Early Mobilization in Critically Ill Children: A Systematic Review

ARTICLE IN PRESS THE JOURNAL OF PEDIATRICS • www.jpeds.com

ORIGINAL ARTICLES

Early Mobilization in Critically Ill Children: A Systematic Review Carlos A. Cuello-Garcia, MD, PhD1, Safiah Hwai Chuen Mai, PhD1, Racquel Simpson, MA1, Samah Al-Harbi, MD2, and Karen Choong, MD, BCh, MSc1 Objective To characterize how early mobilization is defined in the published literature and describe the evidence on safety and efficacy on early mobilization in critically ill children. Study design Systematic search of randomized and nonrandomized studies assessing early mobilizationbased physical therapy in critically ill children under 18 years of age in MEDLINE, Embase, CINAHL, CENTRAL, the National Institutes of Health, Evidence in Pediatric Intensive Care Collaborative, Physiotherapy Evidence Database, and the Mobilization-Network. We extracted data to identify the types of mobility-based interventions and definitions for early, as well as barriers, feasibility, adverse events, and efficacy outcomes (mortality, morbidities, and length of stay). Results Of 1199 titles found, we included 11 studies (2 pilot trials and 9 observational studies) and 1 clinical practice guideline in the analyses. Neurodevelopmentally appropriate increasing mobility levels have been described for critically ill children, and “early” mobilization was defined as either a range (within 48-72 hours) from admission to the pediatric intensive care unit or when clinical safety criteria are met. Current evidence suggests that early mobilization is safe and feasible and institutional practice guidelines significantly increase the frequency of rehabilitation consults, improve the proportion of patients who receive early mobilization, and reduce the time to mobilization. However, there were inconsistencies in populations and interventions across studies, and imprecision and risk of bias in included studies that precluded us from pooling data to evaluate the efficacy outcomes of early mobilization. Conclusions The definition of early mobilization varies, but seems to be feasible and safe in critically ill children. The efficacy for early mobilization in this population is yet undetermined because of the low certainty of the evidence available. (J Pediatr 2018;■■:■■-■■). See editorial, p •••

hildren are at risk of physical, neurocognitive, and psychosocial sequelae as a result of critical illness.1-3 These complications significantly impact the functional recovery and quality of life of critically ill children and their families after hospital discharge.4,5 As a result, there is great interest in acute rehabilitation interventions initiated in the intensive care unit (ICU) setting for both children and adults. There is a growing body of evidence demonstrating safety, efficacy, and cost effectiveness of early mobilization in critically ill adults.6-12 Multimodal, interdisciplinary approaches to mobility-based physical therapy are associated with decreased muscle weakness, sedation requirements, delirium, length of mechanical ventilation, and length of hospital stay in adults.8-12 However, the evidence in children is unclear, particularly with respect to what constitutes mobilization, the timing, appropriateness, and approaches to mobilizing children in the pediatric ICU (PICU). The objective of this review was to systematically evaluate the literature on early mobilization in critically ill children. Our specific aims are to characterize the spectrum of definitions of (1) mobility-based therapies or interventions, (2) “early” mobilization, and (3) safety criteria for mobilization. Also, we aim to assess adverse events and efficacy outcomes (ie, mortality, morbidities, days in PICU) related to mobilization in critically ill children.

C

Methods We followed the PRISMA guidelines and the Cochrane Handbook for conducting systematic reviews and meta-analysis13,14 and the protocol was registered on PROSPERO.15

ICU PICU RCT

Intensive care unit Pediatric ICU Randomized controlled trial

From the 1Department of Pediatrics and Critical Care, Master University, Hamilton, Ontario, Canada; and 2 Pediatric Department of Medical College at King Abdulaziz University, Jeddah, Saudi Arabia C. C.-G. is an Editorial Board member for The Journal of Pediatrics. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. © 2018 Elsevier Inc. All rights reserved. https://doi.org10.1016/j.jpeds.2018.07.037

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THE JOURNAL OF PEDIATRICS • www.jpeds.com Search Strategy The electronic databases MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for eligible studies from inception to April 2017 and updated in March 2018, using a detailed strategy (Appendix 1; available at www.jpeds.com) We manually searched the reference list of included studies, and the following databases for published or ongoing registered trials or studies: US National Institutes of Health (https:// clinicaltrials.gov/), Randomized Trials in Paediatric Intensive Care (http://picutrials.net), Physiotherapy Evidence Database (http://www.pedro.org.au/), and the Mobilization Network (http://mobilization-network.org/). Eligibility Criteria for Review Studies were included if they were (1) completed or registered protocols of randomized, controlled trials or nonrandomized studies, (2) specifically conducted in critically ill children under 18 years of age admitted to a PICU, (3) evaluated a mobilization intervention, and (4) were published in full text or as abstracts describing ongoing registered clinical trials in any language. We included clinical practice guidelines on mobilization published specifically in critically ill children to evaluate descriptions of timing and interventions. Children aged 31 days to 18 years admitted to a PICU (constituting >50% of the study population) were included, and studies conducted in adults or neonates were excluded from our analyses. Studies including exercise or mobility-based physiotherapy delivered in the PICU were considered for inclusion. We excluded studies if they focused primarily on nonmobility or chest physiotherapy interventions or initiated the intervention after PICU discharge. Our primary outcome was to present and characterize the spectrum of how “early mobilization” is defined in published literature, types of mobility therapy, patient selection, and safety criteria for initiating or suspending mobilization. Secondary endpoints were the feasibility, safety, and efficacy outcomes related to early mobilization, such as mortality, length of stay, and PICU-acquired morbidities (ie, weakness, pressure ulcers, delirium). Data Extraction Citations were reviewed and managed using Covidence (https:// www.covidence.org/). Titles and abstracts were screened by 2 independent reviewers. Disagreements were resolved by consensus. Full texts of included and uncertain studies were reviewed in duplicate, with a third reviewer as necessary. Data were extracted by 2 independent researchers. Disagreements were resolved by consensus and by a third reviewer when necessary. Study authors were contacted for additional information or clarification when necessary. Assessment of Methodological Quality We used the Newcastle-Ottawa Scale 16 to assess the methodologic quality of nonrandomized studies. The Newcastle-Ottawa Scale contains 3 major domains: selection of subjects, comparability between groups, and the outcome

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measures. The maximum score for each area is 4, 2, and 3 points, respectively. A total score of 3 or lower indicates low methodologic quality, and a score of 4-5 indicates moderate, and 6 or greater indicates high quality for an observational study. We assessed quality of randomized trials with the Cochrane risk of bias tool.17 Quality assessments were done independently by researchers who were not coauthors on any of the included papers. Data Synthesis and Statistical Analyses Subgroups analyses, sensitivity analyses, or specific assessment of publication bias for the efficacy outcomes were not set a priori because we deemed it improbable to find an important number of published randomized or registered clinical trials in pediatrics. The data was summarized descriptively in tables using counts, proportions, means and SD, or medians and IQR where appropriate. Summary statistics and combined data from eligible studies are presented as means and SD, or risk ratios with 95% CI. For efficacy outcomes, we performed an overall assessment of the certainty of the body of evidence (also called quality of the evidence or confidence in the effect estimates) for each outcome following the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach.18 We used the GRADEpro Guideline Development tool (www.gradepro.org) to produce a summary of findings table and evidence profiles.

