Chapter 37: Procedural Sedation

Procedural sedation is the administration of sedatives or dissociative anesthetics to induce a depressed level of consciousness while maintaining cardiorespiratory function so that a medical procedure can be performed with little or no patient reaction or memory.¹ Procedural sedation and analgesia is the addition of agents to reduce or eliminate pain.¹ Levels of sedation are defined by the patient's level of responsiveness and cardiopulmonary function, not by the agents used (Table 37-1).² By definition, patients receiving procedural sedation do not require routine airway protection with endotracheal intubation or other airway adjuncts, as opposed to general anesthesia, which typically requires airway protection. Procedural sedation is commonly done for scheduled outpatient medical procedures by nonanesthesiologists^3,4 and is an accepted technique in emergency medicine.^5,6,7,8 Procedural sedation performed in the ED presents different issues to the practitioner than scheduled outpatient sedation (Table 37-2).^1,7,8

There are several key principles that must be followed to safely perform procedural sedation and analgesia (Table 37-3).^1,2,7,8 Despite careful planning and performance, the depth of sedation needed or achieved cannot always be predicted. It is therefore important to prepare for managing deeper levels of sedation than anticipated. Most of the agents used can produce variable levels of sedation, so pay particular attention to dosing and to the patient's responses to the medications.

Minimal sedation is characterized by anxiolysis but with normal, although sometimes slowed, response to verbal stimuli. Minimal sedation is typically used for procedures that require patient cooperation and those in which pain is controlled by local or regional anesthesia. Minimal sedation procedures might include abscess incision and drainage, lumbar puncture, simple fracture reductions, and laceration repair. During minimal sedation, ventilatory function is usually maintained with a low risk of hypoxia or hypoventilation. Agents typically used for minimal sedation in adults include nitrous oxide, midazolam, fentanyl, pentobarbital, and low-dose ketamine.

Moderate sedation is characterized by a depressed level of consciousness and a slower but purposeful motor response to simple verbal or tactile stimuli. Moderate sedation most closely matches the formerly used term "conscious sedation." Patients at this level generally have their eyes closed and respond slowly to verbal commands. Moderate sedation can be used for procedures in which detailed patient cooperation is not necessary, and muscular relaxation with diminished pain reaction is desired. During moderate sedation, the patient is usually able to maintain a patent airway with adequate respirations.⁹ Depending on the agent, the incidence of hypoxia and/or hypoventilation during moderate sedation is 10% to 30%.^10,11,12 Procedures performed using moderate sedation include reduction of dislocated joints, thoracostomy tube insertion, and synchronized cardioversion. Agents used for moderate sedation in adults include propofol, etomidate, ketamine, methohexital, and the combination of fentanyl and midazolam.

Dissociative sedation is a type of moderate sedation. Dissociation is a state in which the cortical centers are prevented from receiving sensory stimuli, but cardiopulmonary activity and responses are preserved. Ketamine is the agent most commonly used for dissociative sedation.¹³

Deep sedation is characterized by a profoundly depressed level of consciousness, with a purposeful motor response elicited only after repeated or painful stimuli. Deep sedation may be required with procedures that are painful and require muscular relaxation with minimal patient reaction. The risk of losing airway patency or developing hypoxia or hypoventilation is greater with deep sedation than with moderate or minimal sedation.^10,14,15 Examples of ED procedures sometimes requiring deep sedation are reducing fracture dislocations, open fracture reductions, and burn wound care. Deep sedation generally is achieved in the ED with the same agents as moderate sedation, but with larger or more frequent doses.

