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Propofol versus midazolam with or without short-acting opioids for sedation in colonoscopy: a systematic review and meta-analysis of safety, satisfaction, and efficiency outcomes
Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, CanadaInstitute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, CanadaLi Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, CanadaDepartment of Surgery, St Michael’s Hospital, Toronto, Ontario, Canada
Reprint requests: Nancy Baxter, MD, PhD, Division of General Surgery, St Michael’s Hospital, 040-16 Cardinal Carter Wing, 30 Bond St, Toronto, ON, M5B 1W8, Canada.
Affiliations
Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, CanadaInstitute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, CanadaLi Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, CanadaDepartment of Surgery, St Michael’s Hospital, Toronto, Ontario, Canada
Propofol is increasingly being used for sedation in colonoscopy; however, its benefits over midazolam (± short-acting opioids) are not well quantified. The objective of this study was to compare safety, satisfaction, and efficiency outcomes of propofol versus midazolam (± short-acting opioids) in patients undergoing colonoscopy.
Methods
We systematically searched Medline, Embase, and the Cochrane library (to July 30, 2018) for randomized controlled trials of colonoscopies performed with propofol versus midazolam (± short-acting opioids). We pooled odds ratios for cardiorespiratory outcomes using mixed-effects conditional logistic models. We pooled standardized mean differences (SMDs) for patient and endoscopist satisfaction and efficiency outcomes using random-effects models.
Results
Nine studies of 1427 patients met the inclusion criteria. There were no significant differences in cardiorespiratory outcomes (hypotension, hypoxia, bradycardia) between sedative groups. Patient satisfaction was high in both groups, with most patients reporting willingness to undergo a future colonoscopy with the same sedative regimen. In the meta-analysis, patients sedated with propofol had greater satisfaction than those sedated with midazolam (± short-acting opioids) (SMD, .54; 95% confidence interval [CI], .30-.79); however, there was considerable heterogeneity. Procedure time was similar between groups (SMD, .15; 95% CI, .04-.27), but recovery time was shorter in the propofol group (SMD, .41; 95% CI, .08-.74). The median difference in recovery time was 3 minutes, 6 seconds shorter in patients sedated with propofol.
Conclusions
Both propofol and midazolam (± short-acting opioids) result in high patient satisfaction and appear to be safe for use in colonoscopy. The marginal benefits to propofol are small improvements in satisfaction and recovery time.
Sedation used in colonoscopy can improve the experience for both patients and endoscopists. Globally, there is considerable variation in sedative practices.
Propofol—which, in many countries, is administered by an anesthesia professional whose sole responsibility is patient monitoring—is increasingly being used as an alternative to midazolam for endoscopy,
In the United States, where propofol is administered by anesthesia providers, anesthesia services for GI procedures, a surrogate for propofol use, increased from 14% of procedures in 2003 to 30% in 2009.
Anesthesia service use during outpatient gastroenterology procedures continued to increase from 2010 to 2013 and potentially discretionary spending remained high.
Given the increasing use of propofol globally, quantifying the true benefit and safety of propofol sedation for colonoscopy is important. Several meta-analyses have compared propofol with a group of alternative sedatives used for sedation during endoscopy, demonstrating improved patient satisfaction, decreased sedation and recovery times, and lower rates of cardiorespiratory adverse events with propofol use.
Similar risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy: a systematic review and meta-analysis.
However, the comparison between propofol and a group of dissimilar sedatives, with varying mechanisms of action and safety profiles, has been criticized.
More questions than answers: comparison of the risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy.
Some agents included in the comparator group, such as diazepam and meperidine, are no longer commonly used for reasons that may include their safety profiles. By combining a group of dissimilar sedatives for comparison with propofol, the true estimate of differences between propofol and commonly used alternative agents, known to be safe, may be concealed. Specifically, the benefits of propofol over the most common alternative, midazolam (± short-acting opioids), remains unclear. The objective of this systematic review and meta-analysis was to compare safety, satisfaction, and efficiency endpoints between colonoscopies performed with propofol and those performed with midazolam (± short-acting opioids).
Methods
The protocol for this systematic review was prospectively registered with PROSPERO (CRD41017059353).
Search strategy
In consultation with a senior information specialist, we developed a maximally sensitive search strategy to identify eligible studies (Appendix 1, available online at www.giejournal.org). We searched Medline, Embase, and the Cochrane Library, each from inception to July 30, 2018. This study was part of a larger project evaluating the use of sedation for both upper and lower endoscopy, and so our search was designed to identify randomized controlled trials (RCTs) comparing any sedatives used for GI endoscopy (not limited to colonoscopy). We supplemented search results with hand searching through the references of previously published meta-analyses.
Similar risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy: a systematic review and meta-analysis.
Our literature search necessitated the use of broad terms, and so we expected that many citations retrieved would not meet inclusion criteria. For this reason, we performed screening in 3 stages: title, abstract, and full text. At each stage, 2 reviewers independently assessed citations for eligibility using standardized electronic screening forms. All disagreements were resolved by discussion. We included RCTs comparing propofol (± short-acting opioids) and midazolam (± short-acting opioids) for elective colonoscopy only. We excluded studies reporting the results of emergency or upper/advanced endoscopic procedures and those that combined propofol or midazolam with longer-acting opioids (ie, meperidine), used uncommon formulations of either study drug (eg, fospropofol), compared alternative sedative combinations, or evaluated special populations (patients with cirrhosis, sleep apnea, obesity, patients ≥80 years of age, pregnant women, children). We also excluded conference abstracts, non–English language studies, and studies that did not report at least 1 of our outcomes of interest.
Data extraction
Data were extracted by 2 independent reviewers (F.D., B.M.) unblinded to study author and journal using electronic data extraction forms. Extracted data included study characteristics (author, journal, country, date of publication, sample size, number of endoscopists), patient characteristics (age, sex, comorbidity burden), sedative characteristics (sedative type, administrator, induction and supplemental doses, mean total dose), and outcomes (definitions, time of measurement, number of events per group). All disagreements between the 2 reviewers were resolved by discussion. We attempted to contact study authors for information not reported in published trials.
Outcomes
We used safety endpoints (cardiorespiratory events) as the primary outcomes for this study because these were most often the primary outcome reported in RCTs. We separately compared the number of patients in each group who experienced hypotension (defined as an intraprocedural systolic blood pressure <90 mm Hg, mean arterial pressure <60 mm Hg, or a ≥20% decrease in systolic blood pressure or mean arterial pressure from baseline), bradycardia (heart rate <50 beats per minute or ≥20% decrease from baseline), and hypoxia (arterial saturation <90%). These definitions were chosen because they were the most frequently used definitions in primary studies of this topic.
