Accepted Manuscript Etomidate Versus Propofol Sedation For Complex Upper Endoscopic Procedures: A Prospective Double-Blinded Randomized Controlled Trial Mi Gang Kim, M.D, Se Woo Park, M.D, Jae Hyun Kim, M.D, Jin Lee, M.D. & Ph.D, Sea Hyub Kae, M.D. & Ph.D, Hyun Joo Jang, M.D, Dong Hee Koh, M.D. & Ph.D, Min Ho Choi, M.D PII:
S0016-5107(17)30176-1
DOI:
10.1016/j.gie.2017.02.033
Reference:
YMGE 10445
To appear in:
Gastrointestinal Endoscopy
Received Date: 17 June 2016 Accepted Date: 23 February 2017
Please cite this article as: Kim MG, Park SW, Kim JH, Lee J, Kae SH, Jang HJ, Koh DH, Choi MH, Etomidate Versus Propofol Sedation For Complex Upper Endoscopic Procedures: A Prospective Double-Blinded Randomized Controlled Trial, Gastrointestinal Endoscopy (2017), doi: 10.1016/ j.gie.2017.02.033. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Etomidate Versus Propofol Sedation For Complex Upper Endoscopic
Short title: Etomidate in complex upper endoscopic procedure
Authors:
RI PT
Procedures: A Prospective Double-Blinded Randomized Controlled Trial
SC
Mi Gang Kim M.D. a, Se Woo Park M.D. a, Jae Hyun Kim M.D. a, Jin Lee M.D. & Ph.D. a, Sea Hyub Kae M.D. & Ph.D. a, Hyun Joo Jang M.D. a, Dong Hee Koh M.D. & Ph.D. a, Min
M AN U
Ho Choi M.D. a
Departmental and institutional affiliation: a
Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan
Correspondence to:
TE D
Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Korea
EP
Professor Se Woo Park, Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine,
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7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do, 18450, Korea Tel: +82-31-8086-2858, Fax: +82-31-8086-2029, E-mail: [email protected]
Word Count: 3,911
ACCEPTED MANUSCRIPT ABSTRACT Background and Aims Although a growing body of evidence demonstrates that propofol-induced deep sedation can
RI PT
be effective and performed safely, cardiopulmonary adverse events have been frequently observed. Etomidate is a new emerging drug that provides hemodynamic and respiratory stability, even in high-risk patient groups. The objective of this study was to compare safety
SC
and efficacy profiles of etomidate and propofol for endoscopic sedation. Methods
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A total of 128 patients undergoing endoscopic ultrasound were randomized to receive either etomidate or propofol blinded administered by a registered nurse. The primary outcome was the proportion of patients with any cardiopulmonary adverse event. Results
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Overall cardiopulmonary adverse events were identified in 22 patients (34.38%) of the etomidate group and 33 patients (51.56%) of the propofol group without significant difference (P=0.074). However, The incidence of oxygen desaturation (4/64 [6.25%] vs 20/64
EP
[31.25%], P=0.001) and respiratory depression (5/64 [7.81%] vs 21/64 [32.81%], P=0.001) was significantly lower in the etomidate group than in the propofol group. The frequency of
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myoclonus was significantly higher in the etomidate group (22/64 [34.37%]) compared with the propofol group (8/64 [12.50%]) (P=0.012). Repeated measure analysis of variance revealed significant effects of sedation group and time on systolic blood pressure (etomidate group > propofol group). Physician satisfaction was greater in the etomidate group than in the propofol group. Conclusion
1
ACCEPTED MANUSCRIPT Etomidate administration resulted in fewer respiratory depression events and had a better sedative efficacy than propofol; however, it was more frequently associated with myoclonus
RI PT
and increased blood pressure during endoscopic procedures.
Trial registration: the International Clinical Trials Registry Platform (no. KCT0001701)
SC
Key words: safety; etomidate; propofol; sedation; endoscopic ultrasound
M AN U
INTRODUCTION
The type of sedative agent used for GI endoscopy varies among regional groups according to the each domestic healthcare policy and trends [1]. The most common agent is the propofol as single use or combination with other medications, with a better pharmacokinetic profile
TE D
than benzodiazepines or opioids in regard to onset time and recovery time [2, 3]. Although propofol is routinely administered for GI endoscopy, it is associated with several adverse events such as hypoxia, hypotension, arrhythmia, and risk of respiratory depression including
EP
apnea [4, 5].
Etomidate, a traditional anesthesia-inducing drug, is an appropriate hypnotic agent with
AC C
rapid onset (5-15 seconds) and recovery (5-15 minutes) [6]. It also leads to minor adverse effects on cardiovascular and respiratory parameter, protects the brain, and does not stimulate histamine release [7, 8]. The hemodynamic stability of etomidate makes it the drug of choice for the sedation of hypotensive patients, as well comprising a suitable option for patients with intracranial pathology, or even for children, when hypotension must be avoided [9].
