Anesthesia drugs for the small animal patient (Proceedings)

The development of a successful anesthesia plan is built on an understanding of several factors. The patient's physiological needs, the demands of the procedure that necessitates the anesthesia, the capabilities of the personnel involved in the procedure and the resources available to the anesthetist, all have a role. An important resource for the anesthetist is a good knowledge and understanding of the pharmacology of the anesthesia and adjunct drugs used to provide anesthesia care. Also important is an understanding of the principles and techniques of their administration.

There are a variety of drugs and techniques used for anesthesia management in modern veterinary medicine today. Unfortunately, no one anesthetic drug is appropriate for every patient, under all conditions. All anesthetic drugs have the potential for undesirable effects. The goal for the anesthetist is to understand which drugs positive effects outweigh the negative effects for a given condition of the patient. Which anesthetic drugs are most likely to provide the best support that will result in a successful anesthesia course and uneventful recovery?

Anticholinergics

The use of anticholinergics in an anesthetic plan is a safe and effective way to avoid the effects of parasympathetic reflexes. Although their use is controversial, they can be a very effective tool for the anesthetist. Anticholinergics are used to block vagal reflexes, preventing cardiac dysrythmias, decreasing secretions, and reducing the risks associated with gastric reflux during anesthesia. At higher doses they can cause tachycardia and increase myocardial oxygen consumption and decrease GI motility, or at low doses cause A-V Block. Most anesthetic drugs elicit a cholinergic response from the patient's autonomic nervous system; however the indiscriminate use of anticholinergics in every patient is not appropriate. These drugs are contraindicated in patients with pre-existing tachycardia as seen in thyrotoxicosis or fever.

Phenothiazines

Phenothiazines such as acepromazine are used to sedate patients for simple non painful procedures, relieve patient anxiety or as premedication for general anesthesia. They provide good sedation and reduce the amount of anesthetic agents needed to induce and maintain anesthesia. Acepromazine reduces the occurrence of catecholamine induced arrhythmias, causes vasodilation that can result in hypotension, and in some breeds such as the boxer has been associated with cardiovascular collapse. Acepromazine is not reversible and has long acting effects. These effects may be prolonged in patients with reduced liver function or when administered to patients at higher doses. Inhibition of platelet aggregation and mild respiratory depression has also been reported with the use of this drug.

Benzodiazepines

Benzodiazepines produce a calming or decreased anxiety effect, muscle relaxation, and provide excellent anticonvulsant effects. These drugs are frequently used as anticonvulsants for seizure control, as tranquilizers that provide muscle relaxation and sedation, and for behavior modification to controlling fear-induced behaviors. The effects of these drugs can be reversed with flumazenil. Benzodiazepines enhance the action of GABA (gamma-aminobutyric acid), the major inhibitory neurotransmitter in the brain. When benzodiazepines are used 1) as a preanesthetic agent or 2) with an opioid for neuroleptic sedation, or 3) with an anesthesia induction drug as an anesthesia co-induction agent; the quantity of other anesthetic drugs required to both induce and maintain adequate anesthesia is reduced. They have minimal cardiopulmonary effects; the analgesic effects from benzodiazepine drugs are minimal. The negative effects would include: excitement in cats and some dogs and prolonged effects in patients with liver disease. Diazepam is not water soluble which may result in unpredictable results due to unreliable absorption when administered IM or SQ. Administration of diazepam IM can cause pain and possibly the development of a sterile abscess at the injection site.

Analgesics

The assessment of pain represents one of the greatest challenges in veterinary medicine. Since our patients cannot verbally communicate their pain, we must rely on observations to evaluate the animal's comfort level. Various studies have been performed trying to establish a satisfactory objective scale to consistently assess pain in animals without success.

