Failed sedation for routine gastrointestinal (GI) endoscopy is extremely rare, warranting a return to endoscopist-directed sedation, rather than costly anesthesia-assisted sedation, as the default sedation standard.
Objectives: Use of anesthesia-assisted (AA) sedation for routine gastrointestinal (GI) endoscopy has increased markedly. Clinical uncertainty about which patients are most likely to benefit from AA sedation contributes to this increased use. We aimed to estimate the prevalence of failed endoscopist-directed sedation and to identify patients at elevated risk of failing standard sedation.
Study Design: Retrospective longitudinal study of national Veterans Health Administration (VA) data of all patients who underwent esophagogastroduodenoscopy and/or colonoscopy in 2009-2013.
Methods: Using multivariable logistic regression, we sought to identify patient and procedural risk factors for failed sedation. Failed sedation cases were identified electronically and validated by chart review.
Results: Of 302,247 standard sedation procedures performed at VA facilities offering AA sedation, we identified 313 cases of failed sedation (prevalence, 0.10%). None of the factors found to be associated with increased risk of failed sedation (eg, high-dose opioid use, younger age) had an odds ratio greater than 3. Even among the highest-risk patients (top decile), the prevalence of failed sedation was only 0.29%.
Conclusions: Failed sedation among patients undergoing routine outpatient GI endoscopy with standard sedation is very rare, even among patients at highest risk. This suggests that concerns regarding failed sedation due to commonly cited factors such as chronic opioid use and obesity do not justify forgoing standard sedation in favor of AA sedation in most patients. It also suggests that use of AA sedation is generally unnecessary. Reinstatement of endoscopist-directed sedation, rather than AA sedation, as the default sedation standard is warranted to reduce low-value care and prevent undue financial burdens on patients.
Am J Manag Care. 2021;27(12):e413-e419. https://doi.org/10.37765/ajmc.2021.88796
Recently, costly anesthesia-assisted (AA) sedation has increasingly replaced endoscopist-directed sedation as the default sedation standard. However, failed endoscopist-directed sedation in routine gastrointestinal endoscopy is rare, even among high-risk patients. Thus, concerns regarding failed sedation due to commonly referenced factors such as chronic opioid use, obesity, or increased comorbidity do not justify use of AA sedation in most patients.
Millions of routine gastrointestinal (GI) endoscopic procedures are performed annually in the United States. Historically, endoscopic sedation was considered inherent to the procedure because it was administered under the endoscopist’s supervision. However, in recent years, use of anesthesia-assisted (AA) sedation for routine GI endoscopy has increased markedly in fee-for-service environments, now accounting for upward of 50% of procedural sedation in Medicare and commercially insured patients.1-4 Indeed, AA sedation use has grown to the point that in many places it has become community standard.
AA sedation is defined by the presence of an anesthesiology provider and typically involves administration of propofol, leading to a deeper form of sedation. Although AA sedation may be indicated for patients with severe cardiopulmonary comorbidities or potential for airway compromise, greater than two-thirds of AA sedation is used in healthy, low-risk patients who do not clearly require it for medical reasons.1 Although routine use of AA sedation has potential benefits, such as shorter recovery and discharge times and improved patient satisfaction, these potential benefits must be balanced against the high cost of AA sedation and potentially greater risk of complications.1,5-7 Indeed, the costs of specialized endoscopic sedation not only are shouldered by the health system, but often are borne by patients. In a recent study, nearly 1 in 8 commercially insured patients nationwide who underwent an elective colonoscopy between 2012 and 2017 performed by an in-network provider received “surprise” bills for out-of-network expenses.8 In a majority of cases, these bills were the result of use of an out-of-network anesthesiologist, with a median surprise bill of $488.
In this study, we utilized longitudinal data from the Veterans Health Administration (VA), the largest integrated health care delivery system in the United States, to determine the prevalence of failed standard sedation and identify those patients at highest risk who may benefit most from AA sedation. Between 2009 and 2013, AA sedation use for routine GI endoscopy was 4.1% across the VA nationally, much lower than in the private sector, providing an ideal setting to understand the prevalence of failed standard sedation. We hypothesized that the prevalence of failed GI endoscopic sedation even in this setting was very low, suggesting that endoscopist-directed conscious sedation should be reinstated as the default sedation standard, reversing recent trends toward AA sedation.
