Accepted Manuscript

Efficacy of early passive tilting in minimizing ICU-acquired

weakness: A randomized controlled trial

Céline Sarfati, Alex Moore, Catherine Pilorge, Priscilla Amaru,

Paula Mendialdua, Emilie Rodet, François Stéphan, Saïda
Rezaiguia-Delclaux

PII: S0883-9441(18)30108-4
DOI: doi:10.1016/j.jcrc.2018.03.031
Reference: YJCRC 52900
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Paula Mendialdua, Emilie Rodet, François Stéphan, Saïda Rezaiguia-Delclaux , Efficacy
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Please check if appropriate. Yjcrc(2017), doi:10.1016/j.jcrc.2018.03.031

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 ACCEPTED MANUSCRIPT

Efficacy of Early Passive Tilting in Minimizing ICU-Acquired Weakness: A

Randomized Controlled Trial

Running title: Early Tilting and ICU-Acquired Weakness

Céline Sarfati, PT1, Alex Moore, PT1, Catherine Pilorge, MD, PhD2, Priscilla Amaru, MD2;

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Paula Mendialdua, PT1, Emilie Rodet, PT1; François Stéphan, MD, PhD2; Saïda Rezaiguia-

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Delclaux, MD2

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Author affiliations
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1
Physiotherapy Unit, 2Cardiothoracic Intensive Care Unit, Hôpital Marie Lannelongue, Le

Plessis Robinson, Université Paris Sud, Paris, France

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This study was done at the Hôpital Marie Lannelongue, Le Plessis Robinson, France.
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Sources of financial support: Hôpital Marie Lannelongue, Le Plessis Robinson, France.

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Competing interests

The authors declare that no competing interests.

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Authors' contributions

Céline Sarfati contributed to the research design, data collection, writing of the paper, editing

of the paper, and approval of the final version.

Alex Moore contributed to the research design, data collection, writing of the paper, editing of

the paper, and approval of the final version.

 ACCEPTED MANUSCRIPT

Dr Catherine Pilorge contributed to the data collection, editing of the paper, and approval of

the final version.

Dr Priscilla Amaru contributed to the data collection, editing of the paper, and approval of the

final version.

Paula Mendialdua contributed to the data collection, editing of the paper, and approval of the

final version.

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Emilie Rodet contributed to the data collection, editing of the paper, and approval of the final

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version.

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Pr François Stéphan contributed to the research design, analysis of the results, editing of the

paper, and approval of the final version.

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Dr Saïda Rezaiguia-Delclaux contributed to the research design, data collection, analysis of

the results, writing of the paper, editing of the paper, and approval of the final version.
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Dr Saïda Rezaiguia-Delclaux is the guarantor of the entire manuscript.

Dr Saïda Rezaiguia-Delclaux state that all authors had full access to the data and vouches for
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the integrity of the data analysis.

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Corresponding author: Saïda Rezaiguia-Delclaux

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Hôpital Marie Lannelongue

Unité de réanimation adulte

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133, avenue de la résistance

92350 Le Plessis Robinson, France

Tel.: +33 140 942 563

Fax: +33 140 948 586

s.rezaiguia@ccml.fr
 ACCEPTED MANUSCRIPT

Abstract

Purpose: To investigate whether passive tilting added to a standardized rehabilitation therapy

improved strength at Intensive Care Unit (ICU) discharge.

Material and Methods: This single-center trial included patients admitted to an adult

surgical ICU and ventilated for at least 3 days. Patients were randomized to daily standardized

rehabilitation therapy alone or with tilting on a table for at least 1 hour. The primary outcome

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was the Medical Research Council (MRC) sum score at ICU discharge. Muscular recovery

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was a secondary outcome.

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Results: Of 145 included patients, 125 received mobilization, 65 in the Tilt group and 60 in

the Control group. Total mobilization duration (median [25th-75th percentiles]) in the Tilt
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group was 1,020 [580-1,695] versus 1,340 [536-2,775] minutes in the Control group

(p=0.313). MRC sum scores at ICU discharge were not significantly different between groups
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(Tilt, 50 [45-56] versus 48 [45-54]; p=0.555). However, the number of patients with weakness

was higher in the Tilt group at baseline (Tilt: 60/65 versus 48/60, p=0.045) and muscular
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recovery was better in the Tilt group (p=0.004).

