Anesthetic drugs: a review for technicians (Proceedings)

Sedation and anesthesia is something that most of us administer and/or perform in practice on a daily basis. While we as technicians may not make the final decision on what drugs will be administered, we should be educated about the various drugs available and how each of them works alone and in combination with each other.

Goals of premedicaiton and sedation: why are premedications so important?

Providing patients with a premedication can make catheter placement and anesthetic induction less stressful for both the technician and the patient. Premedicating the patient can also help facilitate handling and restraint which in turn increases safety. Lastly, many premedications not only provide analgesia, but they also contribute to a multi-modal "balanced" technique which reduces the overall amount of drugs needed for anesthetic induction and maintenance.

Ideal properties of premedication and sedation drugs should include the following:

     • Produce reliable sedation and anxiolysis

     • Have minimal effects on the cardiovascular system

     • Have minimal effects on the liver and kidneys

     • Cause minimal respiratory depression

     • Produce analgesia

     • Have the ability to reverse the drug

Unfortunately there is not one single drug that possesses all of these characteristics, therefore we must carefully choose a combination of drugs to obtain the desired effects. When appropriate combinations of drugs are used in conjunction with each other, it often allows for overall lower doses to be administered. Many drug combinations work synergistically with each other. Common drug combinations include alpha2-agonists given with opioids and phenothiazines such as acepromazine given with opioids (neuroletanalgesia). Opioids with midazolam and/or acepromazine is also another common combination.

Common routes of administration include intravenous, intramuscular, subcutaneous, or oral. The route of administration can greatly affect the time to peak effect and the bioavailability of the drug. This will vary by drug therefore a formulary should be consulted prior to administration.

Common drugs used for sedation and/or analgesia

Phenothiazines

Acepromazine is the most commonly used phenothiazine used in veterinary medicine. Phenothiazines are not controlled, do not cause significant respiratory or cardiac depression and have a wide margin of safety in healthy patients when given at appropriate doses. Acepromazine can cause profound sedation that at higher doses can last up to 24 hours. It also has an antiemetic effect and may prevent animals from vomiting when given several minutes prior to opioid administration. Phenothiazines can prevent histamine release and therefore help reduce allergic reactions. The downside of phenothiazines include peripheral vasodilation which can lead to heat loss and hypotension, the inability to reverse the drug, and lack of analgesia.

Alpha2-agonists

Dexmedetomidine is the most commonly used alpha2-agonist used in small animal medicine. Alpha2-agonsits are not controlled, provide some analgesia, and are reversible. Alpha2-agonists are potent sedatives that can be used alone or in combination with other drugs such as opioids or tranquilizers. When these drugs are used in combination with opioids or tranquillizers, they have a synergistic or additive effect. Dexmedetomidine works great when given at micro doses intravenously for patients having a rough recovery from anesthesia.

Alpha2-agonits can have significant cardiovascular side effects. These drugs should only be given to healthy patients and are generally avoided in geriatric, diabetic, pregnant, pediatric, or sick animals. Common adverse effects include profound hypertension, bradycardia and reduced cardiac output. Administration of an anticholinergic to treat bradycardia is contraindicated. Administration of an anticholinergic is not always effective and can actually increase the workload and exacerbate hypertension. It is often better to reverse the drug rather than treat the bradycardia. Dexmedetomidine is usually reversed with atipamezole.

Benzodiazepines

Diazepam and midazolam and the two most commonly used benzodiazepines in veterinary medicine today. Benzodiazepines cause skeletal muscle relaxation, have anticonvulsant properties, are very safe to use on sick and geriatric patients, and have an antianxiety or calming effect on most patients. Benzodiazepines are best used in combination (working synergistically) with other drugs such as ketamine and opioids. Benzodiazepines can be used as both pre-medications and induction agents, but they are not often effective when used alone or in young, healthy animals. In rare cases, excitation can be caused rather than tranquilization. Benzodiazepines can be reversed with flumazenil.

Due to the solubility of diazepam, it should only be given IV. The uptake of diazepam is variable when given IM or SQ. Midazolam is safe and effective when given IV, IM, or SQ.

     • Opioids are commonly used as part of a balanced pre-medication regime. Different intensities of analgesia are obtained based on the type of opioid chosen. There are few negative effects associated with administration of opioids and they are safe to use in pediatric, geriatric, and sick patients. Respiratory depression can occur, but is generally only seen when higher doses of opioids are administered.

