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The oxygen cost of rehabilitation interventions in mechanically ventilated patients
Accepted Manuscript Title: The oxygen cost of rehabilitation interventions in mechanically ventilated patients Author: Claire Black Micheal Grocott Mervyn Singer PII: DOI: Reference:
S0031-9406(18)30301-8 https://doi.org/doi:10.1016/j.physio.2019.06.008 PHYST 1117
To appear in:
Physiotherapy
Received date: Revised date: Accepted date:
22 October 2018 11 March 2019 21 June 2019
Please cite this article as: Claire Black, Micheal Grocott, Mervyn Singer, The oxygen cost of rehabilitation interventions in mechanically ventilated patients, (2019), https://doi.org/10.1016/j.physio.2019.06.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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The oxygen cost of rehabilitation interventions in mechanically ventilated patientsI
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Abstract
Objective: Early rehabilitation is assumed to be a crucial intervention to
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facilitate weaning from mechanical ventilation in critically ill patients and to limit their long-term functional dependence. However, little is
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known about the physiological load imposed on patients during such interventions. Without the ability to quantify the exercise intensity of re-
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habilitation interventions it is impossible to establish a clear separation
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between usual care and intervention groups in randomised controlled trials. This may explain the lack of definitive benefit of rehabilitation
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in published trials. We sought to characterise the physiological load, ˙ 2 ), of the physical activities carmeasured as oxygen consumption (VO
ried out during rehabilitation interventions in mechanically ventilated participants.
Design: Observational Study Setting: Single centre medical-surgical university hospital ICU.
Participants: 26 mechanically ventilated participants ventilated >7 days, able to participate in a rehabilitation program. Intervention: Oxygen consumption (measured by the Medgraphics Ultima Preprint submitted to Physiotherapy
July 1, 2019
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breath-by-breath gas exchange analysis system) and heart rate were
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measured continuously pre-, during and post-standard rehabilitation sessions.
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Results: 52 sessions were recorded in 26 participants. There was considerable variation in the oxygen cost of the physical activities between
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participants. The recovery time for 1 in 4 rehabilitation sessions was longer than the rehabilitation activity time.
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Conclusions: Absolute exercise intensity in mechanically ventilated ICU
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participants, as measured by oxygen consumption, is not activity-dependent. Contribution of paper
We present novel data regarding the oxygen cost of rehabilitation inter-
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following:
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ventions in mechanically ventilated participants in ICU and demonstrate the
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• the oxygen cost of rehabilitation activities varies between participants, • oxygen consumed during rehabilitation interventions may be influenced by factors such as the participants active contribution to the activity.
Keywords: Rehabilitation, Exercise, Oxygen consumption, Mechanical ventilation, Critical illness,
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1. Introduction
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Patients who survive critical illness have a severely reduced exercise ca-
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pacity [1, 2]. However, the metabolic cost of individual rehabilitation ac-
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tivities in mechanically ventilated patients is, as yet unknown. The current 2
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assumption is that the metabolic cost of an individual rehabilitation activity,
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such as siting over the edge of the bed (SOEB) is the same for each patient
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and similar to that of a healthy individual.
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A failure to appropriately tailor individualised exercise programs may
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lead to under-training of some patients, delaying their recovery by not al-
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lowing them to reach their full rehabilitation potential, while over-training
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others, potentially placing them under considerable physiological stress.
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The available evidence suggests that active rehabilitation interventions
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[3],[4], increase a patients energy expenditure beyond their resting metabolic
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rate. However the intensity at which an intervention becomes a training load
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will be dictated by the patients duration of exposure to both bed rest and
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sepsis, along with their incumbent level of physiological fitness before they
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arrive in ICU. Without the ability to quantify the exercise intensity of re-
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habilitation interventions [5] it is impossible to establish a clear separation
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tima (MGU) (St Paul, Minneapolis, MN, USA) device in mechanically venti-
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lated (MV) ICU patients [10] and demonstrated the feasibility of measuring
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˙ 2 during rehabilitation interventions [11]. Here we report a pilot study to VO
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between usual care and intervention groups in randomised controlled trials. This may be why we have yet to see evidence of a definitive benefit of rehabilitation in published trials.[6, 7, 8, 9]
The gold standard for measuring energy expenditure is breath-by-breath
gas exchange analysis (BBGEA). We recently validated the Medgraphics Ul-
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investigate the oxygen cost of rehabilitation activities in mechanically venti-
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lated patients recovering from critical illness.
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The primary objective of this study was to describe rehabilitation ac-
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tivities in mechanically ventilated ICU patients in terms of duration and
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˙ 2. intensity, as given by VO
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2. Methods and materials
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Ethical approval was granted for the study by the UK National Research
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Ethics Service (REC reference number 11/LO/1646). This single-centre ob-
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servational study was conducted between August 2012 and March 2015 in
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a 26-bed medical surgical ICU in London, UK. Participants were included
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if they were aged 18 years or over, had been receiving mechanical ventila-
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tion for over >7 days, had a tracheostomy, and they or their representative
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gave informed consent/surrogate approval. Exclusion criteria were an in-
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ability to exercise due to pre-existing conditions or current morbidity e.g.
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severe dementia, motor neurone disease, severe stroke, severe critical illness neuromyopathy, moderate-to- severe stenotic valvular heart disease, primary pulmonary hypertension, hypertrophic cardiomyopathy, or unstable angina. 2.1. Participant methodology Before each session, participants were assessed for suitability to exercise
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by the ICU physiotherapist, as per normal practice at University College
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Hospital (Supplementary material: Screening participants prior to exercise).
