EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Handgrip strength (HGS) is used to evaluate muscle strength in different classes of patients, and it has predictive value to define sarcopenia and other clinical and functional outcomes,^1-4 even in acute patients.^5,6 Handgrip strength seems to be positively and moderately associated with lung function in healthy and unhealthy adults.⁷

As recommended by the American Society of Hand Therapists, HGS should be measured with an adjustable handle dynamometer, and 3 successive grip determinations should be recorded in kilograms or pounds. The test should be performed with the patient in a sitting position with shoulders adducted and neutrally rotated, elbow flexed at 90 degrees, and forearm and wrist in neutral position.⁸

Among the physical examinations that should be performed to assess disability, functional status, and exercise capacity of the lung transplant (LT) candidate, HGS has been strongly recommended in the inter-national consensus recommendations released in November 2021 by the following groups: the European Association of Cardio-Thoracic Anaesthesiologistsand Intensive Care, the Society of Cardiovascular Anesthesiologists, the International Society for Heart and Lung Transplantation, the European Society for Organ Transplantation, the European Society of Thoracic Surgeons, and the American Society of Transplantation.⁹ Another consensus report of the Asian Working Group for Sarcopenia has emphasized that HGS is a feasible and convenient measure of muscle strength and has also provided discriminatory values.¹⁰ Reference values for HGS are available for different classes of patients, healthy adults, and youth populations and for patients from various world regions.^11-14 For LT candidates, the preoperative physical conditions predict and influence posto-perative outcomes.^15,16 The evaluation of sarcopenia and the rehabilitative potential before and after LT have been shown to significantly affect the postoperative recovery and long-term results; as such, these details should be considered and implemented during the preoperative screening of candidates for LT.¹⁷ The International Society for Heart and Lung Transplantation guidelines empha-size incorporation of assessments of posttransplant survival on the overall evaluation of patient eligibility for transplant.¹⁸ From this perspective, it is crucial to identify frailty that could portend either poor eligibility for transplant or to identify an intervention opportunity intended to improve the likelihood of a durable benefit from LT.¹⁹ The simplicity and repeatability of HGS makes it an appealing means of prognostication and assessment of response to therapy that may be used at the bedside or in an outpatient setting.

Although HGS is increasingly used in patients receiving or awaiting LT, there is no consensus regarding interpretation of HGS measurements or cutoff values in these patient contexts.

Here, we review and summarize the literature about HGS in LT candidates and LT recipients and consider the associations between HGS and dyspnea intensity, respiratory muscle strength, and functional performance.

Materials and Methods

Study design
For this integrative review,²⁰ we searched 8 databases: the United States National Library of Medicine PubMed system, Scopus, Web of Science, ProQuest Central, Scientific Electronic Library Online (ie, SciELO), Latin American and Caribbean Health Sciences Literature (ie, LILACS), Cochrane Library, and Cumulated Index to Nursing and Allied Health Literature (ie, CINAHL). The integrative review method allows for the simultaneous inclusion of experimental and nonexperimental research in order to fully understand the presentation of varied perspectives on a phenomenon.²⁰ The present study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.²¹

Search strategy
Databases were searched from inception through February 2023. Two keyword entries, “handgrip strength” and “lung transplantation,” were matched using the Boolean operator AND. In each database, the following fields were searched: PubMed (all fields), Scopus (title, abstract, keywords), Web of Science (all fields), ProQuest Central (abstract, summary text), SciELO (all indexes), LILACS (title, abstract, subject), Cochrane Library (title, abstract, keywords), and CINAHL (all text). No filters were applied for document type, age, sex, publication date, language, and subject. The references listed in the retrieved articles were searched for additional material. The search process was completed in February 2023.

Inclusion and exclusion criteria
To be included, citations were required to be published in English and to describe HGS assessment procedures in adult patients awaiting or receiving LT. For this study, we included randomized controlled trials, observational studies, research letters, and case reports. All citations that lacked a description of the HGS assessment in patients awaiting or receiving LT and/or were published in languages other than English were not eligible for inclusion. Abstracts, conference proceedings, editorials, letters to editor, and study protocols were also not suitable for inclusion.

Selection process
Duplicates were removed from the retrieved citations, and the remaining documents were screened for eligibility according to the abstract content. For those articles with abstracts that met the inclusion criteria, the full text was also screened for suitability, and confirmed citations were considered eligible for the final analysis. The studies gathered from the literature were assessed by 3 independent reviewers who evaluated and agreed on the results.

