Moderate. Sedation. Learning. Module

Transcription

1 Moderate Sedation Learning Module Original by: Robert DeVore, M.D., Scripps Hospital East County Edited for Oak Valley Hospital District, Revised 07/03 (approved MEC 08/03)

2 Page 2 Table of Contents Section Section Title Page # I Introduction 3 II Learning Objectives 3 III Definitions 4 IV Patient Criteria 4 V Comparison of Moderate Sedation and General Anesthesia 6 VI Medications Used for Moderate Sedation 6 VII Mechanisms of Action for Medications used in Moderate Sedation 6 VIII Narcotic Analgesics 8 IX Benzodiazepines 11 X Other Medications Used for Moderate Sedation 14 XI Antagonist Used in Moderate Sedation 16 XII Medication Administration 17 XIII Assessment 18 XIV Pulse Oximetry 22 XV Potential Complications of Moderate Sedation 24 XVI Conclusion 30 Appendix A - Common IV Drugs Used in Moderate Sedation 31 Appendix B - Pre-Procedure Sedatives in Children 33 Appendix C - Medical Staff Policy: Moderate Sedation 34 Appendix D - Test 35 Appendix E - Reference List 38

3 Page 3 I. Introduction This module has been developed to assist physicians administering moderate sedation to patients within Oak Valley Hospital District. It provides an introduction to the standardized method of assessing, monitoring, and treating patients in diverse locations within the system. Standards set forth here have been determined to be minimum safe standards, and, therefore, are a requirement. These standards may be exceeded, if clinically indicated. Why is a Protocol and Learning Module needed for moderate sedation? Regulations concerning moderate sedation resulted from publicized adverse outcomes to patients receiving medications outside the operating room shortly after the introduction of the benzodiazepine midazolam (Versed ). By 1990, the FDA had received reports of more than 66 deaths associated with its use, mostly outside the operating room. Most of these reports were associated with administration of midazolam to the patient with little or no monitoring. In an attempt to increase patient safety, accrediting organizations have now required that patients receiving moderate sedation receive the same standard of care as patients in the Operating Room. This Learning Module attempts to provide information and bring all professionals to a common level of basic knowledge. Why do I need to prove that I am competent in moderate sedation? While there is some measure of satisfaction about learning and improving professional performance, regulations and position statements now mandate such training. Acquaintance with these standards and good practice will reduce your personal risk if a legal action occurs. The Joint Commission requires evidence of competence be documented and reviewed on a periodic basis. II. Learning Objectives 1. Define moderate sedation and its objectives. 2. Be familiar with monitoring criteria needed to reduce complications during moderate sedation. 3. Be familiar with dosage, actions, side effects of medications that are administered during moderate sedation. 4. Identify nursing implications and treatment interventions of moderate sedation. 5. Describe the function of pulse oximetry during moderate sedation. 6. Identify and describe the limitations of pulse oximetry. 7. Be familiar with medications used for the reversal of moderate sedation. 8. Be familiar with common possible complications of moderate sedation. 9. A privileged RN is required to assist with procedures under moderate sedation. 10. Be familiar with cardiac dysrhythmias that may occur as a result of administration of moderate sedation. 11. Be familiar with airway management maneuvers essential for treatment of moderate sedation. 12. Be familiar with the requirements for a pre-procedure assessment for a patient undergoing moderate sedation. 13. Understand the American Society of Anesthesiologists Physical Status categories.

4 Page 4 III. Definitions Moderate Sedation: A level of lesser consciousness produced by the administration of pharmacologic agents to enable a patient to tolerate a medical procedure that is invasive, manipulative or constraining for diagnostic, surgical or therapeutic reasons. A patient under moderate sedation has a depressed level of consciousness but retains the ability to independently and continuously maintain a patent airway and respond appropriately to physical stimulation and / or verbal commands. Light Sedation: The administration of medications for the reduction of anxiety. In this stage the following should be present: 1) normal respirations; 2) normal eye movement; 3) intact protective reflexes. Deep Sedation: A medically controlled state of depressed consciousness or unconsciousness from which the patient is not easily aroused. It may be accompanied by a partial or complete loss of protective reflexes, and includes the inability to maintain a patent airway independently and respond purposefully to physical stimulation or verbal command. Amnesia: Elimination or impairment of memory. Anterograde Amnesia: Memory loss or impairment from the point of reference. Retrograde Amnesia: Memory loss or impairment that takes place before the point of reference. Analgesia: Diminution or elimination of pain in the moderate patient. Local Anesthesia: Elimination of sensation in a part of the body by direct injection of local anesthetic into the area being numbed. Anesthesia: Dr. Prys Robert s definition encompasses four discrete physiologic categories. 1) Amnesia (the inability to remember), 2) analgesia (pain relief), 3) muscle relaxation and 4) the ablation of the autonomic stress response. The autonomic responses are further defined to include ablation of sympathoadrenal activity that elevates blood pressure and heart rate, diaphoretic response, and attenuation or elimination of peptide release associated with stress. The important point to understand, in contrast to moderate sedation, under anesthesia a patient s ability to maintain a patent airway may be lost at any time. IV. Patient Criteria Why use moderate sedation compared to other anesthesia techniques? Moderate sedation is used to minimize patient discomfort associated with invasive procedures where local or no anesthesia might produce unacceptable patient pain or anxiety. A second reason to select moderate sedation would be to avoid general or major conduction anesthesia with the associated increased patient risk. Monitored anesthesia care would be selected when a general or regional anesthetic is not chosen, and the patient s hemodynamics, physiologic parameters, and airway management merit continuous attention by an airway management specialist. It should be emphasized the transition between moderate sedation and an intravenous general anesthetic can be achieved with only small incremental doses of medications. A comparison of moderate sedation and general anesthetics is provided in the next section.

