The goals of general anesthesia are analgesia, amnesia/hypnosis, suppression of autonomic and sensory reflexes, and skeletal muscle relaxation.⁹ Stages of anesthesia, defined by Guedel around World War I, were initially used to identify the patient’s physiologic state and monitor anesthetic depth. These stages are less relevant today due to technologic advances in monitoring and anesthetic agents with faster onset and elimination, limiting the usefulness of the classic signs and symptoms associated with the stages to assessment and care of the patient after surgery.¹⁰

Stage I, commonly called the stage of analgesia, begins with the initiation of an anesthetic agent and ends with the loss of consciousness. This stage has been described as the lightest level of anesthesia and represents mild sensory and mental depression. Patients can open their eyes on command, breathe normally, and maintain protective reflexes. The patient’s pain threshold is not appreciably lowered during this stage.

Stage II, also called the stage of delirium, begins with the loss of consciousness and ends with the onset of a regular pattern of breathing and the disappearance of the eyelid reflex. It is characterized by excitement, which can include uncontrolled movement and potentially dangerous responses to noxious stimuli. Other responses include vomiting, laryngospasm, tachycardia, and even cardiac arrest. If vomiting occurs, the patient is at risk for aspiration because of the loss of protective reflexes that is associated with this stage of anesthesia. With the use of newer and faster-acting anesthetic agents, this stage is passed through rapidly, decreasing the risk of complications. The use of propofol, etomidate, or short-acting barbiturates during the induction of anesthesia also facilitates rapid transition through stage II.

Stage III is the stage of surgical anesthesia. It lasts from the onset of a regular pattern of breathing to the cessation of breathing. This is the goal for anesthesia, because the response to surgical incision is absent. Patients experience a depression in all elements of nervous system function (i.e., sensory depression, loss of recall, reflex depression, and some skeletal muscle relaxation). Each anesthetic agent affects the patient’s clinical signs differently; therefore, monitoring the effects of anesthesia depends on the specific properties of each agent.

Stage IV is considered the stage of overdose and occurs when the patient receives too much anesthesia. In this stage, the patient shows signs of circulatory failure, and full cardiovascular and pulmonary support must be provided.

During general anesthesia, the goal is to keep the patient insensate, immobile, and safe. Recall or awareness during surgery can occur when the depth of anesthesia is inadequate (Box 42-2). Excessive anesthesia may stress the patient and increase emergence and recovery time. The level of anesthesia is monitored by continual assessment of the patient’s clinical presentation. Basic anesthetic monitoring standards adopted by the American Society of Anesthesiologists (ASA) mandate the use of pulse oximetry, capnography, an oxygen analyzer, disconnect alarms, body temperature measurements, and a visual display of an electrocardiogram (ECG) during the intraoperative period in all patients undergoing anesthesia.¹¹ The standard may be exceeded as warranted by the patient’s condition and additional monitors used. External monitoring devices used to assess levels of anesthesia include lower esophageal contractility, heart rate variability, surface electromyogram, spontaneous electroencephalographic activity monitors, and evoked potentials.

Box 42-2

Patient Safety Alert

Preventing and Managing the Impact of Anesthesia Awareness

Anesthesia awareness, also called unintended intraoperative awareness, occurs under general anesthesia when a patient becomes cognizant of some or all events during a procedure and has direct recall of those events. Because of the routine use of neuromuscular blocking agents (paralytics) during general anesthesia, the patient is often unable to communicate with the surgical team when this occurs.

The frequency of anesthesia awareness has been found in multiple studies to range between 0.1% and 0.2% of all patients undergoing general anesthesia.1–3 General anesthesia is administered to 21 million patients annually in the United States, so 20,000 to 40,000 cases of anesthesia awareness occur each year. Patients experiencing awareness report auditory recollections (48%), sensations of not being able to breathe (48%), and pain (28%).¹ More than 50% experience mental distress after surgery, including an indeterminate number with post-traumatic stress syndrome.^2,3 Some patients describe these occurrences as their “worst hospital experience,” and some determine to never again undergo surgery.

