Clinical Pharmacology in Athletic Training

292 | Clinical Pharmacology in Athletic Training conditions when discussing appropriate anesthetic agents.24 The AT is an important resource to the surgical team who can relate the patient’s medical history and monitor complications secondary to surgery. The AT can counsel patients prior to surgery...

292 | Clinical Pharmacology in Athletic Training conditions when discussing appropriate anesthetic agents.24 The AT is an important resource to the surgical team who can relate the patient’s medical history and monitor complications secondary to surgery. The AT can counsel patients prior to surgery on what to expect when having anesthesia. This chapter details the importance of inhaled versus intravenous (IV) anesthesia, various nerve blocks used for regional anesthesia, and valuable information for patient care prior to and after surgery. Concepts of Anesthesia Analgesia—Loss of response to pain Amnesia—Loss of memory Immobility—Loss of motor reflexes Coma (hypnosis)—State of being unconscious or unresponsive to stimulus 5. Paralysis—Skeletal muscle relaxation 1. 2. 3. 4. None of the currently available anesthetic agents when used alone can achieve all 5 of these desired effects well. An ideal anesthetic drug would induce rapid and smooth loss of consciousness, be rapidly reversible on discontinuation, and possess a wide margin of safety.10 In practice, anesthesiology (figure 22.1) relies on the use of combinations of BSIP/Universal Images Group via Getty Images For minor procedures, conscious sedation techniques combine IV agents with local anesthetics. These drugs can provide profound analgesia while retaining the patient’s ability to maintain a patent airway and respond to verbal commands.10,15 For more extensive surgical procedures, anesthesia protocols commonly include intravenous drugs to induce the anesthetic state. These drugs are often combined with inhaled anesthetics to maintain an anesthetic state and neuromuscular blocking agents to effect muscle relaxation. When monitoring patients during surgery, vital signs are the standard method of assessing depth of anesthesia. Electroencephalography (EEG) monitoring, an automated technique based on quantification of anesthetic effects, is also useful.15 The neurophysiologic state produced by general anesthetics is characterized by 5 primary anesthesia end points:10,20,24 FIGURE 22.1 Operating room with equipment for administering anesthesia with integrated systems for monitoring several vital parameters. M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics. Chapter 22 • Surgery | 293 intravenous and inhaled drugs (balanced anesthesia techniques) to take advantage of the favorable properties of each agent while minimizing their adverse effects. Drugs are chosen to provide safe and efficient sedation based on the type and duration of the procedure and patient characteristics, such as organ function, medical conditions, and concurrent medications.20,32 Different types of anesthesia affect the end points differently. For example, sedation, or twilight anesthesia, uses benzodiazepines to induce amnesia, while general anesthetics affect all end points. The goal of anesthesia is to achieve the end points required for the given surgical procedure with the least risk to the patient.6 Effects of General Anesthesia General anesthetics induce a generalized, reversible depression of the CNS. Under general anesthesia, there is a lack of perception of all sensations. The anesthetic state includes loss of consciousness, amnesia, and mobility (or a lack of response to noxious stimuli) but not necessarily complete analgesia. Other desirable effects provided by anesthetics or adjuvants during surgery may include muscle relaxation, loss of autonomic reflexes, analgesia, and light sedation (anxiolysis). All these effects facilitate safe and painless completion of the procedure; some effects are more important in certain types of surgery than others. For example, abdominal surgery necessitates near-complete relaxation of the abdominal muscles, whereas neurosurgery often requires light anesthesia that may be lifted rapidly when the neurosurgeon needs to judge the patient’s ability to respond to commands.32 The primary responses to general anesthesia are systemic vascular, pulmonary, hypothermic, and neurologic (figure 22.2).24 Systemic Vascular and Cardiac Effects The hemodynamic effects produce a decrease in systemic arterial blood pressure. The causes of this hypotension include direct vasodilation, which in turn causes decreased vascular resistance and venous preload, myocardial depression, or