5 Page 5 It is the physician s responsibility to differentiate between light sedation (no special monitoring required) versus moderate sedation (special monitoring required) versus Monitored Anesthesia Care (anesthesiologist required). What are the patient goals of conscious sedation? Alter the mood of the patient; Depress but maintain consciousness; Elicit patient cooperation; Elevate the patient s pain threshold; Achieve control of patient physiologic parameters; Provide sedation. What procedures utilize moderate sedation? Moderate sedation may include but not be limited to: Fiber optic bronchoscopy Gastrointestinal endoscopy Central line placement Bone marrow aspiration Liver biopsy Cardioversion CT Scans MRI Invasive radiologic procedures Chest tube insertion Suturing Where might moderate sedation be administered? Intensive Care Units Emergency Department Cardiac Cath Lab Endoscopy Suite Post Anesthesia Care Unit Ambulatory / Outpatient Surgery Unit Radiology Other locations where monitors and monitoring personnel as appropriate Privileged RN s must be present during and after a procedure performed under moderate sedation. It is to the physician s advantage to assure, well in advance, that qualified personnel and the appropriate monitoring equipment is available for the planned procedure. Who may not be a candidate for moderate sedation? Patients who are hemodynamically unstable, neurologically impaired or challenged, have severe cardiopulmonary disease, or in whom it is anticipated that loss of the airway is likely, are generally not candidates for moderate sedation.

6 Page 6 V. Comparison of Moderate Sedation & General Anesthesia Medications administered for moderate sedation and general anesthesia frequently differ only in dosage. There is no absolute quantity of medication that is considered to achieve moderate sedation. The table that follows characterizes clinical findings of moderate sedation and general anesthesia: Moderate Sedation Patient maintains his/her own airway Mood altered Patient moderate Patient cooperative Protective reflexes active and intact Vital signs stable Analgesia may be present Amnesia may be present Risk of complications low Post operative complications infrequent Extremely difficult or mentally handicapped cannot always be managed General Anesthesia & Other Anesthesia Techniques Airway support likely Patient unconscious, uncooperative Protective reflexes obtunded Vital signs labile Pain eliminated centrally Amnesia always present Risk of complications higher Post operative complications not infrequent May be only method by which extremely difficult or mentally handicapped patients can be managed Ref.: CR Bennett Moderate Sedation in Dental Practice 2 nd Edition CV Mosby St. Louis 1978 VI. Medication Used for Moderate Sedation A vast number of medications in the hospital formulary have the potential to produce airway reflex loss. For the purpose of this study module, only the most commonly used medications are discussed. It is incumbent upon the physician and RN to be aware of dosages, effects, and side effects of any medication that she/he administers. Monitoring guidelines developed by the Department of Surgery, Anesthesia Section should be followed. Major types of medications discussed in this learning model will be opiates, benzodiazepines and their respective reversal agents. Other medications such as propofol and sodium thiopental that are not routinely used in specialty areas for moderate sedation have been excluded from the study module. VII. Mechanisms of Action for Medications Used in Moderate Sedation A. Receptor Theory: Like many drugs administered to patients, opiates and benzodiazepines have been found to interact with specific receptors in the human body. The effect on the patient is directly related to the attachment of a given drug to the receptor(s). The drug and receptor complex initiate a cascade of intracellular events via second messengers that terminate with the end effect of the drug. Drug receptor theory is based on structural specificity (stereo-specific) schematized as a lock and key model. Imagine a drug as the key trying to fit into the receptor, the lock. One can easily see that only a drug with specific biochemical structure will interact with a certain shaped receptor. Once the key fits into the lock, the actions of the drug become manifest.

