Updated: Apr 1, 2009
The American College of Emergency Physicians (ACEP) defines procedural sedation as "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. Procedural sedation and analgesia (PSA) is intended to result in a depressed level of consciousness that allows the patient to maintain oxygenation and airway control independently."1
The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Medications that elicit pharmacologic effects, such as anxiolysis, amnesia, or analgesia, provide patient comfort during various procedures. Understanding the efficacy and safe administration of these agents is essential to the practitioner performing interventional procedures.
Sedation and analgesia introduces an independent risk factor for morbidity and mortality in addition to the procedure itself. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) recognizes the risks involved with sedation and analgesia for procedures and mandates that sedation practices throughout an institution be monitored and evaluated by the department of anesthesia. The American Society of Anesthesiologists (ASA) has responded to this challenging responsibility by developing practice guidelines for nonanesthesiologists who provide sedation and analgesia. For more information, see Guidelines for Office-Based Anesthesia, a statement on the Qualifications of Anesthesia Providers in the Office-Based Setting, and Practice Guidelines for Sedation and Analgesia by Nonanesthesiologists.2,3
The information described in this article does NOT apply to the following types of patients:
Understanding the various depths of sedation is essential to provide safe and effective procedural sedation and analgesia. The ASA has defined the various sedation depths. As defined below, minimal sedation or moderate sedation is used for PSA.1
Minimal sedation (anxiolysis)
Additionally, clinicians must recognize procedures performed outside of the operating room that may require monitored anesthesia care (MAC). For more information, see ASA’s Distinguishing Monitored Anesthesia Care (“MAC”) From Moderate Sedation/Analgesia (Conscious Sedation).2
Various drugs are available to provide procedural sedation; their pharmacodynamic descriptions are described below.4 A short-acting benzodiazepine (eg, midazolam), either alone or in combination with an opioid analgesic (eg, fentanyl, morphine), is commonly selected for procedural sedation. Combining use of a benzodiazepine and an opiate may be preferable for longer procedures but increases the risk of oxygen desaturation and cardiorespiratory complications. Specific reversal agents for opiates (naloxone [Narcan]) and benzodiazepines (flumazenil [Mazicon]) must be readily available during the procedure. Evidence in the literature is emerging that also supports the use of other sedatives (eg, etomidate, propofol) for procedural sedation. Etomidate is gaining popularity because it elicits minimal hemodynamic effects and has a very reliable onset of action. Ketamine results in a dissociative state, and patients may not be able to speak or respond purposefully to verbal commands. Ketamine is typically not used in adults because of frequent association with emergence delirium; however, ketamine is used frequently in the pediatric population, where this effect is not typically observed.
Benzodiazepines
Benzodiazepines (BZPs) elicit beneficial effects for PSA that include amnesia, anticonvulsant, anxiolysis, and sedation. Benzodiazepines potentiate gamma-aminobutyric acid (GABA) inhibitory action in the CNS by binding to benzodiazepine-specific receptors on the GABAA -benzodiazepine receptor complex. Binding of this complex potentiates GABA-mediated chloride influx that results in sedation, amnesia, anxiolysis, and anticonvulsant effects and respiratory depression.
Midazolam (Versed) is the benzodiazepine most commonly used for PSA, since it produces earlier sedation, more complete amnesia, less pain on injection, and improved awakening when compared with diazepam. Midazolam possesses a relatively high volume of distribution (Vd) compared with other benzodiazepines because of its lipophilicity. The Vd is greatly amplified in obese patients, resulting in an increased half-life from 2.7 hours to 8.4 hours. Midazolam is cleared by hepatic hydroxylation to 1-hydroxymidazolam (elicits about 10% of the pharmacologic activity as parent compound). In comparison, diazepam has an extremely long half-life (0.8-2.25 d) that is markedly increased in obese or elderly patients (3.9 d and 3.29 d, respectively). Additionally, its active metabolites have long half-lives (ie, N -desmethyldiazepam [1.6-4.2 d]; nordiazepam [about 8 d]).
Lorazepam (Ativan) is another benzodiazepine that may be used for mild-to-moderate sedation; however, unlike midazolam, its onset of action does not peak until 15-20 minutes after administration. The duration of action of lorazepam is longer (ie, 6-8 h) than that of midazolam (30-60 min). Because of this, lorazepam is typically used for long-term sedation, such as in an ICU setting.
When combined with alcohol or opioids, the sedative and respiratory-depressant effects of benzodiazepines are greatly increased, as is the risk for cardiovascular depression.Opiates
Opiates provide analgesia and sedation during painful procedures. Fentanyl is favored because of its prompt onset and short duration of action. Unlike morphine, fentanyl has minimal cardiovascular depressive effects and hypotension rarely occurs. Fentanyl binds with stereospecific receptors at many sites within the CNS and increases pain threshold, alters pain reception, and inhibits ascending pain pathways. In addition to analgesia, opioid agonists suppress the cough reflex and cause respiratory depression, drowsiness, and sedation. The half-life is 2-4 hours. Meperidine is a poor choice for analgesia because of its active metabolite that has neurotoxic effects.
