Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units: A Systematic Review : Journal of Acute Care Physical Therapy

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Early Mobilization of Patients Receiving Vasoactive Drugs in Critical Care Units: A Systematic Review

Jacob, Prasobh; Surendran, Praveen Jayaprabha; E M, Muhamed Aleef; Papasavvas, Theodoros; Praveen, Reshma; Swaminathan, Narasimman; Milligan, Fiona

Author Information
Journal of Acute Care Physical Therapy: January 2021 - Volume 12 - Issue 1 - p 37-48
doi: 10.1097/JAT.0000000000000140
  • Open


The overall mortality of patients admitted to intensive care units (ICUs) has declined due to the advancement of critical care medicine. However, the prevalence of morbidity has increased among critical care survivors.1–8 Previously, patients who were critically ill and admitted to ICUs were often treated with sedation and prolonged bed rest9 as a means of giving rest to the affected organs and reducing energy consumption.10 However, deleterious effects of bed rest appear to outweigh its benefits.11–14

Prolonged bed rest in critical care patients contributes to short-term as well as long-term complications.3,4,8,15,16 Short-term complications include ICU-acquired weakness and muscle wasting that increases hospital length of stay and reduces quality of life (QOL).8,15 Long-term complications include neuromuscular weakness, low functional capacity, deficits in activities of daily living, reduced QOL, hospital readmission, and death.3,4,16

Several studies have shown that early progressive mobilization is feasible, safe, and beneficial for most patients admitted to ICUs.2,17–20 Early mobilization refers to any form of physical activity within the first 2 to 5 days of critical illness.21 Early mobilization has been shown to prevent or minimize ICU-acquired weakness, improving functional recovery, walking distance at hospital discharge, and reducing hospital length of stay.22–25

Although early mobilization is shown to be safe and feasible,2,17–20 extended periods of bed rest are still prevalent in ICUs.26–28 The barriers hindering early mobility in ICUs can be classified as patient-related (patient symptoms and conditions), structure-related (human and technical resources), and ICU culture (staff attitudes) or process (unclear roles and responsibilities).22,23,29,30 The most commonly reported patient-related barrier is hemodynamic instability requiring vasoactive drug support.30,31 A multicenter cohort study of Australian and New Zealand ICUs reported that vasoactive therapy was the third most common barrier for early mobilization,32 with several studies recommending a cautious approach to mobilizing critically ill patients on vasoactive drugs.2,9,32

Vasoactive drugs are administered to critically ill patients with severe hemodynamic impairment to restore adequate tissue perfusion. Vasoactive drugs consist of inotropes, which increase cardiac output through enhanced myocardial contractility, and vasopressors, which increase vascular tone.31Table 1 shows a summary of clinical indications, dose ranges, and significant side effects of the most commonly used vasoactive drugs.33

TABLE 1. - Clinical Indications, Dose Range, and Significant Side Effects of the Commonly Used Vasoactive Drugsa
Drug Clinical Indication Dose Range Major Side Effects
Dopamine Cardiogenic and vasodilatory shock, heart failure, symptomatic bradycardia, unresponsive to atropine or pacing 2-20 μg/kg/min (maximum 50 μg/kg/min) Severe hypertension, ventricular arrhythmia, cardiac ischemia, tissue ischemia/gangrene (high dose)
Dobutamine Low cardiac output, unresponsive to atropine or pacing 2-20 μg/kg/min (maximum 40 μg/kg/min) Tachycardia, increased ventricular response rate in patients with atrial fibrillation, ventricular arrhythmias, cardiac ischemia, hypertension
Norepinephrine Cardiogenic and vasodilatory shock 0.01-3 μg/kg/min Arrhythmias, bradycardia, peripheral ischemia, hypertension
Epinephrine Cardiogenic and vasodilatory shock, cardiac arrest, bronchospasm/anaphylaxis
symptomatic bradycardia/heart block unresponsive to atropine or pacing
0.01-0.10 μg/kg/min
1 mg IV 3-5 min (maximum 0.2 mg/kg)
0.1-0.5 mg
Ventricular arrhythmias, severe hypertension, cardiac ischemia, sudden cardiac death
Milrinone Low cardiac output Bolus
50 μg/kg bolus over 10-30 g
0.375-0.75 μg/kg/min
Ventricular arrhythmias, hypotension, cardiac ischemia
IV, intravenous.
aUsed with permission from Overgaard and Dzavik.33