both; a blunting of baroreceptor control; and a generalized decrease in central sympathetic tone.24 Pulmonary Effects Nearly all general anesthetics reduce or eliminate both ventilatory drive and the reflexes that maintain Neurologic Loss of consciousness Amnesia Headache Pulmonary Secretions Dilation Constriction Irritation Hypothermic Chills Shivering FIGURE 22.2 Cardiac Systemic vascular resistance Venous preload Gastric Nausea Vomiting Effects of general anesthesia. E7960/Cleary/F22.02/642682/JB-R2 airway patency. Therefore, ventilation generally must be assisted or controlled for at least some period during surgery. The gag reflex is lost and the stimulus to cough is blunted. Lower esophageal sphincter tone also is reduced, so both passive and active regurgitation may occur,24 leading to undesirable outcomes such as respiratory aspiration. Reducing the potential of regurgitation and aspiration of the stomach contents into the lungs when a patient is under anesthesia is a major concern. An AT can help inform the patient of the importance of taking these precautions prior to surgery (see Preparation for a Surgical Procedure). Hypothermic Effects Patients commonly develop hypothermia (body temperature <36°C) during surgery. The reasons for this include low ambient temperature, exposed body cavities, cold intravenous fluids, altered thermoregulatory control, and reduced metabolic rate. Prevention of hypothermia is a major goal of the anesthesiologist during anesthetic care.24 Neurologic Effects General anesthetics distribute well to all parts of the body, becoming most concentrated in the fatty tissues. The CNS is the primary site of action of anesthetics. Most likely, loss of consciousness and amnesia ensue from supraspinal action (i.e., action in the brain stem, midbrain, and cerebral cortex), while immobility in response to noxious stimuli is caused by depression of both supraspinal and spinal sensory and motor pathways. Different sites in the M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics. 294 | Clinical Pharmacology in Athletic Training CNS are observed differentially with increasing depth of anesthesia.32 Levels of Sedation The levels of sedation occur in a dose-related continuum, which is variable and depends on individual patient response to various drugs. These artificial levels of sedation start with minimal or light sedation (anxiolysis), continues to moderate sedation, then deep sedation, and finally a state of general anesthesia. The hallmarks of escalation from 1 level to the next are recognized by changes in mentation, airway competency, respiratory competency, and cardiovascular effects (table 22.1).1,10,20 This escalation in levels of sedation is often very subtle and unpredictable; therefore, the anesthesiologist must always be ready to manage the unanticipated next level of sedation.20 Stages of Anesthesia The order of general anesthesia occurs through induction, maintenance, and recovery. Induction is the time from the administration of a potent anesthetic to the development of unconsciousness, while maintenance is the sustained period of general anesthesia. Recovery starts with the discontinuation of the anesthetic and continues until the return of consciousness and protective reflexes. Induction of anesthesia depends on how fast effective concentrations of the anesthetic reach the brain. Recovery is essentially the reverse of induction and depends on how fast the anesthetic diffuses from the brain. The depth of general anesthesia is the degree to which the CNS is depressed, which is evident in EEGs.20 Traditionally, anesthetic effects on the brain produce 4 stages or levels of increasing depth of CNS depression (figure 22.3; Guedel’s classification). Modern anesthetics act very rapidly and achieve deep anesthesia quickly. The progressively greater depth of CNS depression is associated with increasing dose or time of exposure and is traditionally described as stages of anesthesia.6,10,16,20,32 Stage I: Analgesia or Induction In stage I, the patient has decreased awareness of pain, sometimes with amnesia. Consciousness may be impaired, but it is not lost. The patient initially experiences analgesia without amnesia. Later in stage I, both analgesia and amnesia are produced. The analgesia of stage I is variable and depends on the specific anesthetic agent. With fast induction, the patient passes rapidly through the undesirable excitement phase (stage II). TABLE 22.1 Levels of Sedation Minimal sedation anxiolysis Moderate sedation or analgesia Responsiveness Normal response to verbal stimulation Purposeful* response to verbal or tactile stimulation