The search process identified 73 citations. After the removal of duplicates, 14 documents were screened for eligibility. Nine articles were included in the final analysis (Figure 1); 3 studies involved LT recipients, 2 were conducted on patients awaiting LT, and 1 included both LT candidates and LT recipients. Seven studies were observational,^22-28 and 2 studies were randomized controlled trials.^29,30 The present review included 487 patients (49% female); 292 (60%) were LT recipients, and 195 (40%) were LT candidates (Table 1). In 5 of 9 studies HGS was measured for the patient’s dominant hand,^{22,24,27,29,30} in 2 studies HGS was measured in both hands,^25,26 and in 2 studies this information was not provided.^23,28 The HGS was measured in 7 studies with a hydraulic dynamometer,^24-30 1 study reported the use of an electric device,²³ and 1 study did not specify the particular device.²²

Handgrip strength in lung transplant candidates
Lung transplant candidates included in this review were all participating in prehabilitation, and HGS measurements were recorded while the candidates were on the wait list. Handgrip strength improved with rehabilitation, although differences were not statistically significant, as shown in (Table 1). The lowest HGS value was detected in a group of female patients who scored 23.5 ± 4.5 kg at 4 weeks after placement on the wait list. Overall, patients with interstitial lung disease (ILD) have greater impairment of HGS versus patients with chronic obstructive pulmonary disease (COPD). The highest HGS values were observed in a cohort of patients who attended a prehabilitation program 3 times each week (90-minute sessions) and demonstrated strength of 36.8 ± 8.3 kg, as shown in (Table 1).

Dyspnea in lung transplant candidates
In patients who attended prehabilitation, dyspnea improvements were accompanied by higher HGS, as shown in (Table 1) and (Table 2). Dyspnea intensity in this cohort was evaluated according to the modified Medical Research Council (mMRC) dyspnea scale; the intensity fell by 0.4 points, although differences before and after rehabilitation were not significant.

In patients who did not attend rehabilitation, dyspnea was evaluated with the Borg scale; intensity was higher in patients with COPD (6.7 ± 2.7 points) versus patients with ILD (6.3 ± 2.1 points).

Respiratory muscle strength in lung transplant candidates
Respiratory muscle strength assessments were lower among patients with COPD (Table 2), although their HGS was 89 ± 18% of predicted. Indeed, patients with ILD had higher respiratory muscle assessments, but HGS was 79 ± 18% of predicted (Table 1). For patients who attended prehabilitation, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were compared between patients with COPD and patients with ILD. The results showed that HGS for patients with COPD seemed to be negatively associated with MIP (74 ± 25%) and MEP (79 ± 29% predicted) versus patients with ILD (MIP 87 ± 23%; MEP 90 ± 25% predicted) ((Table 1) and (Table 2)). This could be explained by respiratory mechanical disadvantage related to hyperinflation observed in advanced cases of COPD. Notably, patients attending prehabilitation had MIP and MEP values >100% of predicted.

Functional performance in lung transplant candidates
The functional performance of patients with COPD versus patients with ILD was assessed with the 6-minute walking test (6-MWT), and patients with ILD performed better at the 6-MWT (334 m) versus patients with COPD (320 m) but had lower HGS (79% vs 89% of predicted).

Handgrip strength in lung transplant recipients
Patients in this review who had undergone LT were not all attending a specific rehabilitation program. The lowest HGS value was detected postoperatively in a group of patients with sarcopenia who scored 14 kg (IQR 11.8-17.3); nonsarcopenic patients who did not attend rehabilitation scored higher (24-30 kg). Furthermore, patients readmitted to the hospital for medical reasons showed lower HGS values versus patients measured postoperatively.

The highest HGS values (37.5 kg) were detected in a cohort of patients who attended 60-minute sessions of a high-intensity interval training program. Handgrip strength substantially improved in a cohort of individuals who attended 90-minute sessions of exercise, reaching 94% of predicted, as shown in (Table 1).

Dyspnea in lung transplant recipients
Dyspnea in LT recipients was evaluated by the mMRC dyspnea scale, and differences detected before and after rehabilitation were not significant. Improvements ranged from 0.2 to 0.9 points (Table 3).

Respiratory muscle strength in lung transplant recipients
Respiratory muscle strength improved substantially in patients whose HGS was >90% of predicted. Signifi-cant increases of 26 and 16 cm H2O were detected in MIP and MEP, respectively ((Table 1) and (Table 3)).

Functional performance in lung transplant recipients
Nonsarcopenic patients walked longer distances at the 6-MWT (>450 m) versus sarcopenic patients (<310 m) and had higher HGS values (>20 kg vs <20 kg, respectively). Overall, patients attending postoperative rehabilitation demonstrated substantial improvement in functional performance (6-MWT: from 303 ± 124 m before rehabilitation to 407 ± 120 m after rehabilitation), which was accompanied by HGS improvement (from 27.1 ± 8.1 kg before rehabilitation to 29.2 ± 7.9 kg after rehabilitation), as shown in (Table 1) and (Table 3).

In some cases, the 1-minute sit-to-stand test was used as an alternative to the 6-MWT. The number of repetitions performed at the 1-minute sit-to-stand test was higher (19.1) in postoperative patients versus medical patients (14.3).

