Fatigue, fear of being mobilized and residual limb pain limit independent basic mobility and physiotherapy for patients early after major dysvascular lower extremity amputation: A prospective cohort study

Early mobilization of patients with a major lower extremity amputation (LEA) is often a challenge because of lack of compliance. Therefore, we investigated factors limiting independent mobility and physiotherapy on the first day with physiotherapy (PTDay1) and the following 2 days after LEA.


Introduction
A major dysvascular lower extremity amputation (LEA) is associated with a high risk of mortality, 1 multimorbidity 2,3 and loss of physical function. 4,5Few LEA patients achieve independent mobility within the first post-amputation days, and this increases to approximately 50% at discharge from the acute hospital. 6Studies have shown that early mobilization out of bed starting as early as on the first postoperative day for patients with LEA seems to increase physical function, [8][9][10][11] and reduce mortality and complications. 6,7Yet, early mobilization is complex and not achievable for all LEAs. 6Thus, identifying factors that limit early mobilization and the ability to achieve independent mobility after LEA is essential for planning effective strategies to enhance recovery.In comparison, factors that limit early mobilization and participation in physiotherapy have been established for patients with hip fracture 12 and after acute high-risk abdominal surgery, 13,14 but to our knowledge, not after LEA.
The primary aim was to examine the most frequent factors limiting independent mobility during the first postoperative days after a major dysvascular LEA.Second, to examine factors that limit completion of planned physiotherapy on the first day with physiotherapy (PTDay1) and the following 2 days (Day2-3), in addition to exploring the association between the most frequent limiting factors and patient characteristics.

Study design and patients
A prospective observational cohort study of patients who consecutively underwent a major dysvascular LEA at the Copenhagen University Hospital Hvidovre, Denmark, was carried out between mid-November 2018 and June 2019.Inclusion criteria were objectively assessed with the Basic Amputee Mobility Score (BAMS) 6 on PTDay1.Patients provided informed consent before participation.Exclusion criteria were residual limb revision, and when a patient had not received physiotherapy during admittance.
The study was approved by the local ethics committee (wz19001024-2019-14). Data collection was registered with the regional data protection agency (J.no.01 HVH-2012-053).The study adheres to the STROBE checklist. 15

Treatment program
All patients followed an enhanced multimodal perioperative program adapted to patients with a major LEA, standardized for elements, such as rehabilitation, blood transfusion and pain management. 7he program encompasses the initiation of physiotherapy on PTDay1 regardless of what day of the week.Thereafter, physiotherapy was only offered on weekdays.Thus, in the present study, data for Day2-3 only includes those patients offered physiotherapy on three consecutive days.The physiotherapy sessions are focused on patients achieving independent basic mobility, increasing balance/muscle strength and possibly preparing the patient for a prosthesis.This includes training in getting from a supine position to sitting, transfer, use of assistive devices and wheelchair maneuvering, and progressed on an individual level.

The Basic Amputee Mobility Score
The BAMS was used for the daily assessment of basic mobility, 6 and is defined by four activities: (1) from supine lying in bed to sitting on the edge of the bed and back, (2) from sitting on the edge of the bed to a chair/wheelchair and back, (3) indoor wheelchair mobility, and (4) from a chair/wheelchair to standing and back.Each of the four activities was scored from 0 to 2 by one of two experienced physiotherapists, where "0 = not able to despite extensive help from one or more persons, 1 = able to with verbal instruction to extensive help from one or more persons, and 2 = able to safely, without verbal instruction or support from a person, even for safety reasons".It provides a daily cumulated BAMS score of 0-8, with 8 points being equivalent to the patient having independent basic mobility.
BAMS is utilized in several Danish and international hospitals.It has shown excellent inter-rater reliability (Kappa 0.98), high responsiveness, validity for known age groups and proven as a strong predictor of 30-day mortality after LEA. 6

Outcomes and assessments
The following patient demographics were recorded: sex, age, the American Society of Anesthesiologists grade (1-4) of physical status, 16 amputation level, the final amputation status (transtibial-, transfemoral-or bilateral), primary diagnosis, primary reason for amputation, number of days since amputation until PTDay1 and weekday of surgery.On discharge, the length of stay and discharge destination (another ward, own residence/nursing home or temporary 24-h setting in municipality) were recorded.Mortality during admittance, after 30 days, and 6 months were verified by national register data.

