 75 mg/kg + 0.25 mg/kg ip | Surgical anaesthesia | 20–30 | 120–240 |
| Ketamine + medetomidine | 75 mg/kg + 0.5 mg/kg ip | Surgical anaesthesia | 20–30 | 120–240 |
| Ketamine + xylazine | 75–100 mg/kg + 10 mg/kg ip | Surgical anaesthesia | 20–30 | 120–240 |
| Ketamine + xylazine + | 40–50 mg/kg + 2.5 mg/kg | |||
| acepromazine | + 0.75 mg/kg im | |||
| Medetomidine-Midazolam-Fentanyl | 0.15 mg/kg + 2.0 mg/kg + 0.005 mg/kg | Surgical anaesthesia | 30-45 | Reverse with atipamezole, flumazenil, butorphanol (0.75 mg/kg+ 0.2 mg/kg + 2 mg/kg) |
| Pentobarbital | 40–50 mg/kg ip | Light anaesthesia | 15–60 | 120–240 |
| Propofol | 10 mg/kg iv | Surgical anaesthesia | 5 | 10 |
| -Urethane | 1000 mg/kg ip | Surgical anaesthesia | 360–480 | Non-recovery only |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
| Dose in millilitres per kilogram of a mixture of one part ‘Immobilon’, one part midazolam (5 mg/ml initial concentration) and two parts water for injection. | ||||
| † Dose in millilitres per kilogram of a mixture of one part ‘Hypnorm’ plus two parts water for injection, and one part midazolam (5 mg/ml initial concentration). | ||||
Guinea Pig
Table: Injectable Anaesthetic Dose Rates in the Guinea Pig| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Fentanyl/Climazolam/Xylazine | 0.05mg/kg + 2.0mg/kg + 2.0mg/kg im | Surgical anaesthesia | ||
| Fentanyl/fluanisone | 8.0 ml kg ip* | Surgical anaesthesia | 45–60 | 120–180 |
| (Hypnorm)/midazolam | ||||
| Ketamine/acepromazine | 100 mg/kg + 5 mg/kg im | Immobilisation/anaesthesia | 45–120 | 90–180 |
| Ketamine/dexmedetomidine | 40 mg/kg + 0.25 mg/kg ip | Moderate anaesthesia | 30–40 | 90–120 |
| Ketamine/diazepam | 100 mg/kg + 5 mg/kg im | Immobilisation/anaesthesia | 30–45 | 90–120 |
| Ketamine/medetomidine | 40 mg/kg + 0.5 mg/kg ip | Moderate anaesthesia | 30–40 | 90–120 |
| Ketamine/xylazine | 40 mg/kg + 5 mg/kg ip | Surgical anaesthesia | 30 | 90–120 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
| *Dose in millilitres per kilogram of a mixture of one part ‘Hypnorm’ plus two parts water for injection, and one part midazolam (5 mg/ml initial concentration). | ||||
Dog
Table: Anaesthetic Dose Rates in the Dog| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Alphaxalone | 2 mg/kg iv | Surgical anaesthesia | 10–15 | 15–20 |
| Ketamine/dexmedetomidine | 2.5–7.5 mg/kg im + | Light to medium | 30–45 | 60–120 |
| 20 ug/kg im | anaesthesia | |||
| Ketamine/medetomidine | 2.5–7.5 mg/kg im + | Light to medium | 30–45 | 60–120 |
| 40 ug/kg im | anaesthesia | |||
| Ketamine/xylazine | 5 mg/kg iv + | Light to medium | 30–60 | 60–120 |
| 1–2 mg/kg iv or im | anaesthesia | |||
| Propofol | 5–7.5 mg/kg iv | Surgical anaesthesia | 5–10 | 15–30 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
Non-human primate
Table: Anaesthetic Dose Rates in the Non-human Primate| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Ketamine/diazepam | 15 mg/kg im + 1 mg/kg im | Surgical anaesthesia | 30–40 | 60–90 |
| Ketamine/dexmedetomidine | 5 mg/kg im + 25 ug/kg im | Surgical anaesthesia | 30–40 | 60–120 |