Complications are primarily determined by the interaction of the depth of sedation and the patient's current medical condition. A common tool for assessing the patient's underlying medical condition is the American Society of Anesthesiologists' physical status classification system.¹⁶ The risk of a significant complication from ED procedural sedation and analgesia in American Society of Anesthesiologists class I (healthy normal patient) and II (patient with mild systemic disease) is low, usually less than 5%.^1,5,6,7,8 The risk of an adverse procedural sedation and analgesia event is correspondingly higher in patients with an American Society of Anesthesiologists class of III (patient with severe systemic disease) or IV (severe systemic disease that is a constant threat to life).^17,18

PATIENT EVALUATION

To prepare for procedural sedation, perform a focused history and physical examination.^1,3,4,8 The focused history should determine the fasting state, prior experiences with sedation or anesthesia, current medications, and allergies. The focused physical examination identifies a potentially difficult airway or cardiorespiratory problems. A potentially difficult airway should be anticipated when the following findings or conditions are present: short neck, micrognathia, large tongue, trismus, morbid obesity, a history of difficult intubation, or anatomic anomalies of the airway and neck. The implications of these individual factors vary,^19,20,21 partially due to the weak interobserver reproducibility.²² Additionally, studies on the association between these findings and difficult intubation are usually done on patients going to the operating room for general anesthesia, and these findings may not be entirely relevant to the ED patient.²³ If time allows and an anesthesiologist is available, consultation may be advisable before undertaking procedural sedation in a patient with a potentially difficult airway. At a minimum, difficult airway equipment should be present and available.

Cardiorespiratory conditions increase the complication rate. Most agents can cause vasodilatation and hypotension, particularly in patients with preexisting hypovolemia. Clinically active obstructive pulmonary disease and active upper respiratory infections may predispose the patient to heightened airway reactivity during the procedure and promote hypoventilation. Drug or alcohol intoxication or reduced level of consciousness increases the risk of hypoxemia and hypoventilation. If possible, delay procedural sedation in intoxicated patients until mental status improves.

Routine laboratory studies are not necessary in otherwise healthy patients. Directed ancillary testing may be useful in patients with conditions such as airway abnormalities, infections, advanced age, hepatic or renal disease, dehydration, fever, or hypovolemia. Such conditions may increase the risk of hypotension, prolonged sedation, or hypoxemia. These should be corrected if possible. If correction before procedural sedation is not possible, either delay the procedure or use the lowest possible level of sedation.

The need for sedation is sometimes more urgent than a full preprocedure evaluation. Emergent indications include cardioversion for life-threatening arrhythmias, neuroimaging for head trauma, reduction of fractures or dislocations with soft tissue or vascular compromise, care of contaminated wounds, or intractable pain. Stable fractures, abscess incision and drainage, care of clean wounds, foreign body removal, and laceration repair require less urgent procedural sedation. Nonurgent indications for sedation include the removal of a soft tissue foreign body, placing splints on fractures that require minimal manipulation, or changing splints on fractures that have already been reduced.

FASTING STATE

There is no primary evidence that the risk of aspiration during procedural sedation is increased with recent oral intake.^24,25,26 Current guidelines regarding the safe fasting period prior to procedural sedation were developed by expert consensus,²⁷ and the American Society of Anesthesiologists guidelines for fasting prior to general anesthesia are of limited relevance to the risk of aspiration with ED procedural sedation.²⁵ Thus recent food intake is not a contraindication.²⁷ If the risk of aspiration is concerning, waiting 3 hours after the last oral intake before performing procedural sedation is associated with a low risk of aspiration, regardless of the level of sedation.²⁷

NUMBER OF PHYSICIANS NEEDED

The anesthesia model for procedural sedation consists of two physicians, one to perform sedation and monitor the patient and the other to perform the procedure. In theory, if one physician is dedicated to administering procedural sedation, it should be possible to monitor the level of sedation, titrate the medication carefully, and identify adverse events earlier. Despite such potential benefits, clinical experience indicates that one emergency physician—providing sedation and performing the procedure—may achieve the same low risk of adverse events as having two physicians.^1,28 Thus, for minimal and moderate levels of sedation, one emergency physician simultaneously administering sedation and performing the procedure with a nurse monitoring the patient appears to be an appropriate practice. If available, a clinical pharmacist can provide useful information and assist during procedural sedation, with the potential to reduce the likelihood for medication errors.²⁹

The sedation area should include all necessary size-appropriate equipment for airway management and resuscitation, including oxygen, a bag-mask ventilation device, suction, oral/nasal airway(s), and intubation equipment.^1,3,4,8 A defibrillator should be available. Reversal agents, such as opioid receptor and benzodiazepine receptor antagonists, should also be readily available.