Results We retrieved a total of 1199 citations (after removal of 185 duplicates), of which, after title and abstract screening, 92 fulltexts articles were assessed, yielding 12 studies on mobilization in the PICU (Figure; available at www.jpeds.com) consisting of 1 clinical practice recommendation19 and 11 individual studies. These 11 studies evaluated mobilization in a total of 1178 children with a range of medical-surgical and neurocritical care diagnoses, conducted across 3 different countries. Of these studies, there were 2 pilot randomized controlled trials (RCTs),20,21 3 prospective single arm studies,22-24 4 pre-post intervention (before-after) studies,25-28 and 2 retrospective cohort studies.29,30 The characteristics of these studies and main results for definitions are summarized in Table I and Table II. Details of excluded studies are provided in Appendix 2 (available at www.jpeds.com). Risk of Bias Assessment In nonrandomized studies, the Newcastle-Ottawa Scale quality score ranged from 5 to 7, that is, moderate to high quality (Table III). The 2 included RCTs were pilot feasibility trials with a low risk of bias from the randomization process (selection bias), incomplete outcome data (attrition bias), or selective reporting. There is some potential for performance and detection bias in both RCTs owing to the inability to blind participants and investigators to the intervention.

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Author

Year

Design

n

Inclusion criteria

Interventions

2012

Single center retrospective study

91

Children aged 0-17 years who required a >24-h PICU stay

None. Description of acute rehabilitation practices.

Abdulsatar22

2013

Prospective single arm study

12

Children aged 3-18 years with a ≥48-h PICU stay

Choong29

2014

Multicenter Retrospective study

600

Children aged 0-17 years who required a >24-h PICU stay

Interactive video game using Nintendo Wii Boxing for minimum 20 min, twice a day, for 2 d. None. Description of acute rehabilitation practices.

Choong23

2015

Prospective single arm study

31

Hemodynamically stable children with an anticipated >24-h PICU length of stay

Tsuboi25

2016

Pre–post study

Age <16 years, after liver transplantation.

Wieczorek26

2016

Pre-post design (“PICU-Up!” study)

Choong20

2017

Pilot RCT (“wEECYCLE”)

57 (23 in the period before early mobilization, 34 in the period after early mobilization) 200 (100 in each; pre and post intervention) 30

Fink21

2017 (abstract only)

Pilot RCT

58

Alqaqaa28

2018 (abstract only)

Observational, quality improvement project; pre-post design

183; 73 in the preintervention group, 110 in the postintervention group

Arteaga27

2018 (abstract only)

Observational pre-post design

Sargent24

2017 (abstract only)

Observational prospective single arm study

40 11 in the preintervention group, 29 in the postintervention group 6

OT, Occupational therapy; PT, physical therapy; SLP, speech and language therapy.

Passive (using in-bed cycling) and/or active (using interactive video games), according to patient's level of consciousness and cognition, for a minimum of 10 and a maximum of 20 minutes on day 1, and a minimum of 20 minutes on day 2. Early mobilization implementation for postoperative liver transplant recipients in the PICU.

Children 1 day to 17 years old with a PICU stay of >72 h

Implementation of an interdisciplinary early mobilization program.

Children 3-17 years, not being mobilized at the time of screening and expected to stay in the PICU for additional 48 hours

Early mobilization with usual care PT (control arm) or addition of in-bed cycling for 30 min/d, 5 d/ wk (intervention arm). Early, protocolized assessment and therapy consisting of PT, OT, and SLP (intervention arm) versus usual care. Education and training on the benefits of early mobilization and techniques to safely mobilize critically ill children. Family advisors assisted in incorporating patient and family feedback into staff education. ABCDEF bundle quality improvement collaborative: (A), readiness for extubation (B), sedation choice (C), delirium management and prevention (D), early mobilization (E), and family engagement (F) in the PICU. In-bed cycling.

Children 3-17 years old with a new traumatic/nontraumatic brain insult and PICU admission of >48 h Not described

2 months to 18 years of age; expected PICU length of stay of ≥3 days, and requirement for invasive or noninvasive ventilation; patients with severe disability, coma or vegetative state, and brain death were excluded Patients 10-18 years old, hemodynamically stable with calf length of >10 inches, intact skin integrity and no contraindications to exercise

Outcome(s) assessed Rehabilitation practices in PICU. Clinical outcomes in patients who were mobilized vs not mobilized. Feasibility and safety, limb accelerometry, muscle strength, and caregiver/ participant satisfaction. Rehabilitation practices in 6 PICUs, predictors of mobilization. Clinical outcomes in patients who were mobilized vs not mobilized. Feasibility and safety.

Proportion of PT consults and comparisons of PT before and after; safety and clinical outcomes (duration of mechanical ventilation, length of stay, and mortality). Feasibility and safety. Proportion of PT and OT consultations and mobilization activities by PICU day 3. Feasibility, time to mobilization and safety. Clinical outcomes: PICU acquired morbidities, length of stay, mortality, and functional outcomes. PT, OT, and SLP consultation rate and adverse events. Mobilization rate; incidence of safety events, PT, OT, SLP orders, ICU and hospital days, discharge disposition.

A comparison of preimplementation and postimplementation bundles of care (median) in mechanical ventilation days, and PICU and hospital days. Functional status and performance were also measured. Heart rate, blood pressure, respiratory rate, oxygen saturations, and tidal volumes. These were measured before, during and after treatments.

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Choong30

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Early Mobilization in Critically Ill Children: A Systematic Review

Table I. Characteristics of included studies

Author

Year

Definition of early mobilization

Time to mobilization, d*

Contraindication of mobilization

Criteria for terminating early mobilization

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2012

Any mobility activity within 48 hours of PICU admission. All activities focused on enhancing physical function and strength.

1.5 (0.3-2.7)

Not described.

Not described.

Abdulsatar22

2013

Not defined.

9.5 (range, 1-56).

Cardiorespiratory instability, inability to comply/ comprehend instructions, physical inability to mobilize limb.

Accidental tube dislodgement, musculoskeletal injury, pain or discomfort, cardiorespiratory instability.

Choong29

2014

Any mobility activity within 48 hours of PICU admission. All activities focused on enhancing physical function and strength.

2 (1-6)

Not described.

Not described.

Choong23

2015

Not defined.

5 (3-10)

Tsuboi25

2016

Not defined.

9 (range, 7-13)

Cardiorespiratory instability, intracranial hypertension, unstable spine or musculoskeletal injury, surgery/fixed deformities or extremities. Hemodynamic instability, intracranial hypertension, cervical spine instability, day of thoracic or abdominal surgery.