Purposeful* response following repeated or painful stimulation Unarousable even with painful stimulus Airway Unaffected No intervention required Intervention may be required** Intervention often required** Spontaneous ventilation Unaffected Adequate May be inadequate Frequently inadequate Cardiovascular function Unaffected Usually maintained Usually maintained May be impaired Level of sedation Deep sedation or analgesia General ­anesthesia *Reflex withdrawal from a painful stimulus is not considered a purposeful response. **Intervention or rescue of a patient from a level of sedation that is deeper than intended must be performed by a practitioner who is proficient in airway management and advanced life support. The qualified practitioner corrects the adverse physiologic consequences of the deeper-than-intended level of sedation (such as hypoventilation, hypoxia, and hypotension) and returns the patient to the originally intended level of sedation. It is not appropriate to continue the procedure at an unintended level of sedation. M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics. Chapter 22 • Surgery | 295 Awake Awake Deepening anesthesia • Analgesia • Amnesia Stage II: Excitement • Hyperactivity • Delirium • Combative behavior Stage III: Surgical Anesthesia • Unconsciousness • Normal respiration • Normal blood pressure Commence surgery Recovery from anesthesia Stage I: Analgesia Surgery completed Stage IV: Medullary Depression • Cardiac depression and arrest • No eye movement • Coma • Death FIGURE 22.3 Stages of anesthesia. E7960/Cleary/F22.03/642684/mh-R2 Stage II: Disinhibition or Excitement During this stage, the patient appears delirious and may vocalize but is completely amnesic. Respiration is rapid and heart rate and blood pressure increase. The patient appears to be delirious and excited. Amnesia occurs, reflexes are enhanced, and respiration is typically irregular. Retching and incontinence may occur. Stage III: Surgical Anesthesia This stage begins with slowing of respiration and heart rate and extends to complete cessation of spontaneous respiration (i.e., apnea). In this stage, the patient is unconscious and has no pain reflexes. The skeletal muscles relax, vomiting stops, and eye movements slow and then stop. The patient is unconscious and ready for surgery. Stage IV: Medullary Depression or Overdose This deep stage of anesthesia represents severe depression of the CNS, including the vasomotor center in the medulla and the respiratory center in the brain stem. Without circulatory and respiratory support, death would rapidly ensue in stage IV.10 The anesthesiologist must take care to avoid stage IV, when the patient develops severe respiratory and cardiovascular depression that requires mechanical and pharmacologic support to prevent death.16,32 This stage is lethal without cardiovascular and respiratory support. Types of Anesthesia Some surgeries often involve a singular choice of anesthesia, whereas others incorporate multiple options. Options for the anesthesiologist and surgeon include general anesthesia (inhaled and intravenous), neuromuscular blockade, and nerve blocks (central, peripheral, and local). General Anesthesia General anesthesia induces analgesia, sedation, amnesia, suppression of reflexes, and relaxation of muscles.17 General anesthesia can be delivered by inhalation or intravenously and is well distributed to all parts of the body. The CNS is the primary site of action. Loss of consciousness and amnesia ensue from supraspinal action. Immobility is caused by depression of both supraspinal and spinal sensory and motor pathways. Different sites in the CNS are differentially affected by general anesthetics, giving rise to the classical stages observed with increasing anesthetic depth.32 Inhaled General Anesthesia Inhaled anesthetics, such as ketamine (Ketalar), are gases delivered from a machine that is operated by an anesthesiologist. They work through gas exchange in the alveoli of the lungs. Uptake from the alveoli into the blood and distribution and partitioning into the compartments within the body are important determinants of the kinetics of these agents. The ideal anesthetic should have a rapid onset (induction) and offset (emergence).8,10 Pharmacology of inhaled anesthetics relate to potency; an anesthetic that is more potent causes anesthesia at lower partial pressures. Typically, there is a tradeoff between fast induction and high potency. An anesthetic that has a rapid induction typically has a low potency. Conversely, a very potent anesthetic typically has a long induction time.32 Inhaled gases are used primarily for maintenance