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Anesthesia/Pain Management Sandra Z Perkowski, VMD, PhD, DACVA School of Veterinary Medicine, University of Pennsylvania Anesthetizing the Small Animal Patient: The Basics PRE-OPERATIVE EVALUATION AND MANAGEMENT Preoperative evaluation and preparation of the patient prior to anesthesia are crucial when managing any patient. Proper preoperative management helps minimize any deleterious effects anesthesia and surgery may have on the patient and helps promote recovery in the postoperative period. Decisions as to which anesthetic agents are selected and how they are administered are based upon several different factors including history, signalment (species, breed, age), size and temperament of the particular patient, physical exam, reason for presentation and procedure(s) to be performed, and experience (both your own and that of any available help) History An effort should be made to get as complete a history as possible. This should include presenting complaint, known medical conditions, any current medications, and previous anesthetic history. Physical Exam A complete physical examination should always be done prior to anesthesia. Special care should be made to evaluate the following: Weight and body condition
Laboratory tests for the determination of intravascular volume include packed cell volume (PCV) and total solids (TS), urine specific gravity and blood urea nitrogen (BUN). PCV and TS should always be evaluated together and used in conjunction with history and clinical presentation. Remember, acute blood loss is not immediately reflected by changes in PCV and TS.
In the absence of renal dysfunction, urine specific gravity and BUN may be helpful in assessing the degree of dehydration. Urine production can also be monitored and will decrease secondary to decreased renal perfusion in the hypovolemic patient. Whenever possible, a complete blood count (CBC, white blood cell count and differential) should be done prior to anesthesia and used in conjunction with history and clinical presentation. A white cell count may reveal underlying infectious disease which will be exacerbated by the anesthesia. Ideally, a complete chemistry screen should also be performed prior to surgery to identify any underlying metabolic disease (renal disease, hepatic disease, endocrinopathies). This is especially important in older patients (>6 yr of age, or >5 yr for giant breed dogs) or patients with a known medical condition. The minimum blood work required for healthy, older patients at VHUP includes a CBC, PCV, TS and creatinine. Additional diagnostic tests may be run depending on the individual patient. Fluid Therapy Prior to anesthesia, evaluation of hydration status is made on the basis of physical exam findings and laboratory results. The most common cause of hypotension is inadequate volume due to inadequate fluid replacement pre-operatively or failure to keep up with intra-operative fluid and/or blood loss. When time and the animal's condition permits, any electrolyte abnormalities present (especially potassium and calcium) should be normalized prior to the induction of anesthesia via the appropriate fluid therapy and supplementation. Mildly elevated or decreased values generally do not represent a contraindication to anesthesia. Intravenous access should ALWAYS be available when anesthetizing a patient. Normal maintenance fluid rates for animals in the awake state are 2 - 4 ml/kg/hr. Maintenance fluid rates for the average anesthetized patient are 6 - 12 ml/kg/hr, with adjustments made for patients with cardiopulmonary disease, renal disease, or head trauma. Additional volume replacement for blood loss may be required. Approximately 3 mls of crystalloid (i.e. a balanced electrolyte solution) are required to replace every 1 ml of blood loss, due to fluid distribution between the intravascular and extravascular spaces. MANAGEMENT OF ANESTHESIA Once preoperative evaluation of the patient is complete and the patient is adequately hydrated and otherwise stabilized, anesthesia is ready to begin. Selection of anesthetic agents should be dependent on the condition of the patient and the procedure to be performed. Preanesthetic Drug Selection Preanesthetic medications are frequently used prior to induction of anesthesia. Reasons include:
Act as competitive antagonists of acetylcholine at the postganglionic autonomic muscarinic receptor. They are frequently used as a premedication to help prevent vagally-mediated bradycardia (secondary to other anesthetic drugs (opioids, alpha-2 agonists), secondary to surgical manipulation (ocular, laryngeal, visceral traction) or in patients with high resting vagal tone. They also decrease salivation and excessive airway secretions. Other side effects include decreased intestinal motility, increased myocardial oxygen consumption due to increased heart rate, and increased incidence of cardiac arrhythmias and decreased threshold for ventricular fibrillation. Atropine and glycopyrrolate differ primarily in duration of action, with glycopyrrolate lasting about twice as long as atropine. In addition, glycopyrrolate is a quaternary ammonium structure (meaning it is a charged molecule!) and does not cross the blood brain barrier or placenta. Phenothiazine Tranquilizers (acepromazine, promazine) Acepromazine is commonly used to provide calming prior to anesthetic induction or in the post-anesthetic period. It is useful in relatively healthy patients; however should be avoided in patients where volume status or cardiovascular stability is a concern.
Barbiturates (thiopental, methohexital)
Propofol is a non-barbiturate intravenous anesthetic agent (substituted isopropyl phenol) that is highly lipid soluble. Current available preparations provide the active ingredient in a soybean oil/lecithin emulsion and should be handled with strict aseptic technique. The manufacturer states that propofol should not be refrigerated (or frozen!) and, once opened, the contents should be used within several hours due to the potential for significant bacterial contamination. Newer preparations are currently under development and will hopefully increase the shelf life of the opened containers. Induction of anesthesia is generally smooth and intubation is usually achieved after a total intravenous dose of 4 - 6 mg/kg titrated slowly to effect (i.e. given as an infusion over a 5 minute period or as 1-2 mg/kg IV slowly administered boluses). The emphasis on slow administration of the agent is due to the fact that clinically significant side effects (both cardiovascular and respiratory) occur with propofol administration and the incidence of these side effects is both dose and rate dependent. It is recommended that oxygen be administered via face mask during induction. Propofol, given by itself, is ultrashort acting with a 5 - 10 minute duration of anesthesia after induction. This can be both an advantage and a disadvantage, depending on the case. It is rapidly redistributed and cleared by both hepatic and extrahepatic metabolism and does not significantly accumulate with repeated dosing or constant infusion (0.05 - 0.2 mg/kg/min). Patients are remarkably alert upon recovery. Due to the presence of extrahepatic sites of metabolism, propofol may be useful in patients with impaired hepatic function (e.g. portosystemic shunts). Similarly, it may be useful when performing a Caesarian section. Although propofol freely crosses the placental barrier, the majority of the drug will redistribute back to the larger maternal circulation over a 5 - 10 minute period . Residual propofol in the neonatal circulation at birth will eventually be cleared. Propofol is a potent peripheral vasodilator and may cause significant cardiovascular depression in volume-deplete or cardiovascularly compromised patients, greater even than that seen with barbiturates, and should not be used in these cases. Decreases in myocardial contractility also occur at higher doses. CV depression is especially pronounced, even in healthy patients, if propofol is given as a large, rapid bolus - therefore, it is recommended that it be given slowly in small repeated boluses or as an infusion. Propofol may be given in combination with 0.2 - 0.5 mg/kg diazepam IV, which has minimal cardiovascular and respiratory side effects. Although the animal will take slightly longer to recover than with propofol alone, the amount of propofol required for induction is decreased and blood pressure is better maintained. Use of preoperative medication may also help decrease the dose of propofol required. Since propofol does NOT provide analgesia, preoperative administration of an opioid or other analgesic is recommended for patients undergoing a surgical procedure. Opioids, in general, also have minimal cardiovascular side effects. Adverse cardiovascular effects may be exacerbated if acepromazine, which is also a vasodilator, has been given. Propofol can also cause significant respiratory depression, again more pronounced with large, rapid boluses. It is recommended that the patient receive supplemental oxygen throughout the anesthetic period and preferably be intubated. Other occasional side effects include myoclonic twitching which may be controlled by diazepam or thiopental. Opisthotonus is seen rarely. Propofol is useful for rapid sequence inductions where cardiovascular function is not a concern. It is ideal for short procedures (eg transtracheal wash) and sedations (e.g. for radiographs or bandage changes). Because recovery is relatively rapid, it is also useful for brachycephalic patients undergoing anesthesia for any reason, as long as the animal is cardiovascularly stable. Effects on the central nervous system are similar to the effects of thiopental and continuous propofol infusions (0.05 - 0.1 mg/kg/min) have been used successfully to control seizures in animals refractory to other medication. Care should be taken when using propofol in cats. Because it is a phenol derivative, Cats will occasionally have an unexpectedly prolonged recovery. In addition, hematologic abnormalities (Heinz body formation) have been seen in cats after repeated use. Opioids
Etomidate is an ultrashort acting intravenous anesthetic causing rapid induction of anesthesia after intravenous bolus (0.5 - 1.5 mg/kg) with a duration of action of 5-10 minutes. Rapidly metabolized by liver and plasma by nonspecific plasma esterases, therefore recovery is rapid and etomidate does not accumulate with repeated boluses or a continuous infusion. It is useful for anesthetic induction in patients with cardiovascular instability, and causes minimal effects on heart rate and rhythm, cardiac output, and blood pressure. In addition, it causes minimal respiratory depression. Etomidate may induce vomiting and/or myoclonic twitching when used alone, but this reaction is significantly diminished when given in combination with an opioid and a benzodiazepine tranquilizer. Etomidate suppresses adrenocortical activity for several hours after a single bolus, which may be of concern in debilitated patients. Etomidate is solubilized in propylene glycol, which is hypersosmotic and administration of large amounts may lead to hemolysis and pigmenturia which may be of concern in patients with renal compromise. This can be avoided by diluting the etomidate with saline to prevent further insult to the kidney (e.g. although etomidate is the drug of choice for cats undergoing renal transplants at VHUP, it is diluted 1:10 before it's use!) Etomidate does not provide analgesia. It is also relatively expensive. MAINTENANCE OF ANESTHESIA Inhalant Anesthetics Inhalant anesthesia is the mainstay of anesthetic maintenance. Duration of action is not dependent on metabolism and anesthetic depth can be rapidly adjusted The two inhalant agents currently used most frequently in small animal practice are isoflurane and halothane. However, halothane has recently been removed from the market. Sevoflurane, which is similar in cardiovascular properties to isoflurane, is being used with increasing frequency, but is still very expensive at this time. All potent inhalants produce dose-dependent cardiovascular depression but, at equipotent doses, isoflurane and sevoflurane produce less myocardial depression than halothane. Isoflurane and sevoflurane cause vasodilation, but cardiac output is maintained by increases in heart rate. All the potent inhalants cause respiratory depression (shift the CO2 response curve to the right) Injectable Anesthetics Occasionally, very sick animals will not tolerate inhalant anesthesia and an injectable technique must be used
Minimum monitoring used at VHUP includes an EKG, indirect blood pressure measurement using a Doppler or oscillometric measuring device (e.g. Dinamap, MDE Escort) and esophageal stethoscope. As indicated, other monitoring should be added
POST-OPERATIVE CARE In most healthy patients, fluids do not need to be continued in the post-operative period. However, the importance of post-operative fluid therapy in the critical patient cannot be overemphasized. The use of analgesics has become increasingly popular in small animal practice, as the awareness of pain and its detrimental effects in veterinary patients has increased. USE THEM! SPECIAL CONSIDERATIONS Anesthetizing the Patient with Increased Intracranial Presssure Elevated intracranial pressure, due to head trauma, intracranial masses, etc. place the patient at an increased risk of cerebral ischemia and brain stem herniation. Any increase in total intracranial volume will cause an increase in intracranial pressure (ICP) The three major compartments found intracranially are the cells and interstitial fluid, blood, and cerebrospinal fluid (CSF). Cerebral blood volume is the only compartment able to increase or decrease its volume quickly, therefore, anesthetic management is directed at controlling CBV. The aim of anesthesia is to minimize increases in cerebral blood flow (CBF, and, therefore, CBV) while maintaining sufficient blood flow to meet the oxygen requirements of the brain. This is accomplished by maintaining adequate arterial pressure and oxygenation, while decreasing CO2 concentrations and cerebral metabolism. Normally, the brain autoregulates its blood flow over a pressure range of 50 - 150 mmHg. However, autoregulation may be disrupted in the diseased or injured brain. Cerebral perfusion pressure = mean arterial pressure - ICP. Cerebral perfusion is usually maintained with a minimum arterial pressure of 50 - 60 mmHg. Under conditions of increased ICP, arterial pressures must be maintained at higher levels CBF begins to increase below a PaO2 of 60 mmHg. O2 content and delivery is more important than PaO2 and a decrease in hemoglobin will lead to an increase in CBV. PaCO2 is the most potent factor controlling CBF and CBV and hyperventilation is these patients is of utmost importance. CBF increases 2 ml/100g/min for every mmHg increase in PaCO2 Cerebral metabolic rate (CMR) is coupled to CBF. Factors increasing CMR include: fever, pain, seizures, and ketamine. The reduction in ICP seen with barbiturates are due to their depressive effects on CMR In addition to the above, cerebral venous pressure should be minimized. Two common problems are a head-down position and jugular compression Most patients require little, if any, premedication other than glycopyrrolate. Opioids, which are respiratory depressants, should be avoided to prevent hypercarbia. Acepromazine may cause an increased potential for seizures. Ketamine is contraindicated in any patient with increased ICP! Mannitol, furosemide, and/or glucocorticoids are frequently given prior to induction to decrease cerebral edema. Mannitol alone may cause a transient increase in ICP due to transient increases in CBV. This is prevented by prior administration (e.g. by 20 minutes) of furosemide. Glucocorticoids may cause vomiting which is contraindicated. Anesthetic induction should always be followed with intubation and ventilation with 100% oxygen. Make sure anesthesia is adequate to prevent coughing on intubation. Thiobarbiturates are an excellent choice for induction as long as the patient is cardiovascularly