PLoS ONE plos plosone PLOS ONE 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0230971 PONE-D-19-29730 Research Article Medicine and health sciencesHealth careHealth care facilitiesHospitalsIntensive care units People and placesGeographical locationsSouth AmericaBrazil People and placesPopulation groupingsProfessionsMedical personnelNurses Medicine and health sciencesHealth careHealth care providersNurses Medicine and health sciencesCritical care and emergency medicineRespiratory failureVentilatory support Medicine and health sciencesPulmonologyRespiratory failureVentilatory support Medicine and health sciencesPulmonologyVentilatory support Medicine and health sciencesPharmacologySedation Medicine and health sciencesHealth careHealth care facilitiesHospitals Medicine and health sciencesPublic and occupational healthPhysical activityPhysical fitnessExercise Medicine and health sciencesSports and exercise medicineExercise Biology and life sciencesSports scienceSports and exercise medicineExercise People and placesPopulation groupingsProfessionsMedical personnelMedical doctorsPhysicians Medicine and health sciencesHealth careHealth care providersMedical doctorsPhysicians Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil http://orcid.org/0000-0002-4176-2445 Timenetsky Karina T. Conceptualization Data curation Formal analysis Investigation Methodology Project administration Supervision Writing – original draft Writing – review & editing 1 * Neto Ary Serpa Conceptualization Data curation Formal analysis Methodology Writing – original draft Writing – review & editing 1 2 3 Assunção Murillo S. C. Conceptualization Methodology Resources Writing – original draft Writing – review & editing 1 Taniguchi Leandro Investigation Resources Writing – original draft Writing – review & editing 3 4 Eid Raquel A. C. Conceptualization Methodology Resources Writing – original draft Writing – review & editing 1 Corrêa Thiago D. Conceptualization Data curation Formal analysis Investigation Methodology Supervision Writing – original draft Writing – review & editing 1 5 on behalf of the e-MOTION group Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands Department of Pneumology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil Department of Intensive Care, Hospital Sírio Libanês, São Paulo, São Paulo, Brazil Brazilian Research in Intensive Care Network (BRICNet), São Paulo, Brazil Crivellari Martina Editor Vita Salute University of Milan, ITALY

The authors have declared that no competing interests exist.

¶ Membership of the complete list of investigators in the e-MOTION study is provided in the Acknowledgments.

 * E-mail: karina.timenetsky@einstein.br 2 4 2020 2020 15 4 e0230971 29 10 2019 12 3 2020 2020 Timenetsky et al This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background

Mobilization of critically ill patients is safe and may improve functional outcomes. However, the prevalence of mobilization activities of ICU patients in Brazil is unknown.

 Methods

A one-day point prevalence prospective study with a 24-hour follow-up period was conducted in Brazil. Demographic data, ICU characteristics, prevalence of mobilization activities, level of patients’ mobilization, and main reasons for not mobilizing patients were collected for all adult patients with more than 24hs of ICU stay in the 26 participating ICUs. Mobilization activity was defined as any exercise performed during ICU stay.

 Results

In total, 358 patients were included in this study. Mobilization activities were performed in 87.4% of patients. Patients received mobilization activities while under invasive mechanical ventilation (44.1%), noninvasive ventilation (11.7%), or without any ventilatory support (44.2%). Passive exercises were more frequently performed [46.5% in all patients; 82.3% in mechanically ventilated patients]. Mobilization activities included in-bed exercise regimen (72.2%). Out-of-bed mobility was reported in 39.9% of mobilized patients, and in 16.3% of patients under invasive mechanical ventilation. The presence of an institutional early mobility protocol was associated with early mobilization (OR, 3.19; 95% CI, 1.23 to 8.22; p = 0.016), and with out-of-bed exercise (OR, 5.80; 95% CI, 1.33 to 25.30; p = 0.02).

 Conclusion

Mobilization activities in critically ill patients in Brazil was highly prevalent, although there was almost no active mobilization in the mechanically ventilated patients. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

 The author(s) received no specific funding for this work. Data Availability All relevant data are within the manuscript and its Supporting Information files. Introduction

Muscle weakness with impaired physical function is a common complication of critical illness [1–4]. Muscle weakness can be defined as a “clinically detected weakness in patients in which there is no plausible etiology other than the critical illness itself” [5]. The reported incidence of muscle weakness in critically ill patients is between 30 to 50%, reaching up to 64% in septic patients [6]. The presence of muscle weakness has been associated with difficulties of weaning from mechanical ventilation, increased length of intensive care unit (ICU) and hospital stay, increased hospital costs, and long-term morbidity and mortality [7,8]. Early mobilization of critically ill patients may decrease the incidence of muscle weakness, and therefore improve outcomes [5–9].

Mobilization of critically ill patients is safe and feasible [10,11]. It improves, if applied early, independent physical status at hospital discharge [12,13], decreases the duration of mechanical ventilation [12], the number of days in delirium [12,13] and hospital length of stay [13], enhances recovery of functional exercise capacity [14], self-perceived functional status and muscle force at hospital discharge [14]. Nevertheless, recent studies have reported a low prevalence of mobilization activities in critically ill patients [15–18]. Moreover, mobilization is often limited to in-bed exercise [15–18]. For instance, Jolley and colleagues reported a 65% prevalence of mobilization activities in 42 ICUs in the United States of America [17]. In their study, non-mechanically ventilated patients were more likely to receive mobilization than mechanically ventilated patients, and approximately one third of mobilized patients received only passive activities [17]. A study performed in 11 Southern Brazilian ICUs reported a prevalence of 85% of mobilization activities in mechanically ventilated patients [18]. Nevertheless, this study evaluated only mechanically ventilated patients, and it reflects a regional pattern rather than a nationwide practice [18]. Therefore, we aimed to evaluate the prevalence of mobilization activities of critically ill patients in Brazilian ICUs through a nationwide one-day point prevalence study.

 Methods Design and setting

This was a 1-day prospective multicenter point prevalence study with a 24-hour follow-up period of mobilization activities of critically ill patients in Brazilian ICUs. The study was performed on June 29th, 2017. It was approved by the Hospital Israelita Albert Einstein’s Ethics Committee (CAAE: 43545015.3.1001.0071), and each site obtained ethics approval for the study. Informed consent was obtained for all patients as requested by the ethics committee. The process used to obtain consent involved approaching the family member or patient when they met the study inclusion criteria, then explain the objective of the study and the possible uses of the information obtained from it. The person responsible for the study in each center was responsible for obtaining consent.

 Participants selection

Methods for recruitment of participating institutions included emailing members of the Brazilian Association of Intensive Care (Associação Brasileira de Medicina Intensiva, AMIB), announcements at national meetings and symposium, and emailing contacts and collaborators of each writing committee member. Adult patients (≥ 18 years old) were eligible for inclusion if they were expected to stay at ICU for at least 24 hours. Exclusion criteria were patients with terminal disease or pregnancy.

Convenience sampling was used to include patients in the study.

 Data collection and study variables

Study data were collected and managed using Research Electronic Data Capture (REDCap) hosted at Hospital Israelita Albert Einstein [19]. The main investigators of each participating ICU completed an online survey about the hospital and the ICU characteristics, including type of hospital (public, private, and university), type of ICU (medical, surgical, mixed), number of ICUs beds, number of physiotherapists during a 6 hour shift, physiotherapist to patient ratio and nurse to patient ratio during a 6 hour shift, professional responsible for initiating patients’ mobilization (physician, nurse, physiotherapist) and presence of institutional early mobility, sedation and delirium protocols. The full survey is presented in S1 Text.