Factors limiting basic mobility and physiotherapy
Patients were BAMS scored by the physiotherapist, and those unable to carry out one or more of the four BAMS activities independently, equal to a score of 0 or 1, were considered limited in their basic mobility.For activities with a BAMS <2 points, the primary and possibly a secondary factor reported by the patient was recorded from a set of predefined limitations (Table S1).Likewise, a primary and possibly a secondary factor limiting physiotherapy was reported by the patient if unable to complete the planned physiotherapy.In rare cases, patients were unable to report a limitation, in which case the physiotherapist did so to the best of their ability.
The factors limiting independent basic mobility and physiotherapy were predefined by experienced amputee physiotherapists at the hospital, and were based on consensus discussions and inspiration from a similar study. 12The predefined limiting factors were: (1) residual limb pain, (2) pain elsewhere, (3) fear of being mobilized, (4) fatigue, (5) nausea/vomiting, (6) acute cognitive dysfunction (delirium), or (7) other limitations.In the cases where the limitation was "other," the patient individually defined the limitation, and it was recorded on the scoring sheet (Table S1).

Physical therapy
After each physiotherapy session, the physiotherapist assessed whether the patient had fully completed, partially completed or not completed the planned physiotherapy using a method from a similar study. 12One of the three options was noted on the scoring sheet with Y/P/N, where Y = Yes when the patient had completed the session, P = Partially completed when the patient had only been able to participate partially or had to give up exercises and N = Not completed.The same predefined factors limiting mobility were used for patients not able to fully complete the planned physiotherapy.

Statistical analysis
Data were examined for normality of distribution using the Kolmogorov-Smirnoff test.The study population was described by the mean and standard deviation when normally distributed, and otherwise by median and 25%-75% quartiles, or as numbers with percentages, as appropriate.The BAMS score, completion of physiotherapy on PTDay1 and Day2-3, and the most frequent primary limitations on PTDay1 and Day2-3 for not achieving a BAMS score of 2 per activity and not completing the planned physiotherapy, were described with numbers (n) and percentages.Very few secondary limitations (Table S2) were reported by patients for both assessments, and therefore not included in results and analysis.Analyses for factors limiting independent basic mobility were a priori focused on BAMS activity 2, transferring from bed to chair/wheelchair and back.This activity is particularly challenging for patients with LEA, and provides knowledge of whether the patient has been mobilized out of bed or not.
The χ 2 -test was used to evaluate the association between the most frequent limitations for BAMS activity 2 on PTDay1 and for the following subgroups: sex (male vs female), age (≤74 years vs >74 years), American Society of Anesthesiologists grade score (2-3 vs 4), the final amputation status (transtibial vs transfemoral/bilateral) and the primary diagnosis (diabetes mellitus vs atherosclerosis/other).
Statistical analyses were carried out using SPSS version 25 (IBM Corporation, Armonk, NY, USA), and the level of statistical significance was set at P < 0.05.Figures were developed using GraphPad Prism 10.1 (San Diego, CA, USA).

Results
During the 7-month recruitment period, a total of 70 patients underwent LEA at the hospital, of whom four were excluded due to stump revision surgery, four died before PTDay1, one had missing data and one had not received physiotherapy during admittance leaving 60 included patients.
The characteristics of the study population are presented in Table 1.PTDay1 occurred on the first postoperative day for 55 (91.7%) patients, and on day 2 for three patients (5%); one due to late return to the ward after surgery, and two for unknown reasons.For two patients (3.3%), PTDay1 was on postoperative day 4 due to an intensive care unit stay for 3 days after amputation.

Basic mobility and its limitations
The frequency of BAMS scores for the four activities separately on PTDay1 and Day2-3 are presented in Table 2.Only three patients (5%) had an independent basic mobility score of 2 on all four BAMS activities on PTDay1.This was unchanged on day 2, whereas it increased to six patients (10%) on day 3.
The number of patients evaluated with the BAMS on Day2-3 was lower than on PTDay1, mainly because many patients underwent LEA on a Friday (35%; Table 1), and as physiotherapy is only offered during weekends on postoperative day 1.
Fatigue and fear of being mobilized were the most frequent factors limiting all four BAMS activities on all 3 days, and followed by residual limb pain and acute cognitive dysfunction (Table 3).The results for BAMS activity 2 (transfer from bed to chair and back) are shown in Figure 1a.The factor, "other limitations," for non-independency in activity 2 was reported as problematic blood pressure/blood sugar, unconsciousness or not motivated.Overall, the patients primarily utilized the predefined factors limiting them, and rarely the individually defined "other" option.Likewise, only in very rare cases did the physiotherapist have to decide the factor limiting patients.
There was no significant association between fatigue or fear of being mobilized as a limitation for BAMS activity 2 on PTDay1 and the previously described subgroups for sex, age, American Society of Anesthesiologists grade, the final amputation status, and the primary diagnosis.