stable. Thiopental reduces CMR and CBF in a coupled fashion to near half of the awake values, causing a decrease in ICP (even that refractory to hyperventilation and mannitol). Etomidate or propofol may also be used. Opioids (used in combination with a benzodiazepine) are often used for induction, as the patient will be intubated and ventilated. Fentanyl has been the most completely studied opioid and causes minimal increases in CBV as long as PaCO2 is maintained at normal levels. Lidocaine is frequently given as part of the induction and helps to desensitize the airway and prevent coughing on intubation. All of the potent inhalants are cerebrovasodilators, leading to an increase in ICP. These agents also impair autoregulation Halothane produces the greatest increase in ICP and isoflurane the least. Cerebral vasodilation can be avoided if low concentrations of the agent are used in conjunction with hyperventilation. When using isoflurane, hyperventilation may be instituted simultaneously with administration to prevent cerebrovasodilation. Intravenous boluses of oxymorphone, hydromorphone, fentanyl, thiopental, propofol or etomidate may also be used for maintenance. Alternatively, fentanyl and propofol may be given as a continuous infusion. The patient should ideally be normovolemic prior to anesthesia. Fluid rates should be adjusted to match urine output. Maintenance rates (4-6 ml/kg/hr) are generally adequate, although higher rates may be needed in patients that are cardiovascularly unstable. Ideally, recovery should be rapid with little to no excitement. The endotracheal tube is left in as long as possible so the patient can continue being ventilated. Lidocaine may be given just prior to extubation to help prevent coughing. Anesthetizing the Patient with Hepatic Dysfunction Patients with hepatic dysfunction often have difficulty with drug metabolism, including metabolism or most intravenous anesthetic agents; prolonged anesthetic recovery may result. Choice of anesthetic is based upon the underlying disease and an estimation of the degree of hepatic dysfunction (remember that small elevations in liver enzymes may be quite significant in cats) Preanesthetics are usually not required. If a premedicant is necessary, an opioid is preferred since it can be reversed. Use of intravenous induction agents should be minimized. If necessary opioids (especially those with short duration of action such as fentanyl) in combination with a benzodiazepine are preferred for induction since they can be reversed. Propofol may be used in patient where cardiovascular concerns are minimal. In cases of severe disease, intravenous agents are best avoided altogether and a mask induction using an inhalant anesthetic is usually done. Remember that the liver receives its blood supply from two sources: the hepatic artery and the portal vein. Since part of the blood supply is venous, the liver is at high risk for suffering hypoxic cellular damage during periods of low perfusion. To prevent an exacerbation of hepatic dysfunction postoperatively, patients should always receive supplemental oxygen and drugs should be chosen to optimize cardiovascular function. Hypoalbuminemia may result in an increase in the unbound, active form of intravenous drugs and administration of normal doses may result in relative drug overdose. Coagulopathies may result from a decrease in vitamin K dependent clotting factors and fresh frozen plasma or whole blood may be required preoperatively. Hypoglycemia may also be present and require dextrose infusion intraoperatively Anesthetizing the Patient with Renal Disease All anesthetics can cause depression of renal function due to the decrease in sympathetic tone that occurs during anesthesia. In patients with underlying renal disease, changes in renal blood flow may produce additional damage, especially during periods of hypotension, resulting in acute renal failure post-operatively. Fluids should be administered preoperatively (preferably 24 hrs prior to anesthesia) to maximize renal function and assure adequate intravascular volume. Electrolytes should be measure preoperatively; common abnormalities include hyperkalemia and hypocalcemia, both of which may precipitate cardiac arrhythmias on induction of anesthesia Anesthetic agents should be chosen to maximize cardiovascular stability. Anesthetic agents excreted by the kidney unchanged should be minimized (ketamine in cats, pancuronium). Urine output should be monitored intraoperatively; if urine flow should decrease markedly, mechanical obstruction should be excluded first. Urine production generally decreases under anesthesia, both due to decreased blood flow and the antidiuretic effect of decreased body temperature. If a fluid challenge fails to return urine output to normal levels (0.5 - 1.0 ml/kg/h) drug therapy may be required. Mannitol (0.5 - 1 g/kg given as a slow IV bolus over 10 - 20 min) acts as an osmotic diuretic. Furosemide (1 mg/kg) is a loop diuretic and may be used is intravascular volume is adequate. Dopamine (1-3 mcg/kg/min) acts as a renal vasodilator due to dopaminergic effects, but also acts has beta activity which will increase cardiac output and renal blood flow- n.b. higher doses (> 10 mch/kg/min) may result in vasoconstriction (alpha effects). Diuretic effects of all these agents may be enhanced if more than one agent is used in conjunction (e.g. dopamine at 2 mcg/kg/min with furosemide as a constant infusion of 0.1 mg/kg/hr). Close monitoring of renal function should be continued postoperatively Anesthetizing the Animal with Endocrine Disease Animals with pre-existing endocrine disease should have medications continued up until the time of anesthesia. Check the records carefully to be sure that all appropriate pre-operative medications were administered. Prior to induction be sure that all supplies and drugs that may be needed during the procedure are on hand. Diabetes Mellitus Potential problems are: hypovolemia (due to polyuria); hyperglycemia; hypoglycemia; Diabetic Ketoacidosis; hyperosmolarity; autonomic dysfunction. The aim is to avoid hypoglycemia. Patients should receive only half of their insulin dose on the day of anesthesia since they are fasted overnight. Anesthesia should be done early in the day so that the patient can return to normal schedule as soon as possible. Monitor dextrose every hour during surgery and make glucose supplements as needed. Fluid composition is adjusted according to the animal`s blood glucose level:
Potential problems are: hypertension, hypovolemia, tachycardia, thyroid storm. Post-op: airway obstruction due to laryngeal paralysis or tracheal collapse. Propranolol may be instituted prior to anesthesia to control tachycardia (esmolol, an IV beta-blocker, may be used during anesthesia). Avoid excitement. Unless euthyroid, avoid atropine and ketamine and use care with opioids so as to avoid dysphoria and excitement. An acepromazine pre-op may be used. Barbiturates, Diazepam, Etomidate, Propofol and inhalants may be used for induction and maintenance. Hypoadrenocorticism Correct electrolyte imbalances prior to surgery especially Sodium and Potassium. Continue steroid supplementation if applicable up until anesthesia is begun. Administer Dexamethasone 0.25 mg/kg IV at induction of anesthesia, repeat at the end of the procedure. Avoid using Etomidate since it supresses adrenocortical production. Hyperadrenocorticism The potential problems of an adrenalectomy are pneumothorax and adrenal crisis. Observe for hypotension, hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. Use appropriate IV fluids. A short-acting glucocorticoid; hydrocortisone sodium phosphate 5.0 mg/kg, prednisolone sodium succinate 1.0 mg/kg, or dexamethasone sodium phosphate 0.2 mg/kg should be administered as an IV bolus at the beginning of surgery.For a bilateral adrenalectomy administer an additional dose of glucocorticoid before the removal of the second adrenal gland or give as a CRI. COMMONLY USED DRUG DOSAGES*
(* Dog and cat doses may differ.) ANESTHESIA FOR THE DOG Anticholinergics are used routinely unless contraindicated. Although there are differences between atropine and glycopyrrolate, in general, choice often depends upon personal preference. Acepromazine in the recommended dosages, used alone, has mild sedative effects and may or may not provide the desired amount of pre-operative sedation. The benzodiazepines used alone are not recommended as they are not good sedatives by themselves. The alpha 2 agonists may provide good sedative effects but are infrequently used as preanesthetics due to cardiovascular concerns. Opioids are used as premeds for their sedative effects as well as for the analgesic effects. They are usually administered with an anticholinergic. However, the addition of acepromazine (or a benzodiazepine) to an opioid will potentiate the sedative effects of the opioid and may reduce the likelihood of dysphoria, panting, or other excitatory reactions. If using an intramuscular (IM) pre op,it should be given at least 15-20 minutes prior to the insertion of the IV catheter and the induction of anesthesia. Healthy dog IM pre-op protocol: -ATROPINE 0.02 mg/kg and HYDROMORPHONE 0.2 mg/kg -ATROPINE 0.02 mg/kg and OXYMORPHONE 0.1 mg/kg -ACEPROMAZINE 0.02 - 0.1 mg/kg -ATROPINE 0.02 mg/kg and ACEPROMAZINE 0.02 - 0.05 mg/kg and HYDROMORPHONE 0.1 mg/kg -ATROPINE 0.02 mg/kg and ACEPROMAZINE 0.02 - 0.05 mg/kg and OXYMORPHONE 0.05 mg/kg -ATROPINE 0.02 mg/kg and BUPRENORPHINE 0.01 mg/kg -ATROPINE 0.02 mg/kg and ACEPROMAZINE 0.02 - 0.05 mg/kg and BUPRENORPHINE 0.006 - 0.01 mg/kg -ATROPINE 0.02 mg/kg and BUTORPHANOL 0.5 mg/kg -ATROPINE 0.02 mg/kg and ACEPROMAZINE 0.02 - 0.05 mg/kg and BUTORPHANOL 0.1 - 0.4 mg/kg *GLYCOPYRROLATE 0.01 mg/kg may be substituted for ATROPINE. Healthy dog IV induction protocol: THIOPENTAL (2.0%) is given in a 2 mg/kg bolus while an assistant is monitoring the pulse and checking for arrhythmias. The animal is observed for any adverse reaction. The second bolus of 4 mg/kg is given after a 15 second pause. The drug is given in 2 - 4 mg/kg boluses until the dog is deep enough to intubate. PROPOFOL is administered slowly in boluses of 1 -2 mg/kg. MIDAZOLAM (0.2 - 0.5 mg/kg) or DIAZEPAM (given in a separate syringe) may be added to either of the above protocols if desired PROPOFOL-DIAZEPAM INDUCTION PROPOFOL 2 mg/kg and DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV Continue with PROPOFOL at 1 - 2 mg/kg until intubation is possible. May cause hypotension. KETAMINE (10 mg/kg) and DIAZEPAM (0.5 mg/kg) Give half of the Ketamine and all of the diazepam. Then give rest of the ketamine to desired effect. If the ketamine and diazepam are mixed together in the syringe, the volume of diazepam must be equal to or greater than the ketamine volume. Typically, 5 mg/kg ketamine and 0.5 mg/kg diazepam (1:2) is adequate for intubation. PROTOCOL FOR A SICK OR DEBILITATED DOG IM premedication is usually avoided in the very sick or debilitated dog. If necessary, an opioid is generally used. After placement of an IV catheter, an ECG should be placed prior to induction (if available). Pre-oxygenation is advisable. Use appropriate fluids and caution with heart disease. Induction Depending upon how ill the patient is, thiopental, propofol or ketamine/diazepam may be appropriate if used in small amounts. In very ill patients, IV administration of a potent opioid pure agonist (but NOT morphine) and a benzodiazepine will significantly reduce the dosage of, or eliminate the need for, a hypnotic induction agent. If intubation cannot be accomplished etomidate may be administered. Lidocaine administered IV may also reduce the dosage of the induction agent due to its sedative effects. OPIOID INDUCTION ATROPINE 0.01mg/kg IV OR GLYCOPYRROLATE 0.005 mg/kg IV *Use anticholinergic only if necessary. FENTANYL 0.005mg/kg OR HYDROMORPHONE 0.1-0.2 mg/kg IV DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV LIDOCAINE (2%) 2 mg/kg IV (if not contraindicated) You may need to give additional opioid to achieve intubation. Start with 1/2 the original dose. OPIOID - ETOMIDATE INDUCTION ATROPINE 0.01mg/kg OR GLYCOPYRROLATE 0.005 mg/kg IV *Use anticholinergic only if necessary. FENTANYL 0.005mg/kg OR HYDROMORPHONE 0.2 mg/kg IV DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV ETOMIDATE 0.2 - 1.5 mg/kg IV MASK INDUCTION with ISOFLURANE or SEVOFLURANE Note that a mask induction may lead to clinically significant hypotension due to the need for relatively high concentrations of inhalant. A slow titrated induction with an opioid and benzodiazepine is preferred. Maintenance Isoflurane or Sevoflurane in O2 may be used as long as the blood pressure is adequate. If blood pressure is poor the inhalant should be decreased or turned off and injectable anesthetics used. INJECTABLE ANESTHESIA FENTANYL 0.0025 - 0.005 mg/kg IV boluses HYDROMORPHONE 0.05 - 0.1 mg/kg boluses DIAZEPAM 0.2 mg/kg OR MIDAZOLAM 0.2 mg/kg IV boluses Given as needed to maintain sedation and analgesia. CONTINUOUS INFUSIONS FENTANYL 0.0007 - 0.0015 mg/kg/min MORPHINE 0.1 - 0.2 mg/kg/hr KETAMINE 0.1 - 0.2 mg/kg/hr (note : morphine and ketamine are often used in combination to increase analgesia and decrease MAC intraoperatively) ANESTHESIA FOR SIGHT HOUNDS Because of the smaller volume of distribution and lower clearance of thiopental in these dogs the anesthetic technique should be modified. Note that thiopental may be used if indicated (e.g. patients with head trauma or increased intracranial pressure for any reason), but doses should be adjusted and adjunct medication used to decrease the total amount of the thiopental given. Oxybarbiturates (e.g. methohexital) may be used in place of thiopental. IM Preop Any pre-op may be given from the NORMAL DOG protocol (see page 10). Many Greyhounds are nervous and can become agitated after a pure opioid premed. Induction PROPOFOL 1 - 2 mg/kg IV. Repeat until intubation is achieved. DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 mg/kg IV can be added if desired. or DIAZEPAM 0.5 mg/kg OR MIDAZOLAM 0.5 mg/kg and KETAMINE 5 - 10 mg/kg IV or FENTANYL 0.005 mg/kg OR HYDROMORPHONE 0.2 mg/kg and DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV ETOMIDATE 0.2 - 1.5 mg/kg IV can be added if desired. Maintenance Remember that all potent inhalants may trigger "malignant hyperthermia", an increase in metabolic rate and CO2 production, in susceptible animals. Increased respiratory rate, heart rate, and blood pressure CO2 absorber consumption are often seen before increased temperature. MAST CELL TUMOR PROTOCOL Patients with mast cell tumors are at risk for complications due to the potential for histamine release i.e. vasodilation/hypotension, airway swelling and bronchiolar constriction, gastric acid secretion. The use of opioids for mast cell cases may be controversial. There have been studies that demonstrate that oxymorphone and hydromorphone do not release histamine; however, care should still be taken with their use. Premed with Benadryl 2 mg/kg IM. and if needed, any of the pre-meds before mentioned. Famotidine 0.5 mg/kg IV and Dexamethasone 0.2 - 0.5 mg/kg IV may be given VERY SLOWLY before or after induction. Any of the following drugs may be used for induction and maintenance: Thiopental, Diazepam, Propofol, Etomidate. ANESTHESIA FOR C-SECTION The general aim is to minimize the amount of inhalant given to the bitch prior to removal of the puppies. Note that the only anesthetics that have been associated with an INCREASED morbidity and mortality of the neonates are the alpha-2 agonists (xylazine, medetomidine) and these drugs should NOT be used. Generally a line block with lidocaine is performed prior to induction (if possible). An epidural may also be done (morphine/lidocaine or bupivacaine), although the local anesthetic should NOT be included if the animal is hemodynamically unstable. Propofol IV given as slow 1 mg/kg boluses. Although propofol freely crosses the placental barrier, the majority of the drug will redistribute back to the larger maternal circulation over a 5 - 10 minute period . Residual propofol in the neonatal circulation at birth will eventually be cleared.