Collected variables included demographics, comorbidities, ICU admission diagnosis, Sequential Organ Failure Assessment (SOFA) score [20], supportive therapy (need for vasopressors, invasive mechanical ventilation and noninvasive mechanical ventilation) during index ICU stay, type of ventilatory support, use of sedation (if receiving any type of sedation) and mobilization activities. The following patient variables were related to the study day: SOFA, supportive therapy, type of ventilatory support, sedation practices and mobilization activities.

 Mobilization activities

Mobilization activity was defined as any mobilization performed. Data on patients’ mobility were collected during a 24-hour period in a single day (June 29th, 2017). Prevalence of mobilization activities, the highest level of mobilization performed during the study day (in-bed or out-of-bed exercises), type of exercise performed (passive, assisted, active-assisted, active, and resisted exercises) and reasons for non performance of mobilization were collected. Contra indications for mobilization were considered as respiratory, cardiovascular, neurological or other considerations as described in the study published by Hodgson and colleagues [21]. Contra indication was considered present after the health care and research team reached consensus on this topic.

 Statistical analysis

Categorical variables are presented as absolute and relative frequencies. Continuous variables are presented as median with interquartile ranges (IQR).

Logistic regression models were used to evaluate factors associated with mobilization activity and with out-of-bed exercises. Predictors (independent variables) included into the logistic regression models were SOFA score [20], the use of invasive and noninvasive mechanical ventilation, the use of vasoactive drugs, type of hospital, type of ICU, number of physiotherapists per 6-hour shift, number of patients per physiotherapist, and the presence of institutional early mobility protocol. Multi-collinearity was checked for all variables. Results were presented as odds ratio (OR) along with 95% confidence interval (95%CI). Statistical tests were two-sided. A p<0.05 was considered statistically significant. All analyses were done in R (version 3.6.0).

 Results Characteristics of participating centers

A total of 26 ICUs participated in this study (Fig 1). The participating ICUs were located in Brazilian state capitals, mainly in the southeast (50% [13/26]), followed by the northeast (23% [6/26]), south (15.3% [4/26]), midwest (7.7% [2/26]), and north (3.8% [1/26]) of the country. Approximately half of them were ICUs located in public hospitals [53.8% (14/26)], followed by ICUs located in private [34.6% (9/26)] and university [11.5% (3/26)] hospitals. The majority of the participating ICUs (92.3%) were medical-surgical with a median (IQR) ICUs beds of 18 (10.0–31.5).

10.1371/journal.pone.0230971.g001 Study flowchart.

Most hospitals reported physiotherapy-initiated mobility [84.6% (22/26)]. A mobility protocol was reported in 57.7% (15/26) of ICUs while sedation and delirium protocols were reported in 50% (13/26) and 38.5% (10/26), respectively, of the ICUs.

During a six-hour shift, the median (IQR) number of physiotherapists and patient to physiotherapist ratio were 2.0 (1.0–3.2) and 8.0 (6.7–10.0), respectively. The median (IQR) patient to nurse ratio was 6.0 (4.0–8.5). The median (IQR) patient to nurse assistant ratio was 2 (2.0–3.0).

 Studied population

The final sample included 358 patients (Fig 1). No patients were excluded from the analysis. The median (IQR) age was 65 (53–76) years, 53% of patients were male (Table 1). The prevalence of invasive and noninvasive mechanical ventilation during the study day was 44% and 11.7%, respectively (Table 1). Approximately one third of patients (27.9%) were receiving vasoactive drugs. The median (IQR) ICU length of stay to the study day was 6 (3–13) days for all included patients. A total of 117 (32.6%) patients were included within 72 hours of ICU admission.

10.1371/journal.pone.0230971.t001 Baseline characteristics of study participants.
Characteristics All Patients (n = 358)
Age, years 65 (53–76)
Men, n (%) 190 (53)
SOFA score 4.0 (2–7)
Reason for index ICU admission, n (%)
    Mixed 332 (92.7)
    Surgical 19 (5.3)
    Medical 7 (2)
Reason for ICU admission, n (%)
    Respiratory 120 (33.5)
    Neurological 68 (18.9)
    Cardiologic 61 (17.0)
    Elective surgery 50 (13.9)
    Metabolic 27 (7.5)
    Gastric Intestinal 24 (6.7)
    Trauma 6 (1.6)
    Transplant 2 (0.5)
Hospital category, n (%)
    Public 184 (51.4)
    Private 130 (36.3)
    University 44 (12.3)
Sedation, n (%) 80 (22.3)
Vasoactive drugs, n (%) 100 (27.9)
Ventilatory support, n (%)
    Mechanical ventilation 158 (44.1)
    Noninvasive ventilation 42 (11.7)

Values represent median (IQR) or n (%). SOFA: Sequential Organ Failure Assessment.

 Mobilization activities

The overall prevalence of mobilization activities reported was 87.4% (313/358 patients). The prevalence of mobilization among mechanically and non-mechanically ventilated patients was 85.4% (135/158 patients) and 89% (178/200 patients), respectively (Table 2). The decision to initiate mobilization was most commonly related to the ICU physician evaluation [34.5% (108/313) of patients], followed by the physician and physiotherapist combined evaluation [29.0% (91/313) of patients], by the physiotherapist alone [22% (69/313) of patients], and a shared decision between physician, physiotherapist and nurse [14.37% (45/313) of patients].

10.1371/journal.pone.0230971.t002 Prevalence of mobilization activities and type of exercises performed according to ventilatory support.

Values represent n (%).

Mobilization activities All Patients (n = 358) Mechanically Ventilated (n = 158) Non-mechanically ventilated (n = 200)
Prevalence of mobilization, n (%) 313 (87.4) 135 (85.4) 178 (89)
Type of exercises, n (%)
    Passive 145 (46.3) 112 (82.3) 34 (19.1)
    Assisted 26 (8.3) 9 (6.6) 17 (9.5)
    Active-assisted 60 (19.1) 11 (8.1) 49 (27.5)
    Active 77 (24.6) 2 (1.5) 74 (41.6)
    Resisted 5 (1.6) 2 (1.5) 3 (1.7)
In-bed exercise, n (%)
    Passive 188 (60.1) 113 (83.7) 59 (33.1)
Out-of-bed exercises, n (%) 125 (39.9) 22 (16.3) 119 (66.8)
    Passively moved to chair 8 (6.4) 2 (9.1) 6 (5.0)
    Sitting over the edge of bed 30 (24.0) 10 (45.4) 20 (16.8)
    Standing 7 (5.6) 3 (13.6) 31 (26.0)
    Transfering bed to chair 17 (13.6) 3 (13.6) 5 (4.2)
    Marching on spot 3 (2.4) 0 (0) 11 (9.2)
    Walking with assistance of 2 or more people 13 (10.4) 2 (9.1) 23 (19.3)
    Walking with assistance of 1 person 24 (19.2) 1 (4.5) 5 (4.2)
    Walking independently with a gait aid 5 (4.0) 0 (0) 17 (14.3)
    Walking independently without a gait aid 18 (14.4) 1 (4.5) 1 (0.8)

Passive exercises were more frequently performed [46.3% (145/313) of patients], followed by active [24.6% (77/313) of patients] and active-assisted [19.1% (60/313) of patients]. Passive exercises were more common among mechanically ventilated patients than non-mechanically ventilated patients (Table 2). In bed exercises were more frequently performed than out of bed exercises, especially in patients under mechanical ventilation (Table 2). Patients without any ventilatory support were more frequently mobilized out of bed.