Secondary outcomes were satisfaction and efficiency measures. These included postprocedure and delayed (≥24 hours after procedure) patient satisfaction, endoscopist-reported satisfaction and procedure difficulty, time to sedation, total procedure time, and time to recovery and/or discharge. We did not include adenoma detection rate, cecal intubation, or withdrawal time as outcomes because they were infrequently reported in primary studies.
Quality assessment
Two reviewers (F.D., B.M.) independently assessed studies for methodologic quality using the Cochrane Risk of Bias Tool.
All disagreements were resolved by discussion. Because of the small number of included studies, we were unable to assess for publication bias.
Data synthesis
We first narratively synthesized the characteristics and results of included trials. Next, we assessed clinical heterogeneity to determine whether a meta-analysis could be performed.
To compare the number of patients who experienced cardiorespiratory events between sedative groups, we used mixed-effects conditional logistic models based on a noncentral hypergeometric distribution (an exact likelihood approach). Exact likelihood approaches avoid known limitations of the more commonly used meta-analytic models, which use normal approximations. These limitations include an underestimation of standard errors, disregard for correlations between effect estimates and standard errors, and the need to apply arbitrary corrective factors when zero cells are encountered.
The superiority of exact likelihood approaches is greatest in situations of rare outcomes, as was expected for these comparisons.
To compare satisfaction and efficiency outcomes, which were reported using different scales, we pooled standardized mean differences (SMDs) using random-effects models with restricted maximum likelihood estimators. For studies where the direction of the scale was opposite to the direction in most studies, we subtracted reported means from the maximum value of the scale; adjustments were not made to standard deviations.
We assessed statistical heterogeneity using the I2 statistic. We were unable to perform subgroup analyses or meta-regression to explore sources of heterogeneity because of the small number of studies. Where single studies appeared to contribute excessively to heterogeneity, we performed sensitivity analyses using the leave-one-out method to test the robustness of our findings after exclusion of these studies.
We also performed 2 additional sets of sensitivity analyses: (1) meta-analyses using only those studies that administered propofol monotherapy (ie, did not combine propofol with an opioid) and (2) meta-analyses excluding studies with patients who were American Society of Anesthesiologists (ASA) class >II, because these patients may be less likely to be administered midazolam in current practice.
In cases in which median values were reported by studies, we used the methods of Wan et al
to estimate means and standard deviations when required for meta-analysis. When studies only reported relevant outcomes in figures, we used DigitizeIt software (version 1.6.1, I. Bormann, Germany, https://www.digitizeit.de) to extract values from figures. All statistical analyses were performed using the meta and metafor packages in R.
Patient and public involvement
This research was done without patient and public involvement. Patients were not invited to comment on the study design and were not consulted to develop patient-relevant outcomes. The results of this study were presented to a multidisciplinary stakeholder panel that included public representatives. Patients and the public were not invited to contribute to the writing or editing of this document for readability or accuracy.
Results
Study selection
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for study selection is presented in Figure 1. Our search identified 9487 citations in Medline, Embase, and the Cochrane Library. After removal of duplicates, 6382 citations underwent title screening and 763 citations underwent abstract screening. We performed full-text reviews of 333 articles and identified 9 studies that met all inclusion criteria.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Because our original search was designed to be inclusive of studies of both upper and lower endoscopy and any sedative used, the most frequent reasons for exclusion at the full-text stage were for studies of only upper/advanced endoscopic procedures (n = 181) or studies that did not compare propofol (± short-acting opioids) with midazolam (± short-acting opioids) (n = 104).
Study and patient characteristics are presented in Table 1. Most studies included a single endoscopist who performed all procedures. Only 2 studies described insufflation techniques, both of which reported use of air insufflation.
Fentanyl was coadministered with midazolam in all but 1 study; propofol was administered with short-acting opioids (fentanyl, remifentanil, alfentanil) in 4 of 9 studies.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
We found large variation between studies in initial and supplemental doses of propofol and midazolam administered (Supplementary Tables 1 and 2, available online at www.giejournal.org). Mean total doses and administrators are presented in Table 2. Five studies reported administration of propofol by an anesthesiologist or nurse anesthetist; in 2 studies, propofol administration was patient-controlled. Mean total doses of propofol ranged from 98 to 442 mg. Administrators of midazolam included anesthesiologists, nurse anesthetists, gastroenterologists, fellows, nurses, and patients. Mean total midazolam doses ranged from 2.9 to 7.6 mg.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
A syringe containing a mixture of the study drugs (propofol/remifentanil and midazolam/fentanyl) was prepared by an anesthesiologist and loaded into the PCA pump. The propofol-remifentanil mixture contained 10 mg/mL propofol and 10 μg/mL remifentanil. The midazolam-fentanyl mixture contained .5 mg/mL midazolam and 12.5 μg/mL fentanyl
A syringe containing a mixture of the study drugs (propofol/remifentanil and midazolam/fentanyl) was prepared by an anesthesiologist and loaded into the PCA pump. The propofol-remifentanil mixture contained 10 mg/mL propofol and 10 μg/mL remifentanil. The midazolam-fentanyl mixture contained .5 mg/mL midazolam and 12.5 μg/mL fentanyl
NR, Not reported; PCA, patient-controlled anesthesia; —, not applicable.
∗ Mean doses represent the average dose for a 70-kg patient based on the mean dose/kg used in the study.
† A syringe containing a mixture of the study drugs (propofol/remifentanil and midazolam/fentanyl) was prepared by an anesthesiologist and loaded into the PCA pump. The propofol-remifentanil mixture contained 10 mg/mL propofol and 10 μg/mL remifentanil. The midazolam-fentanyl mixture contained .5 mg/mL midazolam and 12.5 μg/mL fentanyl
Most studies described appropriate randomization and concealed allocation processes (Supplementary Fig. 1, available online at www.giejournal.org). The most common source of bias was lack of blinding. Although patients were blinded in all but 1 study,
endoscopists and outcome assessors were infrequently blinded. Several studies demonstrated selective reporting, when certain outcomes described in the methods were not reported in the results (n = 4). Another frequent source of bias was the use of a single endoscopist with minimal description of experience or technique (n = 5).
