Sedative combinations for dogs

Acepromazine as sole agent: Acepromazine alone is not a particularly effective sedative. See monograph for further information. Because larger breeds seem to be more sensitive to acepromazine, it is recommended not to exceed a total dose of 1 mg/patient.

Acepromazine/opioid mixtures (neuroleptanalgesia): Acepromazine used in combination with opioid analgesics reduces the dose requirement of both components and also the incidence of adverse effects. Acepromazine (0.01–0.03 mg/kg, except in Boxers 0.005–0.01 mg/kg, use lower doses i.v.) can be combined with:

• Pethidine (2–10 mg/kg i.m.)
• Methadone (0.1–0.5 mg/kg i.m., i.v.)
• Papaveretum (0.05–0.4 mg/kg i.v., i.m.)
• Buprenorphine (0.02–0.03 mg/kg i.v., i.m)
• Butorphanol (0.1–0.4 mg/kg i.v., i.m.).

Alpha-2 agonists as sole agents: Although authorized for single-agent use, it is generally preferable to use medetomidine or dexmedetomidine in combination with opioids (see below).

Recommended dose in dogs and cats of medetomidine is 5–20 μg (micrograms)/kg i.m. and of dexmedetomidine is 2.5–10 μg/kg i.m. Lower doses of medetomidine (1–10 μg/kg) or dexmedetomidine (1–5 μg/kg) may be given i.v. At higher doses, marked cardiovascular effects (mainly bradyarrhythmias) should be expected.

Adverse effects may be antagonized with i.m. atipamezole at 5 times the agonist dose rate. The (unauthorized) i.v. route is preferable in critical situations.

See below for information on xylazine.

The use of alpha-2 agonists for sedation is only recommended in healthy animals.

Medetomidine/Vatinoxan: Zenalpha is licensed to be used as a sole agent for sedation in dogs. It is administered i.m. at a dose based on body surface area. The dose will result in administration of 1 mg medetomidine and 20 mg vatinoxan per square metre of body surface area (m2). The duration of action of Zenalpha (sedation and analgesia) is shorter than that of dexmedetomidine, therefore it is licensed for sedation for procedures lasting 30 minutes or less that are non-painful or only mildly painful. Due to the short duration of action, reversal with atipamezole is unlikely to be necessary. If deemed necessary, atipamezole should be given at half the volume of administered Zenalpha i.m., although i.v. administration can be used in critical situations. Heart rate should be monitored after atipamezole administration as tachycardias have been reported.

Alpha-2 agonist/opioid mixtures: Including opioids with medetomidine or dexmedetomidine lowers the dose required to achieve a given level of sedation, limiting the marked effects that alpha-2 agonists exert on cardiopulmonary function. If sedation is still inadequate, it is better to proceed to induction of general anaesthesia using an i.v. induction agent, such as alfaxalone or propofol, rather than by giving a repeated or higher dose of alpha-2 agonist.

Medetomidine or dexmedetomidine, at the doses described above, can be combined with:

• Pethidine (2–10 mg/kg i.m.)
• Methadone (0.1–0.5 mg/kg slow i.v., i.m.)
• Buprenorphine (0.02–0.03 mg/kg slow i.v., i.m.)
• Butorphanol (0.1–0.4 mg/kg slow i.v., i.m.).

Although xylazine (1–3 mg/kg) may be used alone or in combination with opioids, given i.m. or i.v. (unauthorized), its use in dogs and cats has been superseded by use of medetomidine or dexmedetomidine and it is not recommended. Adverse effects may be antagonized with i.m. or i.v. atipamezole, although this use is unauthorized.

Acepromazine/alpha-2 agonist/opioid mixtures: Combining low doses of acepromazine (0.01 mg/kg) and medetomidine (5–10 μg (micrograms)/kg) or dexmedetomidine (2.5–5 μg/kg) with opioid agonist drugs provides profound sedation with less cardiovascular depression than with an alpha-2 agonist or acepromazine as a sole agent.

A mixture of acepromazine (up to 0.03 mg/kg) with any of the combinations given above for alpha-2 agonists and alpha-2 agonist/opioid mixtures (higher end of dose ranges) is suitable for the chemical restraint of aggressive dogs. Severe depression can be antagonized using naloxone and atipamezole.

An effective combination to sedate aggressive dogs is medetomidine (20 µg (micrograms)/kg) or dexmedetomidine (10 µg/kg) combined with ketamine (2 mg/kg) and an opioid (e.g. methadone, 0.3 mg/kg or butorphanol, 0.3 mg/kg) i.m. Choose methadone when the procedure is likely to cause pain or in dogs with pre-existing pain.

Benzodiazepines and benzodiazepine/opioid mixtures: Benzodiazepines do not reliably sedate healthy dogs when used alone; indeed, stimulation ranging from increased motor activity to gross excitation may be seen. The risk of excitation is proportional to the health of the recipient: the chances of producing sedation are highest (but not guaranteed) in very sick, young or older animals.

Opioid/benzodiazepine mixtures are satisfactory and relatively safe in critically ill animals. These combinations are more effective when given i.v. (with the exception of pethidine). Transient excitation may occur when given by this route. When given i.m., excitation is unlikely although the depth of sedation is also reduced. Midazolam or diazepam (0.2–0.3 mg/kg i.v.) can be given with:

• Pethidine (2–10 mg/kg i.m.)
• Methadone (0.1–0.5 mg/kg i.v., i.m.)
• Papaveretum (0.2–0.5 mg/kg i.v., i.m.)
• Buprenorphine (0.02–0.03 mg/kg i.v., i.m.)
• Butorphanol (0.1–0.4 mg/kg i.v., i.m.)
• Fentanyl (0.01 mg/kg slow i.v.).

