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Anesthesia/Pain Management Sandra Z. Perkowski, VMC, PhD, DACVA University of Pennsylvania Anesthetizing the Small Animal Patient PATIENT EVALUATION Proper preanesthetic evaluation and management of the patient helps minimize any deleterious effects anesthesia and surgery may have on the animal and helps promote recovery in the postoperative period. In order to individualize care, each patient should be independently assessed. 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). Good medicine can also be good business and decisions regarding pre-anesthetic evaluation of the patient, anesthetic drug selection, selection of monitoring equipment and supportive care all influence patient care and the bottom line. 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. Any recent change in exercise tolerance should be noted. 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 - Respiratory system including evaluation of respiratory rate, respiratory effort and auscultation of breath sounds, mucous membrane color, cough with or without palpation of trachea and nasal discharge - Cardiovascular system including evaluation of heart rate and rhythm, auscultation, presence of any heart murmurs, the character of peripheral pulses and assessment of tissue perfusion and general hydration status (e.g. mucous membrane color and character, capillary refill time) A Grade II-III/V systolic murmur is common in older dogs due to various degrees of mitral regurgitation. If no other clinical signs referable to the heart (i.e., dyspnea, cyanosis, syncope, or exercise intolerance) are present and chest films are normal, further evaluation may not be necessary. - Neurologic system including mental status, any history of seizures or other CNS signs, signs of head trauma, evidence of cervical instability and signs of spinal cord damage which may be associated with large fluctuations in heart rate and blood pressure and a decrease in compensatory responses - Gastrointestinal system including emesis, diarrhea or melena, or abdominal distension (which may be associated with difficulty ventilating during anesthesia), pain on abdominal palpation - Musculoskeletal system including evaluation of thoracic conformation, evidence of thoracic trauma, fractures, penetrating wounds, facial injuries, ability to open mouth - Urogenital system, including the presence of palpable bladder Laboratory Tests Gathering some basic laboratory work is generally recommended prior to anesthesia, with the specific diagnostic tests requested dependent on the anesthetic and procedural risk determined for that patient. Again, not only is this good medicine but can also help generate revenue for the practice. Laboratory tests for the determination of intravascular volume include packed cell volume (PCV) and total solids (TS), 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. A blood glucose is often included in the "minimum" data base and should always be included in patients < 3 months of age. Normal values:
Whenever possible, a complete blood count (CBC, white blood cell count and differential) should also be recommended prior to anesthesia and used in conjunction with history and clinical presentation. A white cell count may reveal underlying infectious disease which can worsen after anesthesia (inhalants decrease immune system function). The minimum blood work required for healthy, older patients should include a CBC, PCV, TS and creatinine. Additional diagnostic tests may be run depending on the individual patient. Ideally, a complete chemistry screen should be performed 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. A urinalysis may also be performed. Thyroid function testing is recommended for cats over 7 yrs of age. Electrocardiography, thoracic radiographs, and cardiac ultrasound are among additional diagnostic tests that may be recommended for specific patients. These suggestions are based on the increasing likelihood of diagnosing sub-clinical disease in aging patients which in turn allows for intervention to prevent disease progression. Knowledge of this prior to anesthesia allows one to make appropriate drug, fluid and supportive therapy decisions and affords the opportunity to educate the client and build a foundation for a long term relationship and monitoring of this animal. Again it is not only good medicine, but also good business! 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 under anesthesia 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. Evaporative losses are increased with anesthesia and surgery, so 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 In addition to patient factors, procedural risk factors should also be determined when developing an anesthetic plan. For example, if blood loss is thought to be likely, steps may be taken to blood type the patient and/or have blood products (or a universal donor) available. Synthetic colloids and pressure support drugs might also be readily available. Costs for planned additional patient support and personnel costs may be built in to the quote provided. Once preoperative evaluation 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 Premedication drugs are generally administered to provide sedation and chemical restraint, preemptive analgesia, to reduce the amount of induction drugs required and to smooth the entire anesthetic period. Opioids are commonly included as part of the technique for their sedative effects as well as for their analgesic effects. The addition of a phenothiazine (acepromazine) tranquilizer, benzodiazepine (diazepam, midazolam) tranquilizer, or alpha-2 agonist to an opioid will potentiate the sedative effects of the opioid and may reduce the likelihood of dysphoria, panting, or other excitatory reactions occurring from the opioid. (NEUROLEPTOANALGESIA). Phenothiazine Tranquilizers (acepromazine) Acepromazine is commonly used to provide calming prior to anesthetic induction or in the post-anesthetic period. The onset of action is relatively slow (30 minutes after IM injection, 5 - 15 minutes after IV) while the duration of action may be up to 3 - 6 hours or longer (especially in very young or very old animals - decrease dose). The dose on the package insert is about 10 X too high. 0.02 - 0.1 mg/kg IM is usually effective if the preop is given enough time to work. Acepromazine is useful in relatively healthy patients; however should be avoided in patients where volume status or cardiovascular stability is a concern. Phenothiazines are alpha-blockers and cause peripheral vasodilation. The hypotension secondary to vasodilation may be especially severe in hypovolemic patients and may also increase bleeding. Platelet function is also affected. Acepromazine causes few respiratory effects and can be helpful in patients with laryngeal paralysis or if ventilation is a concern (take care in brachycephalic patients, as it can cause pharyngeal relaxation and obstruction) - Does not provide analgesia - May decrease the seizure threshold in some patients (idiopathic epileptics) Benzodiazepine Tranquilizers (diazepam, midazolam) Act by facilitating the actions of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, in the central nervous system. These drugs are generally not used alone as a premedication since they may cause increased agitation and restlessness, especially in healthy patients. The actions of diazepam and midazolam are similar. Cardiovascular and respiratory side effects are minimal. However, diazepam is dissolved in a 40% propylene glycol solution, causing pain at the injection site and making absorption unpredictable following IM injection. Midazolam is water soluble and is absorbed well from IM sites, and may be slightly more potent than diazepam (i.e. used at about one half the dose). At one time, midazolam was relatively expensive but this is no longer the case. Dissociatives (ketamine, tiletamine) Ketamine is often used IM as a premedication in cats (in dogs, the seizure threshold is close to the therapeutic dose and ketamine is rarely used as a premed, and should not be used alone; it is generally given IV with a benzodiazepine as noted above) Ketamine is generally considered cardiovascularly sparing. It causes catecholamine release which leads to increases in heart rate and cardiac output, which maintain blood pressure. However, myocardial contractility and oxygen consumption are increased; therefore, avoid in patients with underlying cardiac disease or in cats with hyperthyroidism. In debilitated patients that have used up their endogenous catecholamines, ketamine may act as a direct myocardial depressant and cause hypotension, so care should be taken with using these drugs in critically ill patients. Ketamine can cause dose dependent respiratory depression, although the patient will continue to ventilate. It may be useful in cats with feline asthma, due to it's action as a bronchodilator. Ketamine causes an increase