Surgical Intensive Care Unit Optimal Mobilisation Score · Waak, Karen; Massachusetts General...

For peer review only

Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) Trial: a protocol for an international, multicentre,

randomised controlled trial focused on goal-directed early mobilisation of surgical ICU patients

Journal: BMJ Open

Manuscript ID: bmjopen-2013-003262

Article Type: Protocol

Date Submitted by the Author: 21-May-2013

Complete List of Authors: Meyer, Matthew; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine; Harvard Medical School, Stanislaus, Anne; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Lee, Jarone; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Waak, Karen; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ryan, Cheryl; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine

Saxena, Richa; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ball, Stephanie; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Schmidt, Ulrich; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine; Harvard Medical School, Piva, Simone; University of Brescia at Spedali Civili, Anesthesia, Intensive Care and Perioperative Medicine Walz, Matthias; UMass Memorial Medical Center, Anesthesia Talmor, Daniel; Beth Israel Deaconess Medical Center, Anesthesiology; Harvard Medical School, Blobner, Manfred; Technischen Universität München,

LATRONICO, NICOLA; UNIVERSITY OF BRESCIA, ANESTHESIOLOGYINTENSIVE CARE Eikermann, Matthias; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine

<b>Primary Subject Heading</b>:

Intensive care

Secondary Subject Heading: Rehabilitation medicine, Intensive care, Surgery, Neurology, Respiratory medicine

Keywords:

Adult intensive & critical care < ANAESTHETICS, REHABILITATION MEDICINE, Change management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Adult neurology < NEUROLOGY, RESPIRATORY MEDICINE

(see Thoracic Medicine), Adult surgery < SURGERY

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol for an

international, multicentre, randomised controlled trial focused on goal-directed early

mobilisation of surgical ICU patients

Matthew J. Meyer MD&, Anne B. Stanislaus MS*, Jarone Lee MD, MPH^, Karen Waak DPT@,

Cheryl Ryan RN!, Richa Saxena PhD§, Stephanie Ball RN, DNS!, Ulrich Schmidt MD, PhD¥,

Simone Piva MD¤, Matthias Walz MD++, Daniel S. Talmor MD, MPH**, Manfred Blobner MD§,

Nicola Latronico MD$, and Matthias Eikermann MD, PhD+#

& Research Fellow, Department of Anesthesia, Critical Care, and Pain Medicine,

Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

* Research Assistant, Department of Anesthesia, Critical Care, and Pain Medicine,

Massachusetts General Hospital, Boston, MA, USA

^ Instructor in Surgery, Trauma, Emergency Surgery, Surgical Critical Care, Massachusetts

General Hospital and Harvard Medical School, Boston, MA, USA

$ Professor, Department of Anesthesia, Intensive Care and Perioperative Medicine, University

of Brescia at Spedali Civili, Brescia, Italy

§ Professor, Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität

München, Munich, Germany

@ Clinical Specialist, Department of Physical and Occupational Therapy, Massachusetts

General Hospital, Boston, MA, USA

! Clinical Nursing Supervisor, Department of Clinical Nursing Services, Massachusetts General

Hospital, Boston, MA, USA

§ Assistant Professor, Department of Anesthesia, Critical Care and Pain Medicine,

Massachusetts General Hospital, Harvard Medical School, Boston, MA

¥ Assistant Professor, Department of Anesthesia, Critical Care and Pain Medicine,

Massachusetts General Hospital, Harvard Medical School, Boston, MA

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¤ Assistant Professor, Department of Anesthesia, Intensive Care and Perioperative Medicine,

University of Brescia at Spedali Civili, Brescia, Italy

++ Associate Professor, UMass Memorial Medical Center and UMass Medical School,

Worcester, MA, USA

** Associate Professor, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel

Deaconess Medical Center, Harvard Medical School, Boston, MA

# Director of Research, Critical Care Division, Massachusetts General Hospital and Associate

Professor, Harvard Medical School; +Associate Professor, Universitaet Duisburg-Essen,

Germany

Corresponding Author:

Matthias Eikermann

Department of Anesthesia, Critical Care and Pain Medicine

Massachusetts General Hospital

55 Fruit Street

Boston, Massachusetts 02214

[email protected]

Phone: 617-643-4408

Keywords: early rehabilitation, mobilisation, muscle weakness, critical care, holistic nursing

Word Count: 4550

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Introduction: Immobilisation in the intensive care unit (ICU) leads to muscle weakness and is

associated with increased costs and long-term, functional disability. Prior studies show early

mobilisation of medical ICU patients improves clinical outcomes. The Surgical ICU Optimal

Mobilisation Score (SOMS) Trial aims to test if a financially cost-free intervention to facilitate

goal-directed early mobilisation in the surgical ICU improves subject mobilisation and

associated clinical outcomes.

Methods and analysis: The SOMS trial is an international, multicentre, randomised clinical

study being conducted in the United States and Europe. We are targeting 200 patients. The

primary outcome is average daily SOMS level and key-secondary outcomes are ICU length of

stay until discharge readiness and “mini” modified functional independence measure (mmFIM;

ICU and hospital discharge). Additional secondary outcomes include quality of life assessed at

three months after hospital discharge and global muscle strength at ICU discharge. Exploratory

outcomes will include: ventilator-free days, ICU and hospital length of stay and three month

mortality. We will explore genetic influences on the effectiveness of early mobilisation and

center-specific effects of early mobilisation on outcomes.

Ethics and dissemination: Following IRB approval in three institutions, we started study

recruitment and plan to expand to additional centers in Germany and Italy. Safety monitoring will

be the domain of the Data and Safety Monitoring Board. The SOMS Trial will also explore the

feasibility of a transcontinental study on early mobilisation in the surgical ICU. Results of this

study, along with those of ancillary studies, will be made available in the form of manuscripts

and presentations at national and international meetings.

Registration: This study has been registered at clinicaltrials.gov (NCT01363102).

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ARTICLE SUMMARY

Article Focus

o Early mobilisation is important for critically ill patients who are at risk of developing

intensive care unit (ICU) acquired weakness.

o ICU acquired muscle weakness is associated with increases in duration of mechanical

ventilation, intensive care unit length of stay, and mortality.

o In the surgical ICU, contraindications to early mobilisation exist in subsets of patients.

We evaluate the value of the surgical ICU optimal mobilisation score score (SOMS)

guided algorithm for goal-directed early mobilisation.

Key Messages

o This protocol presents an international, multicentre, randomized controlled clinical trial in

the surgical ICU analysing the efficacy of goal-directed early mobilisation compared to

standard of care on clinically important outcomes.

o The results of this trial should be broadly generalizable and provide a cornerstone for

future early mobilisation research in the surgical ICU.