7 Page 7 Using the lock and key model, it is possible to understand how drug antagonists function. The antagonist may fit the lock mechanism in a slightly different way and cause difficulty in opening the lock or cause the lock not to open. Both the agonist and antagonist fit into the lock, but only the agonist is able to turn the tumblers and actuate an effect. B. Opiate Receptors: Opioids are exogenous substances that bind specifically to the opioid receptors and produce an agonist response. The affinity of most opioid agonists for their receptors correlates with agonist analgesic activity. Endogenous opioids known as endorphins also stimulate opioid receptors. Opioid receptors are found throughout the entire nervous system. Presently, five receptor types (mu, delta, kappa, sigma, and epsilon) are known. Mu, delta, and kappa receptors have a number of other functions but all are believed to be involved in pain relief. The mu receptor is believed to be the most important of the three opiate receptors concerned with pain relief. Like the adrenergic receptors, there appear to be mu1 and mu2 receptors. Mu1 receptors modulate analgesia, mu2 receptors modulate respiratory depression. The mu receptor (µ) is found mainly in the brain and is stimulated by morphine, meperidine, fentanyl and fentanyl analogs. Mu receptors are responsible for supraspinal analgesia, ventilatory depression, most cardiovascular effects and physical dependence. Kappa receptors mediate spinal analgesia and respiratory depression but to a lesser extent than mu receptors. C. Benzodiazepine Receptors: Benzodiazepines and barbiturates exert their pharmacologic effects by interaction with gamma aminobutyric acid (GABA) receptors. GABA is the major inhibitory neurotransmitter located within the central nervous system. GABA modulates and counterbalances excitatory neurotransmitters such as norepinephrine or acetylcholine. The greatest concentrations of benzodiazepine (BZ) receptors are located in the cerebral cortex, cerebellum, hippocampus, substantia nigra, inferior colliculus and olfactory bulb. Lesser concentrations are found in the stratium, lower brain stem and spinal cord. Pharmacological effects seem to be related to the percentage of bound receptors although BZ s amnestic or anticonvulsant manifestations remain poorly understood. Barbiturates enhance the effect of GABA at lower concentrations producing sedation and hypnosis. At higher concentrations, barbiturates mimic the GABA molecule. This mimicry is believed responsible for barbiturate anesthesia. D. Agonist-Antagonist: An agonist-antagonist is a drug that is an agonist (stimulates) at one type receptor, but an antagonist (inhibits) at a second. A goal in drug research has been to identify a drug that stimulates mu1, kappa, and delta receptors without producing stimulation of mu2 (respiratory depression). Attempts at synthesis have been less than successful probably because mu1 does not exclusively produce pain relief and mu2 does not exclusively produce respiratory depression. Clinically, agonist-antagonists are used as pre-medicants, analgesics, and anesthetic adjuncts, but rarely as the primary anesthetic agent. These drugs appear to have a ceiling effect on respiratory depression. After a certain amount is given, there is no further respiratory depression; it plateaus no matter how much additional medication is given. To further complicate matters, at higher dose levels, these mixed agonist-antagonists reverse their own analgesia.

8 Page 8 VIII. Narcotic Analgesics A. Opiates: Narcotics have many categorization methods. They may be classified as naturally occurring opioids (morphine, codeine), semi synthetic (heroin, buprenophine) and synthetic (meperidine, fentanyl and nearly all other opiates used in clinical practice). A second method of classification is determined by whether or not there is stimulation or nonstimulation of the opiate receptor. As such they may be classified as 1) agonists (morphine, fentanyl, meperidine); 2) mixed agonists (nalbuphine, butorphanol); and 3) antagonists (naloxone). These drugs variously mimic naturally occurring endogenous substances (endorphins) on the opiate receptors. For the purposes of this learning module, the terms opioids, opiate, narcotic, and narcotic analgesic may be used interchangeably. General properties of opioids include production of analgesia without loss of touch, proprioception, or consciousness. At one time special attributes were identified and attributed to narcotics. The general perception in the 1990 s is that all opiates given at equal analgesic levels - with few exceptions - have similar side effects. That is to say, if a nurse administers an equianalgesic dose of codeine and meperidine, the depression, cough suppression, muscular rigidity, histamine release, itching, nausea and vomiting, constipation, biliary colic, urinary retention are equally likely to occur providing an equivalent dose of narcotics has been administered. The opiates differ in their metabolism, duration of action, method of accumulation, and active metabolites. A few will have side effects that differ from the general effects listed. Those not described will be listed under morphine sulfate, which is the opiate to which all narcotics should be compared. Analgesic Equivalents to Morphine 10mg IM Opioid Agonist IM (mg) PO (mg) Morphine Codeine Heroin 3-5 Meperidine Oxycodone Hydromorphone Source: Anesthesia Clinics North America Vol.7-1, 1989 p.55 Signs and Symptoms of Opiate Over-dose: 1. Depressed consciousness (with eventual coma); 2. Miotic pupils (unless hypoxia is present where dilated pupils may be present); 3. Muscle flaccidity (especially of the airway); and 4. Respiratory depression with a dose-dependent decrease in respiratory rate. 5. Rapid injection of moderate to high dose narcotic can cause muscle rigidity to the point that a muscle relaxant must be given to ventilate the patient.

9 Page 9 B. Morphine Because of the above factors, airway obstruction may easily develop. The triad of hyperventilation (especially decreased respiratory rate), coma and miotic pupils is pathognomonic of opiate overdose. General: Morphine is the oldest and most widely used of all opiates. It remains the standard to which all other narcotics are compared. Morphine causes analgesia, sedation and mood alteration. Analgesia can occur without loss of consciousness, although in large doses morphine produces obtundation and coma. When therapeutic doses are given to a patient in pain, pain relief or analgesia is reported. When an identical dose is administered to a pain-free individual, nausea and vomiting are common. Furthermore, the patient may experience an inability to concentrate with drowsiness or euphoria. Cardiovascular System: Morphine has no direct effect on myocardial contractility. Large doses in healthy, supine, normovolemic patients rarely produces hypotension. However, upon standing, about forty percent of healthy patients may exhibit orthostatic hypotension. Hypotension is produced primarily through histamine release, although some can be attributed to reduction in sympathetic tone. Bradycardia occasionally develops from direct vagal nucleus stimulation. Ventilation and Respiration: Morphine (as other opioids) causes a dose dependent depression of respiratory centers and elevation of resting pco2. Further, the brain stem becomes less responsive to carbon dioxide. A dose-dependent decrease in respiratory rate and increase in tidal volume occurs. The alteration of pulmonary volumes is insufficient to prevent the development of hypercapnia. Death from opiate overdose is almost always associated with respiratory depression. If the patient is able to remain conscious however, he will be able to initiate ventilation when asked. Morphine may cause bronchoconstriction that is mediated through a histamine release mechanism. Neuro: Morphine, in the absence of hypoventilation, causes decreased cerebral blood flow. Opioids should be used with caution in head injured patients because of alteration of wakefulness and mental status. Elevation of pco2 effecting the respiratory center may increase cerebral blood flow & elevate intracranial pressure. Other Side-Effects: Biliary spasm of smooth muscle may be confused with angina pectoris. Other GI effects include decreased peristalsis and increased pyloric sphincter tone. Opiates directly stimulate the chemotrigger receptor zone within the brain stem and produce nausea and vomiting. Because of these events and pyloric and esophageal sphincter tone changes, patients receiving opiates should be considered to have full stomachs. Additional problems include prolonged post-operative somnolence, respiratory depression, and incomplete intraoperative amnesia. These side-effects are common to all opiates. C. Meperidine (Demerol ) General: Meperidine is a synthetic opiate developed in the 1930 s as an atropine like agent. While exhibiting opiate-like properties, it is chemically dissimilar. Meperidine is about one tenth as potent as Morphine with a shorter duration of action of about 2-3 hours. Meperidine is available in an oral form.