Two types of monitoring are used for ED procedural sedation: interactive monitoring by dedicated observers and electronic monitoring with equipment connected to the patient. The recommended extent of monitoring is determined by the level of sedation (Table 37-4). No matter which method is used, patients must be checked after each dose of medication to assess the response, determine the need for further doses, and make appropriate interventions if adverse events arise.

INTERACTIVE MONITORING

Interactive monitoring is the direct observation of the patient to assess the depth of sedation and observe for hypoventilation or apnea, upper airway obstruction, laryngospasm, vomiting, or aspiration. Thus interactive monitoring requires an unobstructed view of the patient's face, mouth, and chest wall.

For minimal sedation, the risk of adverse events is so low that observation by the physician performing the procedure is usually adequate. For moderate and deep sedation, a dedicated observer—typically a nurse in the one-physician model—should continuously monitor the patient while the physician oversees drug administration and performs the procedure.

ELECTRONIC MONITORING

Electronic monitoring uses equipment to assess arterial oxygenation, ventilation, blood pressure, and cardiac rate and rhythm. Moderate and deep sedation require constant observation and continuous monitoring. Cardiac monitoring is particularly recommended for patients with preexisting cardiac disease or dysrhythmias or during procedures in which the cardiac rhythm is of interest, such as during cardioversion. Arterial oxygen saturation is monitored with pulse oximetry. For almost all patients undergoing minimal sedation and many undergoing moderate sedation, pulse oximetry is adequate as the sole mechanical monitoring modality. However, pulse oximetry is not a substitute for monitoring ventilation, as hypoventilation or apnea develop before oxygen saturation decreases, especially in patients who receive supplemental oxygen.^30,31,32,33

Ventilation can be electronically monitored using capnography, the measurement of the partial pressure of carbon dioxide in exhaled breath.^32,33 Many experts suggest that capnography should be used to monitor procedural sedation.^34,35,36 The capnography device uses an infrared carbon dioxide detector placed at the nares to sample inhaled and exhaled gases. The partial pressure of carbon dioxide detected at the nares during the respiratory cycle is represented by the carbon dioxide waveform (capnogram) that can be displayed on the monitor (Figure 37-1). A value commonly reported on the capnography device is the end-tidal carbon dioxide: the maximum carbon dioxide concentration at the end of each tidal breath. The end-tidal carbon dioxide correlates with arterial partial pressure of carbon dioxide so that an end-tidal carbon dioxide above 50 mm Hg or an increase in end-tidal carbon dioxide >10 mm Hg indicates hypoventilation. Capnography can assess the severity of ventilatory abnormalities and the response to interventions. Most importantly, capnography can detect changes in ventilation before clinical observation.^32,33

Variations in the capnogram can identify specific conditions, such as apnea, upper airway obstruction, laryngospasm, bronchospasm, and respiratory failure.³² A flat-line capnogram can be due to apnea, upper airway obstruction, or complete laryngospasm. Normalization of the waveform after airway alignment maneuvers (chin lift, jaw thrust, or oral airway placement) confirms that apnea was due to upper airway obstruction.

Capnography during procedural sedation allows the early recognition of adverse events.^1,32,33 Because the risk of respiratory depression increases with the depth of sedation, capnography should be considered for moderate sedation and is recommended for prolonged deep sedation.

FREQUENCY OF MONITORING

Vital signs (pulse, blood pressure, and respiratory rate) and oxygen saturation should be obtained and recorded before the procedure, after each dose of medication, upon completion of the procedure, at the beginning of the recovery period, and before discharge.^1,3,4,8 For mild sedation, intermittent measurements are sufficient. For moderate and deep sedation, it is recommended that blood pressure be assessed every 5 minutes and heart rate and pulse oximetry be continuously monitored. Patients are at the highest risk of hypoxia and hypoventilation during the period immediately after IV medication administration (until the peak effect of the medication has been reached) and during the immediate postprocedure period (when external stimuli are discontinued and the stimulating pain of the procedure has subsided).

