Literature DB >> 31839876

Propofol vs traditional sedatives for sedation in endoscopy: A systematic review and meta-analysis.

Aureo Augusto de Almeida Delgado1, Diogo Turiani Hourneaux de Moura1, Igor Braga Ribeiro2, Ahmad Najdat Bazarbashi3, Marcos Eduardo Lera Dos Santos1, Wanderley Marques Bernardo1, Eduardo Guimarães Hourneaux de Moura1.   

Abstract

BACKGROUND: Propofol is commonly used for sedation during endoscopic procedures. Data suggests its superiority to traditional sedatives used in endoscopy including benzodiazepines and opioids with more rapid onset of action and improved post-procedure recovery times for patients. However, Propofol requires administration by trained healthcare providers, has a narrow therapeutic index, lacks an antidote and increases risks of cardio-pulmonary complications. AIM: To compare, through a systematic review of the literature and meta-analysis, sedation with propofol to traditional sedatives with or without propofol during endoscopic procedures.
METHODS: A literature search was performed using MEDLINE, Scopus, EMBASE, the Cochrane Library, Scopus, LILACS, BVS, Cochrane Central Register of Controlled Trials, and The Cumulative Index to Nursing and Allied Health Literature databases. The last search in the literature was performed on March, 2019 with no restriction regarding the idiom or the year of publication. Only randomized clinical trials with full texts published were included. We divided sedation therapies to the following groups: (1) Propofol versus benzodiazepines and/or opiate sedatives; (2) Propofol versus Propofol with benzodiazepine and/or opioids; and (3) Propofol with adjunctive benzodiazepine and opioid versus benzodiazepine and opioid. The following outcomes were addressed: Adverse events, patient satisfaction with type of sedation, endoscopists satisfaction with sedation administered, dose of propofol administered and time to recovery post procedure. Meta-analysis was performed using RevMan5 software version 5.39.
RESULTS: A total of 23 clinical trials were included (n = 3854) from the initial search of 6410 articles. For Group I (Propofol vs benzodiazepine and/or opioids): The incidence of bradycardia was not statistically different between both sedation arms (RD: -0.01, 95%CI: -0.03-+0.01, I 2: 22%). In 10 studies, the incidence of hypotension was not statistically difference between sedation arms (RD: 0.01, 95%CI: -0.02-+0.04, I 2: 0%). Oxygen desaturation was higher in the propofol group but not statistically different between groups (RD: -0.03, 95%CI: -0.06-+0.00, I 2: 25%). Patients were more satisfied with their sedation in the benzodiazepine + opioid group compared to those with monotherapy propofol sedation (MD: +0.89, 95%CI: +0.62-+1.17, I 2: 39%). The recovery time after the procedure showed high heterogeneity even after outlier withdrawal, there was no statistical difference between both arms (MD: -15.15, 95%CI: -31.85-+1.56, I 2: 99%). For Group II (Propofol vs propofol with benzodiazepine and/or opioids): Bradycardia had a tendency to occur in the Propofol group with benzodiazepine and/or opioid-associated (RD: -0.08, 95%CI: -0.13--0.02, I 2: 59%). There was no statistical difference in the incidence of bradycardia (RD: -0.00, 95%CI: -0.08-+0.08, I 2: 85%), desaturation (RD: -0.00, 95%CI: -0.03-+0.02, I 2: 44%) or recovery time (MD: -2.04, 95%CI: -6.96-+2.88, I 2: 97%) between sedation arms. The total dose of propofol was higher in the propofol group with benzodiazepine and/or opiates but with high heterogeneity. (MD: 70.36, 95%CI: +53.11-+87.60, I 2: 61%). For Group III (Propofol with benzodiazepine and opioid vs benzodiazepine and opioid): Bradycardia and hypotension was not statistically significant between groups (RD: -0.00, 95%CI: -0.002-+0.02, I 2: 3%; RD: 0.04, 95%CI: -0.05-+0.13, I 2: 77%). Desaturation was evaluated in two articles and was higher in the propofol + benzodiazepine + opioid group, but with high heterogeneity (RD: 0.15, 95%CI: 0.08-+0.22, I 2: 95%).
CONCLUSION: This meta-analysis suggests that the use of propofol alone or in combination with traditional adjunctive sedatives is safe and does not result in an increase in negative outcomes in patients undergoing endoscopic procedures. ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

Entities:  

Keywords:  Adverse events; Benzodiazepines; Digestive endoscopy; Opioids; Propofol; Sedation

Year:  2019        PMID: 31839876      PMCID: PMC6885729          DOI: 10.4253/wjge.v11.i12.573

Source DB:  PubMed          Journal:  World J Gastrointest Endosc


Core tip: Propofol is commonly used for sedation during endoscopic procedures with increasing data suggesting its superiority to other sedatives, however with reported concerns about possible adverse events. This systematic review and meta-analysis discusses different variants of propofol-based sedation and how they compare to alternative sedatives such as those utilizing benzodiazepines and opioids. We demonstrate that the use of propofol, alone or in conjunction with alternative sedatives, is safe and carries no particular negative outcomes when compared to the widely available combination of alternative sedatives using in endoscopy.