in intracranial pressure due to an increased cerebral metabolic rate and, therefore, contraindicated in head trauma or other patients with suspected increased intracranial pressure. It can also increase intraocular pressure. Ketamine provides selective analgesia, with the best results in peripheral or somatic pain models (e.g. limb amputation, thoracotomy). It is less effective for visceral pain. Acts as an NMDA receptor antagonist - may play a role in preemptive analgesia. It is used most frequency in combination with an opioid as part of a multimodal approach to pain management. Addition of the NMDA receptor antagonist delays the onset of opioid tolerance. Tiletamine has properties similar to those of ketamine. It is marketed in combination with the benzodiazepine tranquilizer zolazepam as Telazol Opioids Opioids are frequently given pre-operatively to provide both sedation and excellent "pre-emptive" analgesia. Opioids act by binding to specific opioid receptors in the CNS (mu, kappa, delta). Although opioids are grouped together due to similar pharmacological properties, their behavioral and physiological effects may be qualitatively quite different. In healthy animals, opioids cause behavioral changes ranging from sedation to excitement. Cats frequently get excited after opioid administration, therefore, a partial agonist such as butorphanol or buprenorphine may be preferred In general, cardiovascular function is well maintained after opioid administration. Since opioids are relatively sparing of the cardiovascular system, their use as a premedication allows for a decrease in the amount of other cardiovascular depressant agents needed to provide anesthesia. They can cause a vagally-mediated bradycardia (generally given in combination with an anticholinergic). Histamine release may occur, especially after meperidine or morphine; therefore, these agents should be used with care in patients with mast cell tumors or GI ulcers Opioids are respiratory depressants and decrease sensitivity to increased CO2 concentrations. Opioids should be used carefully for induction in patients with airway obstruction when intubation may be difficult or impossible. Similarly, they should be used judiciously in patients with increased intracranial pressure (e.g. head trauma) unless the patient will be immediately intubated and ventilated; if not, butorphanol or buprenorphine may be preferred in these patients Vomiting is commonly seen. Other side effects which may be clinically significant include decreased GI motility and increased sphincter tone (e.g. pyloric, biliary duct) Pure Opioid Agonists (Schedule II): 1) Morphine
Morphine may be used as a continuous infusion (0.1 - 0.2 mg/kg/hr) (often in combination with ketamine at 0.1 - 0.6 mg/kg/hr +/- lidocaine at 0.02 - 0.05 mg/kg/hr) as an adjunct to anesthesia intraoperatively and can be continued postoperatively for analgesia 2) Oxymorphone
3) Hydromorphone
4) Meperidine
5) Fentanyl
6) Methadone
Opioid agonist-antagonists or partial agonists 1) Butorphanol
2) Buprenorphine
Alpha-2 Agonists (xylazine, medetomidine, dexmedetomidine) Alpha-2 adrenergic agonists are often used in small animal practice to produce sedation, muscle relaxation and analgesia. However, they also produce significant changes in cardiovascular function following administration and care must be taken with their use. Alpha - 2 agonists bind to pre-synaptic alpha-2 receptors centrally, causing a decrease in norepinephrine release from the nerve terminal. This causes sedation but also decreases sympathetic outflow to the heart, leading to a pronounced decrease in heart rate and cardiac output. They also bind to post-synaptic alpha-2 receptors peripherally, causing vasoconstriction. The net result of the central and peripheral effects on the cardiovascular system is transient hypertension (peripheral effect) followed by prolonged hypotension (central effect). Due to significant cardiovascular side effects, these agents should only be used in young, healthy patients. Other side effects include respiratory depression, vomiting, inhibition of insulin release, and diuresis Medetomidine was originally marketed as a more specific alpha-2 agonist than xylazine (i.e. ?-2: ?-1 for medetomidine: 1620:1; for xylazine;160:1). It is important to remember, however, that clinically significant cardiovascular side effects including significant bradycardia (HR < 40 bpm) and intense peripheral vasoconstriction (with pale mucous membranes) are mediated by the alpha-2 receptor. In addition, medetomidine lasts longer than xylazine (45 - 90 min vs. 20 - 40 min, respectively). Medetomidine is a racemic mixture, containing a 50:50 ratio of dextro and levo isomers with the levo isomer being pharmacologically inactive. An analog of medetomidine comprised only of the active dextro isomer, dexmedetomidine, is now available in the US. In dogs, dexmedetomidine is considered 2 times as potent as medetomidine. In other words, half the dose will be used. Cardiac output decreases after drug administration due to decreased heart rate, direct myocardial depression and increased afterload (decreased stroke volume). In addition, coronary vasoconstriction can lead to myocardial hypoxia and dysfunction. Studies have shown that 1 ug/kg dexmedetomidine in anesthetized dogs increased coronary vascular resistance, decreased coronary blood flow in all myocardial layers and increased oxygen extraction. Administration of an anticholinergic drug such as atropine either in combination with the ?-2 sedative or as a treatment for bradycardia is not recommended as it provides only a minimal increase in cardiac output in concert with an increased myocardial work load and increased incidence of cardiac arrhythmias. Reversal of the drug with atipamezole is the preferred treatment. Anticholinergics (atropine, glycopyrrolate) Competitive antagonists of acetylcholine at the postganglionic autonomic muscarinic receptor. They are frequently used as part of the premedication to help prevent vagally-mediated bradycardia (secondary to other anesthetic drugs such as opioids), secondary to surgical manipulation (ocular, laryngeal, visceral traction) or in patients with high resting vagal tone (brachycephalic dogs). They also decrease salivation and excessive airway secretions. Anticholinergics may be helpful in pediatric patients which do not have a well-developed sympathetic nervous system. Young patients are very dependent on heart rate to maintain cardiac output and blood pressure, since they are less able to increase heart contractility or to increase vascular resistance if blood pressure begins to fall. Atropine and glycopyrrolate differ primarily in duration of action (glycopyrrolate lasting about twice as long). In addition, glycopyrrolate is a quaternary ammonium structure (meaning it is a charged molecule!) and does not cross the blood brain barrier or placenta. INDUCTION AGENTS Barbiturates (thiopental, methohexital) Thiopental and methohexital are ultrashort acting barbiturates. Induction of anesthesia is rapid following IV bolus (30 - 60 sec), allowing titration to effect. Theduration of action is 5 - 30 minutes due to redistribution to lean body tissues. Eventually cleared by hepatic metabolism (caution in patients with liver disease). Barbiturates are 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). In addition, thiopental mixed 50:50 with propofol, is a useful induction combination (dosed at 1 - 2 mg/kg titrated to effect). Barbiturates may cause a transient fall in blood pressure which is dose-dependent. They should be avoided in patients where volume status or cardiovascular function is a concern. They may cause cardiac (especially ventricular) arrhythmias. Administration of diazepam (0.2 - 0.5 mg/kg) or lidocaine (2 mg/kg) may help decrease the dose of barbiturate required for induction. Respiratory depression (rate and dose dependent) also occurs. Barbiturates are especially useful in patients with suspected head trauma or space-occupying cranial lesions since barbiturates cause a decrease in cerebral metabolic rate and cerebral blood flow, decreasing intracranial pressure. Associated with splenic enlargement and should be avoided if the condition of the spleen is suspect or an exploratory laparotomy of the cranial abdomen is planned. Barbiturates do not provide analgesia. Thiobarbiturates are in a highly alkaline solution which is extremely irritating to the tissues. Perivascular, SQ, or IM administration may cause sloughing, especially at concentrations > 5%. Always use an intravenous catheter for administration. May cause precipitation of other drugs (e.g. diazepam) Methohexital causes excitement on induction and may cause convulsive-like behavior on recovery. Pentobarbital has a long duration of action Ketamine Generally given as an induction agent in combination (eg with diazepam) to minimize the possibility of ketamine-induced seizures and muscle rigidity. Cardiovascular