DOCUMENTATION

Predesigned documentation forms are a good practice because such forms can guide the providers through the procedure, improve the quality of the documentation of the procedure,³⁷ and better tabulate sedation-related events for quality-auditing purposes.³⁸

SCALES FOR MONITORING DEPTH OF SEDATION

The level of sedation can be assessed using structured scoring techniques, such as the Ramsay Sedation Scale© and the Observer's Assessment of Alertness/Sedation Scale©. However, regular patient monitoring is more important than the application of scales. Specific central nervous system monitoring, such as the bispectral index scale that uses processed electroencephalogram signals to measure the depth of sedation, is primarily a research tool for procedural sedation.^11,15,39,40

PREPROCEDURE PAIN MANAGEMENT

The administration of morphine or fentanyl for pain control before the start of procedural sedation will provide the patient with analgesia during the procedure. Pain should be controlled so the patient is comfortable, but if preprocedure pain is intractable and if the procedure itself will result in pain relief, do not wait for complete pain control to begin.

Begin procedural sedation after the last dose of analgesic has reached its peak effect (3 to 5 minutes for IV morphine and 2 to 3 minutes for IV fentanyl). The administration of propofol or etomidate concurrently with analgesics may increase the likelihood of adverse events, so these medications should be titrated separately.^18,41

The opioid dose needed before a procedure is typically more than the amount required after the procedure. Shorter-acting agents are preferred to drugs with a longer duration of action to minimize postprocedure respiratory depression. (See chapter 35, Acute Pain Management, for further discussion).

SUPPLEMENTAL OXYGEN

The incidence of oxygen desaturation during ED procedural sedation ranges from 6% to 40% without supplemental oxygen.^{10,11,12,30,42,43} Supplemental oxygen reduces the incidence of hypoxemia^30,31,42,43 and has no adverse clinical effects. However, the administration of supplemental oxygen can delay the recognition of respiratory suppression, because oxygen saturation is maintained despite rising carbon dioxide noted by capnography.^32,33,42 In morbidly obese patients, bilevel positive airway pressure may be useful to facilitate adequate sedation while averting hypoventilation.⁴⁴

SEDATION MANAGEMENT

After the patient has been evaluated, the appropriate sedation target level is selected, the monitoring modalities are applied, and preparations are made for possible adverse events, then procedural sedation can begin (Table 37-5). Observe and monitor the patient until the peak effect of the initial sedative dose has been reached. If necessary, titrate with additional medications to the desired sedation level. Once the patient has achieved the target sedation level, the actual procedure may begin. If the patient begins to regain alertness before completion of the procedure, additional sedative doses may be required. However, additional sedative doses given to extend procedural sedation are associated with an increased risk of respiratory depression. As larger cumulative doses of the drug are given, the half-life of each bolus will increase. After the patient recovers from sedation, analgesics are administered as needed, for patient comfort.

NITROUS OXIDE

Nitrous oxide is typically supplied in a 50:50 mixture with oxygen (Table 37-6). Nitrous oxide can be used alone for minimal sedation or as an adjunct with IV medications for moderate sedation (Table 37-6).^45,46 Technical aspects of nitrous oxide administration include the use of a demand delivery system triggered by the patient's inspiratory force and a disposal or scavenger system to prevent accumulation of nitrous oxide in the room. Nitrous oxide has a rapid onset (1 to 2 minutes) and a rapid recovery (3 to 5 minutes) when inhalation of the gas is discontinued.

Nitrous oxide has few adverse side effects.⁴⁷ Nitrous oxide is a mild cardiac depressant and pulmonary vasoconstrictor so it is relatively contraindicated in patients with pulmonary hypertension. Nitrous oxide is an inhibitor of folate metabolism and is therefore contraindicated in pregnant women. Nitrous oxide may promote expansion of internal gas-filled structures and should be avoided in patients with pneumothorax, pneumocephalus, and vascular air embolism.

