E. Monteiro
Animal Medicine Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Introduction
Injectable anesthetics constitute the cornerstone of drugs used to provide unconsciousness and immobility in dogs and cats. These drugs are used to allow handling of animals for diagnostic and surgical procedures. Currently, there is a great number of injectable anesthetics recommended for use in dogs and cats, but availability can vary between countries according to local policies.
The anesthetist must be aware that all injectable anesthetics can induce adverse effects that may result in severe complications, even when administered at clinically recommended doses. In addition, routes of administration may vary such that some drugs should be administered intravenously, whereas others may have more flexible routes of administration.
The choice of anesthetic should be tailored to individual needs. Good understanding of the pharmacological properties of injectable anesthetics will allow the anesthetist to provide safe and effective anesthesia according to the needs of each patient.
Main Injectable Anesthetics Available for Use in Dogs and Cats
Five injectable anesthetics are currently more employed for anesthesia in dogs and cats: propofol, alfaxalone, etomidate, ketamine and tiletamine/zolazepam. Propofol, alfaxalone and etomidate are general anesthetics and induce unconsciousness. Ketamine and tiletamine are dissociative agents that induce a cataleptic state. Of the above anesthetics, propofol and etomidate are exclusively administered by intravenous injection. Alfaxalone can be administered intravenously or subcutaneously and the dissociative agents can be administered intravenously or intramuscularly.1
Adverse Effects
It is important to be aware that adverse effects are dependent upon dose and rate of injection. Titration of the dose according to individual needs by administering small intravenous bolus doses "to effect" may reduce the intensity of such effects, but does not ensure complications will not occur.
All injectable anesthetics can cause respiratory depression and apnea during induction of anesthesia. Therefore, orotracheal tubes, a means to perform mechanical ventilation (ambu bag, breathing system) and oxygen supplementation should be available throughout anesthetic procedures.
Propofol decreases cardiac output, systemic vascular resistance and blood pressure.1 These effects are well tolerated by healthy dogs and cats, but may be devastating in patients with hemodynamic instability such as in hypovolemia, shock syndromes or heart diseases.
Alfaxalone was also shown to reduce blood pressure in dogs by decreasing systemic vascular resistance, but cardiac output was well maintained.2 Dissociative agents increase heart rate, cardiac output, myocardial oxygen demand and blood pressure.1 Etomidate provided the most stability in the cardiovascular system with no clinically relevant changes in cardiovascular parameters after recommended doses.3
Metabolism of propofol is not exclusively dependent on liver function. Therefore, anesthetic recovery in patients with liver disease is not more prolonged than in normal patients. Conversely, recovery may be prolonged after anesthesia with the other four agents if the patient has impaired liver function. Furthermore, hepatic metabolism of dissociative agents produce active metabolites which are eliminated unchanged in urine (mostly in cats) and patients with kidney disease may present prolonged recovery.1
General anesthetics are expected to maintain unchanged or to decrease cerebral blood flow provided that the patient remains normocapnic. Conversely, dissociative agents increase cerebral blood flow which can rise intracranial pressure in patients with head trauma.1
Clinical Use
Recommended doses for induction of anesthesia with each drug are summarized in Table 1. Injectable agents provide anesthesia of short duration, usually not exceeding 15-20 minutes. For anesthetic procedures of longer duration, maintenance can be performed by intermittent boluses or constant rate infusion of the injectable anesthetic. Duration of effect will depend upon dose and the use of anesthetic adjuncts. Higher doses result in deeper anesthesia, longer duration of effect and longer recovery.
In addition to the injectable agent, the anesthetic plan usually contains sedative/tranquilizers (phenothiazines, alpha-2 adrenoceptor agonists), opioid analgesics and/or muscle relaxants (benzodiazepines). This will improve quality of anesthesia and reduce the dose of the injectable anesthetic needed to maintain an adequate depth of anesthesia. The use of a lower dose is thought to result in fewer adverse effects compared to the use of the injectable anesthetic alone. The choice of anesthetic must be based on the physical condition of the patient, the restrictions imposed by the adverse effects of each drug and pharmacokinetic characteristics of the anesthetic compound.