effects when given IV are similar to those when given IM as a preanesthetic agent (may cause arrhythmias) 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 may be desirable. Can also cause bronchodilation, which may be helpful in cats with feline asthma. Other effects include increases in skeletal muscle tone and maintenance of corneal and laryngeal reflexes which may be inappropriate for certain surgical procedures. Ketamine causes an increase in intracranial pressure and, therefore, contraindicated in patients with head trauma or space occupying intracranial lesions May provide selective analgesia, and is useful as an adjunct for procedures such as limb amputation or lateral thoracotomy, but visceral pain does not appear to be completely abolished. Excreted primarily by the kidneys in cats (as compared to hepatic metabolism in other species) - therefore, use sparingly in patients with renal disease. Recoveries may be rough - patients may be hyperresponsive to external stimuli Telazol is a combination of tiletamine (a dissociative anesthetic) and zolazepam (a benzodiazepine) and has effects similar to those seen with a ketamine/diazepam combination. Recoveries tend to be rough, especially in dogs receiving Telazol alone (i.e. no general anesthesia). Can be useful for immobilization of aggressive dogs Benzodiazepines Associated with minimal cardiac and respiratory depression. Useful as an adjunct to other induction drugs, since they decrease the dose necessary to induce and maintain anesthesia. Can be used in combination with opioids to produce neuroleptanalgesia (e.g. for short term sedation and restraint) and with ketamine or propofol to produce short-term general anesthesia (these combinations are also useful for induction of anesthesia) Useful as a skeletal muscle relaxant. May be used as a short-acting anticonvulsant. Do not provide analgesia. Propofol 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 diazepam (0.2 - 0.5 mg/kg) or midazolam (0.2 - 0.) IV, which will minimize cardiovascular and respiratory side effects. A small amount of propofol (1-2 mg/kg) may be given prior to the benzodiazepine to prevent excitement. The remaining propofol is then titrated to effect. 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) and neurologic signs have been seen in cats after repeated use. Opioids Oxymorphone, hydromorphone and fentanyl are useful intravenous induction agents, especially in combination with benzodiazepine tranquilizers in critically ill patients; however, normal, healthy patients may go through a pronounced excitement stage during a narcotic induction. Cardiovascular function (left ventricular contractility, cardiac output and systemic blood pressure) is well maintained. Bradycardia may be seen after intravenous oxymorphone or fentanyl and can be treated with anticholinergics if necessary Provide excellent analgesia. 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. 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 inhalant agent currently used most frequently in small animal practice is isoflurane. Sevoflurane, which is similar in cardiovascular properties to isoflurane, is being used with increasing frequency, but is still very expensive at this time and the cost differential should be considered when choosing between the two agents. Advocacy to switch to sevoflurane has been largely driven by marketing of its rapid onset and offset. However, the literature is mixed as to whether differences between the two agents are significant. Clinical impression suggests that in the presence of premedications, injectable induction agents, analgesics, and other modifiers commonly used in peri-anesthetic period, little difference between the two agents is seen. In fact, some may argue that a more rapid change in depth of anesthesia may actually be deleterious unless someone knowledgeable is present during the entire anesthetic period to closely monitor the patient. All potent inhalants produce dose-dependent cardiovascular depression. Cardiovascular and respiratory effects are very similar for the two agents. Isoflurane and sevoflurane cause vasodilation, but cardiac output is maintained by increases in heart rate. All the potent inhalants cause respiratory depression, decreasing the response to increased CO2 concentrations, so patients should be ventilated at least 2 - 3 times/minute while under anesthesia. In addition, although not likely to be clinically important in the majority of patients, the question of sevoflurane use in patients with renal compromise remains. Injectable Anesthetics Occasionally, very sick animals will not tolerate inhalant anesthesia and an injectable technique must be used. IV boluses of short-acting opioids (eg oxymorphone, hydromorphone, fentanyl), tranquilizers (diazepam, midazolam) and etomidate may be given as needed. Fentanyl or propofol may also be given as continuous infusion Intraoperative Monitoring The standard of care for monitoring of veterinary patients is changing. Minimum monitoring used at the University of Pennsylvania 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, including: Note: an informal poll of board-certified anesthesiologists recommended that, IF ONLY ONE MONITORING DEVICE was available, the DOPPLER ULTRASONIC FLOW PROBE would be their number one choice, due to it's versatility of use. 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! Opioids Opioids are frequently used for pain control in veterinary patients. Opioids 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 methnadone 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 (0.1 - 0.4 mg/kg IM, IV q 1 - 4h). Studies in man and canine models also suggest that butorphanol may be useful for its anti-emetic properties in patients that are nauseated. Buprenorphine, a partial mu agonist, provides effective analgesia for many types of procedures and has a relatively long duration of action (6 - 20 microgram/kg IM,IV q 6 - 8h; peak effect at 2h). It has recently enjoyed a resurgence of use due in part to the ready absorption of buprenorphine across the oral mucosa in cats. 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 agents, 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 analgesia 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. 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(e.g. butorphanol at a dose of 0.05 mg/kg iv). Side Effects Opioids are most frequently given systemically. Although most opioids are relatively sparing of the cardiovascular system, other clinically significant side effects can occur. These include sedation, dysphoria or excitement, respiratory depression, hypotension, and vomiting. Therefore, 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. Cats may get excited or pyrexic when given pure opioid agonists, but are less likely to get excited with butorphanol or buprenorphine. If the animal becomes excessively dysphoric or excited after opioid use, a tranquilizer such as acepromazine or diazepam may be added, although other side effects such as respiratory depression or hypotension may be exacerbated. Respiratory Depression All of the opioids are respiratory depressants, causing a shift in the CO2 ventilatory response curve. Respiratory depression may be exacerbated by the use of additional drugs such as diazepam. Do not mistake panting with effective ventilation. Look carefully at the depth of each breath as well as the rate. Opioids should not be used in patients with head trauma or intracranial lesions unless they are being monitored closely. 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 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. Remember that hypotension after opioid administration may be exacerbated by concomitant administration of other drugs (e.g. diazepam). Nausea and vomiting 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 opioids. 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 or impossible to reverse. 