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Chapter 3 T&L Chapter 3 Anesthetic Agents and Adjuncts 1 Chapter 3 Anesthetic Agents and Adjuncts Propofol, etomidate, and alfaxalone are used only in small animals, small ruminants, and neonates of any species, but not in adult large animals because of the high expense of these agents. The ultra-short injectable barbiturate anesthetics are no longer used in general practice in the US due to recent changes in anesthetic practice and limited availability. 2 Chapter 3 Anesthetic Agents and Adjuncts Since its introduction to the veterinary market almost two decades ago, its popularity has gradually increased, and now it is the most commonly used ultra– short-acting injectable agent in small animals for brief procedures or for anesthetic induction before intubation and maintenance with inhalant agents. 3 Chapter 3 Anesthetic Agents and Adjuncts The propofol macroemulsion contains propofol at a concentration of 10 mg/mL as well as egg lecithin, glycerin, and soybean oil. It has a milky appearance but is given by the IV route and consequently is the sole exception to the general rule that milky liquids should never be given intravenously. Although the mode of action is not completely understood, propofol appears to affect GABA receptors in a similar manner to other hypnotics. Propofol has a rapid onset and short duration of action because it is highly fat-soluble. Propofol is rapidly taken up by vessel-rich tissues such as the brain, heart, liver, and kidneys but is very quickly redistributed to muscle and fat and is subsequently rapidly metabolized. This accounts for the rapid recovery and minimal residual sedative effects seen even after repeated injections. The onset of action is about 30 to 60 seconds, and the duration of action is 2 to 5 minutes after a single bolus, with complete recovery in 20 minutes (dogs) and 30 minutes (cats). 4 Chapter 3 Anesthetic Agents and Adjuncts 95% to 99% of propofol travels in the blood bound to plasma proteins and 1% to 5% freely circulates. Only the free (unbound) molecules of propofol are able to enter the brain to induce anesthesia because the molecules bound to proteins are unable to cross cell membranes. In hypoproteinemic animals (that is, those with total plasma protein less than 3 g/dL) there is less plasma protein to bind propofol molecules and more propofol in the active, unbound form. The tendency of a drug to dissolve in fats, oils, or lipids is referred to as lipid solubility (also called partition coefficient) and is related to the ability to penetrate the fatty layer of the cell membranes. Propofol is highly lipid-soluble and therefore passes into the brain cells quickly, causing a faster onset of action as compared with other drugs with low lipid solubility. 5 Chapter 3 Anesthetic Agents and Adjuncts Tissue redistribution is a phenomenon that occurs because of the way in which this drug is distributed to various tissues based on blood flow. After IV administration, absorption is most rapid in tissues with very high blood flow, known as the vessel-rich group (the CNS, heart, liver, kidney, and endocrine tissues), which make up only about 10% of total body weight but receive about 75% of the total blood flow. Absorption is less rapid in muscle, which makes up about 50% of the body weight but receives only 20% of the blood flow, and slowest in fat, which makes up about 20% of body weight but receives a meager 5% of the blood flow. Propofol is highly lipid-soluble, and its entry into brain tissue is enhanced by the high lipid content of the brain. The rapid absorption of propofol into the brain causes the animal to lose consciousness within 30 to 60 seconds of injection. 6 Chapter 3 Anesthetic Agents and Adjuncts 7 Chapter 3 Anesthetic Agents and Adjuncts 8 Chapter 3 Anesthetic Agents and Adjuncts TECHNICIAN NOTE Major effects and adverse effects of propofol are as follows: • CNS depression ranging from sedation to general anesthesia • Transient excitement, muscle tremors, and seizure-like activity during induction • Bradycardia, decreased cardiac output, and hypotension that can be significant and prolonged in some patients • Respiratory depression including apnea especially after rapid injection or high doses • Prolonged apnea, decreased oxygen saturation, and cyanosis • Muscle twitching during induction • Muscle relaxation • Antiemetic effect • Decreased intracranial and intraocular pressure • Pain on IV injection 9 Chapter 3 Anesthetic Agents and Adjuncts 10 Chapter 3 Anesthetic Agents and Adjuncts A longer recovery time is needed if multiple injections were used. In dogs, recovery from propofol anesthesia is rapid and smooth, even after multiple injections. Because of the rapid recovery seen with this agent, it is useful for patients that need to be released immediately after surgery. Dogs that have received propofol may appear completely recovered within 20 minutes of the final dose. Cats recover within about 30 minutes after a single injection but may experience longer recoveries after multiple injections owing to the fact that they metabolize propofol more slowly. Chapter 3 Anesthetic Agents and Adjuncts TECHNICIAN NOTE Propofol should be handled in a strictly aseptic manner. The manufacturer recommends that unused propofol macroemulsion that contains no preservative should be discarded within 6 hours of opening to avoid contamination. Unused portions of PropoFlo™28 and propofol microemulsions can be stored at room temperature for up to 28 days after opening. 