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Sick, Sicker, Sickest: Anesthesia in the Critically Ill Patient Kim Spelts, CVT, VTS (Anesthesia), CCRP, CCMT Peak Performance Veterinary Group No anesthetic procedure is entirely safe, but critically ill patients present a much higher level of risk and likelihood of perianesthetic complications. Awareness and anticipation of drug side effects as well as physiologic complications associated with various pathologies will help reduce the risk of and improve the likelihood of a favorable outcome. The selection of drugs for all phases of anesthesia (premedication, induction, and maintenance) must include an analysis of the risk-to-benefit ratio. In critically ill patients the side effects of anesthetic drugs may be greater than what would be seen in a normal, healthy patient. There are no perfect drugs, and only a safe anesthetist can reduce the impact of any drug’s negative side effects. All anesthetic agents can significantly alter cardiac output. One must consider the effects of chosen drugs on the formula CO = HR x SV, where CO = cardiac output, HR = heart rate, and SV = stroke volume (a function of preload, afterload, and contractility). The goal with any anesthetic procedure should be balanced anesthesia: providing adequate hypnosis, amnesia, analgesia, and muscle relaxation. Rather than using a few drugs, balanced anesthesia is best achieved with lower doses of multiple drugs. This is an especially important concept when anesthetizing critical patients as a way to help minimize potential side effects associated with higher drug doses. Proper patient assessment prior to anesthesia is crucial when developing an anesthetic plan. One should of course consider the patient’s underlying health status, such as age and concurrent chronic disease (cardiovascular, renal, hepatic, endocrine). What is the patient’s status upon presentation? What is his or her mentation (alert, depressed, obtunded, moribund)? Is the patient painful? Are there any bloodwork abnormalities? Most importantly for our critical patients, what is the cardiovascular status? Is the patient hemorrhaging? In shock? Have any fluids or pain medications been administered? Is the patient responding to stabilizing measures? One must also anticipate complications such as hypotension, cardiac dysrhythmias, and hemorrhage, which vary from procedure to procedure. Premedication Premedication of any patient will allow lower doses of induction and maintenance agents to be used. Premedication can also provide preemptive analgesia. It is important to remember, however, that critically ill patients will require lower than normal doses of premeds, and for those patients who are most compromised, premedication may be contraindicated. Acepromazine is a tranquilizer and anxiolytic agent that is commonly used in healthy patients. It has antidysrhythmic effects and can reduce afterload, which may make it an appropriate drug for use in some compromised patients (such as those with mitral regurgitation or a left-right shunt). It should be avoided in patients with ventricular hypertrophy, coagulopathy, seizures, or shock. Alpha-2 agonists such as dexmedetomidine and xylazine have profound effects on cardiac output (via a decrease in heart rate and increase in afterload) and their use should generally be avoided in critically ill patients. Extremely low doses of dexmedetomidine (0.5-1 mcg/kg) may be utilized in the postoperative period to provide analgesia and anxiolysis. Dexmedetomidine is reversible with atipamazole (0.1 mg/kg IV or IM), but IV administration of atipamazole during the use of inhalant anesthetics should be avoided due to the risk of unresuscitatable cardiac arrest. Benzodiazepines such as midazolam and diazepam have minimal cardiovascular effects. Alone, they often cause excitement, but combined with an opioid can result in sedation. Because it is water soluble, midazolam is preferred over diazepam when administered IM or SQ, or when combined in the same syringe with other drugs. Benzodiazepines are reversible with flumazenil (0.01 mg/kg IV). The use of anticholinergics should be considered if opioids are used as a concurrent premedication and/or as an induction agent. Glycopyrrolate (0.01 mg/kg SQ/IM, 0.005 mg/kg IV) and atropine (0.02-0.04 mg/kg SQ/IM, 0.01 mg/kg IV) both help maintain cardiac output by maintaining or increasing heart rate in the presence of opioid-induced bradycardia. Opioids provide both sedation and analgesia. Patients occasionally