Sedative combinations for ferrets

• Ketamine (5–8 mg/kg i.m.) plus medetomidine (80–100 μg (micrograms)/kg i.m.) or dexmedetomidine (40–50 μg (micrograms)/kg i.m.) to which can be added butorphanol (0.1–0.2 mg/kg i.m.) or buprenorphine (0.02 mg/kg i.m.) based on studies in healthy ferrets a,b.
• Ketamine (5–20 mg/kg i.m.) plus midazolam (0.25–0.5 mg/kg i.m.) or diazepam (0.25–0.5 mg/kg i.m.) will provide immobilization or, at the higher doses, a short period of anaesthesia.
• Ketamine (7–10 mg/kg i.m., s.c.) plus medetomidine (20 μg (micrograms)/kg i.m., s.c.) plus midazolam (0.5 mg/kg i.m., s.c.) will provide anaesthesia; concurrent oxygenation is recommendedb.
• Midazolam (0.2-0.3 mg/kg i.m.) plus butorphanol (0.2-0.3 mg/kg i.m.) provides moderate sedation for non-invasive proceduresc.

References

a Ko JC, Heaton-Jones TG and Nicklin CF (1997) Evaluation of the sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, medetomidine-ketamine and medetomidine-butorphanol-ketamine in ferrets. Journal of the American Animal Hospital Association 33(5), 438–448

b Schernthaner A, Lendl CE, Hartmann K  et al. (2011) Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations. Veterinary Anaesthesia and Analgesia 38(5), 439–450

cKapaldo N and Eshar D (2022) Ferret sedation and anesthesia. Veterinary Clinics of North America: Exotic Animal Practice  25(1), 273-296

Sedative combinations for rabbits

• Ketamine (3–5 mg/kg i.v. or 5–10 mg/kg i.m., s.c.) in combination with medetomidine (0.05–0.1 mg/kg i.v. or 0.1–0.3 mg/kg s.c., i.m.) or dexmedetomidine (0.025–0.05 mg/kg i.v. or 0.05–0.15 mg/kg s.c., i.m.) and butorphanol (0.05–0.1 mg/kg i.m., i.v., s.c.) or buprenorphine (0.02–0.05 mg/kg i.m., i.v., s.c.).
• Fentanyl/fluanisone (0.1–0.3 ml/kg i.m.) plus diazepam (0.5–1 mg/kg i.v., i.m. or 2.5–5.0 mg/kg i.p.) or midazolam (0.25–1.0 mg/kg i.v., i.m., i.p.).

The combinations above will provide immobilization/light anaesthesia, usually sufficient to allow intubation for maintenance with a volatile agent.

• Ketamine (15 mg/kg i.m.) in combination with medetomidine (0.25 mg/kg i.m.) and buprenorphine (0.03 mg/kg i.m.) will provide general anaesthesia based on studies in healthy animalsa,b,c, but use of lower doses of medetomidine and ketamine followed by intubation and use of a volatile agent is recommended in practice.
• Midazolam (0.5-2 mg/kg i.m.) plus butorphanol (0.5-2 mg/kg i.m.) provides moderate sedation for non-invasive proceduresd. Can also be given i.v. starting at the lower end of dose range.

The doses above are for use in clinically healthy animals. As prey species are good at hiding signs of disease and because subclinical disease, especially respiratory tract disease, is common, careful preanaesthetic assessment of such patients and titration of doses to effect by i.v. administration, where possible, is advised.

