Sedation with propofol during ERCP: is the combination with esketamine more effective and safer than with alfentanil? Study protocol for a randomized controlled trial

Abstract

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is a gastrointestinal procedure that requires a relatively motionless patient during the intervention. Deep sedation by intravenous propofol combined with an opioid has recently become the preferred sedation technique. However, when high doses of propofol are used, side effects, namely respiratory depression, may occur. Esketamine has hypnotic, analgesic, and sympathomimetic effects. Our assumption is that a combination of propofol with esketamine reduces the dosage of individual drugs, thereby minimizing sedation side effects while keeping the same satisfaction level of patients and endoscopists.Methods/designThe study will be performed as a randomized controlled multicenter trial. Patients undergoing ERCP, ≥ 18 years old, with American Society of Anesthesiologists (ASA) classification I–III will be randomized after written informed consent to group K (propofol/esketamine) or to group A (propofol/alfentanil). The primary outcome, reflecting effectiveness of sedation, is the total dose of propofol. Secondary outcome parameters are patients’ and endoscopists’ satisfaction with the procedure and the number of sedation-related pulmonary and cardiovascular events. Data on sedation-related events are collected by recording of oxygen saturation (SpO2), respiratory rate (RR), end-tidal CO2 (etCO2), heart rate (HR), arrhythmias (electrocardiogram (ECG)), and non-invasive blood pressure (NIBP) measurements. Satisfaction parameters are collected by means of questionnaires before and after the procedure and on the following day.DiscussionEsketamine is known for its effective anesthetic and analgesic effects maintaining spontaneous breathing and airway reflexes. Due to an increase in sympathetic tone, hypotension and cardiac depression is less common. Unfortunately esketamine is also known for its psychotomimetic effects. We aim to demonstrate that the combination of esketamine with propofol for sedation in patients subjected to ERCP interventions is nevertheless superior to a combination of propofol with an opioid.Trial registrationNederland’s Trial Register, NTR5486. Registered on 17 September 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2197-8) contains supplementary material, which is available to authorized users.

<p>Comparison of ketamine-propofol mixture (ketofol) and midazolam-meperidine in endoscopic retrograde cholangiopancretography (ERCP) for oldest old patients</p>

“…Andolfatto and Willman26 used ketofol (1:1) and found adequate sedation in emergency procedural sedation. Eberl et al28 suggested that ketamine and propofol be used together to reduce the total amount of propofol.…”

The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients：a randomized controlled trial

“…Many studies also demonstrated that the requirements of propofol are reduced in elderly individuals [27,28] because of the age-related changes in pharmacodynamics, pharmacokinetics or both [29]. Some studies are exploring the medication strategy of propofol for endoscopic procedure, such as combination medication to reduce the dosage of propofol requirement [9,[30][31][32]. A randomized, double-blinded and controlled trial for elderly patients subjected to colonoscopy showed that EC 50 of propofol was reduced when combined with 1 μg/kg fentanyl and there was no significant difference in adverse events but prolonged awake and discharge time [9].…”

“…Mortero et al [30] demonstrate that the combination of propofol with small-dose ketamine reduced hypoventilation caused by propofol, induced positive mood effects, and produced earlier recovery of perception compared with propofol alone during monitored anesthesia for surgical interventions. Recently, Susanne Eberl et al [32] found that the combination of esketamine with propofol for sedation in patients undergoing ERCP is superior to a combination of propofol with an opioid.…”

Comparison of two supplement oxygen methods during gastroscopy with intravenous propofol anesthesia in obese patients: study protocol for a randomized controlled trial

“…In this study, hypoxemia is defined as SpO 2 of 75–89% for < 60 s, and severe hypoxemia is defined as SpO 2 < 75% at any time or SpO 2 of < 90% for > 60 s [ 20 , 21 ]. Hypotension is defined as a decrease in mean arterial pressure (MAP) > 20% or non-invasive blood pressure of not more than 90/60 mmHg; hypertension is defined as an increase in MAP > 20% or non-invasive blood pressure of at least 140/90 mmHg; bradycardia is diagnosed if HR is < 50 beats/min; tachycardia is diagnosed when HR stays above 100 beats/min.…”

“…Hypotension is defined as a decrease in mean arterial pressure (MAP) > 20% or non-invasive blood pressure of not more than 90/60 mmHg; hypertension is defined as an increase in MAP > 20% or non-invasive blood pressure of at least 140/90 mmHg; bradycardia is diagnosed if HR is < 50 beats/min; tachycardia is diagnosed when HR stays above 100 beats/min. If necessary, ephedrine or phenylephrine, urapidil, atropine, and esmolol were intravenously injected to treat hypotension, hypotension, bradycardia and tachycardia, respectively [ 21 – 23 ].…”