Digestive Endoscopy 2014; 26: 701–706
doi: 10.1111/den.12342
Review
Propofol versus traditional sedative agents for endoscopic submucosal dissection Toshihiro Nishizawa,1,2 Hidekazu Suzuki,2 Juntaro Matsuzaki,3 Takanori Kanai2 and Naohisa Yahagi1 1
Division of Research and Development for Minimally Invasive Treatment, Cancer Center, 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine and 3 Center for Preventive Medicine, Keio University Hospital, Tokyo, Japan Background and Aim: Propofol has been suggested to be superior to benzodiazepines when used as a sedative agent for endoscopic examination. The aim of the present study was to systematically evaluate the safety and efficacy of propofol sedation for endoscopic submucosal dissection (ESD). Methods: PubMed, the Cochrane library, and the Igaku-ChuoZasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data from the eligible studies were combined to calculate pooled odds ratios (OR) of developing restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension. Results: We identified three randomized trials (298 patients) from the database search. Compared with traditional sedative agents, the pooled OR of restlessness and full awakening at 1 h
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) has recently been developed as a new technique, enabling en bloc endoscopic resection of large lesions.1,2 ESD requires a high level of technical expertise as well as a longer operation time than conventional endoscopic procedures. Therefore, the sedation required for ESD is deeper than that for conventional endoscopic procedures. Traditional sedative agents such as midazolam have been used for sedation of patients who receive endoscopic therapy. Effective dose ranges of such agents differ considerably among patients, making it difficult to achieve stable sedation. Propofol is a phenolic derivative with satisfactory sedative and amnesic properties. It is highly lipophilic, and thus
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Corresponding: Hidekazu Suzuki, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: [email protected] Received 20 May 2014; accepted 4 August 2014.
post-ESD with propofol sedation were 0.41 (95% confidence interval [CI]: 0.21–0.81) and 8.59 (95% CI: 4.29–17.2), respectively, without significant heterogeneity. Compared with traditional sedative agents, the pooled OR of hypoxia and hypotension with propofol sedation were 1.13 (95% CI: 0.58–2.21) and 0.92 (95% CI: 0.25–3.41), respectively, indicating no significant differences between the groups.
Conclusion: Propofol sedation during ESD is more effective as compared with traditional sedative agent. The risk of complications is similar. Key words: endoscopic submucosal dissection (ESD), metaanalysis, midazolam, propofol, sedative agent
can rapidly cross the blood–brain barrier, resulting in an early onset of action. Propofol is a short-acting agent with rapid metabolism, and has a short recovery profile regardless of the depth or length of the sedation period. Although propofol may lead to deep sedation or even dangerous adverse events that require cardiopulmonary support, it has been frequently used as a sedative agent for standard endoscopic procedures worldwide. Recent meta-analysis found that propofol, when used as a sedative for endoscopic examination, provides a shorter recovery time and better sedation than traditional sedative agents without causing an increase in cardiopulmonary complications.3,4 Furthermore, several randomized controlled trials (RCT) have evaluated the efficacy of propofol in comparison with traditional sedative agents for ESD in the upper gastrointestinal tract.5–7 However, the results of individual studies have been inconclusive. We propose that systematic pooling of all data from available studies may provide a better understanding of propofol as a sedative agent during ESD. Our objective was to carry out a systematic review and meta-analysis on RCT comparing propofol and traditional sedative agents on the
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
701
702
T. Nishizawa et al.
safety and efficacy during ESD. Safety end-points were full awakening at 1 h post-ESD, hypoxia, and hypotension. Efficacy end-point was the absence of body movements (restlessness) forcing discontinuation of ESD.
METHODS
B
EFORE CARRYING OUT the meta-analysis, we developed a simplified protocol including search strategies, criteria for selection of studies, and methods for extracting relevant data, assessing the quality of studies, and statistical analysis.
Search strategy Electronic databases, PubMed, the Cochrane library, and the Igaku-Chuo-Zasshi database in Japan (from 1950 to April 2014), were used for a systematic literature search. A search strategy was constructed by using a combination of the following words: (endoscopic submucosal dissection or ESD) AND (propofol or diprivan). Articles published in any language were included. A comprehensive search was carried out in the reference lists of all review articles and original studies retrieved by this method in order to identify additional reports.
