Clinical policy: Procedural sedation and analgesia in the emergency department

Article Outline

• Preface
• Introduction
• Definitions
• Methodology
• Critical questions
  • I. What are the personnel requirements needed to provide procedural sedation and analgesia in the ED?
  • Personnel recommendations: what are the personnel requirements needed to provide procedural sedation and analgesia in the ED?
  • II. What are the key components of the patient assessment before initiating procedural sedation?
  • Patient assessment recommendations: what are the key components of the patient assessment before initiating procedural sedation?
  • III. Is preprocedural fasting necessary before initiating procedural sedation?
  • Preprocedure fasting recommendations: is preprocedural fasting necessary before initiating procedural sedation?
  • IV. What equipment and supplies are required to provide procedural sedation and analgesia?
  • Equipment and supplies recommendations: what equipment and supplies are required to provide procedural sedation and analgesia?
  • V. What assessment and monitoring are required to provide procedural sedation in the ED?
  • General recommendations: what assessment and monitoring are required to provide procedural sedation in the ED?
  • VI. How should respiratory status be assessed?
    • Pulse oximetry
    • Capnometry
    • Bispectral Index
  • Respiratory status recommendations: how should respiratory status be assessed?
  • VII. Can ketamine, midazolam, fentanyl, propofol, and etomidate be safely administered for procedural sedation and analgesia in the ED?
• Drug administration recommendations: can ketamine, midazolam, fentanyl, propofol, and etomidate be safely administered for procedural sedation and analgesia in the ED?
• Appendix A. Literature classification schema.∗
• Appendix B. Approach to downgrading strength of evidence
• References
• Copyright

Back to Article Outline

Preface 

Emergency medicine training provides physicians with expertise in critical care, airway and pain management. Accordingly, expertise in procedural sedation and analgesia is a core competency in emergency medicine practice.¹, ² Emergency physicians routinely provide sedation, analgesia, respiratory, and hemodynamic management of critically ill patients.

Procedural sedation has received a great amount of attention in recent years. Several groups have produced documents covering its use, including the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), which has made it an area of intense review. Unfortunately, most of these promulgated advisory materials are not truly evidence-based.

The following clinical policy, developed by the Clinical Policies Committee of the American College of Emergency Physicians (ACEP), updates the original clinical policy approved on January 13, 1998.³ This clinical policy attempts to remove the bias from recommendations for procedural sedation by creating a document that is, to the degree possible, evidence-based. There remains a relative lack of high-quality data in some areas of procedural sedation. It must be carefully noted, however, that despite the statements made in this policy, individual institutions will still be accredited on the basis of the criteria of the respective accrediting organization, such as the JCAHO.

A MEDLINE search of original research on sedation and analgesia from the past decade revealed that emergency physicians are doing the majority of research in this area. A substantial body of evidence supports the routine safe use of procedural sedation and analgesia by emergency physicians.⁴, ⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹, ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹

Back to Article Outline

Introduction 

The emergency department (ED) is a unique environment where a variety of patients with emergent and urgent conditions are managed. Many of these conditions result in significant pain and are associated with varying degrees of anxiety. Accordingly, the management of sedation and analgesia is an important component of comprehensive emergency medical care for patients of all ages and, therefore, a primary concern for the emergency physician. Pain control often is not adequately provided for a variety of reasons, including fear of oversedation, concern of altering physical findings, or underestimation of patient needs.²², ²³ However, proactively addressing pain and anxiety may improve quality of care and patient satisfaction by facilitating interventional procedures and minimizing patient suffering. Many of the drugs used for sedation and analgesia have the potential to cause central nervous system, respiratory, or cardiac depression. According to the JCAHO 2004 Comprehensive Accreditation Manual for Hospitals, the standards for sedation and anesthesia care apply when patients in any setting receive, for any purpose and by any route, moderate or deep sedation, as well as general, spinal, or other major regional sedation and anesthesia.²⁴ To minimize complications, the appropriate drug(s) and dosages must be chosen, monitored, and administered in the proper setting, and a patient evaluation should be performed before, during, and after their use. Many drug and dosing regimens used in procedural sedation and analgesia have been discussed in-depth in other publications.²⁵, ²⁶, ²⁷, ²⁸

It is good medical practice to discuss with patients all medications and interventions that will be provided. The discussion should include the risks, benefits, potential side effects, and alternatives. There is no literature to support that the use of an informed consent form separate from the general informed consent obtained at registration in the ED has an effect on patient satisfaction or on clinical outcome. In some cases, procedural sedation and analgesia is provided in situations when the patient is in severe pain or extremely anxious because of the circumstances surrounding the ED visit; such situations limit the patient's ability to comprehend issues presented in the informed consent process. In other circumstances, the informed consent process is limited by an altered mental status, which affects the patient's capacity to understand risk and benefit. Procedural sedation and analgesia under implied consent may be appropriate in these circumstances.

Recommendations offered in this policy are not intended to represent the only diagnostic and management options that the emergency physician should consider. ACEP clearly recognizes the importance of the individual physician's judgment. Rather, this guideline defines for the physician those strategies for which medical literature exists to provide support for answers to the critical questions addressed in this policy.

