ANESTHESIOLOGISTS possess specific expertise in the pharmacology, physiology, and clinical management of patients receiving sedation and analgesia. For this reason, they are frequently called on to participate in the development of institutional policies and procedures for sedation and analgesia for diagnostic and therapeutic procedures. To assist in this process, the American Society of Anesthesiologists (ASA) has developed these “Guidelines for Sedation and Analgesia by Non-Anesthesiologists.”
Practice guidelines are systematically developed recommendations that assist the practitioner and patient in making decisions about health care. These recommendations may be adopted, modified, or rejected according to clinical needs and constraints. Practice guidelines are not intended as standards or absolute requirements. The use of practice guidelines cannot guarantee any specific outcome. Practice guidelines are subject to revision as warranted by the evolution of medical knowledge, technology, and practice. The guidelines provide basic recommendations that are supported by analysis of the current literature and by a synthesis of expert opinion, open forum commentary, and clinical feasibility data.
This revision includes data published since the “Guidelines for Sedation and Analgesia by Non-Anesthesiologists” were adopted by the ASA in 1995; it also includes data and recommendations for a wider range of sedation levels than was previously addressed.
Definitions
“Sedation and analgesia” comprise a continuum of states ranging from minimal sedation (anxiolysis) through general anesthesia. Definitions of levels of sedation–analgesia, as developed and adopted by the ASA, are given in table 1. These Guidelines specifically apply to levels of sedation corresponding to moderate sedation (frequently called conscious sedation) and deep sedation, as defined in table 1.
Table 1. Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia
Minimal Sedation (Anxiolysis) = a drug-induced state during which patients respond normally to verbal commands. Although cognitive function and coordination may be impaired, ventilatory and cardiovascular functions are unaffected.
Moderate Sedation/Analgesia (Conscious Sedation) = a drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained.
Deep Sedation/Analgesia = a drug-induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. The ability to independently maintain ventilatory function may be impaired. Patients may require assistance in maintaining a patent airway, and spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained.
General Anesthesia = a drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation. The ability to independently maintain ventilatory function is often impaired. Patients often require assistance in maintaining a patent airway, and positive pressure ventilation may be required because of depressed spontaneous ventilation or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired.
Because sedation is a continuum, it is not always possible to predict how an individual patient will respond. Hence, practitioners intending to produce a given level of sedation should be able to rescue patients whose level of sedation becomes deeper than initially intended. Individuals administering Moderate Sedation/Analgesia (Conscious Sedation) should be able to rescue patients who enter a state of Deep Sedation/Analgesia , while those administering Deep Sedation/Analgesia should be able to rescue patients who enter a state of general anesthesia.
* Reflex withdrawal from a painful stimulus is not considered a purposeful response.
Developed by the American Society of Anesthesiologists; approved by the ASA House of Delegates October 13, 1999.
Focus
These Guidelines are designed to be applicable to procedures performed in a variety of settings (e.g. , hospitals, freestanding clinics, physician, dental, and other offices) by practitioners who are not specialists in anesthesiology. Because minimal sedation (anxiolysis) entails minimal risk, the Guidelines specifically exclude it. Examples of minimal sedation include peripheral nerve blocks, local or topical anesthesia, and either (1) less than 50% nitrous oxide (N2O) in oxygen with no other sedative or analgesic medications by any route, or (2) a single, oral sedative or analgesic medication administered in doses appropriate for the unsupervised treatment of insomnia, anxiety, or pain. The Guidelines also exclude patients who are not undergoing a diagnostic or therapeutic procedure (e.g. , postoperative analgesia, sedation for treatment of insomnia). Finally, the Guidelines do not apply to patients receiving general or major conduction anesthesia (e.g. , spinal or epidural/caudal block), whose care should be provided, medically directed, or supervised by an anesthesiologist, the operating practitioner, or another licensed physician with specific training in sedation, anesthesia, and rescue techniques appropriate to the type of sedation or anesthesia being provided.
Purpose
The purpose of these Guidelines is to allow clinicians to provide their patients with the benefits of seda-tion/analgesia while minimizing the associated risks. Sedation/analgesia provides two general types of benefit: (1) sedation/analgesia allows patients to tolerate unpleasant procedures by relieving anxiety, discomfort, or pain; and (2) in children and uncooperative adults, sedation–analgesia may expedite the conduct of procedures that are not particularly uncomfortable but that require that the patient not move. At times, these sedation practices may result in cardiac or respiratory depression, which must be rapidly recognized and appropriately managed to avoid the risk of hypoxic brain damage, car-diac arrest, or death. Conversely, inadequate sedation– analgesia may result in undue patient discomfort or patient injury because of lack of cooperation or adverse physiologic or psychological response to stress.
Application
These Guidelines are intended to be general in their application and broad in scope. The appropriate choice of agents and techniques for sedation/analgesia is dependent on the experience and preference of the individual practitioner, requirements or constraints imposed by the patient or procedure, and the likelihood of producing a deeper level of sedation than anticipated. Because it is not always possible to predict how a specific patient will respond to sedative and analgesic medications, practitioners intending to produce a given level of sedation should be able to rescue patients whose level of sedation becomes deeper than initially intended. For moderate sedation, this implies the ability to manage a compromised airway or hypoventilation in a patient who responds purposefully after repeated or painful stimulation, whereas for deep sedation, this implies the ability to manage respiratory or cardiovascular instability in a patient who does not respond purposefully to painful or repeated stimulation. Levels of sedation referred to in the recommendations relate to the level of sedation intended by the practitioner. Examples are provided to illustrate airway assessment, preoperative fasting, emergency equipment, and recovery procedures; however, clinicians and their institutions have ultimate responsibility for selecting patients, procedures, medications, and equipment.