Ketamine
Propofol provides potent, ultra–short-acting sedation and anesthesia. It is a phenolic compound, and its mechanism of action is unknown, but it is thought to mediate GABA activity. Propofol has no analgesic properties. It is associated with rapid deepening of a sedation level to that of general anesthesia. Because of this, an anesthesiologist or sedation team often administers it and monitors its use outside the operating room.
Recent literature has described increasing use of propofol for emergency department procedural sedation.7,8,9,10 Hohl et al described propofol as slightly more cost-effective than midazolam because of shorter recovery times with propofol.7 A prospective study using propofol in a standard protocol in 113 patients in an emergency department concluded propofol as safe and effective for procedural sedation with high patient and physician satisfaction.8 Other studies have confirmed the safety of propofol in the emergency department setting.9,10
Etomidate
Etomidate is an ultra–short-acting nonbarbiturate hypnotic used for anesthesia. It produces rapid induction without histamine release and with minimal cardiovascular and respiratory effects. As with ketamine or barbiturates, etomidate transiently lowers cerebral blood flow by 20-30% and slightly reduces intracranial and intraocular pressure. It has no analgesic properties.
Question the patient or caregiver regarding the following:
Practitioners must be skilled in providing procedural sedation, must be proficient in airway management and cardiovascular support, and must possess the skills required to rescue a patient from sedation deeper than intended. Continually evaluating and monitoring respiratory and circulatory requirements prior to, during, and following the procedure is essential. A recent analysis describes emergency department physicians' knowledge of procedural sedation.11 Additionally, the JCAHO requires practitioners to be competent in managing reversal of sedation from one level deeper than anticipated.
For more information, see ASA Standards for Basic Anesthetic Monitoring.2
Table 1. Commonly Used Drugs for Procedural Sedation and Analgesia in Adults
| Drug | Adult Dose | Onset of Action | Duration of Action* | Comments |
| Midazolam (Versed) | 0.02-0.1 mg/kg IV initially; if further sedation is required, may repeat with 25% of initial dose after 3-5 min; not to exceed 2.5 mg/dose (1.5 mg for elderly persons) and 5 mg cumulative dose (3.5 mg for elderly persons) | 1-2 min | 30-60 min | Respiratory depression or hypotension may occur, particularly when rapidly administered or combined with fentanyl (may need to decrease midazolam dose); does not provide analgesia; action reversed by flumazenil |
| Fentanyl | 1-2 mcg/kg slow IV push (over 1-2 min); may repeat dose after 30 min | 1-2 min | 30-60 min | May cause chest wall rigidity, apnea, respiratory depression, or hypotension; elicits minimal cardiovascular depression; may cause dysphoria, nausea, vomiting, or EEG changes; action reversed by naloxone |
| Etomidate (Amidate) | 0.1-0.2 mg/kg slow IV push over 30-60 sec | <1 min | 3-5 min | Commonly causes myoclonus, pain upon injection, adrenal suppression (typically no clinical significance); may cause nausea, vomiting, and lower seizure threshold; does not alter hemodynamics; causes a slight to moderate decrease in intracranial pressure that only lasts for several minutes; does not cause histamine release; useful for patients with trauma and hypotension |
| Propofol (Diprivan) | 0.5-1 mg/kg IV loading dose; may repeat by 0.5-mg increments q3-5min | <1 min | 3-10 min | Provides rapid onset and recovery phase, and brief duration of action; has anticonvulsant properties; can rapidly cause deepening sedation; causes cardiovascular depression and hypotension |
The selection of sedative and analgesic agents differs slightly when these agents are used in children. Benzodiazepines, chloral hydrate, and barbiturates have been used for decades to provide sedation for pediatric procedures.12,13,14,15,6 Propofol is also beginning to be used outside the operating room to induce anesthesia for pediatric procedures (mostly by pediatric anesthesiologists or a sedation team). Recent data suggest greater variability in children younger than 1 year for the loading dose, whereas more variability is seen with the maintenance dose in children older than 7 years.16
Data are limited for the use of etomidate for procedural sedation in children. A recent review by den Brinker et al summarizes the information currently available. The potential for etomidate to inhibit cortisol production may make its use in children limited.17
None of the aforementioned sedative agents provide analgesia. For painful procedures, an opioid analgesic (eg, fentanyl) is required; ketamine, which provides sedation and analgesia, may be considered instead.15
Midazolam is the most commonly prescribed benzodiazepine for pediatrics and can be administered via various routes (eg, oral, intranasal, rectal, intramuscular, intravenous). It provides excellent amnesia and anxiolytic effect. Chloral hydrate has been used for routine sedation for many years; however, the development of safer and more effective agents have largely replaced it. Barbiturates may be considered for procedures requiring immobilization.