Safety
Seven studies (n = 1301) reported hypotensive events in 109 patients. In the study by Eberl et al,
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
hypotensive events requiring medical intervention (decreasing sedative level or administration of phenylephrine) were higher in the propofol group. No other studies reported hypotensive events that required medical intervention. There was no statistically significant difference in the number of patients who experienced hypotension between propofol and midazolam groups (odds ratio, 1.63; 95% confidence interval [CI], .37-7.15) (Fig. 2A); however, we encountered considerable heterogeneity (I2 = 78%). In sensitivity analyses, heterogeneity was found to be largely driven by a single study. After exclusion of this study,
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
results remained nonsignificant, but heterogeneity was greatly reduced (I2 = 5%) (Supplementary Table 3, available online at www.giejournal.org). Results were unchanged in sensitivity analyses of studies with propofol monotherapy and in studies including only ASA class I to II patients (Supplementary Table 4, available online at www.giejournal.org).
Figure 2Pooled odds ratios for patients experiencing cardiorespiratory events. Studies are sorted by mean propofol dose (lowest to highest). A, Hypotension. B, Hypoxia. C, Bradycardia between patients sedated with propofol versus midazolam. CI, Confidence interval.
Seven studies (n = 1301) reported 102 patients who experienced hypoxic events. Twenty-six of these patients were enrolled in trials that did not routinely administer supplemental oxygen to all patients undergoing colonoscopy or did not report whether oxygen was routinely administered. Studies variably reported the need for intervention because of hypoxia. Bastaki et al
reported that 2 patients sedated with propofol and no patients sedated with midazolam required intervention by the anesthesiologist (2 breaths of 100% oxygen and facemask), and Schroeder et al
reported that 3 patients (2.4%) sedated with propofol and 2 patients (1.5%) sedated with midazolam/fentanyl required airway interventions (jaw support or oral/nasal airways). Furthermore, Kostash et al
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
hypoxic patients sedated with midazolam could be stimulated verbally, whereas those sedated with propofol/alfentanil required tactile stimulation (jaw thrust, chin lift). In contrast, Ulmer et al
reported that 5 patients in the midazolam/fentanyl group and no patients in the propofol group required intervention for hypoxia or apnea. There was no significant difference in the odds of patients experiencing hypoxia between sedative groups (odds ratio, .44; 95% CI, .10-1.93); however, heterogeneity was large (I2 = 77%) (Fig. 2B). In the leave-one-out analysis, the greatest heterogeneity was found to arise from the study by Padmanabhan et al,
which accounted for 22 of 26 episodes (84.6%) of hypoxia in studies that did not routinely administer or did not report whether patients routinely received supplemental oxygen. Results remained nonsignificant after exclusion of this study (Supplementary Table 3). Results were unchanged in a sensitivity analysis of studies with propofol monotherapy and in studies including only ASA class I to II patients (Supplementary Table 4).
In 5 studies (n = 1154), 50 patients experienced bradycardia. Fewer episodes required intervention with atropine. Fanti et al
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
each reported 1 patient in the midazolam and propofol groups, respectively, who required atropine for a heart rate <50 beats per minute. The difference in bradycardia between groups was not statistically significant (odds ratio, 1.12; 95% CI, .61-2.04; I2 = .1%) (Fig. 2C). Results were unchanged in a sensitivity analysis of studies with propofol monotherapy and in studies including only ASA class I to II patients (Supplementary Table 4).
Patient and endoscopist satisfaction
Patient satisfaction was assessed immediately after colonoscopy in 7 studies (n = 1338). An additional study asked patients questions related to satisfaction but did not assess global satisfaction and therefore did not contribute to assessment of this outcome.
Differences in satisfaction reported by individual studies were small: In the largest study (n = 600), authors reported a 2.0% difference in satisfaction scores in favor of propofol (mean score 4.8 for propofol group and 4.7 for midazolam group on a 5-point scale).
In the meta-analysis, we found higher patient satisfaction with propofol versus midazolam (SMD, .54; 95% CI, .30-.79) (Fig. 3); however, heterogeneity was large (I2 = 75%). In the sensitivity analysis, no single study was found to contribute excessively to heterogeneity or to unduly influence the results (Supplementary Table 3). Results were unchanged in a sensitivity analysis of studies with propofol monotherapy and in studies including only ASA class I to II patients (Supplementary Table 4).
Figure 3Pooled standardized mean differences for immediate patient satisfaction outcomes. Studies are sorted by mean propofol dose administered (lowest to highest). SD, Standard deviation; CI, confidence interval.
Delayed assessments of patient satisfaction (≥24 hours after colonoscopy) were made in only 3 studies. One study reported no differences in satisfaction scores at delayed assessment (9.6/10 for both groups).
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Notably, although these 2 studies used the same scale for assessment (100-mm visual analog scale), the differences in satisfaction between patients in the arms of the 2 studies were dissimilar (9.6 and 18.9 points, respectively). Results were not pooled because of considerable heterogeneity.
Four studies asked patients about their feelings toward future colonoscopies. Willingness to undergo future procedures with the same sedative regimen was high in both groups, albeit slightly higher in the propofol groups (Supplementary Table 5, available online at www.giejournal.org). In the largest study (n = 600), 98.7% of patients in the propofol group and 94.0% of patients in the midazolam group reported they would recommend the sedative they received to others.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
1 patient could not tolerate the procedure with midazolam and was therefore administered propofol. This patient had a history of chronic opioid use for pain.
Endoscopists’ reports of procedure difficulty were provided in 3 studies. We did not find a statistically significant difference in procedure difficulty in the meta-analysis (SMD, –.10; 95% CI, –.36 to .16; I2 = 19%) (Fig. 4A). Results were unchanged in a sensitivity analysis of studies with including only ASA class I to II patients (Supplementary Table 4). Endoscopist satisfaction was adequately reported for a meta-analysis in 3 studies (n = 278). Differences between groups within studies were small, ranging from 4% to 11% of scale length, but statistically significant in the meta-analysis, favoring the use of propofol (SMD, .59; 95% CI, .34-.85; I2 = 11%) (Fig. 4B).
Figure 4Pooled standardized mean differences for endoscopist-reported outcomes. Studies are sorted by mean propofol dose administered (lowest to highest), (A) procedure difficulty, and (B) endoscopist-reported satisfaction for colonoscopies performed on patients sedated with propofol versus midazolam. SD, Standard deviation; CI, confidence interval.
Time to achieve adequate sedation was reported in 4 studies; however, sedation targets were variable. Two studies did not report how sedation adequacy was measured.
Absolute differences in time to achieve sedation ranged from 35 seconds to 4 minutes, 12 seconds. Because of the heterogeneity in sedation targets, results were not pooled.
