Among the diagnostic procedures for which moderate sedation is most commonly used are routine endoscopic examinations, the number of which has escalated because of their value in colorectal cancer screening [23]. According to a 2006 survey of American Society for Gastrointestinal Endoscopy (ASGE) members, 45% of the 724 respondents did not routinely offer unsedated endoscopic procedures and more than 70% said they would choose to be sedated for a routine endoscopic procedure [23]. In a more recent survey of American College of Gastroenterology (ACG) physician members, more than 98% of 1,353 respondents said they used sedation during their endoscopic procedures [24]. People scheduled for endoscopic procedures have come to expect sedation; in the ASGE survey, lack of patient acceptance was the most common reason given for not offering unsedated endoscopy [23].

In their guidelines on moderate sedation for endoscopy, the AGA Institute and the ASGE follow the ASA guidelines and recommend that the use of an anesthesia professional be strongly considered for patients classified as having ASA physical status IV or V [28,31]. In addition, several other patient-related and procedure-related factors are "possible indications" for an anesthesia specialist, including a history of alcohol or substance abuse, morbid obesity, neurologic disorders, and complex therapeutic procedures [28,31]. The ACEP guidelines note that there are no specific level A or B recommendations regarding personnel requirements needed to provide procedural sedation and analgesia in the emergency department. However, the guidelines state that a "nurse or other qualified individual" should be present during procedural sedation and analgesia for continuous monitoring of the patient in addition to the provider performing the procedure (level C recommendation) [7]. The guidelines also state that emergency physicians working or consulting in the emergency department should coordinate procedures that require administration of procedural sedation and analgesia [7]. All clinicians providing moderate sedation must be trained to administer drugs to achieve a desired level of sedation, monitor patients and maintain a desired level of sedation, and manage complications [7]. In 2011, the ACEP published comprehensive recommendations for physician credentialing, privileging, and practice; the ACEP also strongly supports the administration of propofol, ketamine, and other sedatives by qualified emergency department nurses under the direct supervision of a privileged emergency physician [7,33]. The AAP guidelines note similar requirements for training and add that clinicians must have training in how to oxygenate a child in whom airway obstruction or apnea develops and in advanced pediatric airway skills [13].

The guidelines agree that routine laboratory or other diagnostic testing is not needed before moderate sedation [7,11,31]. However, if the results of testing may affect the management of sedation, such testing should be done before the patient is sedated [7,11,31].

A noninvasive method of assessing the level of consciousness is bispectral index (BIS) monitoring, which has been used since the mid-1990s in the setting of general anesthesia. BIS records electroencephalographic (EEG) waveforms from a probe adhered to the forehead, and the EEG recording is analyzed with an algorithm to generate a score on a scale of 0 to 100. EEG activity is a sensitive measure of sedation, with a low-amplitude, high-frequency signal representing the awake state and a high-amplitude, low-frequency signal representing sedation. BIS monitoring is helpful in ensuring that patients are not oversedated or undersedated, and research has shown that BIS results correlate with validated sedation scales. The ASA guideline does not mention BIS explicitly and notes that although monitoring of the level of consciousness reduces the risk of deep sedation, no data have shown that such monitoring improves outcomes [11]. The ACEP and the ASGE found insufficient or poor evidence to recommend the routine use of BIS [31,69]. The AAP recommends against the routine use of BIS monitoring in children [13].

Recommendations about noninvasive monitoring of end-tidal carbon dioxide with capnography have evolved. At the time of their guidelines on monitoring during moderate sedation, the ASA and the AGA Institute found insufficient evidence to recommend the routine use of capnography, and the ASA only recommended capnography during moderate sedation when ventilation could not be directly observed. The ACEP noted only that procedural monitoring "may include" capnography, and the ASGE stated that capnography may improve patient safety [7,11,28,31]. However, since the publication of those guidelines, several studies have demonstrated that capnography readings are a more sensitive measure of ventilatory function, detecting hypoventilation earlier than changes in vital signs, clinical observations, or pulse oximetry [70,71,72,73]. In a study in the emergency department setting, capnography had a sensitivity of 100% (and specificity of 64%) in detecting hypoxia before onset [72]. In addition, a meta-analysis (five studies) demonstrated that respiratory depression was more than 17 times more likely to be detected during procedural sedation when capnography was used than when it was not used [73]. In 2010, the ASA issued standards for anesthetic monitoring (reaffirmed in 2020) stating that monitoring for the presence of exhaled carbon dioxide should be carried out during moderate (or deep) sedation. This is supported in the 2018 ASGE guidelines [31,74]. In 2018, the ASA issued updated guidelines for moderate procedural sedation that include a new recommendation for continual monitoring with capnography to supplement observation and pulse oximetry [11]. Use of capnography during sedation is also recommended by the Emergency Nurses Association, and, in a joint position statement, the ASGE, the AASLD, the ACG, and the AGA Institute acknowledge that capnography reduces the occurrence of apnea and hypoxemia during gastrointestinal endoscopy with propofol sedation [41,75]. A multisociety-developed curriculum on sedation during gastrointestinal endoscopy notes that proper training should include interpretation of capnography readings [69].

