Sedation with propofol TCI during ERCP: Is the combination with esketamine more effective and safer than with alfentanil (SPEKA): A randomized controlled multicentre trial

Endoscopic retrograde cholangiopancreatography (ERCP) is a complex, often
painful gastrointestinal procedure. Since any movement of the patient could
considerably affect success of the ERCP, procedures are usually performed under
deep sedation. ERCP is often combined with endoscopic ultrasound (EUS) in order
to obtain images and information about the digestive tract and the surrounding
tissue and organs. Over the last decade the combination of propofol and an
opioid has become the standard sedative regime during ERCP in many countries,
despite known side effects, such as hypotension and respiratory depression,
leading eventually to severe hypoxemia. Opioids, especially when used in
combination with sedative-hypnotics, can not only aggravate clinically
significant respiratory depression but also increase the incidence of
postoperative nausea and vomiting.
Esketamine, the s-enantiomer of ketamine - is not only a well-known sedative,
but also has strong analgesic properties. Furthermore, its sympathomimetic
qualities can counteract the hemodynamic depression of propofol, reducing the
risk of cardiovascular or respiratory depression during sedation. Esketamine
could thus be a safer additive to propofol than opioids to achieve an adequate
level of sedation and analgesia with less negative cardiopulmonary side effects
due to reduction of the required dosage of propofol and omission of opioids.

The aim of this study is to demonstrate that procedural sedation with propofol
and esketamine is more effective and will result in less cardiopulmonary
depression than sedation with propofol and the opioid alfentanil. Less side
effects should also lead to higher safety profiles of this sedation regime.


The primary objective of this study is to determine the effectiveness of
propofol/esketamine compared to propofol/alfentanil sedation, both administered
by anaesthetic nurses trained in procedural sedation and analgesia (PSA).
Considering effectiveness there are four aspects to determine the effectiveness
of the propofol/esketamine regime. First, will the synergistic combination of
propofol and esketamine result in a dosage reduction of propofol? Secondly, are
the levels of sedation and analgesia (without opioids) sufficient to perform
the procedure? Thirdly, are patients more satisfied by the combination
propofol/esketamine concerning side effects? Fourth, is recovery time shorter?
Secondary objectives concern patient safety. Safety is thereby a synonym for a
reduction in pulmonary and cardiovascular incidents and complications
(hypotension, respiratory depression, hypoxemia) that could be attributed to
the respective sedation regime.

The study will be performed as a randomized controlled multicentre trial.

Patients will be randomized to an esketamine and propofol regime
(interventional arm) or to an alfentanil/propofol regime (control arm) and
studied during the endoscopic procedure.

Esketamin is a registered drug, used for analgesia and sedation purposes. Many
of the sedationists have experience with this drug due to its common place in
general anaesthesia. Potential side effects of esketamin are psychotomimetic
effects such as vertigo or visual disturbances. Potential benefits of esketamin
are the reduction of cardiopulmonary incidents due to its symphaticomimetic
effects and maintenance of airway reflexes as well as breathing properties,
making it a potentially safer sedative agent in combination with propofol than
alfentanil. Vital signs will be recorded during ERCP, which is already standard
clinical practice. There will be no significant additional burden compared to
standard clinical practice.
Patients and gastroenterologist will be asked to fill in questionnaires before
and after the intervention; this can be considered as a minimal burden for the
patients.