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Rehabilitation sessions consisted of sitting the participant over the edge of
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the bed (SOEB), SOEB and balance activities, then progressing them, as 4
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able, to standing, transferring and walking. Early termination of exercise
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was based upon criteria described in the supplementary material (Indication
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for termination of rehabilitation sessions). The participant was encouraged
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to achieve their maximum functional level of activity during each rehabilita-
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tion session.
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The MGU flow sensor was calibrated using the manufacturers instruc-
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tions and placed in the participants ventilator circuit 30 minutes prior to
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the rehabilitation session. Individual participant data were recorded during
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rehabilitation sessions up to 3 times a week until they were liberated from
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mechanical ventilation. The variables, recorded by the Breeze Suite soft-
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˙ 2 ware supplied with the MGU, were: time from the beginning of the VO
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˙ 2 (mL.min-1 ), carbon dioxide production (mL.min-1 ), resrecording (sec), VO
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piratory rate (bpm), minute ventilation (l.min-1 ) and respiratory exchange
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ratio (RER). Additionally, we recorded the time at which each rehabilita-
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tion activity occurred to allow retrospective analysis of individual activities.
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Blood pressure was recorded from either an indwelling arterial cannula or a non-invasive cuff, and ECG monitoring continued throughout. Resting (HRrest ) and peak (HRpeak ) heart rate during exercise were recorded from the participants bedside monitor. 2.2. Breath by breath gas exchange analysis
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The Medgraphics Ultima (MGU) BBGEA device provides a direct mea-
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surement of oxygen consumption during exercise. It measures both inspira-
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tory and expiratory flow through a bi-directional, patented flow-sensor. The
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MGU device is widely used for exercise testing in spontaneously breathing 5
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individuals and, more recently, in mechanically ventilated participants [10].
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2.3. Assessments of functional status
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The ICU Functional Status Score (ICU-FSS) was measured in all partic-
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ipants at each testing session [12]. The FSS-ICU examines the participant’s
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ability to perform the five functional tasks: rolling, transfer from supine to
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sit, SOEB, transfer from sit to stand, and walking. Each task is evaluated
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using an eight-point ordinal scale ranging from 0 (unable to perform) to
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7 (complete independence). The total score ranges from 0-35, with higher
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scores indicating better physical functioning. The minimally minimum clin-
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ically important difference is reported to be 2 - 5 [13].
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Pre-admission activity levels were estimated from a General Practice
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Physical Activity Questionnaire (GPPAQ) score [14]. This information was
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obtained from either the participant and/or relatives. The GPPAQ is a val-
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idated screening tool for use in primary care to assess adult (16 - 74 years)
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physical activity levels. It provides a simple, 4-level Physical Activity Index categorising participants as active, moderately active, moderately inactive, or inactive. Participants were asked to report their perceived exertion at the beginning and end of the rehabilitation sessions using the Borg rate of perceived exertion scale, a self-reported tool with a category scale ranging from 6 to 20 points [15]. 3. Analysis
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The total session VO2 (mL.kg-1 ) was estimated by calculating the area
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˙ 2 (mL.kg.-1 min-1 ) curves bound by the start of the under the individual VO 6
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rehabilitation session, defined as the time the participant initially began to
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˙ 2 returned to within 10% of the baseline resting value SOEB and the time VO
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before exercise (Figure 1). Total session VO2 (mL.kg-1 ) was thus calculated
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˙ 2 as the product of the duration of the session (minutes) and the mean VO
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(mL.min-1 ) of the session.
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˙ 2 (mL.min-1 ) was calculated as the mean VO ˙ 2 (mL.min-1 ) durResting VO
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˙ 2 at rest ing 10 consecutive minutes where there was a <10% variation in VO
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within the 30 minutes prior to the rehabilitation session. The VO2 (mL.kg-1 )
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attributable to the rehabilitation session itself, i.e. the VO2 (mL.kg-1 ) con-
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sumed above resting VO2 , was calculated by subtracting the equivalent VO2
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(mL.kg-1 ) at rest from the total session VO2 (mL.kg-1 ) (Figure 1). The VO2
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values attributable to the rehabilitation session are presented as a percent-
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age of the resting VO2 . To draw comparison between the percentage change
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in VO2 between different rehabilitation activities, the activities were cate-
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gorised as either sitting or standing.
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testing, increase in pressure support during the session (PSinc ), Haemoglobin
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(Hb), Sequential Organ Failure Score (SOFA), GPPAQ, weight, gender, age.
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A step down approach was used to remove non-significant variables from the
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For hypothesis generating purposes, multilevel univariate regression [16]
was performed with percentage change in VO2 as the dependent variable. A beyond optimal model was created. The explanatory variables used were; rehabilitation activity; categorised as either sitting (SOEB and SOEB ± balance exercises) or standing (STS, MOS or BCT), ICU-FSS on the day of
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model and a restricted maximum likelihood estimation used to estimated
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the variance of the model. The interaction between ICU-FSS and rehabilita-
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tion activity was assessed using ANOVA of the log-likelihoods of the relevant
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models. This was to test if the ICU-FSS was influencing the rehabilitation
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activity i.e the higher the ICU FSS the more likely it would be for the par-
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ticipant to carry out a higher level of activity. The residuals of the final
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model were then plotted and examined for heterogeneity. This method of
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regression was used to control for the within-participant nature of the reha-
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bilitation sessions, i.e allowing for correlation between multiple observations
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from the same participant.