INTRODUCTION

In recent years, the use of propofol for sedation during endoscopy has been shown to be safe and effective. Propofol is associated with rapid onset of action and a short time to recovery of patient's cognitive functions post procedure[1-4]. Propofol may be administered alone or in combination with other sedative agents, such as benzodiazepines or opioids[5-7]. Sedation using propofol alone can be associated with risks and complications since it requires administration of larger doses to achieve an adequate level of sedation, which in turn can lead to dose-dependent adverse events[5,8]. Additionally, the isolated use of this drug has disadvantages related to its pharmacokinetic properties. Propofol can induce deep sedation, has no antidote for reversibility, has a narrow therapeutic index and causes adverse events including cardiopulmonary compromise requiring resuscitation[9,10]. However, previous studies have shown that the use of propofol as an adjunct to traditional sedatives such as benzodiazepines and opioids with moderate patient sedation is associated with lower risk of complications, improved patient cooperation and satisfaction, and shorter time to recovery post procedure[5,11]. Several studies have compared the use of propofol alone versus its use with adjunctive sedatives[5,6,8,12-19]. However, these studies included insufficient numbers of patients to produce significant and conclusive results regarding the differences between propofol and alternative sedation. In this study, we perform a systematic review and meta-analysis comparing sedation with propofol to traditional sedatives (with or without propofol) during endoscopic procedures.

MATERIALS AND METHODS

Protocol and registration

A protocol was established and documented prior to initiating the study to specify eligibility criteria and analytical methods for the studies included in this systematic review and meta-analysis in keeping with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This study was documented in a protocol registered in International Prospective Register of Systematic Reviews (PROSPERO) database (CRD 42017057305)[20].

Eligibility criteria

Eligibility criteria were based on population, intervention, comparison, outcomes and study design strategy. Only randomized clinical trials with full texts published were included.

Search strategy, study selection and data collection process

A literature search was performed using MEDLINE, Scopus, EMBASE, the Cochrane Library, Scopus, LILACS, BVS, Cochrane Central Register of Controlled Trials, and The Cumulative Index to Nursing and Allied Health Literature databases. The last search in the literature was performed on March, 2019 with no restriction regarding the idiom or the year of publication. The titles and abstracts of all potentially relevant studies were screened for eligibility. Duplicates were removed. If necessary, we accessed complementary and supplemental information in the research protocols of the studies available on the online registration platforms (for example, Clinical Trials or PROSPERO). The reference lists of studies of interest were then manually reviewed for additional articles by cross checking bibliographies. Two reviewers (Delgado AAA and Ribeiro IB) independently screened the titles and abstracts of all the articles according to predefined inclusion and exclusion criteria as described below. Any differences were resolved by mutual agreement and in consultation with the third reviewer (de Moura DTH). For the systematic review, we included studies that met all the eligibility criteria, and for the meta-analysis, those that allowed the extraction of data from text, tables or graphs. Selection process is summarized in Figure 1.
Figure 1

Flow diagram of included and excluded clinical trials.

Flow diagram of included and excluded clinical trials.

Inclusion criteria

(1) Adults (over 18 years of age); (2) Undergoing endoscopic examination of the gastrointestinal tract (including esophagogastroduodenoscopy. and colonoscopy); and (3) Outpatient and elective procedures.

Exclusion criteria

Studies meeting any of the following criteria were excluded: (1) Types of participants: (a) Under the age of 18 years; and (b) Group of patients with specific comorbidities (obesity, pregnant and lactating women, cardiovascular diseases, pulmonary diseases, ascites, renal failure and abdominal surgeries); (2) Types of intervention and outcomes: (a) Studies not using propofol in one of the treatment arms; (b) Studies that did not evaluate the outcomes of interest; and (c) Studies without extractable data; and (3) Intervention and control: (a) Patients receiving propofol alone or in combination with traditional combined sedative agents (benzodiazepines and opioids); and (b) Traditional combined sedatives (benzodiazepines and opioids) with or without concurrent propofol use.