become dysphoric with their use, so a concurrent tranquilizer or sedative may be required. Opioids have minimal cardiovascular effects, the most common being bradycardia. As a result, a concurrent or subsequent dose of an anticholinergic may be required. Pure mu agonists (morphine, fentanyl, hydromorphone, oxymorphone, methadone, and remifentanil) provide the best analgesia. Methadone has the added benefit of acting as an NMDA receptor antagonist. Mu agonists can be completely reversed with naloxone (10 mcg/kg, usually given 1/2 IV and 1/2 SQ) and partially reversed with nalbuphine (0.5 mg/kg IV). Induction The induction phase of anesthesia is one of the most dangerous, especially for critical patients. While the effects of most induction drugs are transient, they are significant enough to potentially push a compromised patient close to cardiovascular collapse. All induction agents cause some degree of respiratory and cardiovascular depression. Propofol is a rapid-onset, ultra-short-acting injectable anesthetic. Its effects are noncumulative, and recovery is generally rapid and smooth. It can be administered as intermittent boluses or as a constant rate infusion (10-20 mg/kg/hr), with or without concurrent opioids, to reduce or replace inhalant anesthetic. Propofol causes a decrease in contractility, can predispose the heart to ventricular dysrhythmias, and can cause splenic engorgement. Propofol can also have significant vasodilatory effects. Its negative effects are dose-dependent. The required dose of propofol can be reduced by a slower administration and/or the concurrent administration of an IV benzodiazepine. An average induction dose of propofol is 4-8 mg/kg in sicker patients, but this can be reduced to 2-4 mg/kg with concurrent benzodiazepine use. Propofol is an appropriate induction drug for generally healthy or mildly compromised patients, but it should be avoided or used with extreme caution in patients suffering from anemia, hypovolemia, sepsis, or shock. Opioids, such as fentanyl (5-10 mcg/kg IV) or hydromorphone (0.1-0.2 mg/kg IV) do not provide true induction of anesthesia; rather, they result in sedation heavy enough to allow endotracheal intubation. Induction can be lengthy, and intubation can be difficult (especially in alert patients). While preoxygenation is always recommended prior to induction of anesthesia, it is especially crucial when inducing with opioids due to the significant respiratory depression that occurs. Concurrent use of a benzodiazepine can provide a smoother induction and additional muscle relaxation. Opioid inductions are generally not smooth in cats. Opioids have minimal effects on contractility, but they can cause a decrease in heart rate that may be significant enough to cause a decrease in cardiac output. Consequently, an anticholinergic should be used to help the patient maintain at least a high-normal heart rate. This is especially true in severely compromised patients (endotoxemia, shock, hypovolemia) who require a high heart rate to maintain their cardiac output. Opioid inductions are appropriate in sick, compromised patients. Of all the induction drugs available, etomidate has the fewest cardiovascular and respiratory effects. It comes in a propylene glycol base, and due to the hyperosmolarity of this solution it can cause acute hemolysis at the injection site. It is recommended that the drug be administered through a fluid line and/or diluted 1:1 with sterile saline when administered to small patients. Significant myoclonus can occur, but this risk is reduced if an adequate premedication is administered or if a concurrent benzodiazepine is used. Etomidate can also cause transient adrenocortical suppression, so it should be used with caution in Addisonian patients. While etomidate has the fewest respiratory and cardiovascular effects of all the induction drugs available, it is also the most expensive. An average induction dose is 1-2 mg/kg IV, but this dose can be reduced to 0.5-1 mg/kg with concurrent administration of a benzodiazepine and opioid. Concurrent use of benzodiazepines (midazolam or diazepam, 0.1-0.3 mg/kg IV) can reduce the amount of primary induction drug required, thereby minimizing the negative side effects of the primary induction drug. Benzodiazepines provide excellent muscle relaxation as well as amnesia. They can be administered intraoperatively as intermittent boluses or as a constant rate infusion of 0.1 mg/kg/hr. Diazepam has the potential to precipitate when mixed with other