Strengths and limitations

Strengths

o International, multicentre, randomised controlled clinical trial

o Straightforward, intuitive, and easily implementable algorithm designed by a

multidisciplinary team interested in critical care medicine

o No added financial cost to implement the SOMS algorithm

o Exploratory testing of genetic polymorphisms which may explain parts of the variance in

the effectiveness of early mobilisation

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Limitation

o Contamination bias may occur when clinical experience with intervention activities

affects mobilisation therapy in the standard of care group

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INTRODUCTION

Background

Prior studies have shown that early mobilisation improves outcomes in the medical intensive

care unit (ICU).1-3 Currently there is little data on the effects of early mobilisation in the surgical

ICU, with some fear that surgical patients could be harmed by premature immobillisation

following major surgery.4 The risks of immobilising patients are well established4, 5 especially

ICU-acquired weakness.6, 7 ICU-acquired weakness is associated with increased risk of

aspiration,8 increased length of hospital stay (LOS)9 and increased mortality.9 Moreover, the

consequences of ICU acquired muscle weakness can result in persistent functional disability for

at least five years10, 11 which affects the quality of life of ICU survivors.12

Moderate exercise can mitigate the adverse consequences associated with immobility by

improving muscle strength13 and physical function3 and it can translate into improved patient

outcomes. Three prospective studies conducted in the medical ICU demonstrate improved

outcomes when mobilisation was made a priority: patients have less exposure to

benzodiazepines,2 shorter durations of delirium,2, 3 less time on mechanical ventilation,3 fewer

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ICU days,1, 2 fewer hospital days1, 2 and better functional independence at hospital discharge.3

Mobilising patients following surgery has been part of the surgical culture for over a century.14, 15

A variety of different surgical procedures and conditions have been deemed safe for early

mobilisation including: blunt trauma,16 full thickness skin grafts,17 left ventricular assist device

placement18 and lung surgery.19 In elderly patients, early mobilisation following treatment for

acetabular fractures has improved outcomes.20 Establishing early mobilisation as safe following

certain procedures, such as peripheral angioplasty,21 has helped allocate hospital resources

more efficiently.22 However, there is evidence that early mobilisation may have negative effects

in disease-specific subgroups such-as brain trauma.23

In the surgical ICU, research on early mobilisation is limited. Barriers to mobilisation include:

surgical wound pain, musculoskeletal trauma, unstable fractures, open wounds, drains and

other medical devices physically attached to the patient, and the patient’s proximity to or from

surgery. Perceived difficulties to mobilisation also depend on the profession and training of the

health care provider.24 In surgical patients, optimally tailored mobilisation is desirable to avoid

the potential morbidity from excessive or inappropriate mobilisation.

In response, our team, including critical care nurses, physical therapists and physicians,

developed the Surgical ICU Optimal Mobilisation Score (SOMS)24 and we are applying it as an

algorithm for goal-directed early mobilisation in the surgical ICU. The SOMS is a simple “0” to

“4” score ranging from “No activity” to “Ambulation.” The achieved SOMS on the first day of

surgical ICU admission is an independent predictor of surgical ICU and hospital LOS, and in-

hospital mortality.25 The SOMS facilitates the nominal classification of mobility in the surgical

ICU and has adequate inter-rater reliability.25

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Objectives

The primary objective is to:

1) Evaluate the effectiveness of the SOMS guided algorithm for goal-directed early mobilisation

compared to standard of care on the primary outcome of average daily patient mobilisation,

and the key-secondary outcomes of surgical ICU LOS and patient functional mobility at

surgical ICU and hospital discharge.

2) Explore the effects of goal-directed early mobilisation compared to standard of care on

quality of life after hospital discharge and global muscle strength at ICU discharge.

The secondary objectives are to:

1) Generate data for hypotheses and power calculations for future trials.

2) Analyze relationships between polymorphisms in genes associated with circadian rhythm,

sleep cycle, and muscle homeostasis and response to early mobilisation treatment.

Hypotheses for the primary outcome

H1) Subjects in the intervention group, receiving SOMS guided goal-directed early mobilisation

treatment, compared with standard care will have a higher average daily SOMS level,

shorter length of surgical ICU stay, and better functional mobility at discharge.


treatment, compared with standard care will have better quality of life following hospital

discharge and better muscle strength at surgical ICU discharge.

METHODS AND ANALYSIS

Trial design

The SOMS group has designed an international, multicentre, randomized controlled trial. The

ClinicalTrials.gov registration number is NCT01363102. An outline of the study design and daily

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work is in Figure 1. We pledge to adhere to the CONSORT 2010 Statement 26 for reporting of

our trial.

Subjects

All adult surgical ICU patients who have been ventilated for less than 48 hours and are

expected to continue ventilation for at least another 24 hours, and who meet baseline criteria for

functional independence (Barthel Index score ≥70 two weeks prior to admission27) are

considered for the study. Table 1 contains the exclusion criteria.

Exclusion Criteria Justification

Irreversible disorders with 6-month

mortality estimated at greater than 50%

Incomplete outcome data

Rapidly developing neuromuscular disease Incomplete study procedures

Cardiopulmonary arrest Unable to ensure future independent

mobility

Brain injury with Glasgow Motor Score <5 Unable to ensure future independent

mobility

Elevated intracranial pressure Intervention contraindicated

Rupture / leaking aortic aneurysm Intervention contraindicated

Acute MI before peak troponin has been

reached

Intervention contraindicated

Absent lower extremities Incomplete study procedures

Unstable fractures Intervention contraindicated

Prolonged hospitalization > 5 days at

enrolment hospital or at an outside hospital

Inability to adequately assess outcome

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Pregnancy (women 18 – 55 years old) Intervention contraindicated

Enrolment in another clinical trial Potential confounding factors

Table 1. Study exclusion criteria.

Recruitment timeframe

This trial is occurring currently in the surgical ICU at three academic medical centers in the

United States with expectations of expansion to one academic medical center in Germany and

one in Italy. The trial began June 2011 and is expected to be complete in three years.

Recruitment and randomisation

The local investigator will screen surgical ICU patients daily. Any patient who is eligible for the

study will have his health care proxy approached to obtain informed consent, except when the

subject has been recently extubated and is able to consent without a proxy. The health care

proxy and/or potential subject will be able to discuss the study with the investigator as well as

seek any additional counsel prior to agreeing to participate.

After obtaining consent, subjects will be immediately randomly allocated into the intervention or

standard of care group by study staff. We stratify according to Glasgow Coma Scale (GCS; ≤8,

>8) and Acute Physiology and Chronic Health Evaluation II (APACHE II; ≤12, >12) at each

center. Subjects are stratified into four groups: 1) GCS ≤8, APACHE II ≤12; 2) GCS ≤8,

APACHE II >12; 3) GCS >8, APACHE II ≤12; 4) GCS >8, APACHE II >12. Into each sub-group

(1-4), the stratified randomisation is restricted to 50:50 (intervention:standard of care) initially.

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Administrative structure

The clinical coordinating center is at the Massachusetts General Hospital in Boston, MA, USA

and responsible for preparation of the protocol and revisions, managing communications and

publishing study results. In each surgical ICU there is a clinical member of the unit (for example

a clinical nurse specialist or a nurse practitioner) who helps facilitate the implementation of the

SOMS guided goal-directed early mobilisation (see Table 2).

Roles of the SOMS Facilitator

Standard of care

• Record activity level and SOMS achieved

• Identify adverse events and report them to study staff

Intervention

• Facilitate the discussion related to setting a daily SOMS goal with the rounding

team, nurses, physical therapists, and respiratory therapists

• Assist nurses with mobilisation strategies to achieve SOMS goal

• Give advise on how to address barriers to early mobilisation

• Present barriers to mobilisation to rounding team for solutions


Table 2. The role of the SOMS facilitator pertaining to intervention and standard of care

subjects.

Surgical optimal mobilisation score (SOMS) algorithm

The SOMS algorithm for goal-directed mobility ranges from “0 – No mobility” to “4 – Ambulation”

(Figure 2). The intermediate steps are “1 – Passive Range of Motion,” “2 – Sitting,” and “3 –

Standing.” A SOMS of “0” indicates that no mobilisation should be considered due to the clinical

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state of the subject. A SOMS of 1 indicates the nurse can perform passive range of motion

exercises while the patient is in bed. The passive range of motion entails: ankle dorsiflexion,

knee and hip flexion, hip abduction, shoulder flexion, abduction and external rotation, wrist

flexion and elbow flexion. The magnitude and frequency of passive range of motion is based

upon clinical discretion. A subject achieves a SOMS of 2 if able to sit up either on the side of the

bed or on a chair. A SOMS of 3 indicates that a patient is able to stand with or without

assistance. The highest level a patient can achieve is a SOMS of 4, in which the patient is able

to ambulate.