     • Full mu opioids include hydromorphone, morphine, oxymorphone, fentanyl, and methadone. These drugs should be used for moderate to severe pain. Full mu opioids are generally dosed every four hours as needed for pain control.

     • Buprenorphine is a partial agonist opioid and should only be used for mild to moderate pain control. Buprenorphine is long lasting and is generally dosed every 6 to 8 hours as needed for pain control.

     • Butorphanol is agonist/antagonist opioid that is best used for sedation or mildly painful procedures. It is very short acting.

     • Opioids are reversed with the antagonist naloxone. Naloxone works best of full mu opioids.

Cyclohexamines

Ketamine can be used as both a pre-medication and induction agent (often used in combination with a benzodiazepine). It is one of the most commonly used anesthetic drugs in veterinary medicine. Ketamine produces a trancelike anesthesia often termed dissociative anesthesia or catalepsy. Common responses after administration include strong palpebral reflexes, increased muscle and jaw tone, central eye position, and an apneustic breathing pattern (patient holding breath for several seconds between a short and quick breath). Unlike most anesthetic drugs, ketamine does not decrease heart rate or depress myocardial function. Most animals will exhibit tachycardia and vasoconstriction which increases blood pressure. Ketamine should be used with caution in patients with cardiac arrhythmias or some preexisting cardiac disease (hyperthyroidism or cardiomyopathy).

Ketamine provides good analgesia for skin and limb pain, but is a poor analgesic for visceral pain. Ketamine may increase CSF pressure and is often contraindicated in patients with brain trauma, intracranial tumors, or inflammatory disease of the CNS. Ketamine can also increase intraocular pressure and is contraindicated with some ocular procedures or patients with glaucoma.

Telazol is another cyclohexamine that combines tiletamine with zolazepam (benzodiazepine). Telzol can be used as part of a pre-medication regime or as an induction agent. It is a very helpful drug to use on aggressive, hard to handle patients. In some cases, patients will be sedated enough to intubate after pre-medication with telazol and an opioid. This drug can be given IV, IM, or SQ.

Anticholinergics (parasympatholytics)

Atropine and glycopyrrolate are commonly used in veterinary practice to treat (or pre-treat) bradycardia in anesthetized patients. It is a controversial subject to give or not give an anticholinergic as part of a pre-medication combination. Some anesthesiologists feel you should pre-treat the potential bradycardia that may occur when administering opioids and others feel you should only treat if necessary. We currently administer an anticholinergic anytime an opioid is given as a premedication. Atropine has a quicker onset compared to glycopyrrolate and is shorter acting. Glycopyrrolate has a slower onset and is longer lasting. Both drugs can be given IV, IM, or SQ. IV drugs are quicker acting and generally require a lower dose compared to the IM and/or SQ routes. It is important to note that anticholinergics may not work well if the patient is hypothermic.

Common induction drugs

Common induction drugs used in veterinary medicine include propofol used with or without a benzodiazepine, ketamine + a benzodiazepine, etomidate + a benzodiazepine, full mu opioids + a benzodiazepine. At this time thiopental is no longer on the market and will not be discussed in this lecture.

Propofol is a hypnotic phenol which is an oil at room temperature and is highly lipid soluble. Propofol is a popular intravenous induction agent that can be used alone or in conjunction with a benzodiazepine. Use with a benzodiazepine significantly reduces the overall induction dose needed to achieve anesthetic induction. If propofol is going to be used alone, it should be given in ¼ dose increments over about 2 minutes. If it is used with a benzodiazepine, the propofol should be injected first with a ¼ dose given over about 30 seconds. Half the benzodiazepine dose is then administered. If additional propofol and benzodiazepine are necessary, the steps are repeated. The entire calculated dose of propofol is rarely needed when given at the correct speed. It is important to remember that propofol can cause profound periods of apnea and hypotension so it is essential to give is slow and preoxygenate.

Propofol has a rapid onset and a short duration of action (about 10 minutes) when given as a single dose. In canine patients, repeated doses of propofol or CRIs are well tolerated and do not affect the overall recovery. Feline patients are different in that repeated doses or CRIs can contribute to a prolonged recovery.

Propofol is a poor analgesic, therefore analgesic drugs need to be administered if a painful procedure is being performed.

