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Patient Safety: Review Article

Efficacy Outcome Measures for Procedural Sedation Clinical Trials in Adults

An ACTTION Systematic Review

Williams, Mark R. MBBS, BSc*; McKeown, Andrew BS*; Dexter, Franklin MD; Miner, James R. MD‡§; Sessler, Daniel I. MD; Vargo, John MD, MPH; Turk, Dennis C. PhD#; Dworkin, Robert H. PhD*

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doi: 10.1213/ANE.0000000000000934
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Expanding the use of procedural sedation in the recent decades has been mirrored by increased research interest with various medications, drug combinations, and routes of administration being evaluated in clinical trials. Clinically useful evaluations of new medications or devices for procedural sedation must assess clinically meaningful outcomes. Although there are professional society guidelines for procedural sedation1–4,a,b and various methodologic considerations have been discussed,5–7 there are no published recommendations specifically regarding the assessment of efficacy outcomes in sedation clinical trials. Therefore, a variety of methods have been used throughout the literature, with consequent inconsistency among trials that, in turn, complicates comparisons among them.

Our goal here is to provide an evidence-based foundation for improving the design of sedation clinical trials by addressing 3 key questions: Which of the existing measures of procedural sedation have had their validity assessed in multiple ways? Does the validity of any of these measures support use across the range of procedures for which sedation is indicated? Are there categories of procedures that seem to require the use of procedure-specific measures of sedation?

We conducted a systematic review of clinical scales and measures used in the studies of procedural sedation for adults. We first summarize (1) the major sedation scales, (2) observer-rated pain scales, and (3) clinician and patient satisfaction scales used throughout the literature. We highlight the outcome domains these scales assess and review their clinimetric properties (i.e., reliability, validity, and responsiveness). Subsequently, we discuss additional measures relevant to overall sedation efficacy and then conclude by considering the implications of our findings for future clinical research on sedation, especially clinical trials of sedation drugs and devices.

Although important in the evaluation of sedation, we do not address the use of rescue medication. The assessment of adverse events and safety is also critical in evaluating sedation medications and devices, but is beyond the scope of this article, as is the examination of electrophysiologic measures such as the bispectral index, given our focus principally on clinical scales. The primary hypothesis for our analysis was that evidence of reliability, validity, and responsiveness across multiple specific procedures is not available for existing measures of sedation efficacy.


Sedation is strictly defined by reduced activity, alertness, and arousal.8 Procedural sedation encompasses the use of anxiolytic, sedative, hypnotic, analgesic, or dissociative medications that decrease patient awareness and facilitate patient cooperation with and tolerance of diagnostic or therapeutic procedures. Sedatives are given to provide analgesia and anxiolysis, to attenuate detrimental patient movement, and to reduce unpleasant recall.9,10 We will consider all these factors, recognizing that sedation has both patient-centered and clinician-centered components (Fig. 1).

Figure 1
Figure 1:
Patient- and clinician-centered outcomes.

“Procedural sedation and analgesia” is the preferred term for what was previously “conscious sedation,” because it is a more accurate description than the contradictory term it replaced,11 which has been removed from the current sedation guidelines.1,2 Procedural sedation is used in a wide range of settings by a variety of health care providers for multiple indications. The ideal level of sedation is dictated by the category of procedure, patient physiology, and clinician preference. The difficulty is that the actual degree of sedation induced by a given dose of a given sedative varies greatly among individuals, with the range sometimes extending from minimal sedation through moderate and deep sedation to general anesthesia (Table 1).1 In practice, sedation transitions fluidly along this continuum, meaning that sedation levels typically fluctuate subtly, rather than distinctly changing among categories. Dissociative anesthesia, such as that induced by ketamine, has been considered separately, given its unique properties.12

Table 1
Table 1:
Sedation Definitions

Various organizations recommend that level of consciousness be monitored at regular intervals during moderate and deep sedation.1,13 Unfortunately, there is no gold-standard instrument for assessing the sedation level, and there is no consensus as to the best method(s) for clinical practice and research. The ideal clinical scale would be valid, reliable, and responsive to treatment: It would also include multiple easily discriminated levels and be suitable for use with any sedative agent. Clinical sedation scales should be easy to use and quick to administer, although more involved instruments might be used in clinical trials. Although the pharmacology for procedural and intensive care unit (ICU) sedation is similar, the mechanism, period, and patient demographics typically differ considerably. Valid and reliable ICU sedation scales might not be suitable for procedural sedation without specific contextual validation.

Identifying improved drugs or devices for procedural sedation requires appropriate methods for determining efficacy. Methods for assessing sedation should also optimize sedation control and improve administration and patient-focused titration to specific end points in clinical practice. Common outcomes assessed in clinical trials as measures of sedation efficacy include achieved sedation level (as determined by sedation scales), successful completion of the procedure, use of alternative/additional sedatives or rescue medications, patient and clinician satisfaction, pain reported, recall, time to recovery, and time to discharge. For example, dexmedetomidine and fospropofol are the drugs most recently approved by the US Food and Drug Administration for procedural sedation, but different measures of sedation efficacy were used in the phase 3 clinical trials on which these approvals were based.

Table 2
Table 2:
Sedation Efficacy Measures in Clinical Trials of Dexmedetomidine and Fospropofol

Although 2 fospropofol trials14,15 used the same primary end point for sedation efficacy (Table 2), that end point differed from the primary end point used for demonstrating sedation efficacy for dexmedetomidine.16,17 Diverse primary end points were used for the dexmedetomidine studies, including different sedation scales. Using various outcomes across clinical trials complicates comparing results across studies and performing systematic reviews and meta-analyses.


By using a comprehensive search strategy (Appendix 1), we conducted PubMed searches (up to January 2015) for prospective studies that used a clinical assessment in adults having procedures that required sedation. Only prospective studies reported as full-text articles published in English were included. Retrospective and case studies were excluded, as were those involving pediatrics, general anesthesia, and procedures conducted with sedation in ICUs. Relevant studies had to report the use of a sedation scale to measure the level of sedation at least once during the procedure.