Standard of care

Surgical ICU nurses conduct daily neurological assessments using the Richmond Agitation

Sedation Scale for arousal and the Confusion Assessment Method for delirium. Subjects in both

study and control groups are managed by goal-directed sedation and undergo daily decreases

in sedatives and/or narcotics. Contraindications to daily attempts to decrease sedation are:

persistent neuromuscular blockade, sedative infusion for active seizures or alcohol withdrawal,

persistent agitation, active myocardial ischemia and elevated intracranial pressure. All patients

receive early enteral feeding and patients with high glucose concentrations are treated with

protocol-based insulin regiments.

Liberating patients from mechanical ventilation is done via a protocol, with the decision to

extubate made by the clinical team. Daily spontaneous breathing trials occur with all subjects as

long as there are no contraindications (critically elevated intracranial pressure, neuromuscular

blocker requirement, significant hemoptysis, hemodynamic instability, active myocardial

infarction, an unstable airway, fraction of inspired oxygen > 0.6, pressure control > 20 cm H2O,

positive end-expiratory pressure ≥8 cm H2O, expiratory volume ≥ 15 L/min or extracorporeal life

support).

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Intervention

The intervention (SOMS guided goal-directed early mobilisation) will begin on the day following

consent unless signed consent is received prior to the surgical ICU team conducting morning

rounds. The SOMS algorithm (Figure 2) will be discussed during morning rounds when the team

defines a SOMS goal for the day with the assistance of the SOMS facilitator. Once the

mobilisation goal has been determined, a sign will be posted at the subject’s bedside with the

goal for the day. The bedside nurse will work with the subject to achieve the goal. Prior to

afternoon rounds, the nurse will document the highest achieved SOMS for the day. If the goal

SOMS was neither met nor exceeded, the nurse documents barriers to mobilisation. These

barriers will be discussed and attempts will be made to mitigate these barriers (i.e. pain, anxiety,

hemodynamic or respiratory concerns) in order to meet the SOMS goal for the following day.

Blinding

Given the design of the SOMS trial, blinding to the primary outcome is impossible. The

assessors of the key-secondary outcome of mmFIM at surgical ICU and hospital discharge and

the secondary outcome of SF36 three months after hospital discharge will be blinded to the

study assignment. The data analyst will also be blinded to the study group assignments.

Outcome measures

The primary outcome is mean achieved SOMS level over the course of the ICU stay and this

will be recorded daily until ICU discharge. The key-secondary outcome of ICU LOS until

discharge readiness will be recorded once determined by the clinical team. The key-secondary

outcome of mmFIM will be assessed at ICU discharge readiness and hospital ICU discharge

readiness. The secondary outcome of quality of life obtained through SF36 survey will be

completed at least three months following hospital discharge. The secondary outcome of

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medical research council (MRC) scale for testing global muscle strength will be administered

daily while in the ICU.

Exploratory outcomes for this study will include: ICU LOS, hospital LOS, in-hospital mortality,

three month mortality, discharge disposition, ICU delirium days, ventilator-free days, duration of

mechanical ventilation (days), sedation-free days, narcotic-free days, average daily morphine

equivalent dose (mg), neuromuscular blocking agent days, neuromuscular blocking agent

infusion days, corticosteroid days, vasopressor-free days, anti-psychotic medication days, daily

serum glucose high (mg/dL), daily serum sodium high (mEq), and physical therapy visits. All

outcome measures will be calculated from Study Day 1 and stop with surgical ICU discharge

unless otherwise indicated.

“Mini” modified functional independence measure

A trained and blinded member of the study staff will determine the “mini” modified functional

independence measure (mmFIM) at ICU and hospital discharge readiness. The mmFIM is a

shortened version of the mFIM (modified functional independence measure) and contains only

two (locomotion and transfer) of the five components from the mFIM to better reflect the

functional activities of critically ill patients.28 Like the mFIM, the mmFIM is scored from 1 to 4. A

score of 1 indicates near or complete dependence for the aforementioned skill, a 2 indicates

partial independence, a 3 indicates independence with activity set-up or adaptive equipment,

and a 4 indicates complete independence. Previously reported data have indicated a linear

relationship between the standard FIM and the mFIM scales.29 The mmFIM data will be

analyzed dichotomously, with a score of 4 indicating complete independence and scores of 1-3

indicating activity dependent upon others or adaptive equipment.

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Short form 36

The short form 36 (SF36v2; QualityMetric Inc., Lincoln, RI, USA) is a generic health status

questionnaire validated for use across diverse populations.30 It consists of 36 questions which

provide summaries on physical, emotional and social function. The data is gathered using eight

domains: physical function, social function, role limitations secondary to physical health, role

limitations secondary to emotional well-being, bodily pain, vitality, general mental health and

general health.31 The SF36 is applied in our study to assess subject quality of life three months

following hospital discharge.

Medical research council manual muscle strength testing

The MRC is a measure which reliably predicts in-hospital mortality, surgical ICU LOS, and

hospital LOS.9 Study staff will aim to measure the MRC daily. The MRC manual muscle strength

testing may only be assessed if a subject’s level of sedation (Richmond Agitation Sedation

Scale ≥ -1), attention span and ability to follow instructions are adequate. The ability to follow

instructions will be gauged by asking the patient a series of 1- and 2 step instructions, a

modification of the De Jonghe et al. approach6 which we have previously reported.9 If the patient

is unable to complete the steps or deemed not alert, the test will not be conducted for that day.

When appropriate, the MRC will be conducted daily while the patient is in the surgical ICU. The

MRC data will be analyzed as a continuous variable.

Sample size estimation

The sample size calculation is informed by data from Kasotakis et al25 and Schweikert et al.3

From Kasotakis et al25 we predict an intergroup SOMS difference of 1±1.5 and a correlation of

SOMS to surgical ICU LOS of r = -0.54. From Schweikert et al3 we predict an incidence of a

mmFIM score of 4 (complete independence for the activity evaluated) of 59% in the intervention

group and 35% in the standard of care group.3 Allowing for an expected 11% mortality rate and

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11% attrition due to dropouts, enrolling 200 subjects, 100 in each group, will provide us with a

power of >80% to identify an intergroup difference with an alpha error of 0.05.

Enrollment goals will be 1– 4 subjects per site per month. Site enrollment will be evaluated

every three months through communications relayed by site lead investigators and designated

representatives with the clinical coordinating center. Any unexpected delays in enrollment will

be discussed between the clinical coordinating center and the respective site. If the delays in

enrollment are due to limitations brought upon by the inclusion and exclusion criteria, then

changes will be considered. Any changes to these criteria will require the approval of the Data

Safety Monitoring Board (DSMB) and the institutional review board of each institution. If

enrolment is persistently below expectations and no changes to the inclusion or exclusion

criteria are identified, additional clinical sites may be included.

Statistical methods

The study analysis will be by intention to treat. The main outcomes of the study will be tested

using a hierarchical sequence so the hypotheses can be tested with an alpha-error of 0.05

without adjustment for multiple testing.32 The outcomes will be tested in this a priori defined

order: mean daily SOMS level, surgical ICU LOS until discharge readiness, and mmFIM score.