of anesthesia after administration of an IV drug. Depth of anesthesia can be rapidly altered M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics. 296 | Clinical Pharmacology in Athletic Training by changing the concentration of the inhaled gas. Inhalational agents have steep dose–response curves with very narrow therapeutic indices, so the difference in concentrations from eliciting general anesthesia to cardiopulmonary collapse is small. No antagonists exist. To minimize waste, inhaled gases are delivered in a recirculation system that contains adsorbents to remove carbon dioxide and allow rebreathing of the gas.20 Intravenous General Anesthesia Intravenous nonopioid anesthetics are used to facilitate rapid induction of anesthesia and have replaced inhalation as the preferred method of anesthesia induction in most settings. Intravenous agents are also commonly used to provide sedation during monitored anesthesia care. With the introduction of propofol, IV anesthesia also became a good option for the maintenance of anesthesia. These anesthetics do not produce all 5 desired effects of anesthesia (unconsciousness, amnesia, analgesia, inhibition of autonomic reflexes, and skeletal muscle relaxation), thus they are likely to be combined with multiple drugs to result in balanced anesthesia.8 Intravenous medications, commonly propofol or midazolam, are administered to establish a level of unconsciousness. In some cases, oxygen may be administered through a face mask to complement IV medication rather than incorporating an inhaled anesthetic.9 This technique is referred to as total intravenous anesthesia (TIVA). Intravenous anesthetics cause rapid induction of anesthesia, often occurring in ≤1 minute. Their use is the most common way to induce anesthesia before maintenance of anesthesia with an inhalation agent. IV anesthetics may be used as single agents for short procedures or administered as infusions (e.g., TIVA) to help maintain anesthesia during longer surgeries. In lower doses, they may be used solely for sedation.20 Balanced Anesthesia No single drug achieves all desired goals of anesthesia. The ideal anesthetic drug would provide hypnosis, amnesia, analgesia, and muscle relaxation without undesirable changes in blood pressure, pulse, or breathing. In a method called balanced anesthesia, several inhaled or intravenous drugs are used in combination, each with a specific effect, to achieve analgesia, muscle relaxation, unconsciousness, and amnesia. Balanced anesthesia attempts to target each end point with a combination of drugs, thereby reducing the dose and toxicity of each.6 The anesthetic effects of simultaneously administered general anesthetics are additive and offer a better risk profile to the person under anesthesia and rapid recovery.32 For example, propofol (injection) might be used to start the anesthetic, fentanyl (injection) to blunt the stress response, midazolam (injection) to ensure amnesia, and sevoflurane (inhaled) during the procedure to maintain the effects. Adjuvant (Adjunct) Drugs Adjuvant drugs (also called adjuncts) are a critical part of the practice of anesthesia and include drugs that affect gastrointestinal motility, nausea and vomiting, anxiety, and analgesia. Adjuncts are used in collaboration to help make the anesthetic experience safe and pleasant.20 Adjuvant drugs provide additional effects that are desirable during surgery but are not necessarily provided by the general anesthetics.32 Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or in the 24 hours following a surgical procedure. It is an unpleasant complication that affects about 10% of the population undergoing general anesthesia each year. Medications commonly used to prevent PONV are usually administered toward the end of surgery.20 Intravenous Local Anesthesia Local anesthetics can be injected intravenously into a distal extremity to provide regional anesthesia Evidence in Pharmacology Postoperative Nausea and Vomiting Postoperative nausea and vomiting following TIVA is the second most common postsurgical complaint aside from pain. Nausea and vomiting are controlled by the vomiting center, a neuroanatomical site in an ill-defined region within the reticular formation of the brain.27 The first-line approach may include a serotonin antagonist such as the antiemetic ondansetron (Zofran), which inhibits serotonin and reduces nausea and vomiting.31 Ondansetron can be administered as a postsurgical IV (4 mg) or oral (8 mg) medication for home care.27 M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics. Chapter 22 • Surgery | 297 Evidence in Pharmacology General Anesthesia