Procedure time was reported in 7 studies. Among patients sedated with propofol, procedure time ranged from 8.7 to 23.0 minutes; with midazolam, procedure time ranged from 8.8 to 24.4 minutes. Absolute differences in procedure time across studies ranged from 1 minute, 6 seconds shorter with midazolam
In the meta-analysis, there was a negligible difference in procedure time between groups (SMD, .15; 95% CI, .04-.27; I2 = 0%) (Fig. 5A). Results were unchanged in a sensitivity analysis of studies with propofol monotherapy and in studies including only ASA class I to II patients (Supplementary Table 4).
Figure 5Pooled standardized mean differences for efficiency outcomes. Studies are sorted by mean propofol dose administered (lowest to highest), (A) procedure time, and (B) recovery and/or discharge time for patients sedated with propofol versus midazolam. SD, Standard deviation; CI, confidence interval.
Recovery and/or discharge time was reported in 8 studies. We found considerable differences in the definitions used for recovery and criteria for discharge between studies (Supplementary Table 6, available online at www.giejournal.org). Recovery and/or discharge time ranged from 1.1 to 43.3 minutes for patients sedated with propofol and 5.0 to 61.0 minutes for patients sedated with midazolam. Absolute differences in recovery time ranged from 1 minute, 24 seconds shorter with midazolam
; the median difference was 3 minutes, 6 seconds shorter with propofol. In the largest study (n = 600), patients sedated with propofol had a 30-second shorter recovery time, on average, than patients sedated with midazolam.
In the meta-analysis, we found a small but statistically significant difference in discharge and/or recovery time favoring propofol (SMD, .41; 95% CI, .08-.74) with considerable heterogeneity (I2 = 86%) (Fig. 5B); this difference was not seen in the sensitivity analysis including only those studies that administered propofol monotherapy (Supplementary Table 4). In the leave-one-out sensitivity analysis, no single study was found to excessively drive heterogeneity or influence the effect estimate (Supplementary Table 3).
Discussion
Our study combines the results of 9 RCTs and 1427 patients to compare safety, satisfaction, and efficiency outcomes in colonoscopy with propofol versus midazolam (± short-acting opioids). We did not find any statistically significant differences in cardiorespiratory outcomes between sedative agents. Our assessment of satisfaction and efficiency outcomes found marginal benefits to the use of propofol. Patient satisfaction was higher with propofol; however, differences within studies were often small. Patients sedated with propofol had similar procedure times as those sedated with midazolam (± short-acting opioids). We found decreases in recovery and/or discharge time when propofol was used; however, the absolute differences in time saved varied considerably across studies and were often small, with the largest study reporting a difference of 30 seconds.
Our findings are mostly concordant with previous meta-analyses that compare propofol with traditional sedatives in GI endoscopy. Similar to other studies, we did not find differences in procedure time with the use of propofol.
Similar risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy: a systematic review and meta-analysis.
a finding that we were unable to replicate, likely related to their inclusion of multiple dissimilar sedatives in the traditional sedative group. If agents other than midazolam were associated with high rates of cardiorespiratory events, their inclusion in the traditional sedative group may have made propofol appear to be superior despite no difference between propofol and midazolam.
Most studies involved only a single endoscopist; the results of these studies are likely highly dependent on the technique of the endoscopist. In a cross-sectional analysis of factors associated with pain in colonoscopy, after adjustment for modifiable and nonmodifiable factors associated with pain, there were 11-fold differences in patient-reported pain during colonoscopy and 23-fold differences in pain after colonoscopy between endoscopists.
This large variability highlights the relationship between endoscopist and patient experience in colonoscopy; sedative choice may be less important when optimal technique, minimizing patient pain, is used, explaining how sedation-free colonoscopies are tolerable and frequently performed in many countries.
These findings also demonstrate the limited generalizability of the RCTs included in this review given the few endoscopists included.
Several variations on colonoscopy technique have been proposed specifically to reduce patient pain, independently of sedatives, including alterations in method of insufflation. Only 2 studies included in this review provided details on insufflation technique, both reporting the use of air insufflation.
Multiple meta-analyses demonstrate that carbon dioxide, which is rapidly absorbed, is associated with less pain compared with air when used for insufflation.
Carbon dioxide insufflation vs conventional air insufflation for colonoscopy: a systematic review and meta-analysis of published randomized controlled trials.
More recently, water infusion techniques (exchange or immersion) have also been evaluated. When compared with air insufflation, water infusion is associated with lower pain scores and fewer requests from patients for on-demand sedation.
In a meta-analysis comparing water exchange with a combined group of air and CO2 insufflation, water exchange was also associated with a higher patient willingness to undergo repeat procedures.
Recent network meta-analyses comparing air insufflation, CO2 insufflation, water exchange, and water immersion techniques demonstrated that air insufflation is associated with the highest pain scores and water exchange with the lowest pain scores.
provides a standardized approach to training in sedation administration that can help ensure appropriate and safe sedative practices for endoscopy. This curriculum highlights the importance of endoscopist training in drug pharmacokinetics, sedative selection, assessment of levels of sedation and appropriate titration of sedatives to desired levels of sedation, and identification of patients who may be at increased risk of cardiorespiratory adverse events, suggesting the need for an anesthesiologist.
Our review compares the 2 most common sedative agents used for colonoscopy. Whereas previous reviews were criticized for comparing propofol with a group of dissimilar agents, we limited our comparison to midazolam (± short-acting opioids) and retained strict inclusion criteria to ensure comparability between studies. Although we encountered significant statistical heterogeneity for certain outcomes, our findings were robust in sensitivity analyses. Our review does, however, have limitations. Our results need to be interpreted in the context of the clinical heterogeneity between studies. We found considerable variability in sedative doses administered, which may have contributed to the differences in the number of patients experiencing cardiorespiratory events. We did not perform a meta-regression using sedative doses because patient-level data were unavailable; performing a meta-regression at the study level using aggregated patient-level characteristics could lead to the ecologic fallacy whereby the results seen at the study level may not reflect the results that would be seen at the patient level.