Table 1: Recommended anesthetic induction doses of injectable anesthetics
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Dog (mg/kg)
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Cat (mg/kg)
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Propofol
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2–8 IV
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2–10 IV
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Alfaxalone
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0.5–3.0 IV
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1–4 IV
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Etomidate
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0.5–1.5 IV
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0.5–1.5 IV
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Ketamine
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2–5 IV; 5–15 IM
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2–5 IV; 5–15 IM
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Propofol/Alfaxalone
Propofol and alfaxalone can be used for both induction and maintenance of anesthesia in dogs and cats. The main restriction for use of these agents is anesthesia in patients with hemodynamic instability. Premedication in dogs can be performed with an acepromazine/opioid or alpha-2 agonist/opioid combination. The later is more suitable for cats. The use of an alfaxalone-opiod combination administered subcutaneously has also been reported for sedation of cats.4 After induction, anesthesia can be maintained by intravenous constant rate infusion of either drug. The propofol dose for this purpose is 0.2–0.4 mg/kg/min in dogs and cats; for alfaxalone, the doses are 0.07–0.12 mg/kg/min for dogs and 0.18 mg/kg/min for cats.1 For maintenance of anesthesia for painful procedures, co-administration of a constant rate infusion of an opioid analgesic is recommended to improve antinociception.
Ketamine/Tiletamine-Zolazepam
Dissociative agents are the first choice of injectable anesthetics when chemical restraint of aggressive dogs and cats is required. These drugs can be administered intramuscularly which is desired in animals without a venous access. When ketamine is used, it is important to add a muscle relaxant to the anesthetic protocol as dissociative drugs may induce muscle rigidity. This is not a concern when tiletamine is used because it is commercially available as a 1:1 mixture with the benzodiazepine zolazepam. Dissociative agents should be avoided in patients with history of head trauma. The increase in heart rate and myocardial oxygen consumption may be of concern in patients with preexisting heart disease.
Ketamine-midazolam or ketamine-diazepam can be administered after premedication with an acepromazine-opioid combination to provide immobilization for diagnostic and minor, noninvasive procedures. For invasive procedures, better antinociception is achieved when ketamine is combined with an alpha-2 agonist such as xylazine, medetomidine or dexmedetomidine plus an opioid analgesic. In aggressive animals, all the drugs can be mixed in the same syringe and administered as a single injection (e.g., acepromazine-morphine-midazolam-ketamine or medetomidine-morphine-ketamine). The same approach can be used for tiletamine-zolazepam.
Tiletamine-zolazepam has also been used combined with ketamine and xylazine as an anesthesia cocktail named "TKX" for feral cats.5 In the author's institution, tiletamine-zolazepam powder (250 mg) is reconstituted with 200 mg of 10% ketamine, 50 mg of 10% xylazine and 2.5 ml sterile water (final concentrations: 50 mg/ml, 40 mg/ml and 10 mg/ml, respectively). This cocktail is administered for dogs and cats at doses of 0.02 ml/kg (moderate to intense sedation), 0.04 ml/kg (immobility for diagnostic or minor surgical procedures) or 0.06 ml/ kg (surgical anesthesia).
Etomidate
The main indication for etomidate is induction of anesthesia in patients with moderate to severe heart disease. In the author's institution, cardiac dogs usually receive an opioid agent (methadone, morphine) as premedication. Etomidate (1.0 mg/kg) is then mixed with fentanyl (5 µg/kg) and administered intravenously over 2–3 minutes, to effect. This anesthetic protocol provides good conditions for orotracheal intubation and immobility for approximately 10 minutes. Etomidate should not be used for maintenance of anesthesia for prolonged periods because it was found to induce adrenal suppression.1
Final Considerations
Currently, propofol, alfaxalone, etomidate, ketamine and tiletamine are the most frequently used injectable anesthetics in dogs and cats. These drugs are usually administered after premedication with sedative and analgesic drugs to induce unconsciousness/immobility for diagnostic or surgery procedures. Good understanding of the pharmacological properties of the anesthetics will allow the anesthetist to provide safe and effective anesthesia according to the needs of each patient.
References
1. Berry SH. Injectable anesthetics. In: Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA, eds. Veterinary Anesthesia and Analgesia. Ames, IA: Wiley Blackwell; 2015:277–296.
2. Rodríguez JM, Muñoz-Rascón P, Navarrete-Calvo R, Gómez-Villamandos RJ, Domínguez Pérez JM, et al. Comparison of the cardiopulmonary parameters after induction of anaesthesia with alphaxalone or etomidate in dogs. Vet Anaesth Analg. 2012;39(4):357–365.
3. Sams L, Braun C, Allman D, Hofmeister E. A comparison of the effects of propofol and etomidate on the induction of anesthesia and on cardiopulmonary parameters in dogs. Vet Anaesth Analg. 2008;35(6):488–494.
4. Ramoo S, Bradbury LA, Anderson GA, Abraham LA. Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol. Aust Vet J. 2013;91(4):131–136.
5. Cistola AM, Golder FJ, Centonze LA, McKay LW, Levy JK. Anesthetic and physiologic effects of tiletamine, zolazepam, ketamine, and xylazine combination (TKX) in feral cats undergoing surgical sterilization. J Feline Med Surg. 2004;6(5):297–303.