2
ACCEPTED MANUSCRIPT Furthermore, etomidate causes a minimal increase in airway resistance, but to a lesser extent than thiopental, and may be administered in patients with bronchospasm [10]. The insertion of an echoendoscope is more uncomfortable than the standard endoscope.
RI PT
Also, an initially planned simple diagnostic procedure will be frequently converted to more complex and time consuming interventional procedure. Therefore, it is important to select drugs appropriate for deep sedation with fewer adverse events and a specific pharmacokinetic
SC
profile comprising a rapid onset of action and a short half-life [11].
Therefore, it is reasonable to hypothesize that etomidate administered for sedation in
M AN U
EUS may also result in improved safety and faster recovery, with at least equal effectiveness compared with propofol. However, there are few controlled studies that directly compare etomidate and propofol in sedation for EUS. Therefore, we designed a present trial to compare safety profiles including the proportion of patients with any cardiopulmonary
TE D
adverse event and efficacy of sedation between etomidate and propofol targeted for deep sedation in patients undergoing EUS.
Study Population
EP
PATIENTS AND METHODS
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The study was a randomized, double-blinded, prospective study of 128 patients. Potential patients scheduled for an EUS were approached by the research nurses in a consecutive fashion and invited to participate in the study. Patients were eligible to enter the study if they were aged 18 years or older and less than 70 years, had an American Society of Anesthesiology (ASA) risk class I or II, and scheduled for EUS only. Exclusion criteria comprised the following: (1) pregnancy; (2) known hypersensitivity to any 3
ACCEPTED MANUSCRIPT of the study medications or to either soy- or egg-based products; (3) expected intubation difficulty (modified Mallampati Score class III or IV)[12]; (4) obstructive sleep apnea; (5) history of adverse events with previous sedation; (6) severe liver disorders (liver
RI PT
transaminase > 100 IU/L or liver cirrhosis), severe renal failure (serum creatinine level >2 mg/dL) or severe heart disease (New York Heart Association Class III or IV); (7) desire to have endoscopy without sedation; and (8) declining to provide informed consent. In addition,
SC
for patient safety purposes, those with a systolic blood pressure of (SBP) 0.999
12 (21.1%)
13 (24.1%)
0.878
1 (14.3%)
2 (20.0%)
> 0.999
21 (36.8%)
5 (9.3%)
0.001
1 (14.3%)
3 (30.0%)
0.864
M AN U
Respiratory
1 (14.29%)
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EP
TE D
depression
30
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
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SC
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ACCEPTED MANUSCRIPT
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EP
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Abbreviations MAP, mean arterial pressure; EUS, endoscopic ultrasound; ASA, American Society of Anesthesiology; SBP, systolic blood pressure; OAAS scale, the Observer's Assessment of
AC C
EP
TE D
M AN U
SC
RI PT
Alertness/Sedation scale; SpO2, pulse oximetry; ITT, intent-to-treat;
S0016-5107(17)30176-1
DOI:
10.1016/j.gie.2017.02.033
Reference:
YMGE 10445
To appear in:
Gastrointestinal Endoscopy
Received Date: 17 June 2016 Accepted Date: 23 February 2017
Please cite this article as: Kim MG, Park SW, Kim JH, Lee J, Kae SH, Jang HJ, Koh DH, Choi MH, Etomidate Versus Propofol Sedation For Complex Upper Endoscopic Procedures: A Prospective Double-Blinded Randomized Controlled Trial, Gastrointestinal Endoscopy (2017), doi: 10.1016/ j.gie.2017.02.033. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Etomidate Versus Propofol Sedation For Complex Upper Endoscopic
Short title: Etomidate in complex upper endoscopic procedure
Authors:
RI PT
Procedures: A Prospective Double-Blinded Randomized Controlled Trial
SC
Mi Gang Kim M.D. a, Se Woo Park M.D. a, Jae Hyun Kim M.D. a, Jin Lee M.D. & Ph.D. a, Sea Hyub Kae M.D. & Ph.D. a, Hyun Joo Jang M.D. a, Dong Hee Koh M.D. & Ph.D. a, Min
M AN U
Ho Choi M.D. a
Departmental and institutional affiliation: a
Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan
Correspondence to:
TE D
Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Korea
EP
Professor Se Woo Park, Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine,
AC C
7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do, 18450, Korea Tel: +82-31-8086-2858, Fax: +82-31-8086-2029, E-mail: [email protected]
Word Count: 3,911
ACCEPTED MANUSCRIPT ABSTRACT Background and Aims Although a growing body of evidence demonstrates that propofol-induced deep sedation can
RI PT
be effective and performed safely, cardiopulmonary adverse events have been frequently observed. Etomidate is a new emerging drug that provides hemodynamic and respiratory stability, even in high-risk patient groups. The objective of this study was to compare safety
SC
and efficacy profiles of etomidate and propofol for endoscopic sedation. Methods
M AN U
A total of 128 patients undergoing endoscopic ultrasound were randomized to receive either etomidate or propofol blinded administered by a registered nurse. The primary outcome was the proportion of patients with any cardiopulmonary adverse event. Results
TE D
Overall cardiopulmonary adverse events were identified in 22 patients (34.38%) of the etomidate group and 33 patients (51.56%) of the propofol group without significant difference (P=0.074). However, The incidence of oxygen desaturation (4/64 [6.25%] vs 20/64
EP
[31.25%], P=0.001) and respiratory depression (5/64 [7.81%] vs 21/64 [32.81%], P=0.001) was significantly lower in the etomidate group than in the propofol group. The frequency of
AC C
myoclonus was significantly higher in the etomidate group (22/64 [34.37%]) compared with the propofol group (8/64 [12.50%]) (P=0.012). Repeated measure analysis of variance revealed significant effects of sedation group and time on systolic blood pressure (etomidate group > propofol group). Physician satisfaction was greater in the etomidate group than in the propofol group. Conclusion
1
ACCEPTED MANUSCRIPT Etomidate administration resulted in fewer respiratory depression events and had a better sedative efficacy than propofol; however, it was more frequently associated with myoclonus
RI PT
and increased blood pressure during endoscopic procedures.