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Conclusions: Passive tilting added to a standardized rehabilitation therapy did not improve
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muscle strength at ICU discharge in surgical patients even if a faster recovery with tilting is
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suggested.
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ClinicalTrials.gov Identifier: NCT02047617

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Keywords

ICU-acquired muscle weakness

Physiotherapy

Critical illness

Mechanical ventilation

Rehabilitation

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Introduction

Intensive care unit-acquired weakness (ICUAW) is associated with prolonged hospitalization,

delayed weaning off mechanical ventilation (MV), and increased mortality [1–3]. Risk factors

for ICUAW include sepsis [4–6]; systemic inflammatory response syndrome [7,8]; multiple

organ failure [2]; hyperglycemia [9,10]; graft dysfunction [11]; and treatment with

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catecholamines [6], corticosteroids [2,4], or neuromuscular blocking agents [4,10,12].

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Muscle wasting occurs rapidly in critically ill patients, who may lose up to 30% of their

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muscle mass within the first 10 ICU days [13]. Early mobilization has been found feasible and

safe, and guidelines for in-bed and out-of-bed active mobilization are available [14]. In a
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randomized controlled trial in surgical ICUs, early goal-directed mobilization improved the

mobilization score, decreased ICU and hospital stay lengths, and improved functional
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independence at hospital discharge [15].

Many modalities of early mobilization are being investigated as means of minimizing

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ICUAW. Tilting the patient toward the erect position on a table has been advocated to
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minimize the adverse effects of prolonged immobilization [16]. Among physiotherapists in

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Australian ICUs, 67.4% were found to include tilting in their physiotherapy programs [17].
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Tilting may increase ventilation and arousal, benefit muscle and bone by inducing partial

weight bearing, and facilitate antigravity limb exercises [18]. Early tilt-table verticalization of
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ICU patients with severe acquired brain injury was safe and improved functional and

neurological outcomes [19–22]. However, early intensive physiotherapy including tilting has

not been evaluated in other populations of ICU patients.

The objective of this randomized controlled trial was to investigate whether cardiothoracic

surgery patients expected to require prolonged ICU management benefited from the addition

of daily tilting to an early mobilization program.

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Methods

Study design

This parallel-group randomized controlled trial was conducted from October 2013 to October

2014 in the adult ICU of the Marie Lannelongue cardiothoracic surgery hospital. The study

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protocol was approved by an ethics committee (CPP Ile de France VII; ID RCB: #2012-

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A00665-38). Tilting is classified as standard care in France and informed consent was

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therefore not required. Written and oral information was provided to the patient or relatives,

who were free to decline participation. The study was conducted according to the Declaration
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of Helsinki.
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Patients

Inclusion criteria were admission to the ICU, age at least 18 years, and MV for 3 days or more
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with no expectation of weaning on the day of screening for study eligibility. Exclusion criteria
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were transfer from another ICU after a stay longer than 5 days; central nervous system injury;
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multiple injuries; and injury to the spine, pelvis, and/or lower limb(s). Figure 1 is the patient
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flowchart.
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Randomization

Randomization was conducted in blocks of 2 or 4 using a computer-generated (nQuery

Advisor) random-number sequence. Concealment was with opaque envelopes. The attending

physicians randomly assigned patients in a 1:1 ratio to either standardized rehabilitation

therapy with tilting (Tilt group) or without tilting (Control group). The investigators could not
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access the randomization list and were unaware of block size. The nature of the intervention

precluded blinding.

Daily standardized rehabilitation therapy (Figure 2)

The daily standardized rehabilitation therapy used in the current study associated in-bed range

of motion exercises and out-of-bed mobilization sessions, administered 7 days per week.