Planned physiotherapy and its limitations
A total of 36, 22 and 29 patients completed the planned physiotherapy on PTDay1, day 2 and day 3, respectively (Table 4).Fatigue, residual limb pain and "other" were the factors that most often limited patients when only partially completing or not completing planned physiotherapy on PTDay1 and Day2-3 (Table 4, Figure 1B).The factor, "other limitations," was problematic blood pressure/blood sugar, unconsciousness, patient not available or not motivated.

Discussion
The present study shows that fatigue and fear of being mobilized are the most frequent reasons for patients not achieving independent basic mobility early after a major dysvascular LEA.Missing data due to patients not receiving any physiotherapy on weekends and public holidays after postoperative day 1, and due to staff logistics.
Table 3 Limitations for not achieving an independent Basic Amputee Mobility Score of 2 points for each of the four Basic Amputee Mobility Score activities on three consecutive days after major lower extremity amputation  | 473 Additionally, we found that fatigue, residual limb pain and "other" limitations are the most frequent reasons for not completing planned physiotherapy.By gaining this knowledge of what patients perceived as limiting their basic activities, clinicians have a better understanding of the limited resources and challenges that these frail patients are facing.
To our knowledge, this is the first study to describe patientreported factors limiting independent mobility and participation in physiotherapy in the important first days after a major dysvascular LEA.It thereby adds valuable knowledge to further enhance the early rehabilitation and potentially improve outcomes of this frail patient group.The current findings are consistent with studies of patients after acute abdominal surgery 14 and patients with hip fracture, 12,17 which to some extent can be considered a patient group with similar frailty.
We cannot conclude on the cause of fatigue in the present study.However, it is noteworthy that >90% of the patients had a primary diagnosis of either diabetes or atherosclerosis, which are conditions associated with physical and mental fatigue, 18 and peripheral fatigue. 19Additionally, postoperative fatigue, a wellknown condition after surgery, 20 is a plausible explanation for fatigue being a major limitation in the present study.Furthermore, anemia is a common condition among patients with a major LEA, 21 and is likewise associated with fatigue in older and weakened populations, 22,23 that might limit the ability to recover from surgery and participate in rehabilitation. 24,25In patients with hip fracture, 26 anemia has been associated with a low ambulatory level in the first three postoperative days, and the same is plausible for patients in the present study.
The second most frequent factor limiting independent basic mobility was fear of being mobilized, reported by 33% of patients who were not able to independently transfer from bed to wheelchair on PTDay1.The present findings align with previous research, indicating that patients with LEA commonly experience fear of falling not only within the first year, but also several years after LEA, 27 and fear of falling can be a barrier to physical activity. 28][32] Among patients who underwent LEA several years earlier, low balance confidence is associated with reduced mobility 33,34 and a lower degree of daily physical activity. 35A better understanding of fear avoidance and how it influences early mobilization after LEA is needed, and the findings of this study can serve as a backdrop for future strategies to address this issue.
7][38] Likewise, the prevalence of residual limb pain is high shortly after and at long-term follow up in LEAs. 39,40ogether, this highlights the importance of giving high priority to effective pain management in acute care settings after LEA.The variety of "other" limitations highlights the complexity of LEAs and the many factors that must be considered to achieve successful early mobilization.
Contrary to findings of previous studies, we did not find a significant association between the most frequent limitations and patient characteristics on the activity transfer from bed to wheelchair.Thus, a positive association has been reported between postoperative fatigue and age in patients after elective abdominal surgery 41 and gastrointestinal tumor surgery. 42Also, the percentage of older people who experience fatigue in daily activities seems to increase significantly between 70 and 85 years-of-age, and can be related to loss of functional ability. 43This was not the case in the present study.Fear of falling is also associated with older age among older adults, 44,45 but was also not the case in this study.
We also expected more transfemoral/bilateral amputees than transtibial amputees to be limited by fear of being mobilized.This assumption stemmed from the greater challenge individuals with a transfemoral LEA might face in maintaining balance due to the absence of both the ankle and knee joint, in contrast to those with a transtibial amputation. 31,46However, contrary to our expectations, this was not the case.Particularly regarding bilateral amputees, this observation might be linked to many of them already having experience in functioning with one leg before their current amputation.Strengths of the present study are the use of BAMS as a valid and reliable outcome measure developed and recommended for use in LEAs, 47 and the representative sample of patients.With an annual incidence of approximately 1800 major LEAs in Denmark, 60 patients from a single hospital for a period of 7 months can be considered representative. 48Other strengths are the predefined limiting factors defined by experienced amputee physiotherapists, and that patients were included consecutively, regardless of previous functional and cognitive status, strengthening the results' generalizability.However, a limitation might be that the development of the predefined factors did not directly involve patients with a former LEA.The presence of selection bias cannot be ruled out, as a predefined limitation might inadvertently influence the patients toward choosing from the already listed limitations.However, patients had the opportunity to report the factors limiting their abilities whenever they felt it necessary, although they seldom did.This indicates that the predefined factors might adequately cover the patient-perceived limitations for mobilization.
Most patients undergoing a major dysvascular LEA were unable to achieve independent basic mobility during the early postoperative period, and were most often restricted by fatigue and fear of being mobilized.Correspondingly, fatigue, residual limb pain and "other" were the most frequent factors that limited completion of planned physiotherapy.
We suggest that efforts to reduce the influence of the identified patient-reported factors limiting early mobilization and physiotherapy should be considered in acute care settings to potentially increase compliance and ensure better recovery.