SEDATION / CHEMICAL RESTRAINT FOR DOGS
Pre-op KETAMINE 2 - 6 mg/kg and MIDAZOLAM 0.2 - 0.4 mg/kg and HYDROMORPHONE 0.05 - 0.1 mg/kg (or BUTORPHANOL 0.2 - 0.4 mg/kg) IM KETAMINE 8.0 mg/kg IM. This preop may have maximum effect as early as 5 minutes from time of injection. CAUTION - IM ketamine may sting!! Both drugs can be drawn up in the same syringe. KETAMINE 2 - 6 mg/kg and DIAZEPAM 0.25 - 0.4 mg/kg OR MIDAZOLAM 0.25 - 0.4 mg/kg IM TELAZOL 2 - 4 mg/kg IM KETAMINE 8 - 10 mg/kg and ACEPROMAZINE 0.03 - 0.05 mg/kg IM *Atropine 0.02 mg/kg or Glycopyrrolate 0.01 mg/kg may be used with any IM pre-op if desired. Induction KETAMINE 2.0 mg/kg and DIAZEPAM 0.5 mg/kg IV. OR THIOPENTAL 2.0 - 4.0 mg/kg (+/- Diazepam) OR PROPOFOL 1.0 - 2.0 mg/kg (+/- Diazepam) OR ETOMIDATE 0.2 - 1.5 mg/kg (+/- Diazepam) Please note that all Etomidate given to cats will be diluted. The concentration used for healthy cats is 1.0 mg/ml. The concentration for cats with renal disease is 0.1 - 0.2 mg/ml PROTOCOL FOR A SICK OR DEBILITATED CAT INDUCTION DIAZEPAM / MIDAZOLAM-ETOMIDATE INDUCTION DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV. ETOMIDATE 0.2 - 1.5 mg/kg IV. OPIOID INDUCTION HYDROMORPHONE 0.1 - .2 mg/kg OR FENTANYL 0.005 mg/kg IV and DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV. *Atropine 0.01 mg/kg OR Glycopyrrolate 0.005 mg/kg IV may be used if needed. You may also use ETOMIDATE 0.2 mg/kg IV. LIDOCAINE 1 mg/kg may be given IV or used topically. KETAMINE-DIAZEPAM / MIDAZOLAM INDUCTION KETAMINE 2.0 mg/kg IV. DIAZEPAM 0.2 - 0.5 mg/kg OR MIDAZOLAM 0.2 - 0.5 mg/kg IV. BOX OR MASK INDUCTION WITH ISOFLURANE or SEVOFLURANE SEDATION / CHEMICAL RESTRAINT FOR CATS KETAMINE and XYLAZINE MIXTURE 1 ml/10 kg IM, 1 ml/50 kg IV We pre-mix 3 mls Ketamine (100 mg/ml) with 1 ml Xylazine (20 mg/ml). KETAMINE 2.0 - 4.0 mg/kg IV and DIAZEPAM 0.2 0.5 mg/kg IV and BUTORPHANOL 0.1 mg/kg IV and ACEPROMAZINE 0.01 mg/kg IV Repeat if necessary, Double the above combination if giving IM PROPOFOL 1 - 2 mg/kg IV boluses and DIAZEPAM 0.25 - 0.5 mg/kg IV Watch for hypotension and respiratory depression. TELAZOL 2 -4 mg/kg IM *Atropine 0.1 - 0.2 mg/kg or Glycopyrrolate 0.05 - 0.1 mg/kg may be used if desired. TREATMENT OF HYPOTENSION If the animal's systolic blood pressure on the doppler falls to or below 80 mmHg or the mean arterial pressure is less than 60 mmHg by direct pressure measurement or by the dinamap, corrective measures should be taken.
Epinephrine - make an IV drip using 1 mg of epinephrine in a 250 ml bag of 0.9% NaCl. Start slowly and titrate to effect, watch for arrhythmias. Dopamine - Dopaminergic effects (renal vasodilation) are seen at doses of 1 - 3 ug/kg/min. Beta effects (inotropic, chronotropic) are seen at moderate doses of 5 - 10 ug/kg/min. Alpha effects (vasoconstriction) are seen at higher doses of > 10 ug/kg/min. (To make a drip, use the following equation: # of ug/kg/min x weight(in kg) = # of mgs Placed in 250 ml of 0.9% NaCl. Infuse at 15 ml/hr.) Ephedrine - dilute 50 mg (1 ml) ampule in 9 ml of fluid. Beware of arrhythmias. Dose - 0.1 - 0.5 mg/kg. Dobutamine - Start at 5 ug/kg/min. If this dose is not effective go to 10 ug/kg/min. May cause tachycardia without increased pressure. CONTROLLING VENTILATION Respiratory Minute Volume = TV x RR.
Animals with a history of thoracic trauma or evidence of lung contusions should be ventilated very gently to lower airway pressures to minimize risk of a rupture. A higher respiratory rate and smaller tidal volume can be tried to see if adequate ventilation can be achieved with a lower inflation pressure. HOWEVER, THE VENTILATION MUST BE ADEQUATE REGARDLESS OF THE PRESSURE REQUIRED. RE ESTABLISHMENT OF SPONTANEOUS VENTILATION Spontaneous ventilation following a period of controlled ventilation is easily initiated within minutes. Conditions that contribute to prolonged apnea are as follows:
The time period in which ventilation can be stopped to allow for accumulation of CO2 without a drop in O2 tension is dependent on the delivered O2 concentration. On room air for example, hypoventilation or cessation of ventilation for a short period of time will result in hypoxemia. When 100% oxygen is used, ventilation can be stopped for longer periods of time to allow for the accumulation of CO2. Hypoxemia may eventually stimulate ventilation depending on the cause of lack of ventilation but is dangerous and should not be done. Carbon dioxide moves in the opposite direction to oxygen but not as rapidly due to the higher molecular weight, greater solubility in tissues and a subsequent lower pressure gradient. Within 2 3 minutes CO2 tension can increase by mmHg torr. If no ventilatory movement is noted within this time frame, controlled ventilation must be again initiated, and other causes for the lack of spontaneous respiration investigated. Opioids, barbiturates, and other depressants used in the preanesthetic and induction period may be present in sufficient concentrations to depress ventilation. Lack of external stimulation will also contribute to apnea following a period of controlled ventilation. Anesthetic Approach To The Hemodynamically Compromised Patient Anesthesia in patients with cardiovascular instability include patients with primary cardiac disease and patients presenting with cardiac signs (e.g. arrhythmias) secondary to trauma or significant metabolic disease. The choice of anesthetic agent will depend on the underlying disease process, the presence or absence of heart failure and degree of heart failure, and the presence or absence of arrhythmias. Stress during patient handling should be avoided if possible to minimize catecholamine release, tachycardia and increased myocardial work. This may require sedation for pre-operative diagnostic procedures and occasionally requires pre-operative medication in patients that are not already depressed. Patients on medication for heart failure are generally continued on their medication up until the time of surgery. However, intractable hypotension has been reported under anesthesia on patients receiving angiotensin-converting enzyme inhibitors such as enalapril. SEDATION A combination of an opioid agonist (e.g. oxymorphone 0.05 - 0.1 mg/kg or hydromorphone 0.1 - 0.2 mg/kg) or agonist/antagonist (e.g. butorphanol 0.1 mg/kg or buprenorphine 0.006 - 0.01 mg/kg), and a benzodiazepine tranquilizer (diazepam 0.25 mg/kg or midazolam 0.2 mg/kg), may be used to sedate patients for chest radiographs or echocardiography. This combination provides sedation with minimal cardiovascular depression. Some patients may pant if a pure opioid agonist is used. The combination may be repeated IV if necessary or the dosage doubled and given IM. Reversal may be accomplished by using an opioid antagonist such as naloxone (0.02 mg/kg) and/or a benzodiazepine antagonist such as flumazenil (0.01 - 0.02 mg/kg) IV. Phenothiazine tranquilizers such as acepromazine should be avoided in patients where volume status is a concern. However, acepromazine in very low doses (0.02 mg/kg IM) may be beneficial in some circumstances because it calms the patient, decreases afterload, and decreases the incidence of arrhythmias. It should only be used after careful consideration, however, since the alpha blockade may lead to peripheral vasodilation, hypotension and decreased preload. PREMEDICATION Premedication is NOT required for most patients with severe heart disease, significant metabolic disease or patients presenting as an emergency secondary to trauma . However, relatively healthy patients such as puppies with patent ductus arteriosus (PDA) or healthier dogs presenting for pericardectomy may require premedication. If pre-operative sedation is necessary, opioids are generally the drug of choice since they cause minimal cardiovascular depression (left ventricular contractility, cardiac output and systemic blood pressure are well maintained). In addition, they provide excellent analgesia. In healthy animals, opioids cause behavioral changes ranging from sedation to excitement; however, in critically ill patients, opioids usually cause sedation. Opioids may cause bradycardia. Heart rate should be monitored and an anticholinergic such as glycopyrrolate or atropine administered if necessary. Anticholinergics are not used unless indicated since they may predispose to cardiac arrhythmias. Phenothiazine tranquilizers such as acepromazine should be avoided in patients where volume status or cardiovascular stability is a concern, due to the potential for hypotension secondary to alpha blockade. Ketamine provides relative cardiovascular stability. However, it also causes catecholamine release, tachycardia and increased myocardial consumption. In addition, it may predispose to arrhythmias. Therefore, other combinations are preferred and ketamine should only be used after careful consideration in patients with cardiac disease. Alpha-2 agonists such as xylazine or medetomidine should NOT be used in patients with cardiovascular instability, due to a number of potentially significant cardiovascular side effects (vasoconstriction and increased afterload, bradycardia, decreased cardiac output, decreased oxygen delivery to the tissues). Stabilization of fluid balance and cardiovascular function is essential prior to the induction of anesthesia. Cardiac arrhythmias are often seen in patients with primary cardiac disease. However, cardiac arrhythmias, especially ventricular ectopy, are also frequently seen with many conditions requiring emergency surgery (eg gastric dilatation/volvulus, acute abdominal bleed, contusions of the chest). The most common arrhythmias are premature ventricular contractions (PVCs), although ventricular tachycardia and AV heart block are often seen as well. If the patient has an occasional PVC that always arises from the same focus, it probably does not need to be treated; if the patient has frequent, multifocal PVCs, pulse deficits, or paroxysmal ventricular tachycardia, it probably should be treated. If ventricular ectopy is present, conversion to normal sinus rhythm with IV lidocaine (2 mg/kg IV) may be attempted prior to induction; if this is successful wait to see if the arrhythmia returns and how long it takes. If the arrhythmia does not respond to lidocaine, other antiarrhythmic therapy should be instituted (procainamide, bretylium, quinidine). More recently, amiodarone has been suggested as a first line of defense in patients with ventricular tachycardia. Adenosine or digoxin may be used for patients with supraventricular tachycardia. In the acute setting, esmolol, a short-acting beta blocker, may be indicated, although the patient should be carefully monitored as a decrease in cardiac contractility may be seen in addition to the desired decrease in heart rate. INDUCTION In patients where cardiovascular function is a concern, induction should be slow with careful titration of drugs to effect and continuous monitoring of cardiovascular parameters throughout induction (EKG, blood pressure). Patients should be preoxygenated if possible prior to induction. A slow titrated induction using a combination of an opioid agonist such as hydromorphone (0.1 - 0.2 mg/kg), oxymorphone (0.05 - 0.1 mg/kg) or fentanyl (0.0025 - 0.005 mg/kg), and a benzodiazepine tranquilizer such as diazepam (0.2 -0.5 mg/kg) or midazolam (0.2 mg/kg) is preferred. Additional opioids may be given until intubation is possible. Lidocaine (1-2 mg/kg) may be added to this combination and helps to desensitize the airway and smooth induction and intubation. Etomidate (0.5 - 1.5 mg/kg) may be given after administration of the opioid and benzodiazepine. Etomidate has minimal cardiovascular effects and is especially useful in patients with arrhythmias. Large doses of propofol are generally to be avoided, due to potentially profound cardiovascular side effects, including vasodilation, decreased cardiac contractility and hypotension. However, a low dose (e.g. 1 mg/kg) slowly administered bolus may be useful as an adjunct to aid intubation in some situations. MAINTENANCE Inhalational anesthetics are commonly used for maintenance in cardiac patients. Isoflurane, sevoflurane or desflurane are preferred because they cause less myocardial depression than halothane. Hypotension may occur, however, secondary to vasodilation. Some patients may not tolerate inhalational anesthesia and become profoundly hypotensive. In these patients, a continuous infusion of fentanyl (0.7 - 1.5 ug/kg/min) or morphine may be very useful in decreasing the amount of inhalant needed to maintain anesthesia. Similarly, low dose infusions of propofol (0.1 mg/kg/min) may be used, although careful monitoring of cardiovascular parameters should be made. Alternatively, small IV boluses of an opioid and/or etomidate may be given. Neuromuscular blockers (vecuronium, pancuronium, and atracurium) may be used as an adjunct to general anesthesia. These drugs maintain muscle relaxation in the face of decreased amounts of inhalant or injectable anesthetic agents. Vecuronium produces minimal cardiovascular effects. Pancuronium is vagolytic and should be avoided in patients with tachycardia; in addition, its action is prolonged in patients with renal failure. Atracurium may cause histamine release at higher doses; however it is metabolized by Hofmann elimination (i.e. spontaneous degradation in the blood) making it useful in patients with liver or renal failure. Recently, cis-atracurium has been introduced. Although the pharmacokinetics are similar to those of atracurium, histamine is not released. Cis-atracurium may be given as a 100 ug/kg slow IV bolus, with additional boluses of 50 ug/kg as necessary, or as a continuous infusion at 1 - 10 ug/kg/min. Maintenance fluid rates for anesthetized patients are 10 - 15 ml/kg/hr. In patients with heart failure, lower rates (4-6 ml/kg/hr) are used. INTRAOPERATIVE MONITORING Close monitoring of the cardiovascular system is very important. Heart rate, peripheral pulse quality and mucous membrane color and capillary refill time should all be observed closely. An esophageal stethoscope or an electrocardiogram is helpful, especially in patients with cardiac arrhythmias. Blood pressure may be measured directly using an arterial catheter or indirectly with a Doppler ultrasonic flow probe or an oscillometric measuring device. Pulse oximeters measure changes in the saturation of hemoglobin with oxygen by measuring changes in the differential transmission of light at two different wavelengths. Although pulse oximeters do not monitor blood pressure per se, they must be able to detect a pulse in order to work. Therefore, they may stop functioning as peripheral perfusion decreases, which can alert the clinician to changes in cardiovascular status. Measuring central venous pressure (CVP) is also very useful for monitoring the effects of fluid administration in patients with borderline cardiac function. Urine output may be monitored intraoperatively. If urine flow should decrease markedly, mechanical obstruction should be excluded first. Urine production generally decreases during anesthesia. If fluid challenge fails to return urine output to normal levels (0.5 - 1.0 ml/kg/h) drug therapy may be required. Mannitol (0.5 - 1 g/kg given as a slow IV bolus over 10 - 20 min) acts as an osmotic diuretic. Furosemide (1 - 2 mg/kg or as a constant infusion of 0.1 mg/kg/hr) is a loop diuretic and may be used if intravascular volume is adequate. Dopamine (1 - 3 ug/kg/min) may also improve urine production, although studies suggest that the diuretic effect is due to beta-mediated increases in cardiac output and renal blood flow, rather than stimulation of the dopamine receptors at lower doses. Diuretic effects of all these agents may be enhanced if more than one agent is used in combination. Close monitoring of renal function should be continued postoperatively. INTRAOPERATIVE CARDIOVASCULAR CRISES Hypotension Systemic blood pressure must be maintained above the minimum level required for cerebral, coronary, and renal perfusion. Autoregulation of these organs is normally maintained with a mean arterial blood pressure of 50 -150 mmHg. Mean arterial blood pressures less than 60 mmHg (or systolic pressures less than 80 mmHg) are generally considered inadequate. Changes in blood pressure are determined by changes in cardiac output and systemic vascular resistance (BP = Q x SVR). Cardiac output, in turn, is determined by stroke volume and heart rate (Q = SV x HR). Decreases in stroke volume may be seen secondary to decreased venous return (decreased preload) often caused by underlying fluid deficits or peripheral vasodilation (decreased systemic vascular resistance) leading to a relative fluid deficit. In addition, stroke volume may be decreased due to decreased myocardial contractility, increased systemic vascular resistance (increased afterload), and cardiac arrhythmias. Recognition of hypotension includes changes in heart rate and rhythm, assessment of tissue perfusion, and measurement of systemic arterial blood pressure. Tachycardia is a major compensatory response to fluid/blood loss and hypovolemia, although increases