Data items

The following data were collected for each trial: (1) Patient characteristics; (2) Characteristics of intervention and comparison: Type of medication, doses, form of application; and (3) Outcomes as previously described. To simplify our analysis and data representation, we chose to subdivide the included studies into different groups according to the sedation regimens administered to the intervention and control groups (Table 1), as follows: (1) Group I - propofol vs benzodiazepine and opioid; (2) Group II - propofol vs propofol, benzodiazepine and/or opioid; and (3) Group III - propofol, benzodiazepine and opioid vs benzodiazepine and opioid.
Table 1

Characteristics of the studies included in the meta-analysis

AuthorRef.CountryYearPatients (n = 3854)Interven-tionInterven-tion (n = 1834)ControlControl (n = 2004)ProcedureJadad
Seifert[19]Germany2000239PROP120PROP + MDZ119Endoscopy/ERCP5
Sipe[39]USA200280PROP40MDZ + MEP40Colono-scopy4
Vargo[35]USA200275PROP38MDZ + MEP37ERCP/EUS4
Ulmer[40]USA2003100PROP50MDZ + FTN50Colono-scopy4
Riphaus[41]Germany2005150PROP75MDZ + MEP75ERCP5
VanNatta[12]USA2006200PROP50FTN + PROP/MDZ + PROP/MDZ + FTN + PROP150Colono-scopy3
Fanti[42]Italy2007270PROP135PROP + MDZ135EUS5
Dewitt[44]USA200880PROP40MDZ + MEP40EUS5
Kongkam[43]Thailand2008134PROP67MDZ + MEP67ERCP4
Schilling[45]Germany2009150PROP75MDZ + MEP75ERCP/EUS/Enteroscopy5
Pascual[26]Cuba2011512PROP256MDZ + MEP256Colono-scopy4
Lee[25]Korea2011222PROP + MDZ + MEP102MDZ + MEP104Endoscopy/ERCP5
Chun[31]Korea2012135PROP67PROP + MDZ68Stomach ESD3
Angsuwatcharakon[30]Thailand2012205PROP + MDZ + MEP103MDZ + MEP102ERCP3
Lee[29]Korea2012206PROP104PROP + MDZ + FTN102ERCP/EUS5
Zuo[28]China2012100PROP49MDZ + FTN51Endomicroscopy5
Levitzky[27]USA2012110PROP + MDZ + FTN55MDZ + FTN55Endoscopy3
Gurbulak[33]Turkey2014124PROP62MDZ + MEP62Colono-scopy5
Chan[32]Taiwan2014220PROP110PROP + MDZ + AFTN110Endoscopy + colonoscopy5
Hsu[36]Taiwan2015100PROP50PROP + MDZ +FTN50Endoscopy + colonoscopy1
Haytural[34]Turkey201590PROP30PROP + FTN/PROP + RFTN60ERCP1
Li[38]China201690PROP30PROP + FTN60Colono-scopy3
Schroeder[37]USA2016262PROP126MDZ + FTN136Colono-scopy4

MDZ: Midazolam; FTN: Fentanyl; PROP: Propofol; MEP: Meperidine; RFTN: Remifentanil; AFTN: Alfentanil.

Characteristics of the studies included in the meta-analysis MDZ: Midazolam; FTN: Fentanyl; PROP: Propofol; MEP: Meperidine; RFTN: Remifentanil; AFTN: Alfentanil.

Risk of bias in individual studies

As treatment effect size may differ due to detection, performance, selection, and bias, the methodological evaluation of the studies was performed. The adequacy of blinding, randomization, description of withdrawals and dropouts were determined by two authors working independently, using the Jadad scale[21] for the evaluation of randomized clinical trials.

Statistical analysis

This meta-analysis was performed using intention-to-treat data when possible. For all outcomes, absolute or mean risk difference was calculated. We considered statistically significant differences with 95%CI, P < 0.05, using the Mantel Hantzel tests (categorical variables) or inverse variance (continuous variables). The effects of the treatment were expressed graphically through forest plots and the heterogeneity of the studies were evaluated by the method proposed by Higgins et al[22], denominated I2, seeking values lower than 50%, using the fixed effect model. Risk of bias amongst studies was assessed using funnel plot analysis. For treatment effects in which there is strong heterogeneity (I2 - 50%) test with fixed effect, we exclude studies that were outside the limits of the funnel plot and the heterogeneity was reevaluated. If there was a reduction in heterogeneity (I2 < 50%), the excluded study was considered an outlier, that is, responsible for the high heterogeneity due to a publication bias and, consequently, it was not part of the final meta-analysis. If an outlier was not identified and the heterogeneity remained high, the Higgins et al[22] test was randomly selected. Review Manager 5 (RevMan 5) version 5.39 (by the Cochrane Collaboration, 2015) was the software chosen to run the meta-analysis.

Risk of bias across studies

Reporting bias across studies was evaluated by funnel plot graphical analysis. For each trial, the treatment effect was plotted against the measure of study precision and by Egger's test[23]. Asymmetrical funnel plot suggests the presence of reporting bias, methodological bias or true heterogeneity between smaller and larger studies.