References

a Grint NJ and Murison PJ (2008) A comparison of ketamine-midazolam and ketamine-medetomidine combinations for induction of anaesthesia in rabbits. Veterinary Anaesthesia and Analgesia 35(2), 113–121

b Murphy KL, Roughan JV, Baxter MG and Flecknell PA (2010) Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine. Veterinary Anaesthesia and Analgesia 37(3), 222–229

c Orr HE, Roughan JV and Flecknell PA (2005) Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit. Veterinary Anaesthesia and Analgesia 32(5), 271–279

dGardhouse S and Sanchez A (2022) Rabbit sedation and anesthesia.  Veterinary Clinics of North America: Exotic Pet Practice  25(1), 181-210

Sedative combinations for other small mammals

• Medetomidine (50 μg (micrograms)/kg i.m.) or dexmedetomidine (25 μg (micrograms)/kg i.m.) plus, if needed, ketamine (2–4 mg/kg i.m.)a,b,c,d,e,f.
• Sugar gliders: Buprenorphine (0.01 mg/kg i.m.) in combination with midazolamg.
• Other combinations as for rabbits: Combinations can also be administered i.p. in small rodents.

References

a Bakker J, Uilenreef JJ, Pelt ER  et al.  (2013) Comparison of three different sedative-anaesthetic protocols (ketamine, ketamine-medetomidine and alphaxalone) in common marmosets ( Callithrix jacchus ). BMC Veterinary Research 9(1), 113

bBuchanan KC, Burge RR and Ruble GR (1998) Evaluation of injectable anaesthetics for major surgical procedures in guinea pigs. Contemporary Topics in Laboratory Animal Science 37(4), 58–63

cDang V, Bao S, Ault A et al. (2008) Efficacy and safety of five injectable anesthetic regimens for chronic blood collection from the anterior vena cava of guinea pigs. Journal of American Association of Laboratory Animal Science 47(6), 56–60

d  Hedenqvist P, Roughan JV and Flecknell PA (2000) Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats. Laboratory Animals 34(2), 207–211

e  Jang HS, Choi HS, Lee SH, Jang KH and Lee MG (2009) Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole. Veterinary Anaesthesia and Analgesia 36(4), 319–327

f  Nevalainen T, Pyhälä L, Voipio HM and Virtanen R (1989) Evaluation of anaesthetic potency of medetomidine-ketamine combination in rats, guinea pigs and rabbits. Acta Veterinaria Scandinavica 85, 139–143

g Doss G and de Miguel Garcia C (2022) African pygmy hedgehog ( Atelerix albiventris ) and sugar glider ( Petaurus breviceps ) sedation and anesthesia.  Veterinary Clinics of North America: Exotic Animal Practice  25(1), 257-272

Note: Reduce doses if animal is debilitated. For all small mammals, for deeper anaesthesia, intubation (if possible) and use of a volatile agent is recommended, rather than using higher doses of injectable agents.

Sedative combinations for birds

Injectable anaesthesia has largely been avoided in birds since the advent of  'safer' gaseous agents such as isoflurane and sevoflurane. However, systemic agents are becoming increasingly used either as induction agents (e.g. as part of a total intravenous anaesthetic (TIVA) protocol) or as premedication prior to gaseous anaesthesia. The latter is primarily used to reduce the dose of gaseous anaesthesia and therefore reduce stress and hypotensive effects. Parasympathetic agents (such as atropine) are rarely used as their effect is to make respiratory excretions more viscous, thus increasing the risk of tube blockage. TIVA is rarely used except in specialized situations, whilst intravenous induction tends to be used in field situations or in large birds (e.g. ratites) and those with a dive response (e.g. waterfowl, penguins) that may be hard to induce with gaseous agents. In some high-risk cases, sedation may be used in pet birds for non-invasive diagnostic procedures (e.g. blood sampling, radiography) or prior to intravenous euthanasia. In these cases, the intranasal route is much less painful for the bird and is easily used, with midazolam/butorphanol mixtures being effective. For stress relief (e.g. in dyspnoeic birds), midazolam alone may be used. Flumazenil (0.05 mg/kg) is effective in reversing midazolam via the intramuscular or intranasal routes. 

