Open Medicine 2020; 15: 815–821 Research Article Alex Zanvettor, Wolfgang Lederer, Bernhard Glodny, Andreas P. Chemelli, Franz J. Wiedermann* Procedural sedation and analgesia for percutaneous trans- hepatic biliary drainage: Randomized clinical trial for comparison of two different concepts https://doi.org/10.1515/med-2020-0220 patients treated with remifentanil (EudraCT No. 2006- received March 04, 2020; accepted July 17, 2020 003285-34; institutional funding). Abstract: Procedural sedation and analgesia (PSA) is Keywords: biliary tract, cholestasis, procedural sedation, important during painful dilatation and stenting in analgesia, interventional radiology, remifentanil, piri- patients undergoing percutaneous trans-hepatic biliary tramide, midazolam, S-ketamine drainage (PTBD). A prospective, nonblinded randomized clinical trial was performed comparing different an- algesic regimens with regard to the patient’s comfort. Patients were randomly assigned to two treatment 1 Introduction groups in a parallel study, receiving either remifentanil - ( ) or combined midazolam, piritramide, and S-ketamine. Percutaneous trans hepatic biliary drainage PTBD is a The primary study endpoint was pain intensity before, common therapeutic modality in the treatment of biliary during, and after the intervention using the numerical obstruction, in particular when surgical repair is not - rating scale (0, no pain; 10, maximum pain). The practicable and endoscopic retrograde cholangiopan [ ] secondary study endpoint was the satisfaction of the creatography and stenting have failed 1 . In patients ff interventional radiologist. Fifty patients underwent su ering from neoplasms and metastases involving bile PTBD of whom 19 (38.0%) underwent additional ducts and liver tissue, the intervention all too often aims [ ] ffi stenting. During intervention, the two groups did not at palliative treatment 2,3 . Local anesthesia is su cient differ significantly. After the intervention, the need for for most of the steps of the procedure, but dilatation auxiliary opioids was higher (12.5% vs 7.7%; p = 0.571) prior to insertion of the drain can be very painful and - and nausea/vomiting was more frequently observed frequently requires the services of a skilled anesthesiol (33.4% vs 3.8%; p = 0.007) in patients with remifentanil ogist with experience in inducing conscious sedation [ – ] than in patients with PSA. Overall, 45 patients (90.0%) 4 7 . Inadequate sedation and analgesia can induce needed additional administration of non-opioid analge- anxiety and rapid, shallow breathing. Patients may move sics during postinterventional observation. Remifentanil and alter the position when they experience pain, in and combined midazolam, piritramide, and S-ketamine particular during puncture of the visceral peritoneum. obtained adequate analgesic effects during PTBD. After Uncontrollable motions of the patient can even render the intervention, medications with antiemetics and long- the intervention impossible. ff acting analgesics were more frequently administered in The synergistic e ects of sedative and analgesic agents in procedural sedation and analgesia (PSA) allow low-dose administration of analgesics with fewer side effects [8]. PSA induces decreased levels of conscious- * Corresponding author: Franz J. Wiedermann, Department of ness; thus, patients are sleepy but can be aroused by Anesthesiology and Critical Care Medicine, Medical University of [ ] fl - Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria, voice and touch 7 . Airway protective re exes, sponta e-mail: [email protected], tel: +43-512-504-80431 neous breathing, and cardio-circulatory functions are Alex Zanvettor, Wolfgang Lederer: Department of Anesthesiology unaffected [7]. There is a smooth transition from deep and Critical Care Medicine, Medical University of Innsbruck, sedation to general anesthesia. If indicated, pre-inter- Anichstrasse 35, 6020, Innsbruck, Austria ventional fasting allows PSA to be extended to general Bernhard Glodny: Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria anesthesia. Several sedative and analgesic agents are Andreas P. Chemelli: Department of Radiology, Landesklinikum suitable including propofol, etomidate, midazolam, Baden-Moedling, Baden Moedling, Austria ketamine, dexmedetomidine, and various opioids [9]. Open Access. © 2020 Alex Zanvettor et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 International License. 