Inclusion and exclusion criteria Articles were considered eligible if the studies met the following inclusion criteria: (i) study type: RCT; (ii) population: patients who underwent ESD; (iii) intervention: an active treatment with propofol; (iv) comparator: traditional sedative agents; (v) outcome: safety and efficacy of the sedation. Duplicate publications and reviews were excluded.
Outcome measures Correct sedation was defined as the absence of body movements (restlessness) forcing discontinuation of the treatment. Restlessness was used as evaluation target of efficacy. Full awakening at 1 h post-ESD, hypoxia, and hypotension were used as evaluation target of safety.
Data extraction Standardized data abstraction sheets were prepared. Extracted data included study design, study quality, intervention, outcomes, and adverse effects. All articles were examined independently for eligibility by two reviewers (T.N. and H.S.). Disagreements were resolved by consulting a third reviewer (N.Y.).
Assessment of methodology quality The methodological quality of each study was assessed using the risk-of-bias tool outlined in the Cochrane Handbook for
Digestive Endoscopy 2014; 26: 701–706
Systematic Reviews of Interventions (version 5.1.0; The Cochrane Collaboration, Oxford, UK). Two reviewers (T.N. and H.S.) reviewed all studies and assessed six different key aspects that influence the quality of an RCT, including sequence generation, allocation concealment, blinding of participants and outcome assessors, management of eventual incomplete outcome data, completeness of outcome reporting, and other potential threats to validity.
Statistical analysis Data were entered into the StatsDirect statistical package (StatsDirect Ltd, Cheshire, UK). Outcome measures examined were the odds ratios (OR) of developing restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension with propofol versus a traditional sedative agent, midazolam. We used the method of a random-effects model to calculate summary OR and 95% CI. Heterogeneity between studies was assessed by Cochrane’s Q and I-squared tests. Because of the low power of the Q-test, a cut-off value (
doi: 10.1111/den.12342
Review
Propofol versus traditional sedative agents for endoscopic submucosal dissection Toshihiro Nishizawa,1,2 Hidekazu Suzuki,2 Juntaro Matsuzaki,3 Takanori Kanai2 and Naohisa Yahagi1 1
Division of Research and Development for Minimally Invasive Treatment, Cancer Center, 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine and 3 Center for Preventive Medicine, Keio University Hospital, Tokyo, Japan Background and Aim: Propofol has been suggested to be superior to benzodiazepines when used as a sedative agent for endoscopic examination. The aim of the present study was to systematically evaluate the safety and efficacy of propofol sedation for endoscopic submucosal dissection (ESD). Methods: PubMed, the Cochrane library, and the Igaku-ChuoZasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data from the eligible studies were combined to calculate pooled odds ratios (OR) of developing restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension. Results: We identified three randomized trials (298 patients) from the database search. Compared with traditional sedative agents, the pooled OR of restlessness and full awakening at 1 h
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) has recently been developed as a new technique, enabling en bloc endoscopic resection of large lesions.1,2 ESD requires a high level of technical expertise as well as a longer operation time than conventional endoscopic procedures. Therefore, the sedation required for ESD is deeper than that for conventional endoscopic procedures. Traditional sedative agents such as midazolam have been used for sedation of patients who receive endoscopic therapy. Effective dose ranges of such agents differ considerably among patients, making it difficult to achieve stable sedation. Propofol is a phenolic derivative with satisfactory sedative and amnesic properties. It is highly lipophilic, and thus
bs_bs_banner
Corresponding: Hidekazu Suzuki, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: [email protected] Received 20 May 2014; accepted 4 August 2014.
post-ESD with propofol sedation were 0.41 (95% confidence interval [CI]: 0.21–0.81) and 8.59 (95% CI: 4.29–17.2), respectively, without significant heterogeneity. Compared with traditional sedative agents, the pooled OR of hypoxia and hypotension with propofol sedation were 1.13 (95% CI: 0.58–2.21) and 0.92 (95% CI: 0.25–3.41), respectively, indicating no significant differences between the groups.