Persistent hypo/hypertension, brady/tachycardia, oxygen desaturation, pain or discomfort, and safety concerns (eg, tube dislodgement). Threat of or actual device dislodgement, vital signs exceeding a threshold, patient's unacceptability.

Wieczorek26

2016

Passive/active activity within 72 hours of PICU admission. Any increasing activity levels from 1 (repositioning) to 3 (sittingup, out-of-bed or ambulation).

Not described. Report number of children with activities in the first 3 days.

ECMO, open chest or abdomen, unstable fractures, or specific medical orders.

Unexpected extubation or line removal, decline in physiologic status or behavior.

15.1% of patients received early mobilization. A significantly greater duration of vasoactive infusions, mechanical ventilation and PICU stay in patients who were not mobilized was observed. Upper limb activity was significantly greater during intervention compared with the rest of the day. Grip strength did not change from baseline. 9.5% received early mobilization. Significantly greater duration of vasoactive infusions, length of PICU stay and delirium in patients who were mobilized. Interventions are safe and feasible. Cycling increases lower limb activity; interactive videogame is feasible only in a minority of patient. Significantly increased PT consults and proportion of patients who received PT after early mobilization compared with before early mobilization implementation. Significant increase in OT and PT consults post PICU-Up! strategy. No significant difference in clinical outcomes.

Adverse events None reported.

None reported.

No difference between mobility and nonmobility groups.

None reported.

None reported.

None reported.

(continued)

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Choong30

Main results

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Table II. Results: Definitions, time to mobilization, and criteria for terminating early mobilization, main results, and adverse events

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Early Mobilization in Critically Ill Children: A Systematic Review

Table II. Continued Author

Year

Choong20

2017

Fink21

2017 (abstract only)

Alqaqaa28

2018 (abstract only)

Arteaga27

Sargent24

Definition of early mobilization As soon as possible in the absence of contraindications. Any graduated, developmentally appropriate active and or strengthening exercises. Any activity within 48 hours of PICU admission. Bed mobility, transfers, activities of daily living, passive range of motion, OT. Not defined.

2018 (abstract only)

2017 (abstract only)

Time to mobilization, d*

Contraindication of mobilization

Criteria for terminating early mobilization

Main results

Adverse events

1.5 (1-3) cycling group. 2.5 (2-7) control group.

Based on published practice guidelines.

Cardiorespiratory instability, increase work of breathing; pain or discomfort not resolved with analgesia, and patient refusal.

Intervention reported as feasible and acceptable.

None reported.

Not reported.

Not reported.

Not reported.

Intervention reported as feasible and acceptable.

None reported.

Not reported.

Not reported.

Not reported.

None reported.

Not defined.

Not reported.

Not reported.

Not reported.

Not defined.

Not reported.

Not reported.

Not reported.

Intervention was feasible and safe. Increase in the percentage of patients mobilized. For non-MV patients, PICU days decreased a mean of 1.1 days, but no difference for MV patients. Fewer days on mechanical ventilation, length of stay in the ICU, and hospital length of stay in the postintervention group. No deaths reported. In-bed cycling was safe and feasible and acceptable.

None reported.

None reported.

ECMO, extracorporeal membrane oxygenation; MV, mechanical ventilated. *Reported as median (IQR) unless otherwise specified.

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Table III. Newcastle-Ottawa scoring of included observational studies (before-after studies, prospective, and retrospective cohorts)

Selection 1. Representativeness of the exposed cohort 2. Selection of the nonexposed cohort 3. Ascertainment of exposure 4. Demonstration that outcome of interest was not present at start of study Comparability 1. Comparability of cohorts on the basis of the design or analysis Outcome 1. Assessment of outcome 2. Was follow-up long enough for outcomes to occur 3. Adequacy of follow-up Total score

Abdulsatar22 2013

Choong23 2015

Tsuboi25 2016

Wieczorek26 2016

Choong29 2014

Choong30 2012

Alqaqaa28 2017

Arteaga27 2017

Sargent24 2018

*

*

*

*

*

*

—

*

*

NA

NA

*

*

*

*

—

*

NA

* *

* *

* *

* *

* —

* —

* *

* *

* *

NA

NA

—

—

*

*

*

*

NA

* *

* *

* *

* *

* *

* *

— *

— *

— *

* 6

* 6

* 7

* 7

* 7

* 7

* 5

— 6

* 5

NA, not applicable. A study can be awarded a maximum of 1 star for each numbered item within the Selection and Outcome categories. A maximum of 2 stars can be given for Comparability.

Mobility Interventions, Timing, and Definitions of “Early” Mobilization was specifically described by 4 of 11 individual studies and the clinical practice guideline, as graduated, developmentally appropriate, active, and/or strengthening exercises (Table I). These same studies categorized chest physiotherapy, passive range of motion, stretching, and repositioning as “nonmobility” interventions. The studies by Choong et al in 2015 and Wieczorek et al respectively defined levels of increasing mobility activities to objectify physical therapy goals and included neurodevelopmental play as a mobility intervention.23,26 Four studies used interactive videogames and/ or in-bed cycling to facilitate mobilization.3,22-24 “Early” mobilization was defined as within 48 hours of PICU admission in 3 studies21,29,30 and 72 hours of PICU admission in another.26 The wEECYCLE pilot RCT evaluated early mobilization practice guidelines as their standard of care, which recommended screening for appropriateness within 24 hours of PICU admission, and defined early as when contraindications are absent and a set of systems-based safety criteria are met.19,20 Appropriateness, Safety Criteria, and Feasibility of Mobilization All of the interventional studies considered cardiorespiratory instability, intracranial hypertension, and spinal instability as contraindications to mobilization (Table II). The PICU Up! study included extracorporeal life support and having an open chest or abdomen as contraindications.26 However, none of these studies explicitly defined thresholds for cardiorespiratory instability. The wEECYCLE Pilot20 and PICU Up!26 studies both specified that vasoactive infusions and/or high mechanical ventilatory support are not contraindications but

precautions to mobilization. All studies considered similar adverse events for interrupting or terminating mobilization based on acute hypotension or hypertension, arrhythmia, hypoxemia, accidental device dislodgement, patient intolerance, and falls. All 11 included studies reported that mobilization was feasible in the PICU and 3 of these studies identified barriers and threats to implementing mobilization in this population.26,29,30 The most common barriers to mobilizing critically ill children were resource limitations, excessive patient sedation, the need for patient cooperation, and apprehension with early mobilization expressed by healthcare personnel and family caregivers. None of the included studies observed a significant increase in adverse events attributable to mobilization (Table II). We estimated from a total of 11 studies reporting on 1178 children, only 13 patients (1.1%) experienced an adverse event attributable to mobilization. Efficacy of Mobilization The 4 pre-post studies and the wEECYCLE Pilot RCT found that the institution of interdisciplinary early mobilization programs significantly increased the frequency of rehabilitation consults, improved the proportion of patients who receive early mobilization, and reduced the time to mobilization.20,25-28 The following efficacy outcomes have been evaluated as secondary endpoints: duration of mechanical ventilation, PICU duration of stay, mortality, and PICU-acquired morbidities. Only 1 study measured functional outcomes.20 The effect of mobilization on these outcomes and the certainty of the evidence as assessed using GRADE are summarized in Table IV. The overall certainty of evidence for these outcomes was low or very low. We decided not to obtain pooled estimates owing to the