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4. Results
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4.1. Recruitment
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Forty-four participants were recruited between August 2012 and March
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2015, performing 125 tests in total. No data were collected for two partici-
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pants as one weaned from mechanical ventilation before the first test, while
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the other became cardiovascularly unstable before the first test and remained so thereafter. Figure 2 shows the participant recruitment diagram and Table 1 participant characteristics. These participants had been mechanically ventilated for a median 22.5 (range 4 -103) days before their first rehabilitation session and mechanically ventilated for a median of 30 days (range
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11 -103) before their first evaluated rehabilitation session within the study.
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The median highest SOFA score was 10 (range 2 -14). Using the GPPAQ
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classification of participant activity prior to ICU admission, obtained either
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from the participant or a surrogate, 11 participants were classed as inactive, 8
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Median
Min
Max
Age (years)
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31
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Weight (kg)
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MV prior to recruitment
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17 as relatively inactive, 12 relatively active and 4 active.
Highest SOFA
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MV = mechanical ventilation
GPPAQ = General practice physical assessment questionnaire
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SOFA = Sepsis Organ Failure Score
Table 1: Characteristics of the 26 participants
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Table 2 shows the characteristics of the participants during the 52 recorded
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rehabilitation sessions with respect to body temperature, haemoglobin and
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ICU-FSS. During six tests, three participants were receiving total parenteral
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nutrition with the remainder fed enterally via a nasogastric tube. One participant was receiving renal replacement therapy during 4 tests. 4.2. Rehabilitation sessions A total of 104 rehabilitation sessions involving rehabilitation activities to
at least SOEB were assessed in 42 participants. Predominantly related to
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technical issues (listed in Figure 2), the percentage change in VO2 from rest
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could only be calculated in 52 of the 104 tests. These comprised 15 SOEB
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episodes, 11 SOEB and balance work, 7 single sit-to-stand, 10 sit-to-stand
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>1, and 9 bed-chair transfers. The minimum rehabilitation session duration 9
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Min
Max
C Reactive Protein (g.L-1 )
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2
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Haemoglobin (mg.L-1 )
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11
SOFA
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1
10
Temperature (C)
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35.7
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White Blood Cell Count (109 L-1 )
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4
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3
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ICU-FSS total
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SOFA = Sepsis Organ Failure Score
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Median
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n = 52
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Variable
ICU-FSS total = ICU Functional Status Score total
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Table 2: Characteristics of the participants for the 52 recorded rehabilitation sessions.
was 5 minutes and 35 seconds to transfer from bed to chair. The maximum
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duration was 39 minutes and 21 seconds to SOEB and to stand one or more
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times (Table 3). Session duration was the total time from when the partici-
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pant started to move, to when VO2 had recovered to within 10% of baseline.
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Rehabilitation activity duration was the total time from when the partic-
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ipant started to move to returning to supine. Recovery proportion is the proportion of the whole rehabilitation session that was taken with recovery to within 10% of baseline VO2 . For ten rehabilitation sessions participant recovery time was greater than the actual rehabilitation activity duration.
Box plots of the rehabilitation categories (sitting or standing) and the
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˙ 2 (mL.kg.-1 min-1 ) of the session, the total VO2 of the session (mL.kg-1 ), mean VO
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and the percentage change in VO2 of the session are shown in Figure 3. The
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mean (SD) percentage increase in VO2 from rest to SOEB ± balance activi10
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SOEB
Session Duration
Rehabilitation Duration Recovery Proportion
Min Median Max Min Median 15 06:11 15:00 36:36 04:34 08:46
Max
Min Median
Max
23:28
0.20
0.51
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Activity
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Rehabilitation
17:38
0.18
0.34
0.59
STS x1
7 10:55 18:32 26:19 05:06 10:17
16:11
0.29
0.37
0.72
STS > 1
10 07:44 22:04 39:21 05:53 15:13
25:10
0.22
0.31
0.47
MOS or BCT
9 05:35 12:07 28:04 02:52 07:43
28:04
0.00
0.35
0.49
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SOEB & balance 11 13:19 21:04 31:45 06:51 13:38
SOEB = sit over the edge of bed, STS = sit to stand, MOS = march on spot, BCT = bed chair transfer.
Table 3: Session duration = time from initiation of movement to VO2 recovering to within
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10% of baseline, Rehabilitation duration = time from initiation of movement to returning to supine and Recovery proportion = the proportion of the whole rehabilitation session
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taken with recovery.