The incidence of awareness is reported to be greater in patients for whom the dose of general anesthetic must be smaller and carefully titrated to decrease significant side effects, such as a patient who is hemodynamically unstable. Procedures typically identified as falling into this category are some cardiac, obstetric, and major trauma cases.⁴ Factors contributing to the risk of anesthesia awareness include the increasing use of intravenous delivery of anesthesia, as opposed to inhalation, and the premature lightening of anesthesia at the end of procedures to facilitate operating room turnover.

Monitoring of patients under general anesthesia to prevent anesthesia awareness can be challenging. Despite a variety of available monitoring methods, awareness is difficult to recognize while it is occurring. Typical indicators of physiologic and motor response, such as high blood pressure, fast heart rate, movement, and hemodynamic changes, are often masked by the use of paralytic agents to achieve necessary muscle relaxation during the procedure, as well as the concurrent administration of other medications necessary to the patient’s management, such as beta-blockers or calcium channel blockers.

To overcome the limitations of current methods to detect anesthesia awareness, new methods are being developed that are less affected by the medications typically used during general anesthesia. These devices measure brain activity rather than physiologic responses. These electroencephalography devices (also called level-of-consciousness, sedation-level, or anesthesia-depth monitors) include the Bispectral Index (BIS), spectral edge frequency (SEF), and median frequency (MF) monitors. These devices may have a role in preventing and detecting anesthesia awareness in patients with the highest risk, thereby ameliorating the impact of anesthesia awareness. A body of evidence has not yet accumulated to precisely define the role of these devices in detecting and preventing anesthesia awareness; The Joint Commission expects additional studies on these subjects to emerge. In its review of the BIS monitor, the U.S. Food and Drug Administration determined that “Use of BIS monitoring to help guide anesthetic administration may be associated with the reduction of the incidence of awareness with recall in adults during general anesthesia and sedation.”

The anesthesia professional must often balance the psychologic risks of anesthesia awareness against the physiologic risks of excessive anesthesia for many critical medical conditions. The Joint Commission has asked the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) to address the adequacy of current monitoring practices regarding anesthesia levels, including those practices that involve little or no technologic support. The ASA recommends in its 2006 practice advisory that intraoperative monitoring include clinical (e.g., purposeful or reflex movement), conventional monitors (e.g., end-tidal anesthetic analyzer, HR, BP), and brain function monitoring on a case-by-case basis.⁵ Multimodal monitoring is suggested rather than reliance on any single monitor.

Reducing the Risk of Anesthesia Awareness

The ASA and the AANA provide guidelines for administering and monitoring anesthesia. Specific recommendations for the prevention of awareness were addressed in the February 2000 issue of Anesthesiology⁴:

• Consider premedication with amnesic medications (e.g., benzodiazepines, scopolamine), particularly when light anesthesia is anticipated.

• Administer more than a “sleep dose” of induction agents if they will be followed immediately by tracheal intubation. Avoid muscle paralysis unless absolutely necessary and, even then, avoid total paralysis (by using only the amount clinically required).

• Conduct periodic maintenance of the anesthesia machine and its vaporizers, and meticulously check the machine and its ventilator before administering anesthesia.

• Be alert to patients taking beta-blockers, calcium channel blockers, or other medications that can mask physiologic responses to inadequate anesthesia.

Managing the Impact of Anesthesia Awareness

Anesthesia awareness cannot always be prevented. Health care practitioners must be prepared to acknowledge and manage the occurrence of anesthesia awareness with compassion and diligence. The following practices are suggested when patients report awareness ⁴:

• Interview the patient after the procedure, taking a detailed account of his or her experience and including it in the patient’s chart.

• Apologize to the patient if anesthesia awareness occurred.

• Assure the patient of the credibility of his or her account, and sympathize with the patient’s suffering.

• Explain what happened and its reasons (e.g., the necessity to administer light anesthesia in the presence of significant cardiovascular instability).

• Offer the patient psychologic or psychiatric support, including referral to a psychiatrist or psychologist.