The routine use of supplemental oxygen has also been debated. The ASA and ASGE guidelines note that supplemental oxygen should be considered for moderate sedation, and the ASGE states that supplemental oxygen can reduce the magnitude of oxygen desaturation during sedated endoscopy [11,31]. The ASGE additionally states that supplemental oxygen should be administered if hypoxemia is anticipated or develops [31]. However, the AGA Institute asserts that there is little evidence to indicate that the use of supplemental oxygen reduces the incidence of significant cardiopulmonary complications in patients monitored with pulse oximetry [28]. In addition, the results of several studies have shown that supplemental oxygen may actually increase the rate of complications associated with sedation, as its use may delay recognition of hypoxemia and apnea [76,77]. As a result, the AGA Institute recommends the use of supplemental oxygen during endoscopy only for older individuals and people with significant comorbid disease (ASA class IV and V) [28]. According to one survey, approximately 73% of endoscopists routinely use supplemental oxygen [24].

There is no evidence to indicate that continuous electrocardiography (ECG) monitoring is of benefit during moderate sedation, especially for patients who have no underlying cardiopulmonary disease [7]. Guidelines from the ASA, the AGA Institute, and the ASGE all note that ECG monitoring is not needed for low-risk patients [11,28,31]. The ASA guidelines suggest ECG monitoring to decrease risks for patients who have significant cardiovascular disease or dysrhythmia, and the AGA Institute and the ASGE state that ECG monitoring should be considered for high-risk patients, such as patients with a history of significant cardiac or pulmonary disease [11,28,31]. The AAP recommends that an ECG monitor and defibrillator be readily available [13].

Scoring systems for anesthesia recovery are available, but no evidence has established standard discharge criteria; healthcare facilities should establish their own standardized criteria [11,13,28,31]. In general, the following parameters are used to indicate that a patient can be discharged: stable vital signs, alert and oriented status, patent airway, good skin color and condition, minimal nausea and vomiting, adequate pain control, ability to walk without dizziness, and ability to dress independently [11,28]. Many facilities have eliminated criteria related to the ability to eat or drink or void before discharge [28,78]. If a reversal agent has been used, the patient should be observed for two hours after the agent was given to ensure that he or she will not become re-sedated after the effects of the reversal agent wear off [11].

Potential Adverse Events and Side Effects. Respiratory depression may occur, but myoclonus is the most common side effect, reported in 20% to 45% of patients during procedural sedation. In one small study, myoclonus occurred in 72% of patients receiving etomidate [81,90,92,93]. There are protocols for minimizing myoclonus, including pretreatment with a fraction dose of etomidate or a small dose of a short-acting benzodiazepine. Pain at the injection site has also been common, occurring in up to 40% of patients [81]. Nausea and vomiting during emergence have also been reported at low rates [83,90].

Meperidine is contraindicated for patients taking an MAO inhibitor, as life-threatening complications may develop from the interaction of these two drugs [28]. The drug should be used with caution in patients with renal disease because the accumulation of normeperidine can lead to a neurotoxic reaction [69].

Absolute contraindications for ketamine include an age younger than 3 months (because of the high risk of airway-related complications) and known or suspected schizophrenia [79,96]. Relative contraindications include major procedures that stimulate the posterior pharynx; a history of airway instability; active pulmonary infection or disease; significant cardiac arrhythmia, coronary artery disease, or hypertension; CNS abnormalities; glaucoma or acute globe injury; and thyroid disorders [96]. Head trauma, minor oropharyngeal procedures, and an age of 3 to 12 months are no longer contraindications [96].

The ASA recommends that, whenever possible, antagonists should be on hand during the use of moderate sedation [11]. Antagonists are available to reverse the effects of opioids and benzodiazepines, but as yet no antagonist agents exist for propofol, etomidate, or barbiturates [69]. Naloxone hydrochloride can be used to reverse the effect of opioids, and flumazenil (Romazicon) can reverse the effects of benzodiazepines (Table 12) [28,69].

Data on sedation for children and adolescents undergoing endoscopy are limited. The authors of a systematic review published in 2012 (11 randomized and 15 nonrandomized controlled trials) targeted studies involving children and adolescents younger than 18 years of age [106]. Few of the trials compared different drugs, but the review demonstrated that propofol-based sedation had a safety profile similar to that of an opioid and benzodiazepine [106]. Data on midazolam- and ketamine-based sedation were too limited to draw conclusions. Sedation was most effective with propofol; the authors noted that adding midazolam, fentanyl, or ketamine to propofol may enhance the effectiveness without increasing adverse events [106].

Knowledge and skill in managing potential complications of moderate sedation is essential. Most complications occur because of sedation becoming deeper than intended (rather than not reaching adequate sedation) [11]. This is especially important for children, as studies have indicated that children often reach a level of sedation that is deeper than intended [13]. Clinicians who administer moderate sedation must be qualified to rescue patients who reach a deep level of sedation [11].

Determining the number of malpractice claims related to the use of moderate sedation is difficult. It has been estimated that approximately one in every 500 malpractice claims involves complications related to endoscopic sedation [28]. (Data on claims related to sedation in the emergency department setting are not available.) Potential legal issues related to moderate sedation are associated with a failure to administer sedation according to the standard of care, failure to obtain appropriate informed consent, and the patient's discharge status [28,133]. In addition, patient expectation of pain-free procedures may increase the risk of malpractice claims for two reasons: patients' claims of inadequate sedation, and oversedation as a way to ensure a pain-free status [28]. Some key measures can help clinicians reduce their risk of malpractice related to moderate sedation (Table 18) [134]. All clinicians should discuss the possibility that the patient may have pain or discomfort despite appropriate sedation [28]. The discussion about sedation should also note that the patient may not remember the procedure and postprocedure discussion and that there is a risk for allergic drug reactions and local reactions at the IV site [28]. The discussion of these points should be carefully documented to provide proof in the event of legal action. The preprocedure discussion should also address informed consent, as outlined previously.