Additional analysis

In the presence of an asymmetrical funnel plot or high heterogeneity, (I2 ≥ 50%) a sensitivity analysis was conducted to explore how the results of the meta-analysis could change under different assumptions[24]. Heterogeneity and funnel plot analysis before and after the removal of each study from the meta-analysis were assessed to identify the studies accounting for inconsistency among trials. If heterogeneity was reduced to below 50% after the removal of the outlier, the corrected intervention effect estimate was applied and the results were interpreted with caution. If inconsistency did not decrease, it was considered true heterogeneity.

RESULTS

Search and study selection

Among the 6410 articles screened from our initial search strategy, 23 randomized controlled studies were selected, including a total of 3854 patients[12,19,25-45]. Figure 1 summarizes the selection process of the studies. Of the 3854 patients included, 1574 received propofol as the sole sedative while 2280 received midazolam, meperidine, fentanyl, remifentanil, alfentanil in combination with propofol (Table 1). There was wide geographical representation of studies included, encompassing a wide diversity of endoscopic procedures. The Jadad score was greater than 3 in 91.3% of the studies included in the meta-analysis, suggesting adequate methodological quality of these studies. All studies are available online, in full text format.

Results by groups

Group I: In 11 studies evaluating the incidence of bradycardia, there were no observed differences between both treatment arms (RD: -0.01, 95%CI: −0.03–+0.01, I2: 22%, Figure 2A). In 10 studies assessing hypotension, no difference existed between both arms (RD: 0.01, 95%CI: −0.02–+0.04, I2: 0%, Figure 2B). The incidence of desaturation was higher in the propofol group however this did not reach statistical significance (RD: −0.03, 95%CI: −0.06–+0.00, I2: 25%, Figure 2C). Patient satisfaction with the visual analog scale was available in 6 of the included studies with a trend towards greater satisfaction in the benzodiazepine and/or opioid group (MD: +0.89, 95%CI: +0.62–+1.17, I2: 39%, Figure 2D). Endoscopist satisfaction with sedation was evaluated in only 2 studies without differences observed between both arms (MD: −0.02, 95%CI: −0.20–+0.16, I2: 0%, Figure 2E). Recovery time after the procedure was evaluated in 7 studies and revealed high heterogeneity. Even after withdrawal of the outlier, there was no statistical difference in recovery time between both arms (MD: -15.15, 95%CI: −31.85–+1.56, I2: 99%, Figure 2F).
Figure 2

Propofol vs benzodiazepine associated with opioid - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the propofol group and the benzodiazepine + opioid group (BZ + OP). Outcome: Bradycardia (defined as heart rate less than 50 bpm); B: Comparing the occurrence of oxygen desaturation between the propofol group and BZ + OP. Outcome: Hypotension (Defined as systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the propofol group and BZ + OP. Outcome: Oxygen desaturation (Defined as peripheral saturation of O2 defined as < 90%); D: Comparing patient satisfaction with the sedation received for the procedure between the propofol group and BZ + OP. Outcome: Patient satisfaction (Visual analog scale – 0: very dissatisfied to 10: very satisfied); E: Comparing satisfaction of the endoscopists with the sedation administered for the procedure between the propofol group and BZ + OP. Outcome: Endoscopists satisfaction (Visual analog scale – 0: very dissatisfied to 10: very satisfied); F: Comparing patient recovery time after the procedure between the propofol group and BZ + OP. Outcome: Post procedure time to recovery (min).

Propofol vs benzodiazepine associated with opioid - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the propofol group and the benzodiazepine + opioid group (BZ + OP). Outcome: Bradycardia (defined as heart rate less than 50 bpm); B: Comparing the occurrence of oxygen desaturation between the propofol group and BZ + OP. Outcome: Hypotension (Defined as systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the propofol group and BZ + OP. Outcome: Oxygen desaturation (Defined as peripheral saturation of O2 defined as < 90%); D: Comparing patient satisfaction with the sedation received for the procedure between the propofol group and BZ + OP. Outcome: Patient satisfaction (Visual analog scale – 0: very dissatisfied to 10: very satisfied); E: Comparing satisfaction of the endoscopists with the sedation administered for the procedure between the propofol group and BZ + OP. Outcome: Endoscopists satisfaction (Visual analog scale – 0: very dissatisfied to 10: very satisfied); F: Comparing patient recovery time after the procedure between the propofol group and BZ + OP. Outcome: Post procedure time to recovery (min). Group II: Bradycardia was assessed in 5 of the included studies and had a greater trend of occurrence in the Propofol arm with benzodiazepine and/or opioid-associated compared to the propofol alone arm (RD: -0.08, 95%CI: −0.13–−0.02, I2: 59%, Figure 3A). In 6 studies assessing hypotension, there was no difference between the both arms (RD: -0.00, 95%CI: −0.08–+0.08, I2: 85%, Figure 3B). Desaturation was evaluated in 7 studies without significant difference (RD: −0.00, 95%CI: −0.03–+0.02, I2: 44%, Figure 3C). Patient satisfaction with the visual analog scale was available in 2 of the included studies and was different between both arms (MD: -0.62, 95%CI: -1.38–+0.13, I2: 89%, Figure 3D). The recovery time after the procedure was evaluated in 7 studies and the result showed high heterogeneity without statistical difference between the groups (MD: -2.04, 95%CI: −6.96–+2.88, I2: 97%, Figure 3E). The total dose of propofol was evaluated in 5 articles and was noted to be higher in the propofol with benzodiazepine and/or opiates arm but with high heterogeneity. The funnel-plot test did not demonstrate outliers (MD: 70.36, 95%CI: +53.11–+87.60, I2: 61%, Figure 3F).
Figure 3