In mechanically ventilated patients a total of 202 barriers to achieving a higher activity level were reported. The most frequently reported barrier was due to hemodynamics in patient [34/202; 16.8%], followed by the absence of early mobilization protocol [29/202; 14%] and excessive sedation [25/202; 12.3%]. In those mechanically ventilated patients receiving passive exercises a total of 190 barriers were reported. The most frequently reported barriers for these patients were the absence of early mobilization protocol [27/190; 14%] and access to specialized equipment [27/190; 14%], followed by hemodynamics in patient [26/190; 13.7%] and excessive sedation [22/190; 11.5%].

Reasons for not performing mobilization were mostly due to contra indications [55.5% (25/45)], followed by barriers related to the absence of an early mobility protocol [26.6% (12/45) patients] and unavailability of physiotherapists [17.7% (8/45) of patients].

 Factors associated with mobilization activities and out-of-bed exercises

Multivariable logistic regression analysis of factors associated with mobilization activity is provided in Table 3. Multi-collinearity was checked for all variables; no collinearity was present (S1 Table in S1 Text). After adjusting for confounders, the only independent predictor of ICU mobilization was the presence of an institutional early mobility protocol (OR, 3.19; 95% CI, 1.23 to 8.22; p = 0.016) (Table 3).

10.1371/journal.pone.0230971.t003 Multivariable logistic regression model of factors associated with mobilization activities.
Variables OR 95% CI p value
SOFA score 0.95 0.84–1.07 0.39
Ventilatory support
    No support 1.00 (Reference) ---
    Invasive mechanical ventilation 1.46 0.45–4.73 0.52
    Noninvasive ventilation 1.37 0.55–3.42 0.49
Use of vasoactive drugs 0.89 0.37–2.14 0.80
Type of hospital
    Public 1.00 (Reference) ---
    Private 1.04 0.27–3.97 0.95
    University 0.38 0.12–1.16 0.09
Number of physiotherapists per 6-hour shift 0.82 0.59–1.12 0.21
Number of patients per physiotherapist 1.09 0.93–1.27 0.29
Institutional early mobility protocol 3.19 1.23–8.22 0.01

OR: Odds Ratio, 95% CI: 95% Confidence Interval, SOFA score: sequential organ failure assessment.

Multivariable logistic regression analysis of factors associated with out-of-bed exercise is provided in Table 4. After adjusting for confounders, independent predictors for out-of-bed exercise were: SOFA score, use of noninvasive ventilation, use of invasive mechanical ventilation, number of patients per physiotherapist, and the presence of an institutional early mobility protocol (Table 4).

10.1371/journal.pone.0230971.t004 Multivariable logistic regression model of factors associated with out-of-bed exercise.
Variables OR 95% CI p value
SOFA score 0.72 0.60–0.86 < 0.001
Ventilatory support
    No support 1.00 (Reference) ---
    Noninvasive ventilation 0.31 0.10–0.97 0.04
    Invasive mechanical ventilation 0.13 0.04–0.41 < 0.001
Use of vasoactive drugs 1.18 0.34–4.03 0.79
Type of hospital
    Public 1.00 (Reference) ---
    Private 1.63 0.54–4.96 0.38
    University 2.81 0.79–9.94 0.10
Number of physiotherapists per 6-hour shift 1.17 0.90–1.52 0.24
Number of patients per physiotherapist 1.30 1.07–1.59 < 0.001
Institutional early mobility protocol 5.80 1.33–25.30 0.02

OR: Odds Ratio, 95% CI: 95% Confidence Interval, SOFA score: sequential organ failure assessment.

Multivariable logistic regression analysis of factors associated with early mobilization and with out-of-bed exercise in patients included within 72 hours of ICU admission is described in S2 Table in S1 Text.

 Safety

Safety events related to mobilization were reported in 8.6% (27/313) of patients, mainly respiratory distress in 59.2% (16/27) of patients and hemodynamic instability in 22.2% (6/27) of patients. Accidental chest tube, central venous catheter, peripheral catheter and chest drain removal were not reported.

 Discussion

The main finding of this 1-day prospective multicenter point prevalence study was that approximately 90% of critically ill patients treated in Brazilian ICUs received mobilization therapy. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

The vast majority of patients receiving mechanical ventilation included in our study received passive mobilization. Our results, in the mechanically ventilated patients, are in agreement with the results reported in a recent study performed in 11 ICUs located in southern Brazil [18]. Nevertheless, the prevalence of mobilization in mechanically ventilated patients found in our study was higher than the prevalence between 32 to 45% reported by other authors [15–18]. We believe that the high prevalence of mobilization in mechanically ventilated patients found in our study may be explained, at least in part, by the fact that, in Brazil, physiotherapists are part of the multidisciplinary ICU team assisting critically ill patients throughout the ICU stay.

In our study, the average SOFA score was very low. This finding is probably due to the fact that most patients did not require invasive mechanical ventilation at the study day, which influences the SOFA score. The SOFA score was measured for the study day in order to correlate with the mobilization practice. Another aspect to consider is that patients were included on any day during ICU stay, with the majority of patients on the sixth day of ICU admission. They may have been included during an improvement in their clinical setting. This finding may also have an impact on the prevalence of mobilization found in the present study. Similar ICU length of stay, with a median (IQR) of 7 (3–7) days, was also described by Fontela and colleagues [18]. In Brazil, as reported by the Brazilian Intensive Medicine Association, the mean ICU length of stay in 2017 was 16 days. Most Brazilian hospitals do not have step down units. As a result, patients may stay in the ICU longer in order to be clinically stable before receiving ward discharge.

Another important aspect, which differs from ICUs in the USA, but is similar to many ICUs throughout the world, is that Brazilian physiotherapists are part of the ICU team and are responsible for both respiratory and mobilization therapy of critically ill patients. As a result, regarding patients that already have a respiratory therapy prescription, such as mechanically ventilated patients, physiotherapists, since they have an independent practice, can decide when to start mobilization, which may explain the high prevalence of mobilization in these patients. In most ICU patients, the usual decision making to initiate mobilization in most Brazilian ICUs is related to the physician evaluation after ICU admission, in which case the decision to start takes place earlier than the physiotherapy evaluation. All the mobilization events reported in our study were led by physiotherapists; similar results were described by Fontela and colleagues [18]. Quality improvement studies suggest that dedicated ICU therapists enhance access to mobilization [22,23]. Similar results were found in a randomized study with an early involvement of physiotherapists and occupational therapists in mechanically ventilated patients [12]. Another finding in our study similar to the Fontela and colleagues’ study [18], is the nurse to patient ratio of 1:6, which is higher than many international ICUs. Although this is in accordance with the Brazilian Federal Nursing Council, nurses assume a more managerial position having a nurse assistant to deliver patient care managed by the nurses. Due to our national nursing practice, physiotherapists are the ones responsible for performing most of the mobilization therapy, while nurses and nurses’ assistants may help with patient mobilization.