Leroy et al state that procedural sedation for children should only be provided by well-trained and credentialed professionals and that professionals with the needed expertise are available at all times.18
The Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN) have recently published recommendations for standardizing terminology and reporting adverse events involving procedural sedation and analgesia in children. These recommendations will also help guide monitoring and quality assurance of pediatric procedural sedation in emergency departments.19
Table 2. Commonly Used Drugs for Procedural Sedation and Analgesia in Pediatric Patients
| Drug | Pediatric Dose | Comments |
| Midazolam | Intravenous: 0.05-0.1 mg/kg IV 3 min before procedure; not to exceed a total cumulative dose of 0.4 mg/kg or 6 mg Intramuscular: 0.1-0.2 mg/kg IM 30-45 min before procedure Oral: 0.25-0.5 mg/kg PO 30-45 min before procedure Intranasal: 0.2-0.6 mg/kg/dose inhaled intranasally 10 min before procedure Rectal: 0.3-0.5 mg/kg/dose PR 30-45 min before procedure | Reduce dose by 30-50% if combined with opioid analgesic (eg, fentanyl); younger children (ie, <5 y) may require higher doses up to 0.6 mg/kg/dose |
| Pentobarbital | Intravenous: 1-2 mg/kg/dose IV; if needed may repeat dose; not to exceed a cumulative dose of 6 mg/kg or 150-200 mg Intramuscular: 1-6 mg/kg IM; not to exceed 100 mg/dose Oral: 4-6 mg/kg PO; not to exceed 100 mg/dose | Short-acting barbiturate that provides excellent hypnosis and is particularly useful for procedures requiring immobilization (eg, diagnostic radiologic procedures); paradoxical excitation may occur; no reversal agent exists |
| Methohexital | 25 mg/kg/dose PR 15 min before procedure; not to exceed 500 mg/dose | Ultra–short-acting barbiturate providing good immobilization and hypnosis; paradoxical excitation may occur; no reversal agent exists |
| Fentanyl | 1 mcg/kg/dose IV; if needed, may repeat by 1-mcg/kg increments; not to exceed total cumulative dose of 4 mcg/kg | Provides analgesia for painful procedures; increased risk of respiratory depression when combined with sedatives (reduce sedative dose); chest wall rigidity associated with rapid IV push |
| Ketamine | Intravenous: 1-2 mg/kg loading dose IV; 0.25-1 mg/kg IV q10-15min; administer slowly, not to exceed 0.5 mg/kg/min Intramuscular: 2-5 mg/kg/dose IM Oral: 6-10 mg/kg/dose PO mixed in cola or other beverage 30 min before procedure | Provides excellent sedation and analgesia; elicits dissociative state; increases bronchial and salivary secretions; increases heart rate, blood pressure, and intracranial pressure; emergence hallucinations observed in older children (>15 years) and adults; pharmacologic effects NOT reversible |
| Propofol | Data limited: 1-1.5 mg/kg IV loading dose; 0.25-0.5 mg/kg IV q3-5min or 50-150 mcg/kg/min continuous IV infusion | Provides rapid anesthesia; apnea occurs upon induction and unpredictably causes loss of airway reflexes (even at sedative doses); irritation and burning with IV administration; effect NOT reversible |
| Chloral hydrate | 25-75 mg/kg/dose PO/PR; not to exceed 1 g/dose (infants) or 2 g/dose (children); administer 30 min before procedure No longer recommended, see comments | No longer recommended since much safer and more effective alternatives exist; unpredictable effect; paradoxical hyperactivity may occur; may cause nausea and vomiting; decrease dose if combined with opioid analgesic (eg, fentanyl); deaths and permanent neurologic injury from respiratory compromise have been reported, particularly in those with risk factors (eg, ASA class III, Leigh encephalopathy, tonsillar and adenoidal hypertrophy, obstructive sleep apnea); active metabolite has prolonged half-life |
Drug dosages for sedation and analgesia are highly variable, and other factors such as concurrent medications, medical conditions, and age contribute to this variability. Drugs for mild-to-moderate sedation should only be used in settings that provide for continuous monitoring of respiratory and cardiac function. Availability of resuscitative drugs, equipment, and health care personnel experienced with the use of these drugs must be guaranteed. Reversal agents for opioids (ie, naloxone) and benzodiazepines (ie, flumazenil) must also be available.