12 Chapter 3 Anesthetic Agents and Adjuncts 13 Chapter 3 Anesthetic Agents and Adjuncts This agent was originally marketed in the 1970s, but was ultimately taken off the market in most countries due to adverse effects caused by the solubilizing agent in the formulation. The currently available formulation contains a different solubilizing agent that does not cause these undesirable effects. 14 Chapter 3 Anesthetic Agents and Adjuncts 15 Chapter 3 Anesthetic Agents and Adjuncts Major effects and adverse effects of alfaxalone are as follows: • CNS depression ranging from sedation to general anesthesia • Minimal cardiovascular depression • Tachycardia • Hypotension especially when used with inhalant anesthetics • Respiratory depression including apnea especially after rapid injection or high doses • Muscle relaxation • Excitement during recovery may occur 16 Chapter 3 Anesthetic Agents and Adjuncts 17 Chapter 3 Anesthetic Agents and Adjuncts TECHNICIAN NOTE Uses for barbiturates are as follows: The ultra–short-acting barbiturates thiopental sodium and methohexital were used for many years to induce anesthesia primarily in dogs, cats, and horses, although in recent years, these agents have been unavailable or difficult to obtain. The short-acting barbiturate pentobarbital is used to induce and maintain general anesthesia in laboratory animals and to treat status epilepticus in small animals. The long-acting barbiturate phenobarbital is used as a sedative and anticonvulsant. 18 Chapter 3 Anesthetic Agents and Adjuncts Phencyclidine has a high potential for abuse so it not used in veterinary medicine. Ketamine may be given orally to restrain feral cats. Ketamine is a controlled substance. Chapter 3 Anesthetic Agents and Adjuncts 20 Chapter 3 Anesthetic Agents and Adjuncts 21 Chapter 3 Anesthetic Agents and Adjuncts The unusual combination of actions result in a distinctive trancelike state termed dissociative anesthesia (so called because it dissociates various regions of the brain), in which the animal appears awake but immobile and unaware of its surroundings (Figure 3-7). Dissociative anesthesia is described in the section on effects on the central nervous system. The effects of dissociative agents on the cardiovascular and pulmonary systems are also unique and different than effects produced by most other anesthetic agents. 22 Chapter 3 Anesthetic Agents and Adjuncts 23 Chapter 3 Anesthetic Agents and Adjuncts TECHNICIAN NOTE Major effects and adverse effects of dissociatives are as follows: Cataleptoid state Intact reflexes Eyes open, pupils central and dilated Normal or increased muscle tone Analgesia (primarily somatic) Sensitivity to sound, light, or other sensory stimuli, seizure-like activity, or bizarre behavior especially during recovery Nystagmus Increased heart rate, cardiac output, and mean arterial pressure (MAP) secondary to SNS stimulation Decreased inotropy Apneustic respiration at higher doses Increased salivary and respiratory tract secretions Pain after IM injection 24 Chapter 3 Anesthetic Agents and Adjuncts 25 Chapter 3 Anesthetic Agents and Adjuncts 26 Chapter 3 Anesthetic Agents and Adjuncts • Dissociative anesthetics do not affect the respiratory system in the same way as most other anesthetics. Respiratory rate and tidal volume may change, but respiratory depression is usually insignificant at usual doses. At higher doses, animals exhibit apneustic respiration, a breathing pattern in which there is a pause for several seconds at the end of the inspiratory phase, followed by a short, quick expiratory phase. These animals appear to hold their breath. • Although not usually a problem at conventional doses, overdoses may cause severe respiratory depression or respiratory arrest. • Dissociatives also significantly increase salivation and respiratory tract secretions. Care must be taken to ensure that the airway is protected to prevent aspiration. Anticholinergics can be used to control these signs but may further predispose the patient to cardiac arrhythmias. 27 Chapter 3 Anesthetic Agents and Adjuncts 28 Chapter
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