ties was 23.3 (11.2). The mean percentage increase in VO2 from rest to stand-
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ing and/or transferring from bed to chair was 34.8 (13.3). The interaction
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i.e the way ICU-FSS influenced rehabilitation category was non-significant
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(p = 0.31) and not included in the final model (Supplementary Table 1). When residuals were plotted (Supplementary Figure 1), one participant was identified as a significant outlier. ˙ 2 (and VO2 ) The final selected model of the percentage change in VO
included ICU-FSS, the pressure support increment and the rehabilitation ac-
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tivity. Therefore, a participant with an ICU-FSS of 0 who could SOEB with
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a pressure support increment of 0 would expect an 12% (95% CI: 4-20) in-
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˙ 2 . For every point increase in ICU-FSS, a 1% (95% CI: 1-2) crease in their VO 11
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˙ 2 could be expected. For each cm H2 O increase in pressure increase in VO
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˙ 2 could be expected. support, a 1.5% (95% CI: 0-3) increase in VO
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The calculated pseudo R2 for this model was 0.63. This suggests that
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activity, functional status and pressure support increment explain up to 63%
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˙ 2 during a rehabilitation session in the ICU. of the change seen in VO
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5. Discussion
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This study aimed to describe rehabilitation activities in mechanically ven-
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˙ 2 ) and rehabilitation activity tilated patients in terms of the intensity (VO
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duration. We present novel data regarding the oxygen cost and duration of
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rehabilitation interventions in mechanically ventilated participants in ICU
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and demonstrate the following: (i) the oxygen cost of rehabilitation varies
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between participants; (ii) the oxygen cost of the rehabilitation activity was
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associated with the level the participant actively contributed the activity;
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(iii) the recovery time was greater than the duration of the rehabilitation
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activity in one in four rehabilitation sessions.
It is important to acknowledge that the population studied were both
persistently mechanically ventilated and critically ill. Therefore it is not possible to extrapolate the findings of this study to all ICU patients receiving rehabilitation. The large standard deviation of the sample data reflects in
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part the relatively small sample size but also the heterogeneity of the partici-
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pants recruited and the multiplicity of factors influencing energy expenditure
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˙ 2 meaduring a rehabilitation session. Technical issues often prevented VO 12
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surement during rehabilitation sessions in our mechanically ventilated partic-
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ipants indicating that the technique is feasible although challenging. Where
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measurements could be performed, we noted the main factor that influenced
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˙ 2 was the participants’ physical function status, the percentage change in VO
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rather than the actual rehabilitation activity. The regression model showed
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that an increase in ICU-FSS was associated with an increase in the percent-
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˙ 2 . The relationship between ICU-FSS and change in VO ˙ 2 may relate age VO
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to reduced O2 consumption in individuals who are less able to contribute
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actively to the rehabilitation activity. Reasons for being less able to partici-
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pate actively may include general fatigue, less muscle to recruit as a result of
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ICU-acquired sarcopenia, and/or decreased oxygen utilisation due to bioen-
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ergetic dysfunction or changes in fibre type composition. While ICU-FSS
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˙ 2 , this does not assist in estimating in isolation may be associated with VO
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an individual patients’ exercise capacity, nor the intensity at which they are
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working. We found that ICU-FSS was highly correlated with the rehabil-
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itation activity, presumably because the improvement in physical function
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perception of breathlessness will enable them to achieve more in a rehabilita-
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tion session. We noted a trend towards an increase in rehabilitation activity
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duration in those participants in whom pressure support was increased (Sup-
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(measured by ICU-FSS) meant the participant was more likely to engage in a higher level of activity (Supplementary Figure 3). ˙ 2 . This Incrementing ventilatory support could influence the change in VO
is commonly done during a rehabilitation session on the assumption that offloading the participants mechanical respiratory load and/or reducing their
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plementary Figure 2). This may suggest that the perception of breathlessness
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or mechanical respiratory load are potentially important factors that can be
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manipulated in mechanically ventilated participants. However, we cannot
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exclude the possibility that therapists consider this enables them to push
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participants harder. Further study is warranted, but also challenging. A
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participant would need to perform the same rehabilitation activity twice,
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with or without an increase in pressure support. We found many partici-
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pants were fatigued after just one activity and could perform no more.
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There are several limitations to the current study. It was not possible
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to test repeatability as participants were often too fatigued at the end of a
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rehabilitation session to repeat the same activity. The few comparisons that
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were possible between different days were not necessarily valid due to changes
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in the participants physiological status. There were insufficient repeated
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episodes to test the sensitivity of the measurement technique to measure
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change over time. The regression analysis did not detect any alteration in
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˙ 2 over time. This is likely due to insufficient the percentage change in VO numbers of participants repeating the same activity over time. Given the nature of rehabilitation in the ICU, participants were rehabilitated to their maximum functional level on each occasion. Reasons for ceasing exercise were unfortunately not recorded; these may have provided useful insights into the limitations to exercise experienced.
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6. Conclusion Breath-by-breath gas exchange analysis remains a challenging technique
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to perform consistently. However, it can provide valuable information regard-
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ing the participants oxygen consumption during rehabilitation. We found
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˙ 2 , is not activity-dependent. that absolute exercise intensity, as measured by VO
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Therefore the assumption that a rehabilitation activity such as SOEB has the
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same absolute exercise intensity for each patient is not valid. This highlights
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the need to monitor each individual patients’ workload during rehabilitation
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in real time at the point of care.
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List of changes
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7. Ethical Approval
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8. Funding
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UK National Research Ethics Service (REC reference number 11/LO/1646).
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This work was funded by a National Institute for Health Research (NIHR)
Clinical Academic Training Fellowship. 9. Conflict of Interest None.
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10. Disclaimer This report presents independent research funded by the NIHR. The views
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expressed are those of the author(s) and not necessarily those of the NHS,
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the NIHR, or the Department of Health.