10 Page 10 Cardiovascular System: Meperidine has more cardiovascular side effects than morphine, including a negative inotropic effect when used in high doses. Because of its chemical similarity to atropine it can cause tachycardia. Ventilation and Respiration: Meperidine s effects on ventilation and respiration are similar to morphine. Central Nervous System: Large doses can produce tremors, muscle twitching and seizures. This is largely thought to be secondary to an active metabolite (normeperidine) whose accumulation is a known convulsant. Nausea and vomiting are more common with Demerol than morphine or fentanyl. D. Fentanyl (Sublimaze ) General: Fentanyl (Sublimaze ) is more rapid in onset than morphine and is of much shorter duration. It is about 100 times more potent than morphine. Analgesic effect starts within two (2) minutes of IV administration and lasts minutes. Ninety-nine (99%) percent of the medication is cleared form the body within one hour. Fentanyl in low doses (1-2 µg/kg) is used for analgesia; in moderate doses (2-10 µg/kg) as an adjunct for the volatile anesthetics; and in high doses ( µg/kg) as a sole anesthetic. Generally not used alone but in combination with a benzodiazepine. Cardiovascular System: High dose fentanyl lacks a direct myocardial depressant effect, lacks histamine release, and is effective in suppressing the stress response associated with surgery. High dose fentanyl requires less intraoperative fluid replacement compared to morphine. Disadvantages of high dose fentanyl include intraoperative awareness, postoperative respiratory depression requiring controlled mechanical ventilation and in the cardiovascular system, increase in heart rate and blood pressure on painful stimulation. It rarely causes bradycardia. Ventilation and Respiration: Fentanyl and its analogs when given rapidly intravenously in moderate or high doses produce skeletal muscle rigidity, especially in the truncal area. This stiff chest syndrome is occasionally so severe that adequate lung ventilation is not possible. In that case, rapid paralysis with a muscle relaxant may be required. Rapid fentanyl injection speed increases the incidence of rigidity. Table: Comparison of Morphine, Demerol and Fentanyl Morphine Demerol Fentanyl Overall Dose 0.1 mg/kg 1 mg/kg 1-2 mcg/kg (Titrate to effect) Onset 2 minutes 1-5 minutes 1 minute Peak minutes minutes 2-15 minutes Duration 1-2 hours 1-2 hours 0.5 hours Half Life 3-7 hours 2-6 hours 3-4 hours Max Dose 10 mg in 60 minutes 100 mg in 60 minutes 200 mcg in 60 minutes

11 Page 11 E. Butorphanol (Stadol ) General: Butorphanol is a mixed agonist-antagonist about five times more potent than morphine. Because it is not an opiate but an agonist-antagonist, its respiratory depression is less than morphine. Given IM, it peaks within one hour. Duration of action is similar to morphine. As with other agonist antagonist agents, abuse potential is considered low. Many patients report an unpleasant dysphoria with this drug; some patients become hypertensive. Cardiovascular System: In healthy volunteers, 0.03 to 0.06 mg/kg IV produces no significant cardiovascular changes. In patients with cardiac disease, similar doses produce and increase cardiac output, blood pressure and pulmonary artery pressure increasing myocardial oxygen demand. Given as a supplement to volatile anesthetics, adequate analgesia is provided. F. Nalbuphine (Nubain ) General: Nalbuphine is similar to morphine and its onset, duration and potency. When these drugs are used with the pure mu agonists, such as morphine, fentanyl, or meperidine, the agonist-antagonists reverse the mu receptor induced respiratory depression. Dysphoria is uncommon with this drug. Cardiovascular System: Compared to butorphanol, it has little or no hemodynamic effect. IX. Benzodiazepines Benzodiazepines are some of the most widely used agents employed for moderate sedation. While several dozen are presently being or have been marketed, only diazepam (Valium ) and midazolam (Versed ) and lorazepam (Ativan ) will be discussed. A benzodiazepine antagonist, flumazenil (Romazicon ) is now available. Benzodiazepines have similar effects. Given in equipotent doses benzodiazepines have comparable effects. A major difference is the method of metabolism. Indications for benzodiazepines include: amnestic, anxiolytic, anesthesia, anticonvulsant, hypnotic, muscle relaxant. The following table demonstrates pharmacodynamics of benzodiazepines and barbiturates: Hypnosis Analgesia Amnesia Barbiturates Good None Poor Benzodiazepine Good None Excellent Benzodiazepines have a rapid onset and a short duration of action. They lack analgesic properties. Benzodiazepines are rapidly taken into the brain and other highly perfused organs. These effects are rapidly reversed by the benzodiazepine antagonist, flumazenil (Romazicon ). Benzodiazepines and opiates have synergistic effects. The most noteworthy is an increased incidence of airway obstruction and apnea when these medications are used together. All benzodiazepines undergo hepatic biotransformation. For this reason, benzodiazepines clinical presentation may differ when age and disease states such as cirrhosis are present. Furthermore, if hepatic blood flow is changed (cimetidine), or microsomal oxidase system