in heart rate may also be seen due to inadequate anesthesia, hypercarbia, hypoxemia, or drug administration (e.g. anticholinergic). Tissue perfusion may be assessed by changes in mucous membrane color and character, capillary refill time, evaluation of peripheral pulses, temperature of the extremities, and urine production. As noted above, although pulse oximeters do not detect blood pressure per se, as peripheral perfusion and pulse pressures decrease, the pulse oximeter will stop functioning and may alert the clinician to the presence of cardiovascular depression. Arterial blood pressure may be measured using noninvasive measuring techniques including Doppler ultrasonographic flow probes, newer oscillometric measuring devices (e.g. Dinamap ), or by direct arterial blood pressure measurements. A casual poll of board-certified anesthesiologists found that, if limited to having only one monitoring device available in their practice, the Doppler flow probe would be the monitor of choice. Although only systolic pressures are measured with this device, advantages include portability, flexibility of it's use in a wide range of animal species, relative reliability, and the availability of an audible signal which allows one to monitor heart rhythm and rate as well as blood pressure. The underlying cause of hypotension should be identified and corrected as rapidly as possible. Hypotension is most commonly due to inadequate preoperative fluid replacement or failure to keep up with intra-operative fluid and/or blood loss. Evaluate losses, volume status, PCV/TS and administer fluids as indicated. Maintenance fluid rates for the anesthetized patient (6-12 ml/kg/hr) are greater than those for the awake patient due to greater evaporative losses from the respiratory tract as dry air passes through the endotracheal tube, greater evaporative losses via exposed body cavities, and greater third space losses with surgical manipulation. Higher fluid rates are usually needed in emergency patients with preexisting deficits or ongoing blood losses. Low diastolic pressures (< 40 mmHg), large positional changes in blood pressure, or difficulty in tolerating positive pressure ventilation may all alert the clinician to the presence of inadequate volume. Fluid replacement is generally accomplished using an isotonic balanced electrolyte solution, with a 3:1 ratio used for replacement of blood loss. Several commercial solutions similar in composition and indications are available, including Normosol-R, Lactated Ringers, and normal saline. Colloid may be added to the resuscitation (a dose of 20 ml/kg is roughly equivalent to a shock dose of 90 ml/kg crystalloid with plasma volume expansion being similar to the volume of colloid given) as necessary. Several synthetic colloid solutions are available. Dextrans are supplied in low and high molecular weight forms, Dextran 40 and 70 respectively. Dextran 70 (MW=70,000) is given as a 6% solution in normal saline at a rate of 10-20 ml/kg/day. The plasma half life is estimated at 2 to 6 hours. Plasma volume expansion is 20 - 25 ml/ gram dextran. Advantages include that they are relatively inexpensive (vs. other colloids). Disadvantages include a tendency toward coagulopathies due to interference with fibrin clot formation, decreases in factor VIII and von Willebrand's factor (increased activated PTT and buccal mucosal bleeding time), nonspecific platelet binding interfering with platelet function and dilution of clotting factors. In addition, allergic reactions and anaphylactic shock have been reported. Hydroxyethylstarch (HES, hetastarch) is a synthetic polymer of glucose with a average MW=450,000, although it is a polydisperse solution with both larger and smaller molecular portions. It is generally given as a 6% solution in normal saline at a suggested rate of up to 10 - 20 ml/kg/day. Advantages include a more persistent effect than dextran (40 % remains in plasma after 24 hrs) with the plasma volume returning to normal in 48 hours. Disadvantages include it's relative expense and coagulopathies which are frequently seen at volumes > 24 ml/kg/day. Allergic reactionS are seen, although anaphylactic shock has not been reported. Fresh frozen plasma may be used not only for intravascular volume replacement but for replacement of albumin, coagulation factors (including Factor VIII and VWF), and other important plasma proteins. Fresh frozen plasma is generally given at a dose of 6-10 ml/kg. In man, 10% of the transfused albumin is cleared within 2 hours. Disadvantages for volume replacement include limited availability, expense, the relatively transient nature of the effect, and the possibility of a transfusion reaction (urticaria,+/- fever). Blood or blood products may be administered as needed based upon estimation of blood loss, PCV/TS, and clinical presentation. Cross match should be done if possible, although the likelihood of a transfusion reaction is decreased if the dog has not previously received a transfusion. They are generally given at a beginning dose of 10-20 ml/kg. Hypotension will be aggravated by the myocardial depression and peripheral vasodilation caused by many anesthetic agents, especially at deeper planes of anesthesia. While attempting to discover the cause for hypotension, it is generally a good idea to increase the fluid rate (unless the patient has other disease in which fluid loading may be detrimental) and decrease the depth of anesthesia. All inhalant anesthetics depress the cardiovascular system to some extent, either by direct effects on the myocardium (halothane) or by decreases in systemic vascular resistance (isoflurane, sevoflurane, desflurante). In some cases, maintenance of anesthesia may need to be changed to an injectable technique, such as fentanyl infusion, causing less cardiovascular depression than inhalant techniques. Pharmacological Support Pharmacologic support may be required if hypotension is severe and does not respond to fluids or changes in anesthetic depth. Drugs are selected based on the patient's condition and physiologic response and based on their interaction with alpha and beta receptors. Alpha agonists stimulate alpha receptors in the peripheral vasculature and increase blood pressure by causing vasoconstriction. They should be used with care if the patient is bleeding profusely or volume deplete, since blood flow to vital organs could be compromised. Common pressors include phenylephrine, epinephrine, dopamine, and norepinephrine. Beta 1 agonists increase both heart rate and contractility, increasing blood pressure by an increase in cardiac output. Common inotropes include epinephrine, dopamine and dobutamine. All of these may cause tachyarrhythmias at higher doses. Beta 2 agonists cause peripheral vasodilation (especially in skeletal muscle) and bronchodilation. Drugs with mixed beta 1 and 2 activity may cause an increase in contractility and heart rate, without an increase blood pressure, due to the decrease in systemic vascular resistance. It is important to realize that recommended doses are determined using healthy subjects. Receptor affinities and volumes of distribution change in critically ill patients. Drugs which work in part through an indirect effect by causing release of endogenous norepinephrine stores (dopamine, ephedrine) may not be the best choice in critically ill patients where these stores are somewhat depleted.
Other drugs used for pressure support include phosphodiesterase inhibitors (amrinone, milrinone) which exert a positive inotropic effect by increasing cAMP, and calcium. Calcium increases myocardial contractility and cardiac output, as well as increasing vascular tone. It is used to treat myocardial depression secondary to hypocalcemia, hyperkalemia, hypermagnesemia, or aminoglycosides. Calcium should be used with caution due to untoward effects during ischemia reperfusion injury. Recent studies have suggested that vasopressin (ADH) may be efficacious at increasing blood pressures in patients with refractory hypotension due to chronic ACE inhibitor therapy, or in patients with hypotension refractory to other agents. An infusion rate of .0005 U/kg/min may be used. Similarly, vasopressin has recently been recommended for use during cardiac arrest given as a bolus IV dose at 0.4 - 0.8 U/kg. Cardiac Rhythm Disturbances Although a marked change in heart rate may not be of concern in and of itself, it often serves as an important sign of other clinical problems that must be identified and treated accordingly. Any heart rate that appears to be outside the "normal" range should be compared to the "normal" heart rate for that animal. A marked increase in heart rate may be detrimental if it prevents adequate ventricular filling or increases myocardial work and oxygen consumption, especially in patients with underlying cardiac disease. Common causes of tachycardia include inadequate anesthesia, inadequate blood volume and poor tissue perfusion, hypercarbia with consequent sympathetic stimulation, and hypoxemia. Bradycardia may be of concern if there are concurrent signs of inadequate tissue perfusion or cardiac arrhythmias, such as ventricular escape beats, occur. Common causes include excessive anesthesia, increased vagal tone due to opioid administration or surgical stimulation, hypoxemia, or hypothermia. Although almost any arrhythmia is possible in the anesthetized patient, those most commonly seen include premature ventricular contractions (PVCs), and second degree AV block. First, determine the significance of the arrhythmia. Identify the rhythm as atrial or ventricular. Was the rhythm pre-existing or did it occur after induction of anesthesia (and, if so, what drugs were used for induction)? How frequently is the arrhythmia occurring and is the frequency changing? Is the arrhythmia multifocal or unifocal (similar in shape and size)? Is the arrhythmia causing a decrease in cardiac output, pulse deficits and/or hypotension? As stated previously, if the animal has an occasional PVC that always arises from the same focus, it probably does not need to be treated, but should be monitored to assure that frequency and/or malignancy does not increase. If the patient has frequent, multifocal PVCs or paroxysmal ventricular tachycardia, lidocaine (1 - 2 mg/kg bolus +/- 0.05 mg/kg/min continuous infusion) is usually the first drug of choice. Second degree AV block and sinus bradycardia are also commonly seen in the anesthetized patient, especially after administering opioids. Although it is frequently unnecessary to treat these rhythm disturbances, if the animal is hypotensive or if ventricular escape beats are occurring due to the slow sinus rate, they may be treated with IV atropine (0.005 - 0.02 mg/kg) or glycopyrrolate (0.0025 - 0.01 mg/kg). Identification and correction of the underlying cause for the arrhythmia is the preferred treatment. POSTOPERATIVE CARE Continued fluid support is often critical in patients with cardiovascular instability, although care should be taken in patients in heart failure. Supplemental oxygen is occasionally indicated. Effective analgesia with minimal cardiovascular side effects is also important. It is now known that postoperative pain may actually delay recovery due to significant negative physiologic side effects including immobility, decreased pulmonary function, autonomic nervous system changes and increased oxygen consumption, stress hormone release, inappetance and insomnia. Most importantly, postoperative pain leads to patient suffering. Opioids Opioids are generally preferred for postoperative analgesia in the critical patient due to their preservation of cardiac function. Watch for respiratory depression. They may be used epidurally, intrathecally or systemically to inhibit pain transmission from the dorsal root to higher centers in the somatosensory cortex or to modulate the perception of pain at the level of higher centers. Pure opioid agonists (including morphine, hydromorphone, oxymorphone, and fentanyl) bind to all of the opioid receptors and provide the most profound analgesia. However, the side effects may also be pronounced, especially in debilitated animals. Opioid agonist-antagonists and partial agonists, such as butorphanol and buprenorphine, generally provide less analgesia than pure opioid agonists, but the side effects also tend to be less severe. Therefore, their use may be preferred in certain situations. Butorphanol, a kappa agonist, is generally considered a mild to moderate analgesic, although it has proven effective in models of visceral pain. The duration of analgesia, however, is relatively short (45 minutes - 1 hour). Buprenorphine, a partial mu agonist, provides effective analgesia for many types of procedures and has a relatively long duration of action. However, due to its high affinity for the mu receptor, undesirable side effects may be difficult to reverse with naloxone. One of the difficulties in using one of these agents, rather than a pure agonist, is the presumed bell shape of the dose response curve. For example, butorphanol can act as a mu antagonist at higher concentrations and analgesia may actually decrease at higher doses. Buprenorphine has a similarly shaped dose response curve. In addition, administration of these agents may partially reverse analgesia provided by previously administered pure agonists Alternative routes of opioid administration, such as epidural or intraarticular, are being used with increasing popularity. Since systemic levels of the drug tend to be lower, side effects tend to less severe. Transdermal fentanyl patches are also used for long term pain relief. However, animals should be closely monitored for signs of nausea and inappetance, depression and dysphoria. Before administering an opioid (or any other drug), carefully observe the animal and consider the underlying disease process. If any expected side effects are undesirable, excessive or potentially life-threatening alter your analgesic technique. For systemic administration, hydromorphone (0.05 - 0.2 mg/kg) or oxymorphone (0.02 - 0.1 mg/kg) IV or IM are generally preferred if CV stability is a concern and can provides adequate pain relief for 2 - 4 hours. Morphine is more sedative than oxymorphone at equianalgesic doses and provides pain relief for 4 - 6 hours; however it should not be used IV as a bolus in critical patients due to the possibility of histamine release with secondary hypotension. Therefore, it is generally given SQ or IM or as a continuous low-dose infusion (0,05 - 0.1 mg/kg/hr). Do not use in patients that are vomiting or where GI ulceration is a concern. Butorphanol (0.1 - 0.5 mg/kg) and buprenorphine (0.006 - 0.02 mg/kg) may be less respiratory depressant than the other opioids. Butorphanol may be useful in patients that are vomiting (it has been shown to be an effective anti-emetic in human patients receiving chemotherapy), although it should only be used in situations of mild to moderate pain. Local Anesthetics (lidocaine, bupivacaine) Lidocaine and bupivacaine are local amide anesthetics frequently used in veterinary medicine. These drugs act by blocking the sodium channel in the neuronal membrane, inhibiting action potential generation and propagation. Local anesthetics are extremely useful for providing analgesia for pain arising in discrete locations. Bupivacaine has a longer duration of action than lidocaine (8 hr vs. 2 hr, respectively). Bupivacaine may be infiltrated around the intercostal nerves or given interpleurally to provide analgesia after thoracotomy. For interpleural administration, the dog is placed incision side down before the bupivacaine (1.5 mg/kg of a 0.5% preservative-free bupivacaine solution) is administered via the chest tube or a pediatric feeding tube placed specially for this purpose. The local anesthetic diffuses across the parietal pleura and allows repeated block of the intercostal nerves (every 4 - 6 hours). Lidocaine may also be used but has a shorter duration of action. 