Indications for sedation

• To reduce stress and anxiety:
• Improve animal welfare.
• Reduce risk of catecholamine-induced arrhythmias.
• Reduce risk of handling difficult dogs.
• To enable a thorough clinical examination.
• To perform diagnostic procedures.
• To perform minor surgical procedures.
• As premedication Anesthetic premedication: overview prior to general anesthesia General anesthesia: overview.

General rules

• Allow adequate time for onset of action of the sedative after administration.
• During this time it is very important to keep the dog in a quiet environment to get maximum sedative effect.
• Always monitor a dog that has been sedated.
• Intravenous administration generally produces the greatest sedative effect in the shortest time.
• The time to peak sedation is longer after intramuscular (IM) or subcutaneous (SC) administration, but the effect generally lasts longer.
• Depressive effects on the CNS may be additive or synergistic with other agents.

Sedative agents

Acepromazine

• See acepromazine Acepromazine maleate.
• Antagonist at dopamine excitatory receptors.
• Anti-emetic.
• Purported to cause seizures due to a lowering of the seizure threshold. There is no evidence to support this dogma.
• Reduces the sensitivity of the myocardium to circulating catecholamines, thereby reducing the risk of arrhythmias.
• Some antihistamine activity.
• Metabolized in the liver.

Side-effects

• Inhibits thermoregulation by depressing the hypothalamus thermoregulatory center.
• Peripheral vasodilation also promotes heat loss.
• Cardiovascular effects are dose-dependent:
  • Causes hypotension by alpha-adrenoceptor blockade and vasodilation.
  • Overdose results in a rapid.
    Great care required in brachycephalic dogs. Muscle relaxation of pharynx can result in obstruction and asphyxiation.
• Can cause penile prolapse due to a sympatholytic action causing paralysis of the retractor penis muscle.
• Causes PCV Hematology: packed cell volume to decrease:
  • Increased storage of RBCs in spleen. Splenic capsule relaxes due to alpha-adrenergic blockade.
  • Reduced hydrostatic pressure in arterioles, increases movement of interstitial fluid into vessels.

Uses

• Available in solution for injection (2 mg/ml) and tablet form.
  US is only available as 10 mg/ml - for small animals purposes, dilute with sterile water to 1 or 2 mg/ml.
• Unpredictable effect following oral administration.
• Dose is <0.05 mg/kg IM.
• Increasing the dose does not produce a proportional increase in sedation.
• Allow at least 20 min to take effect after IM administration.
• Duration of action is long - still some effect after 6 h.
• Consistency of sedative effects improved by combining acepromazine with an opioid.
• Suitable premedication dose is 0.03 mg/kg for young, healthy dogs.
• Reduce the dose for the following:
• • Old dogs.
  • Very young dogs.
  • Giant breeds. It is frequently recommended not to exceed a maximum dose of 3 mg (total) to any dog regardless of weight.
  • Boxers are very sensitive to the sympatholytic effects - use a low dose (<0.02 mg/kg).
  • Use at a very low dose or avoid in animals that are hypovolemic or hypotensive.
• In case of overdose and collapse:
  • Keep airway clear.
  • Administer intravenous fluids Fluid therapy.
  • Maintain normal body temperature.
  • Alpha-1-adrenoceptor agonists may improve blood pressure if condition is serious.

Benzodiazepines

• This drug group includes diazepam Diazepam and midazolam Midazolam.
• CNS depression occurs due to facilitation of binding of the inhibitory neurotransmitter GABA to its receptor.
• Reduce anxiety.
• Good muscle relaxation.
• No analgesic effects.
• Degree of sedation depends on species and individual.
• Healthy dogs do not become sedated with a benzodiazepine used alone.
• Excitement or aggression may be seen due to release of inhibited behavior patterns.
• Very wide safety margin. Can also reverse effects with flumazenil.
• Metabolized in the liver.
• Causes retrograde amnesia in humans.

Side-effects

• Minimal cardiovascular or respiratory effects which can be reversed with flumazeril.
• Synergism of respiratory depressive effects if combined with other CNS depressants.

Uses

• Dose of diazepam Diazepam or midazolam Midazolam = 0.2 mg/kg by IV or IM injection.
• Diazepam is insoluble in water and so is supplied as a clear solution in propylene glycol or as a white soya-bean emulsion.
• Propylene glycol is painful to inject and may cause hypotension if injected rapidly intravenously.
• Midazolam is water-soluble.
• Useful sedatives in young puppies, old dogs and debilitated dogs that may not tolerate acepromazine, especially if combined with an opioid Analgesia: opioid.
• Indicated as part of the premedication for animals undergoing contrast myelography as have an inhibitory effect on seizure activity.

Opioids

• Produce sedation if used in dogs that are debilitated, old or very young.
• Do not usually produce sedation if used alone in healthy dogs.
• Synergism with other sedatives generally produces good sedation in healthy dogs.

Side-effects

• Minimal cardiovascular effects at clinical doses. Potent opioids may cause bradycardia.
• Minimal respiratory effects at clinical doses. Significant respiratory depression only seen at very high doses.
• Some opioids may cause vomiting.