• Notify the patient’s surgeon, nurse, and other key personnel about the incident and the subsequent interview with the patient.

Surgical team members should also be educated about anesthesia awareness and its management.

Joint Commission Recommendations

Anesthesia awareness is underrecognized and undertreated in health care organizations. The Joint Commission recommends that health care organizations performing procedures under general anesthesia take the following steps to help prevent and manage anesthesia awareness:

1. Develop and implement an anesthesia awareness policy that addresses the following:

• Education of clinical staff about anesthesia awareness and how to manage patients who have experienced awareness.

• Identification of patients at proportionately higher risk for an awareness experience and discussion with such patients, before surgery, of the potential for anesthesia awareness.

• The effective application of available anesthesia monitoring techniques, including timely maintenance of anesthesia equipment.

• Appropriate postoperative follow-up of all patients who have undergone general anesthesia, including children.

• The identification, management, and, if appropriate, referral of patients who have experienced awareness.

2. Ensure access to necessary counseling or other support for patients who are experiencing post-traumatic stress syndrome or other mental distress.

References

1. Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anesthesia: a multicenter United States study. Anesth Analg. 2004;99(3):833.

2. Lennmarken C, Sandin R. Neuromonitoring for awareness during surgery. Lancet. 2004;363(9423):1747.

3. Osterman JE, Hopper J, Heran WJ, et al. Awareness under anesthesia and the development of posttraumatic stress disorder. Gen Hosp Psychiatry. 2001;23(4):198.

4. Ghoneim MM. Awareness during anesthesia. Anesthesiology. 2000;92(2):597.

5. Practice advisory for intraoperative awareness and brain function monitoring: A report by the American Society of Anesthesiologists Task Force on Intraoperative Awareness. Anesthesiology. 2006;104:847.

Bibliography

Ekman A, Lindholm ML, Lennmarken C, et al. Reduction in the incidence of awareness using BIS monitoring. Acta Anaesthesiol Scand. 2004;48(1):20.

Liska JM. Silenced screams: surviving anesthetic awareness during surgery—a true-life account. Park Ridge, IL: AANA Publishing, Council for Public Interest in Anesthesia; 2002.

Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet. 2004;363(9423):1757.

Modified from The Joint Commission. Sentinel event alert. Issue 32. October 6, 2004. http://www.jointcommission.org/SentinelEvents/SentinelEventAlert/sea_32.htm. Accessed September 2012.

Anesthetic Agents

Typically two or more anesthetic agents are used in combination to achieve the desired level of anesthesia. To anticipate the patient’s response, it is important for the nurse to have knowledge of the anesthetic agents that are used and their usual physiologic effects.² The characteristics of ideal anesthetic agents and adjuncts are listed in Box 42-3.

Inhalation Agents

Inhalation agents are used for induction and maintenance of anesthesia or, in combination with other anesthetic agents, to maintain surgical anesthesia. They can be classified as volatile or gaseous. Volatile agents are further classified as halogenated hydrocarbons or ethers, are liquid at room temperature, and have a boiling point of 20° C. Gaseous agents are gases at room temperature. Inhaled anesthetics are delivered through the respiratory tract and are absorbed into the circulation through the alveoli. The effects of inhalation agents depend on alveolar ventilation, the ventilation-perfusion ratio, co-administered gases, gas flow, and the physicochemical properties of the gas. Their exact mechanism of action is unknown, but all cause central nervous system (CNS) depression and a state of unconsciousness that is deep enough to allow surgery. Table 42-1 lists the inhalation anesthetics presently used and their chief characteristics, effects, and nursing implications.¹⁰