The presence of an institutional early mobility protocol was reported only in 57.7% of ICUs included in our study. This result was similar to those observed in the United States (53%) [17], yet lower than what was observed in Germany (71%) [15]. The absence of an early mobility protocol is considered a structural barrier for mobilization [24]. Without a mobility protocol, the ICU team will not be able to identify the safety criteria to start mobilization nor a standardized protocol to be followed by all team members. Previously published studies [11–14] have also shown that the presence of an early mobility protocol, when compared to usual care, improves hospital length of stay, mechanical ventilation duration, and delirium. In addition, patients get out of bed earlier. We found that the presence of an early mobility protocol was positively associated with mobilization and with out-of-bed exercises, in accordance with these previously randomized published studies.

The mobility protocols in the included ICUs usually start with a patient evaluation and clinical criteria to start mobilization, such as hemodynamic and respiratory reserve and without any contraindications. Based on this evaluation patient may be included in one of the 4 phases of mobilization as previously published and recommended [11,12,21].

Passive exercises were the most frequently performed type of exercise in mechanically ventilated patients in our study. The prevalence of passive exercises in mechanically ventilated patients reported in the USA prevalence study was 62%, while our prevalence was 82.3% [17]. This discrepancy may be related to the fact that the involvement of physiotherapist in patient’s mobilization included in the USA study was lower than our study, with only 20% involvement of physiotherapist compared to 84.6% respectively. The barriers to achieving a higher activity level in mechanically ventilated patients reported in our study may also be responsible for a higher prevalence of passive exercises reported in this population. In our study we found that the use of invasive and noninvasive mechanical ventilation was inversely associated with out-of-bed exercises, in accordance with the USA study [17], and it was also reported as a barrier in the Fontela and colleagues’ study [18].

Safety events related to mobilization activities were reported in 8.62% of patients, which differs from data reported on Germany (21%), Australia and New Zealand (5%), and the United States (0.9%) [15–17]. Most of the safety events were related to respiratory distress. Similar findings were reported by Nydahl and colleagues [10]; however, in their study, safety events were reported in 2.6% of mobilizations. Unfortunately, our study has no data on how long these safety events lasted and the interventions required.

Our study has limitations. First, in order to include more ICUs around Brazil and be able to understand the practice of early mobilization in our country, a total of 100 ICUs were invited from a total of 1291 ICUs in Brazil, of which only 26 ICUs participated in the study, representing at least one ICU from each Brazilian state. The ICUs included represent those invited in terms of type and size. Secondly, this was a one-day observational study, in which a specific date was established for data collection. Nevertheless, in order not to influence the health care team in mobilization activities on the study day, the researchers responsible for each site were previously informed of the study day but oriented to hide this information and keep the health care team blinded to the study’s objectives. The researchers were responsible to collect the data. Thirdly, there is a lack of information on the severity and duration of adverse events.

 Conclusion

In this nationwide one-day point prevalence study in 26 Brazilian ICUs we found a high prevalence of mobilization activities in critically ill patients; however, there was almost no active mobilization in the mechanically ventilated patients. Moreover, the presence of an institutional early mobility protocol was associated with a threefold higher chance of ICU mobilization during that day.

The impact on outcomes of early mobilization of critically ill patients admitted to Brazilian ICUs needs to be further addressed.

List of all authors of e-MOTION investigators

Cintia MC Grion (Hospital Universitário Regional do Norte do Paraná), Edmilson L B de Moura (Hospital Santa Luiza), Clara Gaspari (Instituto Estadual do Cérebro Paulo Niemeyer), Anna Carolina Jaccoud (Instituto Estadual do Cérebro Paulo Niemeyer), Karina T. Timenetsky (Hospital Israelita Albert Einstein), Thiago D. Corrêa (Hospital Israelita Albert Einstein), Ary Serpa Neto (Hospital Israelita Albert Einstein), Raquel AC Eid (Hospital Israelita Albert Einstein), Renato C. de Freitas Chaves (Hospital Israelita Albert Einstein), Denise Carnieli Cazati (Hospital Israelita Albert Einstein), Wellington P Yamaguti (Hospital Sírio-Libanês), Morian Akemi Onoue (Hospital Sírio-Libanês), Ana Lígia Vasnconcellos Maida (Hospital Sírio-Libanês), Carolina M Pellegrino (Hospital Geral do Grajaú), Monique Buttignol (Hospital Municipal Vila Santa Catarina), Renata H Moura (Hospital Municipal Vila Santa Catarina), Eliana B Caser, Betania S Sales (Hospital Unimed Vitória), André Gobatto (Hospital da Cidade), Cristina P Amendola (Hospital de Câncer de Barretos–Fundação Pio XII), Jonathas J da Silva (Hospital de Câncer de Barretos–Fundação Pio XII), Vandack Nobre (Hospital das Clínicas da Universidade Federal de Minas Gerais), Lídia Mourão Barreto (Hospital das Clínicas da Universidade Federal de Minas Gerais), Cintia Mora (Hospital Ministro Costa Cavalcanti), Leandro Taniguchi (Hospital das Clínicas da Faculdade de Medicina da USP),Vivian Sales (UTI do Departamento de Moléstias Infecciosas), Evelin Cechinatti (Hospital Estadual Américo Brasiliense), Cezar Luz, Adriana Toma (Hospital Estadual Américo Brasiliense), Jorge Paranhos (Santa Casa de Misericórida–São João Del Rei), Adilson Carvalho (Santa Casa de Misericórida–São João Del Rei), Louise AR Gondim (UDI Hospital Empreendimentos Medico Hospital Do Maranhão), Lanese M de Figueiredo (Hospital Distrital Evandro Ayres de Moura), Márcio Duarte (Hospital Municipal Evandro Freire), Gleiciana Vargas (Hospital Municipal Evandro Freire), Aline Santos (Hospital Municipal Evandro Freire), Michele Godoy (Hospital das Clínicas da Universidade Federal de Pernambuco), Fabianne Dantas (Hospital das Clínicas da Universidade Federal de Pernambuco), Paulo C N Fortes (Hospital Regional do Sudoeste Walter Alberto Pecóits), Raimundo Nonato (Hospital do Coração Anis Rassi), Paula Vassalo (Hospital Universitário Cassiano Antônio Moraes–Universidade Federal do Espírito Santo), Márcia M P Dantas (Instituto Doutor José Frota), Lenise Fernandes (Instituto Doutor José Frota), Giovanna Carvalho (Hospital Universitário Pedro Ernesto–Universidade do Estado do Rio de Janeiro), Sergio Cunha, Mônica Cruz (Hospital Universitário Pedro Ernesto–Universidade do Estado do Rio de Janeiro).