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. Continuous Rate Infusion Pure opioid agonists (fentanyl, morphine) are frequently used as continuous-rate infusions during the anesthetic period. At lower doses, these infusions may be continued into the post-operative period and provide continued analgesia while minimizing respiratory depression (e.g. fentanyl: anesthetic dose: 0.3 - 0.7 microgram/kg/min; postoperative dose: 2 - 5 microgram/kg/h; n.b. use half the dose in cats). More recently, combination infusions of morphine, lidocaine, and ketamine have been recommended (see below). Use of the NMDA receptor antagonist ketamine has been shown experimentally to attenuate the development of opioid tolerance in man and rodents, thereby providing an opioid sparing effect. Butorphanol may be preferred as a CRI in some cases (0.1 - 0.4 mg/kg/h). With any CRI a small loading dose equivalent to the low end of the CRI range is generally given. Transdermal fentanyl patches Transdermal fentanyl patches are 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 seem to be as severe in dogs. Other side effects that have 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 the animal. There is considerable individual variation in drug absorption. Patients should be monitored both for analgesia and side effects. Some patients may require additional analgesics. If side effects do occur, systemic 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. Tramadol One drawback to using of opioids for prolonged analgesia is the poor bioavailability of these agents after oral administration, due to a high first pass metabolism by the liver. For example, morphine is available as both an immediate release and sustained release tablet. However, Kukanich et al (2005) looking at bioavailability after administration of a 1.5 mg/kg extended release tablet, found that the morphine was "poorly and erratically absorbed" with a 5% bioavailability. The poor oral bioavailability of the opioids has led to an increased interest in and use of tramadol. The parent compound, tramadol, acts as a very weak mu-agonist and acts as an analgesic by inhibiting NE and serotonin reuptake. In the dog, it is very rapidly and extensively metabolized to an active metabolite, O-desmethyltramadol (M1) that is a more potent analgesic than the parent compound. M1 acts as a weak mu agonist with 200X the binding affinity for the receptor than the parent compound. However, the affinity is still only 10% that of morphine. Tramadol (11 mg/kg PO) was 65% bioavailable with a short half life of 1.7 hours. For M1 the half life was also 1.7 hours. Simulated dosing suggested that 5 mg/kg q 6 hours or 2.5 mg/kg q 4 hours was required for adequate analgesic levels. This is in contrast to the 2 - 4 mg/kg bid/tid generally recommended. In the human literature, it is suggested that hepatic metabolism rates decrease with chronic use. Therefore, more frequent dosing may be used early in the post-operative period, with the dosing interval being tapered over a few days. One complaint frequently heard with higher doses or tramadol is excessive sedation in some patients. This may be due to an opioid effect. Tramadol should not be combined with other psychotropic drugs (e.g. amitryptiline) due to the possibility of serotonin syndrome. Seizures have been reported with it's use in man. Tramadol has been used in cats at a dose of 2 mg/kg bid - tid Local Anesthetics Lidocaine and bupivacaine are local 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 block transduction and transmission of the primary afferent pain signal. Given epidurally or intrathecally, 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). Both lidocaine and bupivacaine may be used for local injection at the nerve. With the advent of nerve locators, both of these agents are being used with increased frequency for brachial plexus blockade in patients undergoing forelimb procedures. Generally a maximum dose of 2 - 4 mg/kg lidocaine or 1 - 2 mg/kg bupivacaine is used to prevent toxicity. 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 each 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 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 be administered epidurally or intrathecally. The site for epidural is usually the lumbosacral (LS) 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 LS junction. A 20 or 22G sterile spinal needle is used for most patients. Injection is performed using sterile technique. With the animal in lateral or sternal position, the LS space is found, often using the wings of the ilium as a landmark (the LS space is usually the first space behind the wings). 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. The drug is then injected slowly over 60 seconds. If injected too rapidly, the block may become "spotty" and extend further cranially. 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 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). A combination of morphine and bupivacaine is often recommended to take advantage of the synergistic effect of using analgesic agents from two different classes: 0.1 mg/kg of a 1 mg/ml preservative-free solution (e.g. DuraMorph®) and 0.1 ml/kg of 0.5% bupivacaine. With this particular combination, 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. Intravenous Administration: Lidocaine may be administered as a low dose infusion (25 - 50 ug/kg/min) to enhance the effect of other analgesic agents. For example, it is frequently used in combination with either morphine or fentanyl given as a CRI +/- ketamine (see below). CRIs of lidocaine should be used cautiously, and probably not at all, in cats due to pharmacokinetics which are very different from the dog, leading to relatively high peak levels even at low doses. In addition, cardiopulmonary depression may be pronounced. Bupivacaine should NEVER be given intravenously in any species due to pronounced cardiac toxicity. Transdermal Administration: Recently, lidocaine transdermal patches (Lidoderm ®) have been introduced in human medicine and are being used more frequently in veterinary medicine. Lidoderm is a 5% lidocaine patch, containing a total dose of 700 mg of lidocaine suspended in gel on a felt backing. With application of the patch, penetration of the lidocaine into the skin produces an analgesic effect in the area of the patch, with minimal effect on normal sensation. Clinically, the patch works locally rather than depending on systemic uptake of the drug (in contrast to a transdermal fentanyl patch). In human studies, the patch has been shown to be effective in treating chronic, neuropathic, or osteoarthritic pain. It has been used acutely for back pain or after cruciate repair. Generally, the patch is cut to conform to the area in which the analgesic effect is desired. Overall, little systemic absorption occurs with the amount absorbed dependent on the covered surface area and duration of application. For veterinary use, the area should be clipped and cleaned. In one study in dogs, the patch was safely worn for up to 60 hours with a steady state blood level achieved within 24 hours. Toxic blood levels have not been reported. The most common adverse effect in humans is localized skin irritation. 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). 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 8-11 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 proinflammatory 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. 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 (deracoxib, firocoxib) or are COX-2 preferential (carprofen, meloxicam), result in selective antiinflammatory effects with decreased gastric side effects and minimal effects on coagulation, allowing their use in the perioperative period. However, care must still be taken when using these newer drugs and certain GI and renal side effects still occur. For example, COX-2 derived eicosanoids are increasingly recognized as physiologically important mediators of renal homeostasis, including regulation of vascular tone, blood flow, and salt and water balance. Their role in regulating and maintaining renal blood flow is especially important at times of decreased circulating blood volume or blood pressure, as might occur during the perioperative period and acute renal failure has been reported after NSAID use in the perioperative period. The risk/benefit ratio of using these drugs perioperatively, a time when anesthetic agents may adversely affect blood pressure and/or renal blood flow and oxygen delivery, must be carefully considered. Additionally, it is now recognized that a large part of their analgesic effect is due to inhibition of COX activity, more specifically COX-2 activity, centrally. It may take up to two hours after drug administration to achieve effective inhibitory levels within the dorsal horn of the spinal cord. This time lag should be taken into account when using these drugs "pre-emptively". It should also be recognized that many patients will be intermittently hypoxemic immediately post-extubation and into the early recovery phase due to the depressant effects of most anesthetic agents on ventilatory drive, again putting the kidney at greater risk. 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 NSAID 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 humans, 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) Flunixin meglumine (Banamine *) Phenylbutazone Ketoprofen (Ketofen ®) Piroxicam (Feldene*) Meloxicam (Metacam*) Carprofen (Rimadyl *) Etodolac (Etogesic*) Deracoxib (Deramaxx*) Firocoxib (Previcox®) Tepoxalin (Zubrin*) Naproxen (Aleve *) 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. Use of an NMDA receptor antagonist may prevent the development of opioid tolerance. 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 - two weeks) Ketamine is being used epidurally with increased frequency in human pediatric medicine. However, it is important to note that a preservative-free solution is used, since the preservative contained within the multi-use vials currently available is neurotoxic. 