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As part of standard care in our ICU, in-bed passive and active range-of-motion exercises were

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performed daily in all patients, starting at ICU admission and until out-of-bed mobilization

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was feasible. Passive range of motion included 5 repetitions for each upper and lower

extremity joint. Active range of motion included dorsiflexion, knee flexion and extension, hip
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flexion, elbow flexion and extension, and shoulder flexion. Also as part of standard care, all

patients free of contraindications received out-of-bed mobilization (Figure 2). Out-of-bed

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mobilization sessions consisted of sitting in armchair at least 2 hours per day in Control group.

In addition to sitting in armchair at least 2 hours per day, patients allocated to the Tilt group
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were verticalized on an electrical tilt-table (TF1-2860, Franco&Fils, Pougues les Eaux,

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France) for at least 1 hour per day. The patient was secured to the table by Velcro straps at the
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torso and knees and was gradually tilted from 30° to 60° in 10° steps.
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The ICU physiotherapists assessed the patients twice daily (in the morning and in the

afternoon) for alertness and temporary contraindications (TCI) to out-of-bed mobilization

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(Figure 2). If patients were unconscious at the first assessment, a session of passive in-bed

range of motion exercises was performed. In conscious patients with others TCI, active in-bed

range-of-motion exercises were performed. In both cases, the second assessment done in the

afternoon was followed by exercises depending on consciousness and TCI. Patients free of

contraindications at the first assessment received out-of-bed mobilization, according to

randomization, as described in Figure 2.

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In both groups, the standardized rehabilitation therapy was repeated daily until the patient

could stand up with assistance or was discharged from the ICU. If the out-of-bed mobilization

session was interrupted, the reason for discontinuation was recorded. When the patient was

able to stand up with assistance (Stand Up, Rupiani, Vaulx en Velin, France), rehabilitation

exercises consisted in sitting in armchair, standing up and walking with assistance.

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Other treatments

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Mechanical ventilation (MV) settings and weaning (Appendix 1)

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Ventilator settings were standardized in both groups, using a protective strategy. Patients were

evaluated daily for weaning readiness. Noninvasive ventilation and high-flow nasal cannula
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oxygen therapy (Optiflow®) could be used in extubated patients who developed acute

respiratory failure. Reintubation criteria were those previously reported by our group [23].
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Tracheostomy was performed in the event of prolonged weaning (more than three

spontaneous breathing trials or >7 days of weaning after the first spontaneous breathing trial).
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Insulin, sedatives, and neuromuscular blocking (NMB) agents

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Insulin was administered using a standardized protocol (Appendix 2). Sedation was
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conducted with midazolam and sufentanil according to a goal-directed protocol (Appendix 3)

guided by the Richmond Agitation Sedation Scale (RASS) [24]. In patients with
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hemodynamic instability, the target was light to deep sedation (RASS score, -2 to -5). Patients

with moderate-to-severe acute respiratory distress syndrome [25] were placed in deep

sedation (RASS score, -4 to -5) and given an intravenous NMB agent. After sedation

interruption, propofol was used when analgesics failed to allow nursing care (the target RASS

score was -1 to +1). Neuroleptics were used in case of psychomotor agitation with potential

dangerousness.
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Pain intensity was determined using a numerical rating scale (NRS) or behavioral pain scale

when NRS was not available. The nurses assessed alertness at least 6 times/day, according to

the goal-directed sedation protocol. Readiness for sedation discontinuation was assessed daily

by the ICU team. Train-of-four monitoring was used to assess the depth of neuromuscular

blockade.

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Outcomes

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The primary outcome was the Medical Research Council (MRC) muscle strength sum score

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[26] at ICU discharge, which was compared between the Control and Tilt groups.

Secondary outcomes were muscular recovery during the ICU stay and MRC score at hospital
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discharge. Muscular recovery was expressed as the median change in MRC score from

baseline (MRC score recorded after sedation interruption in alertness patients) to ICU
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discharge. Other secondary outcomes were adverse events during out-of-bed mobilization,

time to ability to stand alone, ICU and hospital stay lengths, MV duration, use of sedatives
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and NMB agents, hospital mortality, infections, and severe ICU complications (requiring
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surgery, interventional radiology, therapeutic endoscopy or chest drainage).