Information was extracted from the articles regarding the sedation scale including when and how it was used. The aim of the study, sedatives used, frequency of sedation assessment, and qualifications of the assessor were recorded. General study characteristics including author, year, study design, setting, procedures, and patient population were also extracted. Sedation scales used in >1 study were reviewed, and the original description of the instrument was identified. The construction of the scale, the context of its original use, and all data about validity and reliability were extracted.c

The original article of each referenced sedation scale was reviewed, and any study pertaining to the validity or reliability of this scale for procedural sedation was sought and reviewed to evaluate the extent to which a given measure had been tested and across what range of procedures it had been assessed. These data were collated and are presented in Table 3 along with psychometric data for other scales used in assessing sedation outcomes (e.g., pain and patient and clinician satisfaction).

Table 3
Table 3:
Validity, Reliability, and Responsiveness Results

Sedation scales with available psychometric data were analyzed using a scoring system used by Robinson et al.32 to evaluate psychometric properties of ICU sedation scales. The highest level of evidence available was scored for each item. Criteria evaluated included item selection, reliability, validity, feasibility, and impact on patient outcomes (Table 4). Weighted scores were used to give more importance to the reliability and validity of a given scale. Consistent with the study by Robinson et al.,32 scores of 15 to 20 represented very good psychometric properties, 12 to 14.9 represented moderate psychometric properties, 10 to 11.9 represented low psychometric properties, and 0 to 9.9 demonstrated very few psychometric properties and/or unacceptable results.

Table 4
Table 4:
Psychometric Scoring Criteria32

We excluded studies that used a sedation measure for which a relatively complete description was not provided, as well as those that provided no information regarding the method of sedation assessment. For example, studies that used a numerical or verbal descriptor scale but did not report the specific scale items or values were excluded. We omitted studies reporting only the use of electrophysiologic measures to monitor sedation level (e.g., bispectral index, auditory evoked potentials). All the abstracts identified through the literature search were screened for relevance with queries solved through discussion among the coinvestigators. References from relevant retrieved articles were also reviewed to identify any pertinent articles missed by the PubMed search.

When assessing the clinimetric properties of a sedation scale, we considered internal consistency as the extent to which items within a measure are associated with each other,33 test-retest reliability as the reproducibility of assessment data over time,34 and interrater reliability as the extent to which ratings by different observers were consistent (as determined by weighted κ or intraclass correlation).33

Validity refers to the extent to which a measure assesses what it is intended to measure.33 Because there is no gold standard for procedural sedation, it was not possible to establish criterion validity—the correlation of a measure with such a standard—for any available measure. Content validity refers to a determination of whether the measure’s content encompasses the most important and relevant aspects of what it is intended to assess and construct validity to the extent to which the measure appears to assess the construct it has been designed to assess.35 Two different types of construct validity are often distinguished: convergent validity, which refers to associations with other measures of the same construct, and discriminant validity, the lack of association of the measure with measures of unrelated constructs (e.g., a valid measure of intelligence would not be expected to correlate with sex).

Responsiveness is often considered the extent to which an instrument can detect change over time.36 Consistent with the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) approach to examining responsiveness in clinical trials, we also consider responsiveness to be the ability of a measure to distinguish between different treatments or between an active treatment and placebo.37 Although responsiveness can be considered a component of validity, we considered it separately, given its pivotal role in clinical trials.


Figure 2
Figure 2:
PRISMA flow chart.

The PubMed search yielded 4396 articles, of which we excluded 4128 after initial review of the title or abstract; 268 were considered relevant and were read in full. Among these, 39 articles did not use a formal measure or scale to assess sedation and were therefore excluded. References of the remaining 229 articles were reviewed, and an additional 16 relevant articles were identified. A total of 245 articles (Fig. 2) were thus included in our initial analysis of the type, characteristics, and use of sedation scales in the procedural sedation literature. Articles that discussed the psychometric assessment of a scale were included in the subsequent analysis of these properties (Table 3).

Sedation Scale Use in Procedural Sedation Studies

The most widely used measures of sedation were the Observer’s Assessment of Alertness/Sedation (OAA/S)19 or one of the multiple modified versions (Modified Observer’s Assessment of Alertness/Sedation scale [MOAA/S])14,15,38–41 that were used in 47% of the studies; the Ramsay scale18 or the modified Ramsay scale42 that was used in 25% of the studies; and the Wilson scale21,22 or modified Wilson scale23 that was used in 5% of the studies. The American Society of Anesthesiologists (ASA) continuum of depth of sedation1 and a visual analog scale (VAS) were each used in 3% of the studies; the Aldrete PostAnesthesia Recovery score43 was used in 2%; and the Hong scale,44 Gillham scale,45 and Gentili scale46 were each used in 1% of studies. Nonstandardized 6-, 5-, and 4-point scales to assess the level of sedation were used in 1%, 8%, and 2% of studies, respectively. The remaining 1% of studies used unique nonstandardized scales. The characteristics of the studies reporting the original use of these sedation scales are presented in Table 5.

Table 5
Table 5:
Sedation Measure Characteristics

Most (51%) of the scales were used to evaluate sedation level. The scale was used to designate a target level of sedation, and sedatives were given to achieve this level in 39% of the studies. The remaining 10% of studies administered the scale so that it could be compared with another method of assessing sedation or with electrophysiologic measures.

We considered both the individual who assessed the level of sedation and how frequently the level was assessed. An anesthesiologist recorded the level of sedation in 25% of studies, other physicians in 13%, nurses in 7%, an observer or a research assistant in 14%, and the individual assessing the sedation level was not reported in 41%. The frequency of sedation assessment was every 5 minutes or less in 47% of studies and every 10 minutes or more in 15%. Sedation level was assessed at procedure-specific time points in 8% of studies and just once during the procedure in 3%; the frequency of assessment was unreported for 27% of the studies.