MIDAZOLAM

Midazolam is a short-acting benzodiazepine commonly used as a sole agent for minimal sedation.⁴⁸ After IV administration, peak effect is seen within 2 to 3 minutes, and duration of retrograde amnesia is 20 to 30 minutes (Table 37-6). Midazolam can be combined with an opioid for moderate or deep procedural sedation, but when given with an opioid, there is an increased risk of respiratory depression.

Midazolam causes mild cardiovascular depression, and hypotension can result when this agent is given to hypovolemic patients. Paradoxical agitation has been reported with the use of midazolam in 1% to 15% of patients, and flumazenil can be given for reversal.⁴⁸

Midazolam can be administered IV, PO, IM, PR, or intranasally. The IV route has the most predictable onset and duration of action. The PO route can result in unreliable levels of sedation as a result of first-pass hepatic metabolism. Because the agent has a low pH and benzyl alcohol is added as a preservative, intranasal midazolam irritates the nasal mucosa, which can be painful and provoke anxiety. Buffering the solution does not decrease the irritation. Both the PR and IM routes have unreliable onset and depth of sedation, but can be easier to administer in some patients.

FENTANYL AND ALFENTANIL

Fentanyl is a potent, relatively short-acting opioid. A single IV dose has rapid onset of <1 minute, peak effect in 2 to 3 minutes, and duration of 30 to 60 minutes. It is easily titratable when used alone for minimal sedation and can be used in combination with midazolam for moderate and deep procedural sedation and analgesia.

Rigid chest syndrome, a rare complication characterized by spasm of the respiratory muscles leading to respiratory depression or apnea, is seen when high doses (>5 micrograms/kg) of fentanyl are given by rapid IV bolus. In small children, this syndrome may be precipitated by rapidly flushing the IV line. Rigid chest syndrome is not reversible with opioid receptor antagonists. Intubation with rapid-sequence induction and pharmacologic paralysis is usually required to ventilate the patient in this situation. Slow administration of fentanyl (1 to 3 micrograms/kg over 5 minutes) followed by slow and careful flushing of the IV line can prevent rigid chest syndrome.

Alfentanil is an effective agent but is associated with a 30% to 40% rate of airway and respiratory adverse effects,^49,50 a rate typically higher than that seen with fentanyl or propofol alone.

METHOHEXITAL

Methohexital is an ultra-short-acting barbiturate that produces sedation within 1 minute of IV administration and has an effective duration of 3 to 5 minutes. Methohexital is best used for brief moderate and deep sedation, such as that needed for joint dislocation reduction. The major adverse effect of methohexital is respiratory depression; the risk increases if additional boluses are given after the initial dose.¹²

PENTOBARBITAL

Pentobarbital is a short-acting barbiturate that is useful when the procedure itself is painless, but the associated circumstances may cause anxiety (e.g., radiologic procedures). Pentobarbital produces sedation within 3 to 5 minutes of IV administration and lasts approximately 15 minutes, and complete recovery occurs in 30 to 40 minutes.

KETAMINE

Ketamine produces a state of dissociation characterized by profound analgesia, sedation, and amnesia. Unlike other agents used for procedural sedation, ketamine possesses both analgesic and anxiolytic properties.¹³ Ketamine is an effective agent for ED procedural sedation^{13,51,52,53,54,55} and for prehospital analgesia and sedation when used by physicians.⁵⁵

Ketamine does not have a typical dose-response continuum with progressive titration. At doses lower than a threshold, analgesia and sedation occur. Once a critical dosing threshold is exceeded (about 1.0 to 1.5 milligrams/kg IV or 3 to 4 milligrams/kg IM), the characteristic dissociative state abruptly appears. This dissociation has no observable levels of depth. The only value of additional ketamine is to prolong the dissociative state for extended procedures.