816 Alex Zanvettor et al. The ideal drug accomplishes rapid onset, with short-time Exclusion criteria were as follows: age <18 years, action, low side effects, and immediate reversibility, pre-interventional fasting <6 h, chronic analgesic treat- because the measures during PTBD may provoke intense ment, emergency, ASA class 4 or 5, known allergy pain sensations of very short duration, such as perito- against PSA medication, pregnancy, or lactation period, neal transgressions or balloon dilatation procedures. and lack of written informed consent to procedure and Remifentanil, a potent opioid with rapid onset and short sedation. Written informed consent regarding the pro- duration of action, has been reported to be safe and cedure and randomized mode of sedation was obtained effective during PTBD [10,11]. Elimination by nonspecific from all patients before intervention. plasma esterases does not depend on hepatic and renal functions [12]. On one hand, the short plasma half-life makes remifentanil an attractive treatment option for day-care patients [13]. On the other hand, remifentanil 2.3 Interventions increases post-interventional hyperesthesia [14]. There- fore, we aimed to investigate whether remifentanil The intervention was performed in a group of four people without additional medication can ensure the patient’s including a specialist in anesthesiology and a specialist in comfort and adequate level of analgesia during the radiology, both with long-standing experience in working intervention and the postoperative observation. The in outsourced radiology intervention rooms. Assistance objectives of this randomized controlled study were to was provided by one anesthesia nursing and one radiology compare two different analgesic regimens in patients technician. Interventions were performed during the undergoing PTBD with regard to patient comfort and daytime usually lasting between 1 and 2 h. Repeated satisfaction of the interventional radiologist. follow-up interventions were not included in this evalua- tion [15]. Analgesic and sedative drugs commonly used in radiological interventions were remifentanil (Ultiva®; GlaxoSmithKline Pharma GmbH), midazolam (Mida- 2 Materials and methods zolam®; ERWO Pharma GmbH),piritramide(Dipidolor®; Janssen-Cilag Pharma GmbH),andS-ketamine (Ketanest®; fi ) 2.1 Trial design P zer corporation Austria . Further medications included metamizole (Novalgin®;Sanofi.Aventis GmbH), diclofenac (Voltaren®; Novartis Pharma GmbH),andparacetamol Aprospective,non-blinded, randomized, controlled clin- (Mexalen®; Ratiopharm GmbH). ical trial for comparison of two different analgesic regimens was conducted from August 3, 2006, to June 20, 2008. In a parallel study, we compared conventional analgesic and 2.3.1 Remifentanil treatment group sedative drugs commonly used in radiological interven- tions in an allocation ratio of 1:1. The study was approved After a loading dose of remifentanil (0.1 μg/kgBW/min) by the local ethics committee (UN 2667_LEK No. 243/2.2.7) administered by an infusion pump (Injectomat®; and registered (EudraCT No. 2006-003285-34). Fresenius Agilia GmbH) for 5 min, dose adjustment according to organ function and anticipated pain was performed with a maximum dose of 0.25 μg/kgBW/min. Perfusion was stopped approximately 5 min before the 2.2 Participants anticipated end of the intervention. All patients consecutively enrolled in the Department of Radiology, Innsbruck University Hospital, Austria, for 2.3.2 PSA treatment group (midazolam, piritramide, planned PTBD and optional biliary stenting were and S-ketamine) screened for eligibility. Inclusion criteria were as follows: age >18 years, pre- Midazolam (0.02 mg/kgBW) and piritramide (0.15 mg/ interventional fasting >6 h, no premedication, elective kgBW) were administered sequentially. S-ketamine procedure, American Society of Anesthesiologists (ASA) (0.2 mg/kgBW) was administered immediately before class 1–3, and written informed consent to procedure the dilatation of the stenosis. During the postoperative and sedation. observation, either piritramide, in case of strong pain, or Procedural sedation and analgesia in PTCD 817 nonopioid analgesics such as metamizole, diclofenac, or biliary sepsis, were recorded. Complication management paracetamol were administered. included chin lift or jaw thrust to relieve airway obstruction placement of an oral or nasal airway and positive pressure ventilatory assistance. Although not 2.3.3 Radiological intervention ideal, specific reversal agents for opioids and benzodia- zepines were available to be administered as a last PTBD and biliary stenting followed a standardized resort. Patients were discharged from the recovery room protocol using a guidewire technique [2]. Patients were when fully alert and responsive, with intact gag and placed in a supine position with skin cleaned and draped cough reflex, proper hydration, and an empty bladder. at the site of puncture. Local anesthesia was achieved with a subcutaneous injection of 10–15 mL of 2% lignocaine (Xylocaine®,GebroPharma).