• Propofol: 10 mg i.v. by slow infusion to effect; supplemental doses up to 3 mg/kga,b; 0.5 mg/kg/min i.v. as CRI.
  • For large birds and those with a dive response: 2–4 mg/kg i.v. to effect.
  • Bengalese finches: 10-50 mg/kg s.c. with or without midazolam and/or butorphanol. Increasing dose linked with increasing length of sedation rather than depth.
  • Budgerigars: 15 mg/kg s.c.; 10 mg/kg suitable for shorter non-invasive investigations.
• Ketamine/diazepam combinations can be used for induction and muscle relaxation. Ketamine (30–40 mg/kg) plus diazepam (1.0–1.5 mg/kg) are given slowly i.v. to effect. May also be given i.m. but this produces different effects in different species and specific literature or specialist advice should be consulted. Ketamine (10 mg/kg i.m.) and diazepam (0.2–0.5 mg/kg i.m.) can be used as premedication/sedation (pigeons, Amazon parrots) prior to the administration of sevoflurane/isofluranec,d.
• Sedation: Midazolam:
  • 0.1–0.5 mg/kg i.m. or 0.05–0.15 mg/kg i.v. (premedicant) or 2–3 mg/kg intranasal. Can be combined with butorphanol (1-3 mg/kg intranasal) for premedication/ sedation.
  • 2 mg/kg intranasal provided sedation in Eurasian buzzards (reversible with 0.05 mg/kg intranasal flumazenil).
  • 1-2 mg/kg i.m. premedication had a significant isoflurane-sparing effect on Quaker parrots without effecting the heart rate or body temperature.
• Sedation: Butorphanol (3 mg/kg intranasal) plus midazolam (3 mg/kg) may prolong anaesthetic recovery e.
• Raptors: Ketamine (2–5 mg/kg i.m.) plus medetomidine (25–100 μg (micrograms)/kg) (lower dose rate i.v.; higher rate i.m.). This combination can be reversed with atipamezole at 65 μg (micrograms)/kg i.m. Ketamine should be avoided in vultures.

References

aFitzgerald G and Cooper JE (1990) Preliminary studies on the use of propofol in the domestic pigeon ( Columba livia ). Research in Veterinary Science 49(3), 334–338

bHawkins MG, Wright BD, Pascoe PJ  et al. (2003) Pharmacokinetics and anesthetic and cardiopulmonary effects of propofol in red-tailed hawks ( Buteo virginianus ) and great horned owls ( Bubo virginianus ). American Journal of Veterinary Research 64(6), 677–683

cAzizpour and Hassani Y (2012) Clinical evaluation of general anaesthesia in pigeons using a combination of ketamine and diazepam. Journal of the South African Veterinary Association 83(1), 12

dPaula VV, Otsuki DA, Auler Júnior JO  et al. (2013) The effect of premedication with ketamine, alone or with diazepam, on anaesthesia with sevoflurane in parrots ( Amazona aestival ). BMC Veterinary Research 9, 142

eDoss GA, Fink DM and Mans C (2018) Assessment of sedation after intranasal administration of midazolam and midazolam/butorphanol in cockatiels ( Nymphicus hollandicus ).  American Journal of Veterinary Research  79(12), 1246-1252