Vasoactive drugs are also used in combinations. Patients who receive multiple vasoactive drugs are categorized into either low, moderate, or high level of support based on the highest level of the individual medication.34 The dose range classifications of the most commonly used vasoactive drugs are presented in Table 2.34

TABLE 2. - Vasoactive Drug Dosage Classificationa
Drug Name Low Dose, μg/kg/min Moderate Dose, μg/kg/min High Dose, μg/kg/min
Dopamine <3 3-10 >10
Dobutamine <3 3-10 >10
Epinephrine <0.05 0.05-0.2 >0.2
Norepinephrine <0.05 0.05-0.2 >0.2
Vasopressin <0.01 0.02-0.03 0.04
Levosimendan <0.05 0.1 0.2
Milrinone 0-0.15 0.15-0.5 0.5
aFrom Boyd et al.34

Vasoactive agents have been lifesaving drugs, but can cause serious adverse events.35 Reflex bradycardia may occur as a compensatory mechanism following administration of vasoactive drugs, which can further induce a reduction in cardiac output.33,36 Vasoactive drug administration can also cause tachycardia, tachyarrhythmias such as supraventricular arrhythmias, ventricular arrhythmias, and cause myocardial ischemia.33,37

The use of vasoactive drugs is an independent risk factor for the development of ICU-acquired weakness, which can be minimized by early mobilization.38 Several recent publications have discussed the safety and feasibility of mobilizing patients with vasoactive drugs.32,34,39–41 These studies have also outlined the various risks, precautions, contraindications, and barriers for mobilizing the patients. Understanding these details continues to be useful for clinicians to implement early mobility in patients with vasoactive drugs. The aim of this review was to synthesize the most recent prevailing evidence pertaining to mobilizing patients receiving vasoactive drugs.


The 3 overarching review questions, which guided the process of data analysis, were as follows:

  1. Are patients in critical care units on vasoactive drugs being mobilized early?
  2. Does a relationship exist between dosage of vasoactive drugs and level of mobility achieved?
  3. What are the adverse events reported while mobilizing patients on vasoactive drugs in critical care units?

PICO Details

Population (P) = Patients admitted in critical care units receiving vasoactive medications.

Intervention (I) = Early mobilization.

Comparison (C) = Bed rest or immobilized.

Outcome (O) = Incidence of mobilization; the level of maximum mobility achieved, adverse events.

Study Selection Criteria

Inclusion Criteria

Clinical trials and cohort studies that discuss the mobilization and safety of critically ill patients receiving vasoactive drugs (publication date range: 2010-2018).

Exclusion Criteria

Studies were excluded if they did not report the number of patients receiving vasoactive drugs or the number of mobilization sessions.

Search Criteria

A literature search was undertaken using PubMed, Physiotherapy Evidence Database (PEDRO), Cochrane Central, and Embase (through Cochrane) for original research, including case studies, cohort studies, and consensus guidelines published in the English language. The details of the search terms were presented in Appendix 1. Three reviewers independently screened all publications, including titles, abstracts, and available full-text publications of the literature searches. The reference lists of the eligible publications and articles were screened for additional eligible publications.

Search Outcome

PRISMA guidelines42 were used to conduct and report this review. A total of 343 articles were retrieved. Articles related to patients receiving vasoactive drugs and mobilizations were included for further analysis. Five articles that specifically discussed the mobilization of patients with vasoactive drugs were identified per the inclusion criteria. Appendix 2 illustrates the PRISMA flow diagram of this study.

Retrieved articles were reviewed and segregated based on vasoactive agents used in critical care patients, their dosage (if reported), criteria for mobilization, percentage of patients who were mobilized, achieved levels of mobility, and adverse events. This information was tabulated for the identification of the variables and drawing conclusions.

The protocol for this systematic review was registered on PROSPERO International Prospective Register of Systematic Reviews (CRD42019127448).