Ketamine can be given either IV or IM. The IM route allows for approximately 40 minutes of sedation, compared with 10 minutes by the IV route. Ketamine is the only sedative agent that typically preserves a patient's ventilatory effort and has minimal effect on blood pressure. Ketamine can induce hypersalivation. Anticholinergics, such as atropine 10 micrograms/kg IV or glycopyrrolate 4 micrograms/kg IV, are often administered to counter this effect. However, studies evaluating this practice of coadministering anticholinergics fail to demonstrate tangible benefit or harm. Thus anticholinergics can be reserved for the treatment of clinically significant hypersalivation or for patients with an impaired ability to mobilize secretions.¹³ Other adverse effects also include laryngospasm, vomiting (most often in the late recovery phase), and emergence reactions. Laryngospasm has been reported primarily in children, with reported rates of occurrence of <1.0% to 2.5%. It is typically transient and responds to positive pressure ventilation with a bag-valve mask. Children with significant upper respiratory tract infectious symptoms and patients who will undergo major stimulation of the oropharynx (e.g., endoscopy) should not receive ketamine due to a possible increased risk of laryngospasm.¹³

Emergence reactions are common with ketamine and range from mild agitation to recurrent nightmares and hallucinations.^53,54 Midazolam can be given along with ketamine to blunt the occurrence of emergence reactions.^56,57 However, the overall clinical benefit of such prophylaxis has not been demonstrated.¹³ It is sufficient to give ketamine without midazolam and then treat patients who develop emergence reactions with midazolam as they occur. Because of these emergence reactions, ketamine should not be used in patients with schizophrenia and psychosis.¹³

It is commonly stated that ketamine increases intracranial pressure, which potentially limits its use in many emergent situations.⁵⁸ The experimental data from animal studies and human observations are conflicting, depending on the specific circumstances.^58,59 Thus there is no clear evidence that ketamine is harmful as an induction or sedation agent in patients with potential head injury. Ketamine does increase intraocular pressure and should be avoided in patients with eye injuries or glaucoma.⁶⁰

ETOMIDATE

Etomidate is a nonbarbiturate sedative-hypnotic with a rapid onset (15 to 30 seconds) and a short duration of effect (3 to 8 minutes). Compared with the other sedative agents, etomidate causes less cardiovascular depression but a similar degree of respiratory depression. Etomidate is an effective agent for ED procedural sedation, with a reported complication rate of 10% to 15%, most complications being minor.^61,62,63,64

Myoclonic jerking occurs in up to 20% of patients and can interfere with the procedure for which the patient was sedated.⁶⁴ Etomidate causes suppression of the adrenal-cortical axis, and when used for rapid sequence induction in critically ill patients, it is associated with adrenal insufficiency and increased mortality.^65,66,67,68 However, no clinically significant adverse event related to adrenal suppression has been detected from etomidate used during ED procedural sedation in stable patients.

PROPOFOL

Propofol is frequently used for moderate and deep procedural sedation in the ED.^{18,69, 70, 71, 72, 73, 74, 75, 76, 77} Propofol is associated with fewer complications than etomidate or methohexital in patients who received multiple doses and is much easier to titrate.^12,64 Because of the short duration of action, propofol results in a shorter recovery time and ED length of stay.^76,77,78,79

The most serious adverse effect of propofol is sudden respiratory depression and apnea,^24,41 so ventilatory support equipment should be at the bedside when using propofol. Propofol can produce hypotension as a result of both negative inotropy and vasodilatation. Hypotension is more common in hypovolemic patients and those with American Society of Anesthesiologists physical status scores of III or IV.⁷⁰ Hypovolemia should be corrected before propofol administration.

Sedation from propofol occurs within 30 to 60 seconds after injection and lasts for about 5 to 6 minutes. Propofol is rapidly distributed into tissues, and once tissues are saturated, subsequent doses will have a greater effect than the initial bolus. The recommended dose for ED procedural sedation in healthy nonelderly adults is 0.5 to 1.0 milligram/kg IV, followed by 0.5 milligram/kg IV every 3 minutes if needed. Higher doses are associated with more respiratory depression.