drugs, so care must be taken to avoid this (do not mix in same syringe with other drugs; do not administer through a line containing other drugs, etc.). Ketamine is a popular induction drug in veterinary medicine. Due to its increase in sympathetic stimulation, its use should be avoided in critically ill patients (who may already be maximally sympathetically stimulated). Ketamine also has dangerous side effects in cats that have not been adequately explained, such as acute blindness and sudden death. Ketamine’s primary uses should be limited to the induction of young, healthy dogs, and as a microinfusion (2-10 mcg/kg/min) for its NMDA receptor antagonist effects. Maintenance Balanced anesthesia should continue during the maintenance phase of anesthesia. Loss of consciousness, awareness, and memory may be provided with inhalant anesthetics, a propofol infusion, and/or an infusion or intermittent boluses of benzodiazepines. Analgesia can be provided by infusions or boluses of opioids or lidocaine, and by performing local anesthetic procedures (such as an incisional line block). An NMDA receptor antagonist such as ketamine can be administered as a microinfusion to prevent central neuronal hypersensitivity (“wind-up”). Immobilization of the patient may be achieved with the use of inhalants, a propofol infusion, or the administration of a neuromuscular blocking agent such as atracurium. For critical patients, isoflurane, sevoflurane, or desflurane are the anesthetic inhalants of choice. They each share and can be compared by the following properties: Potency, which is described by an agent’s mean alveolar concentration (MAC, the concentration at which 50% of patients will respond to a noxious stimulus, or ED50). In humans, ED95 (the dose at which 95% of patients are anesthetized) is 20-40% greater than MAC. Blood:gas solubility coefficient, which describes the rate of change in the agent’s concentration in the blood. The lower the solubility, the faster the change in alveolar concentration, and the faster the change in anesthetic plane. Atracurium is a valuable adjunct to the maintenance of anesthesia in critically ill patients. Some patients are so sensitive to the negative effects of inhalant anesthesia (especially the decrease in cardiac contractility) that it becomes necessary to paralyze the patient and keep the inhalant at a very low setting (less than 0.5%) or turned off completely. Atracurium is a non-depolarizing neuromuscular blocking agent that competes with acetylcholine to produce systemic muscle relaxation (paralysis). The administration of atracurium REQUIRES the use of intermittent positive pressure ventilation, preferably mechanical rather than manual. It is also recommended to apply a peripheral nerve stimulator to the patient to evaluate “train of 4” twitches as a method of assessing the effect and clearance of atracurium. If a nerve stimulator is not available, the anesthetist should watch closely for signs of voluntary movement and spontaneous ventilation. The duration of action is highly pH- and temperature-dependent, so care must be taken to manage both of these parameters during the perianesthetic period. Dosing of atracurium is 0.2 mg/kg for the first dose, then 0.1 mg/kg thereafter. It is not recommended to dose more frequently than every 20-30 minutes in critical patients unless (a) a peripheral nerve stimulator is applied, or (b) voluntary movement is observed. Atracurium can be reversed with neostigmine (0.02-0.04 mg/kg IV) or edrophonium (0.5 mg/kg IV), but since the duration of action may be longer than the duration of either of these reversal agents, the potential for reparalysis exists. Careful monitoring in the postanesthetic period is crucial. If the inhalant is turned off completely, administer intermittent boluses of midazolam (0.1 mg/kg IV) or place the patient on a midazolam infusion (0.1 mg/kg/hr) to provide amnesia during the perianesthetic period. Summary Critical patients have a high risk of experiencing potentially life-threatening anesthetic complications. One can help minimize the anesthetic risk by being aware of the physiologic effects of all anesthetic drugs administered and anticipating, monitoring, and rapidly responding to changes in the status of the patient. References/Suggested Reading Muir W, Hubbell J. Handbook of Veterinary Anesthesia. 3rd ed. St. Louis: Mosby, Inc., 2000. Thurmon J, Tranquilli W, Benson GJ. Essentials of Small Animal Anesthesia & Analgesia. Baltimore: Lippincott Williams & Wilkins, 1999.