 Supporting information <p>(DOCX)</p> </caption> </supplementary-material> </sec> </body> <back> <ack> <p>We want to express our gratitude to all the participating ICUs of this study. The authors thank Helena Spalic for proofreading this manuscript.</p> </ack> <ref-list> <title>References Herridge M, Cameron JI. Disability after critical illness. N Engl J Medicine 2013; 369(14):1367–69. Herridge MS, Tansey CM, Matteé A, Tomlinson G, Diaz-Granados N, Cooper A et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011; 364(14): 1293–304. doi: 10.1056/NEJMoa1011802 21470008 Wunsch H, Guerra C, Barnato AE, Angus DC, Li G, Linde-Zwirble WT. Three-year outcomes for Medicare beneficiaries who survive intensive care. JAMA 2010; 303(9):849–56. doi: 10.1001/jama.2010.216 20197531 Fan E, Dowdy DW, Colantuoni E, Mendez-Tellez PA, Sevransky JE, Shanholtz C, et al. Physical complications in acute lung injury survivors: a two-year longitudinal prospective study. Crit Care Med 2014; 42(4):849–59. doi: 10.1097/CCM.0000000000000040 24247473 Stevens RD, Marshall SA, Cornblath DR, Needham DM, de Jonghe B, Ali NA, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Crit Care Med. 2009; 37(10 Suppl): S299–308. doi: 10.1097/CCM.0b013e3181b6ef67 20046114 Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med 2014; 190(12): 1437–46. doi: 10.1164/rccm.201411-2011ST 25496103 Latronico N, Herridge M, Hopkins RO, Angus D, Haart N, Hermans G, et al. The ICM research agenda on intensive care unit-acquired weakness. Intensive Care Med 2017; 43(9): 1270–81. doi: 10.1007/s00134-017-4757-5 28289812 Kelmenson DA, Held N, Allen RR, Quan D, Burnham EL, Clark BJ, et al. Outcomes of ICU patients with a discharge diagnosis of Critical illness polyneuromyopathy: A propensity- matched analysis. Crit Care Med 2017; 45(12): 2055–60. doi: 10.1097/CCM.0000000000002763 29019851 Zhang L, Hu W, Cai Z, Wu J, Deng Y, Yu K et al. Early mobilization of critically ill patients in the intensive care unit: A systematic review and meta-analysis. PLoS ONE 2019; 14(10): e0223185. doi: 10.1371/journal.pone.0223185 31581205 Nydahl P, Sricharoenchai T, Chandra S, Kundt FS, Huang M, Fischill M, et al. Safety of Patient Mobilization and Rehabilitation in the Intensive Care Unit. Systematic Review with Meta-Analysis. Ann Am Thorac Soc 2017;14(5):766–77. doi: 10.1513/AnnalsATS.201611-843SR 28231030 McWilliams D, Jones C, Atkins G, Hodson J, Whitehouse T, Veenith T et al. Earlier and enhanced rehabilitation of mechanically ventilated patients in critical care: A feasibility randomized controlled trial. J Crit Care 2018; 44: 407–412. doi: 10.1016/j.jcrc.2018.01.001 29331668 Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373(9678):1874–82. doi: 10.1016/S0140-6736(09)60658-9 19446324 Shaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis I et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomized controlled trial. Lancet 2016; 388(10052): 1377–1388. doi: 10.1016/S0140-6736(16)31637-3 27707496 Burtin C, Clerckx B, Robbeets C, Ferdinande P, Langer D, Troosters T, et al. Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med 2009; 37(9):2499–505. doi: 10.1097/CCM.0b013e3181a38937 19623052 Nydahl P, Ruhl AP, Bartoszek G, Dubb R, Filipovic S, Flohr HJ et al. Early Mobilization of Mechanically Ventilated Patients: A 1-Day Point- Prevalence Study in Germany. Crit Care Med 2013; 42(5): 1178–86. Berney SC, Harrold M, Webb SA, Seppelt I, Patman S, Thomas PJ, et al. Intensive care unit mobility practices in Australia and New Zealand: a point prevalence study. Crit Care Resusc 2013; 15(4):260–65. 24289506 Jolley SE, Moss M, Needham DM, Caldwell E, Morris PE, Miller RR et al. Point prevalence study of mobilization practices for acute respiratory failure patients in the United States. Crit Care Med 2017; 45(2): 205–15. doi: 10.1097/CCM.0000000000002058 27661864 Fontela PC, Lisboa TC, Forgiarini-Júnior LA, Friedman G. Early mobilization practices of mechanically ventilated patients: a 1-day point prevalence study in southern Brazil. Clinics (Sao Paulo) 2018; 73:e241. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. REDCap Consortium, The REDCap consortium: Building an international community of software partners. J Biomed Inform. 2019; 9: 103–08. Vincent JL, Moreno R, Takala J, Willatts D, De Mendonça A, Bruining H et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22(7): 707–10. doi: 10.1007/bf01709751 8844239 Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE et al. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Critical Care 2014; 18: 658. doi: 10.1186/s13054-014-0658-y 25475522 Needham DM, Korupolu R, Zanni JM, Pradhan P, Colantuoni E, Palmer JB et al. Early physical medicine and rehabilitaton for patients with acute respiratory failure: a quality improvement Project. Archives of physical medicine and rehabilitation 2010; 91(4): 536–542. doi: 10.1016/j.apmr.2010.01.002 20382284 Zanni JM, Korupolu R, Fan E, Pradhan P, Janjua K, Palmer JB et al. Rehabilitation therapy and outcomes in caute respiratory failure: na observational pilot Project. Journal of Critical Care 2010; 25(2): 254–262. doi: 10.1016/j.jcrc.2009.10.010 19942399 Dubb R, Nydahl P, Hermes C, Shwabbauer N, Toonstra A, Parker AM et al. Barriers and strategies for early mobilization of patients in intensive care units. Ann Am Thorac Soc 2016; 13(5): 724–730. doi: 10.1513/AnnalsATS.201509-586CME 27144796 10.1371/journal.pone.0230971.r001 Decision Letter 0 Crivellari Martina Academic Editor 2020 Martina Crivellari This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 0

10 Dec 2019

PONE-D-19-29730

EARLY MOBILIZATION IN THE ICU: A 1-DAY POINT- PREVALENCE NATIONWIDE STUDY IN BRAZIL

PLOS ONE

Dear Timenetsky,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In my personal opinion this manuscript contains many concerns and the statistical analysis is not well and rigorously performed. I think that with a rigorous revision the manuscript could be improve. 

Reviewers produced very well performed revisions, I would like you to try to answer to all the questions, specifically with a particular attention to the statistical analysis. 

There are non conflicts between the reviews

We would appreciate receiving your revised manuscript by dec 30th . When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Martina Crivellari

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to review this manuscript that deals with the important issue of mobilisation of ICU patients. I do have some substantial comments that I believe require consideration and potential revision of the manuscript as outlined below:

In the discussion the authors mention that ‘we included patients within the first 24 hours of mechanical ventilation’ however there is nothing in the methods to suggest only patients in the first 24 hours of mechanical ventilation were enrolled. Consequently, I am assuming that patients might have been on any day of their ICU stay when they were included in the study - this should be made clear. Further, it would be beneficial to provide an indication of how many patients were on day 1 day 2, day 3 etc of their ICU stay, otherwise this discussion point (lines 315 – 316) is not valuable as it is not possible to determine if, and how many, day 1 patients were included.

Assuming that my understanding above (that you included patients on any day of their ICU stay) is correct, I do not believe you can use the term ‘early mobilization’ throughout the manuscript as you have not measured ‘early’ mobilization, only ‘any’ mobilization in the ICU.

Lines 164 – 165: why was mobilization performed only by a physiotherapist, rather than by any member of the inter-disciplinary team, recorded as occurring? This is particularly important in the context that you discuss the importance of the inter-disciplinary team in your discussion, and at the very least needs to be included as a study limitation. This also impacts on your discussion (lines 305 – 306)

Your findings indicate that half of the mobilisation, and almost all of the mobilisation in the mechanically ventilated patients, was limited to passive exercises – this is an important finding and needs to be conveyed in the abstract, results and conclusion, as well as discussed more fully. The result is that although there was a high level of mobilisation, there was almost no active mobilisation in the mechanically ventilated patients.