The statistical analysis will be conducted by a statistician blinded to the intervention.

Data collection

Baseline descriptive data collection will occur on the day of enrolment and include: age, gender,

race, ethnicity, height, weight, best pre-admission SOMS, admission diagnosis, pre-existing co-

morbidities (diabetes mellitus, CAD, asthma, PVD, renal failure, psychiatric disease,

musculoskeletal disease, other) and admitting surgical team.

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Clinical data will be collected daily during the surgical ICU admission including: highest blood

glucose level, highest sodium concentration, modal Richmond Agitation Sedation Scale,

Confusion Assessment Method for the ICU, and greatest pain score (1-10). Total daily dose will

be collected for specific subject medications: neuromuscular blocking agents, narcotics,

sedatives, antipsychotics, intravenous vasopressors, and glucocorticoids. Physical therapy visits

will be monitored and time recorded. The data from the paper copies will be uploaded to a

secure database (REDCap). Data stored on REDCap is coded and without protected

information.

Safety guidelines for mobilisation

Oxygen saturation, electrocardiography, blood pressure and heart rate will be monitored

throughout the study as indicated by clinical staff. The health care provider will be responsible

for determining whether the study intervention should be stopped in the individual subject. In the

situation of severe and/or persistent hypoventilation, or when blood pressure or heart rate

change substantially to a threshold defined during morning rounds by the surgical ICU care

team, mobilisation therapy will be terminated. Additionally, the SOMS algorithm has been

designed by a multidisciplinary team to ensure the safety of the subject. Subjects are not to be

advanced to greater mobilisation levels unless they fulfill specific safety-focused criteria (Figure

2).

Adverse events

Adverse events will be recorded daily. Nursing charts and documentation, as well as physicians’

notes will be reviewed daily to identify potential adverse events.

All adverse events will be recorded and are defined as any unfavorable and unintended signs,

symptom, or disease chronologically associated with mobilisation therapy. The relationship of

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any adverse event to mobilisation therapy will be assessed by the investigator and qualified by

association (not related, unlikely, possibly, probably, or definitely related) and intensity of the

effect (mild, moderate, or severe). All adverse events will be summarized by treatment group

and reported to the Data Safety and Monitoring Board (DSMB) at the time of review.

Adverse events will be monitored daily, and, when appropriate, reported to the local human

research committee. Severe adverse events include: fall to knees, endotracheal tube removal

and oxygen desaturation to less than 80%.3 Severe adverse events related to arterial blood

pressure will be defined individually by the clinical team since this condition is greatly dependent

upon pathology, treatment and the overall clinical milieu.

Role of the data safety and monitoring board

A DSMB has been created and is comprised of physicians with relevant critical care and

medical experience. The members are not involved in the study and will be completely

independent of any study related patient recruitment and data collection. One interim review

focused on safety data will be completed when we have data at three month follow-up data on

100 subjects.

ETHICS AND DISSEMINATION

Consent

For the majority of participants in our study written consent will be provided by a healthcare

proxy as the inclusion criteria of critically ill and intubated implies patients have impaired

decision making. Informed consent will be obtained from each potential subject’s healthcare

proxy by a study physician or mid-level provider (physician assistant or nurse practitioner). The

researcher receiving the consent will give a copy of the IRB approved informed consent form to

the healthcare proxy and/or potential subject. The healthcare proxy and/or potential subject will

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have adequate time to read the informed consent form, evaluate the risks of the study, consult

with any family members or clinicians requested, and ask questions of the study staff. If the

healthcare proxy and/or patient decides to participate then the informed consent form will be

signed. All subjects will be informed of their participation in the study following resolution of their

critical illness and any residual delirium.

Ancillary Studies

The SOMS Trial will be conducted in the United States and in Europe. A validation trial of the

SOMS has been conducted in English in the United States.25 Additional validation studies of the

Italian and German SOMS translations in Italy and Germany, respectively, are planned. This

study lends itself to a qualitative assessment of culture change in the surgical ICU from a unit

with predominantly immobilised patients to one with a focus on early mobilisation. We have the

opportunity to assess the manner in which patients are mobilised internationally and discuss

and share any best practices that are identified.

Alongside of our primary trial, subjects will be able to opt-in to a related genetic study. We

anticipate wide variability in the effectiveness of early mobilisation, and speculate that some of

the variability is in part related to circadian dysregulation. In ICU patients, decreased total sleep

time, decreased deep (restorative) sleep, fragmented sleep, as well as altered circadian

patterns have been reported.33, 34 Other preliminary data suggest that treatments to improve

circadian disruption such as intermittent light therapy may facilitate early ambulation in critically

ill patients.35 We also believe some of the variability in the effectiveness of early mobilisation is

related to inherent qualities of the muscles. Therefore, with an exploratory intention, we will

evaluate if the existence of single nucleotide polymorphisms in genes associated with sleep,

circadian rhythm and muscle function explain some variance in the effectiveness of early

mobilisation in ICU patients (Figure 3).

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We will conduct genetic tests to find associations between known polymorphisms related to

sleep quality, circadian rhythm and muscle homeostasis, and muscle strength, mobility and

surgical ICU outcomes. Specifically we will focus on polymorphisms in CLOCK,36 NPAS2,37

PER2,38 PER3,39 PDE4D,40 MUC1,41 ATP2B1,41, 42 DCDC5,41 TRPM6,41 SHROOM3,41, 43 and

MDS141 genes, which are associated with sleepiness, sleep phase, and potentially respiratory

muscle weakness. If consent is received for the genetic study, blood is drawn and stored prior to

transport to The Center for Human Genetic Research at Massachusetts General Hospital where

blood samples will be processed and genetic analysis performed. All laboratory specimens will

be stored with a coded identification to maintain privacy.

Protocol funding

This research received no specific grant from any funding agency in the public, commercial or

not-for-profit sectors. This study is funded through departmental resources and those resources

are used exclusively for administrative study staff salary. There is no additional funding for the

implementation of the SOMS algorithm in the surgical ICU.

Publication and dissemination

The results of this study along with those of ancillary studies will be publicized in the form of

presentations at national and international meetings. The complete study and conclusions

regarding the primary objectives will be presented in manuscript form.

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DISCUSSION

This paper presents the protocol and data analysis plan for the SOMS Trial; an international,

multicentre, randomised controlled clinical study evaluating SOMS guided goal-directed early

mobilisation and its capacity to improve patient mobilisation, reduce surgical ICU LOS and

improve other surgical ICU outcomes. Research associated with mobilisation in the medical ICU

is robust and the associations with improved clinical outcomes strong.1-3 We believe the SOMS

algorithm will help surgical ICU clinicians avoid many of the risks of immobilisation including:

atrophy and decreased contractile function of skeletal muscles5, 44 and the diaphragm,45 motor

and sensory neuropathy,46 and persistent functional deficits10, 11 likely due to ICU acquired

weakness,6, 7 We also believe the structure of the SOMS algorithm will help surgical ICU

clinicians minimize the hazards or mobilising patients: dislodgement of medical devices,

mechanical trauma, hemodynamic instability24 or hypoxia secondary to respiratory failure47

(Figure 4).

The strength of the SOMS Trial comes from three fundamental concepts embedded in the

design: 1) simplicity, 2) clinical team focus, and 3) utilization of resources already available.