Quality Assessment

Quality assessment of the 5 included studies was conducted independently by 3 reviewers. These articles were appraised using the Newcastle-Ottawa Scale for cohort studies.43,44 Any disagreements between reviewers were resolved by consensus. The risk of bias assessment for the included studies was summarized in Appendix 3. The segregated results derived from 5 studies were presented in Table 3. Five studies,32,34,39–41 comprising of 2 prospective, and 3 retrospective cohort studies, were included in this systematic review, representing a total of 528 participants.

TABLE 3. - Segregated Results Derived From 5 Studies
Author Study Design Patient Characteristics Number of Patients Receiving Vasoactive Drugs Vasoactive Drug/Dose Mobilization Sessions Therapeutic Intervention Adverse Events
Boyd et al34 Prospective cohort study Mechanically ventilated patients Not mentioned. Only session of mobilization mentioned. Both inotropes and vasopressors used. Low-, moderate-, and high-dose classification mentioned. 299 In bed exercises = 41 occasions (15 patients on low dose; 24 moderate and 2 on high dose)
Out-of-bed exercises = 114 occasions (67 patients on low dose; 46 moderate and 1 on high dose)
One event of cardiovascular instability in patients with moderate dose during out-of-bed mobilization
Rebel et al32 Retrospective cohort study Mechanically ventilated and nonmechanically ventilated patients 119 Dose classification available for
195 Low-intensity mobilization: IMS 1-2 in 43 patients
Moderate-intensity mobilization: IMS 3-5 in 71 patients
High-intensity mobilization: IMS 6-10 in 25 patients
Hypotension in 14 patients and new onset of dysrhythmia in 1 patient
Abrams et al39 Retrospective cohort study Patients receiving ECMO for refractory respiratory or cardiac failure in the medical intensive care unit 18 Dose classification available for
Norepinephrine and vasopressin
Not mentioned The intervention ranges from active assisted ROM sitting in bed, sitting at the edge of the bed, standing and ambulation There were no patient-related or circuit-related complications as a result of physical therapy treatment sessions in any of the patients
Nievera et al40 Retrospective cohort study Postcardiac surgery patients who are not on mechanical ventilators or VADs 47 Dose classification available for
Not mentioned Most patients (56%) were able to ambulate 50 ft (15 m) 13% of patients experienced a decrease in mean arterial pressure
Hickmann et al41 Prospective cohort study Critically ill patients 58 Dose classification available for
149 sessions Intervention includes in-bed passive and active mobilization; in-bed passive and active cycling; in-bed leg press, in chair sitting, in-chair passive mobilization; in-chair passive and active cycling; in-chair leg press; standing and walking 2 hypotension; 2 hypertension and 3 tachycardia
ECMO, extracorporeal membrane oxygenation; IMS, ICU mobility scale; ROM, range of motion; VAD, ventricular assistive device.

Two of the 5 studies focused only on patients (166 participants) who received vasoactive medication.32,40 One of these studies included only postcardiothoracic surgery patients who were not on mechanical ventilators.40 The remaining 3 studies included all patients admitted in the critical care unit irrespective of the presence or absence of vasoactive drugs.34,39,41 Two of the 3 studies reported that 34%39 and 23%41 received the vasoactive drugs, while the third study reported 45%34 of the patients received vasoactive medications. This study revealed 299 out of 809 mobilization sessions received during the presence of vasoactive drugs.

Participants included in this review were admitted in a general, medical or surgical ICU.32,34,39–41 The patient population was diverse, encompassing cardiovascular disorders, sepsis, respiratory diseases, gastrointestinal diseases, renal diseases, surgical patients, patients on extracorporeal membranous oxygenation (ECMO), and patients requiring mechanical ventilation. Admitting diagnoses of all patients in the studies were indicative of critical illness, while participants in 1 study40 were postcardiac surgery. The mean age of the participants in the studies was 58.6 ± 17 years. APACHE II (Acute Physiology, Age, Chronic Health Evaluation II) was used in 3 studies to measure the severity of diseases.32,39,41 The mean APACHE score in these studies was 21.97, with a standard deviation of 7. A score of 25 represents a predicted mortality of 50% and a score of more than 35 represents a predicted mortality of 80%.45