Propofol vs propofol with benzodiazepine and/or opioids - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the propofol group and the propofol group associated with benzodiazepine and / or opioid (Prop + BZ and/or OP). Outcome: Bradycardia (defined as HR < 50 bpm); B: Comparing the occurrence of hypotension between the propofol group and (Prop + BZ and/or OP). Outcome: Hypotension (Defined as systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the propofol group and Prop + BZ and/or OP. Outcome: Desaturation (Defined as peripheral oxygen saturation of < 90%); D: Comparing patient satisfaction with sedation received for the procedure between propofol group and Prop + BZ and/or OP. Outcome: Patient satisfaction (Visual analog scale - 0 very dissatisfied / 10 very satisfied); E: Comparing patient recovery time after the procedure between the propofol group and Prop + BZ and/or OP. Time to recovery (min); F: Comparing the total dose of propofol administered during procedures between the propofol group and Prop + BZ and/or OP. Outcome: Total dose of propofol given during the procedure (mg).

Propofol vs propofol with benzodiazepine and/or opioids - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the propofol group and the propofol group associated with benzodiazepine and / or opioid (Prop + BZ and/or OP). Outcome: Bradycardia (defined as HR < 50 bpm); B: Comparing the occurrence of hypotension between the propofol group and (Prop + BZ and/or OP). Outcome: Hypotension (Defined as systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the propofol group and Prop + BZ and/or OP. Outcome: Desaturation (Defined as peripheral oxygen saturation of < 90%); D: Comparing patient satisfaction with sedation received for the procedure between propofol group and Prop + BZ and/or OP. Outcome: Patient satisfaction (Visual analog scale - 0 very dissatisfied / 10 very satisfied); E: Comparing patient recovery time after the procedure between the propofol group and Prop + BZ and/or OP. Time to recovery (min); F: Comparing the total dose of propofol administered during procedures between the propofol group and Prop + BZ and/or OP. Outcome: Total dose of propofol given during the procedure (mg). Group III: Two studies examined the incidence of bradycardia which was not different between sedation arms (RD: -0.00, 95%CI: −0.002–+0.02, I2: 3%, Figure 4A). Additionally, two studies examining the incidence of hypotension showed no statistically significant differences between sedation arms (RD: 0.04, 95% CI: −0.05–+0.13, I2: 77%, Figure 4B). Desaturation, however, evaluated in two studies was more commonly seen with propofol + benzodiazepine + opioid arm but with high heterogeneity (RD: 0.15, 95%CI: 0.08–+0.22, I2: 95%, Figure 4C).
Figure 4

Propofol associated with benzodiazepine and opioid vs benzodiazepine associated with opioid - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the benzodiazepine-associated propofol group and the opioid and the benzodiazepine group associated with the opioid (BZ + OP). Outcome: Bradycardia (defined as HR < 50 bpm); B: Comparing the occurrence of hypotension between the benzodiazepine-associated propofol group and the opioid and BZ + OP. Outcome: Hypotension (Systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the benzodiazepine-associated propofol group and the opioid and BZ + OP. Outcome: Desaturation (Peripheral saturation of O2 < 90%).

Propofol associated with benzodiazepine and opioid vs benzodiazepine associated with opioid - Forest plot of the meta-analysis. A: Comparing the occurrence of bradycardia between the benzodiazepine-associated propofol group and the opioid and the benzodiazepine group associated with the opioid (BZ + OP). Outcome: Bradycardia (defined as HR < 50 bpm); B: Comparing the occurrence of hypotension between the benzodiazepine-associated propofol group and the opioid and BZ + OP. Outcome: Hypotension (Systolic blood pressure < 90 mmHg); C: Comparing the occurrence of desaturation between the benzodiazepine-associated propofol group and the opioid and BZ + OP. Outcome: Desaturation (Peripheral saturation of O2 < 90%).

