Patients admitted to the Intensive Care Unit (ICU) are exposed to prolonged periods in bed and to different factors that directly or indirectly affect the muscle and organ structures, which may result in ICU-acquired weakness (ICU-AW)1,2 and functional limitation.3

The aforementioned factors are of a metabolic, pharmacological and organic nature, including particularly sustained hyperglycemia, corticosteroid use, sedoanalgesia, neuromuscular block and multiorgan failure associated with sepsis or septic shock.4 This situation in turn results in direct loss of muscle mass (specifically type II fibers), which is explained by increased myosin protein degradation, decreased protein synthesis and increased proinflammatory cell activity, which favor weakness in the critically ill patient.4

According to Brower et al.,5 the effects of prolonged resting periods include muscle atrophy and deconditioning. After 14 days of immobilization, young individuals and adults suffer a quadriceps muscle loss of 9%, with a resulting loss of muscle strength of up to 27%.6,7 In individuals subjected to invasive mechanical ventilation (IMV), it has been seen that the cross-sectional area of the quadriceps muscle can decrease by up to 12.5% in the first week of ICU stay. This figure, in turn, can reach 15.7% in the presence of multiorgan failure, versus 3% in the presence of single-organ failure.8

Both ICU-AW and functional loss are also directly related to prolonged sedoanalgesia, neuromuscular block and an increased incidence of delirium in the ICU.9 The presence of delirium is associated with low participation in physical therapy due to poor cooperation and/or psychomotor agitation; as a result, it directly impacts upon muscle condition and posterior functional recovery.9

Brummel et al.10 reported that delirium is common in the ICU, affecting 60–80% of all patients subjected to IMV, and 20–50% of those subjected to noninvasive mechanical ventilation (NIMV). It increases the risk of tearing out invasive devices, accidental extubation, and the need for physical restraints that can cause delays in the start of functional recovery.27,28

In order to assess the consequences of prolonged resting periods and quantify ICU-AW, use is made of the Medical Research Council (MRC) score. This validated tool bilaterally measures the strength of 6 muscle groups with a score of 30 points per side of the body, yielding a total score of 60 points. A score of ≤ 48 points indicates the presence of ICU-AW.11,29

On the other hand, in order to assess functionality in the critically ill, use is commonly made of the validated Functional Status Scale – Intensive Care Unit (FSS-ICU), which scores functional performance from 0 to 35 points.12

The present study was carried out to compare the efficacy of the “Start to move” protocol versus conventional treatment in subjects over 15 years of age admitted to the ICU in terms of improvement of functionality, decreased ICU-AW, incidence of delirium, days of mechanical ventilation (MV), length of ICU stay, and mortality at 28 days.

The study included 69 subjects out of a calculated sample of 134 individuals. None of the patients abandoned or rejected participation in the study, and none were eliminated due to failure to meet the established criteria. Thirty-three subjects were allotted to the “Start to move” group (47%) and 36 to the conventional treatment group (52%). There were no significant differences in the sociodemographic or clinical characteristics between the two groups. The mean age of the “Start to move” group was 60 years, with an APACHE II score of 22 points (41% mortality) and a Charlson Index of 3 points (77% survival at 10 years (Table 1).

The incidence of ICU-AW at discharge in the conventional treatment group was 80.7% (95%CI 62.5–92.6) versus 35.7% in the “Start to move” group (95%CI 18.6–55.9) (p=0.001), with OR=0.44 (95%CI 0.26−0.75) (p<0.001). The difference in the MRC score at awakening versus the MRC score at discharge was 4 points (range 2–6) in the conventional treatment group and 10 points (range 8–15) in the “Start to move” group (p<0.001).

The functionality score as assessed with the FSS-ICU at discharge from the ICU was 17 points in the conventional treatment group (95%CI 12–23) versus 26 points in the “Start to move” group (95%CI 18–31; p=0.001). The absolute difference in FSS-ICU score between awakening and discharge was 4 points in the conventional treatment group (95%CI 1–6) and 9 points in the “Start to move” group (95%CI 7–11) (p<0.001).

Functional independence as evidenced by the percentage difference in the Barthel Index was 60% in the conventional treatment group (range −70 to −40) versus 40% in the “Start to move” group (−52.5 to −34.2) (p=0.006)(Table 2).