SOMS guided goal-directed early mobilisation is straightforward, progressive and intuitive. It

was created with input from the fields of nursing, physical therapy, physiatry and critical care to

ensure safety and function. It is written in clinically precise and mutually comprehensible

language. The process of setting a mobilisation goal should add minimal time to morning

rounds. Furthermore, the SOMS algorithm allows nurses to readily contribute to goal setting on

rounds. It also provides structure for the nurses to mobilise the subjects. Consequently, the

SOMS algorithm makes efficient use of existing resources. The results of this study will be

generalizable to the broader clinical community such that the study finding will be externally

valid and should guide clinical standards of mobilisation in the surgical ICU.

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The SOMS is a thoughtful and uncomplicated intervention. However, due to the nature of the

research, there are notable limitations. One limitation in the study is the inability to blind the

assessor of a subject’s achieved SOMS. For study subjects, the achieved SOMS is obtained

daily from the subject’s nurse who is unblinded and part of the intervention. The achieved

SOMS is checked against the nursing documentation. For control subjects, the achieved SOMS

is obtained by the clinical SOMS facilitator during regular afternoon rounds. The numbers

obtained by the nurses and the SOMS facilitator are again checked against the nursing chart.

A second limitation is that we do not add any additional personnel resources to accomplish the

daily SOMS goal, and this is an environment which occasionally has difficulty meeting its current

mobilisation goals.48 We believe the SOMS algorithm for goal-directed early mobilisation is

complementary to the philosophy of nursing and will be fluidly incorporated into their systems

with limited effect upon their workload. Foremost, the SOMS algorithm should improve mobility-

related communication between providers, and thus lead to more frequent mobility of patients

and change in mobilisation culture in the surgical ICU. However, there is the possibility that this

intervention, which adds no additional financial cost, may not improve mobilisation enough to

draw conclusions, and a dedicated mobilisation specialist or team, as applied in other medical

ICU studies,1-3 may be necessary.

The adoption of patient mobilisation into the surgical ICU prompts a third limitation: culture shift

from immobilised patients49 to mobilised patients. As nurses gain more experience mobilising

critically ill patients due to their patients’ participation in our study, they will become more

comfortable applying this same concept to all of their patients: intervention, control and other.

Consequently, we expect mobilisation in the standard of care group to increase with time, which

may lead to a type II error. The multicentric trial design with a high sample size utilizing

individual randomization may help minimize contamination.50

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Furthermore, throughout the world and even in the most affluent nations, mobilising patients in

the surgical ICU is performed by a variety of different healthcare providers with different training

backgrounds24: nurses, nursing assistants, students, respiratory therapists, physical therapists

and physicians of different specialties. Additionally, the availability of resources, both assistive

equipment49 and personnel differs between a tertiary care hospital in Europe and in the United

States. Accordingly, a specific algorithm with decision points explicitly requiring “yes” and “no”

answers to advance, stall, or regress the mobilisation goal must accommodate cultural,

linguistic and resource-based variation. Therefore, our goal-directed early mobilisation algorithm

will be identical across all centers relative to the stages of mobilisation and the focus on

promoting early, and clinically appropriate mobilisation, but the algorithm will have minor, local

adaptations.

Finally, in consideration of the minor effect that genetic differences in sleep, circadian rhythm

and muscle homeostasis may have on variance in surgical ICU outcomes, our study may be

underpowered to identify genetic influence on surgical ICU outcomes.

CONCLUSION

This manuscript provides a description of our study protocol and analysis plans for the SOMS

multicentre randomized control trial. Beyond evaluating the effects of goal-directed early

mobilisation on clinical outcomes and patient mobility, this study is designed to maximize the

efficiency of existing resources without requiring any new personnel or funding. Furthermore,

the design of this study lends itself to ancillary studies related to the cultural issues associated

with mobilisation of surgical ICU patients. This trial is an opportunity to use goal-directed early

mobilisation to improve surgical ICU clinical outcomes safely without adding to the hospital

expenses.

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Authors' contributions: ME, KW and CR conceived of the study. ME, KW and CR initiated the

study design. All authors have helped with implementation of the study. MM, AS and ME wrote

the first draft of the manuscript. All authors assisted in the refinement of the study protocol and

approved the final manuscript.

Competing interests: The authors attest to no competing interests.

Funding statement: This research has received no specific grant from any funding agency in

the public, commercial or not-for-profit sectors.

Registry: ClinicalTrials.gov (NCT01363102)

Trial Sponsor: Massachusetts General Hospital (Matthias Eikermann, MD, PhD,

[email protected])

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Figure 1. Subject progression through the study protocol. APACHE II: acute physiology and chronic health evaluation II, GCS: Glasgow coma scale, ICU: intensive care unit, LOS: length of stay, mmFIM: “mini”

modified functional independence measure, MRC: medical research council, SF-36: short form-36, SOMS:

SICU optimal mobilisation score, SICU: surgical intensive care unit. 215x279mm (96 x 96 DPI)

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Figure 2. SOMS algorithm for goal-directed early mobilisation. Adapted from the SICU optimal mobilisation score with permission from Kasotakis et al (CCM 2012). CVVH: central venovenous hemofiltration, EVD: extraventricular drain, ICP: intracranial pressure, SCI: spinal cord injury, SOMS: SICU optimal mobilisation

score, WB: weight-bearing. 254x190mm (96 x 96 DPI)

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Figure 3. Ancillary study to explore genetic mechanisms contributing to the effectiveness of early mobilisation in the surgical ICU. We target a subset of genes linked to either sleep and circadian rhythm or muscle function. These candidate genes are part of a greater set of genes and polymorphisms that may be

responsible for some of the variance of response to goal-directed early mobilisation. Genetic tests will be performed as an ancillary study linked to the SOMS protocol. SOMS: SICU optimal mobilisation score.

254x190mm (96 x 96 DPI)

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Figure 4. Potential benefits and adverse effects of SOMS guided early mobilisation. The SOMS algorithm is designed to carefully and incrementally advance mobilisation. Based on knowledge gathered in the medical ICU, early mobilisation leads to improved clinical outcome. However, while using the bridge of goal-directed

early mobilisation, possible complications and side effects of mobilisation must be considered. 457x190mm (96 x 96 DPI)

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CONSORT 2010 checklist Page 1

CONSORT 2010 checklist of information to include when reporting a randomised trial*

Section/Topic Item No Checklist item

Reported on page No

Title and abstract

1a Identification as a randomised trial in the title 1

1b Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) 3

Introduction

Background and

objectives

2a Scientific background and explanation of rationale 4-5

2b Specific objectives or hypotheses 5-6

Methods

Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 8,10

3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons NA

Participants 4a Eligibility criteria for participants 8-9

4b Settings and locations where the data were collected 9

Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were

actually administered

11-13

Outcomes 6a Completely defined pre-specified primary and secondary outcome measures, including how and when they

were assessed

13-15

6b Any changes to trial outcomes after the trial commenced, with reasons NA

Sample size 7a How sample size was determined 15

7b When applicable, explanation of any interim analyses and stopping guidelines NA

Randomisation:

Sequence

generation

8a Method used to generate the random allocation sequence 10

8b Type of randomisation; details of any restriction (such as blocking and block size) 10

Allocation

concealment

mechanism

9 Mechanism used to implement the random allocation sequence (such as sequentially numbered containers),

describing any steps taken to conceal the sequence until interventions were assigned

10

Implementation 10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to

interventions

10

Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those 13

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assessing outcomes) and how

11b If relevant, description of the similarity of interventions NA

Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes 16

12b Methods for additional analyses, such as subgroup analyses and adjusted analyses 16

Results

Participant flow (a

diagram is strongly

recommended)