Etomidate is an imidazole drug used for induction of anesthesia in small animals. Etomidate is short acting and produces minimal cardiovascular changes (heart rate, rhythm, cardiac output, and blood pressure). It is therefore a good drug for patients that have cardiovascular compromise. Etomidate is a poor analgesic, therefore analgesic drugs need to be administered if a painful procedure is being performed. It is advised to give etomidate with a benzodiazepine. Etomidate is administerd in a similar manner to propofol. Etomidate should not be used without administering premedications due to the high incidence of myoclonus and pain on injection.

Etomidate can cause depression of adrenal cortical function and should not be given to animals with Addison's Disease.

Ketamine used in conjunction with a benzodiazepine is one of the most common induction agents used in practice today. See ketamine section above for more information.

Opioid inductions are generally used in debilitated patients including those with cardiac compromise. Fentanyl is commonly used as an induction agent, but other opioids such as hydromorphone or oxymorphone can be use as well. A benzodiazepine should be used in conjunction with an IV opioid and the combination is administered in the same manner as propofol. The immediate area should be kept quiet during an opioid induction because patients are not usually fully anesthetized and can be difficult to intubate even when the full calculated dose is administered.

Maintenance anesthesia

Most general anesthesia is maintained via an inhalant such as isoflurane or sevoflurane in oxygen. Isoflurane and sevoflurane are potent vasodilators and can have a dose dependant effect on hypotension. These modern inhalants act rapidly, produce less cardiac sensitivity to catecholamines, and are only minimally metabolized by the liver. Changes in anesthetic depth can be changed rapidly. Minimum alveolar concentration (MAC) is the concentration in the alveoli required to prevent 50% of a group of animals from responding to a painful stimulus. The MAC for isoflurane and sevoflurane for dogs and cats are 1.28/1.63% and 2.35/2.58% respectively. Many factors affect MAC and should be taken into consideration when anesthetizing a patient. These factors include patient status, pregnancy, age, hypothermia, anemia, and pre-anesthetic drugs.

Isoflurane and sevoflurane do not provide analgesia therefore an analgesic drug must be used if performing a painful procedure.

**Mask or chamber inducing a patient should only be done under specific circumstances such as dealing with a fractious cat or when you are unable to place an IV catheter or gain venous access.

Nitrous Oxide is a gas inhalant which can be used in conjunction with other gas inhalants such as isoflurane or sevoflurane. The use of nitrous oxide provides analgesia, but it cannot be used to induce animals because the MAC is close to 200% or higher depending on species. Nitrous oxide is a great adjunct anesthetic because it reduces MAC of other inhalants by 20 to 30%. Nitrous oxide has little effect on the cardiovascular, respiratory, hepatic, or urinary systems and when used correctly, has a wide margin of safety. Using nitrous oxide reduces the amount of oxygen available to the patient. It is therefore important to use an oxygen monitor. Nitrous oxide is usually delivered at a percentage of 60% to 66% with the remaining percentage of gas being oxygen (up to 100%). Oxygen should generally not drop below 33%. Nitrous oxide should be discontinued at least 5 minutes prior to turning off isoflurane or sevoflurane and a high fresh oxygen gas flow should be administered.

Constant rate infusions

CRIs are commonly used as an adjunct to general anesthesia. Common analgesic CRIs include ketamine, lidocaine, fentanyl, dexmedetomidine, and MLK (morphine, lidocaine, and ketamine together). Using an analgesic CRI provides a balanced or "multi-modal" approach to maintaining anesthesia. The use of these drugs often reduces MAC and provides an additional source of pain management.

Propofol can be used for total intravenous anesthesia (TIVA). Even though gas inhalants are not used for TIVA, you should still intubate, provide oxygen, and if needed intermittent positive pressure ventilation (IPPV). Propofol CRIs are useful for surgeries or procedures involving the trachea. They are also useful for patients with increased intracranial pressure concerns undergoing diagnostic procedures such as a brain MRI or a craniotomy.

Post-operative medications

Post-operative medications should be given when a painful procedure was performed. Common post-operative drugs include full mu opioids, buprenorphine, butorphanol, and NSAIDS. NSAIDS used in conjunction with opioid administration help provide multi-modal analgesia and should be used in healthy patients (no evidence of kidney or liver disease) not concurrently receiving steroids.