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11. Figure Legends
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Figure 284 1: Oxygen consumption calculation for rehabilitation sessions. a = VO2 attributable to exercise session, b = Total VO2 at rest, a + b = Total
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session VO2
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Figure 287 2: Recruitment of participants to the study
Figure 288 3: Box plots of a. percentage change in session VO2 , b. session VO2
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12. References
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(mL.kg.-1 min-1 ) and c. session VO2 (mL.kg.-1 ). ** p <0.01
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S0031-9406(18)30301-8 https://doi.org/doi:10.1016/j.physio.2019.06.008 PHYST 1117
To appear in:
Physiotherapy
Received date: Revised date: Accepted date:
22 October 2018 11 March 2019 21 June 2019
Please cite this article as: Claire Black, Micheal Grocott, Mervyn Singer, The oxygen cost of rehabilitation interventions in mechanically ventilated patients, (2019), https://doi.org/10.1016/j.physio.2019.06.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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The oxygen cost of rehabilitation interventions in mechanically ventilated patientsI
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Abstract
Objective: Early rehabilitation is assumed to be a crucial intervention to
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facilitate weaning from mechanical ventilation in critically ill patients and to limit their long-term functional dependence. However, little is
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known about the physiological load imposed on patients during such interventions. Without the ability to quantify the exercise intensity of re-
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habilitation interventions it is impossible to establish a clear separation
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between usual care and intervention groups in randomised controlled trials. This may explain the lack of definitive benefit of rehabilitation
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in published trials. We sought to characterise the physiological load, ˙ 2 ), of the physical activities carmeasured as oxygen consumption (VO
ried out during rehabilitation interventions in mechanically ventilated participants.
Design: Observational Study Setting: Single centre medical-surgical university hospital ICU.
Participants: 26 mechanically ventilated participants ventilated >7 days, able to participate in a rehabilitation program. Intervention: Oxygen consumption (measured by the Medgraphics Ultima Preprint submitted to Physiotherapy
July 1, 2019
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breath-by-breath gas exchange analysis system) and heart rate were
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measured continuously pre-, during and post-standard rehabilitation sessions.
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Results: 52 sessions were recorded in 26 participants. There was considerable variation in the oxygen cost of the physical activities between
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participants. The recovery time for 1 in 4 rehabilitation sessions was longer than the rehabilitation activity time.
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Conclusions: Absolute exercise intensity in mechanically ventilated ICU
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participants, as measured by oxygen consumption, is not activity-dependent. Contribution of paper
We present novel data regarding the oxygen cost of rehabilitation inter-
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following:
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ventions in mechanically ventilated participants in ICU and demonstrate the
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• the oxygen cost of rehabilitation activities varies between participants, • oxygen consumed during rehabilitation interventions may be influenced by factors such as the participants active contribution to the activity.
Keywords: Rehabilitation, Exercise, Oxygen consumption, Mechanical ventilation, Critical illness,
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1. Introduction
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Patients who survive critical illness have a severely reduced exercise ca-
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pacity [1, 2]. However, the metabolic cost of individual rehabilitation ac-
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tivities in mechanically ventilated patients is, as yet unknown. The current 2
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assumption is that the metabolic cost of an individual rehabilitation activity,
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such as siting over the edge of the bed (SOEB) is the same for each patient
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and similar to that of a healthy individual.
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A failure to appropriately tailor individualised exercise programs may
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lead to under-training of some patients, delaying their recovery by not al-
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lowing them to reach their full rehabilitation potential, while over-training
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others, potentially placing them under considerable physiological stress.
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The available evidence suggests that active rehabilitation interventions
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[3],[4], increase a patients energy expenditure beyond their resting metabolic
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rate. However the intensity at which an intervention becomes a training load
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will be dictated by the patients duration of exposure to both bed rest and
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sepsis, along with their incumbent level of physiological fitness before they
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arrive in ICU. Without the ability to quantify the exercise intensity of re-
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habilitation interventions [5] it is impossible to establish a clear separation
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tima (MGU) (St Paul, Minneapolis, MN, USA) device in mechanically venti-
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lated (MV) ICU patients [10] and demonstrated the feasibility of measuring
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˙ 2 during rehabilitation interventions [11]. Here we report a pilot study to VO
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between usual care and intervention groups in randomised controlled trials. This may be why we have yet to see evidence of a definitive benefit of rehabilitation in published trials.[6, 7, 8, 9]
The gold standard for measuring energy expenditure is breath-by-breath
gas exchange analysis (BBGEA). We recently validated the Medgraphics Ul-
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investigate the oxygen cost of rehabilitation activities in mechanically venti-
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lated patients recovering from critical illness.
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The primary objective of this study was to describe rehabilitation ac-
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tivities in mechanically ventilated ICU patients in terms of duration and
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˙ 2. intensity, as given by VO
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2. Methods and materials
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Ethical approval was granted for the study by the UK National Research
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Ethics Service (REC reference number 11/LO/1646). This single-centre ob-
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servational study was conducted between August 2012 and March 2015 in
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a 26-bed medical surgical ICU in London, UK. Participants were included
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if they were aged 18 years or over, had been receiving mechanical ventila-
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tion for over >7 days, had a tracheostomy, and they or their representative
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gave informed consent/surrogate approval. Exclusion criteria were an in-
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ability to exercise due to pre-existing conditions or current morbidity e.g.
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severe dementia, motor neurone disease, severe stroke, severe critical illness neuromyopathy, moderate-to- severe stenotic valvular heart disease, primary pulmonary hypertension, hypertrophic cardiomyopathy, or unstable angina. 2.1. Participant methodology Before each session, participants were assessed for suitability to exercise
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by the ICU physiotherapist, as per normal practice at University College
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Hospital (Supplementary material: Screening participants prior to exercise).