12 Page 12 effected by other metabolites (propranolol or alcohol), distinct changes may occur in the patient s pharmacodynamic presentation. A. Diazepam (Valium ) General: Diazepam is a longer acting benzodiazepine compared to midazolam. Diazepam undergoes extensive hepatic metabolism. These are two major metabolites of diazepam, desmethyldiazepam and oxazepam, and both have pharmacologic activity contributing to diazepam s long duration of action. In the geriatric patient, the half-life may be up to 96 hours. Cardiovascular System: Diazepam administered intravenously in doses of mg/kg results in mild reductions in blood pressure, peripheral vascular resistance and cardiac output. Occasionally hypotension will occur after even small doses of diazepam. Respiratory: Diazepam causes depression of the slope of the ventilatory response to carbon dioxide, but the CO2 response curve is not shifted to the right as it is after opioids. Occasionally small doses of diazepam may result in apnea. Depression of ventilation is exaggerated in the presence of other central nervous system depressant or in COPD. Other: Diazepam reduces skeletal muscle tone via a spinal cord effect. It does not affect the neuromuscular junction. No interaction with paralytic muscle relaxants is present. Diazepam (0.1 mg/kg) has anticonvulsant activity and abolishes seizure activity in patients in status epilepticus or alcohol withdrawal although the effect is short lived. Drug Interactions: Use of alcohol or opiates with diazepam increases central nervous system depressant effects. Cimetidine, by impairing hepatic metabolism increases the elimination half-life of diazepam. Diazepam crosses the placenta easily. An increased risk of congenital malformation has been associated with the use of diazepam during the first trimester of pregnancy. Initial Dose Onset Peak Duration Half Life Max Dose Diazepam mg/kg of weight IV for normal healthy adults and 2-5 mg total IV for elderly and debilitated. 1-4 minutes minutes 2-6 hours hours 10 mg in 60 minutes B. Midazolam (Versed ) General: Midazolam is a shorter acting water soluble benzodiazepine that is two to four times as potent as diazepam. It has an elimination half life of 2.5 hours (range hours) which increased to 5.6 hours in elderly and 8.4 hours in obese patients. In Europe but not in the United States, midazolam is available in tablet form. Like diazepam, midazolam has sedative, anxiolytic, amnestic and anticonvulsant properties.

13 Page 13 Cardiovascular System: When used as a sole anesthetic induction agent, midazolam may produce reduction of cardiac index comparable to thiopental. Midazolam increases the heart rate and lowers blood pressure. The reason appears to be increased venous capacitance and decreased venous resistance. Other benzodiazepines including diazepam produce little reduction in myocardial hemodynamic parameters. However, both diazepam and midazolam are associated with stable cardiac function at induction due to maintenance of the baroreceptor reflexes. Ventilation and Respiration: Benzodiazepines produce a dose related central respiratory system depression. Ventilation is depressed by 0.15 mg/kg midazolam, especially in those patients with COPD. Clinical hypoxemia and hemoglobin desaturation may be seen in patients receiving one tenth of this dose. This decrease in minute ventilation is nearly identical after administering equipotent quantities of midazolam and diazepam. The peak effect of midazolam included respiratory depression occurring at three minutes following injection and remains for approximately fifteen minutes. Respiratory depression is more pronounced in geriatric and COPD patients. Apnea occurred in 20 percent of patients given midazolam and 27 percent of patients given thiopental for induction. Reves and Glass feel that there is a synergistic depression of ventilation when BZ and opioids are used concurrently. Central Nervous System Effects: Compared to the barbiturates, benzodiazepines have similar but lesser effects on cerebral metabolism, cerebral vascular resistance, cerebral perfusion pressure and intraocular pressure. Maximal CNS effects occur approximately three to five minutes after injection. Benzodiazepines, like the barbiturates, also produce either no analgesia or cause a slight hyperalgesia (increased pain). Benzodiazepines produce a consistent amnestic effect compared to the barbiturates. The amnesia may be antegrade (lack of recall) and postoperative. In both cases amnesia is greater than the barbiturates. Dose related decreases of cerebral blood flow and oxygen consumption are observed. Dosage: Midazolam (Versed ): The published dose of midazolam is mg/kg. It is important to remember the dose of midazolam should be individualized. The dose of intravenously administered midazolam necessary to produce adequate sedation in 800 consecutive patients about to undergo upper gastrointestinal endoscopy markedly decreased with increasing age. In this study, a total dose of 0.1 mg/kg midazolam in a 60 year old would be equivalent to a dose of 0.03 mg/kg IV in a 90 year old patient and 0.15 mg/kg in a 20 year old patient. Patients who are more than 60 years of age, debilitated or chronically ill, generally will require 30 percent less Versed than a healthy younger patient. Healthy adults below the age of 60 may respond to as little as 1 mg. No more than 2.5 mg should be given over a period of at least two (2) minutes. Wait several minutes for the medication to work prior to evaluating for sedative effects. If further sedation is necessary, continue to titrate using small increments until the appropriate level of sedation is achieved. Wait two or more minutes after each increment to fully evaluate effect. If the patient has received a narcotic, the dose should be 30 percent less than what normally would be required. The induction dose of benzodiazepines should also be reduced in hemodynamically compromised patients but it is seldom necessary to reduce the dose by 50 percent.