Future work is needed to assess whether dose will impact comparisons of procedure efficiency and satisfaction. Included studies also used variable outcome definitions, outcome assessors, and had different discharge policies, which could have affected certain measurements, such as recovery and/or discharge time. Quality measures, such as adenoma detection rate, cecal intubation rate, and withdrawal time, were infrequently reported in the included studies and therefore could not be evaluated in this review. Few studies used blinded outcome assessors, and study quality was variable. Also, few studies reported insufflation technique (air vs CO2 vs water). This is important because the results of older studies may not reflect current practice, where CO2 is increasingly used. Because of differences in measurement scales, we were required to pool studies using SMDs, which may have overinflated the importance of small differences. We were unable to perform subgroup analyses or meta-regression to explore sources of heterogeneity because of the small number of studies included; however, our conclusions did not change when heterogeneity was reduced in leave-1-out sensitivity analyses. We did not examine longer-term (ie, 30-day) outcomes because they were uncommonly reported in RCTs; however, we comprehensively compared outcomes that are highly considered when deciding on sedative agent, including multiple measures of safety, satisfaction, and efficiency.
Adoption of novel therapies typically requires demonstration of value for money. Based on the number of colonoscopies performed in the United States in 2002, it was estimated that if sedation for all colonoscopies was provided by anesthesiologists, then assuming reimbursement at the mean Medicare allowable charge of $106 per case, anesthesiologist fees for colonoscopy would amount to over $1.5 billion.
Although sedation administration by nurse anesthetists or other trained individuals could attenuate these costs, in some jurisdictions, propofol administration is limited to anesthesiologists and other physicians trained in sedation. In addition to cost, use of anesthesia resources may also require coordination on the part of the endoscopy team, which may prolong wait times for procedures. Our study demonstrates improved patient and endoscopist satisfaction and shorter recovery and/or discharge time with the use of propofol versus midazolam; however, absolute differences in satisfaction and efficiency scores across studies were highly variable and often small. The variability between studies highlights the need for future studies to include a larger number of endoscopists to improve generalizability. Alternative less-costly methods to improve patient experience, such as a focus on optimal technique, CO2 insufflation, and the use of water infusion, may also attenuate the satisfaction and efficiency benefits seen for propofol. Greater efforts in improving and standardizing technique among endoscopists could provide large benefits at lower costs for patients undergoing colonoscopy and should be further explored.
Acknowledgments
We thank information specialists Bridget Morant and Teruko Kishibe at the Scotia Bank Health Sciences Library and Li Ka Shing Knowledge Institute, St Michael’s Hospital, for assisting with development of the search strategy.
Appendix 1. Literature search strategy
The search strategy used in Medline is presented here. Identical searches were conducted in Embase and the Cochrane library.
Database: Ovid Medline epub ahead of print, in-process and other non-indexed citations, and Ovid Medline <1946 to Present>
3 (Endoscop* adj3 (gastro* or intestin* or mucosal resection* or submucosal dissection* or mucous membrane resection* or transanal or anal or capsule* or bowel* or colon* or sigmoid* or duodenum* or esophag* or stomach* or rectum* or sphincter* or papillotom* or ultrasound* or ultrasonograph*)).tw,kf. (42602)
4 Balloon enteroscop*.tw,kf. (1141)
5 Colonoscop*.tw,kf. (24869)
6 Sigmoidoscop*.tw,kf. (4405)
7 Proctosigmoidoscop*.tw,kf. (303)
8 Duodenoscop*.tw,kf. (1209)
9 Strip biops*.tw,kf. (98)
10 Esophagoscop*.tw,kf. (2025)
11 Gastroscop*.tw,kf. (6291)
12 Proctoscop*.tw,kf. (829)
13 Esophagoduodenoscop*.tw,kf. (35)
14 Oesophagoduodenoscop*.tw,kf. (8)
15 Endosonograph*.tw,kf. (2545)
16 cholangiopancreatograph*.tw,kf. (8844)
17 or/1-16 (132927)
18 Propofol/ (12857)
19 Propofol Infusion Syndrome/ (2)
20 NAAP.tw,kf. (46)
21 (Ampofol or Anepol or Anesia or Anesvan or Aquafol or Diprifusor or Diprivan or Diprofen or Diprofol or Disoprivan or Disoprofo or Dyprofol or Dypryvan or Emifol or Fresofol or Gobbifol or Indofol or Ivofol or Lexofol or Lipofol or Lipuro or Neorof or Nirfol or Pofol or Proanes or Profast or Propofol* or Propovan or Propoven or Provive or Recofol or Safol or "Spiva with MCT-LCT" or Trivam or Troyppofol or Ufol or "2,6 Diisopropylphenol" or "2,6-Bis(1-methylethyl)phenol" or "ICI 35 868" or "ICI35 868" or ICI35868 or "ICI 35868").tw,kf. (17711)
22 Analgesics, Opioid/ (34164)
23 exp Fentanyl/ (14370)
24 Morphine/ (36164)
25 exp Meperidine/ (5761)
26 exp Benzodiazepinones/ (35140)
27 (Opioid* or opiate* or Benzodiazepinone* or Anthramycin* or Devazepide* or "MK 329" or MK329 or "L 364 718" or L364718 or "L364 718" or Medazepam*).tw,kf. (88053)