Back to Article Outline

Definitions 

Procedural sedation refers to a technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function.³ Procedural sedation and analgesia is intended to result in a depressed level of consciousness that allows the patient to maintain oxygenation and airway control independently. Moderate sedation, previously referred to as “conscious sedation,” is defined as a drug-induced depression of consciousness during which patients respond purposefully.²⁴ Specifically, the drugs, doses, and techniques used are not likely to produce a loss of protective airway reflexes. As part of the continuum of sedation, deep sedation is defined as a drug-induced depression of consciousness during which patients cannot be easily aroused but respond purposefully after repeated or painful stimulation. These patients may require assistance in maintaining airway patency and ventilatory effort.²⁴ General anesthesia is defined as a drug-induced loss of consciousness during which patients are not arousable and may have an impaired cardiorespiratory function requiring varying degrees of support.²⁴ The patient under general anesthesia is profoundly compromised and does not exhibit movement or autonomic nervous system responses to a standard surgical stimulus. On the basis of recognition that proper administration of sedative medications is a continuum and it is often difficult to predict how an individual will respond to a specific sedative agent, practitioners should possess the skills required to rescue a patient 1 level greater than the intended level of sedation. Therefore, should deep sedation be required to perform a procedure, the practitioner is expected to be competent in skills involving cardiovascular support and airway management as in general anesthesia.²⁶ Due to emphasis in the emergency medicine training curriculum, these qualities are now considered core skills for all board-certified emergency physicians.¹, ²

A separate category of sedation has been suggested in an effort to better classify and describe the dissociative sedative agents. Dissociative sedation is described as a “trancelike cataleptic state characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability.” The terms moderate, deep, and general anesthesia sedation refer to forms of sedation that do not apply to dissociative sedation.²⁹

Back to Article Outline

Methodology 

This clinical policy was created after careful review and critical analysis of the peer-reviewed literature. A MEDLINE search of English-language articles published between January 1992 and January 2004 was performed using combinations of the key words “conscious sedation,” “moderate sedation,” “deep sedation,” “analgesia,” “sedation,” “standards,” “guidelines,” “complications,” and “emergency department.” Terms were then exploded as appropriate. Abstracts and articles were reviewed by subcommittee members, and pertinent articles were selected. These articles were evaluated, and those addressing the questions considered in this document were chosen for grading. Subcommittee members also supplied references from bibliographies of initially selected articles or from their own files.

The reasons for developing clinical policies in emergency medicine and the approaches used in their development have been enumerated.³⁰ This policy is a product of the ACEP clinical policy development process and is based on the existing literature; where literature was not available, consensus of emergency physicians was used. Expert review comments were received from emergency physicians, individual members of ACEP's Pediatric Emergency Medicine Committee and Section, and individual members of the American Society of Anesthesiologists. Their responses were used to further refine and enhance this policy. Clinical policies are scheduled for revision every 3 years; however, interim reviews are conducted when technology or the practice environment changes significantly.

All publications were graded by at least 2 of the subcommittee members into 1 of 3 categories of strength of evidence. Some articles were downgraded on the basis of a standardized formula that considers the size of study population, methodology, validity of conclusions, and potential sources of bias (Appendix A).

During the review process, all articles were given a baseline “strength of evidence” by the subcommittee members according to the following criteria:

Strength of evidence Class I and II articles were then rated on elements subcommittee members believed were most important in creating a quality work. Class I and II articles with significant flaws or design bias were downgraded on the basis of a set formula (Appendix B). Strength of evidence Class III articles were downgraded if they demonstrated significant flaws or bias. Articles downgraded below strength of evidence Class III were given an “X” rating and were not used in formulating recommendations in this policy. An Evidentiary Table was constructed and is included in this policy.

Evidentiary Table.

ASA, American Society of Anesthesiologists; BIS, Bispectral Index Score; EEG, electroencephalogram; ICD, implantable cardioverter defibrillator; IM, intramuscular; IV, intravenous; MPC, meperidine-promethazine-chlorpromazine; NCHS, National Center for Health Statistics; NHAMCS, National Hospital Ambulatory Medical Care Survey; NS, not significant; OAA/S, Observer's Assessment of Alertness and Sedation; PAR, postanesthetic recovery; ROC, receiver operating characteristic; VAS, visual analog scale.

Recommendations regarding patient management were then made according to the following criteria:

There are certain circumstances in which the recommendations stemming from a body of evidence should not be rated as highly as the individual studies on which they are based. Factors such as heterogeneity of results, uncertainty about effect magnitude and consequences, strength of prior beliefs, and publication bias, among others, might lead to such a downgrading of recommendations.

Back to Article Outline

Critical questions 

I. What are the personnel requirements needed to provide procedural sedation and analgesia in the ED? 

Personnel providing procedural sedation and analgesia must have an understanding of the drugs administered, the ability to monitor the patient's response to the medications given, and the skills necessary to intervene in managing all potential complications.

JCAHO anesthesia standards reinforce that sedation-to-anesthesia is a continuum, and it is not always possible to predict how individual patients receiving medications will respond. It is therefore important for individual institutions to ensure that all individuals performing moderate or deep sedation are trained to: (1) administer pharmacologic agents to predictably achieve desired levels of sedation, (2) monitor patients and maintain them at desired levels of sedation, and (3) manage complications observed during procedural sedation and analgesia.²⁴ Procedural sedation and analgesia at both moderate and deep levels has been demonstrated to be both safe and effective when properly administered by experienced emergency physicians.⁴, ⁵, ⁶, ⁸, ⁹, ¹⁰, ¹², ¹⁵, ¹⁸, ¹⁹

The literature does not provide clear evidence on the number of personnel necessary to safely provide procedural sedation and analgesia. The presence of a support person assumes increased importance when the physician is involved in a procedure that precludes the ability to continually assess the patient's clinical status. However, there are situations where exceptions are permissible, such as when low doses of pharmacologic agents are used and the physician is able to maintain visual or verbal communication with the patient. During procedural sedation and analgesia, there must be an individual available who is capable of recognizing and managing respiratory and hemodynamic emergencies. As a result, all physicians who are working or consulting in the ED should coordinate all procedures requiring procedural sedation and analgesia with the ED staff.

Personnel recommendations: what are the personnel requirements needed to provide procedural sedation and analgesia in the ED? 