Page 6 – please clarify that individual patients did not need to provide consent

Line 188 – you indicate that 26 of 100 invited ICUs participated, but do you have data on how many ICUs exist in Brazil? If so, this should be included. Also, did the included ICUs represent those invited and the entire Brazilian cohort of ICUs in terms of type and size? This also needs to be incorporated into the relevant section of your discussion (lines 335 – 337).

Page 9 and elsewhere – the patient to nurse ratio is extremely high for many ICUs internationally, and the average SOFA score is very low; linked to this is that only 44% of patients were mechanically ventilated and a further 12% non-invasively ventilated, leaving 44% not requiring ventilation support at all. This combination of data raises questions about whether the included units were all ICUs or whether some were more representative of what might be referred to as a High Dependency Unit and how this context compares internationally; discussion of this should be included.

Line 206 – does 358 represent all patients who were in the participating ICUs on the study day, or were some excluded and if so how many and why? This information needs to be included in figure 1.

Lines 235 – 237: it would be useful to understand the usual decision making in the practice setting, i.e. do physios normally have independent practice or is it a policy requirement that physicians need to make the decision about who and when to mobilise? Linked with this is detail regarding the early mobility protocols that you refer to – what was normally included in these?

Line 251: can you give more information about the contra-indications and who decided that these were contra-indications?

Lines 251 – 252: it’s not clear to me while the absence of a mobility protocol is a barrier – please clarify.

Tables 3 and 4 – analysis:

- I would expect number of patients per physiotherapist and number of physiotherapists per 6-hour shift to potentially be highly correlated; was multi-collinearity checked for? Similarly, can you confirm that multi-collinearity between type of hospital and SOFA score was checked for?

- It is not clear to me why you have entered ‘invasive mechanical ventilation’ and ‘noninvasive ventilation’ as 2 separate factors in the regression, rather than ‘type of ventilation’ being the factor with 3 possible response categories (invasive, non-invasive, no ventilation support – this latter category should be the reference category)

- Type of hospital – given you have OR for 3 different categories it is not clear to me what the reference category was – can you clarify?

Lines 285 – 287: did you look at how long the safety events lasted, and whether any intervention was required to resolve the safety issue?

Lines 324 – 327 – I am a little uncertain how the number of students available might affect mobilisation rates when you only considered mobilisation performed by a physiotherapist – please clarify.

Minor comments:

- Please write ‘colleagues’ out in full rather than ‘cols’

Reviewer #2: This is a very promising manuscript presenting mobilization data of a 1-day prevalence study in Brazil. Before accepting the manuscript, however, several major points should be clarified in my point of view.

Major points:

A. This prevalence study is not investigating early mobility or early mobilization because it investigates all ICU patients regardless of the length of the ICU stay. Therefore, the manuscript should be rephrased accordingly and “early” should be omitted throughout. Furthermore, the term mobilization or mobilization therapy should be used instead of mobility, because the patients are mobilized mainly.

B. That said, it would be interesting to see early mobilization data. Do the authors have the ICU day of the patients so that they can provide data on early mobilization (e.g. within 72 hours of ICU admission)?

C. You define your “mobilization therapy” by the ICU mobility scale. The ICU mobility scale, however, is a mobilization therapy strategy only incorporating active mobilization forms, while you use passive, active-assisted and active forms. Please change your definition accordingly. Since you do not use the IMS in the presentation of the data, you could omit it? Otherwise, describe your changed definition.

D. Furthermore, I have strong objections of your definition of in- and out-of bed exercises. Sitting (passively in a chair) and sitting at the edge (IMS 3) of bed is a typical out of bed exercise while passive mobilization, sitting in the bed and exercises like bedergometry are typical in-bed exercises (ICU Mobility Scale = 1). Please provide references which have used the definitions you used or change your presentation of the data accordingly.

E. How many ICUs are there in Brazil (approximately)?

F. Please provide the study protocol as supplement.

G. Please provide the appropriate checklist from the https://www.equator-network.org/ as supplement.

H. You have not provided your dataset as required by PLOS One.

Because of these major points the result section and discussion section will have to go substantial changes and will have to be assessed then. For the discussion section, I think the comparison with the other 1-day prevalence studies and differences to their results should be discussed in more detail, since the methods were not identical. Consequently, the prevalence numbers cannot be compared without highlighting the differences.

Minor points:

Background:

1. The authors should reconsider references 5-9 for the statement line 109/110. There is a recent metanalysis for example available (https://doi.org/10.1371/journal.pone.0223185) addressing this point

2. The references 10-13 should be reconsidered as well. Please be accurate with mobilization RCTs which improved independent physical status at hospital discharge, which ones improved ventilation days, etc.

3. Please change “and cols.” to “et al.” through the manuscript

Methods

1. Please provide the date of the prevalence study.

2. Please omit reference 18. Redcap does not need 2 references.

3. Please explain what 6-hour shift means. Does that mean that in Brazil you have physical therapy during 24 hours and you have 4 shifts of 6 hours? Is the ratio unvaried over the day?

4. P. 7 line 160/161: “related to the study day”. Please rephrase since ICU admission diagnosis was not.

5. You use SOFA and need of vasopressors as confounders. Since vasopressors are in the SOFA score, please check for collinearity and provide information.

6. Provide a definition of “sedation” (used in table 1) in the methods section

Discussion

1. P. 14 line 295: change “during the ICU stay” to “that day” or “on XX / XX / 20XX)

2. Line 313-314: In that case I believe that your very good physical therapy staffing might have an influence, since passive mobilization is done by them. I would consider bringing up that argument there.

3. Please omit reference 22.

4. Line 324: Please change to “University hospitals in Brazil…” if this statement is really true, that students support mobilization therapy at your ICUs. This is not a general truth.

5. Limitations: The generalizability depends on the total number of ICUs in Brazil. See question above.

6. Please explain the blinding to the team, since the patients had to give their consent (how was that not seen by the team). Or was the consent waived by the IRB (if so, please change the statement in the methods section accordingly).

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Reviewer #1: No

Reviewer #2: Yes: Friedrich Kuhn & Prof. Dr. Stefan J Schaller

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 10.1371/journal.pone.0230971.r002 Author response to Decision Letter 0 Submission Version 1

24 Jan 2020

We would like to express our gratitude for giving us the opportunity to revise our manuscript. We believe the reviewers made insightful suggestions that have greatly helped address critical unresolved issues to improve the manuscript.

All the changes in the paper are highlighted in yellow in the revised version to indicate the revised portions of the manuscript. We made modifications in the manuscript according to the reviewers’ comments keeping it within the word and referenced limits imposed by the Journal. We have also revised the manuscript taking into consideration the request made by the Editorial Office. We expect our manuscript to be suitable now for publication in PLOS ONE.

We have submitted the Response to Reviewers file addressing all the comments made and suggested.

I remain at your disposal for any clarification you might require.

Yours sincerely,

On behalf of all the authors,

Karina T. Timenetsky

Submitted filename: Response to Reviewers.docx

 10.1371/journal.pone.0230971.r003 Decision Letter 1 Crivellari Martina Academic Editor 2020 Martina Crivellari This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 1

25 Feb 2020

PONE-D-19-29730R1

Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil

PLOS ONE

Dear Dr Timenetsky,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

 ACADEMIC EDITOR: There are not conflicts between the reviews. The manuscript has technically improved. We  ask you just few minor revisions to make it suitable for publication. 

