This systematic review included 17 randomised controlled trials of inspiratory muscle training and early mobilisation. The meta-analyses show that early mobilisation can reduce the duration of mechanical ventilation and the ICU length of stay. On the basis of a single study, we found no effect of early mobilisation on the weaning time. Early mobilisation also had no effect on mortality or hospital length of stay. The analyses revealed no effect of inspiratory muscle training on duration of mechanical ventilation or ventilator weaning, or on hospital mortality.
The evidence base for analysing the effects of inspiratory muscle training was small, and the results must be interpreted with caution. Few adverse events were described in association with the use of early mobilisation or inspiratory muscle training, and only two serious adverse events were reported.
We found that early mobilisation reduced the duration of mechanical ventilation by an average of 1.5 days compared with standard treatment. Connolly et al. also reported a positive effect of early mobilisation on the duration of mechanical ventilation in their review of systematic reviews
(32). We found no effect of inspiratory muscle training on the same outcome measure. Reducing the duration of mechanical ventilation is a stated aim of the Norwegian Intensive Care Registry in their annual report from 2019 (1). Shorter ventilation time is likely to lead to fewer complications, as well as increased capacity and reduced costs for ICUs.
We were unable to identify any studies with a low risk of bias that had examined the effect of early mobilisation on weaning time, and we found only one study that had examined the effect of inspiratory muscle training on this outcome measure. In systematic reviews, Vorona et al. found an effect of inspiratory muscle training on weaning time
(33), while Elkins et al. found that it increased the proportion of successful weaning attempts (34). Weaning time from mechanical ventilation depends on several factors, including the criteria used to confirm the patient as ready for weaning, as well as the manner in which the weaning is performed (34).
Our analyses showed no effect on mortality of either early mobilisation or inspiratory muscle training. Two previous systematic reviews comparing early mobilisation with standard treatment also found no differences in mortality between the groups
Early mobilisation reduced the length of ICU stays by about one day, but we were unable to demonstrate an effect on the total length of stay in hospital. Kayambu et al. found an effect on length of stay both in the ICU and in hospital
(36). Shorter stays in the ICU will, like a shorter duration of mechanical ventilation, lead to fewer complications for patients and potentially give rise to increased capacity and reduced costs for hospitals.
We found few adverse events. They were reported in only 1.4 % of all mobilisation sessions across the studies. A previous systematic review and meta-analysis found that adverse events occurred in 2.6 % of mobilisation sessions, with negative consequences for the patient in 0.6 % of cases
(37). No adverse events were reported in the studies of inspiratory muscle training. Allowance must be made for the possibility that some adverse events went unreported. Another challenge is that adverse events were defined differently across the studies, and in some studies they were not predefined (11). However, primary research studies have shown that early mobilisation in the ICU is safe and feasible (37, 38).
Our analysis has certain methodological limitations. The treatments used in the studies of early mobilisation varied across both the intervention and the control groups, and were poorly described for the control groups in several studies. These factors may have affected the results, which may have become more heterogeneous. We performed subgroup analyses in an attempt to group together studies that were more similar to one another, but found no significant differences between the groups. A known problem in intensive care research, where there is relatively high early mortality is that it can be difficult to obtain good follow-up data. This may have confounded the outcome measures in the current review
Blinding was performed in only two of the studies included in the meta-analyses
(21, 23). It is difficult to blind participants and personnel to the interventions featured in this study. We scored the lack of blinding as high risk, but did not deduct for it when deciding the GRADE rating, because we do not believe it affected the results. In their meta-epidemiological review of 146 meta-analyses, Wood et al. found little evidence to suggest that lack of blinding leads to exaggerated intervention effect estimates when objective outcome measures are used (40).
We reported hard outcome measures that say nothing about quality of life, self-reliance and other patient-reported outcomes. Such outcome measures are clinically relevant and are of great importance to patients and their families. Tipping et al. found that intensive early mobilisation was associated with increased quality of life after six months
Our systematic review and meta-analysis have a number of strengths. We conducted a thorough, systematic literature search. Study selection, data extraction and quality assessment were performed by two authors independently, thereby increasing the quality of the work. The quality of the studies themselves is also relatively high, as we excluded all those with a high risk of bias.
Our findings have clinical implications in that they suggest that mechanically ventilated adults in the ICU should undergo early mobilisation. Studies have shown that this is safe and feasible
(38, 41). However, there are a number of perceived barriers to early mobilisation in the ICU (42), and point-prevalence studies have shown that early mobilisation of ICU patients is rarely performed in practice (43, 44). In a study of mobilisation practices in the ICU at Stavanger University Hospital, Øvrebø found that patients were first mobilised after an average of eight days of mechanical ventilation. Five days passed on average from the point at which the patients were ready for mobilisation until they were first mobilised. On day shifts, 40 % of ventilated patients who were ready for mobilisation were in fact mobilised, and only 21 % on evening shifts. This study reveals a need in Norway, too, for quality assurance work with regard to early mobilisation of ICU patients receiving mechanical ventilation (45).
All the interventions in our meta-analyses are currently the subject of ongoing studies. It will be particularly interesting to see the results of studies of in-bed cycle ergometry, as most studies to date have focused solely on the safety and feasibility of this type of mobilisation.
This systematic review and meta-analysis show that early mobilisation of mechanically ventilated adult ICU patients probably shortens the duration of mechanical ventilation and the ICU length of stay. Early mobilisation and inspiratory muscle training probably have no effect on mortality. Inspiratory muscle training may have little or no effect on the duration of mechanical ventilation or weaning time. Relatively few studies have examined inspiratory muscle training to date, however, and further studies are required. Additional studies should be conducted on long-term patient-reported outcome measures, and studies will hopefully provide more information about the effects of in-bed cycle ergometry.