Task Force Members and Consultants
The ASA appointed a Task Force of 10 members to (1) review the published evidence; (2) obtain the opinion of a panel of consultants, including non-anesthesiologist physicians and dentists who routinely administer sedation–analgesia, as well as of anesthesiologists with a special interest in sedation–analgesia (see Appendix I); and (3) build consensus within the community of practitioners likely to be affected by the Guidelines. The Task Force included anesthesiologists in both private and academic practices from various geographic areas of the United States, a gastroenterologist, and methodologists from the ASA Committee on Practice Parameters.
This Practice Guideline is an update and revision of the ASA “Guidelines for Sedation and Analgesia by Non-Anesthesiologists.”1The Task Force revised and updated the Guidelines by means of a five-step process. First, original published research studies relevant to the revision and update were reviewed and analyzed; only articles relevant to the administration of sedation by non-anesthesiologists were evaluated. Second, the panel of expert consultants was asked to (1) participate in a survey related to the effectiveness and safety of various methods and interventions that might be used during sedation–analgesia, and (2) review and comment on the initial draft report of the Task Force. Third, the Task Force held open forums at two major national meetings to solicit input on its draft recommendations. National organizations representing most of the specialties whose members typically administer sedation–analgesia were invited to send representatives. Fourth, the consultants were surveyed to assess their opinions on the feasibility and financial implications of implementing the revised and updated Guidelines. Finally, all of the available information was used by the Task Force to finalize the Guidelines.
Availability and Strength of Evidence
Evidence-based Guidelines are developed by a rigorous analytic process. To assist the reader, the Guidelines make use of several descriptive terms that are easier to understand than the technical terms and data that are used in the actual analyses. These descriptive terms are defined below.
The following terms describe the strength of scientific data obtained from the scientific literature:
Supportive: There is sufficient quantitative information from adequately designed studies to describe a statistically significant relationship (P < 0.01) between a clinical intervention and a clinical outcome, using metaanalysis.
Suggestive: There is enough information from case reports and descriptive studies to provide a directional assessment of the relationship between a clinical intervention and a clinical outcome. This type of qualitative information does not permit a statistical assessment of significance.
Equivocal: Qualitative data have not provided a clear direction for clinical outcomes related to a clinical intervention, and (1) there is insufficient quantitative information or (2) aggregated comparative studies have found no quantitatively significant differences among groups or conditions.
The following terms describe the lack of available scientific evidence in the literature:
Inconclusive: Published studies are available, but they cannot be used to assess the relation between a clinical intervention and a clinical outcome because the studies either do not meet predefined criteria for content as defined in the “Focus” of these Guidelines, or do not provide a clear causal interpretation of findings because of research design or analytic concerns.
Insufficient: There are too few published studies to investigate a relationship between a clinical intervention and clinical outcome.
Silent: No studies that address a relationship of interest were found in the available published literature.
The following terms describe survey responses from the consultants for any specified issue. Responses were solicited on a five-point scale, ranging from 1 (strongly disagree) to 5 (strongly agree), with a score of 3 being neutral.
Strongly Agree: median score of 5
Agree: median score of 4
Equivocal: median score of 3
Disagree: median score of 2
Strongly Disagree: median score of 1
Guidelines
Patient Evaluation
There is insufficient published evidence to evaluate the relationship between sedation–analgesia outcomes and the performance of a preprocedure patient evaluation. There is suggestive evidence that some preexisting medical conditions may be related to adverse outcomes in patients receiving either moderate or deep sedation/analgesia. The consultants strongly agree that appropriate preprocedure evaluation (history, physical examination) increases the likelihood of satisfactory sedation and decreases the likelihood of adverse outcomes for both moderate and deep sedation.
Recommendations.
Clinicians administering sedation/analgesia should be familiar with sedation-oriented aspects of the patient's medical history and how these might alter the patient's response to sedation/analgesia. These include: (1) abnormalities of the major organ systems; (2) previous adverse experience with sedation/analgesia as well as regional and general anesthesia; (3) drug allergies, current medications, and potential drug interactions; (4) time and nature of last oral intake; and (5) history of tobacco, alcohol, or substance use or abuse. Patients presenting for sedation/analgesia should undergo a focused physical examination, including vital signs, auscultation of the heart and lungs, and evaluation of the airway. (Example I). Preprocedure laboratory testing should be guided by the patient's underlying medical condition and the likelihood that the results will affect the management of sedation/analgesia. These evaluations should be confirmed immediately before sedation is initiated.
Preprocedure Preparation
The literature is insufficient regarding the benefits of providing the patient (or legal guardian, in the case of a child or impaired adult) with preprocedure information about sedation and analgesia. For moderate sedation the consultants agree, and for deep sedation the consultants strongly agree that appropriate preprocedure counseling of patients regarding risks, benefits, and alternatives to sedation and analgesia increases patient satisfaction.
Sedatives and analgesics tend to impair airway reflexes in proportion to the degree of sedation–analgesia achieved. This dependence on level of sedation is reflected in the consultants opinion: They agree that preprocedure fasting decreases risks during moderate sedation, while strongly agreeing that it decreases risks during deep sedation. In emergency situations, when preprocedure fasting is not practical, the consultants agree that the target level of sedation should be modified (i.e. , less sedation should be administered) for moderate sedation, while strongly agreeing that it should be modified for deep sedation. The literature does not provide sufficient evidence to test the hypothesis that preprocedure fasting results in a decreased incidence of adverse outcomes in patients undergoing either moderate or deep sedation.
Recommendations.
Patients (or their legal guardians in the case of minors or legally incompetent adults) should be informed of and agree to the administration of sedation/analgesia, including its benefits, risks, and limitations associated with this therapy, as well as possible alternatives. Patients undergoing sedation/analgesia for elective procedures should not drink fluids or eat solid foods for a sufficient period of time to allow for gastric emptying before their procedure, as recommended by the ASA “Guidelines for Preoperative Fasting”2(Example II). In urgent, emergent, or other situations in which gastric emptying is impaired, the potential for pulmonary aspiration of gastric contents must be considered in determining (1) the target level of sedation, (2) whether the procedure should be delayed,or (3) whether the trachea should be protected by intubation.
