Case by case: Creating the right drug protocols for your canine and feline patients (Proceedings)

Anesthetic patients should be evaluated on a case-by-case basis and an anesthetic protocol created for the individual situation. That being said, it can be overwhelming and intimidating to pick the right drug combination from the multitude of available options. This lecture will briefly review available drug choices and considerations for premedication and induction as well as intra- and post-procedural analgesia and sedation. Several case studies (both routine and emergency) will be provided for interactive discussion.

The reasons to premedicate are many. Premedication allows for less stressful and safer restraint and catheter placement (for patient and technician), it provides for analgesia during a procedure and by and large decreases the amount of drug needed overall. No one drug possesses every desired quality-good sedation, good analgesia, reversibility, minimal side effects-so it is necessary to choose a combination of drugs to decrease negative effects and lower the total amount of drug needed.  An anesthetic protocol should include a drug for sedation and one for analgesia. The specific drugs and amounts used will depend on several factors. The anesthetist creating the plan will have to evaluate the temperament of the patient, the type of procedure being performed, and the co-existing conditions or contraindications each patient may have.

Sedatives

Generally the available sedatives are benzodiazepines (diazepam, midazolam), phenothiazines (acepromazine), and alpha-2 adrenergic agonists (dexmedetomidine).

Benzodiazepines offer sedation but no analgesia.  The sedative qualities are appropriate for patients with calm (or depressed)  personalities. They have minimal negative effect on cardiovascular or respiratory systems and are the sedative of choice for compromised patients. Benzodiazepines have many positive qualities; they provide muscle relaxation, have anxiolytic properties, and are commonly used for seizure patients. Benzodiazepines do not work well alone or on excited patients and may even have an opposite excitatory effect, counter to the desired sedation. As with all sedatives, it is best to combine this type of drug with an analgesic opioid for maximum effectiveness.  Midazolam is a water soluble benzodiazepine and is safe to administer intravenous (IV), intramuscular (IM), or subcutaneous (SC). Diazepam is lipid soluble and should only be given IV; when given IM or SC routes, diazepam injections are painful and absorption is extremely erratic.  Flumazenil is the reversal for benzodiazepines.

Phenothiazines provide good sedation (but again, no analgesia) for patients and are often the best option for aggressive, hyperactive, or extremely anxious animals. Acepromazine is the most commonly available phenothiazine. There are many pros to phenothiazine sedatives, they are good anti-emetics, a benefit when combining with an emetic like opioids, prevent histamine release, and have little effect on the respiratory system. There are a number of cons though, including decreasing the seizure threshold, peripheral vasodilation and resultant hypotension, hypothermia, and inhibition of platelet aggregation.  There is evidence that phenothiazines can cause splenic enlargement. This can cause difficultly for surgeons working in the abdominal cavity.  Unfortunately, phenothiazines are not reversible. Acepromazine can be given IV, IM, or SC.

Alpha-2 adrenergic agonists provide excellent sedation for most patients and provide very minor analgesia (though not enough for any surgical purpose).  Dexmedetomidine is the most commonly used alpha-2. This class of drug can cause respiratory depression, but it varies greatly from patient to patient. This class of drug can cause dark mucous membrane color that is unrelated to oxygenation of tissue. It can cause profound bradycardia and vasoconstriction. It is not advisable to treat the bradycardia with anticholinergics as it increases the workload of the heart. It is best to reverse the drug first, then deal with bradycardia if it continues. This class of drug is only an appropriate choice for relatively healthy patients and cannot be used on any patient with cardiac compromise. Alpha-2s cause vomiting in most cats and many dogs, though this is much less when given intravenously.   Alpha-2 adrenergic agonists are reversible with atipamezole. Dexmedetomidine can be given IV, IM, or SC (the dose is dramatically lower when given IV).

Analgesics

Part two of the premedication composition is an appropriate opioid analgesic. There are a plethora of available choices for any given situation. Opioids fall into three groups: agonist-antagonist, partial agonist, and agonist.

Butorphanol is an agonist-antagonist that provides very minor analgesia and is short acting (30-60 minutes). This drug is best used for minimally painful procedures such as endoscopy, minor biopsies, imaging, or straight-forward dental cleanings. Buprenorphine is a partial agonist. It provides mild to moderate analgesia, lasting about 6-8 hours. It works very well in cats, but not well at all in dogs. Both butorphanol and buprenorphine produce minimal respiratory or cardiovascular depression and usually do not cause vomiting. They both can be reversed with naloxone, however, they bind very tightly to the receptor and can be difficult to reverse. Both drugs also occupy the same receptors used by opioid agonists and thus block the effect if another opioid is given before the butorphanol or buprenorphine have worn off.

Opioid agonists such morphine, hydromorphone, oxymorphone, and fentanyl are the best choices for painful or invasive procedures. With the exception of fentanyl, which only lasts 20-30 minutes, opioid agonists last 3-4 hours. Full mu agonists, when given IM, will cause vomiting and pytalism. All opioids can be given IV, IM, or SC, however, morphine must be given slowly IV as it can cause histamine release and should be avoided in patients with known mast cell tumors or history of allergic reactions. Fentanyl should be given IV as a constant rate infusion (CRI) due to its short duration of action.