TABLE 42-1

INHALATION ANESTHETICS

MEDICATION	CHARACTERISTICS	EFFECTS	CONSIDERATIONS
Nitrous oxide	Light anesthetic; inorganic gas; nontoxic, nonirritating; carrier for other inhalation agents; always given with oxygen	Anesthetic and analgesic; minimal pulmonary, cardiac, or CNS effects; increases intracranial pressure; amnesia	Eliminated by ventilation; postoperative nausea and vomiting; diffusion hypoxia; mild myocardial depression
Isoflurane (Forane)	Pungent, ether-like odor; low potential for toxicity; volatile agent	Higher cardiovascular stability; potentiates muscle relaxants	Mild depression of spontaneous ventilation; may trigger malignant hypothermia; postoperative shivering; fewer dysrhythmias noted
Desflurane (Suprane)	Strong, pungent odor; rapid onset; volatile agent; requires warmed vaporizer for administration	Minimal metabolism; respiratory depression; cardiovascular depression; no lingering analgesia	Observe for breath holding; coughing and laryngospasm; may trigger malignant hypothermia; needs immediate postoperative analgesia
Sevoflurane (Ultane)	Nonirritating to airway; volatile agent; choice for pediatric anesthetic	Minimal airway irritation; rapid elimination; great precision and control over anesthetic depth; decreases SVR	May trigger malignant hypothermia; observe for breath holding; needs immediate postoperative analgesia

CNS, Central nervous system; SVR, systemic vascular resistance.

Intravenous Anesthetics

Because inhalation anesthetics can produce adverse effects such as vasodilation, hypotension, dysrhythmias, and myocardial depression, other medications and methods of delivery have been sought to provide general anesthesia. Intravenous anesthetics are commonly used in the perioperative period. Intravenous anesthetics are grouped by their primary pharmacologic action as nonopioid or opioid intravenous agents.12–14 The nonopioid agents are further divided into the barbiturates, nonbarbiturates, and sedatives. These medications can be administered by intermittent intravenous push dosing to induce anesthesia or by continuous intravenous drip to maintain anesthesia.

Nonopioid Intravenous Anesthetics

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. The nonopioid medications appear to interact with GABA in the brain. Activation of the GABA receptors inhibits the postsynaptic neurons and results in a loss of consciousness. Barbiturates bind to GABA postsynaptic receptors, inhibiting neuronal activity and causing a loss of consciousness. Sedatives such as benzodiazepines potentiate the action of GABA, leading to inhibition of neuronal activity. Nonbarbiturate induction agents, such as etomidate, antagonize the muscarinic receptors in the CNS and work as opioid agonists, resulting in a hypnotic state and loss of consciousness. Table 42-2 presents the nonopioid intravenous anesthetics and their effects and nursing considerations.¹²