DISCUSSION

The use of propofol in endoscopy is increasingly common[46-48] for both diagnostic and advanced therapeutic procedures[48,49,58,50-57]. Propofol has proven to be safe and affordable, yielding satisfactory and efficient sedation for patients undergoing endoscopy[59]. Propofol can be used as a single agent for anesthesia induction and maintenance, leads to rapid induction of anesthesia, carries a low half-life and is associated with fast recovery from anesthesia[46]. However, Propofol can be associated with dose-dependent complications, including the risk of major respiratory depression and several cardiovascular adverse events[54,60]. Our study adds to the plethora of literature describing the use of propofol for endoscopy sedation, but also highlights how it compares to numerous alternative and adjunctive sedatives. After analyzing 23 clinical trials[12,19,25-45], many of good quality and adequate methodological design, including a total of 3854 patients, we note no significant differences in many outcomes measures between the sedation arms involving propofol alone or in combination with alternative sedatives. In contrast to the last meta-analysis published[55], our study demonstrates no statistical difference in outcome measures with regards to hypotension, oxygen desaturation and post-procedure anesthetic recovery when using propofol alone or in combination with benzodiazepines and/or opioids. There was a trend towards increased incidence of bradycardia in patients in the propofol with benzodiazepine and opioid sedation arm compared to those on propofol alone. Incidence of bradycardia did not differ between other arms in the different treatment groups. No differences existed in recovery time between all sedation arms in all treatment groups as reported in the meta-analysis by Wang et al[61]. Previous meta-analyses[2,3,61] also demonstrated significantly fewer adverse effects with propofol sedation. In our study, we observed that propofol used alone or in conjunction with other sedatives including opioids and benzodiazepines is safe and did not result in increased adverse events in patients undergoing endoscopic procedures as demonstrated by Sethi et al[55] which also included sedation for advanced endoscopic procedures such as endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and double-balloon enteroscopy. Due to the properties of propofol, its doses are very volatile[9,60]. Higher doses are associated with elevated cardiovascular risk and low doses are associated with several complications, especially in therapeutic procedures that cause pain. Propofol has a limited analgesic effect and higher doses are often required, when used as single agent for sedation in endoscopy. Several studies have reported that the combination of propofol with other sedative agents is a reasonable option to obtain the adequate depth of sedation, avoiding high dose-related side effects of propofol, allow for improve patient tolerance, prolong recovery time, and control of pain[5,13,15,17]. However, our study did not demonstrate an advantage to propofol alone without significant statistical differences when comparing propofol to alternative agents (with and without propofol). In our meta-analysis, patient satisfaction with the use of a visual analog scale lead to a trend towards greater satisfaction for patients undergoing sedation with benzodiazepine and opioids when compared to propofol use. The satisfaction of the endoscopists was evaluated in a few studies included in this meta-analysis however did not reveal significant differences in endoscopists satisfaction. There are several limitations to our analysis. Similar to prior publications and meta-analysis evaluating sedation in endoscopy, we observe high heterogeneity between the several studies aggregated in the meta-analysis, which must be taken into account in the interpretation of its results. There are several reasons for heterogeneity present in the published literature for studies included. One reason may be due to intrinsic differences in populations examined with each study, specifically age, weight, body mass which may alter the amount of sedation required and tolerability. Additionally, the education level for various populations included may influence patient satisfaction levels. Another reason for heterogeneity is lack of uniformity between the comparisons made, the individual administering sedation (anesthesiologist, non-anesthetist physicians, certified registered nurse anesthetists), acceptable and max doses of sedatives, means of sedative administration (intermittent bolus vs continuous infusion) and criteria for re-administration of sedative if more is required. With regards to the procedures performed, diagnostic and therapeutic interventions can have differences in total procedure times, which in turn can influence the type of sedation, doses required, level of sedation and maintenance of sedation. This can certainly influence heterogeneity. Finally, while it is important to highlight the clinical aspects of sedation use, it is imperative to understand that cost plays a significant role in the choice of sedation. While not assessed in this study, we believe cost effectiveness should be highlighted in future sedation meta-analysis. In conclusion, this meta-analysis suggests that the use of propofol alone or in combination with traditional adjunctive sedatives is safe and does not result in an increase in negative outcomes.

ARTICLE HIGHLIGHTS

Research background

Endoscopy has transformed over the past several decades to encompass significant advances and procedural innovation, with the hope to provide better care for ill patients. However, with technical advances and innovation comes increasingly prolonged and complex procedures. This change in the endoscopic platform, alongside the higher acuity of patients, has demanded a change in the approach for procedural sedation to ensure safe interventions.