We would appreciate receiving your revised manuscript by march 9th. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Martina Crivellari

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for submitting a much improved version of this manuscript. Despite the improvements I do have a small number of remaining queries and suggestions as follows:

Line 122: why were pregnant patients excluded?

Lines 149 – 151: please add in notation of who determined that a contra-indication was present

Line 155: this information belongs in the ‘participant information’ section

Line 190: given you have nursing assistants as well in your environment, the ratio for them should also be reported as the patient to nurse ratio is meaningless in isolation

Line 193: thank you for clarifying that individual patient consent was required; it is highly unusual to have 100% of ICU patients consent to a study (I do not believe I have ever seen it before) so it needs to be made clear in figure 1 that 358 was the total number of patients in study ICUs on the relevant day, and that 358 patients were recruited. In the text I suggest you outline the process used to obtain consent.

Line 199: this is an extremely long ICU LOS, particularly in the context of the very low SOFA – there needs to be further description of the context and usual practices to explain why patients that predominantly do not require invasive mechanical ventilation spend about a week in ICU as this is very different to most international practice and possibly accounts for why your mobilisation rates are high.

Lines 292 – 296: although the role of the physiotherapist might contribute to the mobilisation level you have reported, I suggest that the very low severity of illness and the relatively long ICU length of stay reported in your cohort might contribute as much, if not more, to the opportunity for mobilisation. The influence of these characteristics is discussed much later in the discussion (lines 346 – 352) and needs to be moved earlier to integrate with this discussion.

Lines 297 – 299: I actually disagree with this statement – there are many areas of the world (including UK, some parts of Europe, Australia & New Zealand, possibly others) where the physiotherapists are part of the ICU team responsible for both respiratory and mobilisation therapy; I tend to think you are making your comparison with the USA which is notable for different therapists undertaking different elements of care and not always being part of the ICU team but this does not reflect much of international practice.

Lines 340 – 342 – repetitive of previous page – suggest deleting

Lines 368 – 373: this information repeats what has been provided earlier in the

Limitations: the lack of information about the severity and duration of adverse events should be added as a limitation

Typographical comments:

- Lines 186 – 187 and elsewhere – ‘respectively’ is often better located after the relevant data or at the end of a sentence, for example ‘… delirium protocols were reported in 50% (13/26) and 38.5% (10/26), respectively, of the ICUs’

- Line 334 – should be ‘were’ rather than ‘where’

- Line 360 – delete ‘P’ after ‘Nydahl’

Reviewer #2: Thank you for revising your manuscript; the presentation has improved substantially. Here are my comments:

General comments

- The format of the references must be corrected. PLOS One does not use superscript references.

- I would be very interested to see data on early mobilization (i.e. within 72 hours of ICU admission). You state that 32.6% fall into this category. Please provide information in the appendix similar to table 3 and 4 in the appendix in this cohort

- The main finding of the study – having an early mobility protocol – is part of the first paragraph of the discussion, but not adequately discussed in the discussion section and not mentioned as a conclusion.

- One concern still exists and has to be clarified before that manuscript can be accepted. Both reviewers asked for the numbers of total ICUs so that it can be adequately assessed what the external validity of your findings is. Providing the total number of ICU beds is not satisfactory for that! Accounting the median size of ICUs in your study and use that to calculate the ICU numbers based on the presented number of 45.000 beds, resulting in 2500 ICUs. That would mean that you present data of 1% of ICUs in Brazil. Please provide the accurate number or this estimation in the manuscript to provide the reader with the adequate context and limitation.

- Just to clarify, you answered that there was no patient excluded. So you had a 100% success rate in getting your deferred consent. Is that correct?

Abstract

- Cut the listening of the mobilization levels with %

- Present the main finding – besides frequency of mobilization (especially passive) as you did, present the findings what influences mobilization (early mobility protocol). This is your message! Revise Conclusion accordingly

Introduction

- P. 4, line 86: Please add “, if applied early,” in the sentence, so it reads “it improves, if applied early, independent physical status at hospital discharge…”

Results

- p 8 study population: please shorten the description with main points (e.g. sex and age), referring to table 1 without repetition of all numbers in the text.

- p.12 line 248. Please add a sentence that no collinearity was present.

- p.12/13 line 261-266: It is not necessary to repeat all factors if they are presented in the table. Feel free to state the significant one but do not repeat all please.

Discussion

- p. 14, line 286 please change “The vast majority of patients receiving mechanical ventilation included in our study received mobilization, but mostly no active mobilization was performed

288 in these patients.“ To “The vast majority of patients receiving mechanical ventilation included in our study received passive mobilization.”

- p.13, line 299-302: Sentence has to be revised for better understanding and English grammar

- p. 16 line 340-342: Repetition of p.13

Table 2

- Line 236: “According to” – the O is missing.

**********

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 10.1371/journal.pone.0230971.r004 Author response to Decision Letter 1 Submission Version 2

9 Mar 2020

We have made the necessary changes to the manuscript as suggested by the reviewers and editorial office.

Academic Editor of PLOS ONE

We would like to express our gratitude for giving us the opportunity to revise our manuscript. We believe the reviewers made insightful suggestions that have greatly helped address critical unresolved issues to improve the manuscript.

All the changes in the paper are highlighted in yellow in the revised version to indicate the revised portions of the manuscript. We made modifications in the manuscript according to the reviewers’ comments keeping it within the word and referenced limits imposed by the Journal. We have also revised the manuscript taking into consideration the request made by the Editorial Office. We expect our manuscript to be now suitable for publication in PLOS ONE.

I remain at your disposal for any clarification you might require.

Yours sincerely,

On behalf of all the authors,

Karina T. Timenetsky

Reviewer #1:

Thank you very much for your additional comments and suggestions.

1- Thank you for submitting a much improved version of this manuscript. Despite the improvements I do have a small number of remaining queries and suggestions as follows:

Line 122: why were pregnant patients excluded?

Response: We excluded pregnant patients due to the possible mobilization limitation that these patients may present related to pregnancy itself.

2- Lines 149 – 151: please add in notation of who determined that a contra-indication was present

Response: Thank you for your suggestion. We added a notation of who determined that a contra indication was present as follows:

“Contra indications for mobilization were considered as respiratory, cardiovascular, neurological or other considerations as described in the study published by Hodgson and colleagues (21). Contra indication was considered present after the health care and research team reached consensus on this topic. “ (Lines 157 – 158)

3- Line 155: this information belongs in the ‘participant information’ section

Response: Thank you. We have included this information in the “participant information” as the reviewer recommended.

4- Line 190: given you have nursing assistants as well in your environment, the ratio for them should also be reported as the patient to nurse ratio is meaningless in isolation

Response: Thank the reviewer for the comments. We have added this information in the result section. Lines:_195-196._____

“The median (IQR) patient to nursing assistant ratio was 2 (2.0-3.0).” This ratio is in accordance to the Nursing Federal Council recommendation.

5- Line 193: thank you for clarifying that individual patient consent was required; it is highly unusual to have 100% of ICU patients consent to a study (I do not believe I have ever seen it before) so it needs to be made clear in figure 1 that 358 was the total number of patients in study ICUs on the relevant day, and that 358 patients were recruited. In the text I suggest you outline the process used to obtain consent.

Response: Thank the reviewer for the comments. In fact, 100% for informed consent is very high, but due to the nature of the study design, where there was no intervention made, patients and families usually have no restrictions in signing the informed consent.