Table. Example II.Summary of American Society of Anesthesiologists Preprocedure Fasting Guidelines2*
* These recommendations apply to healthy patients who are undergoing elective procedures. They are not intended for women in labor. Following the Guidelines does not guarantee a complete gastric emptying has occurred.
† The fasting periods apply to all ages.
‡ Examples of clear liquids include water, fruit juices without pulp, carbonated beverages, clear tea, and black coffee.
§ Since nonhuman milk is similar to solids in gastric emptying time, the amount ingested must be considered when determining an appropriate fasting period.
∥ A light meal typically consists of toast and clear liquids. Meals that include fried or fatty foods or meat may prolong gastric emptying time. Both the amount and type of foods ingested must be considered when determining an appropriate fasting period.
Monitoring Level of Consciousness.
The response of patients to commands during procedures performed with sedation/analgesia serves as a guide to their level of consciousness. Spoken responses also provide an indication that the patients are breathing. Patients whose only response is reflex withdrawal from painful stimuli are deeply sedated, approaching a state of general anesthesia, and should be treated accordingly. The literature is silent regarding whether monitoring patients’ level of consciousness improves patient outcomes or decreases risks. The consultants strongly agree that monitoring level of consciousness reduces risks for both moderate and deep sedation. The members of the Task Force believe that many of the complications associated with sedation and analgesia can be avoided if adverse drug responses are detected and treated in a timely manner (i.e. , before the development of cardiovascular decompensation or cerebral hypoxia). Patients given sedatives or analgesics in unmonitored settings in anticipation of a subsequent procedure may be at increased risk of these complications.
Pulmonary Ventilation.
It is the opinion of the Task Force that the primary causes of morbidity associated with sedation/analgesia are drug-induced respiratory depression and airway obstruction. For both moderate and deep sedation, the literature is insufficient to evaluate the benefit of monitoring ventilatory function by observation or auscultation. However, the consultants strongly agree that monitoring of ventilatory function by observation or auscultation reduces the risk of adverse outcomes associated with sedation/analgesia. The consultants were equivocal regarding the ability of capnography to decrease risks during moderate sedation, while agreeing that it may decrease risks during deep sedation. In circumstances in which patients are physically separated from the caregiver, the Task Force believes that automated apnea monitoring (by detection of exhaled carbon dioxide or other means) may decrease risks during both moderate and deep sedation, while cautioning practitioners that impedance plethysmography may fail to detect airway obstruction. The Task Force emphasizes that because ventilation and oxygenation are separate though related physiologic processes, monitoring oxygenation by pulse oximetry is not a substitute for monitoring ventilatory function.
Oxygenation.
Published data suggest that oximetry effectively detects oxygen desaturation and hypoxemia in patients who are administered sedatives/analgesics. The consultants strongly agree that early detection of hypoxemia through the use of oximetry during seda-tion–analgesia decreases the likelihood of adverse outcomes such as cardiac arrest and death. The Task Force agrees that hypoxemia during sedation and analgesia is more likely to be detected by oximetry than by clinical assessment alone.
Hemodynamics.
Although there are insufficient published data to reach a conclusion, it is the opinion of the Task Force that sedative and analgesic agents may blunt the appropriate autonomic compensation for hypovolemia and procedure-related stresses. On the other hand, if sedation and analgesia are inadequate, patients may develop potentially harmful autonomic stress responses (e.g. , hypertension, tachycardia). Early detection of changes in patients’ heart rate and blood pressure may enable practitioners to detect problems and intervene in a timely fashion, reducing the risk of these complications. The consultants strongly agree that regular monitoring of vital signs reduces the likelihood of adverse outcomes during both moderate and deep sedation. For both moderate and deep sedation, a majority of the consultants indicated that vital signs should be monitored at 5-min intervals once a stable level of sedation is established. The consultants strongly agree that continuous electrocardiography reduces risks during deep sedation, while they were equivocal regarding its effect during moderate sedation. However, the Task Force believes that electrocardiographic monitoring of selected patients (e.g. , with significant cardiovascular disease or dysrhythmias) may decrease risks during moderate sedation.
Recommendations.
Monitoring of patient response to verbal commands should be routine during moderate sedation, except in patients who are unable to respond appropriately (e.g. , young children, mentally impaired or uncooperative patients), or during procedures where movement could be detrimental. During deep sedation, patient responsiveness to a more profound stimulus should be sought, unless contraindicated, to ensure that the patient has not drifted into a state of general anesthesia. During procedures where a verbal response is not possible (e.g. , oral surgery, upper endoscopy), the ability to give a “thumbs up” or other indication of consciousness in response to verbal or tactile (light tap) stimulation suggests that the patient will be able to control his airway and take deep breaths if necessary, corresponding to a state of moderate sedation. Note that a response limited to reflex withdrawal from a painful stimulus is not considered a purposeful response and thus represents a state of general anesthesia.
All patients undergoing sedation/analgesia should be monitored by pulse oximetry with appropriate alarms. If available, the variable pitch “beep,” which gives a continuous audible indication of the oxygen saturation reading, may be helpful. In addition, ventilatory function should be continually monitored by observation or auscultation. Monitoring of exhaled carbon dioxide should be considered for all patients receiving deep sedation and for patients whose ventilation cannot be directly observed during moderate sedation. When possible, blood pressure should be determined before sedation/analgesia is initiated. Once sedation–analgesia is established, blood pressure should be measured at 5-min intervals during the procedure, unless such monitoring interferes with the procedure (e.g. , pediatric magnetic resonance imaging, where stimulation from the blood pressure cuff could arouse an appropriately sedated patient). Electrocardiographic monitoring should be used in all patients undergoing deep sedation. It should also be used during moderate sedation in patients with significant cardiovascular disease or those who are undergoing procedures where dysrhythmias are anticipated.