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. These changes occur even at very low doses (e.g. < 5 ug/kg medetomidine or 2.5 ug/kg dexmedetomidine) so they should be used only after careful consideration, especially in debilitated patients. 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, although they may be used as a low dose infusion for patients in the perioperative period, either as an adjunct to low dose opioids infusion or on their own. Anecdotally, they can be useful as a low-dose CRI (e.g. medetomidine at 1.5 microgram/kg/hr) in patients that may be exceedingly dysphoric from opioid use. In addition, combination of these agents with opioids may result in a syngergistic effect, with increased analgesia and prolonged duration of action achieved at lower doses. Cardiovascular effects may still be detrimental in some patients however. Grimm and coworkers (AJVR 2005) found that medetomidine given as a low dose infusion (1.5 ug/kg/h CRI (decreased cardiac index, heart rate and oxygen delivery). Injection of radionuclide labeled microspheres demonstrated decreases in myocardial, muscle and pancreatic blood flow. Myocardial blood flow decreased proportionally to changes in cardiac output. While renal blood flow did not change, oxygen delivery to the kidney was decreased. Similar results would be expected with dexmedetomidine. Recent reports suggest that dexmedetomidine given epidurally can provide analgesia with a decreased incidence of untoward side effects. PERIOPERATIVE ANALGESICS OPIOIDS
NON STEROIDAL ANTI-INFLAMMATORY AGENTS
ADJUNCT THERAPY
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. Autoregulation may be disrupted in the diseased or injured brain. Cerebral perfusion pressure(CPP) = mean arterial pressure (MAP) - ICP. Cerebral perfusion is usually maintained with a minimum MAP 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 it is important to avoid hypoventilation (PaCO2 > 40 mmHg). 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 with barbiturates is 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 increased CO2. 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 (by 20 minutes) of furosemide. Glucocorticoids may cause vomiting which is also 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 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 may have decreased 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 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. Be sure that all appropriate pre-operative medications have been given. 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. Hyperthyroidism 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 suppresses adrenocortical production. ANESTHESIA FOR C-SECTION The general aim is to minimize the amount of inhalant given to the bitch prior to removal of the puppies. 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 are NOT recommended. A line block with local anesthetic may be performed prior to induction. An epidural may also be done (morphine/lidocaine or bupivacaine), although the local anesthetic should NOT be included if the animal is hemodynamically unstable. Possible Induction Protocols:
COMMONLY USED SYSTEMIC DRUG DOSAGES**
* where dog and cat doses may differ ** Please note that there is a wide range of doses listed. The choice of dose will depend on the temperament of the patient, the physical status of the patient, and the combination of drugs being used. PROTOCOLS
ANESTHESIA FOR THE DOG Opioids are used as premedation for their sedative effects as well as for the analgesic effects. They are commonly administered with an anticholinergic. The addition of acepromazine (or a benzodiazepine tranquilizer) to an opioid will potentiate the sedative effects of the opioid and may reduce the likelihood of dysphoria, panting, or other excitatory reactions. The alpha 2 agonists may provide good sedative effects but are less frequently used as preanesthetics due to cardiovascular concerns. They may be used at lower doses in combination with an opioid to provide chemical restraint. Anticholinergics should not be used if an alpha-2 agonist is being used. 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: - HYDROMORPHONE 0.1 - 0.2 mg/kg +/- ATROPINE 0.02 mg/kg or GLYCOPYRROLATE 0.01 mg/kg +/- ACEPROMAZINE 0.02 - 0.05 mg/kg 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. PROPOFOL-THIOPENTAL INDUCTION. Propofol (10 mg/kg) and thiopental (20 mg/ml) are mixed in equal volumes in the syringe. The resulting mixture (15 mg/kg) is then used in a fashion similar to propofol alone (1 - 2 mg/kg boluses) and titrated to effect. 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, a 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, etomidate/diazepam, propofol/diazepam 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 or a low dose (1 mg/kg) or propofolmay 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 - 0.3 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) PROPOFOL 0.1 mg/kg/hr SEDATION / CHEMICAL RESTRAINT FOR DOGS
ANESTHESIA FOR CATS Healthy Cat IM Premedication Protocols
PROTOCOL FOR A SICK OR DEBILITATED CAT INDUCTION
SEDATION / CHEMICAL RESTRAINT FOR CATS
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 2.0 - 4.0 mg/kg IV and DIAZEPAM 0.2 0.5 mg/kg IV or MIDAZOLAM (0.1 - 0.3 mg/kg) BUTORPHANOL 0.1 - 0.2 mg/kg IV and ACEPROMAZINE 0.01 mg/kg IV or DIAZEPAM 0.2 0.5 mg/kg IV or MIDAZOLAM (0.1 - 0.3 mg/kg) Repeat if necessary, Double the above combination if giving IM PROPOFOL 1 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. MEDETOMIDINE (0.001 - 0.010 mg/kg) IM (may go up to 0.02 mg/kg in fractious cats) +/- HYDROMORPHONE 0.05 mg/kg (or METHADONE 0.3 mg/kg or BUTORPHANOL 0.2 mg/kg) +/- KETAMINE (2 - 6 mg/kg) IM KETAMINE (4 - 6 mg/kg) and XYLAZINE (0.2 - 0.5 mg/kg) IM 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. 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 may be used as an adjunct to general anesthesia. These drugs help maintain muscle relaxation despite decreased amounts of inhalant or injectable anesthetics. Vecuronium has minimal cardiovascular effects, but is the most expensive. Pancuronium is vagolytic and can increase heart rates in patients already tachycardic; also, its duration is prolonged in patients with renal failure. Atracurium may cause histamine release and hypotension; however it is metabolized by Hofmann elimination (i.e. spontaneous degradation in the blood) making it useful in patients with liver or renal failure. Cis-atracurium has similar pharmacokinetics to atracurium, but histamine is not released, so is preferred. 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. 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 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 an 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, desflurane). 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 (VPCs), 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 VPCs or paroxysmal ventricular tachycardia, lidocaine (1 - 2 mg/kg bolus +/- 0.05 mg/kg/min continuous infusion) is usually the first drug of choice. 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. 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. 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. Adjunctive therapy with local anesthetics or ketamine may be included. 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. 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 Hypoventilation is caused by insufficient elimination of CO2 relative to CO2 production due to an inadequate respiratory rate, tidal volume (relative to dead space volume), or both. Hypoventilation is common in anesthetized patients, since most anesthetic agents are respiratory depressants. Other causes of hypoventilation include depression of respiratory centers due to increased intracranial pressure or cerebral ischemia, limited chest wall or diaphragm movement (thoracic trauma, diaphragmatic hernia, abdominal distension), and interference with neural conduction to the respiratory muscles (cervical spinal lesions, neuromuscular blockers). Obstruction of the airway or endotracheal tube and inadequate mechanical ventilation are also common causes of hypoventilation under anesthesia. Recognizing hypoventilation is often difficult clinically, especially when ventilation is fixed, but includes changes in respiratory rate and effort as well as signs associated with sympathetic stimulation (tachycardia, hypertension, cardiac arrhythmias). Although moderate hypercapnia may help support blood pressure due to sympathetic stimulation, respiratory acidosis can also lead to myocardial depression. Treat the inciting cause if possible. 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 with a normal respiratory minute ventilation (respiratory rate times tidal volume) of 150 - 350 ml/kg/min. . Usually, a rate of 8 - 15 breaths per minute is used, although higher rates may be required. 