Conclusion: Propofol sedation during ESD is more effective as compared with traditional sedative agent. The risk of complications is similar. Key words: endoscopic submucosal dissection (ESD), metaanalysis, midazolam, propofol, sedative agent
can rapidly cross the blood–brain barrier, resulting in an early onset of action. Propofol is a short-acting agent with rapid metabolism, and has a short recovery profile regardless of the depth or length of the sedation period. Although propofol may lead to deep sedation or even dangerous adverse events that require cardiopulmonary support, it has been frequently used as a sedative agent for standard endoscopic procedures worldwide. Recent meta-analysis found that propofol, when used as a sedative for endoscopic examination, provides a shorter recovery time and better sedation than traditional sedative agents without causing an increase in cardiopulmonary complications.3,4 Furthermore, several randomized controlled trials (RCT) have evaluated the efficacy of propofol in comparison with traditional sedative agents for ESD in the upper gastrointestinal tract.5–7 However, the results of individual studies have been inconclusive. We propose that systematic pooling of all data from available studies may provide a better understanding of propofol as a sedative agent during ESD. Our objective was to carry out a systematic review and meta-analysis on RCT comparing propofol and traditional sedative agents on the
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
701
702
T. Nishizawa et al.
safety and efficacy during ESD. Safety end-points were full awakening at 1 h post-ESD, hypoxia, and hypotension. Efficacy end-point was the absence of body movements (restlessness) forcing discontinuation of ESD.
METHODS
B
EFORE CARRYING OUT the meta-analysis, we developed a simplified protocol including search strategies, criteria for selection of studies, and methods for extracting relevant data, assessing the quality of studies, and statistical analysis.
Search strategy Electronic databases, PubMed, the Cochrane library, and the Igaku-Chuo-Zasshi database in Japan (from 1950 to April 2014), were used for a systematic literature search. A search strategy was constructed by using a combination of the following words: (endoscopic submucosal dissection or ESD) AND (propofol or diprivan). Articles published in any language were included. A comprehensive search was carried out in the reference lists of all review articles and original studies retrieved by this method in order to identify additional reports.
Inclusion and exclusion criteria Articles were considered eligible if the studies met the following inclusion criteria: (i) study type: RCT; (ii) population: patients who underwent ESD; (iii) intervention: an active treatment with propofol; (iv) comparator: traditional sedative agents; (v) outcome: safety and efficacy of the sedation. Duplicate publications and reviews were excluded.
Outcome measures Correct sedation was defined as the absence of body movements (restlessness) forcing discontinuation of the treatment. Restlessness was used as evaluation target of efficacy. Full awakening at 1 h post-ESD, hypoxia, and hypotension were used as evaluation target of safety.
Data extraction Standardized data abstraction sheets were prepared. Extracted data included study design, study quality, intervention, outcomes, and adverse effects. All articles were examined independently for eligibility by two reviewers (T.N. and H.S.). Disagreements were resolved by consulting a third reviewer (N.Y.).
Assessment of methodology quality The methodological quality of each study was assessed using the risk-of-bias tool outlined in the Cochrane Handbook for
Digestive Endoscopy 2014; 26: 701–706
Systematic Reviews of Interventions (version 5.1.0; The Cochrane Collaboration, Oxford, UK). Two reviewers (T.N. and H.S.) reviewed all studies and assessed six different key aspects that influence the quality of an RCT, including sequence generation, allocation concealment, blinding of participants and outcome assessors, management of eventual incomplete outcome data, completeness of outcome reporting, and other potential threats to validity.
Statistical analysis Data were entered into the StatsDirect statistical package (StatsDirect Ltd, Cheshire, UK). Outcome measures examined were the odds ratios (OR) of developing restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension with propofol versus a traditional sedative agent, midazolam. We used the method of a random-effects model to calculate summary OR and 95% CI. Heterogeneity between studies was assessed by Cochrane’s Q and I-squared tests. Because of the low power of the Q-test, a cut-off value (