Uses

• Morphine Morphine :
  • Dose: 0.2-1.0 mg/kg (for premedication/sedation: up to 1 mg/kg is an acceptable dose).
  • Vomiting common shortly after administration.
  • Use in combination with acepromazine for synergism of sedative effect.
• Buprenorphine Buprenorphine :
  • Dose: 0.02 mg/kg.
  • Very unlikely to cause vomiting.
  • Slow onset of action - give at least 30 min before sedation required.
  • Long duration of action. Acepromazine and buprenorphine combination produces useful sedation for up to 4 h.
• Omnopon (not available in US):
  • Dose: 0.4 mg/kg.
  • Produces profound sedation when used in combination with acepromazine.
  • Useful sedation for aggressive dogs.
• Pethidine Pethidine (meperidine or demerol in US):
  • Dose 2-5 mg/kg.
  • Short duration of action - <2 h.
  • Can be used alone in debilitated animals, or in combination with acepromazine in healthy dogs.

Alpha-2 agonists

• Can produce profound sedation Analgesia: alpha-2 agonist.
• Reversible with atipamazole Atipamezole.
• Provide good analgesia.
• Inhibit anti-diuretic hormone release → increase urine production.
• Increase blood glucose concentration Blood biochemistry: glucose.
• Also decrease insulin release (hypoinsulinemia).
• Decrease gut motility.
• Xylazine has an ecbolic effect on the uterus Xylazine (only well-documented in cows, in the last trimester of pregnancy).
• Inhibit body temperature regulation.
• Frequently cause vomiting.

Side-effects

• Cardiovascular effects:
  • Profound bradycardia and second degree heart block may occur. Caused by central stimulation of parasympathetic nervous system.
  • Initial hypertension caused by stimulation of post-synaptic receptors in peripheral vessel walls - results in poor tissue perfusion.
  • The brief initial hypertension is followed by a return to normotension in healthy animals, caused by CNS depression and a sympatholytic effect.
  • Coronary circulation is reduced.
  • May sensitize the heart to catecholamine-induced arrhythmias.
• Respiratory effects:
  • Respiratory rate decreases and arterial oxygen tension tends to decrease.
  • Cyanosis is common, possibly due to increased oxygen extraction and venous desaturation rather than decreased arterial oxygen tension.

Uses

• Alpha-2 agonists are very convenient drugs, producing profound sedation rapidly, which is equally as rapidly reversible.
  Side-effects can be very serious. Even though the animal survives, its organ functions may be permanently impaired.
• Medetomidine Medetomidine has less interaction with receptors (other than alpha-2 adrenoceptors), than xylazine Xylazine.
• Medetomidine is a racemic mixture of dexmedetomidine Dexmedetomidine (active enantiomer) and levomedetomidine (inactive enantiomer).
• Dexmedetomidine is now available as a single agent. It is more specific for the alpha-2 receptor and may provide more reliable sedation and analgesia.
• It is recommended that dexmedetomidine is dosed according to body surface area due to the potency of this drug.
• Sedation achieved with medetomidine/dexmedetomidine administered IM is inconsistent, probably due to poor absorption.
• Side-effects increase with dose, therefore use the minimum dose possible.
• Reduce the dose required by combining with any of the opioids, eg dose can be reduced to 0.005 mg/kg medetomidine Medetomidine.
• Provide supplemental oxygen with a face mask where possible.
  Alpha-2 agonists greatly reduce the dose required of any anesthetic agent used consequently. They also reduce cardiac output so it takes longer for IV induction agents to produce loss of consciousness. Allow plenty of time before giving incremental doses of induction agents.
• Atipamazole Atipamezole is a specific alpha-2 antagonist which rapidly reverses the effects of medetomidine and dexmedetomidine. It reverses analgesia as well as sedative effects.
• It is not recommended to administer atropine to counteract the bradycardic effects of alpha-2 agonists. Atropine increases the heart rate, but also increases hypertension, peripheral vascular resistance and poor peripheral perfusion, increases the risk of dysrhythmias, increases cardiac work and oxygen consumption, and decreases ventricular filling time.
• Although dogs may appear profoundly sedated, on occasion they can suddenly stir and bite in response to stimulation.
• Medetomidine/dexmedetomidine is absorbed well through the oral mucosa, with a similar bioavailability to IM administration. Therefore sublingual administration can be used, with care not to overdose.

Useful sedative protocols

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• Dyson D H (2008) Analgesia and chemical restraint for the emergent veterinary patient. Vet Clin North Am Small Anim Pract 38 (6), 1329-1352 PubMed.
• Granholm M, McKusick B C, Westerholm F C et al (2007) Evaluation of the clinical efficacy and safety of intramuscular and intravenous doses of dexmedetomidine and medetomidine in dogs and their reversal with atipamezole. Vet Rec 160 (26), 891-897 PubMed.
• Leppänen M K, McKusick B C, Granholm M M et al (2006) Clinical efficacy and safety of dexmedetomidine and buprenorphine, butarphanol or diazepam for canine hip radiography. JSAP 47 (11), 663-669 PubMed.
• Johnson C (1999) Chemical restraint in the dog and cat. In Practice 21 (3), 111-118 VetMedResource.
• Short C E, Räihä J E, Räihä M P et al (1992) Comparison of neurologic responses to the use of medetomidine as a sole agent or preanesthetic in laboratory beagles. Acta Vet Scand 33 (1), 77-88 PubMed.
• Vähä-Vahe T (1989) Clinical evaluation of medetomidine, a novel sedative and analgesic drug for dogs and cats. Acta Vet Scand 30 (3), 267-273 PubMed.