0.1 mEq of sodium bicarbonate may be added to an ml of the local anesthetic to reduce the pain on injection. Perineural drug infiltration is also useful for other painful procedures such as amputation. Local anesthetics may also be given intraarticularly (0.3 ml/kg of a 0.5% preservative-free bupivacaine solution) at the time of surgery, and most dogs will not require further analgesics. These drugs may also be administered epidurally or intrathecally. The site for epidural injection in small animal patients is usually the lumbosacral intervertebral space. It is important to remember, however, that when local anesthetics are used, autonomic and motor nerves will be blocked in addition to the sensory blockade. Nerve fibers are affected in proportion to their diameter, the small diameter fibers being affected more rapidly and by lower concentrations of drug. Therefore, sympathetic nerves will be blocked most readily. Vasodilation is commonly seen after epidural administration of local anesthetics, and may cause hypotension in hypovolemic patients. The sympathetic block will extend a couple of dermatomes cranial to the sensory block, potentially causing significant respiratory and cardiovascular side effects. As the dose or concentration of local anesthetic is increased, progressively larger nerves (e.g. motor neurons) become blocked and the cranial extent of the block will increase. Contraindications to epidural injection include hypovolemia and septicemia, coagulopathy, and local skin infection at the site of injection. To achieve a sensory block using bupivacaine, 0.2 ml/kg of 0.25% - 0.5% bupivacaine is given. To achieve a sensory block using lidocaine, 0.2 ml/kg of 2% lidocaine is given (this usually blocks to L1 in a lean, middle-aged dog). The onset of action for epidural lidocaine is relatively rapid (5 to 10 minutes) vs. bupivacaine (15 - 20 minutes), but lidocaine has a shorter duration of action. When given epidurally, local anesthetics are often administered in combination with an opioid (e.g. 0.1 ml/kg 0.5% bupivacaine is generally mixed with 0.1 ml/kg morphine (0.1%, preservative free) and injected at the lumbosacral junction - this combination provides pain relief for up to 24 hours. If cardiovascular stability is a concern or if a higher block is required, the local anesthetic is generally removed from the solution and a pure opioid epidural (e.g. 0.1 ml/kg morphine diluted to 0.2 - 0.3 ml/kg with sterile saline) is used instead. Bupivacaine (0.3 ml of a 0.5% solution) or lidocaine (2mg/kg) may be useful intraperitoneally to decrease inflammation and provide pain relief in some situations (e.g. pancreatitis). Lidocaine (2 mg/kg/h) may also be given as a continuous intravenous infusion, either alone or in combination with morphine or morphine and ketamine, as an adjunct to other methods of analgesia. Bupivacaine should NEVER be used intravenously. Topical administration of lidocaine is efficacious, but care should be taken due to the potential for systemic absorption (especially in cats). EMLA cream is a topical anesthetic consisting of a lidocaine-prilocaine combination. More recently, lidocaine transdermal patches (similar to those containing fentanyl) have been recommended to provide analgesia at discrete areas of injury. Care must be taken when using these drugs by any route, due to their relatively high systemic toxicity. Toxic cardiovascular and neurologic effects (i.e. convulsions) may be seen at doses relatively close to the effective dose. Arrhythmias and myocardial depression from local anesthetics, particularly bupivacaine, can be extremely difficult to treat. The IV seizure dose for lidocaine in dogs has been reported as 11 mg/kg, while that for bupivacaine is 3 mg/kg. Cardiotoxic doses are slightly higher than the seizure dose. These agents rely on hepatic metabolism; therefore, adjustments should be made in patients with liver disease. In addition, half-lives are longer in cats and toxic doses are lower than for dogs. There are no available reversal agents. Non-steroidal Antiinflammatory Agents (NSAIDs) Nonsteroidal anti-inflammatory agents are usually avoided in patients with cardiovascular instability, due to an increased potential for nephrotoxicity and hepatotoxicity during low flow situations. PERIOPERATIVE ANALGESICS
OPIOIDS
ADJUNCT THERAPY
Anesthetic Approach to the Patient with Respiratory Compromise PREOPERATIVE EVALUATION Patients with respiratory disease include those with upper airway disease and an inability to ventilate and those with primary lung disease and an inability to oxygenate. In addition, some patients with intrathoracic disease such as diaphragmatic hernia have difficulty both ventilating and oxygenating. Patients are handled slightly differently depending upon the primary problem, although preoperative manipulations in both groups should occur with a minimum of stress or excitement. Oxygen supplementation is frequently required while the patient is being assessed. Administration of at least 30 - 35% oxygen using a face mask, nasal cannula or oxygen cage is recommended to prevent hypoxemia secondary to hypoventilation Recognition of hypoventilation is often difficult clinically, but includes changes in respiratory rate and effort, hyperemia due to peripheral vasodilation and signs associated with sympathetic stimulation due to increased CO2. Surgical patients commonly at risk include those presenting with airway disease (laryngeal paralysis, neoplasia, collapsing trachea) as well as brachycephalic breeds presenting for any condition. Accurate assessment of ventilatory status requires measurement of PaCO2 , with normal values being between 35 - 45 mmHg. A venous blood gas (PvO2 < 45 - 50 mmHg) can be helpful in ruling out a diagnosis of hypoventilation, although increases in PvCO2 can be caused by decreased tissue perfusion as well as hypoventilation. Non-invasive estimates of ventilatory status can also be made by measuring end-tidal CO2 using a capnograph. There is some variability in the correlation between end tidal and arterial CO2, especially in patients that are hemodynamically unstable, but end-tidal CO2 generally runs 5 - 10 cm H2O lower than arterial CO2 . This difference may increase significantly with increased dead space ventilation. Recognition of hypoxemia can also be difficult clinically. An increase in respiratory rate and effort is often present in the awake animal at PaO2 values < 60 mmHg. Heart rate initially increases in an attempt to increase cardiac output and oxygen delivery to the tissues, but as hypoxemia becomes more severe, myocardial depression and bradycardia result. Cyanosis of the mucous membranes can usually be detected at an arterial oxygen saturation around 85%, which equates with a PaO2 of approximately 50 mmHg. Although accurate assessment of PaO2 requires an arterial blood gas, changes in oxygen saturation can be measured with a pulse oximeter. Pulse oximetry is a noninvasive monitoring technique that measures oxygen saturation of hemoglobin in the arterial blood by measuring the differential transmission (or absorption) of light at two different wavelengths, 660 nm (red) and 940 nm (infrared). Oxygen saturations should remain > 95% in patients with a PaO2 of 85 mmHg or greater. An oxygen saturation of 90% is roughly equivalent to an arterial oxygen tension of 60 mmHg. Common sites for placement of the probe include the tongue, ear, flank, tail base and rectum. PREMEDICATION All anesthetic agents depress respiration to a greater or lesser degree. Before administering any agent, may sure you are familiar with its effects. The choice of anesthetic agent depends on the underlying disease process and the patient's ability to oxygenate and ventilate. Stress during patient handling should be avoided if possible. Premedication is not required if an intravenous catheter can be placed with minimal stress to the patient. Thoracocentesis should be performed to help stabilize the respiratory system in patients with pleural fluid or air showing signs of respiratory distress. Respiratory depressants, such as opioids, should be used judiciously in patients with severe hypoxemia or upper airway obstruction and patients closely monitored after administration. Patients with upper airway disease are frequently anxious, with the increased respiratory effort often resulting in a vicious cycle of increased airway obstruction and patient distress. A complete preoperative examination is frequently difficult to perform without additional stress. Supplemental oxygen should be provided to prevent hypoxemia secondary to hypoventilation. Premedication with acepromazine can be useful in calming the patient without causing significant respiratory depression, although deep sedation should be avoided. Low doses (0.02-0.04 mg/kg IM) should be used if a complete physical examination can not be performed without further stress to the patient. Acepromazine can result in vasodilation and hypotension, so care should be taken in patients that are cardiovascularly unstable. In dogs with brachycephalic syndrome (stenotic nares, elongated soft palate, everted laryngeal ventricles, and/or hypoplastic trachea), premedication may result in relaxation of the pharyngeal musculature, causing severe upper airway obstruction. Ketamine may be used in cats requiring premedication. Ketamine also acts as a bronchodilator and may be useful in patients with feline asthma Every animal presenting with upper airway obstruction should be closely monitored after administration of any anesthetic agent. INDUCTION Preoxygenation in these patients is extremely important! Patient positioning may also be important (e.g. in the patient with diaphragmatic hernia). Keep the good side up (or at least try to maintain sternal recumbency) to aid ventilation! Anesthetizing a patient that cannot ventilate due to airway obstruction is among the most potentially catastrophic inductions you may experience. Remember the ABC's of CPR...Airway, Breathing.......Induction of the animal having difficulty ventilating due to airway obstruction generally involves a rapid sequence intravenous technique and intubation. A mask induction can lead to unwanted excitement and additional respiratory distress. NEVER assume that intubation will be possible. An assortment of endotracheal tubes should be available and occasionally requires some ingenuity. Premeasurement of tube length is important to ensure proper positioning of the tube beyond the lesion, if the site of obstruction is known. Tubes may need to be of much smaller diameter than usually required for the size of the animal. A tracheostomy set should be readily available in case intubation is not possible. Most patients will spontaneously ventilate once the endotracheal or tracheostomy tube has been placed, bypassing the site of obstruction. Opioids should be used judiciously or avoided altogether for induction in patients with airway obstruction when intubation may be difficult or impossible. In these patients, induction with low doses of propofol (e.g. slow administration of 1 mg/kg boluses to effect) +/- diazepam (0.25 - 0.5 mg/kg) or ketamine (2-5 mg/kg) and diazepam.may be preferred. Application of 2% lidocaine to the laryngeal area using an aerosolizer or syringe may help in cats to decrease laryngospasm and trauma on intubation. In patients with hypoxemia, but no airway obstruction, a combination of an opioid (oxymorphone (0.05 - 0.2 mg/kg), hydromorphone (0.1 - 0.2 mg/kg) or fentanyl (2.5 - 10 ug/kg)) and benzodiazepine(diazepam or midazolam 0.2 - 0.5 mg/kg) is useful in allowing a slow, carefully controlled induction with minimal cardiovascular side effects. If a rapid sequence induction is preferred, propofol, ketamine, thiopental, or etomidate may be used in place of, or in addition to, the opioid. Anesthesia is generally maintained with inhalant anesthesia and 100% oxygen. Nitrous oxide should be avoided in patients that are hypoxemic. MAINTENANCE Inhalants are generally used for anesthetic maintenance, since intubation and supplemental oxygen are critical in the majority of patients. Halothane causes less airway irritation and less ventilatory depression than isoflurane, sevoflurane or desflurane. If the site of airway obstruction or tracheal rupture cannot be bypassed, or if the surgical site precludes the use of an endotracheal tube, oxygen may be provided using a small diameter tube and high flows of oxygen (1-7 L/min). Anesthetic maintenance in these cases is achieved with low doses of anesthetic agent, such as propofol and diazepam or ketamine and diazepam, titrated slowly to effect in an attempt to minimize respiratory depression. VENTILATORY SUPPORT Ventilatory support is critical in these patients. Anesthesia of the patient with decreased ventilation or oxygenation should include intubation and delivery of supplemental oxygen. Mechanical ventilation, usually in the form of intermittent positive pressure ventilation (IPPV) is frequently required. Usually, a rate of 8 - 15 breaths per minute is used. Tidal volumes are set at 10 - 20 ml/kg, with maximum airway pressures usually limited to 15 - 20 cm H2O. Higher pressures may be required with some conditions to provide adequate tidal volumes. In patients with pulmonary disease, adjustment of peak airway pressures may be necessary to prevent barotrauma, since the lungs are frequently more susceptible to injury. Positive pressure delivered to the thoracic cavity can decrease venous return and cardiac output, especially if the patient is volume deplete. Therefore, the ratio of inspiratory time to expiratory time is generally limited to a ratio of 1:2 or 1:3. If the patient resists mechanical ventilation, an increase in anesthetic depth or use of neuromuscular blockers, such as atracurium or pancuronium, may be required. In patients requiring a thoracotomy, PPV is required when the thorax is opened to prevent hypoxia, hypoventilation, and respiratory acidosis . Treatment of hypoxemia includes delivery of 100% oxygen. Positive end-expiratory pressure (PEEP) may be necessary in patients that remain hypoxemic on 100% oxygen. Maintenance of airway pressure at end-expiration improves oxygenation by increasing alveolar volumes and recruiting collapsed alveoli, changing areas receiving no ventilation (shunt) to areas of low V/Q, which are then responsive to the delivery of supplemental oxygen. Airway pressures of 5 - 15 cmH2O are usually used. Purpose-made PEEP valves are available or, alternatively, the scavenging hose from the pop-off valve may be restricted to produce the desired pressure. Administration of PEEP may cause hypotension due to decreased venous return and cardiac output. The decrease in blood pressure, in conjunction with the increase in alveolar pressure, can lead to increased dead space ventilation. Therefore, the effects of PEEP on oxygenation can be optimized by concurrent administration of an inotrope such as dobutamine. INTRAOPERATIVE MONITORING Close monitoring of the respiratory system is important in these patients, whether or not a thoracotomy is being performed. Respiratory rate and depth, and mucous membrane color should be watched carefully. Oxygen saturations as measured by pulse oximetry should remain > 95% in patients on 100% oxygen. Measurement of end-tidal CO2 with a capnograph is helpful in assuring adequate ventilation. Use of a spirometer, which measures tidal volume, will also help in assessing the adequacy of ventilation. Respiratory minute volume = tidal volume x breaths per minute. Blood gas analysis, where available, is extremely helpful in assessing respiratory status. Close monitoring of the cardiovascular system is also very important in these patients. Heart rate, peripheral pulse quality and mucous membrane color and capillary refill time should all be observed closely. An esophageal stethoscope may be useful for monitoring heart rhythm. Use of an electrocardiogram is helpful, especially in patients with cardiac arrhythmias. Blood pressure may be measured indirectly with a Doppler ultrasonic flow probe or an oscillometric measuring device. Direct measurements are made using an arterial catheter, usually placed in the dorsal metatarsal or femoral artery. POSTOPERATIVE CARE AND MONITORING Continued evaluation of respiratory function is critical in the post-operative period. In many patients, extubation may be more difficult than intubation. Any patient at risk for upper airway obstruction must be closely monitored during recovery. The airway must be supported until the patient demonstrates an ability to maintain an unobstructed airway. Corticosteroids are given in some cases to decrease postoperative inflammation and swelling. Ventilation is generally depressed for some time in the postoperative period due to the persistence of anesthetic drugs, including inhalants, barbiturates and opioids, and hypothermia. Oxygen should be administered until extubation and may need to be supplemented post-extubation until the patient demonstrates an ability to maintain ventilation. Post-obstruction pulmonary edema may also contribute to hypoxemia during recovery. Suctioning of blood and other material from the pharyngeal area prior to extubation in patients recovering from nasal, pharyngeal and/or laryngeal surgery will decrease the risk of aspiration. The endotracheal tube can be gently removed in these cases with the cuff partially deflated and the head placed down. Recovery should as quiet and stress free as possible. Acepromazine may be helpful for many of these patients in the immediate postoperative period, although relaxation of the pharyngeal area may hinder ventilation in some brachycephalic patients. Extension of the neck and exteriorization of the tongue may help to maintain a patent airway in some cases. Opioids may be used post-operatively, but may also contribute to hypoventilation. Opioid agonist-antagonists (e.g. butorphanol) cause less respiratory depression, but are also less potent analgesics. Alternative methods of analgesia may be preferred. Patients undergoing thoracotomy require additional consideration. Lungs are normally reinflated prior to thoracic closure unless compression has been present for several days (e.g. chronic diaphragmatic hernia). Pneumothorax