It is preferable to use midazolam (unauthorized) when choosing the i.m. route, as the absorption of diazepam via this route can be variable.

Alfaxalone: Although not authorized for this use, 2 mg/kg i.m. will provide sedation in dogs that lasts 10–15 minutes. The volume of injectate precludes use of this technique in medium- to large-breed dogs. Alfaxalone can be used in conjunction with opioids and benzodiazepines.

Notes:

• A well managed light level of general (inhalational) anaesthesia is often safer than heavy sedation in sick animals.
• Neuroleptanalgesic combinations are safer than alpha-2 agonist/opioid mixtures but are less likely to produce adequate conditions for minor operations or investigations involving abnormal body positions. Furthermore, only the opioid component can be antagonized.
• Most of the aforementioned combinations will have a profound sparing effect on i.v. and inhalational anaesthetics, should a general anaesthetic be required after sedation. This is particularly true of combinations containing alpha-2 agonists.
• Any stress induced in the patient may decrease the effectiveness of sedative drugs and higher initial doses may be required.
• Close monitoring of the cardiorespiratory system is recommended during sedation.
• Oxygen supplementation is recommended during sedation.

Sedative combinations for cats

Acepromazine: Acepromazine alone is not a particularly effective sedative and increasing the dose incurs the same problems as in dogs (see above). Doses of 0.01–0.05 mg/kg may be given i.v., i.m. or s.c. Cats often require higher doses of acepromazine than dogs to achieve comparable sedation. Recumbency is normally not achievable in cats with acepromazine sedation.

Neuroleptanalgesia: Neuroleptanalgesic combinations confer the same advantages in cats as in dogs (see above). Acepromazine (0.01–0.05 mg/kg) can be combined with (use the lower end of the dose ranges i.v.):

• Pethidine (2–10 mg/kg i.m.)
• Methadone (0.1–0.5 mg/kg i.v., i.m.)
• Buprenorphine (0.02–0.03 mg/kg i.v., i.m.)
• Butorphanol (0.1–0.4 mg/kg i.v., i.m.).

Alpha-2 agonists as sole agents and alpha-2 agonist/opioid mixtures: See information given for dogs, above. Adverse effects may be antagonized with i.m. atipamezole at 2.5 times the agonist dose rate; the (unauthorized) i.v. route is preferable in critical situations.

Benzodiazepines: Diazepam (0.2–0.3 mg/kg) or midazolam (0.2–0.3 mg/kg) i.v. can provide satisfactory sedation in very sick cats. The inclusion of opioids at doses given for alpha-2 agonist/opioid mixtures (see above) may improve conditions, but benzodiazepine/opioid combinations do not provide reliable sedation in most cats.

Ketamine and ketamine-based techniques: Ketamine is relatively safe in ill animals, but high doses cause prolonged recoveries and are associated with muscle rigidity. Acepromazine (0.05–0.1 mg/kg) with midazolam (0.25 mg/kg) and ketamine (2.5–7.5 mg/kg), mixed and injected i.m., provides good conditions with only modest cardiopulmonary depression. The higher doses of ketamine should be used in excitable animals undergoing more stimulating interventions.

Alternatives: Ketamine (2.5 mg/kg) combined with diazepam or midazolam (0.2–0.3 mg/kg) i.v. provides profound sedation which lasts for about 15–20 minutes. Higher doses of ketamine (5 mg/kg) may be required if given i.m. This combination is preferred over ketamine/acepromazine combinations in sick cats. Diazepam can cause pain on injection; use of midazolam is preferred.

Ketamine (5 mg/kg) with medetomidine 10–40 μg (micrograms)/kg i.m. produces profound sedation but should only be used in healthy cats. An opioid can be added to this mixture to provide analgesia or further sedation. Atipamezole may be given if severe problems are encountered.

Although ketamine elimination depends heavily on renal function in cats, a full recovery still occurs, albeit more slowly, in cats with renal disease or urinary tract obstruction. However, low doses should be used in such cases.

Alfaxalone: Although not authorized for this use, 2–3 mg/kg i.m. or s.c. provides sedation lasting 10–15 minutes in cats. Alfaxalone can be combined with an opioid and/or midazolam to improve sedation.

Notes:

• Careful handling and restraint to achieve injection of sedative is preferred, but a crush cage may be useful for restraining feral cats. Most fearful cats can be injected i.m. by putting them in a top-opening cat carrier and covering most of the body and head with a towel. If injection of sedatives proves impossible, anaesthesia can be induced using a large induction chamber into which volatile anaesthetic agents can be delivered via an anaesthetic machine.
• Most of the aforementioned combinations will have a profound sparing effect on i.v. and inhalational anaesthetics, should a general anaesthetic be required after sedation. This is particularly true of combinations containing alpha-2 agonists.
• The high body surface area:volume of cats results in rapid heat loss compared with dogs. Attention to thermoregulation must be diligent.
• A well managed light level of general (inhalational) anaesthesia is frequently safer than heavy sedation in sick animals.
• Any stress induced in the patient may decrease the effectiveness of sedative drugs and higher initial doses may be required.
• Close monitoring of the cardiorespiratory system is recommended during sedation.
• Oxygen supplementation is recommended during sedation.