Authors contributions
MTK, AØN and SBS designed the study.ALB carried out the analysis and drafted the work in consultation with MTK.AØN and SBS revised it, and all authors approved the final version.| 475

From 3 )
supine lying in bed to sitting on the edge of the bed and back From sitting on the edge of the bed to a chair/wheelchair and back Indoor wheelchair mobility From chair/wheelchair to standing on the non-amputated leg and back BAMS 0Total n = 60.Data are shown as the number (%).PTDay1 and Day2-3: the first day with physiotherapy and the following 2 days.BAMS score: 0 = not possible, 1 = possible with assistance, 2 = independent.† One patient had missing data on activity 4 on all 3 days.‡

Figure 1
Figure1(a) Limitations for not achieving an independent Basic Amputee Mobility Score (BAMS) of 2 points for activity 2: getting from bed to wheelchair and back, on the first day with physiotherapy (PTDay1) and the two following days (Day2-3), and (b) limitations for partially or not completing planned physiotherapy on the corresponding days.

Table 1
Characteristics of the study population with a major dysvascular lower extremity amputation † Embolism, paraplegia, cancer, hypertension.‡Ischemic pain without ulceration.ASA: American Society of Anesthesiologists grade.PTDay1: first post-amputation day with physiotherapy.

Table 2
Frequency of the Basic Amputee Mobility Score (BAMS, 0-8 points) on three consecutive days after a major lower extremity amputation Data are shown as numbers (%).PTDay1 and Day2-3: the first day with physiotherapy and the following 2 days.A1-A4: Basic Amputee Mobility Score Activity 1-4.A1. from supine lying in bed to sitting on the edge of the bed and back, A2. from sitting on the edge of the bed to a chair/wheelchair and back, A3. indoor wheelchair mobility and A4. from a chair/wheelchair to standing and back.
†Missing data due to patients not receiving any physiotherapy on weekends and public holidays after postoperative day one, and due to staff logistics.A prospective cohort study © 2024 The Authors.Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Table 4
Planned physiotherapy, completed, partially completed, or not completed, and limitations for those not completed on three consecutive days after major lower extremity amputation Total n = 60.Data are shown as numbers (%).PTDay1 and Day2-3: the first day with physiotherapy and the following 2 days.Other: Not able to collaborate, not motivated, low blood pressure, low blood sugar, and unconsciousness.
†Missing data for unknown reasons.‡ Physiotherapy not offered due to weekends, public holidays, dementia, discharge, transfer to another ward and poor condition.