is a common post-operative complication in patients undergoing thoracotomy. Thoracotomies are considered highly painful procedures and adequate post-operative analgesia is essential to encourage adequate ventilation. Patients with inadequate pain relief may breathe with smaller tidal volumes which predisposes to hypoventilation, atelectasis, and hypoxemia. Systemic opioids may be used post-operatively, but may contribute to hypoventilation. Opioid agonist-antagonists, such as butorphanol, or partial agonists, such as buprenorphine, cause less respiratory depression, but may not provide adequate analgesia. Epidural morphine (0.1 mg/kg of a preservative-free solution diluted to 0.3 ml/kg and administered at the lumbosacral junction) may also be used for analgesia in the post-thoracotomy patient. Pain relief is comparable to that with systemic opioids, with fewer systemic side effects. Alternative methods of analgesia may be preferred or used as an adjunct therapy. Intercostal nerve blocks using 1 - 2% lidocaine (total dose up to 4 mg/kg) or 0.25 - 0.5% bupivacaine (1.5 mg/kg) may be used after lateral thoracotomy. Bupivacaine is preferred, since it provides a longer duration of analgesia than lidocaine (6-8 hours vs. 1-2 hours, respectively). Normally, two intercostal spaces on either side of the incision are blocked, due to overlap of the nerve supply. The block may be performed on entry into the chest and help with analgesia throughout the anesthetic period. Intercostal nerve blocks are difficult to repeat once the incision is closed and the patient is awake, with inadvertent laceration of an intercostal vessel or pneumothorax resulting. Interpleural lidocaine (2% lidocaine, 2-4 mg/kg) or bupivacaine (0.5% bupivacaine, 1.5 mg/kg) may be infused via a pediatric feeding tube placed for this purpose or via the chest tube. The patient in placed with the incision side down as the local anesthetic is infused and left in that position for up to five minutes so that the anesthetic can diffuse across the parietal pleura and block the intercostal nerves. Interpleural administration of local anesthetic may also provide analgesia for the patient undergoing median sternotomy. Opioids for Analgesia The use of analgesics has increased dramatically in veterinary practice over the last several years, as the awareness of pain and its detrimental effects in our patient population has increased. Traditionally, it was believed that some pain persisting into postoperative period was beneficial, encouraging immobility and, therefore, healing and recovery. We now know that postoperative pain may actually delay recovery due to significant negative physiologic side effects which far outweigh any potential benefits. These include immobility, decreased pulmonary function, catecholamine release and increased oxygen consumption, stress hormone release, inappetance and insomnia. Most importantly, postoperative pain leads to patient suffering. The use of analgesics is especially important in critical patients where any negative physiologic effects may have a profound impact on outcome. Assessment of Pain Pain is, by definition, a subjective experience and can be quite difficult to quantify, especially in our veterinary patients where we are obviously limited in terms of verbal communication. However, some basic strategies can be followed to help manage pain in our patients. 1) Learn to Anticipate Learning to anticipate when a patient will be painful is extremely useful, since pain is much easier to manage if the patient is treated before they become painful and upset, then if they are treated afterward. Frequently, knowing the patient's underlying disorder, whether or not a procedure has recently been performed, and, if so, what type will guide your use of analgesics. Most patients going to surgery at the University of Pennsylvania receive some sort of analgesic before awakening. Usually, analgesics are given before surgery to take advantage of pre-emptive analgesia: that is, providing analgesia before causing pain. Research in both man and animals suggests that this actually decreases the amount of analgesics required post-operatively. Certain procedures are considered "high pain" procedures, and the need for profound analgesia should be anticipated. These include thoracotomies, proximal joint surgeries, many ophthalmologic procedures, aural surgery and any surgery involving a lot of tissue trauma. In addition, an inexperienced surgeon may cause more tissue trauma, and consequently more pain, than an experienced surgeon. Remember that very young and very old patients, as well as critically ill patients, tend to be less tolerant of pain and the neurohormonal and autonomic changes associated with pain. 2) Observe When assessing the degree of pain in your patient, you should first observe the patient. This should be done with the patient both on its own and while interacting with others. Is the patient displaying one or more signs indicative of pain? This includes both physiologic signs associated with sympathetic nervous system stimulation (increased heart rate, respiratory rate, blood pressure and temperature, salivation and dilated pupils) as well as other signs such as vocalization, restlessness and agitation, resenting handling of the area, depression and inactivity, insomnia or reluctance to lie down, inappetance, aggression, abnormal posturing, disuse or guarding, licking and chewing at the painful area, trembling and facial expression. Most people tend to focus on vocalization and agitation as signs of pain. Unfortunately, these two behaviors are frequently the least specific, especially in the postoperative period when many animals are disoriented or excited due to the anesthetic drugs that were used. Cats are especially difficult to assess for pain. Analgesics are frequently overlooked in feline patients, since they tend not to vocalize. Most cats will merely sit quietly in the back of the cage and not move when they are painful. They may be inappetent, insomnolent, or mildly pyrexic. A dramatic improvement in attitude and appetite may be seen after administering analgesics. 3) Reevaluate Veterinary patients frequently require analgesics for a period of time after surgery. Close attention should be paid as to whether the initial treatment provides the desired effect (i.e. analgesia!) and how long the analgesic effect lasts. Reevaluate the effectiveness of treatment regularly! Do not wait for obvious signs of pain before repeating the treatment, unless you feel that the side effects are excessive. Before administering any drug, carefully observe the animal and consider the underlying disease process. If any expected side effects are undesirable or potentially life threatening, alter your analgesic technique. Treatment - Opioids Opioids are frequently used for pain control in veterinary patients. Opioids are a diverse group of agents that are classified together due to their affinity for the opioid receptors and produce analgesia by their actions on specific opioid receptors (mu, kappa, delta). These receptors vary in their pharmacological effects (although all three produce analgesia) and their distribution throughout the body. Mu and kappa effects are responsible for much of the analgesia seen after exogenous opioid administration. Delta receptors are located primarily within the spinal cord and are important binding sites for endogenous opioids, such as the enkephalins. Pure opioid agonists, including morphine, oxymorphone, hydromorphone, fentanyl and meperidine bind to all of these receptors and provide the most profound analgesia. However, the side effects may also be pronounced, especially in the debilitated patient. Opioid agonist-antagonists and partial agonists (butorphanol, buprenorphine) generally provide less analgesia than pure opioid agonists, but the side effects also tend to be less severe. Therefore, their use may be preferred in certain situations. Butophanol, a kappa agonist, is generally considered a mild to moderate analgesic, although it has proven effective in models of visceral pain. Buprenorphine, a partial mu agonist, provides effective analgesia for many types of orthopedic procedures and has a relatively long duration of action. However, due to its high affinity for the mu receptor, undesirable side effects may be difficult to reverse with naloxone. One of the difficulties in using these agenst, rather than a pure agonist, is the bell shape of the dose response curve. For example, butorphanol also acts as a mu antagonist (or partial agonist) and anlagesia may actually decrease at higher doses. This antagonistic effect should be kept in mind when considering their use in conjunction with a pure agonist (e.g. in conjunction with a transdermal fentanyl patch!) Administration of these agents may partially reverse the effects of previously administered pure agonists. This may be advantageous if the effect you are trying to reverse is sedation or respiratory depression. Unfortunately, it will also reverse some of the analgesia. Side Effects Opioids are most frequently given systemically. Although most opioids are relatively sparing of the cardiovascular system, opioid administration may produce other clinically significant side effects. These include sedation, dysphoria or excitement, respiratory depression, hypotension, and vomiting. Therefore, parenteral use of these agents requires a thorough knowledge of both their potential benefits and shortcomings. Alternative routes of opioid administration, such as epidural or intraarticular, are being used with increasing popularity. Since systemic levels of the drug tend to be lower, side effects tend to be less severe. Sedation All of the opioids cause a certain degree of sedation. This may be helpful if an animal has not been able to sleep due to pain, stress, etc. However, overzealous use of opioids may cause the patient to become excessively sedate and unarousable. Excitement or dysphoria Many animals become excited on emerging from general anesthesia. This is especially true if they have received opioids during the anesthetic period. Cats may get excited when given pure opioid agonists, but are less likely to get excited with butorphanol or buprenorphine. If your patient becomes excessively dysphoric or excited after giving an opioid, a sedative such as acepromazine or diazepam may be required, although other side effects such as respiratory depression or hypotension may be exacerbated. Respiratory Depression Respiratory depression is one of the more serious complications of systemic opioid administration. All of the opioids are respiratory depressants, causing a shift in the CO2 ventilatory response curve. Respiratory depression may be exacerbated by concomitant administration of other drugs such as diazepam. For this reason, opioids should be used with close monitoring after thoracotomy. Analgesia needs to be effective both for patient comfort and to improve ventilation by encouraging normal respiration, thereby decreasing the risk of pulmonary atelectasis and ventilation/perfusion abnormalities. However, ventilation also must be closely monitored if giving a respiratory depressant. Do not mistake panting with effective ventilation. Look carefully at the depth of each breath as well as the rate. Increased CO2 as a result of respiratory depression also causes cerebral vasodilation and increased intracranial pressure. Therefore, opioids should not be used in patients with head trauma or intracranial lesions unless they are being ventilated. In addition, sedation may make neurologic assessment more difficult. Hypotension Although most opioids are relatively sparing of the cardiovascular system, they must be used with care, especially in debilitated patients. In addition, there are some differences between the various drugs. Most opioids may cause a vagally-mediated bradycardia which is easily treated with anticholinergics (e.g. atropine). Oxymorphone, hydromorphone and fentanyl tend to provide the most cardiovascular stability of the opioids commonly used as analgesics in veterinary medicine. Both morphine and meperidine given IV may cause hypotension secondary to histamine release and vasodilation. This is quite pronounced with meperidine and this drug should not be given IV. If there are other reasons histamine release may be contraindicated in your patient (e.g. mast cell tumor, GI ulceration), morphine and meperidine should be avoided. Meperidine is not commonly used for post-operative analgesia due to its relatively short duration of action (< 1 hr). Remember that hypotension after opioid administration may be exacerbated by concomitant administration of other drugs (e.g. diazepam). Nausea and vomiting Opioids cause stimulation of the medullary chemoreceptor trigger zone for emesis. When used as a premedication, some opioids (e.g. morphine) are especially prone to causing vomiting. This is usually not as common when using opioids post-operatively, but may be difficult to differentiate from other causes of vomiting (e.g. pancreatitis). If vomiting is a concern, butorphanol is a good alternative due to its anti-emetic properties. Sometimes the patient will show prolonged or excessive side effects from a previous treatment. In this case, consider alternative methods of analgesia before repeating systemic opioid administration. Other opioid agonists or partial agonists, epidural administration of opioids, regional analgesia with lidocaine or bupivacaine, or administration of nonsteroidal antiinflammatory agents may provide alternative solutions. If you have not achieved the desired analgesic effect at the high end of the dose, change your analgesic protocol! If undesirable side effects should occur after opioid administration, the opioid can be reversed by giving naloxone (0.01 - 0.02 mg/kg IV or IM). Buprenorphine may be difficult to reverse and require up to 10X the naloxone dose. Opioid reversal with naloxone will also remove the analgesia. Therefore, it is usually preferable to titrate the dose of naloxone by using smaller boluses (one-eighth to one-quarter of the usual dose) until the desired effect is achieved. Alternatively, small doses of butorphanol (0.05 mg/kg) may be titrated to reverse some of the sedative effect of a pure opioid agonist, while retaining some of the analgesia by enhancing the kappa effects. Pure Opioid Agonists (Schedule II):
Transdermal fentanyl patches Transdermal fentanyl patches are being used with some regularity in veterinary patients. They are marketed for use in human patients with chronic pain disorders. The respiratory depression caused by the fentanyl is clinically significant when used in the post-operative period in humans and has led to death. Respiratory depression does not appear to be as severe in dogs. Other side effects that have also been reported include nausea, vomiting, inappetance, sedation and bradycardia. The patch must be applied for 12-24 hrs before therapeutic drug levels are achieved. 25, 50, or 100 ug/hr size patches are used depending on the size of your patient. There is considerable individual variation in drug absorption. Therefore, patients should be monitored both for analgesia and side effects. Some patients may require additional analgesics. If side effects do occur, systemic drug levels decrease rapidly after the patch is removed. Epidural administration of opioids Epidural administration in small animal patients is generally made in the lumbosacral space. Morphine: 0.1 mg/kg of a 1 mg/ml preservative-free solution (e.g. DuraMorph ) diluted to 0.2 or 0.3 ml/kg (for thoracotomy) with sterile saline - delayed onset (2 - 4 hr), long lasting (24 hr) Morphine and Bupivacaine: 0.1 mg/kg of a 1 mg/ml preservative-free solution (e.g. DuraMorph ) and 0.1 ml/kg of 0.5% bupivacaine. This particular combination is the one most frequently used at the University of Pennsylvania. The bupivacaine begins to work within the first 30 minutes and lasts about 8 hours, while the morphine's peak effect occurs about 4 - 8 hours after administration and lasts 24 hours Oxymorphone: 0.1 mg/kg - lasts 10 hours Fentanyl, butorphanol, and buprenorphine have also been proven effective when given epidurally. Intraarticular administration Morphine: 0.1 mg/kg of a 1 mg/ml preservative-free solution diluted up to 0.3 ml/kg with sterile saline Alternatives for Perioperative Analgesia Nociception involves the series of electrochemical events that start at the site of tissue injury and result in the perception of pain. Nociception generally involves at least four distinct processes: 1) Transduction of the noxious stimulus into an electrical stimulus which can then be transmitted by the primary afferent sensory fibers (nociceptors). 