Vasoactive Therapy and Early Mobilization

In all 5 included studies, the participants who received vasoactive drugs were mobilized safely, irrespective of dose and characteristics of patients.32,34,39–41 Patients who had compromised heart and lung function requiring life support such as ECMO and vasoactive drugs were mobilized without serious adverse events.39 The studies underlined that vasoactive medications should not be considered as a contraindication for early mobilization.32,34,39–41 One study reported that the primary barrier for mobilizing the patients receiving vasoactive drug was the clinician-perceived physiological instability of the patient including hemodynamic, cardiovascular, respiratory, and neurological instability.32

Vasoactive Drug Dosage and Level of Mobility

Details of vasoactive drugs and dosages were identified in all the 5 studies included in this review.32,34,39–41 Activities included in these studies were passive cycling, range-of-motion exercises, bed mobility activities, transfers, and ambulation. In all of the studies, participants who received a low, moderate, and high dose of vasoactive drugs were mobilized.32,34,39–41 However, only 3 studies identified the level of mobility achieved by patients with respect to drug dosage.32,34,40

The first study reported that patients on low doses of vasoactive drugs were 5 times more likely to be mobilized than those on high doses (odds ratio [OR] = 5.50; 95% confidence interval [CI] = 2.23-13.59),32 while patients on moderate doses were twice as likely to be mobilized than those on high doses (OR = 2.50; 95% CI = 0.95-6.59).32 The second study34 reported similar conclusions; the study revealed that 59% of mobilized patients received a low dose of vasoactive drugs, 40% received a moderate dose, and 0.87% received a high dose.34 Contrary to the above findings, the third study found no relationship between vasoactive drug dose and achieved level of mobility.40 According to the authors, the achieved level of mobility might have been related to other factors, such as comorbid conditions and baseline physical fitness.40 Another factor that might have contributed to these inconsistent findings may be the functional status of the participants. In the first 2 studies the participants were patients who required mechanical ventilation, whereas in this study40 the participants did not require mechanical ventilation and, consequently, had higher functional status than the participants of the first 2 studies.

Only 1 study19 quantified the level of mobility achieved by using a validated scale, namely the ICU mobility scale (IMS).46,47 However, the data assessor converted the mobilization descriptions from the documentation to the IMS score. This study showed 31% of the patients achieved an IMS score of 1 to 2, 51% achieved an IMS score of 3 to 5, and 18% achieved an IMS score of 6 to 10.32

Adverse Events

Serious adverse events were defined as a fall to the ground, cardiac arrest, unplanned extubation, new onset of cardiac dysrhythmias, removal of invasive lines and tubes, loss of consciousness, hypotension necessitating escalation of medical therapy (as determined by the treating clinicians, rather than an absolute threshold), and death.23,29,32,48 None of the included studies reported any serious adverse events associated with early mobilization.32,34,39–41 Overall, the most commonly cited adverse event was reversible hypotension.32,34,41

One study34 followed a standard traffic light system recommended by an international multidisciplinary expert consensus group9 for predicting the adverse events while mobilizing patients. Green indicates a low risk of an adverse event, yellow indicates a potential risk of an adverse event, and significant potential risk of an adverse event is categorized as red.9 In this study, no adverse events were reported during in-bed exercise sessions, whereas 1 minor adverse event, without any clinical significance, was reported during the out-of-bed exercise sessions.34 The adverse event reported was cardiovascular instability in a patient who received a moderate dose of a vasoactive drug while using a tilt table, but the type of cardiovascular instability was not reported.34 They identified that a holistic clinical assessment including patient's age, level of exercise tolerance, functional independence prior to ICU admission, current hemodynamic status, and the amount of ventilatory and cardiac support required minimized the risk of an adverse event.32,34,49

A study that included solely patients who received vasoactive drugs reported an adverse event rate of 7.8%, but none of these was life-threatening.32 Early cessation of mobilization occurred in 5.1% of the patients as a result of transient physiological changes (ie, desaturation, hypotension, bradycardia, and nausea). The adverse events were more likely to be experienced in patients with lower mean arterial pressure (OR = 0.72; 95% CI = 0.58-0.88) and higher FiO2 (OR = 1.38; 95% CI = 1.10-1.72).32 The other 2 studies did not report any significant adverse events during mobilization.39,40 Another study provided limited data regarding adverse events specific to patients with vasoactive drugs, including only the statement that hypotension occurred in 2 patients receiving low-dose vasopressors, hypertension in 2, and tachycardia in 3.41


Currently, several reviews and studies have addressed early mobilization of the patients in critical care.2,8,9,17,30,48–51 This systematic review focused specifically on patients receiving vasoactive drugs and explored the early mobilization practices, the relationship between drug dosage and the achieved level of mobility, and the reported adverse events associated with early mobilization.