Recording of Monitored Parameters
The literature is silent regarding the benefits of contemporaneous recording of patients’ level of consciousness, respiratory function, or hemodynamics. Consultant opinion agrees with the use of contemporaneous recording for moderate sedation and strongly agrees with its use for patients undergoing deep sedation. It is the consensus of the Task Force that, unless technically precluded (e.g. , uncooperative or combative patient), vital signs and respiratory variables should be recorded before initiating sedation/analgesia, after administration of sedative–analgesic medications, at regular intervals during the procedure, on initiation of recovery, and immediately before discharge. It is the opinion of the Task Force that contemporaneous recording (either automatic or manual) of patient data may disclose trends that could prove critical in determining the development or cause of adverse events. In addition, manual recording ensures that an individual caring for the patient is aware of changes in patient status in a timely fashion.
Recommendations.
For both moderate and deep sedation, patients’ level of consciousness, ventilatory and oxygenation status, and hemodynamic variables should be assessed and recorded at a frequency that depends on the type and amount of medication administered, the length of the procedure, and the general condition of the patient. At a minimum, this should be: (1) before the beginning of the procedure; (2) after administration of sedative–analgesic agents; (3) at regular intervals during the procedure, (4) during initial recovery; and (5) just before discharge. If recording is performed automatically, device alarms should be set to alert the care team to critical changes in patient status.
Availability of an Individual Responsible for Patient Monitoring
Although the literature is silent on this issue, the Task Force recognizes that it may not be possible for the individual performing a procedure to be fully cognizant of the patient's condition during sedation/analgesia. For moderate sedation, the consultants agree that the availability of an individual other than the person performing the procedure to monitor the patient's status improves patient comfort and satisfaction and that risks are reduced. For deep sedation, the consultants strongly agree with these contentions. During moderate sedation, the consultants strongly agree that the individual monitoring the patient may assist the practitioner with interruptible ancillary tasks of short duration; during deep sedation, the consultants agree that this individual should have no other responsibilities.
Recommendation.
A designated individual, other than the practitioner performing the procedure, should be present to monitor the patient throughout procedures performed with sedation/analgesia. During deep sedation, this individual should have no other responsibilities. However, during moderate sedation, this individual may assist with minor, interruptible tasks once the patient's level of sedation–analgesia and vital signs have stabilized, provided that adequate monitoring for the patient's level of sedation is maintained.
Training of Personnel
Although the literature is silent regarding the effectiveness of training on patient outcomes, the consultants strongly agree that education and training in the pharmacology of agents commonly used during sedation–analgesia improves the likelihood of satisfactory sedation and reduces the risk of adverse outcomes from either moderate or deep sedation. Specific concerns may include: (1) potentiation of sedative-induced respiratory depression by concomitantly administered opioids; (2) inadequate time intervals between doses of sedative or analgesic agents, resulting in a cumulative overdose; and (3) inadequate familiarity with the role of pharmacologic antagonists for sedative and analgesic agents.
Because the primary complications of sedation/analgesia are related to respiratory or cardiovascular depression, it is the consensus of the Task Force that the individual responsible for monitoring the patient should be trained in the recognition of complications associated with sedation/analgesia. Because sedation/analgesia constitutes a continuum, practitioners administering moderate sedation should be able to rescue patients who enter a state of deep sedation, whereas those intending to administer deep sedation should be able to rescue patients who enter a state of general anesthesia. Therefore, the consultants strongly agree that at least one qualified individual trained in basic life support skills (cardiopulmonary resuscitation, bag-valve-mask ventilation) should be present in the procedure room during both moderate and deep sedation. In addition, the consultants strongly agree with the immediate availability (1–5 min away) of an individual with advanced life support skills (e.g. , tracheal intubation, defibrillation, use of resuscitation medications) for moderate sedation and in the procedure room itself for deep sedation.
Recommendations.
Individuals responsible for patients receiving sedation–analgesia should understand the pharmacology of the agents that are administered, as well as the role of pharmacologic antagonists for opioids and benzodiazepines. Individuals monitoring patients receiving sedation/analgesia should be able to recognize the associated complications. At least one individual capable of establishing a patent airway and positive pressure ventilation, as well as a means for summoning additional assistance, should be present whenever sedation–analgesia is administered. It is recommended that an individual with advanced life support skills be immediately available (within 5 min) for moderate sedation and within the procedure room for deep sedation.
Availability of Emergency Equipment
Although the literature is silent, the consultants strongly agree that the ready availability of appropriately sized emergency equipment reduces risks associated with both moderate and deep sedation. The literature is also silent regarding the need for cardiac defibrillators during sedation/analgesia. During moderate sedation, the consultants agree that a defibrillator should be immediately available for patients with both mild (e.g. , hypertension) and severe (e.g. , ischemia, congestive failure) cardiovascular disease. During deep sedation, the consultants agree that a defibrillator should be immediately available for all patients.
Recommendations.
Pharmacologic antagonists as well as appropriately sized equipment for establishing a patent airway and providing positive pressure ventilation with supplemental oxygen should be present whenever sedation–analgesiais administered. Suction, advanced airway equipment, and resuscitation medications should be immediately available and in good working order (Example III). A functional defibrillator should be immediately available whenever deep sedation is administered and when moderate sedation is administered to patients with mild or severe cardiovascular disease.
Use of Supplemental Oxygen
The literature supports the use of supplemental oxygen during moderate sedation and suggests that supplemental oxygen be used during deep sedation to reduce the frequency of hypoxemia. The consultants agree that supplemental oxygen decreases patient risk during moderate sedation, while strongly agreeing with this view for deep sedation.
Recommendations.
Equipment to administer supplemental oxygen should be present when sedation/analgesia is administered. Supplemental oxygen should be considered for moderate sedation and should be administered during deep sedation unless specifically contraindicated for a particular patient or procedure. If hypoxemia is anticipated or develops during sedation/analgesia, supplemental oxygen should be administered.