The management of pain has moved to the forefront in veterinary medicine. The focus is to prevent pain perception rather than to treat pain once the patient has become cognoscente of it. Pain can be much more difficult to control once the patient has become conscious of it. The use of analgesics is becoming more prevalent in the practice of veterinary medicine. Therapy plans have evolved over the past several years to include the use of local anesthetic drugs, opioids, alpha2-adrenergic agonists, NSAIDs, or combinations of these drugs to provide good analgesic levels and patient comfort.

Opioids-Agonists

These drugs have provided the most consistent and effective analgesia for many years and are arguably still the best drugs available for pain control in small animals. The use of opioid drugs in practice is sometimes deterred due to the fact that these drugs are controlled substances. Their use requires a DEA license and additional paperwork as well as security, due to their abuse potential. The extra work is well justified by the analgesic benefit to the patient. There are multiple types of opiate receptors in the CNS and they each have different roles to play in the activity of the nervous system. The two most important receptors with respect to pain are the mu and the kappa receptors. The drugs we use have different affinities for these receptors and this explains the differences in duration and efficacy between the available drugs. None of the opioids produce a loss of consciousness in veterinary patients, therefore opioids are not used solely to induce general anesthesia. They are used in conjunction with other drugs such as benzodiazepines and inhaled agents to produce general anesthesia. There is wide variation in the dosage of these drugs. Each patient's response to these drugs should be assessed and the dose adjusted according to the patient's response. Opioids effects are reversible with pure opioid antagonists such as naloxone. The beneficial effects of the opioids include 1) excellent analgesia with mild cardiopulmonary effects that are dose dependent, 2) reduce the quantity of other anesthetic drugs needed to produce general anesthesia, 3) dose dependent CNS depression. Sedation produced by these drugs can outlast the analgesic effects.

Opioids Agonist-Antagonist

These drugs in general act as an antagonist at the mu opioid receptor and act as an agonist at the kappa opioid receptors or provide a partial agonist response from the mu receptor. They may be used to reverse the effects of the pure mu agonists. These drugs are not as effective analgesics as the pure mu agonists, but are thought to cause less dysphoria and vomiting than mu agonists.

Neuroleptanalgesic Combinations

Tranquilizers (a phenothiazine, benzodiazepine or butyrophenone) can be combined with an opioid to provide both sedation and analgesia. The effect of these drug combinations tend to be synergistic, therefore lower doses of each drug are required to produce the desired effect. When these drug combinations are used in an anesthesia plan they provide preemptive analgesia and sedation to facilitate catheter placement and further reduce the quantity of other drugs needed to induce and maintain general anesthesia.

Alpha2 Adrenergic-Agonists

The alpha-adrenergic family of receptors is subclassified into alpha1 and alpha2. Alpha2 adrenergic receptors located within the CNS induce both sedation and analgesia not unlike that produced by opioid receptor activation. Alpha2 and opioid receptors are found in similar regions of the CNS, even on some of the same neurons. The functional CNS effects are quite similar between alpha2 and opioid receptors. The primary advantages of these drugs are that they provide analgesia and sedation while producing minimal respiratory depression and their effects are reversible with the use of alpha-adrenergic antagonists. Typical patient response to the IV administration of these drugs alone is CNS depression, analgesia, profound hemodynamic changes (increased blood pressure initially, due to vasoconstriction, followed by hypotension and bradycardia as sympathetic tone decreases and vagal tone increases), and respiratory rates may decrease (tidal volume increase). Perhaps the best advice with respect to these drugs would be to use as low a dose as possible and proceed cautiously with their administration. Great caution is advised if using alpha-adrenergic agonists in the compromised patient and they should not be used in patients with a reduced cardiopulmonary reserve.

Alpha2 Adrenergic Antagonists

A significant advance in veterinary medicine during the last decade has been the utilization of antagonists for the reversal of some injectable anesthetic regimes. The ability to reverse the effects of alpha2 adrenergic agonists has helped to promote their use in veterinary anesthesia. Yohimbine and Atipamezole may be used to reverse the effects of the alpha2 adrenergic agonists.