This study was approved by the institutional review board of the VA Ann Arbor Healthcare System in Michigan. This was a retrospective longitudinal study of national VA administrative data obtained through the VA Corporate Data Warehouse (CDW).
The study population consisted of all patients who underwent a colonoscopy and/or esophagogastroduodenoscopy (EGD) in fiscal years 2009 to 2013. Cases were identified via Current Procedural Terminology (CPT) codes for colonoscopy and EGD without interventions such as polypectomy, dilation, or injection (EGD: 43235 [diagnostic; no biopsy], 43239 [biopsy], 43250 [hot biopsy]; colonoscopy: 45378 [diagnostic; no biopsy], 45380 [biopsy], 45384 [biopsy with cautery], G0105 [colorectal cancer screening, high risk], G0121 [colorectal cancer screening, average risk]). This narrowed list of codes was intentionally utilized to eliminate cases in which factors other than sedation intolerance (eg, need for advanced polypectomy with an interventional endoscopist) may have influenced the decision to select AA sedation for the subsequent procedure. Sedation type (AA or standard sedation) was identified by the presence or absence of CPT codes for AA sedation (00810, anesthesia assistance for lower endoscopy; 00740, anesthesia assistance for upper endoscopy) occurring on the same day as the primary procedure CPT code, using a validated algorithm.9 In 2009-2013, AA sedation use for routine GI endoscopy was 4.1% across the VA nationally.
Identifying Failed Sedation Outcomes
Failed sedation cases were identified electronically using CDW data as patients who had a routine procedure (without polypectomy, dilation, or injection) with AA sedation within specified time windows following the same procedure with standard sedation. We identified the optimal time window between index procedure with standard sedation and repeat procedure with AA sedation by first reviewing medical charts of 50 random cases each in windows of less than 3 months, 3 to 6 months, 6 to 9 months, 9 to 12 months, and 1 to 5 years; the less-than-3-month window was found to be most specific for identifying failed sedation as the cause for repeat procedure. We then electronically identified all cases of failed sedation defined by the 3-month window and manually validated all cases by chart review (index endoscopy report or other records) documenting patient discomfort/agitation and/or medical instability resulting in either an incomplete procedure or specific mention of need for AA sedation for future procedures.
Using multivariable logistic regression, we sought to identify patient- and procedure-level risk factors for the outcome of failed sedation. Only variables that were significant (P < .1) on unadjusted analysis were included in the adjusted (multivariable) analysis, in which P < .05 was used as the threshold for significance. Specific patient-level variables examined included age, sex, body mass index (BMI), history of obstructive sleep apnea (OSA), home oxygen use, primary pulmonary hypertension, alcohol abuse or dependence, drug abuse or dependence, history of physical and/or sexual abuse, history of military sexual trauma (MST), history of psychiatric disease, chronic obstructive pulmonary disease, fibromyalgia, Charlson Comorbidity Index (CCI) score, and history of a functional GI disorder as determined by specified International Classification of Diseases, Ninth Revision codes or VA-specific administrative flags (in the case of MST) (eAppendix [available at ajmc.com]). We also analyzed patient-level variables reflecting use of specific outpatient pharmaceuticals, including chronic opioids (defined as the daily morphine equivalent dose [MED], in mg, dispensed in the 6 months prior to the procedure), benzodiazepines (defined as the daily diazepam equivalent dose [DED], in mg, dispensed in the 6 months prior to the procedure), and use of other psychoactive drugs (any). We also examined the effect of procedure type (EGD, diagnostic colonoscopy, screening colonoscopy) using a validated algorithm.10 In addition, we tested for the presence of possible interactions between procedure indication and all other predictors, as well as between a patient’s history of psychiatric disease and use of psychoactive drugs. Penalized maximum likelihood estimation was utilized to minimize risk of bias, given that failed sedation was a rare event.11
Ten-fold cross validation was used to validate the final model. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Discrimination was determined by the area under the receiver operating characteristic curve (AUC). All statistical analyses were conducted using SAS version 7.1, of the SAS Enterprise Guide for Linux (SAS Institute).