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Rehabilitation sessions consisted of sitting the participant over the edge of
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the bed (SOEB), SOEB and balance activities, then progressing them, as 4
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able, to standing, transferring and walking. Early termination of exercise
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was based upon criteria described in the supplementary material (Indication
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for termination of rehabilitation sessions). The participant was encouraged
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to achieve their maximum functional level of activity during each rehabilita-
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tion session.
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The MGU flow sensor was calibrated using the manufacturers instruc-
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tions and placed in the participants ventilator circuit 30 minutes prior to
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the rehabilitation session. Individual participant data were recorded during
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rehabilitation sessions up to 3 times a week until they were liberated from
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mechanical ventilation. The variables, recorded by the Breeze Suite soft-
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˙ 2 ware supplied with the MGU, were: time from the beginning of the VO
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˙ 2 (mL.min-1 ), carbon dioxide production (mL.min-1 ), resrecording (sec), VO
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piratory rate (bpm), minute ventilation (l.min-1 ) and respiratory exchange
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ratio (RER). Additionally, we recorded the time at which each rehabilita-
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tion activity occurred to allow retrospective analysis of individual activities.
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Blood pressure was recorded from either an indwelling arterial cannula or a non-invasive cuff, and ECG monitoring continued throughout. Resting (HRrest ) and peak (HRpeak ) heart rate during exercise were recorded from the participants bedside monitor. 2.2. Breath by breath gas exchange analysis
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The Medgraphics Ultima (MGU) BBGEA device provides a direct mea-
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surement of oxygen consumption during exercise. It measures both inspira-
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tory and expiratory flow through a bi-directional, patented flow-sensor. The
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MGU device is widely used for exercise testing in spontaneously breathing 5
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individuals and, more recently, in mechanically ventilated participants [10].
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2.3. Assessments of functional status
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The ICU Functional Status Score (ICU-FSS) was measured in all partic-
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ipants at each testing session [12]. The FSS-ICU examines the participant’s
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ability to perform the five functional tasks: rolling, transfer from supine to
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sit, SOEB, transfer from sit to stand, and walking. Each task is evaluated
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using an eight-point ordinal scale ranging from 0 (unable to perform) to
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7 (complete independence). The total score ranges from 0-35, with higher
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scores indicating better physical functioning. The minimally minimum clin-
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ically important difference is reported to be 2 - 5 [13].
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Pre-admission activity levels were estimated from a General Practice
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Physical Activity Questionnaire (GPPAQ) score [14]. This information was
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obtained from either the participant and/or relatives. The GPPAQ is a val-
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idated screening tool for use in primary care to assess adult (16 - 74 years)
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physical activity levels. It provides a simple, 4-level Physical Activity Index categorising participants as active, moderately active, moderately inactive, or inactive. Participants were asked to report their perceived exertion at the beginning and end of the rehabilitation sessions using the Borg rate of perceived exertion scale, a self-reported tool with a category scale ranging from 6 to 20 points [15]. 3. Analysis
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The total session VO2 (mL.kg-1 ) was estimated by calculating the area
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˙ 2 (mL.kg.-1 min-1 ) curves bound by the start of the under the individual VO 6
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rehabilitation session, defined as the time the participant initially began to
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˙ 2 returned to within 10% of the baseline resting value SOEB and the time VO
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before exercise (Figure 1). Total session VO2 (mL.kg-1 ) was thus calculated
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˙ 2 as the product of the duration of the session (minutes) and the mean VO
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(mL.min-1 ) of the session.
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˙ 2 (mL.min-1 ) was calculated as the mean VO ˙ 2 (mL.min-1 ) durResting VO
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˙ 2 at rest ing 10 consecutive minutes where there was a <10% variation in VO
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within the 30 minutes prior to the rehabilitation session. The VO2 (mL.kg-1 )
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attributable to the rehabilitation session itself, i.e. the VO2 (mL.kg-1 ) con-
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sumed above resting VO2 , was calculated by subtracting the equivalent VO2
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(mL.kg-1 ) at rest from the total session VO2 (mL.kg-1 ) (Figure 1). The VO2
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values attributable to the rehabilitation session are presented as a percent-
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age of the resting VO2 . To draw comparison between the percentage change
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in VO2 between different rehabilitation activities, the activities were cate-
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gorised as either sitting or standing.
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testing, increase in pressure support during the session (PSinc ), Haemoglobin
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(Hb), Sequential Organ Failure Score (SOFA), GPPAQ, weight, gender, age.
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A step down approach was used to remove non-significant variables from the
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For hypothesis generating purposes, multilevel univariate regression [16]
was performed with percentage change in VO2 as the dependent variable. A beyond optimal model was created. The explanatory variables used were; rehabilitation activity; categorised as either sitting (SOEB and SOEB ± balance exercises) or standing (STS, MOS or BCT), ICU-FSS on the day of
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model and a restricted maximum likelihood estimation used to estimated
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the variance of the model. The interaction between ICU-FSS and rehabilita-
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tion activity was assessed using ANOVA of the log-likelihoods of the relevant
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models. This was to test if the ICU-FSS was influencing the rehabilitation
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activity i.e the higher the ICU FSS the more likely it would be for the par-
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ticipant to carry out a higher level of activity. The residuals of the final
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model were then plotted and examined for heterogeneity. This method of
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regression was used to control for the within-participant nature of the reha-
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bilitation sessions, i.e allowing for correlation between multiple observations
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from the same participant.