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Data collection

The demographic and clinical data listed in Table 1 were recorded. The Simplified Acute
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Physiology Score II (SAPS II) and MacCabe score were collected on ICU admission. The

Sequential Organ Failure Assessment (SOFA) score was evaluated daily from inclusion to

discharge. The drugs used were recorded, as well as MV duration. The highest blood glucose

value each day was recorded from ICU admission to discharge.

For each session of out-of-bed mobilization, session duration, lowest mean arterial pressure

(MAP), RASS and pain scores were assessed.

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Patients were monitored for adverse events requiring a medical intervention or

discontinuation of mobilization, such as a greater than 20% change in MAP or heart rate,

arrhythmia, a greater than 10% decrease in SpO2, accidental catheter withdrawal or extubation,

and falls during transfer to the armchair or tilt table. Interruptions of mobilization session for

discomfort or fatigue were also recorded.

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Muscle strength evaluation

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For the baseline muscle strength evaluation, patients were screened twice daily after sedation

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discontinuation. An Attention Screening Examination was used to assess attention and

comprehension, according to the confusion assessment method for ICU [27]. Patients who
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responded appropriately underwent a muscle strength evaluation by a physiotherapist. Twelve

muscle groups were assessed (shoulder abduction, elbow flexion, and wrist extension at upper
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limbs and hip flexion, knee extension, and foot dorsiflexion at lower limbs). Strength in each

muscle group was scored using the 0-5 Medical Research Council (MRC) scale [26] and
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ICUAW is defined as a sum score <48 [2].

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The same method was used to assess muscle strength at ICU discharge and at hospital
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discharge.
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The MRC scores were blindly assessed by physiotherapists distinct from the ICU

physiotherapists who undertook the intervention.

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Power and Statistical Analysis

Based on literature we estimated the mean MRC sum score that would be observed at ICU

discharge (end-point). The sample size was estimated assuming an MRC sum score at ICU

discharge of 47 in the standard group with a 3-point improvement to 50 in the Tilt group [28].

To obtain 85% power for detecting this difference, assuming a common standard deviation of
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8 MRC points, with a two-tailed t test and the alpha risk set at 0.05, 50 evaluable patients

were required in each group. Assuming a mortality rate of 20% after enrollment, we planned

to increase this number by about 30% to correct for patient attrition. Thus, we planned to

enroll 150 patients in all (105 evaluable patients). The trial was therefore stopped after 145

inclusions due to a lower observed mortality/attrition rate.

Values are reported as medians with the 25th to 75th percentiles. The main results of the

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frequency distributions are expressed as % and 95% confidence interval (CI). Continuous

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variables were compared using Mann–Whitney U-test while comparisons between qualitative

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variables were evaluated by chi-square test or Fisher's exact test when necessary. Correlations

were evaluated using Spearman’s rank correlation coefficient. No correction for multiplicity
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of testing was done [29]. Statistical significance was defined as P<0.05. Statistical analysis

was conducted using Statview 5.0 software (SAS Institute, Berkeley, CA).
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Results
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Patients
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Between October 2013 and October 2014, 988 patients were admitted to the ICU, of whom
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145 were included in the study and randomized (Figure 1). Among them, 17 (12%) died and

3 were transferred to another ICU before out-of-bed mobilization. The randomly assigned
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mobilization protocol was administered in 61 of the 65 patients assigned to tilting and in 50 of

the 60 patients assigned to control therapy; thus, 111 patients were included in the per

protocol analysis. Table 1 reports the baseline characteristics, which were similar in the two

groups.

MRC sum score at ICU discharge and muscle strength recovery (Table 2)
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The MRC sum scores at ICU and hospital discharge were not significantly different between

the two groups in either the intention-to-treat or the per-protocol analysis. Neither was the

proportion of patients with weakness at ICU or hospital discharge different between the two

groups. For the two groups combined, in the intention-to-treat analysis, out-of-bed

mobilization was possible on 1,018 (89%) of 1,139 study days. Neither time to first out-of-

bed mobilization nor total duration of mobilization differed between groups.

