Conscious sedation is an essential element of advanced endoscopic procedures in selected institutes where general anesthesia is not commonly used. Aside from conventional endoscopic gastroduodenoscopy, endoscopic retrograde cholangiopancreatography- (ERCP-) related procedures may cause discomfort and stress in patients undergoing unpleasant and prolonged procedures [
Propofol is an anesthetic that has been routinely used for anesthesia since 1984 [
We enrolled 182 consecutive patients who had obstructive jaundice and who underwent ERCP under propofol (1% Diprivan Injection-Kit; AstraZeneca, Cheshire, UK) sedation between July 2011 and October 2013 at Yuri Kumiai General Hospital, Japan.
Acute cholangitis is classified into 3 groups according to severity on the basis of the updated 2013 Tokyo guidelines [
cardiovascular dysfunction hypotension requiring dopamine ≧5 neurological dysfunction disturbance of consciousness, respiratory dysfunction PaO2/FiO2 ratio <300, renal dysfunction oliguria, serum creatinine >2.0 mg/dL, hepatic dysfunction PT-INR >1.5, hematological dysfunction platelet count <100,000/mm3.
abnormal WBC count (12,000/mm3, <4,000/mm3), high fever (≧39°C), age (≧75 years old), hyperbilirubinemia (total bilirubin ≧ 5 mg/dL), hypoalbuminemia (<STD × 0.7) (STD: lower limit of normal value; reproduced from [
Therefore, it is recommended that patients with acute cholangitis who do not respond to the initial medical treatment (general supportive care and antimicrobial therapy) undergo early biliary drainage or treatment for etiology.
The patients were classified into Group A or Group B. Group A consisted of patients with mild acute cholangitis or without acute cholangitis who underwent elective ERCP (control group). Group B consisted of patients with a more severe general condition and who required emergent ERCP, namely, patients with severe or moderate acute cholangitis. The procedure time, details of propofol administration, the patient’s resedated condition when returning to the ward, blood pressure, oxygen saturation, and heart rate during ERCP were retrospectively reviewed for all the patients. Adverse events, procedure time, and details of propofol administration were investigated. Patients were excluded from the study if they were <18 years old or had a history of sulfite, egg, soybean, or propofol allergies or did not provide informed consent.
Local pharyngeal anesthesia was performed using an 8% topical lidocaine spray before the intravenous administration of the sedative. Patients received a slow initial intravenous bolus of propofol given at 0.5 mg/kg/10 seconds. Additional intravenous boluses of propofol given at 0.5 mg/kg were slowly administered until sedation, as determined by a Ramsay sedation score [
When a patient showed signs of discomfort or exhibited restlessness following verbal stimulation, an additional 10 mg of propofol was given as a bolus injection and the maintenance infusion rate was increased by 1 mg/kg/hr as resedation. Conversely, if an adverse event occurred, such as hypotension with a systolic blood pressure (SBP) of <80 mmHg or an oxygen desaturation of <90%, the maintenance dose was reduced by 1 mg/kg/hr. Propofol infusion was continued until endoscope removal. The delayed awakening of propofol is defined as the state of sedation for 15 minutes after the cessation of propofol administration [
Patients received supplemental oxygen (2 L/min) by nasal cannula in the endoscopy room as their vital signs and oxygen saturation were continuously monitored and recorded every 5 minutes using a standard three-lead electrocardiogram, pulse oximetry, and automatic blood pressure equipment. Chest excursion and respiratory rates were monitored visually, and consciousness levels were assessed initially after the induction of sedation using the Ramsay sedation score. Patients were discharged from the endoscopy room following the ERCP after confirming that they were fully awake and responding to questions and that their vital signs were stable.
Adverse events were considered to be indicated by a decline in oxygen saturation to <90% or an SBP of <80 mmHg. If a patient developed oxygen desaturation of <90% for more than 10 seconds, supplemental oxygen was used to immediately increase the oxygen flow until the saturation level was >95%. If supplemental oxygen failed to improve the patient’s oxygenation condition within 3 minutes, ERCP and sedation were interrupted to secure the airway.
When hypotension was recognized as SBP < 80 mmHg every 5 minutes of standard observation, blood pressure was immediately rechecked. When SBP < 80 mmHg was confirmed, the rate of intravenous drip was immediately increased from 100 to 150 mL/hr, and decreased the propofol infusion rate was decreased by 1 mg/kg/hr. If supplemental SBP did not improve the patient’s SBP condition within 3 minites, ephedrine administered at 8 mg by bolus intravenous injection.
Normally distributed data were expressed as mean ± SD. Statistical significance was analyzed using the chi-square test or Fisher’s exact probability test and Aspin-Welch’s
A total of 182 patients (men/women = 90/92) receiving ERCP with propofol sedation were registered. The patients were classified into 2 groups: Group A (
Baseline characteristics of 182 patients receiving ERCP with propofol sedation.