13a For each group, the numbers of participants who were randomly assigned, received intended treatment, and

were analysed for the primary outcome

Figure 1

13b For each group, losses and exclusions after randomisation, together with reasons NA

Recruitment 14a Dates defining the periods of recruitment and follow-up 9

14b Why the trial ended or was stopped NA

Baseline data 15 A table showing baseline demographic and clinical characteristics for each group NA

Numbers analysed 16 For each group, number of participants (denominator) included in each analysis and whether the analysis was

by original assigned groups

NA

Outcomes and

estimation

17a For each primary and secondary outcome, results for each group, and the estimated effect size and its

precision (such as 95% confidence interval)

NA

17b For binary outcomes, presentation of both absolute and relative effect sizes is recommended NA

Ancillary analyses 18 Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing

pre-specified from exploratory

NA

Harms 19 All important harms or unintended effects in each group (for specific guidance see CONSORT for harms) NA

Discussion

Limitations 20 Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses 21-23

Generalisability 21 Generalisability (external validity, applicability) of the trial findings 22-23

Interpretation 22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence NA

Other information

Registration 23 Registration number and name of trial registry 24

Protocol 24 Where the full trial protocol can be accessed, if available NA

Funding 25 Sources of funding and other support (such as supply of drugs), role of funders 24

*We strongly recommend reading this statement in conjunction with the CONSORT 2010 Explanation and Elaboration for important clarifications on all the items. If relevant, we also

recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, non-pharmacological treatments, herbal interventions, and pragmatic trials.

Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see www.consort-statement.org.

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Journal: BMJ Open

Manuscript ID: bmjopen-2013-003262.R1


Date Submitted by the Author: 26-Jun-2013

Complete List of Authors: Meyer, Matthew; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Stanislaus, Anne; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Lee, Jarone; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Waak, Karen; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ryan, Cheryl; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine

Saxena, Richa; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ball, Stephanie; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Schmidt, Ulrich; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Poon, K. Trudy; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Piva, Simone; University of Brescia at Spedali Civili, Anesthesia, Intensive Care and Perioperative Medicine Walz, Matthias; UMass Memorial Medical Center, Anesthesia Talmor, Daniel; Beth Israel Deaconess Medical Center, Anesthesiology;

Harvard Medical School, Blobner, Manfred; Technischen Universität München, LATRONICO, NICOLA; UNIVERSITY OF BRESCIA, ANESTHESIOLOGYINTENSIVE CARE Eikermann, Matthias; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine


Intensive care


Keywords:

Adult intensive & critical care < ANAESTHETICS, REHABILITATION

MEDICINE, Change management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Adult neurology < NEUROLOGY, RESPIRATORY MEDICINE (see Thoracic Medicine), Adult surgery < SURGERY


BMJ Open on N



jopen.bmj.com

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Cheryl Ryan RN!, Stephanie Ball RN, DNS!, Ulrich Schmidt MD, PhD¥, K. Trudy Poon MSӨ,

Simone Piva MD¤, Richa Saxena PhD§, Matthias Walz MD++, Daniel S. Talmor MD, MPH**,

Manfred Blobner MD§, Nicola Latronico MD$, and Matthias Eikermann MD, PhD+#















Ө Biostatistician Epidemiologist, Department of Anesthesia, Critical Care, and Pain Medicine,



Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA






Worcester, MA, USA

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Deaconess Medical Center, Harvard Medical School, Boston, MA, USA



Germany


Matthias Eikermann



55 Fruit Street


[email protected]

Phone: 617-643-4408


Word Count: 4725

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Mobilisation Score (SOMS) Trial aims to test if a budget-neutral intervention to facilitate goal-

directed early mobilisation in the surgical ICU improves subject mobilisation and associated

clinical outcomes.




stay until discharge readiness and “mini” modified functional independence measure (mmFIM)

at hospital discharge. Additional secondary outcomes include quality of life assessed at three

months after hospital discharge and global muscle strength at ICU discharge. Exploratory











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ARTICLE SUMMARY

Article Focus








Key Messages







Strengths




o No specific budget expenditure to implement the SOMS algorithm



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Limitation



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INTRODUCTION

Background














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Objectives




and the key-secondary outcomes of surgical ICU LOS until discharge readiness and patient

functional mobility at surgical ICU and hospital discharge.















Trial design



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our trial.

Subjects


expected to continue ventilation for at least another 24 hours at the time of screening, and who

meet baseline criteria for functional independence (Barthel Index score ≥70 two weeks prior to

admission27) are considered for the study. Table 1 contains the exclusion criteria.







mobility


mobility




reached






Potential confounding factors

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The local investigator will screen surgical ICU patients daily and patients will be included into

the study according to locally dependent consenting standards. Subjects will be immediately

randomly allocated into the intervention or standard of care group by study staff. We stratify

according to Glasgow Coma Scale (GCS; ≤8, >8) and Acute Physiology and Chronic Health

Evaluation II (APACHE II; ≤12, >12) at each center. Subjects are stratified into four groups: 1)

GCS ≤8, APACHE II ≤12; 2) GCS ≤8, APACHE II >12; 3) GCS >8, APACHE II ≤12; 4) GCS >8,

APACHE II >12. Into each sub-group (1-4), the stratified randomisation is restricted to 50:50

(intervention:standard of care) initially.

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Standard of care



Intervention




• Give advice on how to address barriers to early mobilisation




subjects.





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to ambulate.

Standard of care


Sedation Scale for arousal and the Confusion Assessment Method for the ICU for delirium.

Subjects who are documented as positive for the Confusion Assessment Method for the ICU will

be considered delirious. Subjects in both study and control groups are managed by goal-

directed sedation and undergo daily decreases in sedatives and/or narcotics. Contraindications

to daily attempts to decrease sedation are: persistent neuromuscular blockade, sedative

infusion for active seizures or alcohol withdrawal, persistent agitation, active myocardial

ischemia and elevated intracranial pressure. All patients receive early enteral feeding and

patients with high glucose concentrations are treated with protocol-based insulin regiments.






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support).

Intervention




defines a SOMS goal for the day with the assistance of the SOMS facilitator. The SOMS

algorithm establishes a minimum standard for subject advancement to the next mobilisation

level and contains both polar (yes-no) and non-polar questions. Clinical staff member involved

with mobilising the subject should be able to verify the polar questions (i.e. intracranial pressure

< 20 cm H2O). The non-polar questions which involve clinical judgment (i.e. no excessive

predicted mortality within the next 24 hours) are discussed with the assistance of the SOMS

facilitator.

Once the mobilisation goal has been determined, a sign will be posted at the subject’s bedside

with the goal for the day. The bedside nurse will work with the subject to achieve the goal. Prior

to afternoon rounds, the nurse will document the highest achieved SOMS for the day. If the goal




Blinding


assessors of the key-secondary outcome of “mini” modified functional independence measure

(mmFIM) and the secondary outcome of SF36 three months after hospital discharge will be

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blinded to the study assignment. The data analyst will also be blinded to the study group

assignments.

Outcome measures




outcome of mmFIM, representing functional mobility, will be assessed at hospital discharge.

The secondary outcome of quality of life obtained through SF36 survey will be completed at

least three months following hospital discharge. The secondary outcome of medical research

council (MRC) scale for testing global muscle strength will be administered daily while in the

ICU.


three month mortality, discharge disposition, ICU delirium-free days, ventilator-free days, ICU

sedation-free days, average daily morphine equivalent dose (mg), neuromuscular blocking

agent-free days, vasopressor-free days, corticosteroid days, daily serum glucose high (mg/dL)

and daily serum sodium high (mEq). All outcome measures will be monitored from Study Day 1

and stop with surgical ICU discharge unless otherwise indicated. The pre-defined period for

outcome-free days is 28 days and any subject who dies will receive 0.