Cutoff values
Handgrip strength reference values may vary according to age, weight, hand side, and sex.^11-14 Nor-mative values can be calculated for both sexes: in men these range from 44.9 ± 7.8 kg (18-24 years) to 27.1 ± 9.4 kg (80-85 years) and in women from 26.6 ± 6.4 kg (18-24 years) to 19.4 ± 4.0 kg (80-85 years).¹¹

From the present review, cutoff values for LT candidates should be distinguished from those who did attend rehabilitation and those who did not. (1) HGS ranged from 27.1 kg (before rehabilitation) to 31.2 kg (after rehabilitation). (2) The highest HGS of 36.8 kg was detected in a cohort of male patients 4 weeks after listing while participating in a prehabilitation program. (3) In LT candidates not attending prehabilitation, HGS ranged from 79% to 89% of predicted (Table1).

To the same extent, cutoff values for LT recipients should be distinguished from those who did attend rehabilitation and those who did not. (1) For LT recipients in rehabilitation, HGS ranged from 21.1 kg (before rehabilitation) to 35.7 kg (after rehabilitation). (2) In LT recipients who did not attend rehabilitation, HGS ranged from 14 to 30.4 kg (Table 1).

Handgrip strength may be used, together with other tools such as the Fried frailty phenotype, cognition and depression assessments, and disease severity assessments, to determine whether frailty is reversible postoperatively in LT recipients who had been considered frail before transplant.³¹ In a previous study conducted among LT patients, in a percentage of those who were considered frail before LT, HGS did not improve despite their participation in both preoperative and postoperative rehabilitation.³¹ On the other hand, the minimal clinically important difference for HGS has been estimated to range from 5 to 6.5 kg.³² From the present review, patients who did attend a rehabilitation program had more chances to improve HGS, although only in a single study²⁶ the minimal clinically important difference was >5 kg. In addition, we also found that HGS was lower in patients with ILD; we speculate this was due to long-term corticosteroid treatment causing peripheral myopathy and the presence of inflam-matory arthritis and connective tissue diseases associated with ILD.^33-36 The present review highlights that HGS can be linked to dyspnea intensity, res-piratory muscle strength, and functional performance in LT recipients or LT candidates. In addition, HGS has been found to be a reliable, inexpensive, and simple tool for detection of physical impairments of rehabilitative interest.

Although the 6-MWT was the most used test to evaluate functional performance, other interesting tests have been used for the same purpose, raising interest in their feasibility. For example, in an observational study conducted among LT recipients, the Biering-Sørensen endurance test was used to evaluate the back extension endurance time.²⁶Patients were positioned in a prone decubitus on an examination bed with iliac crests matching the edge of the bed; they were then asked to take over the load of their trunk gradually and actively and to maintain the position for as long as possible. Handgrip strength was correlated with back strength. There are no other published experiences describing the use of the Biering-Sørensen endurance test in LT.

The MIP and MEP are commonly evaluated in patients with respiratory diseases to drive rehabilitation interventions on respiratory muscles. From the present review, both variables improved, particularly in patients who attended rehabilitation either before or after LT.^25,27,28 Such improvements were accompanied by an increase in HGS.

Ulnar hand sign
Hand muscle weakness may critically impair a patient’s daily routine and can result from peripheral nerve injuries. In this regard, HGS testing is a diagnostic tool for immediate detection of peripheral nerve impairments.

For example, patients with sarcopenia are more likely to develop peripheral nerve injuries evoked by a compressive mechanism, because of the paucity of muscle mass and soft tissues protecting nerves and bones. This eventuality can be more common in limbs, because several conflict points can affect the passage of nerves when the nerves run closest to the skin surface. Particularly during the acute posto-perative phase, peripheral nerve injuries due to compression can result from in-bed mispositioning.³⁷

In (Figure 2), a case of radial nerve damage that resulted in the insufficiency of the carpal extensor muscles during the examination is illustrated. Once the person is asked to execute the test by pinching their fingers (Figure 2A), the hand goes into ulnar flexion (Figure 2B), and the test score is 0 kg. Such insufficiency of the hand extensor muscles can be detected if the person has the elbow flexed at 90 degrees and is sitting during the examination. This specific condition should be defined as the “ulnar hand sign.”

Limitations
Data retrieved from the included studies were heterogeneous; therefore, it is difficult to generalize the results of this review. Nevertheless, our findings in the present study could be a solid basis to define HGS cutoff values in LT recipients or LT candidates.

Furthermore, it was not possible to identify specific HGS values for prediction of rehabilitative outcomes; however, HGS has been found to be linked to dyspnea intensity, respiratory muscle strength, and functional performance.

The limited number of studies included in this review could be perceived as a limitation; however, this scarcity of published data could simply indicate that HGS in LT remains a narrow area of research, as confirmed by other authors.⁷ Although this review included 487 individuals from 9 studies, further research and additional studies should be conducted to define specific HGS cutoff values for LT recipients versus LT candidates.

It is well known that patients arriving at LT should exhibit preserved physical function to reduce postoperative complications related to motor and respiratory outcomes. At the same time, postoperative rehabilitation is a cornerstone of the recovery function. Therefore, HGS should be implemented in both contexts to evaluate physical potential of patients and drive rehabilitative activities toward the most impaired domains.

Volume: 21 Issue: 7 July 2023

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