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4. Results
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4.1. Recruitment
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Forty-four participants were recruited between August 2012 and March
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2015, performing 125 tests in total. No data were collected for two partici-
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pants as one weaned from mechanical ventilation before the first test, while
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the other became cardiovascularly unstable before the first test and remained so thereafter. Figure 2 shows the participant recruitment diagram and Table 1 participant characteristics. These participants had been mechanically ventilated for a median 22.5 (range 4 -103) days before their first rehabilitation session and mechanically ventilated for a median of 30 days (range
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11 -103) before their first evaluated rehabilitation session within the study.
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The median highest SOFA score was 10 (range 2 -14). Using the GPPAQ
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classification of participant activity prior to ICU admission, obtained either
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from the participant or a surrogate, 11 participants were classed as inactive, 8
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Median
Min
Max
Age (years)
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31
85
Weight (kg)
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MV prior to recruitment
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n = 26
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17 as relatively inactive, 12 relatively active and 4 active.
Highest SOFA
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4
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GPPAQ
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MV = mechanical ventilation
GPPAQ = General practice physical assessment questionnaire
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SOFA = Sepsis Organ Failure Score
Table 1: Characteristics of the 26 participants
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Table 2 shows the characteristics of the participants during the 52 recorded
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rehabilitation sessions with respect to body temperature, haemoglobin and
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ICU-FSS. During six tests, three participants were receiving total parenteral
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nutrition with the remainder fed enterally via a nasogastric tube. One participant was receiving renal replacement therapy during 4 tests. 4.2. Rehabilitation sessions A total of 104 rehabilitation sessions involving rehabilitation activities to
at least SOEB were assessed in 42 participants. Predominantly related to
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technical issues (listed in Figure 2), the percentage change in VO2 from rest
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could only be calculated in 52 of the 104 tests. These comprised 15 SOEB
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episodes, 11 SOEB and balance work, 7 single sit-to-stand, 10 sit-to-stand
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>1, and 9 bed-chair transfers. The minimum rehabilitation session duration 9
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Min
Max
C Reactive Protein (g.L-1 )
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2
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Haemoglobin (mg.L-1 )
8
7
11
SOFA
3
1
10
Temperature (C)
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35.7
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White Blood Cell Count (109 L-1 )
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4
26
3
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ICU-FSS total
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SOFA = Sepsis Organ Failure Score
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Median
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n = 52
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Variable
ICU-FSS total = ICU Functional Status Score total
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Table 2: Characteristics of the participants for the 52 recorded rehabilitation sessions.
was 5 minutes and 35 seconds to transfer from bed to chair. The maximum
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duration was 39 minutes and 21 seconds to SOEB and to stand one or more
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times (Table 3). Session duration was the total time from when the partici-
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pant started to move, to when VO2 had recovered to within 10% of baseline.
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Rehabilitation activity duration was the total time from when the partic-
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ipant started to move to returning to supine. Recovery proportion is the proportion of the whole rehabilitation session that was taken with recovery to within 10% of baseline VO2 . For ten rehabilitation sessions participant recovery time was greater than the actual rehabilitation activity duration.
Box plots of the rehabilitation categories (sitting or standing) and the
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˙ 2 (mL.kg.-1 min-1 ) of the session, the total VO2 of the session (mL.kg-1 ), mean VO
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and the percentage change in VO2 of the session are shown in Figure 3. The
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mean (SD) percentage increase in VO2 from rest to SOEB ± balance activi10
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SOEB
Session Duration
Rehabilitation Duration Recovery Proportion
Min Median Max Min Median 15 06:11 15:00 36:36 04:34 08:46
Max
Min Median
Max
23:28
0.20
0.51
0.69
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Activity
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Rehabilitation
17:38
0.18
0.34
0.59
STS x1
7 10:55 18:32 26:19 05:06 10:17
16:11
0.29
0.37
0.72
STS > 1
10 07:44 22:04 39:21 05:53 15:13
25:10
0.22
0.31
0.47
MOS or BCT
9 05:35 12:07 28:04 02:52 07:43
28:04
0.00
0.35
0.49
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SOEB & balance 11 13:19 21:04 31:45 06:51 13:38
SOEB = sit over the edge of bed, STS = sit to stand, MOS = march on spot, BCT = bed chair transfer.
Table 3: Session duration = time from initiation of movement to VO2 recovering to within
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10% of baseline, Rehabilitation duration = time from initiation of movement to returning to supine and Recovery proportion = the proportion of the whole rehabilitation session
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taken with recovery.
ties was 23.3 (11.2). The mean percentage increase in VO2 from rest to stand-
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ing and/or transferring from bed to chair was 34.8 (13.3). The interaction
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i.e the way ICU-FSS influenced rehabilitation category was non-significant
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(p = 0.31) and not included in the final model (Supplementary Table 1). When residuals were plotted (Supplementary Figure 1), one participant was identified as a significant outlier. ˙ 2 (and VO2 ) The final selected model of the percentage change in VO
included ICU-FSS, the pressure support increment and the rehabilitation ac-
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tivity. Therefore, a participant with an ICU-FSS of 0 who could SOEB with
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a pressure support increment of 0 would expect an 12% (95% CI: 4-20) in-
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˙ 2 . For every point increase in ICU-FSS, a 1% (95% CI: 1-2) crease in their VO 11
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˙ 2 could be expected. For each cm H2 O increase in pressure increase in VO
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˙ 2 could be expected. support, a 1.5% (95% CI: 0-3) increase in VO
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The calculated pseudo R2 for this model was 0.63. This suggests that
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activity, functional status and pressure support increment explain up to 63%
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˙ 2 during a rehabilitation session in the ICU. of the change seen in VO
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5. Discussion
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This study aimed to describe rehabilitation activities in mechanically ven-
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˙ 2 ) and rehabilitation activity tilated patients in terms of the intensity (VO
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duration. We present novel data regarding the oxygen cost and duration of
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rehabilitation interventions in mechanically ventilated participants in ICU
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and demonstrate the following: (i) the oxygen cost of rehabilitation varies
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between participants; (ii) the oxygen cost of the rehabilitation activity was
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associated with the level the participant actively contributed the activity;
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(iii) the recovery time was greater than the duration of the rehabilitation
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activity in one in four rehabilitation sessions.