Combinations of Sedative–Analgesic Agents
The literature suggests that combining a sedative with an opioid provides effective moderate sedation; it is equivocal regarding whether the combination of a sedative and an opioid may be more effective than a sedative or an opioid alone in providing adequate moderate sedation. For deep sedation, the literature is insufficient to compare the efficacy of sedative–opioid combinations with that of a sedative alone. The consultants agree that combinations of sedatives and opioids provide satisfactory moderate and deep sedation. However, the published data also suggest that combinations of sedatives and opioids may increase the likelihood of adverse outcomes, including ventilatory depression and hypoxemia; the consultants were equivocal on this issue for both moderate and deep sedation. It is the consensus of the Task Force that fixed combinations of sedative and analgesic agents may not allow the individual components of sedation/analgesia to be appropriately titrated to meet the individual requirements of the patient and procedure while reducing the associated risks.
Recommendations.
Combinations of sedative and analgesic agents may be administered as appropriate for the procedure being performed and the condition of the patient. Ideally, each component should be administered individually to achieve the desired effect (e.g. , additional analgesic medication to relieve pain; additional sedative medication to decrease awareness or anxiety). The propensity for combinations of sedative and analgesic agents to cause respiratory depression and airway obstruction emphasizes the need to appropriately reduce the dose of each component as well as the need to continually monitor respiratory function.
Titration of Intravenous Sedative–Analgesic Medications
The literature is insufficient to determine whether administration of small, incremental doses of intravenous sedative/analgesic drugs until the desired level of sedation or analgesia is achieved is preferable to a single dose based on patient size, weight, or age. The consultants strongly agree that incremental drug administration improves patient comfort and decreases risks for both moderate and deep sedation.
Recommendations.
Intravenous sedative/analgesic drugs should be given in small, incremental doses that are titrated to the desired end points of analgesia and sedation. Sufficient time must elapse between doses to allow the effect of each dose to be assessed before subsequent drug administration. When drugs are administered by nonintravenous routes (e.g. , oral, rectal, intramuscular, transmucosal), allowance should be made for the time required for drug absorption before supplementation is considered. Because absorption may be unpredictable, administration of repeat doses of oral medications to supplement sedation/analgesia is not recommended.
Anesthetic Induction Agents Used for Sedation/Analgesia (Propofol, Methohexital, Ketamine)
The literature suggests that, when administered by non-anesthesiologists, propofol and ketamine can provide satisfactory moderate sedation, and suggests that methohexital can provide satisfactory deep sedation. The literature is insufficient to evaluate the efficacy of propofol or ketamine administered by non-anesthesiologists for deep sedation. There is insufficient literature to determine whether moderate or deep sedation with propofol is associated with a different incidence of adverse outcomes than similar levels of sedation with midazolam. The consultants are equivocal regarding whether use of these medications affects the likelihood of producing satisfactory moderate sedation, while agreeing that using them increases the likelihood of satisfactory deep sedation. However, the consultants agree that avoiding these medications decreases the likelihood of adverse outcomes during moderate sedation and are equivocal regarding their effect on adverse outcomes during deep sedation.
The Task Force cautions practitioners that methohexital and propofol can produce rapid, profound decreases in level of consciousness and cardiorespiratory function, potentially culminating in a state of general anesthesia. The Task Force notes that ketamine also produces dose-related decreases in level of consciousness, culminating in general anesthesia. Although it may be associated with less cardiorespiratory depression than other sedatives, airway obstruction, laryngospasm, and pulmonary aspiration may still occur with ketamine. Furthermore, because of its dissociative properties, some of the usual signs of depth of sedation may not apply (e.g. , the patient's eyes may be open while in a state of deep sedation or general anesthesia). The Task Force also notes that there are no specific pharmacologic antagonists for any of these medications.
Recommendations.
Even if moderate sedation is intended, patients receiving propofol or methohexital by any route should receive care consistent with that required for deep sedation. Accordingly, practitioners administering these drugs should be qualified to rescue patients from any level of sedation, including general anesthesia. Patients receiving ketamine should be cared for in a manner consistent with the level of sedation that is achieved.
Intravenous Access
Published literature is equivocal regarding the relative efficacy of sedative–analgesic agents administered intravenously as compared with those administered by nonintravenous routes to achieve moderate sedation; the literature is insufficient on this issue for deep sedation. The literature is equivocal regarding the comparative safety of these routes of administration for moderate sedation and is insufficient for deep sedation. The consultants strongly agree that intravenous administration of sedative and analgesic medications increases the likelihood of satisfactory sedation for both moderate and deep sedation. They also agree that it decreases the likelihood of adverse outcomes. For both moderate and deep sedation, when sedative–analgesic medications are administered intravenously, the consultants strongly agree with maintaining intravenous access until patients are no longer at risk for cardiovascular or respiratory depression, because it increases the likelihood of satisfactory sedation and decreases the likelihood of adverse outcomes. In situations where sedation is initiated by nonintravenous routes (e.g. , oral, rectal, intramuscular), the need for intravenous access is not sufficiently addressed in the literature. However, initiation of intravenous access after the initial sedation takes effect allows additional sedative–analgesic and resuscitation drugs to be administered if necessary.
Recommendations.
In patients receiving intravenous medications for sedation/analgesia, vascular access should be maintained throughout the procedure and until the patient is no longer at risk for cardiorespiratory depression. In patients who have received sedation–analgesia by nonintravenous routes, or whose intravenous line has become dislodged or blocked, practitioners should determine the advisability of establishing or reestablishing intravenous access on a case-by-case basis. In all instances, an individual with the skills to establish intravenous access should be immediately available.
Reversal Agents
Specific antagonist agents are available for the opioids (e.g. , naloxone) and benzodiazepines (e.g. , flumazenil). The literature supports the ability of naloxone to reverse opioid-induced sedation and respiratory depression. Practitioners are cautioned that acute reversal of opioid-induced analgesia may result in pain, hypertension, tachycardia, or pulmonary edema. The literature supports the ability of flumazenil to antagonize benzodiazepine-induced sedation and ventilatory depression in patients who have received benzodiazepines alone or in combination with an opioid. The consultants strongly agree that the immediate availability of reversal agents during both moderate and deep sedation is associated with decreased risk of adverse outcomes. It is the consensus of the Task Force that respiratory depression should be initially treated with supplemental oxygen and, if necessary, positive pressure ventilation by mask. The consultants disagree that the use of sedation regimens that are likely to require routine reversal with flumazenil or naloxone improves the quality of sedation or reduces the risk of adverse outcomes.
