Impact of PReOperative Midazolam on OuTcome of Elderly patients (I-PROMOTE): study protocol for a multicentre randomised controlled trial

Abstract

Introduction: Premedication of surgical patients with benzodiazepines has become questionable regarding risk-benefit ratio and lack of evidence. Though preoperative benzodiazepines might alleviate preoperative anxiety, a higher risk for adverse events is described, particularly for elderly patients (≥ 65 years). Several German hospitals already withhold benzodiazepine premedication from elderly patients, though evidence for this approach is lacking. The patient-centred outcome known as global postoperative patient satisfaction is recognised as a substantial quality indicator of anaesthesia care incorporated by the American Society of Anesthesiologists. Therefore, we aim to assess whether the postoperative patient satisfaction after premedication with placebo compared to the preoperative administration of 3.75 mg midazolam in elderly patients differs.

Methods: This study is a multicentre, randomised, placebo-controlled, double-blinded, two-arm parallel, interventional trial, conducted in nine German hospitals. In total 614 patients (≥ 65-80 years of age) undergoing elective surgery with general anaesthesia will be randomised to receive either 3.75 mg midazolam or placebo. The primary outcome (global patient satisfaction) will be assessed with the validated EVAN-G questionnaire on the first postoperative day. Secondary outcomes will be assessed until the first postoperative day and then 30 days after surgery. They comprise among other things: functional and cognitive recovery, postoperative delirium, health-related quality of life assessment, and mortality or new onset of serious cardiac or pulmonary complications, acute stroke, or acute kidney injury. Analysis will adhere to the intention-to-treat principle. The primary outcome will be analysed with the use of mixed linear models including treatment effect and study centre as factors and random effects for blocks. Exploratory adjusted and subgroup analyses of the primary and secondary outcomes with regard to gender effects, frailty, pre-operative anxiety level, patient demographics, and surgery experience will also be performed.

Discussion: This is, to the best of our knowledge, the first study analysing patient satisfaction after premedication with midazolam in elderly patients. In conclusion, this study will provide high-quality data for the decision-making process regarding premedication in elderly surgical patients.

Trial registration: ClinicalTrials.gov, NCT03052660 . Registered on 14 February 2017. EudraCT 2016-004555-79 .

Keywords: General anaesthesia; Midazolam; Patient satisfaction; Placebo; Premedication.

Conflict of interest statement

AK is an associated editor of the Trials journal. The other authors declare that they have no competing interests.

Figures

Fig. 1

Participant timeline according to the SPIRIT Statement. **Visit 0: preoperative screening and baseline visit, Visit 1: 30–45 min before surgery, Visit 2: operating room, Visit 3: surgery day postoperatively within 0.5–1.5 h after surgery, Visit 4: first postoperative day; Visit 5: 30th postoperative day. AE adverse event, APAIS Amsterdam Preoperative Anxiety and Information Scale, ASA American Society of Anesthesiologists physical status, BMI body mass index, CAM Confusion Assessment Method, EVAN-G Evaluation du Vécu de l’Anesthésie Générale, EQ-5D-5 L health-related quality of life assessment, IADL Instrumental Activities of Daily Living scale, ICU intensive care unit, RRsys systolic blood pressure, SAE serious adverse event, SBT Short Blessed Test, SpO2 peripheral oxygen saturation, VAS visual analogue scale