Vasoactive Therapy and Early Mobilization

Overall, the studies included in this review indicated that mobilization of critically ill patients receiving vasoactive drugs with stable hemodynamics could be safely conducted without serious adverse events. Even patients on mechanical ventilators, ECMO, and renal replacement therapy were mobilized safely.32,34,39,41

The most common barrier to mobilizing the patients were clinician-perceived hemodynamic instability and lack of multidisciplinary approach.32,50 A study in medical ICUs found that 43% of physicians, 59% of nurses, and 42% of physiotherapists disagreed with the mobilization of a patient on vasopressor agents.50 The reluctance to embrace new mobilization practices, lack of collaborative approach, reduced knowledge regarding the appropriateness of mobilization, and absence of guidelines were the major barriers reported for early mobilization.50 The study concluded that even though the majority of the critical care clinicians were knowledgeable about the benefits of early mobilization, most of them disagreed with mobilizing patients on vasoactive drugs.50

Some of the published expert-driven protocols recommended that the presence of a high dose of vasoactive drugs was a contraindication for mobilization.52–54 McWilliams et al52,53 in their 2 studies considered high doses of vasoactive agents (>0.2 μg/kg/min noradrenaline or equivalent) as exclusion criteria, and a low dose of vasoactive agents (0.01-0.02 μg/kg/min noradrenaline, or equivalent) as a restriction to sitting at the edge of bed. Sommers et al54 in their evidence-based, expert-driven practical statement, and rehabilitation recommendation considered dopamine ≥10 μg/kg/min and nor/adrenaline ≥0.1 μg/kg/min as an absolute contraindication for mobilization.

This review revealed that a team-based, protocol-driven approach made mobilization feasible to patients with vasoactive drugs, irrespective of the dosage.41,55 A detailed assessment by an interprofessional team was useful to determine the readiness for exercise/mobilization of patients with vasoactive drugs.26,39–41

Vasoactive Drug Dosage and Level of Mobility

The relationship between dosage of vasoactive drugs and achieved level of mobility was inconsistently documented across studies included in this review.32,34,39–41 This review was not able to synthesize the correlation between vasoactive drug dosage and level of mobility because of the lack of standard outcome measures.

One important finding of this review was that, as a general practice, patients on high and moderate doses were less likely mobilized, compared with patients on a low dose. Conversely, the evidence demonstrates that many patients on high and moderate doses were mobilized without serious adverse events.32,34,40

A case series of sedated mechanical ventilated patients concluded that passive cycling was safe even with a high dose of norepinephrine (maximum concentration was 0.47 μg/kg/min).56 The important component that influences the clinical decision to initiate mobilization was the hemodynamic stability of the patient, not the dosage, or the number of vasoactive drugs.32,40

This review's findings were consistent with an expert consensus statement,9 which reported that the presence of vasoactive drugs was not an absolute contraindication to mobilization.

Adverse Events

The description of adverse events during mobilization varied widely among the included studies.32,34,39–41 The incidence of adverse events associated with early mobilization of patients receiving vasoactive drugs was low, and most of them were not serious.32,34,39–41 One study identified that adverse events were more likely to occur in patients with higher peripheral capillary oxygen saturation (SpO2), a higher fraction of inspired oxygen (FiO2), and lower mean arterial pressure during mobilization.32 They reported that clinicians were more likely to attempt mobilization of patients with higher SpO2, presuming they have adequate respiratory reserve. According to their study, the mean arterial pressure was more clinically significant in predicting the adverse events than SpO2 and FiO2.32 These hemodynamic parameters need to be considered in predicting the adverse events during mobilization.32

The consensus recommendation of 23 multidisciplinary experts outlining safety consideration was and will be a valuable tool in guiding the exercise rehabilitation or early mobilization of patients.9 In conjunction with a thorough assessment, this tool was and will be useful to avoid adverse events during mobilization.9,34

Clinical Implications

This review covers a broad spectrum of patients who received different doses of vasoactive drugs; therefore, this could be useful for clinicians working in all ICUs. The presence of vasoactive drugs should not be considered as an independent factor to determine the early mobilization of critically ill patients. The decision to mobilize a patient receiving vasoactive drugs should depend on the clinical status of the patient at the time of the planned mobilization and the direction of trends in the past hours, rather than the dose of vasoactive drugs. A cautious approach with slow progressive mobilization would help to achieve higher levels of mobility, even with a higher dose of vasoactive drugs.