Trial registration: the International Clinical Trials Registry Platform (no. KCT0001701)
SC
Key words: safety; etomidate; propofol; sedation; endoscopic ultrasound
M AN U
INTRODUCTION
The type of sedative agent used for GI endoscopy varies among regional groups according to the each domestic healthcare policy and trends [1]. The most common agent is the propofol as single use or combination with other medications, with a better pharmacokinetic profile
TE D
than benzodiazepines or opioids in regard to onset time and recovery time [2, 3]. Although propofol is routinely administered for GI endoscopy, it is associated with several adverse events such as hypoxia, hypotension, arrhythmia, and risk of respiratory depression including
EP
apnea [4, 5].
Etomidate, a traditional anesthesia-inducing drug, is an appropriate hypnotic agent with
AC C
rapid onset (5-15 seconds) and recovery (5-15 minutes) [6]. It also leads to minor adverse effects on cardiovascular and respiratory parameter, protects the brain, and does not stimulate histamine release [7, 8]. The hemodynamic stability of etomidate makes it the drug of choice for the sedation of hypotensive patients, as well comprising a suitable option for patients with intracranial pathology, or even for children, when hypotension must be avoided [9].
2
ACCEPTED MANUSCRIPT Furthermore, etomidate causes a minimal increase in airway resistance, but to a lesser extent than thiopental, and may be administered in patients with bronchospasm [10]. The insertion of an echoendoscope is more uncomfortable than the standard endoscope.
RI PT
Also, an initially planned simple diagnostic procedure will be frequently converted to more complex and time consuming interventional procedure. Therefore, it is important to select drugs appropriate for deep sedation with fewer adverse events and a specific pharmacokinetic
SC
profile comprising a rapid onset of action and a short half-life [11].
Therefore, it is reasonable to hypothesize that etomidate administered for sedation in
M AN U
EUS may also result in improved safety and faster recovery, with at least equal effectiveness compared with propofol. However, there are few controlled studies that directly compare etomidate and propofol in sedation for EUS. Therefore, we designed a present trial to compare safety profiles including the proportion of patients with any cardiopulmonary
TE D
adverse event and efficacy of sedation between etomidate and propofol targeted for deep sedation in patients undergoing EUS.
Study Population
EP
PATIENTS AND METHODS
AC C
The study was a randomized, double-blinded, prospective study of 128 patients. Potential patients scheduled for an EUS were approached by the research nurses in a consecutive fashion and invited to participate in the study. Patients were eligible to enter the study if they were aged 18 years or older and less than 70 years, had an American Society of Anesthesiology (ASA) risk class I or II, and scheduled for EUS only. Exclusion criteria comprised the following: (1) pregnancy; (2) known hypersensitivity to any 3
ACCEPTED MANUSCRIPT of the study medications or to either soy- or egg-based products; (3) expected intubation difficulty (modified Mallampati Score class III or IV)[12]; (4) obstructive sleep apnea; (5) history of adverse events with previous sedation; (6) severe liver disorders (liver
RI PT
transaminase > 100 IU/L or liver cirrhosis), severe renal failure (serum creatinine level >2 mg/dL) or severe heart disease (New York Heart Association Class III or IV); (7) desire to have endoscopy without sedation; and (8) declining to provide informed consent. In addition,
SC
for patient safety purposes, those with a systolic blood pressure of (SBP) 0.999
12 (21.1%)
13 (24.1%)
0.878
1 (14.3%)
2 (20.0%)
> 0.999
21 (36.8%)
5 (9.3%)
0.001
1 (14.3%)
3 (30.0%)
0.864
M AN U
Respiratory
1 (14.29%)
AC C
EP
TE D
depression
30
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
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SC
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ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Abbreviations MAP, mean arterial pressure; EUS, endoscopic ultrasound; ASA, American Society of Anesthesiology; SBP, systolic blood pressure; OAAS scale, the Observer's Assessment of
AC C
EP
TE D
M AN U
SC
RI PT
Alertness/Sedation scale; SpO2, pulse oximetry; ITT, intent-to-treat;