Sedation Scales

The OAA/S was developed as a research measure by Chernik et al.19 for assessing the benzodiazepine antagonism with flumazenil (Appendix 2). The scale includes 4 domains: responsiveness (5 items), speech (4 items), facial expression (3 items), and eyes (3 items). The scale can be used in 2 ways. The composite score corresponds to the lowest sedation level recorded in any of the categories from 5 (alert) to 1 (deep sleep). Alternatively, the sum of the component scores can be used. MOAA/S refers to modified versions of the OAA/S that typically record only the “responsiveness” category. There is no standardized MOAA/S, and there are variations among these scales, including definitions of scale items and scale length with 7 points (6–0 scale),38,39 6 points (5–0 scale),16,17 and 5 points (5–1 scale)40,41 versions being used.

The clinimetric properties of the OAA/S scale were assessed in healthy volunteers sedated with midazolam when it was first described19; interrater reliability, responsiveness, and correlation with an observer-rated 100-mm-long VAS were excellent (Table 3). The responsiveness component corresponded most often with composite score (78%). Although the OAA/S is the most commonly used scale in the procedural sedation studies, its convergent validity has been compared only with the Ramsay scale (convergent validity correlation = −0.96; P < 0.001) in one study of monitored anesthesia care (MAC) sedation during surgery.20 No other studies of validity or reliability for procedural sedation were identified; therefore, extensive testing of this scale across different categories of procedures has not been performed. The total weighted score as assessed by the psychometric scoring criteria32 for the OAA/S is 6.3, which represents a very low level of psychometric adequacy for the assessment of procedural sedation (Table 6).

Table 6
Table 6:
Psychometric Sedation Scores

The Ramsay scale18 (Appendix 2) was developed in 1974 to assess the level of responsiveness in ICU patients sedated with alphaxalone-alphadolone. It is a single-item, 6-point scale that has been used extensively in ICU clinical trials with several studies reporting data on validity and reliability in this setting.47–49 Unfortunately, the only data on the validity of the Ramsay scale in this context are the significant correlation with the OAA/S noted earlier.20 The Ramsay scale was expanded to 8 points by Gill et al.42 in 2003 to reflect Joint Commission on Accreditation of Healthcare Organizations (JCAHO) sedation definitions,13 but validity and reliability data for this version are lacking. The Ramsay scale also scored only 6.3, because of a very low level of psychometric adequacy for procedural sedation (Table 6) and the similarly limited testing of this scale in a single study.

The Wilson scale (Appendix 2) is a single-item, 5-point scale initially used for assessing sedative medications during spinal anesthesia.21,22 Némethy et al.23 demonstrated good interrater agreement of the scale (Table 3). The authors combined levels 2 and 3 to create the 4-point modified Wilson Scale with improved interrater agreement (Table 3); however, the investigators did not validate either scale and we did not identify any other validation in our search, indicating insufficient publicly available evaluation of this scale. The total weighted score for the Wilson scale was 5, corresponding with a very low level of psychometric adequacy (Table 6).

VASs have been used as observer-rated or patient-reported measures of sedation. They are typically 100 mm long, with anchors that vary and depend on intended use. Typically, they are anchored at one end with “alert” and at the other end with “unresponsive” for observer scales, and with “awake” to “almost asleep” for patient scales. Patient-reported VASs are quick to administer but require a considerable degree of cooperation and are therefore less useful at higher degrees of sedation. Substantial associations were found between patient and observer scores in patients having propofol sedation and regional anesthesia for urologic procedures (Table 3).24 There was good interrater agreement of an observer VAS, and it demonstrated very good responsiveness and excellent agreement between observer VAS scores and composite and sum OAA/S scores (Table 3).19

The ASA continuum of depth of sedation1 has been used in several studies to document the level of sedation. As discussed earlier, it consists of 3 levels of sedation (minimal, moderate, and deep) and general anesthesia. The levels and corresponding descriptions were developed by anesthesiologists and approved by the ASA House of Delegates (1999) and therefore can be assumed to have content validity. However, no other formal psychometric testing of the continuum has been reported.

Pain and Related Scales

To augment the assessment of sedation, various studies have used additional measures, including evaluation of pain, satisfaction, recall, and recovery. Therefore, we discuss those measures that have been validated in a procedural or an operative sedation context.

There are several well-validated approaches to assessing patient-reported acute, chronic, and procedural pain, including VASs and numerical rating scales50,51; however, the effect of sedatives on patients’ ability to rate their pain on these measures has not been evaluated systematically. An alternative to patient-reported assessment of pain is the use of observer-rated pain scales, which attempt to quantify the patients’ pain severity from their apparent discomfort and other observable behaviors. We identified validity and/or reliability data for 3 observer-rated pain scales related to procedural sedation.

The Colorado Behavioral Numerical Pain Scale (CBNPS) is a single-item, 6-point numerical rating scale developed to assess a patient’s comfort during sedation for gastrointestinal procedures.27 There was high agreement on the content validity among sedation nurses and good interrater reliability for gastrointestinal procedures under sedation (Table 3).

The La Crosse Wisconsin Intra-Endoscopy Sedation Comfort (L-WISC) scale26 is a descriptive 4-point scale used to rate overall comfort. There was adequate interrater agreement but poor agreement between nurse–patient ratings (κ = 0.10). No studies examining the validity of the scale have been reported.

The Nurse Assessed Patient Comfort Score (NAPCOMS)25 consists of 3 subscales assessing pain: intensity, frequency, and duration as well as separate “sedation” and “global tolerability” domains. Validity and reliability of the measure were assessed during colonoscopies under sedation. The intraclass correlation for the overall NAPCOMS score was 0.84, and there were substantial correlations between the NAPCOMS and the comfort ratings by endoscopists (intraclass correlation [ICC] = 0.77) and patients (ICC = 0.61).

Behavioral scales are frequently used in pediatric procedural sedation research5—e.g., the Frankl52 and Houpt53 scales—but seldom in adults. The Ellis scale54 has been used in adult dental sedation studies and grades behavioral characteristics of patient cooperation, movement, or interference with the procedure on a 5-point scale. The literature search revealed no behavioral scales used in adult procedural sedation have had formal validity or reliability assessment.

The recently published Procedural Sedation Assessment Survey (PROSAS)55 was developed to assess sedation quality in gastroenterology procedures. External validity was suggested by a high correlation of patient-reported discomfort with nurse and proceduralist assessment. Further testing of this tool is important to examine further aspects of reliability and validity in this setting.