A total of 710,252 procedures meeting inclusion criteria were performed with standard sedation during the study period. The electronic algorithm (3-month window) identified 873 cases of failed sedation (370 colonoscopy and 503 EGD). After manual validation through chart review, a total of 398 validated cases of failed sedation (225 colonoscopy and 173 EGD) were identified. For purposes of our analysis, we then narrowed the cohort to procedures performed at VA facilities that had the capability to provide AA sedation during the study period, resulting in a final analysis cohort of 302,247 procedures (313 validated cases of failed sedation, including 180 colonoscopy and 133 EGD procedures) and an overall prevalence of failed sedation of 0.10%. Patients were generally healthy (54% had a CCI score of 0) and male, with a median age of 62 (interquartile range, 55-67) years (Table 1 [part A and part B]). The majority of procedures were screening colonoscopies (54%), followed by EGDs (27%) and diagnostic colonoscopies (19%).
Of all factors evaluated, 5 variables (BMI, OSA, history of fibromyalgia, alcohol abuse/dependence, and personal history of physical and/or sexual abuse) were not significant on unadjusted analysis (P > .1) and therefore were not included in the adjusted analysis (Table 2 [part A and part B]). In addition, there were no failed sedation outcomes involving patients with a history of home oxygen use or pulmonary hypertension; therefore, odds ratios (ORs) could not be calculated for these variables. All other covariates were included in the adjusted analysis. In a prior study, we demonstrated that patients receiving AA sedation and conscious sedation in the VA health care system have similar clinical characteristics.9
Variables found to be associated with increased risk of failed sedation on adjusted analysis included younger age (OR18-29, 2.59; 95% CI, 1.48-4.56, compared with a reference age of 50-59 years), chronic opioid use (ORdaily MED >30 mg, 2.23; 95% CI, 1.52-2.30), and moderate chronic benzodiazepine use (ORdaily DED >0-4 mg,1.58; 95% CI, 1.07-2.34). An interaction was present between patient comorbidity and procedural indication, so an interaction term was included in the analysis. No other interactions were found. Patients with any comorbidity level undergoing EGD were more than twice as likely to experience failed sedation (OREGD with any CCI score, 2.45; 95% CI, 1.76-3.41) than healthy patients undergoing screening colonoscopies. However, none of the factors found to be associated with increased risk of failed sedation had an OR greater than 3. The model was well calibrated (Hosmer-Lemeshow P = .89), but even patients in the top decile of risk (young patients on high-dose [daily MED >30 mg] chronic narcotics undergoing upper endoscopy) had a failed sedation prevalence of only 0.29% (Table 3). Ten-fold cross validation yielded a mean AUC of 0.67 (95% CI, 0.61-0.68).
In this study, we found the prevalence of failed sedation among patients undergoing routine GI procedures to be extremely low, present in only 0.10% of standard sedation cases meeting study criteria. Although patient-related factors such as obesity, OSA, and alcohol abuse/dependence are frequently cited by providers as influential factors in decisions to select anesthesia assistance for endoscopic sedation, in our study none of these factors were identified as significant risk factors for failed sedation. In fact, even among significant risk factors (including younger age, chronic opioid use, chronic benzodiazepine use, and EGD procedure), none were strongly correlated with the outcome of failed sedation (OR < 3). Even among patients in the highest decile of risk, failed sedation was present in only 0.29% of cases. This suggests that concerns regarding failed sedation due to commonly cited factors such as chronic opioid use, obesity, or increased comorbidity do not justify forgoing standard sedation in favor of AA sedation in most patients. It also suggests that use of AA sedation is generally unnecessary because failed sedation is extremely uncommon.