Sedative combinations for reptiles

• Alfaxalone or propofol (see monographs) can be used to provide deep sedation or induce anaesthesia in reptiles. Additional analgesia should be provided as part of the pre-anaesthetic sedation (see below) for any potentially painful proedure and maintenance with a volatile inhalation agent will be required for prolonged anaesthesia.
• Ketamine as sole agent: Ketamine alone may result in variable sedation, poor muscle relaxation and prolonged recovery at higher dose rates. Usually combined with alpha-2 agonists and/or opioids/midazolam to provide deep sedation/light anaesthesia (see below).
• Alpha-2 agonists as sole agents: Although single agent use has been reported, it is generally preferable to use medetomidine or dexmedetomidine in combination with opioids and/or ketamine and/or midazolam for more reliable sedation (see below). Should be reversed with atipamezole (see monograph).
• Benzodiazepines as sole agents: Although single agent used has been reported, it is generally preferable to use midazolam in combination with opioids and/or ketamine and/or alpha-2 agonists for more reliable sedation (see below). Can be reveresed with flumazenil if required (see monograph).
• Ketamine/alpha-2 agonist/opioid/benzodiazepine mixtures:
  • Most species for pre-anaesthetic sedation: Midazolam (1-2 mg/kg i.m.) plus butorphanol (0.5-2 mg/kg i.m.) or morphine (1-1.5 mg/kg i.m.) if required may be administered pre-anaesthetic for sedation or in combination with alfaxalone. Choice of opioid will depend on whether just sedation (butorphanol can be used) or sedation plus analgesia (morphine is preferred) is required
  • Chelonians: 
    • Ketamine (5–10 mg/kg i.m., i.v.) plus medetomidine (100–200 μg (micrograms)/kg i.m., i.v.) (deep sedation to light anaesthesia in Gopher tortoises and Red-eared sliders) a, b 
    • Ketamine (10 mg/kg intranasal) plus dexmedetomidine (200 μg) micrograms)/kg intranasal) (deep sedation to light anaesthesia in red-eared sliders) c 
    • Ketamine (2 mg/kg s.c.) plus dexmedetomidine (100 μg (micrograms)/kg s.c.) and midazolam (1 mg/kg s.c.) (moderate sedation in Red-eared sliders) d 
    • Ketamine (10 mg/kg i.m.) plus dexmedetomidine (100 μg (micrograms)/kg i.m.) and midazolam (1 mg/kg i.m.) (deep sedation to light anaesthesia in Red-footed tortoises and Ornate box turtles) e, f.
  • Lizards:
    • Midazolam (0.5–2 mg/kg i.m., s.c.) plus dexmedetomidine (50–100 μg (micrograms)/kg i.m., s.c.) plus ketamine if required (1–5 mg/kg i.m., s.c.) (sedation in variety of lizards) g 
    • Midazolam (1 mg/kg i.m.) plus dexmedetomidine (200 μg (micrograms)/kg i.m.) (sedation in Tegus) h
    • Midazolam (1 mg/kg i.m.) plus dexmedetomidine (100 μg (micrograms)/kg i.m.) (light to moderate sedation in Leopard geckos) i. 
  • Snakes:
    • Midazolam (0.5 mg/kg i.m.) plus dexmedetomidine (50 μg (micrograms)/kg i.m.) (moderate sedation in Royal pythons) j
    • Butorphanol (10 mg/kg i.m.) followed by midazolam (0.5 mg/kg i.m.), dexmedetomidine (50 μg (micrograms)/kg i.m.) and ketamine (5 mg/kg i.m.) (light anaesthesia in Bullsnakes) k.

References

aDennis C and Heard DJ (2002) Cardiopulmonary effects of a medetomidine-ketamine combination administered intravenously in gopher tortoises.  Journal of the American Veterinary Medical Association  220(10), 1516-1519

bGreer LL, Jenne KJ and Diggs HE (2001) Medetomidine-ketamine anesthesia in red-eared slider turtles (T rachemys scripta elegans ).  Journal of the American Association for Laboratory Animal Science  40(3), 8-11

cCermakova E, Ceplecha V and Knotek Z (2018) Efficacy of two methods of intranasal administration of anaesthetic drugs in red-eared terrapins ( Trachemys scripta elegans ). Veterinární Medicína 63(2), 87-93

dMans C, Drees R, Sladky KK, Hatt JM and Kircher PR (2013) Effects of body position and extension of the neck and extremities on lung volume measure via computed tomography in red-eared slider turtles ( Trachemys scripta elegans ).  Journal of the American Veterinary Medical Association  243(8), 1190-1196

eEshar D, Rooney T A, Gardhouse S and Beaufrère H (2021) Evaluation of the effects of a dexmedetomidine-midazolam-ketamine combination administered intramuscularly to captive red-footed tortoises ( Chelonoidis carbonaria ). American Journal of Veterinary Research 82(11), 858-864

f Rooney TA, Eshar D, Gardhouse S and Beaufrère H (2021) Evaluation of a dexmedetomidine–midazolam–ketamine combination administered intramuscularly in captive ornate box turtles ( Terrapene ornata ornata ). Veterinary Anaesthesia and Analgesia 48(6), 914-921