14 Page 14 Other Side Effects: Untreated glaucoma (narrow angle) and hypersensitivity are also known contraindications to its use. Midazolam crosses the placenta, although the effects are not known. Complications: Benzodiazepines have few side effects. The incidence of anaphylactic and anaphylactoid reactions is extremely low. The major complication with diazepam appears to be pain upon IV injection (after first appearing on the market). Midazolam, due to its greater potency, produced significant episodes of respiratory depression and death due to apnea. With increased physician awareness, doses have been reduced and this problem seems to have declined. C. Lorazepam (Ativan ) General: Lorazepam is an intermediate acting benzodiazepine with similar indications and actions as diazepam and midazolam. Lorazepam undergoes only a single step in its hepatic biotransformation to an inactive metabolite, therefore it has a relatively short half-life and duration of action. Lorazepam may be the drug of choice for sedation in the elderly and in patients with impaired liver function because of its simple one step inactivation. Diazepam and midazolam both have active metabolites which can build up in patients with impaired hepatic function, leading to cumulative effects if used for a long period of time. Pharmacokinetics: Following IV administration, lorazepam has an anticonvulsant, anxiolytic and sedative onset of action of 1 to 5 minutes. The duration of action can be as long as 12 to 24 hours. This compares with a similar onset for midazolam of 1 to 5 minutes, but midazolam has a duration of action ranging from 2 to 6 hours. These durations of action appear to be dose related. After IM administration, the onset of action for lorazepam is 15 to 30 minutes and the duration of action is 12 to 24 hours. Indications: Lorazepam has been used as an anxiolytic/hypnotic, as well as an anticonvulsant in the treatment of status epilepticus, and as a treatment for chemotherapyinduced nausea and vomiting. Parentally, lorazepam is used in adults as a preanesthetic medication, producing sedation, relief of anxiety and a decreased ability to recall events related to surgery. Dosing: Orally, lorazepam can be given 2 to 6 mg/day in divided doses. Preoperatively, lorazepam can be given IM at a dose of 0.05 mg/kg up to a maximum of 4 mg. For optimum effect, administer at least 2 hours before the operative procedure. IV, an initial dose is 2 mg total, or mg/kg (whichever is smaller). This dose will sedate most adults and normally should not be exceeded in patients >50 years old. For optimum effect, administer 15 to 20 minutes before the procedure. Lorazepam must be diluted with an equal amount of compatible solution (such as 0.9% saline) before IV injection. A. Chloral hydrate X. Other Medications Used for Moderate Sedation Chloral hydrate is a nonbarbiturate sedative-hypnotic. The mechanism of action by which the CNS is affected is not known. Hypnotic dosages produce mild cerebral depression and quite, deep sleep. Higher doses may lead to general anesthesia and concurrent depression of respiratory and vasomotor centers; death may result from respiratory failure. In therapeutic doses, chloral hydrate has little effect on respiration, blood pressure and

15 Page 15 reflexes. Hangover is less common than with most barbiturates and some benzodiazepines. Indications: Primarily, chloral hydrate is used for preoperative sedation to lessen anxiety and induce sleep without depressing sleep or cough reflex. It can also be used postoperatively in adjunct with opiates and analgesics for the control of pain. It is effective as a hypnotic only for short-term use; it loses much of its effectiveness for inducing and maintaining sleep after two weeks of use. The drug may also be effective in reducing anxiety associated with withdrawal of other drugs such as opiates and barbiturates. Chloral hydrate is often used in elderly patients, infants, and young children because many clinicians believe that it produces paradoxical excitement less frequently than do barbiturates. Pharmacokinetics: Oral administration of 500 mg to 1 gm of chloral hydrate usually produces sleep in 30 minutes to 1 hour in adults. The effects last 4 to 8 hours. Chloral hydrate is metabolized by the liver to active metabolites. The plasma half-life of the active metabolite is 8 to 11 hours. The conversion of chloral hydrate to the active metabolite is catalyzed by alcohol dehydrogenase. Drug Interactions: Alcohol and chloral hydrate have synergistic affects. Additive CNS depression may occur when chloral hydrate is administered concomitantly with other CNS depressants. A reaction characterized by diaphoresis, flushes, tachycardia, variable blood pressure including hypertension have occurred after administration of chloral hydrate followed by IV furosemide (Lasix). Patients who are being administered chloral hydrate and who are currently taking Coumadin may experience slightly elevated prothrombin times. Adult Dosing: The usual hypnotic dose of chloral hydrate for adults is 500 mg to 1 gm given minutes before retiring or, when used as a preoperative medication, 30 minutes before surgery. The usual sedative dosage is 250 mg 3 times daily after meals. When used for the management of alcohol withdrawal, the usual dose is 500 mg to 1 gm repeated at 6- hour intervals. Generally, single doses or daily doses should not exceed 2 gm. Pediatric Dosing: In neonates, the normal rectal or oral dose is 25 mg/kg for sedation prior to a procedure. In children the dose as a sedative or anxiolytic is 25 to 50 mg/kg/day divided every 6 to 8 hours with a maximum dose of 500 mg per dose. As a pretreatment for an EEG, 25 to 50 mg/kg may be given 30 to 60 minutes prior to the procedure. This dose may be repeated in 30 minutes to a maximum of 100 mg/kg or 2 gm total. To produce sedation prior to a nonpainful procedure, 50 to 75 mg/kg/dose may be given 30 to 60 minutes prior to the procedure, repeating the dose in 30 minutes if needed, to a total dose not to exceed 120 mg/kg or 2 gm.