This review has several limitations. First, the methodological quality of the included studies was variable. Second, the mobility achieved by the patients was not assessed using validated tools. Third, the optimal dose of vasoactive drugs for safe mobilization could not be determined due to lack of data.


This review concludes that mobilizing patients in critical care units who are on vasoactive drugs appears to be safe for most patients. Expert consensus is lacking regarding the dose of vasoactive drugs that would allow safe mobilization of patients and the highest level of mobility that could be achieved in critical care. The criteria that have been used to determine the eligibility and progression of mobilization of patients on vasoactive drugs were not consistent. Current available studies indicate no serious adverse events associated with mobilization. However, a holistic approach remains vital to reduce or avoid any adverse events.

Future multicenter prospective cohort studies with large patient samples, diverse clinical diagnosis, and utilizing appropriate outcome measure will be essential to determine the optimal dose of vasoactive drugs for safe mobilization and the level of mobility achieved.


The authors are grateful to Dr Steve Milanese for his valuable inputs and guidance throughout this review. They are also thankful to Pramod Divakar Shenoy and Sheena Maria John for their valuable suggestions for this review.


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Search terms:

The following are the details of the search terms used.

#1 “critical ill patient*” OR “intensive care unit*” OR “ICU”

#2 “vasoactive drug*” OR “vasoactive agent*” OR Dopamine OR Noradrenaline OR inotrope* OR vasopressor OR adrenaline OR epinephrine OR norepinephrine OR dobutamine OR milrinone OR “vasoactive medicine*” OR “vasoactive medication*”

#3 “early mobilization” OR “early mobilisation” OR “early ambulation” OR “early walking” OR ambulation OR walking OR “active transfer” OR “passive transfer” OR “passive mobilization”

#1 and #2 and #3



APPENDIX 3 - Newcastle–Ottawa Quality Assessment Scale for Cohort Studies43,44
Quality Assessment Criteria Rebel et al32 Boyd et al34 Nievera et al40 Abrams et al39 Hickmann et al41
Representativeness of the exposed cohort
Selection of the nonexposed cohort
Ascertainment of exposure
Demonstration that outcome of interest was not present at start of study
• Somewhat representative of the average in the community
No description of the derivation of the nonexposed cohort
• Secure record (medical record)
• Yes
• Somewhat representative of the average in the community
No description of the derivation of the nonexposed cohort
• Secure record (medical record)
• Yes
• Somewhat representative of the average in the community
No description of the derivation of the nonexposed cohort
• Secure record (medical record)
• Somewhat representative of the average in the community
No description of the derivation of the nonexposed cohort
• Secure record (medical record)
• Somewhat representative of the average in the community
No description of the derivation of the nonexposed cohort
• Secure record (medical record)
Comparability of cohorts on the basis of the design or analysis
Assessment of outcome
Was follow-up long enough for outcomes to occur
Adequacy of follow-up of cohorts
No description
• Yes, adequate follow-up period for outcome of interest
October 2016 to December 2016
• Complete follow-up (no dropout mentioned in this study)
No description
• Yes, adequate follow-up period for outcome of interest
February 2015 to December 2016
• Complete follow-up (no dropouts mentioned in this study)
No description
• Yes, adequate follow-up period for outcome of interest
November 2010 to July 2011
• Complete follow-up (no dropout mentioned in this study
No description
• Yes, adequate 100 patients
No dropout mentioned
• Independent blind assessment
• Yes, adequate period December 1, 2014, to January 31, 2015
No dropout mentioned
Note: 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 (each asterisk represents if individual criterion with in the subsection was fulfilled).

© 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Academy of Acute Care Physical Therapy, APTA