g Budden L, Doss GA, Clyde VL and Mans C (2018) Retrospective evaluation of sedation in 16 lizard species with dexmedetomidine-midazolam with or without ketamine. Journal of Herpetological Medicine and Surgery 28(1-2), 47-50

hBisetto SP, Melo CF and Carregaro AB (2018) Evaluation of sedative and antinociceptive effects of dexmedetomidine, midazolam and dexmedetomidine-midazolam in tegus ( Salvator merianae ). Veterinary Anaesthesia and Analgesia 45(3), 320-328

iDoss GA, Fink DM, Sladky KK and Mans C (2017) Comparison of subcutaneous dexmedetomidine-midazolam versus alfaxalone-midazolam sedation in leopard geckos ( Eublepharis macularius ). Veterinary Anaesthesia and Analgesia 44(5), 1175-1183

jYaw TJ, Mans C, Johnson S et al. (2020) Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons ( Python regius ). J ournal of the American Veterinary Medical Association 256(5), 573-579

kSadar MJ and Ambros B (2018) Use of alfaxalone or midazolam–dexmedetomidine–ketamine for implantation of radiotransmitters in bullsnakes ( Pituophis catenifer sayi ). Journal of Herpetological Medicine and Surgery 28(3-4), 93-98

Sedative combinations for fish

The dose rates below are for induction of anaesthesia. A lower dose (approximately 20-25% of the induction dose rate) is required for maintenance of anaesthesia in a separate container or using a recirculating system. All anaesthetics are administered by immersion and the stage of anaesthesia reached is determined by the concentration used and the duration of exposure, since absorption continues throughout the period of immersion. There are significant species differences in the response to drugs and it is advised that lower dose rates are used for unfamiliar species, marine and tropical fish. Many products and stock solutions should be kept in a dark bottle and protected from light. Ideally, the anaesthetic solution should be made up using water from the tank or pond of origin to minimize problems due to changes in water chemistry. It should be used on the day of preparation and well aerated during use. Food should be withheld for 12-24 hours before anaesthesia to reduce the risk of regurgitation, which may cause damage to gill tissues. Monitoring heart rate during prolonged procedures using a Doppler probe or ultrasound scanner is advisable since this is a direct reflection of the level of anaesthesia. Following the procedure, anaesthetized fish should be returned to clean water from their normal environment to allow recovery.

• Tricaine mesilate (MS-222) (50–250 mg/l by immersion) produces an acidic solution and should be buffered with sodium bicarbonate to maintain the same pH as the original environmental water conditions. The dry powder is very soluble in water and can be added directly or a stock solution can be made up to facilitate accurate dosing.
• Benzocaine (Optomease Vet) (25–200 mg/l by immersion) is insoluble in water and must be dissolved in acetone or ethanol (e.g. a stock solution of 100 g benzocaine/l of ethanol produces 100 mg/ml to facilitate accurate dosing).
• 2-Phenoxyethanol (Aqua-sed) (0.1–0.5 ml/l by immersion) must be whisked vigorously into the water to improve solubility.
• Alfaxalone (Alfaxan) (5-10 mg/l by immersion) for induction a.
• Propofol (Norofol) (2.5-10mg/l by immersion) produces a cloudy solution and reduces visibility of the patient; therefore, care is required while monitoring vital signs during anaesthesia b.

References

aMinter LJ, Bailey KM, Harms CA, Lewbart GA and Posner LP (2014) The efficacy of alfaxalone for immersion anaesthesia in koi carp ( Cyprinus carpio ). Veterinary Anaesthesia and Analgesia 41(4), 398–405

bOda A, Bailey KM, Lewbart GA, Griffith EH and Posner LP (2014) Physiologic and biochemical assessments of koi ( Cyprinus carpio ) following immersion in propofol. Journal of the American Veterinary Medical Association 245(11), 1286–1291