A trained and blinded member of the study staff will determine the mmFIM. The mmFIM is a



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Short form 36























group and 35% in the standard of care group at hospital discharge.3 Allowing for an expected

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11% mortality rate and 11% attrition due to dropouts, enrolling 200 subjects, 100 in each group,

will provide us with a power of >80% to identify an intergroup difference with an alpha error of

0.05.










Statistical methods

The study analysis will be by intention to treat. Summary statistics of mean and standard

deviation, frequency and percentage will be generated respectively for continuous and

categorical/ordinal variables by the stratification based on GCS and APACHEI II. The

association between the outcome variables and stratification will be evaluated using ANOVA

and Chi-square test respectively.

The main outcomes of the study will be tested using a hierarchical sequence so the hypotheses,

in an a priori specified order, can be tested with an alpha-error of 0.05 without adjustment for

multiple testing.32-34 The outcomes will be tested in this pre-defined order: mean daily SOMS

level, surgical ICU LOS until discharge readiness, and mmFIM score at hospital discharge. If a

p-value is larger than 0.05, the procedure has to stop and no confirmatory conclusions can be

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based on outcomes at or after the outcome whose null hypothesis was the first that was not

rejected.

The average SOMS level is calculated using the achieved mobility scores recorded daily during

each subject’s ICU stay. Trend tests will be used to assess the association between average

ICU stay and other outcomes over levels of SOMS. For the key secondary key outcomes, time-

dependent survival analysis will be employed to assess relationships between the duration of

admission and SOMS, with ventilator-free and the like to be considered as time-dependent

covariates. Statistical significance will be evaluated at alpha = 0.05. All analyses will be

conducted by a statistician blinded to the intervention.

Data collection










will be recorded. Discharge readiness is defined as the time when surgical ICU team requests a

non-ICU room for the subject. The data will be uploaded to a secure database (REDCap). Data

stored on REDCap is coded and without protected information.

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2).

Adverse events












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100 subjects.


Consent

As this is an international trial, the process of informed consent may be different between sites

and will be dependent upon cultural and national standards.35 For the majority of participants in

our study written consent will be provided by a healthcare proxy. Informed consent will be

obtained from each potential subject’s healthcare proxy by study staff. The study staff receiving

the consent will give a copy of the IRB approved informed consent form to the healthcare proxy

and/or potential subject. The healthcare proxy and/or potential subject will have adequate time

to read the informed consent form, evaluate the risks of the study, consult with any family

members or clinicians requested, and ask questions of the study staff. If the healthcare proxy

and/or patient decides to participate then the informed consent form will be signed. Subjects will

be informed of their participation in the study following resolution of their critical illness and any

residual delirium.

Ancillary Studies

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Alongside of our primary trial, subjects will be able to opt-in to a related, hypothesis-generating

exploratory genetic study. We anticipate wide variability in the effectiveness of early

mobilisation, and speculate that some of the variability is related to circadian dysregulation. In

ICU patients, decreased total sleep time, decreased deep (restorative) sleep, fragmented sleep,

as well as altered circadian patterns have been reported.36, 37 Other preliminary data suggest

that treatments to improve circadian disruption such as intermittent light therapy may facilitate

early ambulation in critically ill patients.38 We also believe some of the variability in the

effectiveness of early mobilisation is related to inherent qualities of the muscles. Therefore, with

an exploratory intention, we will evaluate if the existence of single nucleotide polymorphisms in

genes associated with sleep, circadian rhythm and muscle function explain some variance in the

effectiveness of early mobilisation in ICU patients (Figure 3).







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Protocol funding









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DISCUSSION












(Figure 4).







rounds. The role of the SOMS facilitator to assist in the goal-setting and assess the subject’s

progress will require a few minutes spread throughout the day. The results of this study will be



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The SOMS algorithm allows nurses to readily contribute to goal setting on rounds and it

provides structure for the nurses to mobilise the subjects. The act of delivering the intervention,

mobilising subjects from the bed to sitting and so forth, takes time. While we believe the SOMS

algorithm makes efficient use of existing resources, we acknowledge that shifting resources

towards mobilisation may be associated with opportunity costs under certain circumstances.















budget-neutral intervention may not improve mobilisation enough to draw conclusions, and a

dedicated mobilisation specialist or team, as applied in other medical ICU studies,1-3 may be

necessary.

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adaptations.




CONCLUSION

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expenses.










[email protected])

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Worcester, MA, USA

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Germany


Matthias Eikermann



55 Fruit Street


[email protected]

Phone: 617-643-4408


Word Count: 4725

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clinical outcomes.

















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ARTICLE SUMMARY

Article Focus








Key Messages







Strengths







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Limitation



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INTRODUCTION

Background














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Objectives




















Trial design



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our trial.

Subjects











mobility


mobility




reached







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Standard of care



Intervention








subjects.





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to ambulate.

Standard of care















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support).

Intervention










facilitator.







Blinding




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assignments.

Outcome measures








ICU.






and stop with surgical ICU discharge unless otherwise indicated. The pre-defined period for

outcome-free days is 28 days and any subject who dies will receive 0.





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Short form 36
















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0.05.










Statistical methods



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rejected.








Data collection





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2).

Adverse events





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100 subjects.


Consent







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residual delirium.

Ancillary Studies



















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Protocol funding









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DISCUSSION












(Figure 4).











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necessary.

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adaptations.




CONCLUSION

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expenses.










[email protected])

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REFERENCE LIST





Rehabil 2010;91(4):536-42.



2009;373(9678):1874-82.













unit. Phys Ther 2012;92(12):1546-55.







2009;37(10):2702-8.




1899;XXXIII(8):454-56.






72.





2007;55(12):493-8.



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Radiol 2000;55(11):874-7.








2011;3(4):307-13.






1965;14:61-5.






Trauma 1994;37(6):962-8.



groups. Med Care 1994;32(1):40-66.













1985;290(6474):1029-32.


patients. Chest 1992;102(1):288-91.





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2006;103(18):7118-23.





2012;7(9):e45987.








2012;59(4):854-60.









Care 2007;11(1):R11.







2001;322(7282):355-7.

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Figure 2. SOMS algorithm for goal-directed early mobilisation. 254x190mm (96 x 96 DPI)

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254x190mm (96 x 96 DPI)

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Reported on page No

Title and abstract



Introduction

Background and

objectives


2b Specific objectives or hypotheses 8

Methods

Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 8-10






12-13


were assessed

14-16




Randomisation:

Sequence

generation



Allocation

concealment

mechanism



10


interventions

10

Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those 13-14

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Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes 16-17

12b Methods for additional analyses, such as subgroup analyses and adjusted analyses 16-17

Results

Participant flow (a

diagram is strongly

recommended)



Figure 1







NA

Outcomes and

estimation



NA




NA


Discussion




Other information

Registration 23 Registration number and name of trial registry 3, 25






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Journal: BMJ Open

Manuscript ID: bmjopen-2013-003262.R2


Date Submitted by the Author: 22-Jul-2013

Complete List of Authors: Meyer, Matthew; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Stanislaus, Anne; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Lee, Jarone; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Waak, Karen; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ryan, Cheryl; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine

Saxena, Richa; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Ball, Stephanie; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Schmidt, Ulrich; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Poon, K. Trudy; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine Piva, Simone; University of Brescia at Spedali Civili, Anesthesia, Intensive Care and Perioperative Medicine Walz, Matthias; UMass Memorial Medical Center, Anesthesia Talmor, Daniel; Beth Israel Deaconess Medical Center, Anesthesiology;

Harvard Medical School, Blobner, Manfred; Technischen Universität München, LATRONICO, NICOLA; UNIVERSITY OF BRESCIA, ANESTHESIOLOGYINTENSIVE CARE Eikermann, Matthias; Massachusetts General Hospital, Anesthesia, Critical Care and Pain Medicine


Intensive care


Keywords:

Adult intensive & critical care < ANAESTHETICS, REHABILITATION

MEDICINE, Change management < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Adult neurology < NEUROLOGY, RESPIRATORY MEDICINE (see Thoracic Medicine), Adult surgery < SURGERY


BMJ Open on N



jopen.bmj.com

/B

MJ O


ugust 2013. Dow

nloaded from



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Cheryl Ryan RN!, Richa Saxena PhD§, Stephanie Ball RN, DNS!, Ulrich Schmidt MD, PhD¥, K.