TABLE 42-2

NONOPIOID INTRAVENOUS ANESTHETICS

MEDICATION	CHARACTERISTICS	EFFECTS	CONSIDERATIONS
Barbiturates
Sodium thiopental* (Pentothal)	Good patient acceptance; quick onset; very brief duration; no analgesia	CNS depression; spontaneous ventilation arrested; loss of laryngeal reflexes; causes histamine release (vasodilation, hypotension, and flushing)	IV administration painful; may cause myoclonus, coughing, and hiccoughs; increased risk of aspiration
Methohexital (Brevital)	Similar to thiopental but three times as potent; no analgesia; hepatic metabolism; ultra-fast onset of action	Similar to thiopental; lowers seizure threshold (epileptiform)	Similar to thiopental
Nonbarbiturates
Etomidate (Amidate)	Agent of choice in patients with cardiovascular dysfunction	Heart rate and cardiac output remain constant; minimal negative inotropic effects; suppression of adrenal function up to 5-8 hours after a single dose	May cause nausea and vomiting; burns when given IV; may cause myoclonus, laryngospasm, cough, and hiccoughs; no analgesic effects
Propofol (Diprivan)	No analgesic effect; avoid in patients with coronary stenosis, ischemia, or hypovolemia; antiemetic properties; hepatic metabolism	Minimal residual CNS effects; myocardial depressant; may decrease blood pressure 20%-25%	Rapid emergence may hasten pain awareness; low incidence of postoperative side effects; pain on administration; dose reduction in older adults, patients with cardiac disease and hypovolemia; long-term or high-dose infusions can result in hypertriglyceridemia; contraindicated in patients allergic to soybean oil, egg lecithin, or glycerol
Dissociative Anesthetic
Ketamine (Ketalar)	Profound analgesia and unconsciousness; provides amnesia; may be used alone, may be given IV, IM, or PO	Produces cardiovascular and respiratory stimulation; may increase blood pressure and heart rate 10%-50%; increases intracranial pressure	Monitor for and prevent emergent reactions; minimize stimulation of the patient during emergence; titrate pain medications; benzodiazepines or dexmedetomidine may help reduce agitation during emergence
Butyrophenones
Haloperidol (Haldol)	Limited use in anesthesia because of long duration; antipsychotic; antiemetic	—	High incidence of extrapyramidal reactions Potential for torsade de pointes due to prolongation of QT interval
Droperidol (Inapsine)	Major tranquilizer; works with CNS as dopamine antagonist; hepatic metabolism; used in low doses for antiemetic prophylaxis	Prevents and treats nausea and vomiting; in higher doses acts as neuroleptic, causing amnesia or indifference to surroundings; adrenergic blocker, causing extrapyramidal muscle movements, hypotension, and peripheral vasodilation	Postanesthetic dysphoria (internalized overwhelming fear); effects last longer than those of opioids (rare in low doses); prolongs QT interval
Benzodiazepines
Diazepam (Valium)	Rapid onset; long half-life; anterograde amnesic; effective anxiolysis; renal excretion	—	Titrate opioid medications and monitor for respiratory depression; used orally as premedicant
Midazolam (Versed)	Rapid onset; short duration; potent amnesic; effective anxiolysis; hepatic metabolism	—	Reduce dose in older adults, debilitated, use cautiously in patients with myocardial ischemia, COPD, and hepatic disease; titrate opioid medications; monitor for respiratory depression
Lorazepam (Ativan)	Slow onset of action; long duration; anticonvulsant action; hepatic metabolism; renal excretion; no active metabolites	Pronounced sedation; minimal cardiovascular effects	Poor IV compatibility; titrate opioid medications and monitor for respiratory depression; watch for orthostatic hypotension

CNS, Central nervous system; COPD, chronic obstructive pulmonary disease; IM, intramuscular; IV, intravenous; PO, per os (orally).

^*Unavailable in United States since January 2011.

Benzodiazepine Antagonists

Flumazenil (Romazicon) reverses the sedative, amnesic, respiratory depressant, and muscle-relaxant effects of benzodiazepines.¹⁴ This medication is specific for the benzodiazepine receptors and does not reverse the effects of barbiturates or opiates. It should be used with caution in patients who have a history of seizures or chronic benzodiazepine use, as it can precipitate seizures. Because flumazenil has a shorter duration of action than most of the benzodiazepines, the risk of resedation can occur after the initial dose starts to wear off, especially when high doses of benzodiazepines are administered. The patient must be monitored for resedation and other residual effects. If the patient develops signs of resedation, flumazenil is repeated at 20-minute intervals. Flumazenil has proved to be a valuable asset in the care of the patient who has received an excessive dose of a benzodiazepine such as midazolam or lorazepam. Consequently, flumazenil is very useful intraoperatively, postoperatively, and in the critical care unit.

Opioid Intravenous Anesthetics

Intravenous opioid anesthetics play an important role in clinical anesthesia care. These medications enhance the effectiveness of inhalation agents by providing the analgesic portion of the anesthetic process. Intravenous opioids blunt the sympathetic response to painful stimuli during anesthesia. The use of opioids allows for reduction in the concentration of the inhalation agent to be administered, increasing safety. Opioids bind to specific receptors and produce a morphine-like or opioid agonist effect. Opioids are used to manage acute and chronic pain and are administered for general anesthesia, sedation, and pain relief during regional anesthesia; they are important in all phases of the perioperative experience. Table 42-3 presents a summary of clinical uses and nursing implications for the most frequently used opioids.¹³

TABLE 42-3

OPIOID ADJUNCTIVE AGENTS *

CLINICAL USES	IMPLICATIONS	CONSIDERATIONS
Preoperative sedation	Monitor for hypotension	Keep naloxone (Narcan) available
Induction of anesthesia	Monitor for bradycardia	Keep resuscitation equipment available
Maintenance of anesthesia	Monitor for respiratory depression	Respiratory depressant effect may outlast analgesia
Postoperative pain management	May cause nausea and vomiting

^*Agents include alfentanil (Alfenta), fentanyl (Sublimaze), ketorolac (Toradol), morphine, sufentanil (Sufenta), remifentanil (Ultiva), and hydromorphone (Dilaudid).