16 Page 16 XI. Antagonists Used in Moderate Sedation Introduction: Use of antagonists in moderate sedation is discouraged since their half-life is shorter than that of the agonist drugs. They should be administered only when indicated. Any time either naloxone or flumazenil are administered the chart should be flagged or review by Performance Improvement via the occurrence reporting process. A. Naloxone (Narcan ) Naloxone is one of several opiate antagonists presently on the market. Naloxone acts at the opiate receptor by displacing opioid agonists. Naloxone binds to opiate receptors but does not actuate them so antagonism occurs. It is considered among the purest of opioid antagonists. It antagonizes the opioid effect mediated by all receptor types but has a higher affinity for mu compared to kappa. Naloxone has a very short plasma half-life. Its entry and decline in brain tissue is very rapid. Naloxone s duration of clinical effect is frequently less than that of the opioid agonist, so patients must be monitored carefully for signs of renarcotization. Indications: Naloxone s primary use is the reversal of respiratory depression. It also produces a parallel reversal of analgesia. Some feel it is possible to carefully titrate naloxone to reverse respiratory depression leaving analgesia unaffected. This has proved extremely difficult in the clinical setting. Side Effects: Large boluses of naloxone have been reported to cause hypertension, pulmonary edema, ruptured cerebral aneurysms, cardiac arrest and death in narcotized patients. The postulated mechanism of massive cardiovascular stimulation after reversal has been abrupt awakening and pain causing a massive sympathetic response. Naloxone also may unmask physical dependence, precipitate acute withdrawal syndrome and elevate catecholamines. Adult Dose: May be given IV/SQ/IM or via endotracheal tube. Titrating dose in 0.1-mg increments up to 0.4 mg and repeated every 2-3 minutes to the desired level of reversal; i.e. adequate ventilation and alertness without significant pain or discomfort. Giving only the dose needed will minimize the effect of a sudden awakening with pain. Children s Dose: The AHA recommends that a minimum dose of 0.1 mg/kg be given. However, if it is a situation in which pain is a consideration, it is beneficial to draw up 0.4mg (1 cc), dilute it in 10 cc, and titrate 1 cc at a time. Naloxone has a half life of about one (1) hour. Like flumazenil, naloxone has a shorter duration of action than the narcotic agonists it is attempting to reverse. If sustained reversal is desired, naloxone may be administered via the intramuscular route or by infusion. B. Flumazenil (Romazicon ) Mechanism of Action: Benzodiazepines produce sedation by stimulation of a subunit of the GABA receptor. Flumanzenil blocks benzodiazepine agonist from this stimulation making the patient more alert. It is a selective antagonist for such drugs as Valium and Versed.

17 Page 17 Indications: Flumazenil is indicated to reverse the effect of benzodiazepine overdosage. Side Effects: At present, the benzodiazepine antagonist flumazenil appears to have few side effects in the average patient. Adverse effects such as dizziness, headache, N/V, sweating, flushing, pain at injection site have been reported in patients who are dependent on benzodiazepines. No organ toxicity has been noted. Adult Dose: 0.2 mg IV over 15 seconds, wait 45 seconds; may repeat 0.2 mg every 60 seconds up to a maximum total cumulative dose 1.0 mg. No more than 1 mg (10 cc) total should be given in any 5-minute interval. No more than 3-mg total dose should be given in any one hour. Children s Dose: mg/kg up to a maximum total cumulative dose 0.2 mg. Onset: 1-2 minutes. Like naloxone, flumazenil has a shorter duration of action than the benzodiazepine agonists it is attempting to reverse. If sustained reversal is desired, flumazenil must be administered by infusion. The patient must be monitored for two hours following administration of flumazenil (Romazicon ). XII. Medication Administration Guidelines Before administering these psychoactive substances, the following general guidelines are useful: 1. Once the sedative point is achieved, maintain it with dosage increments of about 25 percent of the initial dose used to reach the sedative point. 2. Benzodiazepines potentiate the effects of narcotics. If given concomitantly, reduce narcotic dosage by 30 percent to reduce respiratory depression or airway obstruction. 3. Administer medications over a two-minute period. Allow at least two minutes and perhaps as long as five minutes (depending upon patient s physical condition) to evaluate the effectiveness of your drug therapy. This ensures some equilibration of the patient s physical state. 4. Avoid excessive doses, rapid infusion, or single bolus doses. Rapid administration leads to greater concentrations and enhances the possibility of complications. 5. Individualize doses to age and patient condition. For example, the dose of midazolam recommended should be reduced by about 15 percent per decade over the age of If the pulse oximeter declines 5 percent below the patient s baseline or falls below 92 percent, inform the physician immediately and begin airway management procedures.