Procedural sedation and analgesia in the ED must be supervised by an emergency physician or other appropriately trained and credentialed specialist.

II. What are the key components of the patient assessment before initiating procedural sedation? 

There is a lack of outcome-based studies to mandate more extensive evaluation beyond vital signs, mental status, and airway and cardiopulmonary assessment. An increased risk with procedural sedation and analgesia may exist in select subsets of patients such as those with difficult facial or neck anatomy, patients who are very old, or patients with underlying cardiopulmonary disease.

There is no literature to support the need for routine diagnostic testing before procedural sedation and analgesia; diagnostic testing is driven by the patient's status.

Patient assessment recommendations: what are the key components of the patient assessment before initiating procedural sedation? 

No routine diagnostic testing is required before procedural sedation.

III. Is preprocedural fasting necessary before initiating procedural sedation? 

The combination of vomiting and loss of airway protective reflexes is an extremely rare occurrence with procedural sedation and analgesia, making aspiration an unlikely event.⁶, ¹², ³², ³³, ³⁴, ³⁵ Recent studies and consensus statements have recommended varying fasting periods based on the specific substance ingested, but fasting patterns remain variable with no uniformly accepted practice standards.²⁶, ³², ³⁵, ³⁶, ³⁷, ³⁸, ³⁹, ⁴⁰, ⁴¹ Much of the aspiration data have been extrapolated from the general anesthesia literature where the potential of aspiration is increased with manipulation of the airway during intubation and extubation. Thorough reviews of this topic demonstrate a lack of evidence that gastric emptying has any impact on the incidence of complications or on outcome in procedural sedation and analgesia. A prospective observational study of 1,014 children identified no difference with airway complications, emesis, or other adverse events between patients classified by their preprocedural fasting status. Of the 509 (56%) patients who did not meet preprocedural fasting guidelines for elective procedures as suggested by the American Academy of Pediatrics and the American Society of Anesthesiologists, no episodes of aspiration were documented. The authors correctly acknowledge that the study is underpowered to detect significant differences in the rate of emesis with and without aspiration due to the extremely rare incidence of these combined events.³⁵ Despite the paucity of data and in recognition of the potential risk for aspiration, a number of publications encourage careful consideration of timing and depth of procedural sedation and analgesia in the absence of an adequate fasting period.³², ⁴¹, ⁴² In addition, pharmacologic agents including antacids have not been shown to improve outcomes and are no longer recommended as standard practice.³², ⁴¹, ⁴³ No study has determined a necessary fasting period before initiation of procedural sedation and analgesia. There is insufficient evidence to determine absolute recommendations. Although recent food intake is not a contraindication for administering procedural sedation and analgesia, the emergency physician must weigh the risk of pulmonary aspiration and the benefits of providing procedural sedation and analgesia in accordance with the needs of each individual patient.

Preprocedure fasting recommendations: is preprocedural fasting necessary before initiating procedural sedation? 

IV. What equipment and supplies are required to provide procedural sedation and analgesia? 

Although rare, procedural sedation and analgesia may result in an allergic reaction, respiratory arrest, or cardiopulmonary arrest. The incidence of complications is dependent on the drugs used, rate and dose of administration, and patient sensitivities. Consequently, the appropriate equipment to monitor the patient's condition, to manage airways, allergic reactions, and drug overdoses, and to treat respiratory and cardiopulmonary arrest should be readily available; use of specific monitoring equipment is discussed in the subsequent sections.

Supportive equipment for procedural sedation and analgesia includes oxygen, suction, medications, and advanced life support equipment (eg, a bag-mask ventilation device, and intubation equipment). The need for intravenous access is dependent on the medications, the dose, and the route used.⁴, ¹², ¹⁵, ⁴⁴, ⁴⁵ Ketamine, which has been shown to exhibit a wide safety margin with preservation of protective airway reflexes and no cardiovascular suppression, is often administered intramuscularly.⁴⁵ This is especially beneficial in the pediatric population where additional needle sticks may not be desirable. Procedural sedation and analgesia with opioids or benzodiazepines may result in respiratory suppression or transient hypotension despite route of administration; therefore, physicians may consider intravenous access necessary in select patients.⁴, ⁵, ⁶ When opioids or benzodiazepines are used, the opioid antagonist naloxone and the benzodiazepine antagonist flumazenil should be available.⁶, ⁴⁶, ⁴⁷

Equipment and supplies recommendations: what equipment and supplies are required to provide procedural sedation and analgesia? 

Intravenous access should be maintained when intravenous procedural sedation and analgesia is provided. Intravenous access may not be necessary when procedural sedation and analgesia is provided by other routes.

V. What assessment and monitoring are required to provide procedural sedation in the ED? 

Monitoring the patient's condition involves visual observation and assessment of the level of consciousness and physiologic changes. The monitoring process should be documented. The components of monitoring may include but are not limited to the level of consciousness, respiratory rate, oxygen saturation, exhaled carbon dioxide, heart rate, blood pressure, and cardiac rhythm monitoring. The patient's ability to follow commands is a method of monitoring level of consciousness. There are times when patients receive procedural sedation and analgesia and then must be transported outside the ED. In such cases, every attempt must be made to provide the same level of monitoring during the transport that was used within the ED.

In general, documentation of the patient's preprocedure status and clinical status during and after the procedure is recommended. The available literature provides little guidance as to the minimum frequency at which vital signs should be recorded.