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The proportion of patients with weakness before mobilization was significantly higher in the

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Tilt group than in the Control group (92% versus 80%, P=0.045). Consequently, muscular

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recovery during the ICU stay expressed as the median change in MRC score from baseline to

ICU discharge was significantly better in the Tilt group.

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Factors associated with muscle strength recovery (MRC score improvement)
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The baseline MRC sum score was significantly associated with muscle strength recovery

during the ICU stay (Rho=-0.73, P<0.001). Total mobilization duration was associated with
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muscle strength recovery overall (Rho=0.24, P=0.014); the association was significant in the
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Tilt group (Rho=0.32, P=0.015) and nonsignificant in the Control group (Rho=0.25, P=0.085).
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In the Tilt group, a dose-response effect was demonstrated (Rho=0.41, P=0.002).

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Other secondary outcomes

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No significant between-group differences were found for time to standing (Table 2), ICU and

hospital stay lengths, use of sedation, NMB, or corticosteroids, and MV days (Table 3).

During the ICU stay, infections and severe complications occurred similarly in the two groups

(Table 3).
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Hospital mortality was higher in the Control group (Table 3). Of the 125 patients, 6 patients

in the Control group died, 4 in the ICU and 2 after ICU discharge to a hospital ward. Thus,

mortality was 10% in the Control group and 0% in the Tilt group (P=0.010).

Clinical parameters and the number of adverse events during out-of-bed mobilization sessions

were comparable in the Control and Tilt groups (Table 3). The most frequent adverse events

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were minor cardiovascular effects and interruptions of mobilization sessions for discomfort or

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fatigue. No accidental extubation occurred. No patient died during a mobilization session.

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Discussion
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In our randomized controlled trial, early mobilization including tilting on a table proved
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feasible and safe in patients admitted to the ICU after cardiothoracic surgery. However,

adding tilting to a daily standardized rehabilitation program did not improve muscle strength
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recovery. There was a suggestion of faster muscle strength recovery with tilting.
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Before mobilization, our population had a very high prevalence of muscle weakness defined
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as an MRC score <48 (86%; 95% CI, 80-92%) compared to previous studies (25% to 49%)

[2,4,28]. The incidence rates reported depend on the specific ICU subpopulation that is
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studied, the risk factors to which this population was exposed, the diagnosis criteria used and

the timing of diagnosis during the acute illness [30]. The presence of numerous risk factors

for ICUAW in the studied patients after cardiothoracic surgery may explain this high

incidence. Risk factors such as emergency surgery, ECMO, lung and/or heart transplantation

by promoting bed rest, sepsis and mechanical ventilation probably contributed to our high

incidence. The timing of diagnosis ICUAW in our study occurred after randomization when
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MRC was feasible after a length of TCI before mobilization of 6 days [6.7-11.0] in Control

group and 5 days [3.0-10.0] in Tilt group. For instance, in patients requiring ICU stay of more

than 7 days, Coakley and colleagues found a prevalence of neurophysiological abnormalities

of 37/44 (84%, 95% CI, 73 to 95%) [31]. The prevalence of muscle weakness in our trial

decreased to 49% at ICU discharge and to only about 1% at hospital discharge. In a previous

study of medical ICU patients receiving MV and given early physical and occupational

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therapy, 31% had muscle weakness at hospital discharge [28]. We found an MRC sum score

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at hospital discharge of 57 (54-60) in Control group and 58 (55-60) in Tilt group patients who

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completed hospital follow up that may seem very high. Schweickert and colleagues assigned

scores of 0 for strength testing to patients who died (23% hospital mortality) and reported an
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MRC score of 52 (25-38) at hospital discharge after early physical therapy in mechanically

ventilated ICU patients, compared to an examination score of 48 (0-58) in controls [28]. Thus,
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after excluding deceased patients one may hypothesize that quite similar MRC scores would

be observed.
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Current recommendations for diagnosing ICUAW include a bedside evaluation of muscle

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strength using the MRC sum score [32], which has excellent interrater reliability within
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specific non-ICU patient populations and in ICU survivors. Good reproducibility has been

reported in critically ill patients [33,34]. However, MRC sum score determination requires
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patient cooperation, which may be limited by sedation and delirium. Thus, in earlier studies

10% [35] and 75% [36] of patients could not have the score determined during their ICU stay.