Research motivation

The change in the sedation landscape for endoscopy over the past several decades necessitates a better understanding of sedation types and how they compare to each other for the modern practicing endocsopist.

Research objectives

We aimed to compare sedation with propofol, alone or in combination with adjunctive sedations, to traditional sedation in endoscopy through a systematic review of the literature and meta-analysis.

Research methods

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in International Prospective Register of Systematic Reviews international database. The search was performed in the electronic databases MEDLINE (via PubMed), LILACS (via BVS) and Cochrane/Central Register of Controlled Trials. The quality of the selected papers was evaluated by Jadad score and all articles used were selected by consensus of three authors.

Research results

A total of 23 clinical trials (n = 3854), from an initial search of 6410 articles, were included. For Group I (Propofol vs benzodiazepine and/or opioids): The incidence of bradycardia, hypotension, oxygen desaturation and post procedure recovery time was not statistically different between both arms. For Group II (Propofol vs propofol with benzodiazepine and/or opioids): Bradycardia tended to occur in the propofol group with benzodiazepine and/or opioid-associated but there was no statistical difference in the incidence of bradycardia, desaturation or recovery time between sedation arms. For Group III (Propofol with benzodiazepine and opioid vs benzodiazepine and opioid): Bradycardia, desaturation and, hypotension was not statistically significant between groups.

Research conclusions

Our findings suggest that the use of propofol alone or in combination with traditional adjunctive sedatives is safe and does not result in an increase in negative outcomes in patients undergoing endoscopic procedures.

Research perspectives

Future studies should consider methods for standardization of sedation use to allow for less heterogeneity amongst studies and to improve analysis in future metanalyses to come. Future studies should also highlight cost effectiveness of various sedations used.
  61 in total

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2.  Bias in meta-analysis detected by a simple, graphical test.

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Journal:  BMJ       Date:  1997-09-13

3.  Characterization of cardiovascular depression effect for propofol during anesthesia induction period on morbidly obese patients.

Authors:  Zhufeng Wu; Jiayang Li; Cunchuan Wang; Jingge Yang; Xiaomei Chen; Wah Yang; Zhiling Xiong; Xuemei Peng
Journal:  Biomed Pharmacother       Date:  2018-07-11       Impact factor: 6.529

4.  Balanced propofol sedation versus propofol monosedation in therapeutic pancreaticobiliary endoscopic procedures.

Authors:  Tae Hoon Lee; Chang Kyun Lee; Sang-Heum Park; Suck-Ho Lee; Il-Kwun Chung; Hyun Jong Choi; Sang Woo Cha; Jong Ho Moon; Young Deok Cho; Young Hwangbo; Sun-Joo Kim
Journal:  Dig Dis Sci       Date:  2012-05-22       Impact factor: 3.199

Review 5.  Propofol for gastrointestinal endoscopy.

Authors:  Toshihiro Nishizawa; Hidekazu Suzuki
Journal:  United European Gastroenterol J       Date:  2018-03-22       Impact factor: 4.623

6.  Nurse-administered propofol sedation compared with midazolam and meperidine for EUS: a prospective, randomized trial.

Authors:  John Dewitt; Kathleen McGreevy; Stuart Sherman; Thomas F Imperiale
Journal:  Gastrointest Endosc       Date:  2008-06-17       Impact factor: 9.427

7.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.

Authors:  Alessandro Liberati; Douglas G Altman; Jennifer Tetzlaff; Cynthia Mulrow; Peter C Gøtzsche; John P A Ioannidis; Mike Clarke; P J Devereaux; Jos Kleijnen; David Moher
Journal:  BMJ       Date:  2009-07-21

8.  Sedation with propofol for interventional endoscopy by trained nurses in high-risk octogenarians: a prospective, randomized, controlled study.

Authors:  D Schilling; A Rosenbaum; S Schweizer; H Richter; B Rumstadt
Journal:  Endoscopy       Date:  2009-04-01       Impact factor: 10.093

Review 9.  Efficacy and safety of carbon dioxide insufflation versus air insufflation during endoscopic retrograde cholangiopancreatography in randomized controlled trials: a systematic review and meta-analysis.

Authors:  Marina Lordello Passos; Igor Braga Ribeiro; Diogo Turiani Hourneaux de Moura; Nádia Korkischko; Gustavo Luis Rodela Silva; Tomazo Prince Franzini; Wanderley Marques Bernando; Eduardo Guimarães Horneaux de Moura
Journal:  Endosc Int Open       Date:  2019-04-03

10.  Cardiopulmonary safety of propofol versus midazolam/meperidine sedation for colonoscopy: a prospective, randomized, double-blinded study.