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 . Hypoxemia Normal arterial oxygen tension is dependent upon the inspired oxygen tensions, ventilation, and ventilation/perfusion matching in the lung. For the normal patient breathing room air, PaO2 = 85 - 100 mmHg (hemoglobin saturation > 95%). For the normal anesthetized patient (assuming 100% inspired oxygen), PaO2 should be > 500 mmHg. At arterial oxygen tensions < 60 mmHg (hemoglobin saturations < 90%), oxygen delivery to the tissues becomes severely compromised due to the shape of the oxygen-hemoglobin dissociation curve. Recognition may include low oxygen saturation readings on the pulse oximeter or require measurement of an arterial blood gas. Venous blood gas measurements cannot be used to make determinations of arterial oxygen tensions. Cyanosis generally is not seen until profound hypoxemia occurs. Sudden changes in heart rate may be noted secondary to hypoxemia. Heart rate initially increases as the body attempts to increase cardiac output to maintain oxygen delivery to the tissues. As myocardial oxygen delivery becomes compromised, heart rate will fall, arrhythmias may become apparent, and cardiac arrest ensues. Potential causes of hypoxemia include hypoventilation, diffusion impairment, ventilation/perfusion mismatching, and venous admixture or shunt (either anatomic in origin or caused by blood flow to areas of the lung receiving no ventilation). In addition, failure of oxygen delivery is a concern in the anesthetized patient. Hypoventilation is rarely a cause of significant hypoxemia in patients receiving supplemental oxygen. Diffusion impairment is rarely a cause of hypoxemia, unless the system is under stress (during exercise, at low inspired oxygen concentrations). Ventilation/perfusion mismatching is probably the most common cause of hypoxemia in patients with pulmonary disease. However, hypoxemia due to perfusion of alveoli with low (but not zero) V/Q ratios are very responsive to inspired oxygen concentrations >35%. The primary cause of hypoxemia in the anesthetized patient is the presence of a shunt. This may be due to congenital heart abnormalities, but is more often caused by a variety of disease processes including alveolar collapse secondary to pneumothorax, pyothorax, or lung lobe torsion, alveolar collapse due to compression secondary to neoplasia, diaphragmatic hernia or abdominal distension, and alveolar filling secondary to pneumonia, pulmonary edema or pulmonary hemorrhage. Presence of a shunt adds mixed venous blood directly into the arterial side of the circulation. A shunt is unresponsive to the administration of 100% oxygen due to the fact that, as blood from various parts of lung meet and mix, oxygen contents, not oxygen tensions, are averaged. Since blood leaving non-shunted portions of the lung is already nearly fully saturated, and since relatively little oxygen is carried in dissolved form, administration of 100% oxygen will have a minimal effect on oxygen content. Treatment of hypoxemia includes delivery of 100% oxygen (discontinue nitrous oxide if being used). Institute positive pressure ventilation to optimize tidal volume. 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. Practical Anesthetic Protocols Individualizing Anesthetic Management The following notes and accompanying lecture will follow a case based approach to anesthesia in small animal patients. In addition to case management considerations, questions are included to facilitate discussion as needed during the presentation. Case No. 1: Signalment and Objective Findings: Active, friendly, 3 month old, female boxer puppy presented for an ovariohysterectomy. Normal physical examination including TPR, PCV 36 %, TP 6.2 g/dl, Blood glucose 85 mg/dl, BUN (on azostick) 5-15 mg/dl Assessment: Healthy and active, brachycephalic patient, routine but painful procedure, PCV slightly low, but probably appropriate for this age, normal glucose and BUN. Puppies this age tend to be hypotensive when compared to adult patients and rely on heart rate (rather than increasing vascular tone) to maintain blood pressure. Goals: Good sedation and analgesia without compromise to respiratory (brachycephalic) or cardiovascular (young patient) function. Questions: What are the determinants of blood pressure in any patient? What should normal blood pressure be in the anesthetized patient? Drug and Dose Selection and Rationale: Premedication: Morphine 0.75 mg/kg SC or IM and Atropine 0.03 mg/kg SC or IM 20 - 30 minutes prior to catheter placement / IV induction. These are doses in the upper 1/3rd of the normal dose range. Other Mu agonist opioids (hydromorphone, oxymorphone) and an alternate anticholinergic (e.g., glycopyrrolate) drug would be acceptable, but morphine tends to be more sedating than other opioids and has a longer duration of action. It is also inexpensive, but often causes vomiting when used preoperatively. If the puppy was really active, addition of a 0.01 - 0.02 mg/kg of acepromazine would be appropriate. In this scenario the dogs behavior didn't warrant it (keep in mind that even very active young canine patients will often sedate well with an opioid alone) and since it is a vasodilating drug one is likely to see less hypotension without it. Titrated Intravenous Induction: Propofol (4-6 mg/kg) or Propofol (2-4 mg/kg) with Diazepam/Midazolam (0.25 - 0.5 mg/kg), Ketamine (5 mg/kg) and Diazepam/Midazolam (0.25 mg/kg) or Thiopental (10-15 mg/kg) would be acceptable. Propofol and Thiopental can also be mixed together 50:50 in the same syringe. At 3 months of age the puppy should be able to metabolize any of these drugs. However, given the short duration of the procedure one might choose propofol for induction since it is most rapidly cleared by the liver. Another good reason for selection of propofol in this scenario is that the dog is brachycephalic and propofol allows for rapid control of the airway on induction and a rapid, clear headed recovery. However, propofol is more expensive than ketamine and diazepam/midazolam and there are issues related to drug storage. Hypoxemia in absence of pre-oxygenation and hypotension in absence of prior IV fluid administration may be noted with rapid propofol administration. Maintenance: Inhaled agent. In this healthy patient any of the volatile anesthetics would be acceptable. Of the 3 (halothane no longer being produced in the US), isoflurane is less expensive than sevoflurane and desflurane and in this case scenario with use of premedicants and induction agents any differences in recovery time with appropriate dosing are not likely. Recovery: Line block in spay incision with up to 2 mg/kg bupivacaine (diluted with equal volume of saline). Repeat morphine at lower dose (0.5 mg/kg SC) or choose an alternate opioid (e.g. buprenorphine) as needed until patient can be transitioned to oral analgesic (e.g, tramadol). Information regarding the safe long term use of NSAIDS in this age group is limited. Questions: How long does morphine last? What are the pros and cons of following a morphine pre-med with buprenorphine? With butorphanol? Monitoring: Heart rate and rhythm using an ECG monitor. Non-invasive blood pressure using either a Doppler ultrasonic or Oscillometric monitor. Respiratory rate and character by observation of rebreathing bag and/or chest wall. Body temperature may be monitored using an esophageal thermistor or thermometer placed in the back of the oral cavity or the rectum. Additional monitoring using a pulse oximeter for assessment of oxygen saturation and capnograph for indirect assessment of ventilation may be useful given this patient is brachycephalic. Support and Rationale: Oxygen by loose fitting face mask at approximately 5 L/min for 1-2 minutes immediately prior to and during the anesthetic induction. This is generally not necessary at sea-level for dolichocephalic patients receiving propofol, ketamine or thiopental, but if airway problems and/or a difficult intubation are anticipated, pre-oxygenation will provide a margin of safety. The benefits are magnified if the patient becomes apneic during induction as is fairly common with both propofol and thiopental. It is also advisable to keep the mask accessible for the period immediately following extubation in this patient in case of respiratory complications. Intravenous (via catheter) administration of a balanced electrolyte solution (e.g., lactated Ringers, Normosol-R, Plasmalyte normal saline, etc.) at a rate of 10 ml/kg/hr. Fluids during the peri-anesthetic period help maintain blood volume, improve cardiovascular performance and maintain perfusion of vital organs. The addition of dextrose to fluids may be necessary for debilitated young patients or those in whom the anticipated anesthesia duration is prolonged. Question: How would you modify your anesthetic if the procedure was expected to be longer in duration than a spay (e.g. if the