Opioid Antagonists

Opioid antagonists are used to reverse the effects of opioids, particularly respiratory depression, restoring spontaneous ventilation in patients who are breathing inadequately. The medication of choice in perianesthesia care is naloxone (Narcan). Naloxone competes with and displaces the opioid on the receptor site; it therefore reverses respiratory depressant and analgesic effects of opioids. Naloxone is diluted and then titrated to the patient’s response, minimizing the risk of rapid reversal and subsequent adverse effects. The onset of action is 1 to 2 minutes and the duration of action is 1 to 4 hours. If adequate reversal has not been achieved after 3 to 5 minutes, naloxone administration is repeated until reversal is complete.¹⁵

If long-acting opioids are used, the patient must be monitored for respiratory insufficiency, because the depressant effects of the opioids may return. Often, a low-dose, continuous intravenous drip of naloxone proves effective. Close monitoring of vital signs is critical. Monitor the patient for increased blood pressure, which may occur in response to pain following large doses of naloxone. In addition, tachycardia, nausea, vomiting, or diaphoresis may occur if the reversal is too rapid. Naloxone must be used with caution in patients with cardiac irritability and in patients who are physically dependent on opioids, because reversal may precipitate an acute withdrawal syndrome.

Neuromuscular Blocking Agents

Neuromuscular blocking agents (NMBAs), or muscle relaxants, interrupt the transmission of impulses from the nerve to the muscle, causing a decrease in muscle activity. Decreasing muscle activity allows the surgeon to operate in a quiet field and decreases the need for deep anesthesia. These medications have contributed greatly to clinical anesthesia care. Use of NMBAs is not limited to the operating room; they are used to facilitate endotracheal intubation, to terminate laryngospasm, to eliminate chest wall rigidity that may occur after the rapid injection of potent opioids, and to facilitate mechanical ventilation by producing total paralysis of the respiratory muscles.¹⁵

NMBAs cause paralysis of the respiratory muscles, and the patient receiving these agents requires ventilatory support with a handheld bag-valve-mask device or a mechanical ventilator. NMBAs do not have analgesic, amnesic, anxiolytic, or sedative effects. The paralyzed patient is not able to communicate his or her needs; NMBAs must be used in combination with other medications to prevent pain and provide sedation.

Skeletal muscle contraction occurs when acetylcholine is released from the motor neuron and binds to receptor sites on the muscle fiber (i.e., neuromuscular junction), resulting in depolarization. Skeletal muscle relaxation occurs when the release of acetylcholine ceases and any residual acetylcholine is destroyed by the enzyme acetylcholinesterase, resulting in repolarization. NMBAs interfere with the relationship between acetylcholine and the receptor. There are two general categories of skeletal muscle relaxants: nondepolarizing and depolarizing.

Depolarizing agents compete with acetylcholine at the neuromuscular junction, causing the muscle to depolarize and inhibiting repolarization. The muscle stays in a prolonged depolarized state, and movement is inhibited. The principal depolarizing skeletal muscle agent is succinylcholine (Anectine). After succinylcholine attaches to the receptor, a brief period of depolarization occurs, which is manifested by transient muscular fasciculations. Succinylcholine has a rapid onset, 60 to 90 seconds, and a short duration of action, 5 to 10 minutes. It is frequently used to facilitate intubation. Succinylcholine cannot be pharmacologically reversed.