Vital sign monitoring includes assessment of blood pressure, pulse rate, respiratory rate, and pulse oximetry. A prospectively collected database of 1,367 pediatric patients found the highest risk of serious adverse events occurred within 25 minutes of receiving the last dose of intravenous medications.⁴⁸ Adverse events occurred in 184 (13%) of the patients. Of those, 169 (92%) occurred during the procedure and 14 (8%) occurred in patients after the procedure. The median time for serious adverse events occurred approximately 2 minutes after administration of the final medication.⁴⁸ In 1 study using midazolam and fentanyl, all cases of apnea occurred within 5 minutes of drug administration.⁴⁹ In another study, using diazepam and fentanyl, all episodes of desaturation occurred within 20 minutes.⁵⁰ Despite a recommendation in a consensus statement,²⁶ there is no evidence that cardiac monitoring during procedural sedation and analgesia is of benefit, especially if the patient has no underlying cardiopulmonary disease.

General recommendations: what assessment and monitoring are required to provide procedural sedation in the ED? 

VI. How should respiratory status be assessed? 

Pulse oximetry provides continuous noninvasive estimates of arterial oxygen saturation and is a reliable tool in detecting early decreases in oxygen saturation and changes in the patient's heart rate.⁵¹ Under most circumstances, there is excellent correlation between the pulse oximeter saturation, measured by spectrophotometry, and arterial hemoglobin oxygen saturation measured by oximetry. However, when the hemoglobin saturation decreases below 80%, accuracy may be affected.⁵¹, ⁵² The limitations of oximetry include its inability to detect early decreases in the adequacy of ventilation and, thus, the detection of the onset of hypercarbia that may occur before the development of apnea. The administration of oxygen during procedural sedation and analgesia may delay the onset of hypoxemia and, thus, the detection of hypoventilation.

Many studies have demonstrated the utility of pulse oximetry in detecting decreases in oxygen saturation; most of these studies define hypoxemia as a saturation of less than 90%.⁴, ¹³, ⁴⁵, ⁴⁹

It has been clearly demonstrated that many of the drugs used in procedural sedation and analgesia predispose the patient to the development of hypoxemia, and that drug combinations, especially benzodiazepines and opioids, have a potentiating effect in suppressing respirations.⁴⁹, ⁵³ Despite the evidence that desaturation may occur during procedural sedation and analgesia, there is little information regarding the clinical significance of transient desaturation. Studies have demonstrated that decreases in oxygen saturation occur without clinical consequence, and in fact, transient decreases in oxygen saturation have been reported during sleep in healthy volunteers. In 1 series, 43% of asymptomatic men had desaturation to below 90% during sleep, with 13% below 75%.⁵⁴ The results from at least 2 studies suggested that the only consistent predictor of desaturation during procedural sedation and analgesia was age greater than 55 years.¹⁰, ⁵⁵

It has been hypothesized that failure to properly monitor oxygenation has led to drug-related deaths in procedural sedation and analgesia.⁴⁹ There are no studies showing that detection of a decrease in oxygen saturation alone during procedural sedation and analgesia has an impact on patient outcome. When the patient's level of consciousness or respiratory efforts can be adequately assessed, procedural sedation and analgesia has an extremely low risk of morbidity and mortality.⁶, ⁹, ¹³, ¹⁸, ¹⁹, ⁴⁵, ⁴⁸, ⁵⁰, ⁵⁶, ⁵⁷

However, the rarity of adverse events results in low statistical power for detecting decreases in the adverse event rate. Without devaluing its utility as a monitoring adjunct, pulse oximetry should not substitute for clinical assessment during procedural sedation and analgesia, but rather be utilized as a reliable adjunct.

Procedural sedation and analgesia may cause hypoventilation⁴⁹, ⁵⁸ and an increase in end-tidal carbon dioxide (etco₂).⁵⁹ Capnometry is a technique used to monitor etco₂ and, therefore, may detect early cases of inadequate ventilation before oxygen desaturation takes place.⁶⁰, ⁶¹ An increase in etco₂ might be the only clue to hypoventilation and potential respiratory compromise.⁶² There is an excellent correlation between Paco₂ and etco₂ even when the etco₂ is measured through a nasal cannula while the patient is receiving oxygen.⁶¹

Theoretically, early detection of hypoventilation with capnometry may be beneficial. However, there is no evidence that this benefit has an impact on patient outcome when used in procedural sedation and analgesia. In 1 study of 27 ED patients receiving procedural sedation and analgesia with a benzodiazepine and/or opioids, the average etco₂ increased from 36 to 42 mm Hg while the oxygen saturation decreased from 98% to 94%, but this study had low statistical power to detect differences in outcome. These changes were without clinical consequence.⁶¹ One patient in this study had a desaturation level of 83%, but responded to verbal and tactile stimuli. A more recent prospective study evaluated whether etco₂ could be used to detect respiratory depression and measure depth of sedation.⁶⁰ No correlation was found between the etco₂ and the level of sedation measured by the Observer's Assessment of Alertness and Sedation Scale. A post-hoc analysis of the 74 patients revealed that all patients with respiratory depression demonstrated an etco₂ greater than 50 mm Hg, an absent waveform, or an absolute change from baseline in etco₂ greater than 10 mm Hg. The authors conclude that in the presence of etco₂ monitoring, these identifiers may allow more rapid identification of hypoventilation than pulse oximetry alone. In the study, pulse oximetry would have identified only 11 of the 33 patients meeting the predetermined definitions for respiratory depression of an oxygen saturation less than 90%, etco₂ of greater than 50 mm Hg, or an absent waveform. This study does not address the question as to whether earlier recognition of hypoventilation has any significant impact on outcomes. Hypoventilation and subsequent transient hypercapnea without hypoxemia during procedural sedation and analgesia has no identified impact on outcome.

The Bispectral Index has been validated as an objective measure of sedation depth in the operating room, which has led some researchers to suggest its utility in procedural sedation. The Bispectral Index reflects the varying levels of a patient's sedation as expressed by mathematical evaluations involving relevant, descriptive electroencephalographic measures from the frontal cortex.⁶³, ⁶⁴, ⁶⁵ Although early evidence is supportive,²¹, ⁶⁶ there is insufficient evidence to advocate its routine use in procedural sedation and analgesia.