Satisfaction with sedation can be reported from a patient’s or clinician’s perspective. In studies assessing this component of sedation, a single question about overall satisfaction or willingness to have the same sedation again is often asked. There are 3 validated measures for satisfaction in procedural and operative sedation: (1) clinician satisfaction with the process of sedation, including before, during, and after the procedure; (2) patient satisfaction with the procedural period, limited to colonoscopy and upper endoscopy; and (3) patient satisfaction with surgical anesthesia.

The Clinician Satisfaction with Sedation Instrument (CSSI) was developed by Vargo et al.31 for colonoscopy and upper endoscopy procedures. This 16-item measure scale consists of a total satisfaction score and 2 subscales. Specifically, there are 11 sedation administration items and 5 recovery/postprocedural items, with each having a 7-point Likert scale ranging from very satisfied to very dissatisfied. Correlations of the total satisfaction scores with the recovery/postoperative procedure subscale and the sedation administration subscale were excellent, and internal consistency was uniformly high (Table 3).

The Patient Satisfaction with Sedation Instrument (PSSI)31 was codeveloped with the CSSI and is a 16-item measure consisting of a total satisfaction score and 3 subscales. Specifically, there are 2 sedation delivery items, 4 procedural recall items, and 10 items that evaluate sedation side effects; responses are scored on the same 7-point Likert scale used for the CSSI. The measure is specific to colonoscopy and upper endoscopy (e.g., “abdominal discomfort after the procedure”) but not to the sedation itself (e.g., “your overall level of satisfaction with preprocedural counseling about the procedure and the sedation”).

Total satisfaction score correlated highly with sedation side effects (r = 0.97), procedural recall (r = 0.82), and sedation delivery (r = 0.43). Construct validity was demonstrated by correlations with the Patient Satisfaction Questionnaire 18 (PSQ-18) measure of patient satisfaction (r = 0.23) and the Short Form 12 (SF-12) physical component summary (r = 0.27, P < 0.01) and mental component summary (r = 0.19, P < 0.05). There was no correlation (r = 0.06) with the Socially Desirable Response Scale,56 suggesting discriminant validity. Internal consistency for the PSSI total score was 0.91, with reliabilities (Cronbach α’s) of 0.76 for procedural recall, 0.86 for sedation delivery, and 0.92 for the side effects subscales.

The Iowa Satisfaction with Anesthesia Scale (ISAS) was developed by Dexter et al.28 to measure patient satisfaction with MAC sedation during surgery. The ISAS assesses satisfaction with the anesthetic itself, which based on the qualitative methods and quantitative correlations, the surgical patients consider separate from satisfaction with the preoperative and postoperative periods. The ISAS is an 11-item self-administered questionnaire with each item scored on a 6-point scale (−3, disagree very much to +3 agree very much). The satisfaction score is the mean of the patient’s responses to the 11 questions, after reversing the scores of the negatively worded questions. The scale’s content validity is based on its use for MAC. ISAS test-retest reliability was very good (r2 = 0.76), as was the measure’s unidimensional internal consistency (Table 3). Validity of the ISAS was shown, in part, by correlation of the mean ISAS score with the single item “satisfied with anesthetic care” (Kendall τ = 0.41) and the anesthesiologist’s prediction of the patient’s response (Pearson r = 0.48). The absence of strong correlation shows that neither of the latter 2 items are suitable alternatives to the ISAS.

The ISAS was used to measure satisfaction after cataract surgery with topical local anesthesia and MAC.30 Internal consistency and test-retest reliability were high (Table 3). ISAS was also used in a multicenter study following various procedures under MAC.29 A significant correlation with the single item, “satisfied with anesthetic care,” was found showing validity, and the high internal consistency from the original study28 was confirmed (Table 3). Therefore, the ISAS has undergone multiple psychometric assessments across a range of surgical procedures, but it is limited to MAC.


Recall has been assessed in procedural sedation studies using a single-item question following the procedure or by testing recall of certain procedural events. Although there is a validated questionnaire for assessing recall and awareness during general anesthesia,57 none has been developed for procedural sedation. The discrepancy between the sedation level anticipated by the patient and the actual sedation experienced is an important determinant of recall and awareness in procedures with regional anesthesia and MAC.58 However, it remains unclear whether these results can be extrapolated to procedures, such as endoscopy, for which patients may be less likely to expect to be unconscious.

Recovery and Efficiency

Measurement of total procedure time and time to readiness for discharge can be quantified for use as an outcome measure of procedural sedation. Recovery time has been assessed as a return to baseline on a clinical sedation scale or designated sedation recovery scale; however, neither of these approaches has been validated for this purpose in procedural sedation. There are many tests of psychomotor recovery from sedation that have been tested in various settings. For example, Willey et al.59 found that Letter Cancellation and Multiple Reaction Time had high sensitivity for detecting impaired psychomotor function compared with baseline. Novel methods such as driving simulators have been used60,61 to more closely replicate real-life situations and examine recovery of skills and abilities after sedation. Other measures include the Hopkins Verbal Learning Test-Revised (HVLT-R),14,15,62 Symbol Digit Test,62,63 Stroop Color Word Test,62,63 and Number Connection Test.60,61 Discussion of this approach to assessing recovery from sedation and these specific measures is beyond the scope of this article.

Efficiency is related to a number of different factors, including case load, case mix, time per case including recovery, turn-over times, and scheduled working hours. Pharmacologic profiles of different drugs are often related to reductions in overall time and cost savings, and efficiency should be studied with appropriate statistical methods.64,65


A prerequisite for conducting clinical trials to evaluate drugs or devices for procedural sedation is the identification of appropriate efficacy outcome measures. This systematic review shows that there are few valid and reliable measures for establishing sedation efficacy for multiple categories of procedures, a situation that hampers research progress and potentially impedes the development of improved interventions. The availability of well-accepted clinically meaningful end points with established validity and reliability would benefit investigators, clinicians, industry, and regulatory agencies. Importantly, consensus on, and use of, reliable and consistent outcome measures would facilitate comparisons among drugs and devices for procedural sedation.