Versus Regional Nerve Blocks A single center study compared general anesthesia to regional anesthesia for elderly patients with hip fractures based on the hypothesis that the regional approach would result in less morbidity and save costs. Benefits of regional anesthesia included perioperative pain control and postsurgical pain management with less reliance on opioids. The potential of postoperative hypotension was minimized with regional versus general anesthesia. Further, patients with regional anesthesia had less respiratory depression than those with general anesthesia, resulting in lower incidence of postoperative ventilator requirements that would necessitate intensive care admission. However, regional anesthesia did not reduce hospitalization costs or postoperative morbidity or mortality compared to general anesthesia.19 to that limb. Generally, practitioners encourage venous blood to drain from the limb by elevating the limb above the level of the heart before applying a proximal tourniquet and injecting the anesthetic into the vein. This approach allows high local concentrations of anesthetic to reach the nerves in the limb while limiting the redistribution of the anesthetic and thus preventing systemic toxicity. This type of local anesthesia, also called Bier block, is used for arm and hand surgery. Systemic intravenous lidocaine is used to reduce postoperative pain and is also administered for relief of chronic pain from injury or disease (e.g., diabetic neuropathy). Relief of chronic pain often lasts for weeks following a single, brief lidocaine infusion, even though the drug is cleared from the circulation within a few hours. The mechanism underlying this long duration of effect remains uncertain.5 Neuromuscular Blocks Neuromuscular blocks (or blockades) are used to facilitate endotracheal intubation and provide muscle relaxation when needed for surgery. Their mechanism of action is via blockade of nicotinic acetylcholine receptors on the skeletal muscle cell membrane.20 Paralysis, or temporary muscle relaxation with a neuromuscular blocker, is an integral part of modern anesthesia. The first drug used for this purpose was curare, introduced in the 1940s, which has now been superseded by drugs with fewer side effects and, generally, shorter duration of action. Muscle relaxation allows surgery within major body cavities, such as the abdomen and thorax, without the need for very deep anesthesia.12,20 A variety of techniques (central, peripheral, and local) for blocking neuromuscular function are crucial to the practice of anesthesia. Central Nerve Block Central nerve blocks include a variety of techniques (e.g., spinal anesthesia, also called spinal block or neuraxial blockade) that involve administration of drugs near the spinal cord by delivery into the epidural or intrathecal space (see figure 6.3).17 Central nerve blocks include both epidural and intrathecal (spinal) anesthesia. The early effects of these procedures result primarily from impulse blockade in spinal roots; in later phases, anesthetic drug penetrates and may act within the spinal cord. Bupivacaine is particularly useful as an epidural anesthetic during labor in childbirth because, at low concentrations, it provides adequate pain relief without significant motor block. Reports of bupivacaine cardiotoxicity have led to decreased use of this agent in high concentrations (>0.5% weight:volume), although the dilute solutions used in obstetrics are rarely toxic.5 An adverse event of the central nerve block process is a postdural puncture headache, which occurs if the dura is inadvertently punctured by either the epidural injection itself or the placement of an epidural catheter. This outcome may result in a leak of cerebrospinal fluid (CSF) and cause an extremely intense headache.28 This event is not common, and risk factors include needle diameter size, female patient <60 years old, and the experience of the personnel administering the injection.28,29 The patient is likely to experience the headache within 72 hours after the injection, and pain is exacerbated by standing and head motion and possibly accompanied by nausea, blurred vision, and dizziness.28,29 The most prompt resolution of this condition is the epidural blood patch, an injection of autologous blood (i.e., blood taken from the patient) into the epidural space to stop the CSF leak; this technique has an 85% success rate with 1 injection.28 Typically, the M.A. Cleary, T.E. Abdenour, and M. Pavolvich, Clinical Pharmacology in Athletic Training, Champaign, IL: Human Kinetics, 2022). For use only in Clinical Pharmacology Course 6–Sport Medics.