Induction Agents

Dissociatives

Dissociative anesthetic agents are drugs that interrupt the ascending transmission from the unconscious to conscious parts of the brain. Dissociative anesthesia is characterized by a cataleptic state in which the eyes remain open with a slow nystagmic gaze. Muscle hypertonus and movement often occur unrelated to surgical stimulation, for this reason dissociatives are often combined with other drugs. (ie: phenothiazines, benzodiazepines, alpha2 adrenergic agonists). Good analgesia is provided, however it is of short duration. Dissociative drugs that are commonly used are ketamine and tiletamine (Telazol is a combination of tiletamine and zolazepam). These drugs increase circulating catecholamines resulting in good cardiovascular support for patients that are not catecholamine depleted. Patients that are catecholamine depleted experience myocardial depression that may result in hypotension. Apneustic breathing patterns are seen with the use of the dissociative drugs. Intercranial pressure may also increase with the use of ketamine. Increases salivation and pain on IM injection is common.

Barbiturates

Barbiturates act directly on the CNS neurons in a manner similar to that of the inhibitory transmitter GABA. Barbiturate anesthesia is thought to be produced by a combination of enhanced inhibition and diminished excitation. These drugs can be used to induce sedation and hypnosis, as anticonvulsants, and as anesthetics. Today in veterinary practices barbiturates are used as anesthetic induction agents and anticonvulsants. Thiopental is the most commonly used drug of this group. Thiopental is an ultra-short acting barbiturate whose short duration of action relies on redistribution. Repeat boluses can lead to an accumulation of the drug and may result in a prolonged recovery. Transient respiratory depression/apnea is experienced with thiopental. This drug can sensitize the heart to catecholamine induced arrhythmias but is not associated with excessive myocardial depression.

Non-Barbiturates

Over time barbiturates have been the most common drugs used to produce short duration anesthesia, many other drugs can be used to produce unconsciousness. Newer drugs are finding their way into clinical use in veterinary medicine. These drugs are rapid acting, quickly redistributed and metabolized, and can be titrated to produce from sedation to general anesthesia. They do not provide analgesia.

Propofol is a highly lipid-soluble alkylphenol rapid acting intravenous anesthetic agent. Propofol is formulated in a 1% emulsion that contains egg lecithin, glycerol and soybean oil. This solution contains no preservatives and is a perfect growth medium for bacteria; therefore ascetic handling and shelf life of open containers is critical to patient safety. This drug has an onset similar to thiopental. Inductions are usually smooth, rapid and excitement free. Varying dose dependent levels of sedation, hypnosis and general anesthesia can be achieved with propofol. This drug has no analgesic properties, so it should be used in conjunction with analgesics for painful procedures. Propofol is rapidly metabolized and redistributed. This drug does not exhibit cumulative effects; therefore repeated boluses or constant rate infusions (CRI) may be used for longer procedures without prolonged recovery. The exception to this would be in cats where CRIs at higher doses for longer periods have been reported to produce prolonged recoveries. Patients can experience pain on injection, myoclonus, muscle tremors, and movement during anesthesia with propofol. Patients receiving this drug can experience hypotension due to myocardial depression and vasodilation as well as hypoventilation due to apnea. There is a common misconception that because propofol is a short acting anesthetic agent which is rapidly metabolized; it is a safe anesthetic agent. However it should be noted that if administered at too high a dose or bloused too quickly it can cause significant cardiopulmonary depression. Like with any other anesthetic drug the patient's physical status must be considered in calculating the dose and the drug must be cautiously titrated to effect. Heinz body anemia has been reported with frequent use in cats.