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Table IV. Summary of findings: Early mobilization compared with usual care in children admitted to PICUs. No. of participants (studies)

Outcomes

Certainty of the evidence (GRADE) ⊕⊕○○ Low* ⊕○○○ Very low†,‡,§

Mortality (no. of deaths recorded)

88 (2 RCT)

Mortality (no. of deaths recorded)

1220 (9 observational studies)

Length of stay in PICU (days recorded)

30 (1 RCT)

Length of stay in PICU (days recorded)

1171 (7 observational studies)

PICU-acquired Morbidities¶

30 (1 RCT)

⊕⊕○○ Low*

PICU-acquired morbidities¶

636 (2 observational studies)

⊕○○○ Very low†,§

⊕⊕○○ Low* ⊕○○○ Very low†,‡,§

Narrative results No deaths in any patient were reported in 2 pilot RCTs.20,21 Across 9 studies, 4 deaths were reported among 494 children receiving mobilization (0.8%) vs 27 of 720 (3.75%) in control group.22-30 Authors reported an overall length of PICU stay of 8.0 days (IQR, 5.0-13.8) with no distinction among groups.20 Two studies (n = 257 patients) did not detect a significant difference between groups.25,26 Three studies27,28,30 with 314 patients favor the mobility group; while one multicenter study29 with 600 patients observed a difference favoring the group without mobilization. One study did not present results by group of study.22 6 of 30 patients (20%) developed morbidities. No statistical comparisons were made between early mobilization vs control groups in this pilot RCT.20 Morbidities were present in 5 of 178 participants (2.8%) in the mobility group, and in 6 of 458 (1.31%) in the control group.29,30

GRADE Working Group grades of evidence. High certainty (⊕⊕⊕⊕): We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty (⊕⊕⊕○): We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty (⊕⊕○○): Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty (⊕○○○): We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. *Pilot single-center trial with 30 patients and no events in total mortality. These studies aimed to assess the feasibility of future clinical trials. †Most cohort studies were uncontrolled with no assessment or adjustment of confounders. ‡Important differences in study design, clinical setting, patients' characteristics, and interventions. §Small number of patients. We preferred not to perform a pooled estimate (meta-analysis). The small number of patients and events preclude gives a judgment of serious about imprecision. ¶Composite outcome of at least one morbidity –weakness, pressure ulcer, joint contracture, or delirium.

heterogeneity of interventions, study design, clinical settings, and characteristics of study participants.

Discussion The results of this systematic review of early mobilization in critically ill children demonstrate the following key findings: (1) “early” is defined as either a range (within 48-72 hours) from PICU admission, or when contraindications are absent and clinical safety criteria are met, (2) neurodevelopmentally appropriate increasing mobility levels have been defined for critically ill children, (3) mobility-based physical rehabilitation is safe and feasible, and (4) the efficacy for early mobilization in this population is as yet undetermined because of the low certainty in the currently available evidence. Although the evidence on early mobilization in critically ill adults has been accumulating, this field of research in critically ill children is still in its infancy. There are several reasons why this field of research is lagging behind in pediatrics compared with adults and unique challenges to conducting early mobilization research in this population exist. First, buy-in is challenging. Clinicians and families caring for critically ill children remain skeptical or uncomfortable about early mobilization, not only because of the implications it may have on other concurrent interventions, such as sedation, but also owing to the resources and potential workload required to mobilize a patient.31 Second, the PICU population is heterogeneous; these children span across broad developmental and cognitive ages.

More than 60% of children have chronic comorbidities and one-half have baseline functional disabilities.3,32 Defining mobility is, therefore, not straightforward in critically ill children and needs to consider the cognitive, functional, and developmental abilities for each child. Third, it is challenging to evaluate the dose-response and efficacy of mobility interventions, because the appropriate dosing of this intervention in terms of intensity and duration has yet to be established in children with varying and evolving severity of critical illness. Although there are several tools for assessing, describing, and measuring mobility in critically ill adults,14,33,34 these measures are not validated in children. Levels of permissible mobility activities have been empirically developed for children, but are inconsistent.3,26 Therefore, the patient selection, safety, and feasibility results from this systematic review may be used to advance the development of similar tools in children. The safe timing for initiating mobilization in children with high severity illness who are receiving invasive support and the best timing for a mobility intervention to impact on patient outcomes cannot be answered with the current evidence. The included studies in this review that defined early varied between using a timeframe from PICU admission, that is, within 4872 hours, and empiric clinical measures reflective of current clinician comfort with mobilization surrogates. Traditionally, cardiorespiratory instability is a common reason to immobilize patients.35 The results of this review suggest that levels of comfort with mobilization may be evolving with increasing safety and feasibility data in children and indirect evidence from the adult population. Cardiorespiratory instability

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THE JOURNAL OF PEDIATRICS • www.jpeds.com is no longer a contraindication to mobilization, but rather a precaution to mobilization.20,26 Other reviews agree with our results.6,7,36 Although we did not include retrospective evidence from case series, casecontrol studies, or indirect evidence from adult populations, we were successful at including several prospective interventional studies23-28 and 2 pilot RCTs20,21 in pediatric populations that emerged since the last published review.36 Our inclusion criteria aimed at also including observational studies and guidelines that were helpful with the definition of early mobilization and provide information on feasibility issues. What is consistent from this current body of pediatric literature is that early mobilization is safe and feasible. This study not only highlights the need for more research in this area, but it is also an important first step in prompting the development of standardized descriptions for patient selection, timing, and dosage of mobilization in critically ill children and determining appropriate patient-centered outcomes to evaluate its efficacy and how these may be best measured in future trials on early mobilization. The main strength of our review is that it provides information on 2 fronts: first, for describing how early mobilization interventions are defined and used, as well as feasibility and safety issues; and second, for evaluating the efficacy of clinically important outcomes using GRADE. Our work aims at highlighting the aspects of safety and feasibility, especially on the contraindications for considering early mobilization and the criteria for terminating, as described in Table II. Although pediatric data are scarce, the variability in definitions and contraindications to early mobilization also varies among the adult literature (eg, from <48 hours to <72 hours), even when more evidence from this population is available.7,10,11,37,38 However, both bodies of evidence are in agreement in terms of safety and feasibility of early mobilization interventions. As in any review, our limitations include the possibility of bias in the review process. We tried to avoid this by rigorously following the PRISMA guidelines and reporting process, with a published protocol, and transparently performing all screening, data extraction, and risk of bias assessment in duplicate and with a third assessor when discrepancies were found. The evidence from current interventional studies suggest that the use of institutional early mobilization guidelines and the support of interdisciplinary team education and resources increases the proportion of patients who receive acute rehabilitation consults and assessments, as well as the frequency of and the time to mobilization for these children. However, there are patient-, caregiver-, and resource-related barriers to executing mobility therapy in this population. The impact of early mobilization on the efficacy outcomes in critically ill children remains to be seen owing to the paucity of prospective trials and, therefore, the low certainty in the evidence to date. Although this is a challenging field of study in pediatrics, the evidence for early mobilization in critically ill children is growing and it is clear that further research on its efficacy is needed. ■