Trudy Poon MSӨ, Simone Piva MD¤, Matthias Walz MD++, Daniel S. Talmor MD, MPH**,

























Worcester, MA, USA

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Germany


Matthias Eikermann



55 Fruit Street


[email protected]

Phone: 617-643-4408


Word Count: 4765

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clinical outcomes.

















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ARTICLE SUMMARY

Article Focus








Key Messages







Strengths







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Limitation



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INTRODUCTION

Background














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Objectives




















Trial design



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our trial.

Subjects











mobility


mobility




reached







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Standard of care



Intervention








subjects.





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to ambulate.

Standard of care















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support).

Intervention










facilitator.







Blinding




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assignments.

Outcome measures








ICU.






and stop with surgical ICU discharge unless otherwise indicated, such that a time-dependent

analysis of positive and negative outcomes can be conducted in all patients. The pre-defined

period for outcome-free days is 28 days and any subject who dies prior to day 28 will have all

subsequent days counted as not outcome-free. We will consider all days following surgical ICU

discharge as outcome-free.


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Short form 36
























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0.05.










Statistical methods











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rejected.








Data collection













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2).

Adverse events












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100 subjects.


Consent











residual delirium.

Ancillary Studies

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Protocol funding









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DISCUSSION












(Figure 4).

The strength of the SOMS Trial comes from three fundamental characteristics embedded in the









valid and should guide clinical standards for early mobilisation, or “pre-habilitation,” in the

surgical ICU.

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necessary.

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adaptations.




CONCLUSION

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expenses.










[email protected])

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Figure Legends

Figure 1. Subject progression through the study protocol. APACHE II: acute physiology and

chronic health evaluation II, GCS: Glasgow coma scale, ICU: intensive care unit, LOS: length of

stay, mmFIM: “mini” modified functional independence measure, MRC: medical research

council, SF-36: short form-36, SOMS: SICU optimal mobilisation score, SICU: surgical intensive

care unit.

Figure 2. SOMS algorithm for goal-directed early mobilisation.

Figure 3. Ancillary study to explore genetic mechanisms contributing to the effectiveness of

early mobilisation in the surgical ICU. We target a subset of genes linked to either sleep and

circadian rhythm or muscle function. These candidate genes are part of a greater set of genes

and polymorphisms that may be responsible for some of the variance of response to goal-

directed early mobilisation. Genetic tests will be performed as an ancillary study linked to the

SOMS protocol. SOMS: SICU optimal mobilisation score.

Figure 4. Potential benefits and adverse effects of SOMS guided early mobilisation. The SOMS

algorithm is designed to carefully and incrementally advance mobilisation. Based on knowledge

gathered in the medical ICU, early mobilisation leads to improved clinical outcome. However,

while using the bridge of goal-directed early mobilisation, possible complications and side

effects of mobilisation must be considered.

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REFERENCE LIST





Rehabil 2010;91(4):536-42.



2009;373(9678):1874-82.













unit. Phys Ther 2012;92(12):1546-55.







2009;37(10):2702-8.




1899;XXXIII(8):454-56.






72.





2007;55(12):493-8.



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Radiol 2000;55(11):874-7.








2011;3(4):307-13.






1965;14:61-5.






Trauma 1994;37(6):962-8.



groups. Med Care 1994;32(1):40-66.













1985;290(6474):1029-32.


patients. Chest 1992;102(1):288-91.





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2006;103(18):7118-23.





2012;7(9):e45987.








2012;59(4):854-60.









Care 2007;11(1):R11.







2001;322(7282):355-7.

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Worcester, MA, USA

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Germany


Matthias Eikermann



55 Fruit Street


[email protected]

Phone: 617-643-4408


Word Count: 4765

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clinical outcomes.

















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ARTICLE SUMMARY

Article Focus








Key Messages







Strengths







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Limitation



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INTRODUCTION

Background














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Objectives




















Trial design



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our trial.

Subjects











mobility


mobility




reached







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Standard of care



Intervention








subjects.





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to ambulate.

Standard of care















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support).

Intervention










facilitator.







Blinding




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assignments.

Outcome measures








ICU.






and stop with surgical ICU discharge unless otherwise indicated, such that a time-dependent

analysis of positive and negative outcomes can be conducted in all patients. The pre-defined

period for outcome-free days is 28 days and any subject who dies prior to day 28 will have all

subsequent days counted as not outcome-free. We will consider all days following surgical ICU

discharge as outcome-free.


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Short form 36
























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0.05.










Statistical methods











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rejected.








Data collection













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2).

Adverse events












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100 subjects.


Consent











residual delirium.

Ancillary Studies

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Protocol funding









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DISCUSSION












(Figure 4).

The strength of the SOMS Trial comes from three fundamental characteristics embedded in the









valid and should guide clinical standards for early mobilisation, or “pre-habilitation,” in the

surgical ICU.

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necessary.

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adaptations.




CONCLUSION

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expenses.










[email protected])

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REFERENCE LIST





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2009;373(9678):1874-82.













unit. Phys Ther 2012;92(12):1546-55.







2009;37(10):2702-8.




1899;XXXIII(8):454-56.






72.





2007;55(12):493-8.



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Radiol 2000;55(11):874-7.








2011;3(4):307-13.






1965;14:61-5.






Trauma 1994;37(6):962-8.



groups. Med Care 1994;32(1):40-66.













1985;290(6474):1029-32.


patients. Chest 1992;102(1):288-91.





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2006;103(18):7118-23.





2012;7(9):e45987.








2012;59(4):854-60.









Care 2007;11(1):R11.







2001;322(7282):355-7.

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Figure 2. SOMS algorithm for goal-directed early mobilisation. 160x119mm (300 x 300 DPI)

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160x119mm (300 x 300 DPI)

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Reported on page No

Title and abstract



Introduction

Background and

objectives


2b Specific objectives or hypotheses 8

Methods

Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 8-10






12-13


were assessed

14-16




Randomisation:

Sequence

generation



Allocation

concealment

mechanism



10


interventions

10

Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those 13-14

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Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes 16-17

12b Methods for additional analyses, such as subgroup analyses and adjusted analyses 16-17

Results

Participant flow (a

diagram is strongly

recommended)



Figure 1







NA

Outcomes and

estimation



NA




NA


Discussion




Other information

Registration 23 Registration number and name of trial registry 3, 25






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Surgical Intensive Care Unit Optimal Mobilisation Score · Waak, Karen; Massachusetts General...

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Transcript of Surgical Intensive Care Unit Optimal Mobilisation Score · Waak, Karen; Massachusetts General...