Relaxation for Critically Ill Patient Outcomes and Stress-coping Enhancement (REPOSE 1.0): Pilot Clinical Trial of an Integrative Intervention to Improve Critically Ill Patients' Delirium and Related Outcomes

1. Background 1.1 Risk/Benefits Risks: Anticipated risks from participation in this study are minimal. This and similar relaxation interventions have been tested before and no inconveniences or side-effects have been reported. Adverse events, irrespective of causal relationship, will be collected for all participants Benefits: The direct benefits to participants include the opportunity to receive a relaxation intervention that has been shown helpful in terms of decreasing pain ratings and anxiety and improving quality of sleep in similar settings before.

1.2 Treatment/ Dose Rationale The evidence-based multimodal intervention (duration: 55min) is based on a literature review and the recommendations of the American Holistic Nurses Association (31) and a successful pilot (10). Multimodal integrative interventions demonstrate superior efficacy compared to uni-dimensional ones (32). It includes: a) relaxation and guided imagery (RGI) (40 min, headphones), b) a brief moderate pressure massage session (massage: 15 min). RGI involves: a) guided relaxation, b) a structured guided imagery script and c) music for 15 min (Mozart piano sonata KV283, G major (2 3) II Andante). Moderate pressure, low velocity (4 N, 1-5cm/s) massage consists of squeezing movements with wide area of contact will be applied in the following order and then reverse order, for 2-3 min at each site: over trapezius muscles, lateral arms, forearms, feet and then over the temple and forehead area. Moderate pressure massage is used as it elicits parasympathetic activation, as opposed to light pressure (33). The intervention will be administered once daily (10-11am) for up to 5 consecutive days by trained intervention nurses not involved in patient care. The intervention will start as soon as possible after ICU admission, and will be terminated upon a patient's transfer or discharge from the ICU. Selection of timing of the interventions is based on the daily schedule of the unit, to minimize interference with routine care. A 5-day intervention was selected as most patients develop delirium within the first 5 days of ICU admission (28).

1.3 Trial Conduct This study will be conducted in compliance with the protocol approved by the University of Alberta Health Research Ethics Board (HREB), and according to Good Clinical Practice standards. No deviation from the protocol will be implemented without the prior review and approval of the HREB.

Participants: Adult critically ill patients meeting the eligibility criteria.

Recruitment: Consecutive patients admitted into 2 academic teaching ICUs with Intensive Care Delirium Screening Checklist (ICDSC): 0-3 will be screened by research assistants for admission to the protocol and will be recruited by a research nurse. 2. Trial Objectives Goal: to assess clinical trial feasibility and treatment effect estimates of a multimodal intervention incorporating RGI and moderate pressure massage for prevention of ICU delirium and for improvement of physiological and psychological outcomes in critical illness. 3. Trial Design 3.1 Primary Study Endpoints/Secondary Endpoints Please see below 3.2 Study Design/Type Design: Pilot feasibility, randomized, controlled, double-blinded (clinicians, outcome assessors) trial with 2 parallel groups (intervention and standard care group). Accounting for major risk factors of delirium (28), stratified randomization according to age (<65, ≥65) and surgical or injury trauma (Trauma/ Surgery, non-Trauma/ surgery) with blocking and 1:1 allocation to assure balance in numbers per group will be employed.