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Submitted for publication Apr 23, 2018; last revision received Jun 18, 2018; accepted Jul 11, 2018 Reprint requests: Carlos A. Cuello-Garcia, MD, PhD, Department of Pediatrics and Critical Care, Master University, Hamilton, Ontario, Canada. E-mail: [email protected]

References 1. Rennick JE, Dougherty G, Chambers C, Stremler R, Childerhose JE, Stack DM, et al. Children’s psychological and behavioral responses following pediatric intensive care unit hospitalization: the caring intensively study. BMC Pediatr 2014;14:276. 2. Pinto NP, Rhinesmith EW, Kim TY, Ladner PH, Pollack MM. Longterm function after pediatric critical illness: results from the survivor outcomes study. Pediatr Crit Care Med 2017;18:e122-30. 3. Choong K, Canci F, Clark H, Hopkins RO, Kudchadkar SR, Lati J, et al. Practice recommendations for early mobilization in critically ill children. J Pediatr Intensiv Care 2017;7:14-26. 4. Herrup E, Wieczorek B, Kudchadkar SR. Characteristics of postintensive care syndrome in survivors of pediatric critical illness: a systematic review. World J Crit Care Med 2017;6:124-34. 5. Manning JC, Hemingway P, Redsell SA. Long-term psychosocial impact reported by childhood critical illness survivors: a systematic review. Nurs Crit Care 2014;19:145-56. 6. Adler J, Malone D. Early mobilization in the intensive care unit: a systematic review. Cardiopulm Phys Ther J 2012;23:5-13. 7. Cameron S, Ball I, Cepinskas G, Choong K, Doherty TJ, Ellis CG, et al. Early mobilization in the critical care unit: a review of adult and pediatric literature. J Crit Care 2015;30:664-72. 8. Topp R, Ditmyer M, King K, Doherty K, Hornyak J 3rd. The effect of bed rest and potential of prehabilitation on patients in the intensive care unit. AACN Clin Issues 2002;13:263-76. 9. 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;14:766-77. 10. Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med 2017;43:17183. 11. Ramos Dos Santos PM, Aquaroni Ricci N, Aparecida Bordignon Suster E, de Moraes Paisani D, Dias Chiavegato L. Effects of early mobilisation in patients after cardiac surgery: a systematic review. Physiotherapy 2017;103:1-12. 12. Stiller K. Physiotherapy in intensive care: an updated systematic review. Chest 2013;144:825-47. 13. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. 14. 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. Crit Care 2014;18:658. 15. Simpson R, Al-Harbi S Systematic review on early mobilization in pediatric critically ill children. PROSPERO, 2016. CRD420160385452016. 16. Wells GA, Shea B, O’Connel D. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute. http://www.ohri.ca/ programs/clinical_epidemiology/oxford.asp. Accessed November 15, 2017. 17. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011 www.handbook.cochrane.org. Accessed May 2017. 18. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 2011;64:395-400.

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19. Roeseler J, Sottiaux T, Lemiale V, Lesny M, Beduneau G, Bialais E, et al. Prise en charge de la mobilisation précoce en réanimation, chez l’adulte et l’enfant (électrostimulation incluse). Réanimation 2013;22:207-18. 20. Choong K, Awladthani S, Khawaji A, Clark H, Borhan A, Cheng J, et al. Early exercise in critically ill youth and children, a preliminary evaluation: the wEECYCLE pilot trial. Pediatr Crit Care Med 2017;18:e546-54. 21. Fink E, Beers S, Houtrow A, Richichi R, Burns C, Doughty L, et al. 819: pilot RCT of early versus usual care rehabilitation in pediatric neurocritical care. Crit Care Med 2017;46:394. 22. Abdulsatar F, Walker RG, Timmons B, Choong K. “Wii-Hab” in critically ill children: a pilot trial. J Pediatr Rehabil Med 2013;6:193-204. 23. Choong K, Chacon M, Walker R, Al-Harbi S, Clark H, Al-Mahr G, et al. In-bed mobilization in critically ill children: a safety and feasibility trial. J Pediatr Intensiv Care 2015;4:225-34. 24. Sargent S, Sharp K, Hills J, Johnstone B. Paediatric In-bed cycling: a safety and feasibility evaluation in intensive care. Intensive Care Medicine Experimental Conference: 30th Annual Congress of the European Society of Intensive Care Medicine, ESICM (September 23-27, 2017, Vienna, Austria). 2017;5. 25. Tsuboi N, Nozaki H, Ishida Y, Kanazawa I, Inamoto M, Hayashi K, et al. Early mobilization after pediatric liver transplantation. J Pediatr Intensiv Care 2016;6:199-205. 26. Wieczorek B, Ascenzi J, Kim Y, Lenker H, Potter C, Shata NJ, et al. PICU Up!: impact of a quality improvement intervention to promote early mobilization in critically ill children. Pediatr Crit Care Med 2016;17:e55966. 27. Arteaga G, Kawai Y, Rowekamp D, Rohlik G, Matzke N, Fryer K, et al. The pediatric ICU liberation project impact on patient outcomes: the Mayo experience. Crit Care Med 2018;46(Suppl 1):628. 28. Alqaqaa Y, Herbsman J, Folks T, O’Donnell S, Klien D, Seilikoff L, et al. Early mobilization in the pediatric intensive care unit. Crit Care Med 2018;46(Suppl 1):649.