The process used to obtain consent involved approaching the family member or patient when they met the study inclusion criteria, then explain the objective of the study, and the possible uses of the information obtained from it. The person responsible for the study in each center was responsible for obtaining consent. This information was included in lines 112-116. We have also made changes in Figure 1 as suggested.

6- Line 199: this is an extremely long ICU LOS, particularly in the context of the very low SOFA – there needs to be further description of the context and usual practices to explain why patients that predominantly do not require invasive mechanical ventilation spend about a week in ICU as this is very different to most international practice and possibly accounts for why your mobilisation rates are high.

Response: Our SOFA score represents the study day SOFA and not the ICU admission SOFA and as the majority of patients were included after 72 hours of ICU admission, patients may have improved during ICU stay. Another important point is that most hospitals do not have step down units, and patients may stay in the ICU longer in order to be clinically stable before receiving ward discharge. Similar ICU LOS, with a median (IQR) of 7 (3-7) days was also described by Fontela and colleagues. In Brazil, as reported by the Brazilian Intensive Medicine Association, the mean ICU LOS in 2017 was 16 days.

7- Lines 292 – 296: although the role of the physiotherapist might contribute to the mobilisation level you have reported, I suggest that the very low severity of illness and the relatively long ICU length of stay reported in your cohort might contribute as much, if not more, to the opportunity for mobilisation. The influence of these characteristics is discussed much later in the discussion (lines 346 – 352) and needs to be moved earlier to integrate with this discussion.

Response: We agree with the reviewer and have made the necessary changes moving the discussion of SOFA and length of stay earlier in the discussion as suggested. Lines: 298-311.

8- Lines 297 – 299: I actually disagree with this statement – there are many areas of the world (including UK, some parts of Europe, Australia & New Zealand, possibly others) where the physiotherapists are part of the ICU team responsible for both respiratory and mobilisation therapy; I tend to think you are making your comparison with the USA which is notable for different therapists undertaking different elements of care and not always being part of the ICU team but this does not reflect much of international practice.

Response: We agree with the reviewer and have made changes to this statement in the discussion. Lines: 312-313.

9- Lines 340 – 342 – repetitive of previous page – suggest deleting

Response: We agree with the reviewer and excluded this information.

10- Lines 368 – 373: this information repeats what has been provided earlier in the

Limitations: the lack of information about the severity and duration of adverse events should be added as a limitation

Response: We have removed this information and included the lack of information about the severity and duration of adverse events in the limitation section.

11- Typographical comments:

a) Lines 186 – 187 and elsewhere – ‘respectively’ is often better located after the relevant data or at the end of a sentence, for example ‘… delirium protocols were reported in 50% (13/26) and 38.5% (10/26), respectively, of the ICUs’

Response: Thank the reviewer, we have made the proper corrections in the manuscript.

b) Line 334 – should be ‘were’ rather than ‘where’

Response: Thank the reviewer, we have made the proper corrections in the manuscript.

c) Line 360 – delete ‘P’ after ‘Nydahl’

Response: Thank the reviewer, we have made the proper corrections in the manuscript.

Reviewer #2:

Thank you very much for your additional comments and suggestions.

1- The format of the references must be corrected. PLOS One does not use superscript references.

Response: We have made the proper correction related to the format of the references in the manuscript. We have changed to square brackets as recommended.

2- I would be very interested to see data on early mobilization (i.e. within 72 hours of ICU admission). You state that 32.6% fall into this category. Please provide information in the appendix similar to table 3 and 4 in the appendix in this cohort

Response: Thank the reviewer for the suggestion. We have provided information in the appendix similar to table 3 and 4 in patients within 72 hours as suggested by the reviewer. This information is described in S2 Table and S3 Table.

3- The main finding of the study – having an early mobility protocol – is part of the first paragraph of the discussion, but not adequately discussed in the discussion section and not mentioned as a conclusion.

Response: Thank the reviewer for addressing this important point. We have discussed this point in the discussion section and included in the conclusion as suggested as well.

4- One concern still exists and has to be clarified before that manuscript can be accepted. Both reviewers asked for the numbers of total ICUs so that it can be adequately assessed what the external validity of your findings is. Providing the total number of ICU beds is not satisfactory for that! Accounting the median size of ICUs in your study and use that to calculate the ICU numbers based on the presented number of 45.000 beds, resulting in 2500 ICUs. That would mean that you present data of 1% of ICUs in Brazil. Please provide the accurate number or this estimation in the manuscript to provide the reader with the adequate context and limitation.

Response: We included the total number of ICUs in the discussion section as suggested by the reviewers (total number of 1291 ICUs). Lines: 375

5- Just to clarify, you answered that there was no patient excluded. So you had a 100% success rate in getting your deferred consent. Is that correct?

Response: In fact, 100% for informed consent is very high, but due to the nature of the study design, where there was no intervention made, patients and families usually have no restrictions in signing the informed consent.

6- Abstract

- Cut the listening of the mobilization levels with %

Response: We have made the necessary changes as suggested by the reviewers.

7-

- Present the main finding – besides frequency of mobilization (especially passive) as you did, present the findings what influences mobilization (early mobility protocol). This is your message! Revise Conclusion accordingly

Response: Thank the reviewers for the suggestion. We have made the necessary change as suggested.

8- Introduction

- P. 4, line 86: Please add “, if applied early,” in the sentence, so it reads “it improves, if applied early, independent physical status at hospital discharge…”

Response: We added “if applied early” in the sentence as suggested by the reviewers. (Line: 85-86)

9- Results

- p 8 study population: please shorten the description with main points (e.g. sex and age), referring to table 1 without repetition of all numbers in the text.

Response: We have made the necessary changed as suggested by the reviewers. (lines 199-206)

- p.12 line 248. Please add a sentence that no collinearity was present.

Response: We have added a sentence as suggested by the reviewers.(Line 251)

- p.12/13 line 261-266: It is not necessary to repeat all factors if they are presented in the table. Feel free to state the significant one but do not repeat all please.

Response: We have made the necessary changed as suggested by the reviewers. (261-266)

10- Discussion

- p. 14, line 286 please change “The vast majority of patients receiving mechanical ventilation included in our study received mobilization, but mostly no active mobilization was performed

288 in these patients.“ To “The vast majority of patients receiving mechanical ventilation included in our study received passive mobilization.”

Response: We have made the necessary changed as suggested by the reviewers. (line: 288-289)

- p.13, line 299-302: Sentence has to be revised for better understanding and English grammar

Response: We have revised the sentence as suggested by the reviewers.(Line: 315-319)

- p. 16 line 340-342: Repetition of p.13

Response: We have excluded this sentence in p.16 as suggested by the reviewers.

11- Table 2

- Line 236: “According to” – the O is missing.

Response: Thank the reviewers for addressing this point. We have made the necessary correction as raised by the reviewers.

Submitted filename: Response to Reviewers 2.docx

 10.1371/journal.pone.0230971.r005 Decision Letter 2 Crivellari Martina Academic Editor 2020 Martina Crivellari This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version 2

13 Mar 2020

Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil

PONE-D-19-29730R2

Dear Dr. Timenetsky,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Martina Crivellari

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

 10.1371/journal.pone.0230971.r006 Acceptance letter Crivellari Martina Academic Editor 2020 Martina Crivellari This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

20 Mar 2020

PONE-D-19-29730R2

Mobilization practices in the ICU: A nationwide 1-day point- prevalence study in Brazil

Dear Dr. Timenetsky:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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