Propofol is formulated in a soybean oil, glycerol, and egg lecithin emulsion and is contraindicated in patients who are allergic to eggs or soy protein. Propofol causes local pain at the IV site during administration. Methods to reduce the pain of propofol administration include placing a tourniquet proximal to the IV and injecting 0.05 milligram/kg of lidocaine through the IV approximately 60 seconds before injecting the propofol, mixing the propofol with lidocaine, or coadministering the short-acting opioid alfentanil at 10 micrograms/kg.^80,81

KETAMINE AND PROPOFOL

The combination of ketamine and propofol for ED procedural sedation has a well-documented safety and efficacy profile.^82,83–92 Propofol is an excellent sedative, but respiratory depression and hypotension are its principal adverse events. The sympathomimetic properties of ketamine may mitigate these, in addition to adding analgesia. Ketamine causes emergence reactions and vomiting as adverse events, whereas propofol has antiemetic and hypnotic properties. This combination is safe and effective for ED procedural sedation and analgesia.^83–92 Published "ketofol" ED procedural sedation studies have used a variety of combinations, from equal mixtures of propofol and ketamine to normal doses of propofol with sub-dissociative doses of ketamine for its analgesic properties. Adding ketamine to propofol promotes hemodynamic stability, which is reassuring in patients with known or potentially reduced cardiac function.⁸⁸ There is also evidence of synergism between the two drugs, and data indicate that ketofol provides less erratic sedation depth than propofol alone.⁸⁷ The analgesic properties of ketamine preclude the need for and risks of opioids administered with propofol.^84,88 When the total dose of ketamine administered during ketofol use is less than the reliable dissociative dose (<1.5 milligram/kg), clinical observation suggests that recovery time is longer than that for full doses of propofol (1.6 to 1.8 milligrams/kg) alone^82,86 but shorter than that of full dissociative doses of ketamine (1.0 to 1.5 milligrams/kg) alone.⁸² However, despite the theoretical benefit for decreasing complications, studies to date have failed to demonstrate a consistent difference in complications between ketofol (mixtures of ketamine and propofol from 1:1 to 1:4) compared with propofol alone.^89,90 The advantage of ketofol is that it may be able to achieve adequate sedation with lower total doses compared with when either drug alone is used, and ketofol prolongs the duration of sedation more than propofol alone, which is useful for procedures anticipated to take more time, and without the need for additional doses of propofol.

Reported complication rates for ED procedural sedation range from 2.3% to 11%.^{28,69,93,94,95} Most of these are minor. Factors associated with an increased rate of complications include age >65 years,^93,94 level of sedation,^94,95 premedication with fentanyl,⁹⁴ use of short-acting agents,⁹⁴ and procedural sedation and analgesia performed at night, when procedural sedation and analgesia could be administered by physicians with varying levels of training and experience and when consultant-level supervision is not always physically present.⁹⁵ Serious adverse events include the need for assisted ventilation, endotracheal intubation, or treatment of hypotension or cardiac dysrhythmias. Minor adverse events resolve spontaneously and include sedation to a deeper level than intended, transient hypoxia, or emesis. Complications can occur unexpectedly, so careful preparation, appropriate procedural monitoring, and careful selection of the target sedation level will minimize the rate of occurrence and severity of adverse events.

Failure to successfully complete a procedure during ED procedural sedation occurs in about 5% and is more common with some joint reductions (hips, mandibles) and with patient body weight >100 kg.⁹⁶

At the completion of sedation and the procedure, patients should be monitored until they return to baseline mental status and cardiopulmonary function. A structured assessment, such as the Aldrete Score©,⁹⁷ can be used to assess the patient's recovery and safety for discharge. Such assessment tools are typically part of procedural sedation documentation forms.

The duration of observation before discharge is variable. It depends on the quantity of sedatives given, the patient's response, the duration of the procedure, and the occurrence of any adverse events. Generally, patients who have returned to a baseline level of consciousness are unlikely to have further negative changes in level of consciousness. Most adverse events occur during procedural sedation itself, typically within a few minutes of sedative administration. The occurrence of adverse events >5 minutes after completion of the procedure is rare (<1%).⁹⁸ The occurrence of adverse events after discharge of an ED patient who has undergone procedural sedation has not been reported. Patients should be instructed to return if they develop respiratory complaints or nausea or vomiting. The follow-up interval required for patients who undergo ED procedural sedation is usually related to the procedure rather than the sedation itself.