Sedation Measures

The OAA/S19 has shown good validity, reliability, and responsiveness in healthy volunteers, and the Ramsay scale18 has been tested extensively in critical care settings.47–49,66,67 However, only 1 study has examined the use of these scales for procedural sedation,20 reporting a significant correlation between them. Observer-rated VASs for sedation show evidence of validity, reliability, and responsiveness in procedural sedation24 and in healthy volunteers,19 and the reliability of the Wilson sedation scale has been demonstrated in patients sedated for spinal anesthesia procedures.23

We reviewed existing measures of procedural sedation and found that clinimetric characteristics have been evaluated for a limited number of scales in only a few categories of procedures. None of the sedation scales had validity assessed in multiple ways, and there was insufficient evidence to evaluate whether these scales could be used outside the setting in which they were tested. Specifically, there are data to suspect that the scales are not applicable across the broad range of procedures for which sedation is performed. For example, the PSSI for colonoscopy and upper endoscopy procedures is entirely different from the ISAS for surgical procedures. Yet, both are single-dimension instruments with substantial internal consistency and validity.

Studies generally examined only 1 or 2 aspects of scale validity (e.g., concurrent validity but not responsiveness to change), and the results are typically unique to specific clinical circumstances. Although it is evident that validated ICU sedation scales cannot be assumed valid outside this setting, the validity of a procedural sedation measure may likewise be limited to a given procedure unless further tested in a broader range of sedation encounters. Ideally, an all-encompassing sedation scale could be validated for the general purpose of assessing procedural sedation but, given the diversity of procedures requiring sedation, it is likely that certain procedures will require the use of procedure-specific scales or subscales. In reviewing the literature, we did not find any validated procedure-specific measures of sedation; however, it is apparent that, for example, measures requiring motor stimulation and assessment of movement are clearly impractical when evaluating sedation for procedures where movement is intolerable (e.g., MRI scans).

With the exception of VAS scales, there are common themes across all sedation measures, despite variation in the exact definitions and specific items. As can be seen from Table 7, most scales predominantly assess a single sedation domain with multiple items representing progressive depression of consciousness as assessed by response to verbal and physical stimulation. Criticism of these scales includes the need for repeated verbal and tactile stimulation and poorly defined and subjective levels of sedation that are not necessarily mutually exclusive or evenly distributed.6,68 In addition, assessment of agitation and sedation on the same scale18,45 can be problematic when evaluating restless but sedated patients.68 Although it is possible that scales with fewer items would be more likely to show greater interrater agreement, overlap among different levels of sedation may result in loss of clinically meaningful information.

Table 7
Table 7:
Common and Unique Items in Sedation Scales

Clinimetric data also exist for measures of other aspects of sedation that would be important when conducting a comprehensive evaluation of procedural sedation and could be included as secondary end points in clinical trials. These include observer-rated pain and discomfort,25–27 clinician- and patient-rated satisfaction with the sedation and procedural process,31 and patient satisfaction with the administered sedation.28 Assessment of pain and patient satisfaction are important aspects of patient-centered health care.

Pain Measures

Although there are several well-validated patient-reported pain measures,50,51 obtaining self-reports in patients who are deeply sedated is inherently problematic, and the validity of these scales used subsequent to procedures remains unclear. The effect of sedation on pain perception and the importance of pain that patients cannot subsequently recall remain to be determined.6 In a small study of procedural sedation in emergency departments, for example, patient grimacing was not associated with recalled pain or dissatisfaction.69

Most scoring systems use defined behavioral responses in an attempt to standardize assessment across observers. None of the scoring systems discussed earlier use physiologic responses to pain, such as hemodynamic values. Although an “objective” numerical value would be a panacea for pain assessment, readily assessed physiologic changes have generally proven to be unreliable indicators of individuals’ pain, inconsistent over time, and too often affected by other variables.

The NAPCOMS25 and CBNPS27 are measures for assessing pain in gastrointestinal procedures under sedation with evidence of validity and reliability in this setting. To our knowledge, the CBNPS27 is the only observer-rated measure to have been used in a procedural sedation clinical trial to date.70

Satisfaction Measures

For assessment of satisfaction, single-item and VAS scales that have not been validated are often used despite being oversimplified and imprecise and having poor reliability.71 Such scales do not adequately address the complexity of satisfaction, which is often a balance between expectation and outcome and should be distinguished from gratitude. The 3 satisfaction scales with evidence of validity and reliability are the ISAS,28 the PSSI, and CSSI,31 each of which measures a different domain (i.e., they are not interchangeable). All 3 are multi-item questionnaires that have been used in several clinical trials.16,30,72,73

Additional Measures

Recovery is an additional outcome domain that has been examined in some studies of procedural sedation and that has relevance to evaluating treatment benefits in clinical trials. The amount of time allocated to recovery may potentially influence the efficiency and cost of procedural sedation. Although the reductions in time are similar at various centers, the influence of shorter times on efficiency (capital and labor) will differ among facilities. For example, saving 5 minutes per case will not result in efficiency when there is only a total of 6 hours of cases per day and the facility is staffed for a full 8 hours. From the measured time reductions, the effect on efficiency can be estimated accurately for each facility.64,65 Potential savings are not necessarily purely isolated at the institutional level, but have wider socioeconomic implications. For example, identification of drugs or devices for procedural sedation that permit a faster return to normal function and enable earlier discharge can generate cost savings by reducing time off work and the need for childcare.74 Recovery has been assessed with clinical scales such as the Aldrete Postanesthesia Recovery score,43 but these have yet to be validated for procedural sedation.