patient had a fracture?) In this young patient, it is also important to keep the heart rate in the normal range as cardiac output is dependent on it. The pre-operative anticholinergic should insure this, but occasionally repeat doses are required. Provide external heat to minimize hypothermia. Many options are available including circulating water blankets, heat lamps, the circulating air, etc. Warming IV fluids is only beneficial if warming can be done just prior to the fluid entering the IV catheter. Wrapping the patients' extremities has also been shown to minimize heat loss. Questions for consideration and discussion (as time permits) What are the pros and cons of an inhaled anesthetic induction in this scenario? What are the pros and cons of using an alpha -2 agonist in this scenario? How would you modify the protocol for a kitten with a similar signalment and objective findings? How would you administer dextrose to a patient if needed? Compare and contrast the use of the Doppler ultrasonic technique and Oscillometric technique for monitoring blood pressure in small animal patients. How will you treat this patient if hypotension is observed? What are the pros and cons of withholding food and water prior to anesthesia? Are their circumstances when one might alter 'normal' practice? Is there a 'cut off' for fluid administration or should all patients receive fluids in the peri-anesthetic period? How would you modify the fluids if the patient was 1 month old and a 2 hour anesthetic was anticipated? How does hypothermia influence your anesthetic management? Case No. 2 Signalment and Objective Findings: 12 year old MC Toy Poodle presents for a dental cleaning. On initial presentation 3 weeks prior to today, the dog had a thorough pre-procedural evaluation at which time a heart murmur was auscultated. The BUN and Cr values are elevated to twice the high normal value with a low normal urine specific gravity. Slight elevations in ALP and ALT were also noted. Thoracic radiographs revealed a large left atrium. When questioned further, the owners did reveal that the dog had been coughing more in recent months and not as eager to go for his evening walk with them. A presumptive diagnosis of a mitral regurgitation was made and the dog was sent home on lasix and enalapril to see if clinical signs would resolve prior to anesthesia for his dental procedure. Amoxicillin was also prescribed for administration one day prior to this presentation for his dental cleaning. The dog presents today with a HR 140, 3/6 holosystolic murmur, RR 18 (normal auscultation). A cough is elicited with tracheal palpation. Owners elected not to have laboratory tests or radiographs repeated. They feel the medications are helping the dog but he seems to be urinating more frequently. Assessment: The medications seem to be ameliorating clinical symptoms of the animal's cardiac condition. Unfortunately without repeat diagnostics this is all one has to go on. Antibiotics should help reduce chance of valvular endocarditis with a dental procedure. Renal enzymes are elevated and are of concern since they do indicate significant renal compromise; further compromise is possible with medications the dog is now receiving. Goals: Minimize negative cardiovascular effects while maximizing renal perfusion. Drug and Dose Selection and Rationale: Premedication: Hydromorphone 0.1 mg/kg (or other opioid) +/- Atropine 0.02 mg/kg (or glycopyrrolate 0.01 mg/kg), SC or IM 30 minutes prior to IV catheter placement. Calm and slightly sedate patient and provide analgesia in case of any extractions, maintain normal heart rate, reduce dose requirement for induction and maintenance Titrated IV Induction: Etomidate 1 mg/kg or Fentanyl 10 µg/kg (or Ketamine 5 mg/kg?) and Diazepam/Midazolam (0.25 mg/kg). Etomidate and Fentanyl are extremely safe for cardiovascular system (decrease in HR with fentanyl is generally avoided with anticholinergic use), but do have side effects associated with them (etomidate: adrenocortical suppression, burns on injection, etc. and fentanyl: respiratory depression, occasional excitement on induction). Etomidate is expensive, but in this small patient cost should not be prohibitive. Ketamine may cause cardiovascular depression in compromised patients, but given Henry seems to have compensated for his mitral disease, it may be an acceptable choice. Maintenance: Preference would be isoflurane or desflurane, but sevoflurane could be used with a non-rebreathing circuit or with a high flow rate in a circle breathing system. May need to utilize a balanced technique (i.e., an opioid typically is used with the inhalant to reduce inhaled anesthetic dose) if hypotension seen with inhaled agent alone. Recovery: May not need much else if only a teeth cleaning, but if significant tartar or extractions, local blocks should be administered, SC hydromorphone (short duration) or buprenorphine (longer duration) post-operatively and then transition Henry to liquid formulation of oral analgesic (morphine or buprenorphine) especially if mouth is painful. A NSAID is not recommended given his elevation in renal enzymes. Monitoring: Place ECG and Doppler on the dog prior to anesthetic induction and pre-oxygenate him. Continue heart rate and rhythm monitoring throughout procedure. If Henry has good blood pressure readings on the Doppler, this may be sufficient, but if not direct monitoring of pressure might be indicated (and can be challenging in a toy poodle). This would also facilitate sampling for blood gas analysis should this become necessary. Monitor respiratory rate and character. The dog is definitely a candidate for both capnography and pulse oximetry since his mitral regurgitation predisposes him to pulmonary edema. Monitor body temperature using a rectal thermometer or thermistor. Support and Rationale: Make sure the endotracheal tube cuff is well inflated and oro-pharynx protected from fluid and debris. Mechanical ventilation would be useful to prevent atelectasis and reduce consequences of sub-clinical pulmonary edema. If this is unavailable, periodic manual large breaths (sigh) may be used to recruit collapsed areas of the lung for gas exchange. While anesthetic induced recumbency can confound auscultation, it is useful to periodically listen to the lung fields in patients where the risk for pulmonary edema is high. The intravenous fluid rate should be on the lower end (3 - 5 ml/kg/hr) so as not to fluid overload the patient and possibly cause pulmonary edema. Ideally given the elevation in renal enzymes this should be started 1 - 2 hours prior to anesthetic induction. During anesthesia hypotension that is unresponsive to lightening the anesthetic plane is ideally treated with inotropes as opposed to repeated fluid boluses. It is important to maintain blood pressure in the normal range so as not to exacerbate his renal disease. An ideal inotrope for the dog would be dopamine as it also has renal arteriolar vasodilating properties at low doses and will help maintain renal perfusion. A low dose of dopamine (2 µg/kg/min) is therefore recommended even in the absence of hypotension. Higher doses (5 µg/kg/min) may be used to treat hypotension. Mannitol may also be used to help protect the kidney from further damage during the anesthetic period. In this patient who is at risk of fluid overload, an infusion of 0.1 g/kg/hr is suggested; ideally this is begun prior to induction and discontinued approximately 30 min before the IV fluids are stopped. If possible, IV fluids should be continued during anesthetic recovery. Try to keep the dog dry (during dental procedure) and warm using external means as necessary. Small patients have greater surface area to mass ratios and environmental conditions can significantly influence their body temperature. Patients with mitral regurgitation benefit from having normal heart rate as this will help maintain forward flow. An anticholinergic may be beneficial in these patients especially if the patient is also receiving high doses of opioids. Questions for Consideration and Discussion: Why are pros and cons for using propofol as part of the anesthetic induction in this patient? How would you modify your protocol if the dog was a cat? What if the cat was hyperthyroid? What would you do if Henry got hypoxemic during his anesthetic? Is capnography a useful tool for monitoring of carbon dioxide when using a non-rebreathing circuit? If the pulse oximeter reading progressively decreased from a starting value of 95% to 88% what is likely the problem in this patient and how should it be treated? In the event that premature ventricular beats are observed, how should the patient be assessed and if necessary, treated? Case No. 3: Signalment and Objective Findings: 5 year old male castrated greyhound, hit by car one hour previously. Prior to being hit, dog was normal, healthy and energetic with no known medical abnormalities. On physical examination the dog is mentally depressed, the