It is important to acknowledge that the population studied were both
persistently mechanically ventilated and critically ill. Therefore it is not possible to extrapolate the findings of this study to all ICU patients receiving rehabilitation. The large standard deviation of the sample data reflects in
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part the relatively small sample size but also the heterogeneity of the partici-
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pants recruited and the multiplicity of factors influencing energy expenditure
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˙ 2 meaduring a rehabilitation session. Technical issues often prevented VO 12
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surement during rehabilitation sessions in our mechanically ventilated partic-
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ipants indicating that the technique is feasible although challenging. Where
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measurements could be performed, we noted the main factor that influenced
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˙ 2 was the participants’ physical function status, the percentage change in VO
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rather than the actual rehabilitation activity. The regression model showed
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that an increase in ICU-FSS was associated with an increase in the percent-
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˙ 2 . The relationship between ICU-FSS and change in VO ˙ 2 may relate age VO
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to reduced O2 consumption in individuals who are less able to contribute
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actively to the rehabilitation activity. Reasons for being less able to partici-
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pate actively may include general fatigue, less muscle to recruit as a result of
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ICU-acquired sarcopenia, and/or decreased oxygen utilisation due to bioen-
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ergetic dysfunction or changes in fibre type composition. While ICU-FSS
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˙ 2 , this does not assist in estimating in isolation may be associated with VO
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an individual patients’ exercise capacity, nor the intensity at which they are
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working. We found that ICU-FSS was highly correlated with the rehabil-
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itation activity, presumably because the improvement in physical function
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perception of breathlessness will enable them to achieve more in a rehabilita-
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tion session. We noted a trend towards an increase in rehabilitation activity
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duration in those participants in whom pressure support was increased (Sup-
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(measured by ICU-FSS) meant the participant was more likely to engage in a higher level of activity (Supplementary Figure 3). ˙ 2 . This Incrementing ventilatory support could influence the change in VO
is commonly done during a rehabilitation session on the assumption that offloading the participants mechanical respiratory load and/or reducing their
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plementary Figure 2). This may suggest that the perception of breathlessness
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or mechanical respiratory load are potentially important factors that can be
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manipulated in mechanically ventilated participants. However, we cannot
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exclude the possibility that therapists consider this enables them to push
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participants harder. Further study is warranted, but also challenging. A
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participant would need to perform the same rehabilitation activity twice,
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with or without an increase in pressure support. We found many partici-
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pants were fatigued after just one activity and could perform no more.
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There are several limitations to the current study. It was not possible
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to test repeatability as participants were often too fatigued at the end of a
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rehabilitation session to repeat the same activity. The few comparisons that
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were possible between different days were not necessarily valid due to changes
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in the participants physiological status. There were insufficient repeated
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episodes to test the sensitivity of the measurement technique to measure
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change over time. The regression analysis did not detect any alteration in
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˙ 2 over time. This is likely due to insufficient the percentage change in VO numbers of participants repeating the same activity over time. Given the nature of rehabilitation in the ICU, participants were rehabilitated to their maximum functional level on each occasion. Reasons for ceasing exercise were unfortunately not recorded; these may have provided useful insights into the limitations to exercise experienced.
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6. Conclusion Breath-by-breath gas exchange analysis remains a challenging technique
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to perform consistently. However, it can provide valuable information regard-
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ing the participants oxygen consumption during rehabilitation. We found
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˙ 2 , is not activity-dependent. that absolute exercise intensity, as measured by VO
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Therefore the assumption that a rehabilitation activity such as SOEB has the
268
same absolute exercise intensity for each patient is not valid. This highlights
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the need to monitor each individual patients’ workload during rehabilitation
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in real time at the point of care.
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List of changes
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7. Ethical Approval
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8. Funding
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UK National Research Ethics Service (REC reference number 11/LO/1646).
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This work was funded by a National Institute for Health Research (NIHR)
Clinical Academic Training Fellowship. 9. Conflict of Interest None.
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10. Disclaimer This report presents independent research funded by the NIHR. The views
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expressed are those of the author(s) and not necessarily those of the NHS,
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the NIHR, or the Department of Health.
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11. Figure Legends
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Figure 284 1: Oxygen consumption calculation for rehabilitation sessions. a = VO2 attributable to exercise session, b = Total VO2 at rest, a + b = Total
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session VO2
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Figure 287 2: Recruitment of participants to the study
Figure 288 3: Box plots of a. percentage change in session VO2 , b. session VO2
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12. References
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(mL.kg.-1 min-1 ) and c. session VO2 (mL.kg.-1 ). ** p <0.01
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