29. Choong K, Foster G, Fraser DD, Hutchison JS, Joffe AR, Jouvet PA, et al. Acute rehabilitation practices in critically ill children: a multicenter study. Pediatr Crit Care Med 2014;15:e270-9. 30. Choong K, Trana N, Clarka H, Cupido C, Corsid DJ. Acute rehabilitation in critically ill children. J Pediatr Intensiv Care 2012;1:183-92. 31. Parisien RB, Gillanders K, Hennessy EK, Herterich L, Saunders K, Lati J, et al. Experiences of four parents with physical therapy and early mobility of their children in a pediatric critical care unit: a case series. J Pediatr Rehabil Med 2016;9:159-68. 32. Cremer R, Leclerc F, Lacroix J, Ploin D, GFRUP/RMEF Chronic Diseases in PICU Study Group. Children with chronic conditions in pediatric intensive care units located in predominantly French-speaking regions: prevalence and implications on rehabilitation care need and utilization. Crit Care Med 2009;37:1456-62. 33. Perme C, Nawa K, Winkelman C, Masud F. A tool to assess mobility status in critically ill patients: the Perme Intensive Care Unit Mobility Score. Methodist Debakey Cardiovasc J 2014;10:41-9. 34. Corner EJ, Soni N, Handy N, Brett SJ. Construct validity of the Chelsea Critical Care Physical Assessment tool: an observational study of recovery from critical illness. Crit Care 2014;18:R55. 35. Zheng K, Sarti A, Boles S, Cameron S, Carlisi R, Clark H, et al. Impression of early mobilization of critically ill children-clinician, patient, and family perspectives. Pediatr Crit Care Med 2018;19:e350-7. 36. Wieczorek B, Burke C, Al-Harbi A, Kudchadkar SR. Early mobilization in the pediatric intensive care unit: a systematic review. J Pediatr Intensiv Care 2015;2015:129-70. 37. Hunter A, Johnson L, Coustasse A. Reduction of intensive care unit length of stay: the case of early mobilization. Health Care Manag (Frederick) 2014;33:128-35. 38. Castro-Avila AC, Seron P, Fan E, Gaete M, Mickan S. Effect of early rehabilitation during Intensive Care Unit stay on functional status: systematic review and meta-analysis. PLoS ONE 2015;10:e0130722.

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THE JOURNAL OF PEDIATRICS • www.jpeds.com Appendix 1 Search Strategies. All searches performed on the different databases from inception to February 2016. An updated search and rerun of the strategy was performed on April 5, 2018. MEDLINE. Ovid MEDLINE(R) In-Process and Other NonIndexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present, Ovid OLDMEDLINE(R) 1946 to 1965 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.

Physical Therapy Modalities/ physiotherap*.ti,ab. (mobiliz* or mobilis*).ti,ab. Rehabilitation/ rehab*.ab,ti. Exercise Movement Techniques/ Exercise Therapy/ Exercis*.ti,ab. Ambulat*.ti,ab. or/1-9 (Early or earlier or accelerat* or acute or immediate*).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] 10 and 11 Early Ambulation/ 12 or 13 Intensive Care Units/ or Critical Care/ or Critical Illness/ Burn Units/ or Coronary Care Units/ or Intensive Care Units, Pediatric/ or Respiratory Care Units/ (ICU or intensive care or critical care).ti,ab. Critical* ill*.ti,ab. or/15-18 14 and 19 child/ or child, preschool/ or pediatrics/ or Adolescent/ 20 and 21

Embase. 1974 to 2016 February 12. Updated April 5, 2018. 1. physiotherapy/ or chest wall oscillation/ or home physiotherapy/ or joint mobilization/ or pediatric physiotherapy/ 2. physiotherap*.ti,ab. 3. (mobiliz* or mobilis*).ti,ab. 4. rehabilitation/ 5. pediatric rehabilitation/ 6. rehab*.ab,ti. 7. kinesiotherapy/ 8. Exercis*.ti,ab. 9. Ambulat*.ti,ab. 10. or/1-9 11. (Early or earlier or accelerat* or immediate*).mp. 12. 10 and 11 13. mobilization/ 14. 12 or 13

Volume ■■ 15. 16. 17. 18. 19. 20. 21. 22.

intensive care unit/ or intensive care/ or critical illness/ coronary care unit/ or burn unit/ (ICU or intensive care or critical care).ti,ab. Critical* ill*.ti,ab. or/15-18 14 and 19 pediatrics/ juvenile/ or child/ or boy/ or brain damaged child/ or girl/ or handicapped child/ or hospitalized child/ or preschool child/ or school child/ or toddler/ 23. adolescent/ or hospitalized adolescent/ 24. or/21-23 25. 20 and 24 CINAHL. Searched on February 17, 2016. Updated April 5, 2018. Search ID# S27 S26 S25 S24

S23 S22 S21 S20 S19 S18 S17 S16

S15 S14 S13 S12 S11 S10 S9 S8 S7 S6 S5 S4 S3 S2 S1

Search Terms S23 AND S26 S24 OR S25 (MH “Pediatrics”) (MH “Child”) OR (MH “Adolescent, Hospitalized”) OR (MH “Adolescence”) OR (MH “Child, Disabled”) OR (MH “Child, Hospitalized”) OR (MH “Child, Medically Fragile”) OR (MH “Child, Preschool”) S15 AND S22 S16 OR S17 OR S18 OR S19 OR S20 OR S21 TX Critical* ill* TX ICU or intensive care or critical care (MH “Burn Units”) (MH “Critical Illness”) OR (MH “Critically Ill Patients”) (MH “Critical Care”) (MH “Intensive Care Units”) OR (MH “Coronary Care Units”) OR (MH “Intensive Care Units, Pediatric”) OR (MH “Respiratory Care Units”) S13 OR S14 (MH “Early Ambulation”) S11 AND S12 TX Early or earlier or accelerat* or acute or immediate* S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 (MH “Ambulation Therapy (Saba CCC)”) OR (MH “Assistive Device Therapy (Saba CCC)”) OR (MH “Mobility Therapy (Saba CCC)”) TX Ambulat* TX Exercis* (MH “Exercise Therapy: Joint Mobility (Iowa NIC)”) OR (MH “Exercise Therapy: Ambulation (Iowa NIC)”) (MH “Therapeutic Exercise”) TX rehab* (MH “Rehabilitation”) OR (MH “Rehabilitation, Pediatric”) mobiliz* or mobilis* TX physiotherap* (MH “Physical Therapy”) OR (MH “Pediatric Physical Therapy”) OR (MH “Physical Therapy Assessment”) OR (MH “Physical Therapy Practice, Research-Based”) OR (MH “Physical Therapy Practice, Evidence-Based”) OR (MH “Research, Physical Therapy”)

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CENTRAL. Search strategy (Searched on February 17, 2016). Updated April 5, 2018. ID #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #12 #13 #14 #15 #16 #17 #18 #19 #20 #21 #22 #23 #24 #25

Search MeSH descriptor: [Physical Therapy Modalities] this term only physiotherap*.ti,ab (mobiliz* or mobilis*) .ti,ab MeSH descriptor: [Rehabilitation] this term only rehab*.ti,ab MeSH descriptor: [Exercise Movement Techniques] this term only MeSH descriptor: [Exercise Therapy] this term only Exercis*.ti,ab Ambulat*.ti,ab #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 (Early or earlier or accelerat* or acute or immediate*) .ti,ab #10 and #11 MeSH descriptor: [Early Ambulation] explode all trees #12 or #13 MeSH descriptor: [Intensive Care Units] explode all trees MeSH descriptor: [Critical Care] this term only MeSH descriptor: [Critical Illness] this term only (ICU or intensive care or Critical Care or Critical* ill*) .ti,ab #15 or #16 or #17 or #18 #14 and #19 MeSH descriptor: [Child] explode all trees MeSH descriptor: [Pediatrics] this term only MeSH descriptor: [Adolescent] this term only #21 or #22 or #23 #20 and #24