28 (Abstral or Acref or Actiq or ApoFentanyl Matrix or Breakyl or CoFentanyl or Denpax or Dolforin or Duragesic or Durasic or Durogesic or Durotep MT or Dyurohezik or Effentora or Fantamax or Fencino or Fent or Fenta or Fentaderm or Fentadermal or Fentadur or Fentalis or Fentamax or Fentanest or Fentanila or Fentanilo or Fentanyl or Fentax or Fentora or Fentos or Filtaten or Instanyl or Ionsys or Lazanda or Leptanal or Lunaldin or Matrifen or Mezolar Matrix or MylanFentanyl or Onsolis or One Duro or Opifen or Opiodur or Osmanil or PecFent or Pentyl or Phentanyl or PMSFentanyl or RANFentanyl or Recivit or Sublimaze or Subsys or Tanyl or TevaFentanyl or Trofentyl or Troyfentyl or Vellofent or Victanyl or "R 4263" or R4263).tw,kf. (18258)
29 (FastFen or Fentafienil or Sufenta or Sufental or Sufentanil or Sufentil or Sulfentanil or Sulfentanyl or "R 30730" or R30730).tw,kf. (2336)
30 (Remifentanil Hydrochloride or Remiva or Restinil or Rui Jei or Sagal or Ulremif or Ultiva or GI87084B or "GI 87084B").tw,kf. (46)
31 (Alfast or Alfenil or Alfenta or Alftentanil or Alfentanyl or Fanaxal or Fentalim or Limifen or Rapifen or "R 39209" or R39209).tw,kf. (93)
32 (Anamorph or Astramorph or AVINza or Contalgin or Depolan or Dimorf or Dolcontin or Doloral or Doltard or Duramorph or "Infumorph 200" or "Infumorph 500" or Kadian or Kapanol or La Morph or "M-Elson" or "M.I.R." or "M.C.R." or Morfan or Morfex or Morficontin or Morgesic or Morphanton or Morphia or Morphgesic or Morphine* or "M.O.S. 10" or "M.O.S. 20" or "M.O.S. 30" or "MS Contin" or "M.O.S.-SR" or "M.O.S.-Sulfate" or Moscontin or "MS Mono" or "MS-IR" or "MST Continus Retard" or "NovoMorphine SR" or Oramorph or "P Guard" or Pacif or PMSMorphine or "RA Morph" or
ratioMorphine or Rumorf or SMorphine or SandozMorphine or Sevredol or Statex or TevaMorphine or Vendal or Vermor or Zomorph or "SDZ 2020 250" or "SDZ 202250" or "SDZ202 250" or SDZ202250).tw,kf. (86494)
33 (Aldolan or Clopedin or Cluyer or Deme or Demero or Demerol or Dolantin or Dolantina or Dolantine or Dolargan or Dolcontral or Dolestine or Dolin or Doloblok or Dolosal or Dolsin or Dornot or Isonipecain or Lidol or Lydol or Meperdol or Meperidol or Meperidine or Operidine or Pethidin or Pethidine or Petidin or Petidina or Promedol or Verpat).tw,kf. (6056)
34 (Demerol Hydrochloride or Isonipecaine Hydrochloride or Pethidine Hydrochloride).tw,kf. (51)
35 exp Benzodiazepines/ (61709)
36 Benzodiazepine*.tw,kf. (31031)
37 (Aceprax or Actazolam or Adax or Alcelam or Alnax or Alpax or Alpralid or Alpraline or Alpranax or Alprax or Alpraz or ALPRAZolam or Alpra Zolam or Alprocontin or Alprox or Altrox or Alzam or Alzax or Alzolam or Ansiolit or Antonil or ApoAlpraz or Apraz or Aprazo or Asolan or Axal or Azor or Cassadan or Constan or Dixin or Esparon or Farmapram or Feprax or Frontal or Frontin or Getzpraz or Helex or Irizz or Jamp-Alprazolam or Kalma or Kinax or Manorest or Marzolam or Misar or Moderex or Mylan-Alprazolam or Nalion or Nat Alprazolam or Neupax or Niravam or NovoAlprazol or Nu Alpraz or NuAlpraz or Pacyl or Pazolam or Pharnax or Prazin or Prazol or Prazovex or Prinox or Ralozam or Renax or Riva Alpraz or Solanax or Soxietas or Sublimex or "Tafil D" or Tazun or TevaAlprazolam Xanax or Toranax or Trankimazin Retard or Tranquinal or Tricalma or Valeans or Xanacine or Xanagis or Xanax or Xanor or Xiety or Xolam or Zacetin or Zanapam or Zolam or Zolarem or Zolastin or Zoldac or Zolgen or Zopax or Zotran or Zypraz or Zyren or D 65MT or D65MT or "U 31 889" or "U31 889" or "U31889").tw,kf. (95927)
38 (Akamon or Anxyl or Anxyrex or ApoBromazepam or Benedorm or Brazepam or BromaLich or Bromazanil or Bromaze or Bromazepam or Bromazin or Bromidem or Brominter or Durazanil or Gityl or Lectopam or Lekotam or Lenitin or Lexatin or Lexaurin or Lexavrin or Lexilium or Lexomil or Lexopam or Lexostad or Lexotan or Lexotanil or Lexotanol or Lexzepam or Nervan or Notorium or Octanyl or Otedram or Quietiline or Rem or Sedamax or Seniran or Somalium or Tenil or Teva Bromazepam or Totasedan or Tredum or Zepam or "RO 5 3350" or "RO 53350").tw,kf. (13013)
39 (Benpine or Cetabrium or "Chlordiazepoxid L.F.M." or ChlordiazePOXIDE or Chlordiazepoxidum or Chlozepid or Cozep or Dipoxido or Elenium or Eposal or Equilibrium or Huberplex or Klopoxid or Klorpo or Liberty or Librium or Mebrium or Methaminodiazepoxide or "Nova-Pam" or "O.C.M." or Oasil or Paxium or "Peast C" or Psicodex or Radepur or Retcol or Risolid or Seren or Sophiamin or Trakipearl or "7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide" or "7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide").tw,kf. (121679)
40 (Aedon or Anxirloc or ApoClobazam or Castilium or Clobam or Clobamax or Clobator or Clobazam or Clofritis or Cosium or DomClobazim or Frisium or Grifoclobam or Karidium or Keolax or Lucium or Nebium or Noiafren or NovoClobazam or Onfi or Perizam or PMSClobazam or Sedzam or Sentil or Tapclob or Urbanil or Urbanol or Urbanyl or Veaclob or "HR 376" or HR376).tw,kf. (872)
41 (Aklonil or Amotril or Antaspan or Antelepsin or Anzataz or ApoClonazepam or Clonapam or Clonapilep or Clonaril or Clonatril or Clonatryl or ClonazepamR or Clonazepam or Clonazepamum or Clonex or Clonium or Clonofax or Clonopam or Clonotril or Clozapam or Clozer or Convolsil or Coquan or Dom-Clonazepam or Dom-ClonazepamR or Iktorivil or Jing Kang or Kenoket or KlonoPIN or Kriadex or Leptic or Lonazep or Mylan-Clonazepam or Naza or Neuryl or Paxam or "PHL-Clonazepam"
or "PHL-ClonazepamR" or PMSClonazepam or PMSClonazepamR or Povanil or PROClonazepam or ratioClonazepam or Ravotril or Riklona or RivaClonazepam or Rivatril or Rivopam or Rivoram or Rivotril or SandozClonazepam or TevaClonazepam or Valpax or Xetril or Zepanc or Zymanta or ZYMClonazepam or "Ro 5 4023" or "RO 54023").tw,kf. (3373)
42 (Ansiopax or Ansiospaz or Anxidin or Calner or Cloranxen or Clorazepate or Clozene or Flulium or Mendon or Nansius or Nivelin or Pazidium or Sanor or Serene or Tencilan or Trancon or Transene or Tranxen or Tranxene or Tranxilene or Tranxilium or UniTranxene or Zetran5 or "4306 CB" or 4306CB).tw,kf. (457)