Recommendations.
Specific antagonists should be available whenever opioid analgesics or benzodiazepines are administered for sedation/analgesia. Naloxone or flumazenil may be administered to improve spontaneous ventilatory efforts in patients who have received opioids or benzodiazepines, respectively. This may be especially helpful in cases where airway control and positive pressure ventilation are difficult. Before or concomitantly with pharmacologic reversal, patients who become hypoxemic or apneic during sedation/analgesia should: (1) be encouraged or stimulated to breathe deeply; (2) receive supplemental oxygen; and (3) receive positive pressure ventilation if spontaneous ventilation is inadequate. After pharmacologic reversal, patients should be observed long enough to ensure that sedation and cardiorespiratory depression does not recur once the effect of the antagonist dissipates. The use of sedation regimens that include routine reversal of sedative or analgesic agents is discouraged.
Recovery Care
Patients may continue to be at significant risk for developing complications after their procedure is completed. Decreased procedural stimulation, delayed drug absorption following nonintravenous administration, and slow drug elimination may contribute to residual sedation and cardiorespiratory depression during the recovery period. Examples include intramuscular meperidine–promethazine–chlorpromazine mixtures and oral or rectal chloral hydrate. When sedation–analgesia is administered to outpatients, it is likely that there will be no medical supervision once the patient leaves the medical facility. Although there is not sufficient literature to examine the effects of postprocedure monitoring on patient outcomes, the consultants strongly agree that continued observation, monitoring, and predetermined discharge criteria decrease the likelihood of adverse outcomes for both moderate and deep sedation. It is the consensus of the Task Force that discharge criteria should be designed to minimize the risk for cardiorespiratory depression after patients are released from observation by trained personnel.
Recommendations.
Following sedation/analgesia, patients should be observed in an appropriately staffed and equipped area until they are near their baseline level of consciousness and are no longer at increased risk for cardiorespiratory depression. Oxygenation should be monitored periodically until patients are no longer at risk for hypoxemia. Ventilation and circulation should be monitored at regular intervals until patients are suitable for discharge. Discharge criteria should be designed to minimize the risk of central nervous system or cardiorespiratory depression after discharge from observation by trained personnel (Example IV).
Special Situations
The literature suggests and the Task Force members concur that certain types of patients are at increased risk for developing complications related to sedation/analgesia unless special precautions are taken. In patients with significant underlying medical conditions (e.g. , extremes of age; severe cardiac, pulmonary, hepatic, or renal disease; pregnancy; drug or alcohol abuse) the consultants agree that preprocedure consultation with an appropriate medical specialist (e.g. , cardiologist, pulmonologist) decreases the risks associated with moderate sedation and strongly agree that it decreases the risks associated with deep sedation. In patients with significant sedation-related risk factors (e.g. , uncooperative patients, morbid obesity, potentially difficult airway, sleep apnea), the consultants are equivocal regarding whether preprocedure consultation with an anesthesiologist increases the likelihood of satisfactory moderate sedation, while agreeing that it decreases adverse outcomes. The consultants strongly agree that preprocedure consultation increases the likelihood of satisfactory outcomes while decreasing risks associated with deep sedation. The Task Force notes that in emergency situations, the benefits of awaiting preprocedure consultations must be weighed against the risk of delaying the procedure.
For moderate sedation, the consultants are equivocal regarding whether the immediate availability of an individual with postgraduate training in anesthesiology increases the likelihood of a satisfactory outcome or decreases the associated risks. For deep sedation, the consultants agree that the immediate availability of such an individual improves the likelihood of satisfactory sedation and that it will decrease the likelihood of adverse outcomes.
Recommendations.
Whenever possible, appropriate medical specialists should be consulted before administration of sedation to patients with significant underlying conditions. The choice of specialists depends on the nature of the underlying condition and the urgency of the situation. For severely compromised or medically unstable patients (e.g. , anticipated difficult airway, severe obstructive pulmonary disease, coronary artery disease, or congestive heart failure), or if it is likely that sedation to the point of unresponsiveness will be necessary to obtain adequate conditions, practitioners who are not trained in the administration of general anesthesia should consult an anesthesiologist.
Appendix I: Methods and Analyses
†
The scientific assessment of these Guidelines was based on the following statements or evidence linkages. These linkages represent directional statements about relationships between sedation/analgesia interventions by non-anesthesiologists and clinical outcomes.
A preprocedure patient evaluation, (i.e. , history, physical examination, laboratory evaluation, consultation)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Preprocedure preparation of the patient (e.g. , counseling, fasting)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Patient monitoring (i.e. , level of consciousness, pulmonary ventilation [observation, auscultation], oxygenation [pulse oximetry], automated apnea monitoring [capnography], hemodynamics [electrocardiogram, blood pressure, heart rate])
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Contemporaneous recording of monitored parameters (e.g. , level of consciousness, respiratory function, hemodynamics) at regular intervals in patients receiving sedation or analgesia
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Availability of an individual who is dedicated solely to patient monitoring and safety
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Education and training of sedation and analgesia providers in the pharmacology of sedation–analgesia agents
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
The presence of an individual(s) capable of establishing a patent airway, positive pressure ventilation, and resuscitation (i.e. , advanced life-support skills) during a procedure
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Availability of appropriately sized emergency and airway equipment (e.g. , laryngeal mask airway, defibrillators)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
The use of supplemental oxygen during procedures performed with sedation or analgesia
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Use of sedative agents combined with analgesic agents (e.g. , sedative–analgesic cocktails, fixed combinations of sedatives and analgesics, titrated combinations of sedatives and analgesics)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Titration of intravenous sedative–analgesic medications to achieve the desired effect
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Intravenous sedation–analgesic medications specifically designed to be used for general anesthesia (i.e. , methohexital, propofol, and ketamine)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Administration of sedative–analgesic agents by the intravenous route
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Maintaining or establishing intravenous access during sedation or analgesia until the patient is no longer at risk for cardiorespiratory depression
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Availability of reversal agents (naloxone and flumazenil only) for the sedative or analgesic agents being administered
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Postprocedural recovery observation, monitoring, and predetermined discharge criteria reduce adverse outcomes.