Respiratory status recommendations: how should respiratory status be assessed? 

Consider capnometry to provide additional information regarding early identification of hypoventilation.

VII. Can ketamine, midazolam, fentanyl, propofol, and etomidate be safely administered for procedural sedation and analgesia in the ED? 

Agents such as ketamine result in a dissociative state in which a patient may not speak or respond purposefully to verbal commands. Use of ketamine in the doses recommended for procedural sedation and analgesia does not result in a loss of protective reflexes. The medical literature documents the safety of its use for procedural sedation and analgesia in pediatric populations.⁴⁴, ⁴⁵, ⁶⁷ In a well-designed randomized controlled trial in 260 children aged 5 to 15 years, Kennedy et al⁶⁷ found that a ketamine and midazolam combination was safer and more efficacious than a fentanyl and midazolam combination for sedation in orthopedic procedures. Hypoxia occurred in 6% of patients receiving ketamine and midazolam versus 20% of patients in the fentanyl and midazolam group. Efficacy as determined by objective measures of physician and parental satisfaction were thought to be superior in the ketamine and midazolam study arm.⁶⁷ In a consecutive case series of 1,022 children, Green et al⁴⁵ report that ketamine at doses of 4 to 5 mg/kg intramuscularly produced adequate sedation in 98% of children. They reported airway complications in 1.4% of patients that included laryngospasm, apnea, and respiratory depression, all of which were quickly identified and treated without intubation or sequelae. Emesis occurred in 6.7% without evidence of aspiration.

In regard to nondissociative sedation agents such as midazolam and fentanyl, a key to minimizing complications in procedural sedation and analgesia is the titration of drugs to the desired effect. Rapid administration of drugs may be associated with hypotension or respiratory depression. In addition, the combination of drugs may accentuate the potential side effects associated with each drug individually. In 1 study, use of benzodiazepines alone resulted in no significant respiratory depression, whereas use of an opioid alone caused hypoxemia in 50% of volunteers and caused a decrease in ventilatory response to carbon dioxide, but did not cause apnea. When the benzodiazepine and opioid were used together, hypoxemia occurred in 92% of subjects, and apnea occurred in 50%.⁴⁹ Although there was no clinical correlation of these findings to patient outcome, this study does suggest that the combined use of benzodiazepines and opioids increases the risk of respiratory compromise. Pohlgeers et al⁵⁰ also reported no association of benzodiazepine dose with desaturation. High doses of opioids without careful and slow titration also increased the risk of respiratory compromise. In a case report, Yaster et al⁴⁷ presented a child who had a respiratory arrest after 10 μg/kg of fentanyl was given over approximately 4 minutes.

It has been suggested that when both a benzodiazepine and an opioid are used, the opioid, which poses the greater risk of respiratory depression, should be given first and the benzodiazepine dose titrated.⁶⁸

There is a growing body of evidence supporting the safe use of propofol for procedural sedation by emergency physicians. In a prospective observational study performed in the ED, propofol-induced procedural sedation was reported to have the lowest rate of respiratory depression when compared with methohexital, fentanyl/midazolam, and etomidate.²¹ There were no significant complications. A prospective randomized trial with 103 patients receiving propofol or methohexital within the ED compared the depth of sedation with Bispectral Index scores and rates of respiratory depression assessed by etco₂. Of note, approximately one half of the patients in both groups met predefined criteria for respiratory depression. The study did not detect a difference in either the level of sedation by Bispectral Index or the level of subclinical respiratory depression between the 2 agents. The authors found no significant adverse events with either sedative.²⁰ In another prospective study of 43 children comparing midazolam and propofol, the authors reported successful sedation but also significant hypoxemia and oversedation; however, no significant complications were reported.¹⁵ In another pediatric study involving 40 patients, Skokan et al¹⁶ reported a significant incidence of oxygen desaturation; however, again, there were no clinical sequelae.

The literature regarding safety and efficacy of etomidate in the ED is also mounting. A prospective, double-blinded, randomized trial of 46 adult patients undergoing anterior shoulder dislocation reduction in the ED compared midazolam with etomidate.¹⁷ Burton et al¹⁷ found approximately a 90% procedural success rate for both groups. Patients experienced no episodes of hypotension or arrhythmia. Adverse respiratory events in the 19 etomidate patients included 4 episodes of desaturation with one 75-year-old patient requiring bag-mask ventilation for a brief period of apnea. There was no significant difference between the groups with episodes of hypoxia. Patient and physician visual analog pain assessment scores were similar between groups. Dickinson et al,¹¹ in a retrospective review of 53 children, with the majority of these children older than 10 years, described the drug's use in the reduction of pediatric orthopedic procedures. The authors found an 83% success rate after the first attempt. Documented side effects included 1 patient with nausea and 1 patient requiring a fluid bolus for transient hypotension. There were no reported incidences of patients who required assisted ventilation of any kind.¹¹ Ruth et al¹² performed a prospective study on 51 consecutive patients. Ninety-eight percent of the patients achieved adequate sedation: 5 patients desaturated below 90% and 1 patient vomited; however, no patient required assistance with ventilation or had a clinically significant complication. Vinson and Bradbury¹⁰ retrospectively reviewed 134 patients treated with etomidate for procedural sedation. Ninety-five percent of the patients were “extremely” satisfied with their care. They reported a 5% rate of adverse events including 5 cases of desaturation below 94%, all of whom recovered uneventfully. Another smaller retrospective chart review of 46 adults and 2 children identified 4/48 (8%) patients with procedural failure.¹³ These authors found 10/48 (21%) patients with adverse reactions. Respiratory complications included 1 patient who developed transient apnea requiring bag-mask ventilation, while another patient required a nonrebreather for a desaturation below 90%. Other commonly reported side effects of etomidate include pain with injection and myoclonus.¹², ¹⁷, ⁶⁹, ⁷⁰, ⁷¹ Myoclonus reports ranging from 0% to 21% of patients receiving etomidate usually last less than 1 minute, but can be dramatic and may resemble seizure activity.¹⁰, ¹², ¹⁷, ⁷⁰ These tremors are generally benign and not epileptigenic activity, but they can result in brief desaturation.⁶⁹, ⁷²