temperature is 99F, pulse rate is 180 bpm with an irregular rhythm and weak peripheral pulses, and the respiratory rate is 48 bpm with an increased effort. The heart and lungs auscult normally, other than the irregular rhythm. Mucous membranes are pale, dry and the CRT is > 4 seconds. Distal extremities are cool to the touch. PCV= 54%, TS = 7.2 g/dl, BUN = 30 - 40 mg/dl, blood glucose = 180 mg/dl. Assessment: Previously healthy patient, now hemodynamically compromised due to being hit by the car. Suspect acute abdominal bleeding. Irregular rhythm likely ventricular in origin and may be secondary to traumatic myocarditis. Although lungs auscult normally at this time, pulmonary contusions cannot be ruled out. Goals: Appropriate fluid resuscitation and stabilization of cardiovascular function is essential prior to the induction of anesthesia. Drug and Dose Selection and Rationale: Premedication: Premedication is not required for most patients presenting as an emergency secondary to trauma. If preoperative 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. A combination of a pure opioid agonist (e.g. oxymorphone 0.05 - 0.1 mg/kg, hydromorphone 0.1 - 0.2 mg/kg, or methadone (0.5 - 2 mg/kg) may be used. A benzodiazepine tranquilizer (midazolam 0.2 - 0.3 mg/kg), may be added to provide sedation with minimal cardiovascular depression. 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. Titrated IV 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 (0.005 - 0.01 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: Maintenance using an inhalational anesthetics (isoflurane, sevoflurane or desflurane) is preferred. 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 (0.3 - 0.7 microgram/kg/min) or morphine (0.1 - 0.2 mg/kg/hr) 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. Recovery: Continued fluid support is often critical in patients with cardiovascular instability. Supplemental oxygen may be indicated. Effective analgesia with minimal cardiovascular side effects is also important. Opioids are generally preferred for postoperative analgesia in the critical patient due to their preservation of cardiac function. Watch for respiratory depression. 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. 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. Questions for consideration and discussion: What would you use for fluid replacement? How much? How fast? What route? What type? What are your goals? What are the pros and cons of other anesthetic regimens in this patient? Propofol? Ketamine? Medetomidine? The patient is a greyhound. Does this change any of your drug choices? Would you do anything differently if the patient did have pulmonary contusions? What would you do differently if the patient had evidence of head trauma? Drug choices? Ventilation? Case No. 4: Signalment and Objective Findings: 7 year old MC DSHA which was last normal yesterday. The cat presents to your hospital with a 24 hour history of lethargy, anorexia, vomiting and tachypnea. On physical exam, the cat is anxious. Temperature = 101.2F, pulse rate is 212 bpm with a regular rhythm and the respiratory rate is 60 bpm with an increased respiratory effort. Mucous membranes are pink, slightly tacky and the CRT is 3 seconds. Femoral pulses are moderate. Lungs and heart sounds are dull on the left side. PCV = 53%, TS = 7.8 g/dl, BUN (azo) = 15/26, glucose = 156 mg/dl. Na and K are within normal. Assessment: Cat is moderately dehydrated and in obvious respiratory distress. Dullness on the left side points to interpleural disease on that side. Possibilities include pneumothorax, pleural effusion (chylothorax, pyothorax, hemothorax), space-occupying mass, or diaphragmatic hernia. Goals: Further diagnostics (radiology, +/- thoracocentesis) are indicated. Thoracocentesis should be performed to help stabilize the respiratory system in patients with pleural fluid or air showing signs of respiratory distress Avoid stress and excessive physical restraint! Sedation may be required. All anesthetic agents depress respiration to a greater or lesser degree. Before administering any agent, make sure you are familiar with its effects. Sedation with butorphanol (0.1 - 0.2 mg/kg IV) and diazepam (0.25 - 0.5 mg/kg) or midazolam (0.2 mg/kg) may be useful in patients with respiratory distress. 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 Drug and Dose Selection and Rationale: Again, all anesthetic agents will depress respiration to some degree. 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. In this case, thoracocentesis was performed and resulted in the evacuation of a white, milky fluid containing degenerate neutrophils. Chest radiographs showed the presence of a sewing needle within the thoracic cavity. A thoracotomy is scheduled after fluid resuscitation to remove the needle. Premedication: Premedication is not required if an intravenous catheter can be placed with minimal stress to the patient. Respiratory depressants, such as opioids, should be used judiciously in patients with severe hypoxemia or upper airway obstruction and patients closely monitored after administration. If premedication is required, butorphanol (0.2 - 0.4 mg/kg M) and midazolam (0.2 - 0.3 mg/kg IM) and ketamine (2-6 mg/kg IM) may be useful in cats. A pure opioid agonist may be preferred in place of the butorphanol e.g. oxymorphone (0.05 mg/kg), hydromorphone (0.05 mg/kg), or methadone (0.2-0.3 mg/kg) Induction: Preoxygenation in these patients is extremely important! Patient positioning may also be important. Keep the good side up (or at least try to maintain sternal recumbency) to aid ventilation. A rapid sequence induction using an intravenous technique to allow prompt intubation and control of the airway is preferred. A mask induction can lead to unwanted excitement and additional respiratory distress. Appropriate induction agents include low dose propofol (e.g. slow administration of 1 mg/kg boluses to effect) +/- diazepam (0.25 - 0.5 mg/kg) or midazolam (0.2 - 0.3 mg/kg). Ketamine (2-5 mg/kg) and diazepam or midazolam (+/- propofol or etomidate 0.2 - 1.0 mg/kg) 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, an opioid (oxymorphone (0.05 - 0.1 mg/kg), hydromorphone (0.05- 0.1 mg/kg), fentanyl (0.0025 - 0.005 mg/kg) or methadone (0.2-0.3 mg/kg) may be used. Patients presenting with pneumothorax require special consideration if a chest tube is not in place, as positive pressure ventilation may lead to an increase in air accumulation within the thoracic cavity and rapid deterioration of respiratory and cardiovascular parameters. Under these conditions, induction agents causing minimal respiratory depression should be selected so that spontaneous ventilation is maintained. Maintenance: Inhalants are generally used for anesthetic maintenance, since intubation, supplemental oxygen and ventilatory support are critical in patients undergoing thoracotomy. Constant rate infusions of morphine (0.1 -0.2 mg/kg/hr) or fentanyl (0.3 - 1.0 microgram/kg/min) +/- ketamine (0.1 - 0.6 mg/kg/ hr) may be very helpful in maintaining a stable level of anesthesia in these patients. Lidocaine infusions should be used judiciously in cats, as the pharmacokinetics are quite different from those in dogs 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. 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. Support: 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. Recovery: Continued evaluation of respiratory function is critical in the post-operative period. In many patients, extubation may be more difficult than intubation. Ventilation is generally depressed for some time in the postoperative period due to the persistence of anesthetic drugs, including inhalants 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. 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 using local or regional techniques (e.g. interpleural bupivacaine) may be preferred or used as an adjunct therapy. Questions for consideration and discussion: What are normal blood gas values for a patient breathing room air? 100% oxygen? How useful is a pulse oximeter in monitoring oxygenation in a patient under anesthesia? How does one-lung ventilation (e.g. during thoracoscopy) effect your blood gas values? How would you change your approach to this patient if this was a diaphragmatic hernia instead of a thoracotomy? SUMMARY While we hope this provides useful and applicable information, instances may still arise in which given the constraints and constant advances in veterinary medicine one does not know how to or may not have the ability to meet the standard of care. In those instances it is recommended that one consult or refer the case to an anesthesiologist just as one would for a complex diagnostic (e.g., cardiac ultrasound) or therapeutic (e.g., radiation therapy) procedures. ACKNOWLEDGEMENTS: Dr.Khursheed Mama, DVM, DACVA who helped in the preparation of the case presentations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