The extent to which the methods for assessing recovery from procedural sedation are procedure specific or may apply to diverse procedures has not been examined systematically; for example, can resumption of “normal activities” after dental surgery and colonoscopy be assessed in the same way, or do various sedation contexts require different measures? Patients having stable vital signs who have returned to consciousness and have gross motor function may remain well short of their baseline function. Their ability to safely perform usual daily activities is uncertain, and the delayed or prolonged effects of sedation on cognition and motor skills are unclear, epitomized in the guidance stating that patients should not drive on the day of sedation and need an escort.3 Although psychomotor tests have been used to assess return to baseline function, there may be important differences between clinical recovery and psychomotor recovery59; it remains unclear, for example, that recovery on a test of psychomotor performance indicates that patients can safely return home independently. Given the cost and difficulty imposed by prohibitions against driving, this seems to be an area meriting future research, possibly further exploring the potential of driving simulators after sedation.60,61

Data Collection

The timing and frequency of assessment is also important to consider. Although the frequency of assessment was every 5 minutes or less in nearly half of the studies we reviewed, the range was from every minute to just once during the procedure; and timing was unspecified in a quarter of the reports. Furthermore, qualifications of the person assessing sedation were unrecorded in 41% of studies; in the remaining studies, it was usually unclear what the training comprised. To our knowledge, there has been no systematic research on training raters to more reliably and validly rate existing outcome measures for clinical trials in procedural sedation; possibly relevant in this context, Némethy et al.23 found a higher concordance with attending-attending ratings of the Wilson Scale than with attending-resident or attending-Certified Registered Nurse Anesthetist (CRNA) pairings.

Appropriate data analysis is also critical. Given the discrete levels and defined characteristics of sedation scale items, an average score across an entire procedure may poorly reflect sedation experienced at critical periods. Our analysis was restricted to scales used in >1 clinical trial. However, other measures merit consideration. For example, the Dartmouth Operative Conditions Scale modified for Adults75 is a composite scale assessing pain and movement as well as cardiovascular, oxygen, and ventilation side effects. Modified from the pediatric Dartmouth Operative Conditions Scale,76 it uses expert review of video recording of procedures to quantify sedation by assessing and scoring patients’ state every minute. A score for an optimal sedated state is defined, and the primary end point that has been used is percentage of time patients spent in a suboptimal state.75 Assessing the level of sedation with such methods in clinical trials may be superior to an average score and may more closely represent sedation during the procedure and potentially provide a more clinically meaningful end point for comparing different treatments

Developing Core Sedation Domains and Measures

A lack of consistency among the outcome measures used in sedation clinical trials can impede meaningful evaluations and comparisons between different treatment approaches. Identifying useful measures for assessing core sedation outcome domains followed by their widespread adoption would facilitate the design of clinical trials and the evaluation of new drugs and devices and also make it possible to more meaningfully pool data for systematic reviews and meta-analyses.

Using a single outcome domain is unlikely to reflect overall sedation quality and may neglect important information regarding concomitant effects on other domains, leading to an incomplete evaluation of the overall benefits of a treatment. Given the complexity of sedation, it is necessary to assess multiple domains in a trial to capture key outcome variables. We consider 5 key aspects of sedation assessment to be important, namely sedation level, patient satisfaction, clinician satisfaction, efficiency, and safety (Fig. 3). We propose evaluating each of these dimensions in future clinical trials to provide a comprehensive picture of sedation efficacy.

Figure 3
Figure 3:
Interconnected outcome domains.

Our review suggests that measures having the most evidence of validity to assess these domains include the OAA/S for efficacy, which has been validated for sedation, although not for multiple specific procedures; the CSSI for clinician satisfaction in gastrointestinal procedures; and the ISAS and PSSI for patient satisfaction in operative and gastrointestinal procedures, respectively. Patient-reported pain may also be considered a crucial component of patient satisfaction for certain procedural sedation trials and could be evaluated within a satisfaction scale such as the ISAS or separately using the validated NAPCOMS for gastrointestinal procedures. There are no appropriate measures that can be used in sedation trials across the spectrum of recommended domains for all procedures. Certain trials may be appropriate to study sedation efficiency more broadly using appropriate statistical modeling.64,65 Adverse events should be thoroughly recorded in all clinical trials using standardized definitions.10

There are complex considerations in deciding between the use of composite outcome measures that include multiple subscales versus separate measures of each component. Unfortunately, the advantages and disadvantages of these different approaches to assessing multidimensional outcomes have not been examined for sedation efficacy measures.

Efforts to formally identify core sedation outcome domains and measures and to develop expert recommendations for other critical aspects of sedation clinical trials could be modeled on consortia such as the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT;,77 Broad implementation of a core set of sedation domains and measures would also ensure more comprehensive assessments of sedation efficacy and reporting of study results. Depending on the specific study objectives and circumstances, such core outcome domains and measures could be supplemented by other procedure- or situation-specific outcomes.

Developing new measures may ultimately be required to adequately evaluate core sedation outcome domains. Currently, response to auditory or physical stimuli is the most straightforward and frequently used method for assessing sedation level. Standardizing these stimuli using headphones with a set sound level and constant instruction and algometers to provide reproducible pressure may improve the reliability of these ratings. Future work may focus on validating existing measures across additional procedures, likely with procedure-specific modifications, or developing entirely new measures. An important area on which to focus future efforts is capturing the procedural conditions provided by a sedative. A valid tool for assessing movement during procedural sedation is currently lacking, but would be a useful measure for evaluating one important aspect of such procedural conditions. The clinical application of such a measure might well be procedure specific; for example, with “no movement” imperative for MRI studies but varying degrees of movement tolerated for other procedures.


We restricted our search to the articles published in English and, therefore, may have missed measures or studies relevant to procedural sedation published in other languages. Despite the comprehensive search strategy used, it is likely that some relevant articles published in English were not identified, as suggested by the fact that 16 articles that were not identified through the PubMed search were located by examining reference lists of the published articles. Perhaps most importantly, we are unable to evaluate the extent to which our conclusions have been affected by publication bias; for example, studies finding poor reliability or validity of a measure are presumably less likely to be submitted for publication and less likely to be accepted for publication than those demonstrating that a measure has significant reliability or validity.


Capturing the overall quality of sedation is complex, and the outcome measures used must assess meaningful aspects of procedural sedation that can be compared and ideally improved. Many methods of assessing procedural sedation and diverse outcomes have been used in various clinical trials, making comparisons challenging. A minority of existing measures had undergone psychometric analysis in a procedural sedation setting, typically examining only a few aspects of scale validity, which were limited to a particular category of procedure.