Authors:  Bunyamin Gurbulak; Sinan Uzman; Esin Kabul Gurbulak; Yasar Gokhan Gul; Mehmet Toptas; Sevim Baltali; Osman Anil Savas
Journal:  Iran Red Crescent Med J       Date:  2014-11-15       Impact factor: 0.611

View more
  9 in total

Review 1.  Efficacy and Patient Tolerability of Split-Dose Sodium Picosulfate/Magnesium Citrate (SPMC) Oral Solution Compared to the Polyethylene Glycol (PEG) Solution for Bowel Preparation in Outpatient Colonoscopy: An Evidence-Based Review.

Authors:  Antonio Afonso de Miranda Neto; Diogo Turiani Hourneaux de Moura; Kelly E Hathorn; Francisco Tustumi; Eduardo Guimarães Hourneaux de Moura; Igor Braga Ribeiro
Journal:  Clin Exp Gastroenterol       Date:  2020-10-07

2.  Safety and Recipient Satisfaction of Propofol Sedation in Outpatient Endoscopy: A 24-Hour Prospective Investigation Using a Questionnaire Survey.

Authors:  Yoshihide Kanno; Tetsuya Ohira; Yoshihiro Harada; Shinsuke Koshita; Takahisa Ogawa; Hiroaki Kusunose; Yoshiki Koike; Taku Yamagata; Toshitaka Sakai; Kaori Masu; Keisuke Yonamine; Kazuaki Miyamoto; Megumi Tanaka; Tomohiro Shimada; Fumisato Kozakai; Kazuki Endo; Haruka Okano; Daichi Komabayashi; Takeshi Shimizu; Shohei Suzuki; Kei Ito
Journal:  Clin Endosc       Date:  2020-12-11

Review 3.  Role of pancreatography in the endoscopic management of encapsulated pancreatic collections - review and new proposed classification.

Authors:  Igor Mendonça Proença; Marcos Eduardo Lera Dos Santos; Diogo Turiani Hourneaux de Moura; Igor Braga Ribeiro; Sergio Eiji Matuguma; Spencer Cheng; Thomas R McCarty; Epifanio Silvino do Monte Junior; Paulo Sakai; Eduardo Guimarães Hourneaux de Moura
Journal:  World J Gastroenterol       Date:  2020-12-07       Impact factor: 5.742

4.  Effective dose of propofol combined with a low-dose esketamine for gastroscopy in elderly patients: A dose finding study using dixon's up-and-down method.

Authors:  Yuling Zheng; Yafei Xu; Bixin Huang; Ying Mai; Yiwen Zhang; Zhongqi Zhang
Journal:  Front Pharmacol       Date:  2022-09-20       Impact factor: 5.988

5.  Effect of intravenous lidocaine on the ED50 of propofol for inserting gastroscope without body movement in adult patients: a randomized, controlled study.

Authors:  Xiu-Ru Qi; Jing-Yi Sun; Li-Xin An; Ke Zhang
Journal:  BMC Anesthesiol       Date:  2022-10-17       Impact factor: 2.376

6.  Deep sedation using propofol target-controlled infusion for gastrointestinal endoscopic procedures: a retrospective cohort study.

Authors:  María E García Guzzo; María S Fernandez; Delfina Sanchez Novas; Sandra S Salgado; Sergio A Terrasa; Gonzalo Domenech; Carlos A Teijido
Journal:  BMC Anesthesiol       Date:  2020-08-10       Impact factor: 2.217

7.  Comparison of Lidocaine Spray and Lidocaine Ice Popsicle in Patients Undergoing Unsedated Esophagogastroduodenoscopy: A Single Center Prospective Randomized Controlled Trial.

Authors:  Prasit Mahawongkajit; Nantawat Talalak; Neranchala Soonthornkes
Journal:  Clin Exp Gastroenterol       Date:  2021-05-25

8.  Bispectral Index Monitoring and Observer Rating Scale Correlate with Dreaming during Propofol Anesthesia for Gastrointestinal Endoscopies.

Authors:  Helena Matus; Slavica Kvolik; Andreja Rakipovic; Vladimir Borzan
Journal:  Medicina (Kaunas)       Date:  2021-12-31       Impact factor: 2.430

9.  Stent versus Balloon Dilation for the Treatment of Dominant Strictures in Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis.

Authors:  Marina Tucci Gammaro Baldavira Ferreira; Igor Braga Ribeiro; Diogo Turiani Hourneaux de Moura; Thomas R McCarty; Alberto Machado da Ponte Neto; Galileu Ferreira Ayala Farias; Antônio Afonso de Miranda Neto; Pedro Victor Aniz Gomes de Oliveira; Wanderley Marques Bernardo; Eduardo Guimarães Hourneaux de Moura
Journal:  Clin Endosc       Date:  2021-07-01
  9 in total

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