18 Page 18 XIII. Assessment A. Nursing Psychoprophylaxis: Surgical interventions increase patient stress and anxiety. Although pharmacologic interventions can produce anxiolysis (anxiety reduction), the caregiver can also provide nonpharmacologic measures to assist in reducing patient anxiety. Pre-procedure assessment is focused on determining the patient s physical status, anxiety levels, patient readiness, and the ability to learn. B. Physician Documentation to include: History and Physical Drug allergies and sensitivities Past medical and surgical history History of substance abuse Physical Assessment Current Medications Baseline vital signs and lab data ASA Physical Status Classification Evidence of counseling and discussion of anesthetic alternatives and confirm notation of informed consent for the planned procedure and moderate sedation. NOTE: Physician must be specifically privileged to perform moderate sedation. C. ASA Physical Status and Anesthetic Assessment One of the new requirements of anesthesia care mandated by regulatory agencies and the JCAHO is assessment by non-anesthesia providers using the American Society of Anesthesiologists (ASA) physical status categorization system. The reasons for this requirement ultimately relate to a desire to determine and accumulate hospital specific morbidity and mortality data like currently being released for other procedures such as coronary bypass surgery. While many factors influence anesthesia morbidity and mortality, one important consideration is the patient s overall physical condition. In the ASA physical assessment system, patients are assigned a numeric score ranging between one and five based on preexisting medical conditions. A score of 1 is a completely healthy patient with no medical problems. A score of 5 is a moribund patient not expected to survive with or without surgery. An E for emergency procedure may also be assigned this classification system. The physician is responsible for determining a patient s ASA classification.

19 Page 19 American Society of Anesthesiologists Physical Status Classification System CLASS DEFINITION EXAMPLES I II III IV V No organic pathology or patients in whom the pathologic processes is localized and does not cause any systemic disturbance or abnormality. Mild but definite systemic disturbance caused by either the condition to be treated by surgical intervention or which is caused by other existing pathological processes. Severe systemic disturbance from any cause or causes that limits activity but is not incapacitating. It is not possible to state an absolute measure of severity, as this is a matter of clinical judgment. Extreme systemic disorder which is incapacitating and is constant threat to life regardless of the type of treatment. Because of its duration or nature, there is end organ damage that is irreversible. This class is intended to include patients that are in poor physical state. A moribund patient not expected to survive 24 hours with or without operation. A healthy patient without medical problems. Patients without shock, blood loss, or systemic signs of injury are present in an individual who would otherwise fall into Class I. Congenital deformities unless they are causing a systemic disturbance. Mild diabetes. Psychotic patients unable to care for themselves. Mild hypertension. Acute pharyngitis or sinusitis. Superficial or minor infections without sepsis. Pregnancy, smoker, or age < 6 months or > 70. Complicated diabetes. Two or three drug hypertension with evidence of end organ dysfunction. Angina. Post stroke with resolution. Post MI without evidence of CHF. Severe trauma with Class III or IV hemorrhage. NYHA Class III or IV. Renal failure requiring dialysis. Previous Class III returned to the OR because of poor outcome now in debilitated state. Steroid dependent patient with chronic pulmonary disease. Complete bowel obstruction of long duration in a debilitated patient. D. The intent of monitoring for moderate sedation is to have equivalent monitoring to that performed in the operating room. Monitors such as EKG, pulse oximetry and frequent blood pressure monitoring are now mandated rather than suggested by regulatory agencies such as the JCAHO and DHS. In addition, equipment once thought desirable is now required if routinely employed in the operating room. Patient monitoring is the primary responsibility of the nurse assisting with moderate sedation. Therefore, she/he must be privileged and have no other patient care responsibilities during the procedure. The nurse who will be performing this duty is responsible for assessment and teaching. The RN will connect the patient to the appropriate monitors. After the baseline assessment is completed, the administration of sedative medications may begin. The required monitoring equipment includes: 1. Monitoring equipment to include: continuous pulse oximeter with audible variable-pitched tone indicating oxygen saturation, ECG monitor, and automated blood pressure monitor; 2. Oxygen source (pipeline or H Tank O2 supply) and equipment for oxygen administration (e.g. nasal cannula, masks, etc.); 3. Self inflating resuscitation bag (e.g. Ambu bag); 4. Functioning suction source and aspiration equipment set up for use;

20 Page Crash cart with defibrillator, emergency airway equipment (masks, airways, laryngoscopes and endotracheal tubes), intravenous supplies (tubing, needles, etc.), and emergency medications for the treatment of the potential vascular consequences of sedation (intravenous vasoconstrictors, inotropes, vasodilators, and antihypertensives, etc.); 6. Intravenous reversal agents (naloxone and flumazenil) available on surface of crash cart; 7. Telephone available to call for help or to call a Code Blue; 8. Electrical outlet that is connected to emergency power supply. The RN and physician should be familiar with the operation and function of all monitoring equipment. Equipment must be checked for proper functioning prior to the procedure. Monitoring during the procedure and recovery: The patient will be continuously monitored during the procedure and recovery period. Monitoring and documentation: 1. Vital Signs to include blood pressure, pulse, respirations and pulse oximetry every five- (5) minutes during the procedure and for at least thirty (30) minutes after the last dose of Moderate Sedation medication, then every fifteen- (15) minutes during recovery. Use noninvasive blood pressure monitor with printer if available; 2. Continuous EKG monitoring during procedure and for at least thirty (30) minutes after last dose of Moderate Sedation medication; 3. Venous access will be maintained in all patients receiving Moderate Sedation and remaining until the patient is prepared for discharge; 4. Supplemental oxygen is required throughout the procedure and as needed during recovery until patient has regained baseline status; 5. During the recovery period, the Modified Aldrete Score will be monitored every fifteen- (15) minutes.