Development of improved interventions for procedural sedation will be facilitated by additional research on existing measures or development of novel measures using state-of-the-art methods for developing patient-reported outcomes and other clinical measures.c Such efforts will require the identification of clinically important outcome domains by individuals with clinical and research expertise working collaboratively with patients and other stakeholders, followed by the development of measures that validly and reliably assess these sedation outcomes.


Search Methods

Two searches of PubMed (1946 to present) were conducted by a librarian (Michele Shipley) for the clinical trials covering the use of sedation during medical and dental procedures. The searches were restricted to English language articles and human research. The last search was run on January 30, 2015.

The first search strategy was composed of MeSH subject headings and free-text words for sedation, multiple medical and dental procedures, and clinical trials. The second search strategy was composed of MeSH subject headings and free-text words for procedural sedation and conscious sedation. Citations retrieved as a result of the first search strategy were excluded from the results. The Cochrane filter for Humans only was applied to both searches. Nonindexed citations from both search strategies were manually reviewed by the librarian, and citations covering animal research were excluded.

PubMed Search Strategy 1

A - Terms for Medical and Dental Procedures (Combined with OR)

Angiocardiography[all] OR Tomography[all] OR Gated Blood-Pool Imaging[all] OR Angiography[all] OR Echocardiography[all] OR Myocardial Perfusion Imaging[all] OR Ventriculography[all] OR Magnetic Resonance Imaging[all] OR Cholangiopancreatography[all] OR Diffusion Tensor Imaging[all] OR Echo-Planar Imaging[all] OR Neuroimaging[all] OR Brain Mapping[all] OR Connectome[all] OR Neuroradiography[all] OR Echoencephalography[all] OR Ultrasonography[mh] OR ultrasonography[tiab] OR Myelography[all] OR Pneumoencephalography[all] OR Radiography[mh] OR radiography[tiab] OR Absorptiometry, Photon[all] OR Aortography[all] OR Cineangiography[all] OR Phlebography[all] OR Portography[all] OR Arthrography[all] OR Cineradiography[all] OR Electrokymography[all] OR Fluoroscopy[all] OR Photofluorography[all] OR Hysterosalpingography[all] OR Lymphography[all] OR Mammography[all] OR Xeromammography[all] OR Microradiography[all] OR Neuroradiography[all] OR Pneumoradiography[all] OR Colonography[all] OR Cholangiography[all] OR Cholecystography[all] OR Defecography[all] OR Portography[all] OR Sialography[all] OR Bronchography[all] OR Chest X-Ray[all] OR Urography[all] OR Xeroradiography[all] OR Carotid Intima-Media Thickness[all] OR Endosonography[all] OR Microscopy, Acoustic[all] OR Fine Needle Aspiration[all] OR Cervical Length Measurement[all] OR Nuchal Translucency Measurement[all] OR Whole Body Imaging[all] OR Angioscopy[all] OR Cholangiopancreatography[all] OR Endoscopy[all] OR Colonoscopy[all] OR Sigmoidoscopy[all] OR Duodenoscopy[all] OR Esophagoscopy[all] OR Gastroscopy[all] OR Proctoscopy[all] OR Electroencephalography[all] OR Cortical Synchronization[all] OR Magnetoencephalography[all] OR Neuroendoscopy[all] OR Spinal Puncture[all] OR Transcranial Magnetic Stimulation[all] OR Colposcopy[all] OR Culdoscopy[all] OR Hysteroscopy[all] OR Bronchoscopy[all] OR Laryngoscopy[all] OR Biopsy[mh] OR biopsy[tiab] OR Chorionic Villi Sampling[all] OR Conization[all] OR Arthroscopy[all] OR Cystoscopy[all] OR Fetoscopy[all] OR Laparoscopy[all] OR Mediastinoscopy[all] OR Natural Orifice Endoscopic Surgery[all] OR Thoracoscopy[all] OR Ureteroscopy[all] OR Pneumomediastinum, Diagnostic[all] OR Pneumoperitoneum, Artificial[all] OR Nephrostomy, Percutaneous[all] OR Joint Capsule Release[all] OR Endovascular Procedures[all] OR Angioplasty[all] OR Atherectomy[all] OR Catheterization[all] OR Percutaneous Coronary Intervention[all] OR Dental Implantation[all] OR Blade Implantation[all] OR Dental Implants[all] OR Dentistry, Operative[all] OR Crown Lengthening[all] OR Dental Restoration[all] OR Crowns[all] OR Post and Core Technique[all] OR Inlays[all] OR Endodontics[all] OR Apicoectomy[all] OR Dental Pulp Capping[all] OR Pulpectomy[all] OR Pulpotomy[all] OR Root Canal[all] OR Apexification[all] OR Dental Pulp Devitalization[all] OR Obturation[all] OR Tooth Replantation[all] OR Gingivectomy[all] OR Gingivoplasty[all] OR Glossectomy[all] OR Guided Tissue Regeneration, Periodontal[all] OR Jaw Fixation[all] OR Mandibular Advancement[all] OR Maxillofacial Prosthesis Implantation[all] OR Mandibular Prosthesis Implantation[all] OR Alveolar Ridge Augmentation[all] OR Alveolectomy[all] OR Alveoloplasty[all] OR Vestibuloplasty[all] OR Orthognathic Surgical Procedures[all] OR Genioplasty[all] OR Mandibular Reconstruction[all] OR Osteotomy[all] OR Sinus Floor Augmentation[all] OR Tooth Extraction[all] OR Serial Extraction[all] OR Tooth Replantation[all] OR Orthodontics[all] OR Dental Marginal Adaptation[all] OR Orthodontic Anchorage Procedures[all] OR Periodontics[all] OR Guided Tissue Regeneration, Periodontal[all] OR Periodontal Prosthesis[all] OR Periodontal Splints[all] OR Subgingival Curettage[all] OR Root Planing[all] OR Prosthodontics[all] OR Dental Marginal Adaptation[all] OR Dental Prosthesis[all] OR Dental Abutments[all] OR Dental Clasps[all] OR Dental Veneers[all] OR Dentures[all] OR Inlays[all] OR Palatal Obturators[all] OR Tooth, Artificial[all] OR Tissue Conditioning[all] OR Bone Marrow Examination[all] OR Bone Marrow Aspiration[all] OR Bone Marrow Biopsy[all].