43 (Aliseum or Alsaval or Anlin or Ansiolin or Antenex or Apaurin or Apodiazepam or Apozepam or Assival or Azepam or Azepan or Baogin or Benzopin or Bio Diazepam or Calmpose or Calmvita or Cercine or Ceregulart or Compaz or Condition or "D-Pam" or Dialag or Diapam or Diapine or Diapo or Diastat or Diazem or Diazemuls or Diazepam or Diazepan or Diazepeks or Dipezona or Dizam or Dizep or Doval or Dupin or DZP or Elcion CR or Euphorin or Evalin or Faustan or Gewacalm or Horizon or Ifa Fonal or Kratium or Lembrol or Melode or Nercon or Nivalen or Nixtensyn or Noan or Normabel or Novo Dipam or Orinil or Ortopsique or Paceum or Pacitran or Pamizep or Paranten or Pax or Paxum or "Placidox 10" or "Placidox 2" or "Placidox 5" or Plidan or "PMS Diazepam" or Propam or Prozepam or Psychopax or Radizepam or Ranzepam or Relanium or Relium or Remedium or Renborin or Sedium or Seduxen or Serenzin or Sibazon or Sincronex or Sipam or Solina or Stedon or Stesolid or Stesolid Rectal Tube or Sunzepam or Sybazon or Talema or Tranquirit or Valaxona or Valdimex or Valiquid or Valisanbe or Valium or Valpam or Valzepam or Vanconin or Vatran or Vexepam or Vodin or Zopam or
44 (Domnamid or Esilgan or Eslam or Estalin or Estazolam or "Eszo 2" or Eurodin or Kainever or Kinzolam or Noctal or Nuctalon or ProSom or Sedarest or Somnatrol or Tasedan or "D 40TA" or D40TA).tw,kf. (201)
45 (Demethox or "Ethylis Loflazepas" or Ethyl Loflazepate or "Loflazepato de etilo" or Meilax or Ronlax or Sukarnase or Victan or "CM 6912").tw,kf. (39)
46 (Etizola or Etizolam or Etizolamum or Depas or Dezolam or Palgin or Pasaden or Sedekopan or "Y 7131" or Y7131).tw,kf. (100)
47 (Anexate or Antabenz or Anzenil or Fadaflumaz or Flumage or Flumazen or Flumazenil or Flumazepil or Flumil or Flunexate or Flunexil or Flunil or Fluoxem or Lai Yi or Lanexat or Romazicon or "RO 15 1788" or "RO15 1788" or RO151788).tw,kf. (4125)
48 (Absint or Bibittoace or Darkene or Fluni or Flunibeta or Flunimerck or Fluninoc or Flunipam or Flunita or Flunitrazepam or Flunitrazepamum or "flunizep von ct" or Flupam or Fluridrazepam or Fluscand or Fluserin or Flutrace or Flutraz or Guttanotte or Hipnosedon or Hypnocalm or Hypnodorm or Hypnor or Ilman or Insom or Ipnopen or Narcozep or Neo Nifalium or Nervocuril or Nilium or Noriel or Parsimonil or Primum or Rohipnol or Rohydorm or Roipnol or Ronal or Rohypnol or Sedex or Silece or Somnubene or Stedonil or Valsera or Vulbegal or Zetraflum or "RO 5 4300" or "RO 54200" or RO54200).tw,kf. (4421)
49 (Aluctin or ApoFlurazepam or BioFlurazepam or Dalmadorm or Dalmane or Dalpam or Dormodor or Florapam or Flunox or Fluralema or Fluraz or Flurazepam or Fluzepam or Fordrim or Insumin or Manlsum or Nergart or Noctosom or PMSFlurazepam or Slipam or Somlan or Som Pam or Staurodorm).tw,kf. (927)
50 (Abinol or Ansilor or Anta or Anxiar or Anxira or Anzepam or Aplacasse or ApoLorazepam or Aripax or Ativan or Bonatranquan or Control or Donix or Duralozam or Emotival or Idalprem or Larpose or Laubeel or Lauracalm or Lonza or Lopa or Lopam or Lora or Lorabenz or Lorafen or Loram or Lorans or Loranxil or Loravan or Lorax or Loraxen or Lorazep or Lorazepam or Lorazin or Lorenin or Loridem or Lorivan or Lorsilan or Lozicum or Merlit or Merlopam or "Nervistop L" or Neuropam or Novhepar or NovoLarazem or Nu Loraz or NuLoraz or Orfidal or Renaquil or Rilex or Sedatival or Sedicepan or Sidenar or Silence or Sinestron or Somagerol or Sonamin or Stapam or Tavor or Temesta or Titus or Tolid or Tranqipam or Trapax or Trapex or Vigiten or Zora or "WY 4036" or WY4036).tw,kf. (2166363)
51 (Ansilan or Celium or Medazepam or Medazine or Narsis or Nobrium or Rudotel or Rusedal or "RO 5 4556" or RO54556).tw,kf. (236)
52 (Anespar or Buccolam or Dalam or Domi or Doricum or Dormicum or Dormicum or Dormid or Dormilat or Dormizol or Dormonid or Fulsed or Hipnoz or Hypnofast or Hypnovel or Hypozam or Ipnovel or Midacum or Midazo or Midazolam or Midazol or Midolam or Midozor or Miloz or Mizolam or Nok or Omida or Relacum or Sedacum or Sedoz or Sopnil or Uzolam or Versed or Verzol or "Ro 21 3981" or "Ro 213981").tw,kf. (12756)
53 (Alodorm or Apodorm or Arem or Cerson or Dumoild or Dormalon or Dormo-Puren or Eatan or Epam or Eunoctin or Hipnax or Hypnol or Hypnotex or Imadorm or Imeson or Insomin or Mogadon or Mozepam or Nitavan or Nitrados or Nitrapan or Nitravet or Nitrazadon or Nitrazep or Nitrazepam or Nitredon or Nitrodiazepam or Nitrom or Noctin or Novanox or Numbon or Octon or Onirema or Ormodon or Paxadorm or Radedorm or Remnos or Rohypnol or Serenade or Sleepin or Somnite).tw,kf. (1199)
54 (Calmday or Dealkylprazepam or Demethyldiazepam or Deoxydemoxepam or Desmethyldiazepam or "N-Descyclopropylmethylprazepam" or "N-Descyclopropylmethyl-Prazepam" or Nordazepam or Nordazepamum or "N-Destrifluoroethylhalazepam" or "N-Desalkylhalazepam" or Nordaz or Nordiazepam or Norprazepam or "Tranxilium N" or Vegesan or "RO 5 2180" or "Ro 52180").tw,kf. (722)
55 (Adumbran or Alepam or Alopam or Anastil or Anoxa or Anxiolit or ApoOxazepam or BioOxazepam or Enidrel or Limbial or Medopam or Murelax or Nesontil or Noripam or Novoxapram or Nozepam or Oksazepam or Opamox or OxPam or Oxpram or Oxazepam or Praxiten or Purata or Selars or Serax or Serefar or Serenal or Serepax or Seresta or Simazepan or Sobril or Suxidina or Tazepam or Tranquo or Vaben or Youfei).tw,kf. (1449)