Nondepolarizing NMBAs are typically longer-acting agents than depolarizing agents. Nondepolarizing agents do not cause initial muscle contraction or depolarization. They compete with and block the uptake of acetylcholine at the muscle receptor site and prevent repolarization. Sustained muscle relaxation occurs, and voluntary control of skeletal muscle contraction is weakened or lost.

Table 42-4 presents a pharmacologic overview of the commonly used skeletal muscle relaxants.¹⁶ A number of factors can potentiate or antagonize the effects of nondepolarizing NMBAs; these factors are listed in Box 42-4.¹⁷

Box 42-4 Factors Influencing Neuromuscular Blockade

• Antibiotics (gentamicin, tobramycin, amikacin, kanamycin, neomycin, polymyxin B, clindamycin, tetracyclines, piperacillin, streptomycin)

• Antidysrhythmics (procainamide, lidocaine, quinidine)

• Beta-adrenergic blockers

• Calcium channel blockers

• Diuretics (furosemide, thiazides)

• Hepatobiliary disease

• Renal failure

• Neuromuscular diseases

• Sympathomimetic agents

• Corticosteroids

• Azathioprine

TABLE 42-4

NEUROMUSCULAR BLOCKING AGENTS *

	IMPLICATIONS
CHARACTERISTICS	DEPOLARIZING	NONDEPOLARIZING
Compete with acetylcholine at the myoneural junction	Nonreversible	Reversible with time and anticholinesterases
	Use cautiously in patients with neuromuscular disease, such as myasthenia gravis or muscular dystrophy; contraindicated for pediatric use except in emergencies	Use cautiously in patients with hepatic or renal disease, obesity, asthma, or COPD
Shorter-acting agents are most appropriate for anesthesia	Adverse effects include bradycardia, tachycardia, ventricular dysrhythmias, asystole, hypertension, hyperkalemia	Adverse effects include tachycardia, hypertension, hypotension, bronchospasm, and flushing
Provide surgical relaxation Facilitate intubation	Increases intraocular, intracranial, and intragastric pressure
Assist in ventilatory support	Precipitates muscle fasciculations and pain
	Prolongs respiratory depression
	Histamine release causes hypotension
	Use cautiously in patients with head injury, cerebral edema, trauma, burns, electrolyte imbalances, and renal or hepatic disease
	Monitor for clinical signs of malignant hyperthermia

^*Long-acting agents include pancuronium (Pavulon); intermediate-acting agents include atracurium (Tracrium), vecuronium (Norcuron), and cisatracurium (Nimbex); short-acting agents include rocuronium (Zemuron) and succinylcholine (Anectine), which is a depolarizing agent.

Neuromuscular Blocking Agent Antagonists

The pharmacologic actions of nondepolarizing NMBAs can be reversed by anticholinesterase medications such as neostigmine (Prostigmin). These medications increase the amount of acetylcholine available at the receptor sites by preventing its destruction by acetylcholinesterase. This promotes more effective competition of acetylcholine with the nondepolarizing skeletal muscle relaxant that is occupying the receptor sites. Because of the increased availability and mobilization of the acetylcholine, the concentration gradient favors acetylcholine and the removal of the nondepolarizing agent from the receptors, resulting in the return of normal skeletal muscle depolarization and contraction.¹⁸ These medications also produce undesired side effects by increasing the level of acetylcholine at receptor sites in the heart, the lungs, the eyes, and gastrointestinal tract, which can lead to bradycardia, bronchospasm, miosis, and increased peristalsis and secretion. To prevent or minimize these effects, anticholinergic agents such as atropine or glycopyrrolate (Robinul) are given with the anticholinesterase agent. Table 42-5 outlines the common NMBA reversal agents used in anesthesia and their nursing implications.¹⁸

TABLE 42-5

NMBA REVERSAL AGENTS

MEDICATION	CHARACTERISTICS	EFFECTS	CONSIDERATIONS
Anticholinesterase
Neostigmine (Prostigmin)	Binds with cholinesterase and inactivates it Preserves endogenous anticholinesterase More effective in antagonizing intense blocks than pyridostigmine or edrophonium