B - Terms for Sedation (Combined with OR)

Sedation[all] OR sedate[all] OR sedated[all] OR sedating[all] OR “Hypnotics and Sedatives”[mh] OR sedative*[tiab].

C - Filter for Clinical Trials (Combined with OR)

(Clinical Trial[pt] OR Comparative Study[pt] OR random*[tiab] OR Random Allocation[mh] OR placebo[tiab] OR trial[tiab] OR groups[tiab] OR “cross over”[tiab] OR crossover[title/abstract] OR Cross-Over Studies[mh] OR “double blind”[tiab] OR double-blind method[mesh] OR “double masked”[title/abstract] OR “double dummy”[title/abstract] OR “parallel group”[title/abstract] OR “sham controlled”[title/abstract] OR prospective[title/abstract]) NOT (Editorial[pt] OR Letter[pt] OR Case Reports[pt] OR Comment[pt] OR Meta-Analysis[pt] OR Review[pt]).

(A AND B AND C Filters: English) NOT (Animals[mh] NOT Humans[mh]).

PubMed Search Strategy 2

A - Terms for Sedation (Combined with OR)

Conscious Sedation[mh] OR “conscious sedation”[all] OR “procedural sedation”[all].

B - Filter for Clinical Trials (Combined with OR)

(Clinical Trial[pt] OR Comparative Study[pt] OR random*[tiab] OR Random Allocation[mh] OR placebo[tiab] OR trial[tiab] OR groups[tiab] OR “cross over”[tiab] OR crossover[title/abstract] OR Cross-Over Studies[mh] OR “double blind”[tiab] OR double-blind method[mesh] OR “double masked”[title/abstract] OR “double dummy”[title/abstract] OR “parallel group”[title/abstract] OR “sham controlled”[title/abstract] OR prospective[title/abstract]) NOT (Editorial[pt] OR Letter[pt] OR Case Reports[pt] OR Comment[pt] OR Meta-Analysis[pt] OR Review[pt]).

(A AND B Filters: English) NOT (Animals[mh] NOT Humans[mh]).


Sedation Scales

Observer’s Assessment of Alertness/Sedation19
Ramsay Scale18
Wilson Scale21 , 22
Gentili Scale46
Hong Scale44
Gillham Scale45
Examples of Modified Observer’s Assessment of Alertness/Sedation14,15,38–41


Name: Mark R. Williams, MBBS, BSc.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Mark R. Williams approved the final manuscript.

Conflicts of Interest: Mark R. Williams has no conflicts of interest to declare.

Name: Andrew McKeown, BS.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Andrew McKeown approved the final manuscript.

Conflicts of Interest: Andrew McKeown has no conflicts of interest to declare.

Name: Franklin Dexter, MD.

Contribution: This author helped write the manuscript.

Attestation: Franklin Dexter approved the final manuscript.

Conflicts of Interest: The Iowa Satisfaction with Anesthesia Scale is copyright Franklin Dexter and the University of Iowa Research Foundation, with funds going to the university for research.

Name: James R. Miner, MD.

Contribution: This author helped write the manuscript.

Attestation: James R. Miner approved the final manuscript.

Conflicts of Interest: James R. has no conflicts of interest to declare.

Name: Daniel I. Sessler, MD.

Contribution: This author helped write the manuscript.

Attestation: Daniel I. Sessler approved the final manuscript.

Conflicts of Interest: Daniel I. Sessler’s department is supported by Covidien, which produces the Bispectral Index monitor.

Name: John Vargo, MD, MPH.

Contribution: This author helped write the manuscript.

Attestation: John Vargo approved the final manuscript.

Conflicts of Interest: John Vargo is a consultant for the following: Boston Scientific, Inc., Cook Medical, Inc., Ethicon Endo-Surgery, Inc., and Olympus America, Inc.

Name: Dennis C. Turk, PhD.

Contribution: This author helped design the study and write the manuscript.

Attestation: Dennis C. Turk approved the final manuscript.

Conflicts of Interest: Dennis C. Turk has received in the past 12 months research grants from US Food and Drug Administration and US National Institutes of Health and compensation for activities involving clinical trial research methods from Develco, Mallinckrodt, Orexo, Nektar, and Xdynia.

Name: Robert H. Dworkin, PhD.

Contribution: This author helped design the study and write the manuscript.

Attestation: Robert H. Dworkin approved the final manuscript.

Conflicts of Interest: Robert H. Dworkin has received in the past 12 months research grants from US Food and Drug Administration and US National Institutes of Health, and compensation for activities involving clinical trial research methods from Astellas, AstraZeneca, Avanir, Biogen, Centrexion, Charleston, Chromocell, Concert, Daiichi Sankyo, Eli Lilly, Johnson & Johnson, Lpath, Metys, Nektar, Neura, Olatec, PeriphaGen, Phosphagenics, Q-Med, QRxPharma, Relmada, Salix, Sorrento, Spinifex, and Teva.


Dr. Franklin Dexter is the Statistical Editor and Section Editor for Economics, Education, and Policy for Anesthesia & Analgesia. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. Dexter was not involved in any way with the editorial process or decision.


The authors thank Michele Shipley, MLS, of the University of Rochester Miner Library, Rochester, NY, for her invaluable assistance in conducting the literature searches.


a American Dental Association. ADA Guidelines for the Use of Sedation and General Anesthesia by Dentists. 2007. Available at: Accessed August 17, 2015.
Cited Here

b American College of Radiology. ACR–SIR Practice Guideline for sedation/analgesia. 2010. Available at: Accessed April 11, 2015.
Cited Here

c FDA – US Department of Health and Human Services Food and Drug Administration. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. 2009. Available at: Accessed October 23, 2014.
Cited Here


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