Stringent criteria for defining cooperation may therefore be essential to obtain reliable and

reproducible results [37]. In our study, awake patients were evaluated twice daily for attention

and comprehension. We also carried out a preliminary evaluation of the reproducibility of

MRC sum score evaluation across physiotherapists in our ICU, which was good (kappa=0.78).
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Tilting has been reported to encourage a more erect spinal posture [38]. However, tilting was

not effective on our primary outcome despite the use of One possible explanation is

insufficient intensity of tilt-table therapy. However, we used a high intensity of 1 hour/day. In

an Australian survey, among respondents who included tilting in their management of ICU

patients, 21% reported tilting a new patient more than once a week, with a median duration of

initial tilting of 10 minutes at an initial angle of 45° [17].

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In our trial, 400 tilting sessions were conducted in 65 patients, demonstrating the feasibility of

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this method. Tilting was combined with other modalities of early mobilization. We therefore

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compared a standardardized rehabilitation therapy with versus without tilting. The program

was intensive and was started early in both groups. This point, together with the very low
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prevalence of weakness at hospital discharge, may explain the absence of an added effect of

tilting. However, the data suggest faster recovery with tilting.

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Time spent sitting in the armchair was significantly shorter in the Tilt group, but total

mobilization duration was similar in the two groups. Total mobilization duration showed a
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weak association with the degree of muscle strength recovery.

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Tilting was safe in our postoperative ICU patients. Adverse events occurred similarly in the
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two groups. The frequency of minor adverse events of about 15% including discomfort and
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fatigue was acceptable. In a recent review with meta-analysis, Nydhal and coll. reported a

very low prevalence of adverse events (2.6%) during patient mobilization and physical
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rehabilitation in the ICU [39]. However, the frequency of potential safety events in individual

studies ranged between 0% and 23%, resulting in part from the heterogeneity in the definition

of safety events across studies.

Hospital mortality was higher in the standard group. However, among the 6 deceased patients,

the causes of death do not seem to be related to ICUAW and appear as a direct complication
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of the ICU admitting diagnosis for 3 patients (2 end stage chronic lung allograft dysfunction

after lung transplantation, one pulmonary artery rupture related to bronchopleural fistula after

lung resection).

Limitations of our study include the single-center design, which may affect external validity.

Second, management differences may have occurred between the two groups. However,

standardized protocols were used for sedation, neuromuscular blockade, glycemia control, and

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MV weaning. Third, the bedside ICU staff could not be blinded to group assignment.

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However, trained blinded assessors assessed all study outcomes. Fourth, the MRC sum score

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is a global evaluation of neuromuscular function that does not specifically measure walking

ability. Thus, in a previous randomized trial, walking ability at hospital discharge was better
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in the intervention group, although the MRC sum score was not different between groups [15].
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In summary, this randomized trial provides the first evidence on the effects of early

verticalization on muscle strength in postoperative cardiothoracic surgery patients admitted to

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the ICU and receiving MV. Muscle strength recovery was excellent with both standard
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mobilization alone and standard mobilization plus tilting. However, the MRC sum score was
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not different between groups at ICU or hospital discharge, though the data suggest faster
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recovery with tilting.

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Figure legends.