Opioid agonists can cause depression of the cardiovascular and respiratory systems leading to hypoventilation and hypotension. Negative side effects tend to be greater with higher doses. These drugs allow for sedation and excellent analgesia. All can be given intra-operatively as constant rate infusions. Full reversal (remember, this is reversal of everything, including analgesia) can be achieved quickly with naloxone. If it is desired to only partial reverse the opioid agonist (if a patient is dysphoric or very slow to rouse), butorphanol can be used. This allows for a small amount of analgesia to be maintained.

Anticholinergics

To give or not to give? That is the question. There is much debate on whether or not to include anticholinergics (atropine and glycopyrrolate typically) in a premedication combination. On one side of the argument are those who opt to include anticholinergics with the thought that it is best to treat opioid-induced bradycardia before it occurs. On the other side of the table are those who believe you should treat the problem only if it actually does occur. Atropine has a rapid onset, but is short acting, where glycopyrrolate is the opposite (long onset, long duration). Both drugs can be given IV, IM, or SC.

Induction agents

There are typically three choices for anesthetic inductions: propofol, ketamine/diazepam, and etomidate. Propofol is a sedative-hypnotic that is relatively safe for use in most patients. It does cause transient apnea and a dose-dependent cardiovascular depression. In cats it is known to cause Heinz body formation following repeated administration. Propofol can be used alone, or in combination with a benzodiazepine such as diazepam or midazolam. Propofol has on onset of about 30-60 seconds and lasts about 10-15 minutes. Combining propofol with a benzodiazepine allows for a reduction in the amount of propofol needed, thus lessening some of the negative side effects. It is always a good idea to pre-oxygenate (if possible) when giving propofol as an induction agent.

Ketamine/diazepam is readily available and inexpensive. It is safe for use in most patients. Ketamine can be used as a premedicant, intra-operative analgesic and an induction agent.  Ketamine is a dissociative agent and causes a trance-like state. Patients induced with ketamine and a benzodiazepine maintain jaw tone and palpebral reflexes. Most patients maintain normal to increased heart rate and blood pressure due to the increase in cardiac contractility caused by the ketamine.  Ketamine/benzodiazepine inductions should be avoided in patients with hypertrophic cardiomyopathy or pre-existing tachycardia. Ketamine provides excellent somatic analgesia. It can increase intracranial pressure and should be avoided in neurologic patients. Ketamine can also cause an increase in intraocular pressure and should be used with caution in ophthalamic cases.

Etomidate is an imidazole derivative that has minimal cardiovascular or respiratory effect. It is expensive and tends to be used for extremely critical patients. Etomidate can cause suppression of adrenal functioning and should be avoided in patients with adrenal disease/dysfunction. It can also cause acute hemolysis. Etomidate is given much like propofol-pre-oxygenate, slow, steady administration-but should NEVER be given without appropriate premedication. It often causes nausea, retching and vomiting at induction. This side effect can be avoided if the patient is appropriately sedated and if an adequate amount of the drug is used.

Constant rate infusions (CRIs)

CRIs are used regularly as a complimentary analgesic. They help maintain adequate anesthetic depth and allow inhalant levels to be kept low. Most analgesic agents can be run as a CRI--ketamine, lidocaine, fentanyl, hydromorphine, butorphanol, morphine, and dexmedetomidine. Many work best when in combinations such as MLK (morphine, lidocaine, ketamine), FLK (fentanyl, lidocaine, ketamine) or HLK (hydromorphone, lidocaine, ketamine). CRIs are beneficial in that they allow for a steady plane of analgesia without the side effects usually associated with bolus dosing. Less of the drug is given overall, thus making this approach more cost effective as well.

One additional drug that should be mentioned as a CRI is propofol. It does not provide any analgesia, but can be used as a form of total intravenous anesthesia (TIVA). This type of general anesthesia is useful in cases where it is not possible to intubate a patient, such as tracheal surgeries. It is also relevant for patients with malignant hyperthermia.

General anesthetics

Isoflurane and sevoflurane are the most commonly used gas anesthetics. Some specialty practices may have desflurane available, but as that is not common, we will not discuss it here. Both iso and sevo provide a state of unconsciousness but absolutely NO analgesia. It is imperative that an analgesic be used in combination with inhalants. Both gases have dramatic affects on blood pressure and can cause mild to profound hypotension due to vasodilation. Typically the level of hypotension is dose dependant, but not always.

The minimum alveolar concentration (MAC) of sevo is 2.4% in dogs and 2.6% in cats; for iso the MAC is 1.3% in dogs and 1.6% in cats. The MAC of an inhalant is defined as the level of anesthetic gas required to prevent reaction or movement in the face of painful stimuli in 50% of patients. The higher the number assigned to a MAC value, the less potent the inhalant anesthetic. Thus sevo, which has a higher MAC is less potent than iso, which is why the level of sevo must be run higher to achieve the same result. Sedatives and opioid analgesics help lower the MAC requirements, allowing the inhalant to be run at a lower level, thus reducing the negative effects of the gas.

Post-operative care

The responsibility of affective managing pain does not end once the patient has recovered. Post-operative analgesia should be given for any painful procedure, with the kind of drug and duration of administration dependant on the type and severity of the procedure or surgery. All of the drugs listed in the opioid section can be used in the post-operative period-either as single-dose administrations or CRIs, depending on the situation. Non-steroidal anti-inflammatory agents can and should be used as well, where appropriate.

References

Skarda, Roman T. and Tranquilli, William J. 2007. Veterinary Anesthesia and Analgesia, 4th edition. Ames (IA): Blackwell Publishing.