In conclusion, there is a growing body of literature supporting the safe use of a large variety of agents for procedural sedation and analgesia in the ED. Ketamine, midazolam, fentanyl, propofol, and etomidate are just a few of these agents in common usage. Respiratory depression is the most concerning of side effects related to the use of these agents; however, careful preparation and administration have been shown to prevent harmful sequelae.

Back to Article Outline

Drug administration recommendations: can ketamine, midazolam, fentanyl, propofol, and etomidate be safely administered for procedural sedation and analgesia in the ED? 

Back to Article Outline

Appendix A. Literature classification schema.^∗ 

Back to Article Outline

Appendix B. Approach to downgrading strength of evidence 

Back to Article Outline

References 

1. Core Content Task Force . The model of the clinical practice of emergency medicine. Ann Emerg Med. 2001;37:745–770
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (98 KB)
   • CrossRef
2. Task Force on the Core Content for Emergency Medicine Revision . Core content for emergency medicine. Ann Emerg Med. 1997;29:792–811
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (1107 KB)
   • CrossRef
3. American College of Emergency Physicians . Clinical policy for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 1998;31:663–677
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (95 KB)
   • CrossRef
4. Terndrup TE, Cantor RM, Madden CM. Intramuscular meperidine, promethazine, and chlorpromazine: analysis of use and complications in 487 pediatric emergency department patients. Ann Emerg Med. 1989;18:528–533
   • View In Article
   • Abstract
   • Full-Text PDF (640 KB)
   • CrossRef
5. Chudnofsky CR, Wright SW, Dronen SC, et al. The safety of fentanyl use in the emergency department. Ann Emerg Med. 1989;18:635–639
   • View In Article
   • Abstract
   • Full-Text PDF (453 KB)
   • CrossRef
6. Chudnofsky CR, Weber JE, Stoyanoff PJ, et al. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Acad Emerg Med. 2000;7:228–235
   • View In Article
   • MEDLINE
   • CrossRef
7. Wathen JE, Roback MG, Mackenzie T, et al. Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial. Ann Emerg Med. 2000;36:579–588
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (100 KB)
   • CrossRef
8. Dachs RJ, Innes GM. Intravenous ketamine sedation of pediatric patients in the emergency department. Ann Emerg Med. 1997;29:146–150
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (449 KB)
   • CrossRef
9. Barsan WG, Tomassoni AJ, Seger D, et al. Safety assessment of high-dose narcotic analgesia for emergency department procedures. Ann Emerg Med. 1993;22:1444–1449
   • View In Article
   • Abstract
   • Full-Text PDF (562 KB)
   • CrossRef
10. Vinson DR, Bradbury DR. Etomidate for procedural sedation in emergency medicine. Ann Emerg Med. 2002;39:592–598
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (77 KB)
    • CrossRef
11. Dickinson R, Singer AJ, Carrion W. Etomidate for pediatric sedation prior to fracture reduction. Acad Emerg Med. 2001;8:74–77
    • View In Article
    • MEDLINE
    • CrossRef
12. Ruth WJ, Burton JH, Bock AJ. Intravenous etomidate for procedural sedation in emergency department patients. Acad Emerg Med. 2001;8:13–18
    • View In Article
    • MEDLINE
    • CrossRef
13. Keim SM, Erstad BL, Sakles JC, et al. Etomidate for procedural sedation in the emergency department. Pharmacotherapy. 2002;22:586–592
    • View In Article
    • MEDLINE
    • CrossRef
14. Swanson ER, Seaberg DC, Mathias S. The use of propofol for sedation in the emergency department. Acad Emerg Med. 1996;3:234–238
    • View In Article
    • MEDLINE
    • CrossRef
15. Havel CJ, Strait RT, Hennes H. A clinical trial of propofol vs. midazolam for procedural sedation in a pediatric emergency department. Acad Emerg Med. 1999;6:989–997
    • View In Article
    • MEDLINE
    • CrossRef
16. Skokan EG, Pribble C, Bassett KE, et al. Use of propofol sedation in a pediatric emergency department: a prospective study. Clin Pediatr (Phila). 2001;40:663–671
    • View In Article
    • MEDLINE
    • CrossRef
17. Burton JH, Bock AJ, Strout TD, et al. Etomidate and midazolam for reduction of anterior shoulder dislocation: a randomized, controlled trial. Ann Emerg Med. 2002;40:496–504
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (78 KB)
    • CrossRef
18. Guenther E, Pribble CG, Junkins EP, et al. Propofol sedation by emergency physicians for elective pediatric outpatient procedures. Ann Emerg Med. 2003;42:783–791
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (118 KB)
    • CrossRef
19. Bassett KE, Anderson JL, Pribble CG, et al. Propofol for procedural sedation in children in the emergency department. Ann Emerg Med. 2003;42:773–782
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (130 KB)
    • CrossRef
20. Miner JR, Biros M, Krieg S, et al. Randomized clinical trial of propofol versus methohexital for procedural sedation during fracture and dislocation reduction in the emergency department. Acad Emerg Med. 2003;10:931–937
    • View In Article
    • MEDLINE
    • CrossRef
21. Miner JR, Biros MH, Heegaard W, et al. Bispectral electroencephalographic analysis of patients undergoing procedural sedation in the emergency department. Acad Emerg Med. 2003;10:638–643
    • View In Article
    • MEDLINE
    • CrossRef