56 (Cevanil or Demetrin or Droxol or Gastropiron or Gastrotsepin or Gastrozepin or Gastrozepina or Hastrotsepin or Lysanxia or Pin or Piren basan or Pirenbasan or Pirenzepin or Pirenzepine or Pyrenzepine or Reapam or Stomazepin or Ulcoprotect or Ulgescum or "LS 519" or LS519).tw,kf. (15470)
57 (Centrac or Centrax or Demetrin or Equipaz or Lysanxia or Mono Demetrin or Pozapam or Prazene or Prazepam or Reapam or Verstran).tw,kf. (194)
58 (Doral or Dorme or Dormyl or Prosedar or Quazepam or Quazium or Quiedorm or "Sch 16134" or Sch16134).tw,kf. (152)
59 (Dasuen or Euhypnos or Euipnos or Hydroxydiazepam or Levanxol or Mabertin or Methyloxazepam or Nocturne or Normison or Normitab or Nortem or NovoTemazepam or NuTemazepam or Oxydiazepam or Planum or "PMS-Temazepam" or "Pronervon T" or Remestan or Restoril or Signopam or Signopharm or Temador or Temaze or Temazepam or Temazin or Temtabs or Tenox or "RO 5 5345" or Ro55345 or "SAH 47 603" or "SAH 47603" or SAH47603 or "WY 3917" or WY3917).tw,kf. (2032)
60 (Grandaxin or Seriel or Grandaxin or Bydaxin or Clasopan or Cobandaxin or dextofisopam or Emandaxin or Grandaxin or Granpam or Hymidin or levotofisopam or Myronin or Tofiel or Tofilsin or Tofisopam or Tofisopamum or Tofis or Tofizopam or Tolbanasin or Tronheim or Tsurubel or Grandaxin or Grandaxin or "EGYT 341").tw,kf. (125)
61 (Arring or Balidon or Drowsy or Halciion or Halcion or Hanlexin or Hypam or Inzolam or Novidorm or Nuctane or Rilamir or Somese or Songar or Trialam or Trilam or Triram or Triazolam or Trycam or Zolmin or "U 33 030" or "U33 030").tw,kf. (2591)
62 or/18-61 (2974422)
63 17 and 62 (13207)
64 Randomized Controlled Trials as Topic/ (109892)
65 randomized controlled trial/ (448635)
66 Random Allocation/ (89868)
67 Double Blind Method/ (143337)
68 Single Blind Method/ (23784)
69 clinical trial/ (508150)
70 clinical trial, phase i.pt. (17995)
71 clinical trial, phase ii.pt. (29018)
72 clinical trial, phase iii.pt. (13142)
73 clinical trial, phase iv.pt. (1406)
74 controlled clinical trial.pt. (91926)
75 randomized controlled trial.pt. (448635)
76 multicenter study.pt. (219272)
77 clinical trial.pt. (508150)
78 exp Clinical Trials as topic/ (304660)
79 or/64-78 (1192582)
80 (clinical adj trial$).tw. (288378)
81 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. (153107)
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Supplementary Table 4Sensitivity analyses pooling results of studies that administered propofol monotherapy only and studies including ASA class I-II patients only
Results of studies that administered propofol monotherapy only
Results of studies that included ASA class I-II patients only
Although this result was statistically significant, the effect size was negligible.
Recovery time
–.25 (95% CI, –.56 to .07)
–.45 (95% CI, –.70 to –.20)
Studies excluded in sensitivity analysis of propofol monotherapy only: Eberl et al, Fanti et al, Kostash et al, and Mandel et al. Studies excluded in sensitivity analysis of ASA class I-II patients only: Eberl et al, Mandel et al, Padmanabhan et al, and Schroeder et al.
ASA, American Society of Anesthesiologists.
∗ Although this result was statistically significant, the effect size was negligible.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Patients were given 3 options: yes, no, or undecided. Of these, 36% of patients in the propofol group were undecided and 59% of patients in the midazolam group were undecided.
Patients were given 3 options: yes, no, or undecided. Of these, 36% of patients in the propofol group were undecided and 59% of patients in the midazolam group were undecided.
Patients asked if they would recommend the sedative that they received to others, %
300
98.7
300
94.0
∗ Patients were given 3 options: yes, no, or undecided. Of these, 36% of patients in the propofol group were undecided and 59% of patients in the midazolam group were undecided.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Full recovery (heart rate and blood pressure within 20% of baseline, oxygen saturation >90% on room air, ability to stand at bedside without assistance), able to drink liquids, subjectively judged as stable
OAA/S, Observer’s Assessment of Alertness and Sedation score.
Anesthesia service use during outpatient gastroenterology procedures continued to increase from 2010 to 2013 and potentially discretionary spending remained high.
Similar risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy: a systematic review and meta-analysis.
More questions than answers: comparison of the risk of cardiopulmonary adverse events between propofol and traditional anesthesia for gastrointestinal endoscopy.
Is “really conscious” sedation with solely an opioid an alternative to every day used sedation regimes for colonoscopies in a teaching hospital? Midazolam/fentanyl, propofol/alfentanil, or alfentanil only for colonoscopy: a randomized trial.
Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: the first double blind randomized controlled trial.
Carbon dioxide insufflation vs conventional air insufflation for colonoscopy: a systematic review and meta-analysis of published randomized controlled trials.
DISCLOSURE: Dr Keng received a speaker honorarium from Pendopharm. All other authors disclosed no financial relationships. Researchsupportfor this study (N.B.) was provided by the Canadian Institutes of Health Research (CIHR) Foundation Grant (grantno. 148470) and with thesupportof Cancer Care Ontario throughfundingprovided by the Government of Ontario. The opinions, results, views, and conclusions reported in this publication are those of the authors and do not necessarily reflect those of Cancer Care Ontario. No endorsement by Cancer Care Ontario is intended or should be inferred.
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