2) Transmission of the nervous impulse from the periphery, through the spinal cord and ascending relay neurons in the thalamus to the somatosensory cortex 3) Modulation of the message as it ascends 4) Integration of the above processes with the unique psychology of the individual, resulting in the final experience of pain perception Understanding mechanisms of pain transmission and antinociceptive mechanisms allows a logical choice in prescribing analgesics for our patients. Analgesia may be directed at minimizing inflammatory changes at the site of injury, at inhibiting transduction or transmission of the nociceptive signal (both at peripheral and spinal endings), or at increasing the activity of descending inhibitory pathways. In addition, the processes involved in the perception of pain are no longer viewed as a static system. Long-term changes occur within the peripheral and central nervous system following noxious stimulation, which then alter the body's response to further sensory input. Local Anesthetics Lidocaine and bupivacaine are local amide anesthetics frequently used in veterinary medicine. These drugs act by blocking the sodium channel in the neuronal membrane, inhibiting action potential generation and propagation. Local anesthetics are extremely useful for providing analgesia for pain arising in discrete locations. When used topically, by local infiltration or for regional nerve blocks, these agents act to block transduction and transmission of the primary afferent signal. These agents also may be administered epidurally or intrathecally where they act to block transmission of the nociceptive signal from the dorsal root of the spinal cord to higher centers. Most veterinarians are familiar with local infiltration of these agents for minor surgical or medical procedures (e.g. laceration repair, skin biopsy, bone marrow aspirate). They may also be used to block peripheral nerves as an aid to more involved surgical procedures. Bupivacaine may be infiltrated around the intercostal nerves or given interpleurally to provide analgesia after thoracotomy. For interpleural administration, the dog is placed incision side down before the bupivacaine (1.5 mg/kg of a 0.5% preservative-free bupivacaine solution) is administered via the chest tube or a pediatric feeding tube placed specially for this purpose. The local anesthetic diffuses across the parietal pleura and allows repeated block of the intercostal nerves (e.g. every 4 - 6 hours). Lidocaine may also be used but has a shorter duration of action (2 hours). 0.1 mEq of sodium bicarbonate may be added to a ml of the local anesthetic to reduce the pain on injection. Perineural drug infiltration is also useful for other painful procedures such as amputation. Local anesthetics also may be given intraarticularly (0.3 ml/kg of a 0.5% preservative-free bupivacaine solution for stifle surgery) at the time of surgery, and most dogs will not require further analgesics. Epidural administration These drugs may also be administered epidurally or intrathecally. The site for epidural injection in small animal patients is usually the lumbosacral intervertebral space. Not only is this space relatively easy to access in the small animal patient, but the spinal cord generally ends cranial to the lumbosacral junction, so intradural (subarachnoid) puncture is uncommon. A 20 or 22G sterile spinal needle is used for most small animal patients. Injection is performed using sterile technique. The needle is inserted perpendicular (or angled slightly cranial) to the skin, directly on the midline. In most cases, the bevel of the needle is directed cranially, although it may be directed caudally if a perineal block is intended. Little resistance is encountered once through the skin until the ligamentum flavum is reached. Usually a distinct "pop" is felt as the needle passes through this ligament and into the epidural space. No cerebrospinal fluid or blood should be noted when the stylet is removed from the needle. If the needle is properly placed in the epidural space, there should be no resistance to injection of a small volume (0.5 ml) of sterile saline or air. Subcutaneous swelling may be noted if the needle is placed improperly. The drug is then injected slowly over 60 seconds. If injected too rapidly, the block may become "spotty" and extend further cranially. It is important to remember that when local anesthetics are used, pain fibers are not the only nerves that are blocked. Autonomic and motor nerves will be blocked in addition to the sensory blockade. Nerve fibers are affected in proportion to their diameter, the small diameter fibers being affected more rapidly and by lower concentrations of drug. Nerves running in the sympathetic nervous system are smaller than sensory pain fibers, which, in turn, are smaller that motor fibers. Therefore, sympathetic nerves will be blocked most readily. Vasodilation is commonly seen after epidural administration of local anesthetics, and may cause hypotension in hypovolemic patients. As the dose or concentration of local anesthetic is increased, progressively larger nerves (e.g. motor neurons) become blocked and the cranial extent of the block will increase. The sympathetic block will extend a couple of dermatomes cranial to the sensory block, potentially causing significant respiratory and cardiovascular side effects. Contraindications to epidural injection include hypovolemia and septicemia, coagulopathy, and local skin infection at the site of injection. To achieve a sensory block using bupivacaine, 0.2 ml/kg of 0.25% - 0.5% bupivacaine is given. Higher concentrations may give a motor block. To achieve a sensory block using lidocaine, 0.2 ml/kg of 2% lidocaine is given (this usually blocks to L1 in a lean, middle-aged dog). Larger doses will increase the cranial extent of the block. The onset of action for epidural lidocaine is relatively rapid (5 to 10 minutes). Bupivacaine has a slightly longer onset time (15 - 20 minutes). Lidocaine has a shorter duration of action (1 - 2 hr) than bupivacaine (4 - 8 hrs). Other routes for administration of lidocaine or bupivacaine have also been used to provide analgesia. Bupivacaine (0.3 ml of a 0.5% solution) may be useful intraperitoneally to decrease inflammation and provide pain relief in some situations (e.g. pancreatitis). Lidocaine (2 mg/kg/h) may also be given intravenously as an adjunct to other methods of analgesia. Topical administration of lidocaine is efficacious, but care should be taken due to the potential for systemic absorption (especially in cats). EMLA cream is a topical anesthetic consisting of a lidocaine-prilocaine combination. Care must be taken when using these drugs by any route, due to their relatively high systemic toxicity. Toxic cardiovascular and neurologic effects (i.e. convulsions) may be seen at doses relatively close to the effective dose. Arrhythmias and myocardial depression from local anesthetics, particularly bupivacaine, can be extremely difficult to treat. The IV seizure dose for lidocaine in dogs has been reported as 11 mg/kg, while that for bupivacaine is 3 mg/kg. Cardiotoxic doses are slightly higher than the seizure dose. These agents rely on hepatic metabolism; therefore, adjustments should be made in patients with liver disease. In addition, half-lives are longer in cats and toxic doses are lower than for dogs. There are no available reversal agents. Non-steroidal Antiinflammatory Agents (NSAIDs) Non-steroidal antiinflammatory agents (NSAIDs) are a heterogeneous group of agents classified together due to their ability to inhibit the cyclooxygenase pathway of arachidonic acid metabolism. Cyclooxygenase (COX) products include the "classic" prostaglandins such as PGE2 and PGF2 , prostacyclin (PGI2) and thromboxane A2(TxA2). Lipoxygenase products include leukotrienes, such as the chemoattractant LTB4 and the bronchoconstrictors LTC4 and LTD4. Prostanoids and leukotrienes, known collectively as eicosanoids, participate in a number of key physiologic functions, including those underlying inflammation and pain transmission. The particular final product formed depends on the cell type being stimulated, the stimulus, and the presence of specific PG synthases within that cell. For example, the primary product of platelet stimulation is TxA2, a potent platelet aggregator and vasoconstrictor, while the primary product of the endothelial cell is PGI2, which has opposing actions to TxA2. In this way, these products form a series of "checks and balances" and participate in many normal day to day physiologic responses. It is now recognized that there are at least two related, but distinct, isoforms of the COX enzyme, COX-1 and COX-2 (recently, a COX-3 isoform has been identified in the brain). COX-1 is constitutively expressed in most tissues, including the gastric mucosa, liver, kidneys and platelets, and is involved in normal "housekeeping" functions. For example, prostanoid products of COX-1 mediate gastric mucosal barrier protection, maintenance of liver and renal blood flow, particularly in low perfusion conditions such as hypovolemia and/or hypotension, and normal platelet aggregation. In contrast, COX-2 is primarily an inducible enzyme found within a more limited subset of cell types, predominantly inflammatory cells (monocytes, macrophages, neutrophils), endothelial cells, articular chondrocytes and synovial fibroblasts , peripheral nerves and the central nervous system. COX-2 has also been found constitutively within the central nervous system and renal vasculature, as well as synovial chondrocytes in some species. COX-2 derived eicosanoids are increasingly recognized as physiologically important mediators of gastrointestinal, cardiovascular, and renal homeostasis. New information and the availability of new drugs are changing the way that NSAIDs are being viewed as part of the multimodal approach to pain management. Until recently, inhibition of peripheral COX activity and the resulting anti- inflammatory effect, was believed to be the primary mechanism of action through which NSAIDs provided analgesia. However, it is now recognized that a large part of their analgesic effect is due to inhibition of COX activity, more specifically the COX-2 isoform, centrally. Development of newer NSAIDs that target the COX-2 enzyme and "spare" the COX-1 enzyme, result in selective antiinflammatory effects with decreased gastric side effects and minimal effects on coagulation. However, care must still be taken when using these newer drugs and certain GI and renal side effects still occur. For example, COX-2 inhibition may influence ulcer healing because of an effect on angiogenesis. Idiosyncratic side effects may also occur. SIDE EFFECTS NSAIDs will not cause sedation, excitement, respiratory depression, or hypotension when used at therapeutic doses. However, they can cause potentially life-threatening side effects if used excessively. Cats appear especially susceptible to many of these side effects since they do not metabolize most of these drugs as rapidly as dogs. GI ulceration and hemorrhage The most common side effects of non-steroidal use are GI ulceration and hemorrhage, due both to direct irritation of the gastric mucosa and as a sequelae to PG inhibition. This is usually seen with chronic use, but some agents may cause ulceration with perforation after only a few doses and patients should be watched carefully for signs of GI upset (nausea, vomiting) or melena. The incidence of ulceration is greatly increased in patients receiving NSAIDs in combination with steroids or other NSAIDs or in patients with a history of previous GI bleeding. For example, the use of aspirin in combination with other NSAIDs GREATLY increases the incidence of aspirin-induced gastric injury. The GI effects of some NSAIDs may be amplified due to enterohepatic cycling. COX-1 and COX-2 enzymes mediate different protective effects on the gastric mucosa. COX-1 regulates mucosal blood flow, mucous production, acidity of the gastric secretions and turnover of gastric epithelial cells, while COX-2 regulates leukocyte adherence to endothelial cells, an event increasingly believed to be involved in the pathogenesis of NSAID gastropathy. Although COX-2 preferential inhibitors generally cause less GI ulceration than non-selective NSAIDs, signs of GI irritation (vomiting, diarrhea) still occur in about 10% of patients. If GI ulceration is suspected, therapy should be discontinued until healing can occur when switching to another NSAID, since COX-2 inhibition caused by using a selective or non-selective inhibitor can inhibit angiogenesis and decrease the rate of ulcer healing by both PG-dependent and independent mechanisms. Nephrotoxicity Although prostanoids do not play a major role in regulating blood flow in the normal healthy kidney, they become increasingly important in conditions of decreased renal perfusion (e.g. hypotension, dehydrations, anesthesia, pre-existing renal disease). Under these conditions, increased PG production (PGE2, PGI2) results in vasodilation and helps to maintain renal perfusion in low flow states. Therefore, NSAIDs (whether non-selective or COX-2 preferential) should be avoided in hypotensive or critically ill patients or patients with underlying renal disease. Prostanoids also play an important role in sodium and water regulation and NSAID use should be avoided in patients with heart failure or hypertension. Hepatotoxicity Prostanoid production may also play a role in maintaining blood flow to the liver. Hepatotoxicity caused by NSAIDs is generally considered idiosyncratic. Administration of carprofen has been associated with an idiosyncratic, cytotoxic hepatocellular reaction. Anorexia, vomiting, icterus, and elevated liver enzymes may be seen. Most dogs recover with discontinuation of the drug and supportive care. Decreased platelet function NSAIDs inhibit platelet function due to inhibition of TxA2 production. This is a COX-1- mediated event. Therefore, care should be taken if bleeding is anticipated or a primary concern (e.g. preoperatively) This is especially important when using aspirin, since this drug causes irreversible inhibition of the COX enzyme by acetylation and new platelets must be produced before clotting function returns to normal. COX-2 preferential drugs should not affect hemostasis when given preoperatively. However, some concerns have been raised regarding the potential for cardiovascular adverse effects and generation of a prothrombotic state with the use of more selective COX-2 inhibitors, due to inhibition of PGI2 production. While canine patients have better collateral circulation of the coronary vasculature than human patients, use of these agents is not recommended in patients at risk for a hypercoagulable state (e.g. Cushing's disease) Specific NSAIDs Aspirin (acetylsalicylic acid)
Ketamine While traditionally considered a dissociative anesthetic, ketamine has recently been recognized as an N-methyl-D-aspartate (NMDA) receptor antagonist. At low doses, ketamine has been used to decrease central hypersensitization ("wind-up") of the dorsal horn neurons. An infusion rate of 0.1 mg/kg/h may be used as an adjunct to other analgesic therapy such as opioid analgesia (e.g. often given in combination with morphine at a rate of 0.1 mg/kg/hr). At the current time, this dosing regimen appears to be efficacious as an adjunct for patients undergoing amputation or thoracotomy or in pain originating for superficial somatic tissues (e.g. burn patients). Amantadine is an oral NMDA receptor antagonist which has been recommended for occasional use to decrease wind- up in patients with chronic pain (e.g. 3 - 5 mg/kg PO sid for one week) Alpha - 2 Agonists Alpha - adrenoceptors are located in several areas within the spinal cord and brain stem concerned with analgesia. Although alpha-2 agonists (e.g. xylazine, detomidine, medetomidine) have traditionally been given systemically, they also cause sedation and pronounced cardiovascular side effects when given by this route. This includes hypertension secondary to peripheral vasoconstriction, followed by hypotension secondary to a decrease in norepinephrine release and sympathetic outflow centrally, with pronounced decreases in heart rate and cardiac output. They may also cause respiratory depression, emesis, and increased urine production. Therefore, they are not usually used as a first choice of agent for analgesia. Alpha-2 agonists given epidurally or intrathecally, however, can provide analgesia with a decreased incidence of untoward side effects. These drugs have already become popular for epidural use in large animal patients, and are likely to become more popular in small animal patients as well. They are occasionally used as a low dose infusion for patients in the perioperative period. Tramadol Weak mu-agonist. Inhibits NE and serotonin reuptake. Extensively metabolized in the dog to an active metabolite with a much greater binding affinity for the mu receptor. Anesthesia for the Emergency Patient Preoperative Evaluation and Management Evaluation and preparation of the patient prior to anesthesia are critical when managing the emergency patient. On presentation, immediate attention should be paid to the ABC's (airway, breathing, circulation). Evaluation of neurological status, including mental status and evidence of head trauma, should be included. A complete history is obtained if possible. Oxygen supplementation and ventilatory support are given as