22. Wilson JE, Pendleton JM. Oligoanalgesia in the emergency department. Am J Emerg Med. 1989;7:620–623
    • View In Article
    • MEDLINE
    • CrossRef
23. Brown JC, Klein EJ, Lewis CW, et al. Emergency department analgesia for fracture pain. Ann Emerg Med. 2003;42:197–205
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (93 KB)
    • CrossRef
24. Joint Commission on Accreditation of Healthcare Organizations . Comprehensive Accreditation Manual for Hospitals, The Official Handbook. Chicago, IL: JCAHO Publication; 2004;
    • View In Article
25. Krauss B, Green SM. Sedation and analgesia for procedures in children. N Engl J Med. 2000;342:938–945
    • View In Article
    • MEDLINE
    • CrossRef
26. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists . Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002;96:1004–1017
    • View In Article
    • MEDLINE
    • CrossRef
27. Blackburn P, Vissers R. Pharmacology of emergency department pain management and conscious sedation. Emerg Med Clin North Am. 2000;18:803–827
    • View In Article
    • Full Text
    • Full-Text PDF (1482 KB)
    • CrossRef
28. Glauser J, Cullison B. Procedural sedation: general principles and specific pharmacotherapeutic strategies-part 1. Emergency Medicine Reports. 2002;23:247–260
    • View In Article
29. Green SM, Krauss B. The semantics of ketamine. Ann Emerg Med. 2000;36:480–482
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (52 KB)
    • CrossRef
30. Schriger DL, Cantrill SV, Greene CS. The origins, benefits, harms, and implication of emergency medicine clinical policies. Ann Emerg Med. 1993;22:597–602
    • View In Article
    • Abstract
    • Full-Text PDF (664 KB)
    • CrossRef
31. Mace SE, Barata IA, Cravero JP, et al., EMSC Grant Panel Writing Committee on Pharmacologic Agents Used in Pediatric Sedation and Analgesia in the Emergency Department  Clinical policy: evidence-based approach to pharmacologic agents used in pediatric sedation and analgesia in the emergency department. Ann Emerg Med. 2004;44:342–377
    • View In Article
    • Full Text
    • Full-Text PDF (355 KB)
    • CrossRef
32. Green SM, Krauss B. Pulmonary aspiration risk during emergency department procedural sedation: an examination of the role of fasting and sedation depth. Acad Emerg Med. 2002;9:35–42
    • View In Article
    • MEDLINE
    • CrossRef
33. Pacifico A, Cedillo-Salazar FR, Nasir N, et al. Conscious sedation with combined hypnotic agents for implantation of cardioverter-defibrillators. J Am Coll Cardiol. 1997;30:769–773
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (150 KB)
    • CrossRef
34. Pena BM, Krauss B. Adverse events of procedural sedation and analgesia in a pediatric emergency department. Ann Emerg Med. 1999;34:483–491
    • View In Article
    • Abstract
    • Full-Text PDF (788 KB)
    • CrossRef
35. Agrawal D, Manzi SF, Gupta R, et al. Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department. Ann Emerg Med. 2003;42:636–646
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (127 KB)
    • CrossRef
36. Ferrari LR, Rooney FM, Rockoff MA. Preoperative fasting practices in pediatrics. Anesthesiology. 1999;90:978–980
    • View In Article
    • MEDLINE
    • CrossRef
37. Maekawa N, Mikawa K, Yaku H, et al. Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis in children. Acta Anaesthesiol Scand. 1993;37:783–787
    • View In Article
    • MEDLINE
    • CrossRef
38. Splinter WM, Schaefer JD, Zunder IH. Clear fluids three hours before surgery do not affect the gastric fluid contents of children. Can J Anaesth. 1990;37:498–501
    • View In Article
    • MEDLINE
    • CrossRef
39. Soreide E, Hausken T, Soreide JA, et al. Gastric emptying of a light hospital breakfast. A study using real time ultrasonography. Acta Anaesthesiol Scand. 1996;40:549–553
    • View In Article
    • MEDLINE
    • CrossRef
40. Ingebo KR, Rayhorn NJ, Hecht RM, et al. Sedation in children: adequacy of two-hour fasting. J Pediatr. 1997;131:155–158
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (817 KB)
    • CrossRef
41. American Society of Anesthesiologists Task Force on Preoperative Fasting . Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures. Anesthesiology. 1999;90:896–905
    • View In Article
    • MEDLINE
    • CrossRef
42. Green SM. Fasting is a consideration—not a necessity—for emergency department procedural sedation and analgesia. Ann Emerg Med. 2003;42:647–650
    • View In Article
    • Full Text
    • Full-Text PDF (58 KB)
    • CrossRef
43. Engelhardt T, Webster NR. Pulmonary aspiration of gastric contents in anesthesia. Br J Anaesth. 1999;83:453–460
    • View In Article
    • MEDLINE
    • CrossRef
44. Green SM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: part 1, a prospective series. Ann Emerg Med. 1990;19:1024–1032
    • View In Article
    • Abstract
    • Full-Text PDF (892 KB)
    • CrossRef
45. Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Ann Emerg Med. 1998;31:688–697
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (92 KB)
    • CrossRef
46. Chudnofsky CR. Safety and efficacy of flumazenil in reversing conscious sedation in the emergency department. Emergency Medicine Conscious Sedation Study Group. Acad Emerg Med. 1997;4:944–950
    • View In Article
    • MEDLINE
    • CrossRef
47. Yaster M, Nichols DG, Deshpande JK, et al. Midazolam-fentanyl intravenous sedation in children: case report of respiratory arrest. Pediatrics. 1990;86:463–467