Prior studies seeking to estimate the prevalence of failed sedation and identify associated risk factors have utilized suboptimally defined outcome variables, resulting in overestimation of the prevalence of failed sedation. In a retrospective, cross-sectional study, Braunstein et al examined all patients undergoing EGD and colonoscopy with standard sedation over a 6.5-year period at a single, large, urban academic center in New York, using electronic endoscopy records.12 They found the prevalence of “difficult sedation” to be greater than 10% for both procedures. However, the outcome of difficult sedation in that study was defined as the patient’s receipt of high doses of sedation (top quintile of both midazolam and fentanyl doses; 98% of cases) or the provider’s subjective documentation of patient agitation and/or discomfort (only 2% of cases). This is not an ideal proxy for failure of standard sedation, because the majority of patients experience some temporary discomfort during endoscopic procedures (which they commonly do not recall after completion of the procedure), and high sedation requirements are not as clinically meaningful as failed sedation leading to an inability to complete the procedure. Furthermore, in the Braunstein et al study, the top quintile of midazolam use was only 4 to 5 mg and the top quintile of fentanyl use was 97 to 133 mcg, depending on procedure type. At our institution, these would not typically be characterized as notably high sedation doses, illustrating the challenges of using medication doses to define difficult sedation outcomes. In addition, the cross-sectional nature of that study prevented any sort of longitudinal analysis of whether those patients subsequently required AA sedation. Thus, our study, which used a longitudinal, information-rich, national database, with a more clinically relevant outcome measure, adds significantly to existing literature. As in our study, younger age, procedural indication, and patient history of chronic benzodiazepine and/or opioid use were identified in the Braunstein et al study as risk factors for difficult sedation with standard sedatives for both EGD and colonoscopy. However, chronic opioid and benzodiazepine use were evaluated in that study as dichotomous variables; thus, the threshold dose of these medications most predictive of failed sedation was not examined.
Similarly, using a case-control design, McCain et al examined roughly 6 years of data from a single academic center in Florida to develop a risk score predictive of either high conscious sedation requirements or a failed procedure in patients undergoing EGD, colonoscopy, or bidirectional endoscopy, but they did not calculate the prevalence of this outcome.13 “Sedation failure” was defined in this study as the existence of 1 or more of the following: receipt of greater than 10 mg midazolam and/or greater than 200 mcg fentanyl during the procedure, need for reversal agents, nurse-documented poor patient tolerance, and aborted procedure, with an estimated failed conscious sedation prevalence of 2.5% to 5%. Age younger than 60 years (compared with a reference age of >70 years), female gender, chronic benzodiazepine use (again, a dichotomous variable), and bidirectional endoscopy all increased the risk of sedation failure, with a score greater than 3.5 out of 5 carrying the highest risk (AUC, 0.68). This study had the same limitations as the Braunstein et al study mentioned earlier.
Our study adds meaningfully to existing knowledge in several notable ways. First, our estimation of failed sedation prevalence was based on validated cases of failed sedation, identified electronically and then verified through manual chart review documenting patient discomfort and/or agitation and/or medical instability resulting in either an incomplete procedure or specific mention of a need for AA sedation for future procedures. Second, to our knowledge, our study represents the first attempt to evaluate chronic opioid and benzodiazepine doses in an effort to identify a threshold dose over which failed sedation is more likely. This is important because providers currently do not have robust evidence to guide decision-making in this area, likely leading to significant overestimation of the need for AA sedation in patients who are taking even small or infrequent doses of opioids. In our study, there was a dose-dependent increase in risk of failed sedation with escalating doses of opioids (ORdaily MED > 30 mg, 2.23 [95% CI, 1.52-3.28], compared with patients with no opioid use), although the absolute difference in risk was small. Curiously, for benzodiazepines, patients with moderate use of benzodiazepines (daily DED >0-4 mg) were at slightly higher risk of failed sedation than those not on benzodiazepines, whereas patients on higher doses (> 4 mg) were not. The explanation for this difference is unclear. In any case, the prevalence of failed sedation was so rare that the absolute difference caused by any of these factors is extremely small.
Our study has several limitations worth mention, including the inherent risk of misclassification using administrative data. This includes the potential for undercoding of comorbidities, as administrative billing codes are used in VA mainly to capture workload. By limiting our review to standard sedation procedures performed within 3 months of a subsequent similar procedure with AA sedation, we also may have missed a few remote failed sedation outcomes. However, prior to focusing on this time period, we performed chart review of 50 cases in the 3-to-6-month, 6-to-9-month, 9-to-12-month, and 1-to-5-year windows, during which we found very few cases of ineffective sedation with repeat endoscopies beyond the 3 months used in our final analysis. We also were unable to study the effect of trainee involvement in the procedure, as VA administrative data lack a flag denoting trainee involvement.