necessary. Indications for securing an airway early include poor ventilation or oxygenation, changing mental status, or signs of developing airway obstruction. Stabilization of fluid balance and cardiovascular function are essential, although assessing the adequacy of intravascular volume can be difficult due to the effectiveness of compensatory mechanisms. History, presenting complaint, physical examination findings and laboratory results (packed cell volume (PCV) and total solids (TS), blood urea nitrogen (BUN), and blood glucose) must all be considered. Tissue perfusion is assessed by evaluating mucous membrane color and character, capillary refill time, temperature of the extremities and mental status (in the absence of head trauma or underlying CNS disease). Urine production may also be monitored. Blood pressures are measured if possible. Cardiac arrhythmias are common in critically ill patients and are often seen with many conditions requiring emergency surgery, including gastric dilatation/volvulus, hemoabdomen and thoracic trauma. They can also occur secondary to electrolyte abnormalities, hypoxemia, or hypercarbia. Determine the type and significance of any arrhythmias present and treat the underlying cause if possible. The most common arrhythmias are premature ventricular contractions (PVCs). Indications for anti-arrhythmic therapy include frequent, multifocal PVCs or paroxysmal ventricular tachycardia that adversely affects blood pressure. Fluid Therapy Most animals presenting for emergency surgery are hypovolemic, due to preexisting fluid deficits or ongoing losses. The response to intravenous fluid administration should be continually monitored and replacement adjusted accordingly. Isotonic crystalloids are the mainstay of therapy and several commercial solutions similar in composition and indications are available. Approximately 3 mls of crystalloid are required to replace every ml of blood loss. Colloid solutions, including blood products and synthetic solutions, may be used in addition to crystalloids for fluid resuscitation. Colloids help increase the plasma oncotic pressure and allow reduction in the total volume of fluid administered for the same increase in plasma volume (1 ml of colloid for each ml of blood loss). Several different synthetic colloid solutions are available, including high molecular weight dextrans and hetastarch solutions. Disadvantages to their use include allergic reactions and coagulopathies. Blood or blood products should be administered as needed. Fresh frozen plasma may be used not only for intravascular volume replacement, but for replacement of albumin, coagulation factors, and other important plasma proteins. Plasma is generally given at a dose of 6-10 ml/kg for initial resuscitation. Disadvantages for volume replacement include limited availability, expense, and the relatively transient nature of the oncotic effect. A PCV > 25% helps to assure adequate oxygen delivery to the tissues, especially if perfusion is decreased. Newer synthetic oxygen-carrying solutions have become recently available if fresh whole blood or packed RBCs are not available. When time and the animal's condition permits, any electrolyte abnormalities should be normalized prior to the induction of anesthesia. Mildly elevated or decreased values generally do not represent a contraindication to anesthesia. Severe hyperkalemia (potassium > 6.0 mMol/L) is frequently seen and is among the most potentially life-threatening, due to effects on cardiac conduction. Preoperative Drug Selection Pre-operative sedation is usually unnecessary in the compromised patient. In addition, it is difficult to predict the effect of IM drug administration on cardiopulmonary function in depressed patients, and the effects may be much more pronounced than desired. Sedation may be helpful in patients with severe respiratory distress. Opioids (oxymorphone, hydromorphone) If pre-operative sedation is necessary, opioids are generally a good option since cardiovascular function is well maintained and they provide excellent analgesia. Oxymorphone (0.05 - 0.1 mg/kg) or hydromorphone (0.1 - 0.2 mg/kg) may be used. Although opioids are relatively sparing of the cardiovascular system, they can cause respiratory depression, decreasing sensitivity to increased CO2 concentrations. Therefore, they should be used only after careful consideration if respiratory depression is contraindicated, as in cases with airway obstruction or increased intracranial pressure. Other clinically significant side effects include vomiting and decreased GI motility. If undesirable side effects should occur, the opioid can be reversed using naloxone (0.01 - 0.02 mg/kg IV or IM). Benzodiazepines (diazepam, midazolam) These drugs, are mild tranquilizers and cause minimal cardiopulmonary depression. They are not generally used alone as a premedication, since the result may be unpredictable and the animal may become more difficult to handle. They are most commonly given in combination with other drugs to increase their effect. Both drugs have similar effects and are given at similar dose ranges (0.2 - 0.5 mg/kg IV or IM), although midazolam is preferred for intramuscular use since it is water soluble and readily absorbed from intramuscular sites. Diazepam is metabolized to active metabolites that can cause a prolonged duration of action in some animals. These effects are readily reversed using the benzodiazepine antagonist flumazenil. Ketamine Ketamine is a dissociative anesthetic with a rapid onset of action after IM injection. It is often used as a premedication in healthy cats, but rarely used in dogs as it may cause seizure-like activity and muscle rigidity. Although ketamine is generally considered cardiovascularly sparing, it can have a variable effect, depending upon the patient's status. Increases in heart rate, cardiac output and blood pressure depend upon a centrally-mediated sympathetic response and endogenous catecholamine release. Ketamine also has a direct myocardial depressant effect. In debilitated patients with a poor catecholamine response, the direct effects may predominate, causing cardiovascular destabilization and hypotension. Due to the potential for increased myocardial contractility and oxygen consumption, ketamine should be avoided in patients with underlying cardiac disease (e.g. hypertrophic cardiomyopathy). Ketamine increases both intracranial and intraocular pressures Ketamine acts as an NMDA receptor antagonist and may play a role in preemptive analgesia. Ketamine is metabolized by the liver in most species other than the cat. In cats, the majority of the ketamine is eliminated unchanged by the kidney. When faced with a recalcitrant feline patient where premedication is required, but a decrease in ketamine dose is desired, a combination of ketamine (2-4 mg/kg), oxymorphone (0.05 mg/kg) or hydromorphone (0.1 mg/kg) and midazolam or diazepam (0.2 - 0.5 mg/kg) provides excellent restraint. Phenothiazines Phenothiazine tranquilizers such as acepromazine are generally avoided in patients where volume status or cardiovascular stability is a concern. Phenothiazines are alpha-antagonists, causing peripheral vasodilation and potentially severe hypotension in hypovolemic patients. Acepromazine may be useful in cases of airway obstruction where calming of the patient may decrease respiratory effort and improve ventilation. Respiratory depression is minimal and IM administration is usually effective if given adequate time to work (20 - 30 minutes). Use only at lower doses (0.02 - 0.05 mg/kg IM), especially if a complete physical examination has been difficult to perform due to the animal's respiratory distress. Anticholinergics (atropine, glycopyrrolate) Although commonly used in healthy patients, anticholinergic drugs are not used routinely in critically ill patients since they may increase myocardial oxygen consumption by increasing heart rate and can precipitate cardiac arrhythmias and decrease the threshold for ventricular fibrillation. They may be indicated in patients with high resting vagal tone or high vagal tone secondary to opioid administration. They can also be used in anticipation of surgical manipulation where sudden vagal stimulation may have a pronounced effect on the heart (ocular, laryngeal, or visceral traction or entry into the joint capsule) or in situations where cardiac output is dependent on heart rate (cardiac tamponade, neonates). Alpha-2 agonists (xylazine, medetomidine) Alpha-2 agonists should not be used in critical patients because of the profound changes in cardiac output and blood pressure seen after their administration and the ready availability of other cardiovascularly sparing drugs. Medetomidine is more specific for the alpha-2 (vs. alpha-1) receptor than xylazine. The adverse cardiovascular effects are mediated by the effects on the alpha-2 receptor, however. Induction Agents Opioids (oxymorphone, hydromorphone, fentanyl) Opioids are particularly useful intravenous induction agents, especially in combination with benzodiazepine tranquilizers, since they provide the most cardiovascular stability in critically ill patients. Cardiovascular function, including left ventricular function, cardiac output and systemic blood pressure, is well maintained after administration. Bradycardia is occasionally seen and can be treated with anticholinergics if necessary. Excitement after IV administration is uncommon in depressed patients. Benzodiazepines (diazepam, midazolam) These drugs are associated with minimal cardiac and respiratory depression and are clinically useful as an adjunct to other induction drugs. In critically ill patients, small IV doses can cause profound sedation. Ketamine Ketamine is generally given in combination with diazepam (or other tranquilizer) to minimize the possibility of ketamine-induced seizures and muscle rigidity. As with its use as a premedication, ketamine may cause a variable response on the cardiovascular system depending on patient status. Catecholamine release may also predispose to arrhythmias. Ketamine causes dose dependent respiratory depression, but this is usually transient and ketamine may be useful in patients with airway obstruction where maintenance of spontaneous ventilation is desirable. Ketamine also acts as a bronchodilator and may be useful in patients with feline asthma. Telazol is a combination of tiletamine and zolazepam and has effects similar to those seen with a ketamine/diazepam combination, although recoveries may be prolonged or otherwise unsatisfactory. Barbiturates Thiopental and methohexital are ultrashort acting barbiturates useful for providing a rapid sequence induction when rapid control of the airway for protection or ventilation is desirable (if there are no cardiovascular concerns). These drugs cause dose-dependent myocardial and respiratory depression, which may be especially pronounced when given in larger IV boluses or to depressed patients. Therefore, they should be avoided if possible when volume status or cardiovascular function is a concern. They may also precipitate ventricular arrhythmias, although this effect is usually transient. Effects of the drug may be potentiated by concurrent acidosis or hypoproteinemia. If no other option is available, administration of diazepam (0.2 - 0.5 mg/kg) and/or lidocaine (2 mg/kg) may help decrease the dose of barbiturate required for induction in patients with cardiovascular compromise. Barbiturates are useful in patients with increased intracranial pressure. Propofol Propofol is an ultrashort acting intravenous anesthetic with a 5 - 10 minute duration of anesthesia after induction, with the patient being remarkable alert on recovery. Propofol is useful for rapid sequence inductions where cardiovascular function is not a concern. Due to its short duration of action, it is ideal for short procedures and sedations. Propofol is a peripheral vasodilator and myocardial depressant and may cause significant cardiovascular depression in volume-deplete or cardiovascularly compromised patients. Propofol should not be used (or only after careful consideration) in these cases. Cardiovascular depression is especially pronounced if propofol is given as a large, rapid bolus. In healthy patients, induction is smooth and intubation is usually achieved after a total intravenous dose of 4 - 6 mg/kg titrated slowly to effect (either giving the entire dose over a 5 minute period or giving 1-2 mg/kg slow IV boluses to effect). Propofol can cause significant respiratory depression, again more pronounced with large, rapid boluses. Animals should be intubated or receive supplemental oxygen using a face mask when using propofol for sedation. Propofol may be given in combination with other cardiovascular sparing drugs, such as opioids or benzodiazepines, which decreases the amount of propofol required for induction. Diazepam (0.2 - 0.5 mg/kg IV) also helps to control the myoclonic twitching occasionally seen after propofol administration. Propofol can be given as a constant infusion (0.1 - 0.2 mg/kg/min) for maintenance of anesthesia. Propofol has extrahepatic clearance sites, such as the lung, and may be useful in patients with impaired hepatic function or for Caesarian section surgery. Cats will occasionally have a prolonged recovery. Propofol is provided in a soybean oil/lecithin emulsion and should be handled with strict aseptic technique. The manufacturer states that propofol should not be refrigerated and, once opened, the contents should be used within several hours due to the potential for significant bacterial contamination. Etomidate Etomidate is an ultrashort acting intravenous anesthetic causing rapid induction of anesthesia after intravenous bolus (0.5 - 1.5 mg/kg) with a duration of action of 5-10 minutes. It is useful for anesthetic induction in patients with cardiovascular instability, and causes minimal effects on heart rate and rhythm, cardiac output, and blood pressure. In addition, it causes minimal respiratory depression. Etomidate may induce vomiting and/or myoclonic twitching when used alone, but this reaction is significantly diminished when given in combination with an opioid and a benzodiazepine tranquilizer. Etomidate suppresses adrenocortical activity for several hours after a single bolus, which may be of concern in debilitated patients. Etomidate is solubilized in propylene glycol, which is hypersosmotic and administration of large amounts may lead to hemolysis and pigmenturia which may be of concern in patients with renal compromise. This can be avoided by diluting the etomidate with saline. Maintenance of Anesthesia Inhalant Anesthetics Inhalant anesthesia is the mainstay of long term anesthesia in critically ill patients. Duration of action is not dependent on metabolism of the agent and anesthetic depth can be rapidly adjusted. In addition, most emergency patients benefit from intubation, oxygen supplementation and ventilatory support, whether receiving inhalant or injectable anesthetics. All potent inhalants produce dose-dependent cardiovascular depression but, at equipotent doses, isoflurane, sevoflurane and desflurane produce less myocardial depression than halothane. In addition, halothane sensitizes the heart to the arrhythmogenic effects of catecholamines. Isoflurane, sevoflurane and desflurane do cause vasodilation, however, with subsequent hypotension that may be pronounced in hypovolemic patients. All of these agents are relatively insoluble in the tissues, resulting in fairly rapid induction and recovery. The relatively high concentrations of inhalant necessary for mask induction, however, can cause significant cardiopulmonary depression and induction using an injectable technique is usually preferred. Injectable Anesthetics Occasionally, very sick animals will not tolerate inhalant anesthesia. In these cases, IV boluses of short-acting opioids (e.g. oxymorphone (0.05 - 0.1 mg/kg), hydromorphone (0.1 - 0.2 mg/kg) or fentanyl (0.002 - 0.005 mg/kg)), tranquilizers (diazepam, midazolam) and etomidate may be given as needed. Fentanyl is also useful as a continuous infusion (initial rate of 0.7 -1.5 ug/kg/min). Neuromuscular blockade using pancuronium, vecuronium or atracurium may be used as an adjunct to general anesthesia. Recently, cis-atracurium has been introduced. Although the pharmacokinetics are similar to those of atracurium, histamine is not released. Cis-atracurium may be given as a 100 ug/kg slow IV bolus, with additional boluses of 50 ug/kg as necessary, or as a continuous infusion at 1 - 10 ug/kg/min. Postoperative Care Continued fluid support is often critical. In addition, adequate postoperative analgesia is extremely important to decrease detrimental physiologic effects including decreased pulmonary function, catecholamine release and increased oxygen consumption, stress hormone release, inappetance and insomnia. Opioids are most frequently used for postoperative analgesia in the critical patient although potential side effects include excessive sedation, dysphoria, respiratory depression, nausea and vomiting. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