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Appendix 2 Excluded Studies. Author

Year

Anderson et al

2012

Early attention impairment and recovery profiles after childhood traumatic brain injury

Title

Journal of Head Trauma Rehabilitation 2012;27(3):199-209

Arceneaux and Meyer

2009

International Review of Psychiatry 2009;21(6):549-58

Batterham et al

2014

Berney et al

2002

Bower and McLellan

1992

Burnsworth et al

1992

Cameron et al

2015

Carlile et al

2010

Castilho and Beccaria

2009

Caulfield

2013

Choong et al; Canadian Critical Care Trials Group Choong et al

2014 2014

Choong et al

2012

Treatments for common psychiatric conditions among children and adolescents during acute rehabilitation and reintegration phases of burn injury Effect of supervised aerobic exercise rehabilitation on physical fitness and quality-of-life in survivors of critical illness: an exploratory minimized controlled trial (PIX Study) Can Early Extubation and Intensive Physiotherapy Decrease Length of Stay of acute quadriplegic patients in intensive care? A retrospective case control study Effect of increased exposure to physiotherapy on skill acquisition of children with cerebral palsy Immediate ambulation of patients with lower-extremity grafts Early mobilization in the critical care unit: A review of adult and pediatric literature Prophylaxis for venous thromboembolism during rehabilitation for traumatic brain injury: a multicenter observational study Acquired risk factors and of deep-vein thrombosis prophylaxis in ICU The key role of physiotherapy on developmental and health outcomes in paediatric ventricular assist devices Acute rehabilitation practices in critically ill children: a multicenter study Acute rehabilitation practices in critically ill children: a multi-center study Acute rehabilitation in critically ill children

Cui et al

2012

Denes

2009

Dinh et al

2013

Garstka et al

1974

Genc et al

2014

Gobiet

1977

Gobiet

1995

Goldberg

2008

Physical and occupational therapy utilization and patient outcomes in a pediatrics intensive care unit [Consequence of secondary complications during the rehabilitation of patients with severe brain injury] Predictors of transfer to rehabilitation for trauma patients admitted to a level 1 trauma centre–a model derivation and internal validation study Postoperative care for scoliotic children after a corrective surgical procedure (Polish) What are the hemodynamic and respiratory effects of passive limb exercise for mechanically ventilated patients receiving low-dose vasopressor/inotropic support? [Progresses in the treatment of skull-brain injuries in childhood] [Effect of multiple trauma on rehabilitation of patients with craniocerebral injuries] [Commentary on] Fontan fenestration closure has no acute effect on exercise capacity but improves ventilatory response to exercise

Reference

Reason(s) for exclusion Interventions of interest not compared/described non-PICU population non-PICU setting Narrative review

British Journal of Anaesthesia 2014;113(1):130-7

Adult population Interventions of interest not compared/described

Physiotherapy Research International 2002;7(1):14-22

Retrospective study

Developmental Medicine and Child Neurology 1992;34(1):25-39

Non-PICU setting Non-PICU population

Journal of Burn Care & Rehabilitation 1992;13(1):89-92 Journal of Critical Care 2015;30(4):664-72 Journal of Trauma 2010;68(4):916923

Retrospective review Narrative review

Revista Nursing 2009;11(129):92-8

Nonmobility intervention Non-PICU population Non-PICU setting Nonmobility intervention

Pediatric Transplantation 2013;17:84

Case series

Pediatric Critical Care Medicine 2014;15(6):e270-9 Pediatric Critical Care Medicine 2014;15(4 Suppl 1):12-13 Journal of Pediatric Intensive Care 2012;1(4):183-92 Critical Care Medicine 2012;40(12 Suppl 1):202

Retrospective study

Orvosi Hetilap 2009;150(4):165-9

Retrospective study

Injury 2013;44(11):1551-5

Retrospective study Nonmobility intervention

Chirurgia Narzadow Ruchu i Ortopedia Polska 1974'39(4):463-5 Critical Care Nursing Quarterly 2014;37(2):152-8

Nonmobility intervention (changing in ventilation setting) Adult population Retrospective study

Der Chirurg 1977;48(7):461-6

Nonmobility intervention (monitoring of intracranial pressure) Interventions of interest not compared/described Letters/commentary Nonmobility intervention (prefenestration and postfenestration closure exercise testing with expiratory gas analysis) (continued)

Zentralblatt fur Chirurgie 1995;120(7):544-50 ACC Cardiosource Review Journal 2008;17(12):18

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Retrospective study Retrospective study Retrospective study

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ORIGINAL ARTICLES

Author

Year

Goldstein

2011

Hayes et al

2014

Hu et al

2010

Irdesel et al

2007

Jaffe

2008

Jedrzejewska et al

2009

Jones et al

2003

Kasotakis et al

2012

Kuwabara et al

2011

Langhorn et al

2015

Lanthemann et al

2009

Lazar et al

1989

Lippert-Gruner

2010

Lippert-Gruner et al

2006

Lippert-Grüner et al

2003

Maczka et al

2011

Mancin et al

2012

Melchers et al

1999

Meuli and Lochbuhler

1992

Moront and Eichelberger

1994

Moront et al

1994

Munkwitz et al

2010

Pacetti et al

1996

Patman et al

2012

Title

Reference

Acute kidney injury in children: prevention, treatment and rehabilitation. Pediatric ambulatory ECMO

Contributions to Nephrology 2011;174:163-72 Lung 2014;192(6):1005

Early and intensive rehabilitation predicts good functional outcomes in patients admitted to the stroke intensive care unit Rehabilitation outcome after traumatic brain injury Pediatric trauma rehabilitation: a valueadded safety net Rehabilitation of children after craniocerebral injuries with particular attention paid to the reflex stimulation Powiertowski's method: Preliminary study Rehabilitation after critical illness: a randomized, controlled trial The surgical intensive care unit optimal mobility score predicts mortality and length of stay Reconsidering the value of rehabilitation for patients with cerebrovascular disease in Japanese acute health care hospitals Testing a reality orientation program in patients with traumatic brain injury in a neurointensive care unit Swiss Romande burn center: a model of multidisciplinary team work and network organization Prediction of functional outcome by motor capability after spinal cord injury Early rehabilitation of comatose patients after traumatic brain injury Early neurorehabilitation after severe brain trauma Outcome of prolonged coma following severe traumatic brain injury Pulmonary rehabilitation within intensive care units exemplified by traffic collisions casualties Vocal output communication aids for temporarily impaired owners (VOCA.TIO): digital aids for a very early rehabilitation targeting cognition, behavior, communication and motor function in a pediatric intensive care unit: a feasibility study An early onset rehabilitation program for children and adolescents after traumatic brain injury (TBI): methods and first results Current concepts in pediatric burn care: general management of severe burns Advances in the treatment of pediatric trauma The injured child. An approach to care

Disability and Rehabilitation 2010;32:1251-9

A perspective on early mobilization for adult patients with respiratory failure: lessons for the pediatric population A retrospective analysis of timing of mobilisation and start of enteral feeding in 19 patients treated nonsurgically for splenic trauma Exploring the capacity to ambulate after a period of prolonged mechanical ventilation.