Special regimens (e.g. , preprocedure consultation, specialized monitoring, special sedatives–techniques) for patients with special problems (e.g. , uncooperative patients; extremes of age; severe cardiac, pulmonary, hepatic, renal, or central nervous system disease; morbid obesity; sleep apnea; pregnancy; drug or alcohol abuse; emergency–unprepared patients; metabolic and airway difficulties)
a. Improves clinical efficacy (i.e. , satisfactory sedation and analgesia)
b. Reduces adverse outcomes
Scientific evidence was derived from aggregated research literature and from surveys, open presentations, and other consensus-oriented activities. For purposes of literature aggregation, potentially relevant clinical studies were identified via electronic and manual searches of the literature. The electronic search covered a 36-yr period from 1966 through 2001. The manual search covered a 44-yr period from 1958 through 2001. More than 3,000 citations were initially identified, yielding a total of 1,876 nonoverlapping articles that addressed topics related to the 15 evidence linkages. After review of the articles, 1,519 studies did not provide direct evidence and were subsequently eliminated. A total of 357 articles contained direct linkage-related evidence.
A directional result for each study was initially determined by a literature count, classifying each outcome as either supporting a linkage, refuting a linkage, or neutral. The results were then summarized to obtain a directional assessment of support for each linkage. Literature pertaining to three evidence linkages contained enough studies with well-defined experimental designs and statistical information to conduct formal metaanalyses. These three linkages were: linkage 8 [supplemental oxygen], linkage 9 [benzodiazepines combined with opioids vs. benzodiazepines alone], and linkage 13 [naloxone for antagonism of opioids, flumazenil for antagonism of benzodiazepines, and flumazenil for antagonism of benzodiazepine-opioid combinations].
Combined probability tests were applied to continuous data, and an odds-ratio procedure was applied to dichotomous study results. Two combined probability tests were employed as follows: (1) the Fisher combined test, producing chi-square values based on logarithmic transformations of the reported P values from the independent studies; and (2) the Stouffer combined test, providing weighted representation of the studies by weighting each of the standard normal deviates by the size of the sample. An odds-ratio procedure based on the Mantel–Haenszel method for combining study results using 2 × 2 tables was used with outcome frequency information. An acceptable significance level was set at P < 0.01 (one-tailed), and effect size estimates were calculated. Tests for heterogeneity of the independent studies were conducted to assure consistency among the study results. Der Simonian-Laird random-effects odds ratios were calculated when significant heterogeniety was found. To assess potential publishing bias, a “fail-safe N” value was calculated for each combined probability test. No search for unpublished studies was conducted, and no reliability tests for locating research results were performed.
Metaanalytic results are reported in table 2. The following outcomes were found to be significant for combined probability tests: (1) oxygen saturation , linkage 8 (supplemental oxygen); (2) sedation recovery , linkage 13 (naloxone for antagonism of opioids and flumazenil for antagonism of benzodiazepine–opioid combinations); (3) psychomotor recovery , linkage 13 (flumazenil for antagonism of benzodiazepines); and (4) respiratory–ventilatory recovery , linkage 13 (naloxone for antagonism of opioids, flumazenil for antagonism of benzodiazepines, and flumazenil for antagonism of benzodiazepine–opioid combinations). To be considered acceptable findings of significance, both the Fisher and weighted Stouffer combined test results must agree. Weighted effect size values for these linkages ranged from r = 0.19 to 0.80, representing moderate to high effect size estimates.
Table 2. Meta-analysis Summary
* Nonrandomized comparative studies are included;
† Studies in which anesthesiologist administered benzodiazepines, opioids, or reversal agents are included;
‡ Studies in which subjects consist of intensive care unit patients, postoperative patients, or volunteers with no procedures are included.
§ Der Simonian-Laird random-effects odds ratio.
Mantel–Haenszel odds ratios were significant for the following outcomes: (1) hypoxemia , linkage 8 (supplemental oxygen) and linkage 9 (benzodiazepine–opioid combinations vs. benzodiazepines alone); (2) sedation recovery , linkage 13 (flumazenil for antagonism of benzodiazepines); and (3) recall of procedure , linkage 9 (benzodiazepine–opioid combinations). To be considered acceptable findings of significance, Mantel–Haenszel odds ratios must agree with combined test results when both types of data are assessed.
Interobserver agreement among Task Force members and two methodologists was established by interrater reliability testing. Agreement levels using a Kappa (κ) statistic for two-rater agreement pairs were as follows: (1) type of study design, κ= 0.25–0.64; (2) type of analysis, κ= 0.36–0.83; (3) evidence linkage assignment, κ= 0.78–0.89; and (4) literature inclusion for database, κ= 0.71–1.00. Three-rater chance-corrected agreement values were: (1) study design, Sav = 0.45, Var (Sav) = 0.012; (2) type of analysis, Sav = 0.51, Var (Sav) = 0.015; (3) linkage assignment, Sav = 0.81 Var (Sav) = 0.006; (4) literature database inclusion, Sav = 0.84 Var (Sav) = 0.046. These values represent moderate to high levels of agreement.
The findings of the literature analyses were supplemented by the opinions of Task Force members as well as by surveys of the opinions of a panel of consultants drawn from the following specialties where sedation and analgesia are commonly administered: Anesthesiology, 8; Cardiology, 2; Dental Anesthesiology, 3; Dermatology, 2; Emergency Medicine, 5; Gastroenterology, 9; Intensive Care, 1; Oral and Maxillofacial Surgery, 5; Pediatrics, 1; Pediatric Dentistry, 3; Pharmacology, 1; Pulmonary Medicine, 3; Radiology, 3; Surgery, 3; and Urology, 2. The rate of return for this Consultant survey was 78% (n = 51/65). Median agreement scores from the Consultants regarding each linkage are reported in table 3.