There were no significant differences between the two groups in terms of the incidence of delirium, days of IMV, days of ICU stay, or mortality at 28 days (Table 3).

The results of the present study evidence a significant decrease in the incidence of ICU-AW in the “Start to move” group, with a difference of 45% versus the conventional treatment group at discharge from the ICU. This is consistent with the data reported in the literature for ICUs of similar characteristics.18–20,30–33 The gain in strength between awakening and discharge from the Unit was 10 points in the “Start to move” group, with a difference of 6 points versus the conventional treatment group. This is in agreement with the results of Kayambu et al.,21 who reported a difference of 4.6 points between groups, and with those of Zang et al.,22 who reported a difference of 4.5 points on the MRC scale. However, the high ICU-AW rate observed in the conventional treatment group could be influenced by the small sample size, and should be corroborated by studies involving larger samples.

Our results indicate an increase in functionality at discharge in the “Start to move” group, with an absolute difference of 9 points versus the conventional treatment group. At present, no FSS-ICU classifying scores for determining the degree of functionality loss or gain are available for comparison against our findings. There is little evidence of the comparison of such results in ICUs of similar characteristics.

In relation to the Barthel Index, the “Start to move” group showed a 20% lesser decrease in functionality versus the conventional treatment group (60% versus 40%; p=0.006). Our data in this regard are similar to those reported by Symeonidou et al.,23 with a percentage difference of 48%. However, several studies show no significant differences in the Barthel Index scores.17,22 These results therefore could be indicative of improved performance of activities of daily living at discharge from the Unit.

On the other hand, the incidence of delirium in the “Start to move” group was 20% lower than in the conventional treatment group – though the difference failed to reach statistical significance. It should be noted, however, that the study sample for this outcome was too small to secure acceptable statistical power, thus underestimating the capacity of the test to detect significant differences between groups when such differences are present. Studies involving larger sample sizes are thus needed to assess such differences more in-depth.

With regard to the days of IMV, both groups presented a mean duration of 8 days and an absolute difference between them of 0 days (p=ns). Recent studies such as that of Zhang et al.24 have reported similar results, with an absolute difference of −0.33 days of MV (p=ns).24 However, it must be noted that the “Start to move” protocol involves a motor rehabilitation approach that does not necessarily have a direct impact on respiratory rehabilitation with the improvement of this outcome. Further studies are thus advised, with combined therapies involving respiratory muscle strengthening.

In both groups, the mean duration of ICU stay was 9 days, with an absolute difference of 0 days, in line with the results of Morris et al.25 and Kayambu et al.,21 who documented a nonsignificant absolute difference of 0.5 days (p=0.68 and p=0.43, respectively).

The mortality rate at 28 days after admission to the ICU was slightly lower in the “Start to move” group (15.2% versus 16.7%; p=ns). Recent studies such as those of Schwickert et al.,17 Kayambu et al.21 and Zang et al.22 have evaluated mortality in different periods, with differences favorable to the treatment group, but without reaching statistical significance.

Neither of the groups in our study experienced adverse events related to kinesic therapy; this is consistent with the findings published by Morris et al.25

Our study has limitations. In effect, the established sample size was not reached due to administrative issues at our center. However, the necessary post hoc statistical power adjustments were made. In turn, this was a single-center study without the admission of patients from an emergency service. Further studies are needed to address and incorporate these points. As regards the strengths of the trial, it is the only local study involving randomized patients that has been able to evidence potent physical and functional outcomes in the ICU setting.

The application of the “Start to move” protocol for early rehabilitation in the ICU was associated with increased patient functionality as assessed by the FSS-ICU, a lesser incidence of ICU-AW, and greater functional independence as evidenced by the Barthel Index at discharge from the ICU. The “Start to move” protocol was not found to be useful in reducing delirium, the days of MV, the duration of ICU stay or mortality at 28 days. Application of the protocol was safe, with no adverse events being reported in either treatment group.

Sebastián Soto: Study conception, data acquisition, drafting of the manuscript.

Paulina Vivanco: Data analysis and interpretation, drafting of the manuscript.

Rodrigo Adasme: Study design, data analysis and interpretation, final approval of the manuscript.

Paola Figueroa: Final approval of the manuscript.

None.

The authors declare that they have no conflicts of interest.