Reason(s) for exclusion Narrative review Nonmobility (kidney rehabilitation) Letters/commentary (Letter to the Editor) Adult population

Neurocirugia 2007;18(1):5-15

Adult population

Journal of Trauma 2008;64(3):819-23

Narrative review

Wiadomosci lekarskie 2009;62(1):310

Non-PICU population

Critical Care Medicine 2003;31(10):2456-61 Critical Care Medicine 2012;40(4):1122-8

Adult population

Value in Health 2011;14(1):166-76

Adult population

Journal of Neuroscience Nursing 2015;47(1):E2-10

Adult population

Burns 2009;35 (Suppl 1):S10

Qualitative descriptive study

Archives of Physical Medicine and Rehabilitation 1989;70(12):819-22 Neurologia i Neurochirurgia Polska 2010;44(5):475-80 Ceska a Slovenska Neurologie a Neurochirurgie 2006;69(4):302-7 Brain Injury 2003;17(1):49-54

Adult population

Adult population

Adult population Adult population Adult population

Polish Annals of Medicine 2011;18(1):66-75

Adult population

Brain Injury 2012;26(4-5):471-2

Nonmobility Qualitative descriptive study

Restorative Neurology and Neuroscience 1999;14(2-3):15360

Nonmobility intervention

European Journal of Pediatric Surgery 1992;2(4):195-200 Current Opinion in General Surgery 1994;cb8:41-9 Pediatric Clinics of North America 1994;41(6):1201-26 Journal of Pediatric Rehabilitation Medicine 2010;3(3):215-27

Narrative review Narrative review Narrative review Adult population

Swiss Surgery 1996;2(6):235-7

Retrospective study

Journal of Critical Care 2012;27(6):542-8

Retrospective study

(continued)

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Author

Year

Title

Rodriguez et al

2012

Effects of early exercise on the number of joint release interventions in children with severe burns

Journal of Burn Care and Research 2012;33(2 Suppl 1):S73

Roth et al

2013

Neurocritical Care 2013;18(1):33-8

Salem and Ahmed

2014

Salorio et al

2008

Schreiber and Mai

1990

Schultz

2010

Seel et al

2013

Semenova et al

2012

Effect of early physiotherapy on intracranial pressure and cerebral perfusion pressure Use of virtual reality gaming systems for children who are critically ill Intensive care unit variables and outcome after pediatric traumatic brain injury: a retrospective study of survivors Some considerations relative to specific early rehabilitation in patients with severe craniocerebral trauma “Critical illness polyneuropathy” is also an illness in pediatric intensive care medicine Specialized early treatment for persons with disorders of consciousness: program components and outcomes Our experience of severe traumatic brain injury treatment in children

Takaada et al

2012

Tasseau et al

2005

Tederko et al

2006

Tepas et al

2009

Wright Yager et al

2013 2011

Yeung et al

2013

Zieger

1992

Arteaga et al

2018

Cui et al

2017

Hunter et al

2017

Kawai et al

2018

McGibbon et al

2017

Miura et al

2018

Norman et al.

2017

Simone et al

2017

Effectiveness of early phase rehabilitation for pediatric and adolescent traumatic brain injury patients in the critical care and emergency unit [Intensive care handling: specific expectations of rehabilitation] Problems of adaptation to wheelchair in early stage rehabilitation after spinal cord trauma The effect of delay in rehabilitation on outcome of severe traumatic brain injury Physio findings Advances in simulation for pediatric critical care and emergency medicine Delayed mobilization after microsurgical reconstruction: an independent risk factor for pneumonia Early rehabilitation of neurosurgical intensive care patients emerging from coma. On the philosophy and practice of an interdisciplinary approach Bundling the bundles: can we change culture with a holistic approach to patient care in the ICU? Physical and occupational therapy utilization in a pediatric intensive care unit Overcoming nursing barriers to intensive care unit early mobilisation: a quality improvement project PICU liberation collaborative: bundle to eliminate delirium improves ICU culture and outcomes Mobilising within the paediatric intensive care unit: a service evaluation

Normal baseline function is associated with delayed rehabilitation in critically ill children. Delirium in the critically ill child Implementation of an ICU bundle: an interprofessional quality improvement project to enhance delirium management and monitor delirium prevalence in a single PICU

Reference

Reason(s) for exclusion Non-PICU pediatric population (exercise implemented at 6 months postburn) Non-PICU setting Adult population

Journal of Pediatric Rehabilitation Medicine 2014;7(3):273-6 Pediatric Critical Care Medicine 2008;9(1):47-53

Narrative review

Rehabilitation 1990;29(4):238-41

Adult population

Kinderkrankenschwester 2010;29(7):280-1

Case report

Archives of Physical Medicine and Rehabilitation 2013;94(10):190823 Brain Injury 2012;26(4-5):685

Retrospective study

Brain Injury 2012;26(4-5):428

Retrospective study Non-PICU setting

Retrospective study Nonmobility intervention (the monitoring of intracranial pressure) Retrospective study

Annales Francaises d'anesthesie et de reanimation 2005;24(6):679-82 Ortopedia Traumatologia Rehabilitacja 2006;8(6):672-9

Adult population

Journal of Pediatric Surgery 2009;44(2):368-72 Frontline 2013;19(3):18-19 Current Opinion in Pediatrics 2011;23(3):293-7 Laryngoscope 2013;123(12):29963000

Retrospective study

Adult population

Letters/commentary Narrative review Retrospective study Adult population

Zentralblatt fur Neurochirurgie 1992;53(2):92-113

Narrative review

Critical Care Medicine 2018;46(Suppl 1):629.

Different study design

Journal of Critical Care 2017;40:1520 Intensive & Critical Care Nursing 2017;40:44-50

Wrong intervention and study design

Critical Care Medicine 2018;46(Suppl 1):638

Wrong intervention

Intensive Care Medicine Experimental. Conference: 30th Annual Congress of the European Society of Intensive Care Medicine, ESICM, 2017;5(2 Suppl 1). Journal of Intensive Care Medicine 2018.

Different study design

Clinical Nurse Specialist 2017;31(5):276-84. Pediatric Critical Care Medicine 2017;18(6):531-40.

9.e5

Wrong intervention and study design

Different study design

Wrong study design Wrong intervention

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Figure. Study flow diagram.

Early Mobilization in Critically Ill Children: A Systematic Review FLA 5.5.0 DTD ■ YMPD10131_proof ■ August 29, 2018

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