PROCEDURAL SEDATION AND ANALGESIA IN CRITICALLY ILL PATIENTS

Etomidate might arguably be the drug of choice for hypotensive patients who require sedation for an emergency procedure because it produces less cardiovascular suppression than other agents.¹⁷ However, etomidate suppresses the adrenal-cortical axis, and when used for rapid-sequence induction in critically ill patients, it is associated with adrenal insufficiency and increased mortality.^65,66,67,68 Thus other sedation agents should be used in critically ill patients. Patients undergoing extended complex procedures are likely to require sedation longer than can be achieved with a single bolus of methohexital or propofol, or etomidate, and are at a higher risk of complications.^12,17,64 Critically ill patients who require prolonged sedation should be referred for general anesthesia in the operating room.

PROCEDURAL SEDATION AND ANALGESIA IN THE ELDERLY

Procedural sedation in the elderly is associated with increased technical and pharmacologic adverse events.^93,94 Ventilatory drive and the ability to maintain a patent airway are reduced. Remove false teeth or partial dentures before sedation to prevent aspiration of the devices. Risk of pulmonary aspiration increases as a result of reduced gag reflex and gastroesophageal sphincter incompetence. Underlying comorbidities or hepatic or renal insufficiency affect the response to sedatives. The risk of respiratory depression from all agents is increased. All these factors indicate a need for more planning, monitoring, and slow titration of sedative agents in the elderly. With such preparation, procedural sedation of the elderly is safe.⁹³

Etomidate is a good sedative agent in the elderly because of its minimal cardiovascular effects.⁶³ For painful procedures, opioids may be necessary, as etomidate has no analgesic effect. In elderly patients with underlying clonus, etomidate should be avoided, as it can exacerbate that symptom.

Propofol produces greater peak plasma concentrations after a specific IV bolus dose in the elderly, therefore producing a greater risk of respiratory depression and apnea. To counteract this, the initial and subsequent doses should be 50% (0.25 to 0.5 milligrams/kg) of those recommended for younger adults, and more cautious titration is needed. Lower dosing of the sedative with increased age and American Society of Anesthesiologists score may lead to similar complication rates as those for younger patients.⁹³

The elderly, especially those with underlying cerebral disease or dementia, are more sensitive to the neurologic side effects of benzodiazepines and barbiturates. These agents should be used with caution, particularly if opioid analgesics are also given.

PROCEDURAL SEDATION AND ANALGESIA FOR EMERGENCY ENDOSCOPY

Procedural sedation is a standard part of outpatient endoscopy. If an ED patient requires emergency endoscopy, the emergency physician may be asked to perform procedural sedation. Ideally, a protocol during emergency endoscopy should be jointly developed by emergency medicine and gastroenterology. Sedation during endoscopy presents some unique challenges related to the medications used and the performance of the procedure itself.^99,100,101

Endoscopy increases the risk for vasovagal reactions, with bradycardia and hypotension. These reactions can occur with upper gastrointestinal endoscopy during passage of the endoscope through the pharynx or gaseous distention of the small bowel, or with colonoscopy during gaseous distention of the colon. Most reactions are transient, and treatment with atropine should be reserved for rare cases of persistent bradycardia.

Passage of the endoscope through the pharynx into the stomach can exacerbate the risks for hypoxia, apnea, and aspiration. The endoscope can interfere with ventilation and can induce vomiting. Topical agents (benzocaine, lidocaine) are used for pharyngeal anesthesia. The occurrence of methemoglobinemia after benzocaine topical spray can interfere with pulse oximetry monitoring.

Antiemetic agents used during the procedure, such as promethazine or droperidol, can cause complications during the performance of procedural sedation. Promethazine exerts an α-adrenergic blocking effect and may produce hypotension. In addition, the sedative effect of promethazine may last >2 hours, so a prolonged recovery should be anticipated. Droperidol, which is occasionally used, increases the risk of transient hypotension and may also prolong the recovery phase (up to 3 to 6 hours). Ondansetron is an antiemetic without these potential effects and is a reasonable alternative.