    • View In Article
    • MEDLINE
48. Newman DH, Azer MM, Pitetti RD, et al. When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1,367 pediatric procedural sedations. Ann Emerg Med. 2003;42:627–635
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (105 KB)
    • CrossRef
49. Bailey PL, Pace NL, Ashburn MA, et al. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology. 1990;73:826–830
    • View In Article
    • MEDLINE
    • CrossRef
50. Pohlgeers AP, Friedland LR, Keegan-Jones L. Combination fentanyl and diazepam for pediatric conscious sedation. Acad Emerg Med. 1995;2:879–883
    • View In Article
    • MEDLINE
    • CrossRef
51. American Medical Association , Council on Scientific Affairs . The use of pulse oximetry during conscious sedation. JAMA. 1993;270:1463–1468
    • View In Article
    • MEDLINE
52. Aughey K, Hess D, Eitel D, et al. An evaluation of pulse oximetry in prehospital care. Ann Emerg Med. 1991;20:887–891
    • View In Article
    • Abstract
    • Full-Text PDF (510 KB)
    • CrossRef
53. Rubin DM, Eisig S, Freeman K, et al. Effect of supplemental gases on end-tidal CO₂ and oxygen saturation in patients undergoing fentanyl and midazolam outpatient sedation. Anesth Prog. 1997;44:1–4
    • View In Article
    • MEDLINE
54. Block AJ, Boysen PG, Wynne JW, et al. Sleep apnea hypopnea and oxygen desaturation in normal subjects: a strong male predominance. N Engl J Med. 1979;300:513–517
    • View In Article
    • MEDLINE
    • CrossRef
55. Bilotta JJ, Floyd JL, Waye JD. Arterial oxygen desaturation during ambulatory colonoscopy: predictability, incidence, and clinical insignificance. Gastrointest Endosc. 1990;36:S5–S8
    • View In Article
    • MEDLINE
56. Arrowsmith JB, Gerstman BB, Fleischer DE, et al. Results from the American Society for Gastrointestinal Endoscopy/US Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointest Endosc. 1991;37:421–427
    • View In Article
    • Abstract
    • Full-Text PDF (5892 KB)
    • CrossRef
57. Ceravolo FJ, Meyers HE, Michael JJ, et al. Full dentition periodontal surgery using intravenous conscious-sedation. A report of 10,000 cases. J Periodontal. 1986;57:383–384
    • View In Article
58. Tobias JD. End-tidal carbon dioxide monitoring during sedation with a combination of midazolam and ketamine for children undergoing painful, invasive procedures. Pediatr Emerg Care. 1999;15:173–175
    • View In Article
    • MEDLINE
    • CrossRef
59. McQuillen KK, Steele DW. Capnometry during sedation/analgesia in the pediatric emergency department. Pediatr Emerg Care. 2000;16:401–404
    • View In Article
    • MEDLINE
    • CrossRef
60. Miner JR, Heegaard W, Plummer D. End-tidal carbon dioxide monitoring during procedural sedation. Acad Emerg Med. 2002;9:275–280
    • View In Article
    • MEDLINE
    • CrossRef
61. Wright SW. Conscious sedation in the emergency department: the value of capnography and pulse oximetry. Ann Emerg Med. 1992;21:551–555
    • View In Article
    • Abstract
    • Full-Text PDF (398 KB)
    • CrossRef
62. Hart LS, Berns SD, Houck CS, et al. The value of end-tidal CO₂ monitoring when comparing three methods of conscious sedation for children undergoing painful procedures in the emergency department. Pediatr Emerg Care. 1997;13:189–193
    • View In Article
    • MEDLINE
    • CrossRef
63. Rosow C, Manberg PJ. Bispectral index monitoring. Anesthesiol Cl in North America: Annual Anesth Pharm. 1998;2:89–107
    • View In Article
64. Bower AL, Ripepi A, Dilger J, et al. Bispectral index monitoring of sedation during endoscopy. Gastrointest Endosc. 2000;52:192–196
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (35 KB)
    • CrossRef
65. Gill M, Green SM, Krauss B. A study of the Bispectral Index Monitor during procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2003;41:234–241
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (84 KB)
    • CrossRef
66. Agrawal D, Feldman HA, Krauss B, et al. Bispectral index monitoring quantifies depth of sedation during emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2004;43:247–255
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (125 KB)
    • CrossRef
67. Kennedy RM, Porter FL, Miller JP, et al. Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic emergencies. Pediatrics. 1998;102:956–963
    • View In Article
    • MEDLINE
    • CrossRef
68. Bell GD, McCloy RF, Charlton JE, et al. Recommendations for standards of sedation and patient monitoring during gastrointestinal endoscopy. Gut. 1991;32:823–827
    • View In Article
    • MEDLINE
    • CrossRef
69. Helmers JH, Adam AA, Giezen J. Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl. Acta Anaesthesiol Belg. 1981;32:141–147
    • View In Article
    • MEDLINE
70. Van Keulen SG, Burton JH. Myoclonus associated with etomidate for ED procedural sedation and analgesia. Am J Emerg Med. 2003;21:556–558
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (37 KB)
    • CrossRef
71. McDowall RH, Scher CS, Barst SM. Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures. J Clin Anesth. 1995;7:273–280
    • View In Article
    • Abstract
    • Full-Text PDF (759 KB)
    • CrossRef
72. Modica PA, Tempelhoff R. Intracranial pressure during induction of anaesthesia and tracheal intubation with etomidate-induced EEG burst suppression. Can J Anaesth. 1992;39:236–241
    • View In Article
    • MEDLINE
    • CrossRef