Figure 1. Patient flow chart of study of Safety and Efficacy of Early Passive Tilting in

Minimizing ICU-Acquired Weakness

Figure 2. Daily standardized rehabilitation therapy in the intervention and control

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groups

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ICU, Intensive Care Unit. TCI, temporary contraindication. RASS, Richmond Agitation

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Sedation Scale. RASS score of +2: Agitated, frequent nonpurposeful movement, fights

ventilator. RASS score of -2: light sedation, briefly awakens to voice (eye opening and
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contact <10 s)
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Table 1. Baseline characteristics of patients at enrolment

Characteristics All patients Control Tilt P value

Patients, n 145 73 72
Age (years) 64 [53-74] 67 [54-75] 62 [52-73] 0.199
Men/Female, n 98/47 52/21 46/26 0.345
Body mass index (kg/m2) 25.2 [21.8-28.7] 25.3 [21.9-28.4] 25.1 [21.8-29.2] 0.413
McCabe Score 2 [2-2] 2 [2-2] 2 [2-2] 0.368
SAPS II 41 [34-50] 41 [34-50] 40 [33-50] 0.743
SOFA score 9.0 [6.7-12.0] 9.0 [6.0-11.5] 0.998
PaO2/FiO2 (mmHg) 156 [110-195] 161 [105-228] 0.474
ICU admission diagnosis, n (%)
Heart surgery 54 (37) 26 (36) 28 (39)

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Abdominal aorta surgery 5 (3) 4 (5) 1 (1)
Pulmonary endarterectomy 35 (24) 18 (25) 17 (24)
Lung resection 14 (10) 9 (12) 5 (7)

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Lung and/or heart transplant 18 (12) 6 (8) 12 (17)
Emergency surgery 39 (27) 18 (25) 21 (29)
Other surgery 11 (8) 7 (10) 4 (6)

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ECMO 8 (6) 4 (5) 4 (6)
ARDS* 24 (17) 13 (18) 11 (15)
Glycemia
Highest level (mmol/L) 11.9 [10.4-14.4] 11.8 [9.8-14.0] 11.9 [10.7-14.5] 0.228
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Median (mmol/L) 9.4 [8.1-10.6] 9.0 [8.0-10.3] 9.6 [8.2-10.9] 0.258
>7 mmol/L (days) 4 [3-5] 4 [3-5] 4 [3-5] 0.104
>10 mmol/L (days) 2 [1-2] 1 [0-2] 2 [1-3] 0.149
Sepsis (episodes) 0 [0-1] 0 [0-1] 0 [0-1] 0.806
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Sedation (days) 3 [2-4] 3 [2-4] 3 [2-4] 0.455

Neuromuscular blockade (days) 1 [0-2] 0 [0-2] 1 [0-2] 0.165
Corticosteroid therapy (days) 0 [0-0] 0 [0-0] 0 [0-0] 0.881
Norepinephrine and/or 3 [2-4] 3 [2-4] 3 [2-4] 0.703
epinephrine and/or ECMO (days)
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SAPS II, Simplified Acute Physiology Score II; SOFA, Sequential Organ Failure Assessment;
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PaO2/FiO2, ratio of arterial partial pressure of oxygen over fraction of inspired oxygen; ICU, intensive

care unit; ECMO, extracorporeal membrane oxygenation; ARDS, acute respiratory distress syndrome
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*ARDS occurred more than 7 days after the initial surgery in 14 patients (8 in the standard group and

6 in the tilt group).

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Table 2. Muscular recovery

Characteristics Control Tilt P value

Patients with mobilization, n 60 65
Time with TCI before mobilization, days 6.0 [3.7-11.0] 5.0 [3.0-10.0] 0.474
SOFA during TCI 9.0 [6.7-12.0] 9.0 [6.0-11.5] 0.998
Mobilization sessions: patient-days, n 541 598
Armchair, n 487 429 <0.001
Table, n NA 400
Armchair + table, n NA 298
No mobilization, n 54 67 0.504
Total mobilization duration, min 1340 [536-2775] 1020 [580-1695] 0.313
Armchair, min 1340 [536-2775] 752 [472-1120] 0.013

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Table, min NA 232 [90-577]
Armchair per session, min 240 [135-305] 145 [105-210] <0.001
Table per session, min NA 60 [60-90]

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Muscle strength recovery
Baseline MRC 36 [25-45] 32 [24-40] 0.215
MRC<48 before mobilization, n 48 60 0.045