Total | Group A | Group B |
|
|
---|---|---|---|---|
Number of cases | 182 | 149 | 33 | |
Sex (male/female) | 90/92 | 77/72 | 13/20 | |
Age (mean ± SD) | 75.4 ± 10.3 | 74.1 ± 10.3 | 82.2 ± 7.1 | 0.0019 |
Body mass index | 22.7 ± 3.7 | 23.0 ± 3.8 | 21.2 ± 3.0 | 0.0060 |
Body weight (kg) | 54.3 ± 13.1 | 55.3 ± 13.3 | 49.9 ± 11.0 | 0.0223 |
ASA-PS classification | ||||
I/II (%) | 76 (41.8) | 65 (43.6) | 11 (33.3) | 0.2781 |
III/IV (%) | 106 (58.2) | 84 (56.4) | 22 (66.6) | 0.2781 |
Underlying diseases | ||||
OSA (%) | 2 (7.4) | 2 (7.4) | 0 | 0.7999 |
Cardiovascular disease (%) | 29 (15.9) | 23 (15.4) | 6 (18.2) | 0.6966 |
Respiratory disease (%) | 9 (5.0) | 6 (4.0) | 3 (9.1) | 0.4411 |
Renal disease (%) | 7 (3.9) | 6 (4.0) | 1 (3.0) | 0.8174 |
Vascular disease (%) | 18 (10.0) | 16 (10.7) | 2 (6.1) | 0.4154 |
ERCP: endoscopic retrograde cholangiopancreatography.
Group A: control group consisting of patients with mild acute cholangitis or without acute cholangitis.
Group B: group requiring emergent ERCP with severe or moderate acute cholangitis.
ASA-PS classification: American Society of Anesthesiologists Physical Status classification.
SD: standard deviation.
OSA: obstructive sleep apnea.
Details of the laboratory data of each group are shown in Table
Laboratory examination data of Group A and Group B.
Reference range | Total average ( |
Group A ( |
Group B ( |
|
|
---|---|---|---|---|---|
WBC (/ |
2700–8800 | 7819.3 ± 4816.8 | 6238.6 ± 2213.6 | 15353.3 ± 6734.2 | <0.001 |
Platelet (/ |
14–34 | 21.4 ± 8.9 | 22.1 ± 8.5 | 18.6 ± 10.7 | 0.1009 |
AST (U/L) | 8–38 | 136.0 ± 171.3 | 124.4 ± 164.3 | 197.4 ± 198.7 | 0.0884 |
ALT (U/L) | 4–44 | 146.9 ± 184.9 | 146.9 ± 182.0 | 150.7 ± 206.2 | 0.9490 |
|
16–73 | 480.0 ± 609.6 | 484.6 ± 634.6 | 462.0 ± 487.9 | 0.7724 |
T-Bil (mg/dL) | 0.2–1.2 | 4.0 ± 5.7 | 3.8 ± 5.9 | 4.6 ± 5.1 | 0.4991 |
ALB (g/dL) | 3.9–5.3 | 3.1 ± 0.7 | 3.2 ± 0.7 | 2.7 ± 0.8 | 0.0006 |
CRP (mg/dL) | <0.3 | 11.2 ± 73.8 | 10.6 ± 81.0 | 15.1 ± 7.1 | 0.6181 |
Group A: control group consisting of patients with mild acute cholangitis or without acute cholangitis.
Group B: more severe general condition group consisting of patients with severe or moderate acute cholangitis.
WBC: white blood cells, AST: aspartate aminotransferase, ALT: alanine aminotransferase,
The mean procedure time was
Details of propofol administration.
Total average | Group A ( |
Group B ( |
|
|
---|---|---|---|---|
Procedure time (minutes) | 49.1 ± 0.02 | 49.0 ± 0.02 | 49.9 ± 0.02 | 0.2102 |
First bolus induction dose (mg) | 29.2 ± 11.7 | 29.6 ± 11.7 | 25.9 ± 9.0 | 0.0391 |
Number of times of additional bolus injection | 1.5 ± 1.8 | 1.5 ± 1.6 | 1.7 ± 2.3 | 0.5707 |
Additional bolus injection dose (mg) | 34.0 ± 39.4 | 34.0 ± 38.4 | 33.8 ± 7.3 | 0.9862 |
Average maintenance dose (mg/kg/hr) | 0.014 ± 0.008 | 0.014 ± 0.009 | 0.015 ± 0.007 | 0.9610 |
Total infusion dose (mg) | 157.0 ± 93.2 | 158.9 ± 89.2 | 145.6 ± 112.5 | 0.5240 |
Group A: control group consisting of patients with mild acute cholangitis or without acute cholangitis.
Group B: more severe general condition group consisting of patients with severe or moderate acute cholangitis.
There were no patients who showed delayed awakening after discharge from the operating room, or who developed other complications. All adverse events associated with cardiopulmonary functions were temporary. There were no severe adverse events associated with cardiopulmonary functions with sequelae. Moreover, there was no patient who required a vasopressor or endotracheal intubation. The adverse events associated with cardiopulmonary functions included hypoxia in 31 patients, hypotension in 26 patients, and bradycardia in 2 patients. There was no significant difference in the rate of each adverse event of hypoxia and bradycardia associated with cardiopulmonary functions in each group. On the other hand, the rate of adverse event of hypotension associated with cardiopulmonary functions in emergent ERCP in Group B was higher than that in Group A (Table
Adverse events associated with cardiopulmonary functions in each group.