The generalizability of the results to nonveteran populations may also be questioned, particularly among women. However, developing our model using VA data is ideal for several reasons. First, although use of AA sedation has increased somewhat in the VA, the overall proportion of AA sedation use in the VA is quite low compared with in the private sector, meaning that most procedures are done with standard endoscopist-directed sedation. This minimizes the potential selection biases for which patients received standard sedation for the index procedure. During the period between 2009 and 2013, AA sedation was used in only 4.1% of cases, despite higher prevalence of heavy alcohol use, chronic narcotic and benzodiazepine use, and mental health disorders such as posttraumatic stress disorder (associated with functional bowel disorders) than in nonveteran populations.14 Second, national VA administrative databases provide an information-rich, longitudinal source of data not available elsewhere. Finally, the outcome of failed sedation requiring repeat procedure with AA sedation may miss some patients in whom the procedure was completed with standard sedation with difficulty (eg, a combative patient) or aborted short of a complete procedure but a repeat procedure with AA sedation was never performed (eg, if the benefits of repeat procedure with AA sedation were deemed not worth the potential risks and inconvenience). Some veterans also may have been referred from VA to community settings for procedures with AA sedation due to failed sedation, cases which would not have been captured by our algorithm. However, even if true failed sedation outcomes were 10-fold greater than our outcome of failed sedation, the prevalence of such failures would still be only 1%.
Failed sedation among patients undergoing routine outpatient GI endoscopy with standard sedation was extremely rare, even among the highest-risk patients in our model. This suggests that concerns regarding failed sedation due to commonly referenced factors such as chronic opioid use, obesity, and increased comorbidity do not clearly justify forgoing standard sedation in favor of AA sedation in most patients. It also suggests that use of AA sedation is generally unnecessary, because failed sedation is very rare even in the VA, where overall use of AA sedation is quite low compared with the private sector. A return to endoscopist-directed moderate conscious sedation as the default sedation standard, rather than routine adoption of AA sedation, is warranted to reduce low-value care and prevent undue financial burdens on patients, who often must shoulder the cost burden of ancillary endoscopic services such as AA sedation.8 Reversing course is a complex, yet not insurmountable, challenge that will require multilevel strategies to address the incentives and expectations fueling the dramatic rise in use of AA sedation for routine GI procedures. However, strengthening the evidence base regarding who benefits is a critical first step in achieving this outcome.
Author Affiliations: Center for Clinical Management Research, Department of Veterans Affairs, VA Ann Arbor Healthcare System (MAA, SDS, YG, WLW, JHR), Ann Arbor, MI; Division of Gastroenterology, University of Michigan Health System (MAA, SDS, JHR), Ann Arbor, MI; Institute for Healthcare Policy and Innovation (MAA, SDS, JHR), Ann Arbor, MI.
Source of Funding: This study was supported by an American College of Gastroenterology Junior Faculty Development Grant (2018-2021) awarded to Dr Adams.
Author Disclosures: Dr Rubenstein performs endoscopies at an academic hospital that receives reimbursement for anesthesia assistance in endoscopies beyond that which it would receive if he performed endoscopies without anesthesia assistance (ie, the institution stands to lose money based on the results of this study). The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (MAA, JHR); acquisition of data (MAA, YG); analysis and interpretation of data (MAA, SDS, YG, JHR); drafting of the manuscript (MAA); critical revision of the manuscript for important intellectual content (SDS, WLW, JHR); statistical analysis (MAA, YG); obtaining funding (MAA, JHR); administrative, technical, or logistic support (WLW); and supervision (SDS, WLW, JHR).
Address Correspondence to: Megan A. Adams, MD, JD, MSc, Division of Gastroenterology, University of Michigan Health System, 2215 Fuller Rd, Gastroenterology 111-D, Ann Arbor, MI 48105. Email: email@example.com.
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