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MRC at ICU discharge 48 [45-54] 50 [45-56] 0.555
MRC<48 at ICU discharge, n (%) 25/50 (50) 29/61 (47) 0.796
MRC change vs. baseline at ICU
10 [5-15] 14 [10-24] 0.004
discharge
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MRC at hospital discharge 57 [54-60] 58 [55-60] 0.374
MRC change vs. baseline at hospital
33 [18-45] 43 [28-56] 0.022
discharge
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Time to first standing without help

Time from randomization, days 10.0 [6.5-19.5] 9.0 [5.2-14.0] 0.509
Time from mobilization, days 6.0 [2.0-12.0] 4.0[2.0-8.0] 0.364
TCI, temporary contraindications to out-of-bed mobilization; SOFA, Sequential Organ failure
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Assessment; MRC, Medical Research Council scale score for muscle strength; NA, not applicable.
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Baseline MRC was evaluated in ICU after sedation discontinuation and attention assessment, before
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out of bed mobilization.

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Table 3. Other outcomes

Characteristics Control Tilt P value

Patients with mobilization, n 60 65
Hospital mortality, n (%) 6 (10) 0 (0) 0.010
Sepsis (episodes) 1.0 [1.0-3.0] 1.0 [0.0-3.0] 0.414
Severe ICU complications (episodes) 0.0 [0.0-1.0] 0.0 [0.0-1.0] 0.239
Stay lengths
ICU, days 21.0 [14.0-38.0] 21.0 [14.0-37.0] 0.970
Hospital, days 32.0 [22.0-57.5] 33.0 [22.5-58.2] 0.390
MV, days 14.0 [8.0-29.0] 14.5 [9.0-29.0] 0.695
Sedation, days 6.0 [3.0-11.5] 7.0 [3.7-11.0] 0.626
Neuromuscular blocking agent, days 1.0 [0.0-5.2] 1.0 [0.0-6.0] 0.590

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Corticosteroid therapy, days 0.0 [0.0-0.0] 0.0 [0.0-1.2] 0.213
Parameters during mobilization sessions
PaO2/FiO2, mmHg 227 [177-295] 230 [177-299]

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SOFA score 4 [3-6] 5 [3-6]
RASS score 0 [0-0] 0 [0-0]
Armchair, Pain score 0 [0-0] 0 [0-1]

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Table, Pain score NA 0 [0-3]
Armchair, MAP, mmHg 73 [65-82] 76 [66-88]
Table, MAP, mmHg NA 78 [67-91]
Adverse events, n (% of patients-days) 64/487 (13) 86/531 (16) 0.170
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Armchair, n (% of mobilization sessions) 64/487 (13) 35/429 (8) 0.015
MAP, n 17 8 0.132
HR, n 10 7 0.637
Arrhythmia, n 2 0 0.501
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Arterial desaturation, n 9 2 0.070

Catheter/tube removal, n 1 1 1
Falls, n 1 0 1
Discomfort/fatigue, n 24 16 0.376
Other, n 0 1 0.468
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Table, n (% of mobilization sessions) NA 51/400 (13) 0.127

MAP, n 17 0.636
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HR, n 6 0.517
Arrhythmia, n 0 0.137
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Arterial desaturation, n 8 0.346

Catheter/tube removal, n 0 1
Falls, n 0 0.370
Discomfort/fatigue, n 18 0.480
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Other, n 2 0.300

MV, mechanical ventilation; NA, not applicable. A greater than 20% change in mean arterial pressure
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(MAP) or in heart rate (HR) were defined as adverse events. There was one accidental catheter

withdrawal in Tilt group during armchair mobilization and one feeding tube removal in Control group.

Other adverse events were the need to return to bed for a planned medical intervention (one fiberoptic

bronchoscopy, 2 computed tomography in Tilt group). In italics, the comparisons of adverse events of

Control versus whole events (armchair + table) of Tilt group (for instance, total events: 64/487 versus

(35+51)/(429+400)).
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Highlights
Passive tilting added to early physiotherapy improves recovery of those patients who are at
risk for ICUAW

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Figure 1
Figure 2