Table 3. Commonly Used Reversal Agents
| Reversal Agent | Indication | Adult Dose | Pediatric Dose | Comments |
| Naloxone (Narcan) | Reverses opioid agonists | Postanesthetic or opioid dependent: 0.1-0.2 mg/kg IV; may repeat q2-3min prn Opioid overdose: 0.4-2 mg IV; may repeat q2-3min prn | Postanesthetic reversal: 0.005-0.01 mg/kg IV/IM; may repeat q2-3min prn Opiate intoxication: 0.01-0.1 mg/kg dose IV/IM; may repeat every min; not to exceed 2 mg/dose | Onset of action for IV is 1-3 min vs 10-15 min for IM; rebound sedation may occur; if used in patient with chronic opioid use, will precipitate acute withdrawal |
| Flumazenil (Mazicon) | Reverses benzodiazepines | Partial antagonism (for sedation reversal): 0.1-0.2 mg IV infused over 15 sec; may repeat after 45 sec and then every min; not to exceed total cumulative dose of 1 mg Complete antagonism (for overdose): 0.2 mg IV infused over 30 sec; may repeat with additional doses of 0.5 mg over 30 sec at 1-min intervals; not to exceed a total cumulative dose of 3 mg | 0.01 mg/kg/dose IV infused over 15 sec; not to exceed 0.2 mg/dose; may repeat every min; not to exceed total cumulative dose of 0.05 mg/kg or 1 mg (whichever is lower) | Rebound sedation may occur; if used in patient with chronic BZP use, will precipitate acute withdrawal; may precipitate seizures unresponsive to BZPs |
American Society of Anesthesiologists. Continuum of depth of sedation definition of general anesthesia and levels of sedation/analgesia. October 27, 2004. Available at http://www.asahq.org/publicationsAndServices/standards/20.pdf. Accessed March 30, 2009.
American Society of Anesthesiologists Standards, Guidelines, and Statements. Available at http://www.asahq.org/publicationsAndServices/sgstoc.htm. Accessed March 30, 2009.
Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. Apr 2002;96(4):1004-17. [Medline].
Godwin SA, Caro DA, Wolf SJ, et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. Feb 2005;45(2):177-96. [Medline].
Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. Nov 2008;26(9):985-1028. [Medline].
Krauss B, Green SM. Procedural sedation and analgesia in children. Lancet. Mar 4 2006;367(9512):766-80. [Medline].
[Best Evidence] Hohl CM, Nosyk B, Sadatsafavi M, Anis AH. A cost-effectiveness analysis of propofol versus midazolam for procedural sedation in the emergency department. Acad Emerg Med. Jan 2008;15(1):32-9. [Medline].
Zed PJ, Abu-Laban RB, Chan WW, Harrison DW. Efficacy, safety and patient satisfaction of propofol for procedural sedation and analgesia in the emergency department: a prospective study. CJEM. Nov 2007;9(6):421-7. [Medline].
Weaver CS, Hauter WE, Brizendine EJ, Cordell WH. Emergency department procedural sedation with propofol: is it safe?. J Emerg Med. Nov 2007;33(4):355-61. [Medline].
[Best Evidence] Hohl CM, Sadatsafavi M, Nosyk B, Anis AH. Safety and clinical effectiveness of midazolam versus propofol for procedural sedation in the emergency department: a systematic review. Acad Emerg Med. Jan 2008;15(1):1-8. [Medline].
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Shankar V, Deshpande JK. Procedural sedation in the pediatric patient. Anesthesiology Clin N Am. 2005;23:635-654. [Medline].
Doyle L, Colletti JE. Pediatric procedural sedation and analgesia. Pediatr Clin North Am. 2006;53(2):790-807. [Medline].
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Patel KN, Simon HK, Stockwell CA, Stockwell JA, DeGuzman MA, Roerig PL, et al. Pediatric procedural sedation by a dedicated nonanesthesiology pediatric sedation service using propofol. Pediatr Emerg Care. Mar 2009;25(3):133-8. [Medline].
den Brinker M, Hokken-Koelega AC, Hazelzet JA, de Jong FH, Hop WC, Joosten KF. One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis. Intensive Care Med. Jan 2008;34(1):163-8. [Medline].
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Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, et al. Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. Apr 2009;53(4):426-435.e4. [Medline].
procedural sedation, minimal sedation, anxiolysis, moderate sedation and analgesia, conscious sedation, deep sedation, general anesthesia, procedural sedation, sedatives, dissociative agents, minimally invasive procedure, diagnostic procedure, analgesia, benzodiazepines, opiates, propofol, etomidate, anesthesia, reversal agents, procedural sedation and analgesia, PSA
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
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Luis M Lovato, MD, Associate Clinical Professor, David Geffen School of Medicine at UCLA; Director of Critical Care, Department of Emergency Medicine, Olive View/UCLA Medical Center
Luis M Lovato, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Society for Academic Emergency Medicine
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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
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Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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