Total | Group A ( |
Group B ( |
|
|
---|---|---|---|---|
Hypoxia (%) | 31/182 (17.0) | 28/149 (18.8) | 3/33 (9.1) | 0.1798 |
Hypotension (%) | 26/182 (14.3) | 17/149 (11.4) | 9/33 (27.3%) | 0.0185 |
Bradycardia (%) | 2/182 (1.1) | 2 /149 (1.3) | 0/149 (0) | 0.7999 |
|
||||
Total (%) | 59/182 (32.4) | 47/149 (31.5) | 12/33 (36.4) | 0.7416 |
Group A: control group consisting of patients with mild acute cholangitis or without acute cholangitis.
Group B: more severe general condition group consisting of patients with severe or moderate acute cholangitis.
Acute cholangitis due to obstructive jaundice will require emergency ERCP. As the mortality rate of severe acute cholangitis is high at 64.7% [
Propofol has a high rate of conjugation with serum albumin, shows a high perfusion-limited clearance, and undergoes fast metabolism in the liver. Thus, patients who have liver dysfunction have decreased propofol metabolism. This results in the maintenance of high blood levels which inhibit cardiopulmonary functions likely to be manifested as hypoxia, hypotension, or bradycardia. Although there were several limitations in this investigation being retrospective in nature and a single-center study, our preliminary assessment indicated the safety of NAAP sedation in emergent ERCP.
The total rates of adverse events associated with cardiopulmonary functions manifested as hypoxia, hypotension, and bradycardia were 20.4%, 17.1%, and 1.3%, respectively. Notably, the rates of these adverse events in Group B in which the patients had a more severe general condition were 9.1%, 27.3%, and 0%, respectively.
Over the last 2 decades, the safety of propofol administration in ERCP has been wellreported (Table
Summary of reports in the literature on ERCP with propofol sedation.
Author | Year | Sedation | Administrator | Number of cases | Mean age | Adverse event (%) | Hypoxia <90% (%) | Hypotension |
Bradycardia |
---|---|---|---|---|---|---|---|---|---|
Wehrmann et al. [ |
1999 | Propofol | Physician | 99 | 63.6 ± 23.3 | NA | 11 (11.1) | 7 (7.1) | 5 (5.1) |
Krugliak et al. [ |
2000 | Propofol | Anesthesiologist | 15 | 56.8 ± 12.5 | 0 | 0 | 0 | NA |
Jung et al. [ |
2000 | Propofol | Anesthesiologist | 39 | 62 | NA | 2 (5.1) | 1 (2.6) | NA |
Vargo et al. [ |
2002 | Propofol | Physician | 38 | 52.9 ± 2.4 | 20 (52.6) | 14 (36.8) | 6 (15.8) | 0 |
Chen et al. [ |
2005 | Propofol | NA | 35 | 53.89 ± 17.12 | 15 (42.9) | 2 (5.7) | 7 (20.0) | 0 |
Riphaus et al. [ |
2005 | Propofol | Physician | 75 | 83.7 ± 7.8 | NA | 8 (10.7) | 6 (8.0) | 3 (4.0) |
Kongkam et al. [ |
2008 | Propofol | ACLS trained physician, gastroenterologist | 67 | 52.31 | NA | 15 (22.3) | 6 (9.0) | 2 (3.0) |
Angsuwatcharakon et al. [ |
2012 | Balanced-propofol | Endoscopic nurse | 103 | 59.56 ± 13.65 | NA | NA | 14 (13.6) | 1 (1.0) |
Khan et al. [ |
2014 | Propofol | BLS and ACLS trained physician, gastroenterologist | 156 | 54.39 ± 17.0 | 2 (1.3) | 2 (1.3) | 0 | 0 |
Present study | 2014 | Propofol | Endoscopist | 182 | 75.4 ± 10.3 | 59 (38.8) | 31 (20.4) | 26 (17.1) | 2 (1.3) |
ERCP: endoscopic retrograde cholangiopancreatography.
ACLS: advanced cardiac life support.
BLS: basic life support.
NA: not available.
Propofol is metabolized mainly in the liver and has a high rate of the conjugation with serum albumin. Propofol that is not conjugated with serum albumin exerts an anesthetic effect. Therefore, liver dysfunction and hypoalbuminemia may reduce propofol clearance in the liver [
A previous meta-analysis indicated that propofol sedation in ERCP was not associated with any increased risk of complications [
In many countries, it is recommended that propofol should be used by anesthesiologists or that it must be administered under the direct supervision of anesthesiologists. However, propofol is not always available, particularly in small hospitals. Recently, the concept of NAAP sedation has emerged [
In conclusion, NAAP sedation is feasible even in emergent ERCP. Although some transient adverse events associated with cardiopulmonary functions (e.g., hypotension) were observed, no serious adverse events occurred. Thus, propofol may be used in emergent ERCP but careful monitoring is mandatory.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors are indebted to Dr. Edward Barroga, Associate Professor and Senior Medical Editor of the Department of International Medical Communications of Tokyo Medical University, for the editorial review of the English paper.