Table 3. Consultant Survey Summary
* Strongly agree: Median score of 5; Agree: Median score of 4; Equivocal: Median score of 3; Disagree: Median score of 2; Strongly disagree: Median score of 1.
For moderate sedation, Consultants were supportive of all of the linkages with the following exceptions: linkage 3 (electrocardiogram monitoring and capnography), linkage 9 (sedatives combined with analgesics for reducing adverse outcomes), linkage 11 (avoiding general anesthesia sedatives for improving satisfactory sedation), linkage 13b (routine administration of naloxone), linkage 13c (routine administration of flumazenil), and linkage 15b (anesthesiologist consultation for patients with medical conditions to provide satisfactory moderate sedation). In addition, Consultants were equivocal regarding whether postgraduate training in anesthesiology improves moderate sedation or reduces adverse outcomes.
For deep sedation, Consultants were supportive of all of the linkages with the following exceptions: linkage 9 (sedatives combined with analgesics for reducing adverse outcomes), linkage 11 (avoiding general anesthesia sedatives), linkage 13b (routine administration of naloxone), and linkage 13c (routine administration of flumazenil).
The Consultants were asked to indicate which, if any, of the evidence linkages would change their clinical practices if the updated Guidelines were instituted. The rate of return was 57% (n = 37/65). The percent of responding Consultants expecting no change associated with each linkage were as follows: preprocedure patient evaluation, 94%; preprocedure patient preparation, 91%; patient monitoring, 80%; contemporaneous recording of monitored parameters, 91%; availability of individual dedicated solely to patient monitoring and safety, 91%; education and training of sedation–analgesia providers in pharmacology, 89%; presence of an individual(s) capable of establishing a patent airway, 91%; availability of appropriately sized emergency and airway equipment, 94%; use of supplemental oxygen during procedures, 100%; use of sedative agents combined with analgesic agents, 91%; titration of sedatives–analgesics, 97%; intravenous sedation–analgesia with agents designed for general anesthesia, 77%; administration of sedative–analgesic agents by the intravenous route, 94%; maintaining or establishing intravenous access, 97%; availability–use of flumazenil, 94%; availability–use of naloxone, 94%; observation and monitoring during recovery, 89%; special care for patients with underlying medical problems, 91%; and special care for uncooperative patients, 94%. Seventy-four percent of the respondents indicated that the Guidelines would have no effect on the amount of time spent on a typical case. Nine respondents (26%) indicated that there would be an increase in the amount of time they would spend on a typical case with the implementation of these Guidelines. The amount of increased time anticipated by these respondents ranged from 1 to 60 min.
Appendix II: Summary of Guidelines
‡
Except as noted, recommendations apply to both moderate and deep sedation.
Preprocedure evaluation
Relevant history (major organ systems, sedation–anesthesia history, medications, allergies, last oral intake)
Focused physical examination (to include heart, lungs, airway)
Laboratory testing guided by underlying conditions and possible effect on patient management
Findings confirmed immediately before sedation
Patient counseling
Risks, benefits, limitations, and alternatives
Preprocedure fasting
Elective procedures—sufficient time for gastric emptying
Urgent or emergent situations—potential for pulmonary aspiration considered in determining target level of sedation, delay of procedure, protection of trachea by intubation
See ASA Guidelines for Preoperative Fasting 2
Monitoring
(Data to be recorded at appropriate intervals before, during, and after procedure)
Pulse oximetry
Response to verbal commands when practical
Pulmonary ventilation (observation, auscultation)
Exhaled carbon dioxide monitoring considered when patients separated from caregiver
Blood pressure and heart rate at 5-min intervals unless contraindicated
Electrocardiograph for patients with significant cardiovascular disease
For deep sedation:
Response to verbal commands or more profound stimuli unless contraindicated
Exhaled CO2monitoring considered for all patients
Electrocardiograph for all patients
Personnel
Designated individual, other than the practitioner performing the procedure, present to monitor the patient throughout the procedure
This individual may assist with minor interruptible tasks once patient is stable
For deep sedation:
The monitoring individual may not assist with other tasks
Training
Pharmacology of sedative and analgesic agents
Pharmacology of available antagonists
Basic life support skills—present
Advanced life support skills—within 5 min
For deep sedation:
Advanced life support skills in the procedure room
Emergency Equipment
Suction, appropriately sized airway equipment, means of positive-pressure ventilation
Intravenous equipment, pharmacologic antagonists, and basic resuscitative medications
Defibrillator immediately available for patients with cardiovascular disease
For deep sedation:
Defibrillator immediately available for all patients
Supplemental Oxygen
Oxygen delivery equipment available
Oxygen administered if hypoxemia occurs
For deep sedation:
Oxygen administered to all patients unless contraindicated
Choice of Agents
Sedatives to decrease anxiety, promote somnolence
Analgesics to relieve pain
Dose Titration
Medications given incrementally with sufficient time between doses to assess effects
Appropriate dose reduction if both sedatives and analgesics used
Repeat doses of oral medications not recommended
Use of anesthetic induction agents (methohexital, propofol)
Regardless of route of administration and intended level of sedation, patients should receive care consistent with deep sedation, including ability to rescue from unintended general anesthesia
Intravenous Access
Sedatives administered intravenously—maintain intravenous access
Sedatives administered by other routes—case-by-case decision
Individual with intravenous skills immediately available
Reversal Agents
Naloxone and flumazenil available whenever opioids or benzodiazepines administered
Recovery
Observation until patients no longer at risk for cardiorespiratory depression
Appropriate discharge criteria to minimize risk of respiratory or cardiovascular depression after discharge
Special Situations
Severe underlying medical problems—consult with appropriate specialist if possible
Risk of severe cardiovascular or respiratory compromise or need for complete unresponsiveness to obtain adequate operating conditions—consult anesthesiologist