Etomidate is a sedative hypnotic with a rapid onset of action and rapid recovery. Etomidate produces minimal cardiopulmonary depressant effects which makes it a very good choice for patients with cardiovascular disease.The solution is a propylene glycol solution that is very hyperosmotic. This drug should either be diluted in saline at a ratio of at least 1:3 prior to IV administration or it can be administered via a distal injection port of a fluid administration set connected to an IV catheter. By diluting it or allowing it to mix with IV fluids prior to reaching the patient's blood you can reduce the solution's osmolality and avoid hemolysis. Etomidate can produce pain on injection, excitement during induction and recovery, retching, myoclonus and apnea. The use of premedication drugs and a benzodiazepine as a co-induction agent will help reduce the unpleasant side effects experienced by the patient. In man, long term uses of etomidate is associated with adrenal cortical suppression; typically this is not a concern for short term uses in veterinary patients.Despite the negative effects, etomidate is often the induction drug of choice for patients with cardiovascular disease.

Inhalation Agents

Inhalation anesthetic agents are widely used in veterinary medicine today. Volatile anesthetic agents are delivered, and for the most part removed from the body by the lungs. The use of these agents requires an anesthesia machine that provides oxygen, a breathing circuit, and a facemask or endotracheal tube, as well as a way to remove accumulations of carbon dioxide. These components reduce the risk of morbidity or mortality to the patient by facilitating ventilation and increasing oxygenation. Anesthesia induction with an inhaled agent is no safer to the patient than induction with injectable anesthetic agents. It is more that the patient is better supported with oxygen. The use of an inhaled anesthetic agent to maintain anesthesia for a prolonged period of time is a safe and practical method. The main advantage to an inhalation agent induction is the recovery will be rapid, depending on the amount of time the patient is asleep. Less drug metabolism by the liver is required when compared to injectable drugs. The two more common inhalation agents used in veterinary medicine today are halothane and isoflurane, newer agents are on the horizon such as sevoflurane and desflurane. Sevoflurane is experiencing a current rise in popularity due to increased marketing.

Local Anesthetics

A local anesthetic can provide total analgesia to the affected area. They have been applied topically to wounds or by local infiltration to a region of the body (ie: intercostal block or epidural injection) or they have been instilled into a body cavity to provide relief (intrapleural or intraperitoneal infusions). Local anesthetic agents can reduce the quantity of other analgesics needed to provide adequate pain relief.

NSAIDS

Pain management has become a major focus in veterinary medicine, especially in the arena of anesthesia. It has become well established that attacking pain by more than one avenue using a multi modal approach is an effective pain management strategy. The use of NSAIDs has recently been touted as "the most widely used analgesics in veterinary medicine" Historically anesthesiologists have been leery to administer these drugs until the anesthesia period is over and the patient is in recovery. NSAIDs are associated with adverse effects on the GI, renal and hepatic systems as well as coagulation disorders. With the arrival of newer NSAIDs such as carprofen, deracoxib and meloxicam; NSAIDs are finding their way into the anesthetist's toolbox as another resource for pain management. Even with the newer drugs caution must still be advised. The patient's physical status, co-existing diseases, current medications and its physiological homeostasis during the anesthesia period must all be considered when choosing the best pain management. Is the use of an NSAID drug in this individual patient's best interest? If so, then which one and at what dose?

Summary

Analgesia, immobilization, amnesia, muscle relaxation and physiological homeostasis are the desired end-points for an anesthesia drug plan. Often the choice of drugs may be limited and your selection may not include the "optimal" drug of choice for a particular patient or situation. Your knowledge and experience with the drugs available to you is a cornerstone in the anesthesia drug plan. What are the advantages to these drugs? What are the disadvantages of these drugs? What are the needs of the patient and which drugs will best support this patient? Thinking your way through these questions as you develop an effective plan will require knowledge, understanding and experience with the drugs available at your facility. The advantage to a well-designed plan comes from the forethought used to generate the plan and anticipate complications. Know what you have to work with, know what the patient needs, anticipate problems and plan a response. Optimize your knowledge, skills and abilities to provide high quality anesthesia care and support for the patient.