| Ketamine/medetomidine | 5 mg/kg im + 50 ug/kg im | Surgical anaesthesia | 30–40 | 60–120 |
| Propofol | 7–8 mg/kg iv | Surgical anaesthesia | 5–10 | 10–15 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
Pig
Table: Anaesthetic Dose Rates in the Pig| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Alfaxalone | 1-2mg/kg i/v (after azaperone 1-2mg/kg im) | Surgical anaesthesia | 5th October 2019 | 15-20 |
| Ketamine | 10–15 mg/kg im | Sedation, immobilisation | 20–30 | 60–120 |
| Ketamine/acepromazine | 22 mg/kg + 1.1 mg/kg im | Light anaesthesia | 20–30 | 60–120 |
| Ketamine/diazepam | 10–15 mg/kg im + 0.5–2 mg/kg im | Immobilisation/light | 20–30 | 60–90 |
| anaesthesia | ||||
| Ketamine/medetomidine | 10 mg/kg im + 0.08 mg/kg im | Immobilisation/light | 40–90 | 120–240 |
| anaesthesia | ||||
| Ketamine/midazolam | 10–15 mg/kg im + 0.5–2 mg/kg im | Immobilisation/light | 20–30 | 60–90 |
| anaesthesia | ||||
| Propofol | 2.5–3.5 mg/kg iv (6-8mg/kg if no premed given) | Surgical anaesthesia | 5–10 | 10–20 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
Rabbit
Table: Anaesthetic Dose Rates in the Rabbit| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Fentanyl/fluanisone | 0.3 ml/kg im + 1–2 mg/kg iv | Surgical anaesthesia | 20–40 | 60–120 |
| (Hypnorm) + midazolam | or ip | |||
| Fentanyl + medetomidine | 8 ug/kg iv + 330 ug/kg iv | Surgical anaesthesia | 30–40 | 60–120 |
| Fentanyl + medetomidine + midazolam | 20 ug/kg iv + 0.2 mg/kg + 1.0mg/kg i/m | Surgical anaesthesia | 30–40 | 60–120 |
| Ketamine/acepromazine | 50 mg/kg imft | Surgical anaesthesia | 20–30 | 60–90 |
| + 1 mg/kg im | ||||
| Ketamine/dexmedetomidine | 15 mg/kg im + 0.125 mg/kg sc, im | Surgical anaesthesia | 20–30 | 60–90 |
| Ketamine/diazepam | 25 mg/kg im + 5 mg/kg im | Surgical anaesthesia | 20–30 | 60–90 |
| Ketamine/medetomidine | 15 mg/kg s/c + 0.25 mg/kg sc | Surgical anaesthesia | 20–30 | 60–90 |
| Ketamine/xylazine | 35 mg/kg im + 5 mg/kg im | Surgical anaesthesia | 25–40 | 60–120 |
| Propofol | 10 mg/kg iv | Light anaesthesia | 5–10 | 10–15 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||
Sheep and goat
Table: Anaesthetic Dose Rates in the Sheep and Goat| Drug | Dose rate | Effect | Duration of anaesthesia (minutes) | Sleep time (minutes) |
|---|---|---|---|---|
| Alphaxalone/alphadolone | 2–3 mg/kg iv (adult) | Surgical anaesthesia | 5–10 | 10–20 |
| 6 mg/kg iv (lamb or kid) | ||||
| Ketamine/diazepam | 10–15 mg/kg + 1–2 mg/kg im | Light to medium anaesthesia | 20–30 | 60–90 |
| or 4 mg/kg iv + 0.5–1 mg/kg iv | Surgical anaesthesia | 20–30 | 45–90 | |
| Ketamine/dexmedetomidine | 1 mg/kg iv + 125 ug/kg iv | Surgical anaesthesia | 30–60 | 60–90 |
| Ketamine/medetomidine | 1 mg/kg iv + 25 ug/kg iv | Surgical anaesthesia | 30–60 | 60–90 |
| Ketamine/xylazine | 4 mg/kg + 0.2 mg/kg iv (sheep), 0.05 mg/kg iv (goat) | Surgical anaesthesia | 15–20 | 30–90 |
| Propofol | 4–5 mg/kg iv | Light anaesthesia | 5–10 | 10–15 |
| Duration of anaesthesia and sleep time (loss of righting reflex) are provided only as a general guide, since considerable between-animal variation occurs. For recommended techniques, see text. | ||||