**Background:** Mechanical ventilation affects respiratory muscles, but long-term recovery of respiratory muscle weakness (RMW) and its association with physical functioning in survivors of critical illness is poorly understood. This study aimed to investigate the course of recovery of RMW and its associations with functional outcomes up to 6 months after hospital discharge.
**Methods:** A prospective cohort study with 6-month follow-up was conducted among survivors of critical illness who received ≥48 hours of invasive mechanical ventilation. Participants were recruited from 2 university and 5 general hospitals in the Amsterdam area (Netherlands) between April 2019 and February 2021. Baseline measurements were obtained within one week after hospital discharge, with follow-up at 3 and 6 months. Primary outcomes were MIP and MEP (measured with microRPM spirometer, converted to % predicted). Secondary outcomes were FEC (two-minute step test) and HGS (Jamar dynamometer, % predicted). Linear mixed model analyses were used to assess longitudinal changes and associations. Pre-identified predictors included ICU length of stay (LOS), mechanical ventilation (MV) days, hospital LOS, and age.
**Key Results:** 59 participants were included (64% male, median age 62 [IQR 53–66], median ICU LOS 11 days [IQR 8–21], median hospital LOS 35 days [IQR 21–52], median MV duration 10 days [IQR 4–18]). At hospital discharge, all measures were well below predicted: MIP 68.4% (95% CI 61.2–75.7), MEP 76.0% (95% CI 68.5–83.5), HGS 73.3% (95% CI 66.4–80.2), and FEC 54.8 steps/2min (95% CI 47.1–62.5). Significant recovery occurred by 6 months: MIP 98.7% (95% CI 91.4–106.0), MEP 105.5% (95% CI 97.9–113.0), HGS 104.7% (95% CI 97.7–111.6), and FEC 87.0 steps (95% CI 79.2–94.7). The change from T0 to T1 was significant for all outcomes (p<0.001 for MIP, MEP, FEC, HGS). From T1 to T2, MIP (Δ 7.3, p=0.003), FEC (Δ 7.0, p=0.029), and HGS (Δ 10.8, p<0.001) continued to improve significantly, while MEP did not (Δ 4.6, p=0.103). Older age was associated with decreased MIP (β -0.6, p=0.02) and FEC (β -1.03, p<0.001). Longer hospital LOS was associated with decreased HGS (β -0.5, p<0.001). MV days were associated with decreased HGS in both univariate and multivariate models (β -0.8, p=0.001). Significant longitudinal associations were found between MIP/MEP and FEC and HGS in crude models. After adjustment for age and time, associations remained significant for PEmax and FEC in the total sample, but an interaction effect for sex was observed. Stratified analyses showed significant associations in males but not in females for several adjusted models. 83% of participants were classified as having undernutrition at baseline (SNAQ65+). Sensitivity analyses showed no significant differences in outcomes between participants receiving the REACH program versus usual care.
**Clinical Implications:** This is the first study to present longitudinal data on recovery of MIP and MEP up to 6 months after hospital discharge in mechanically ventilated ICU survivors. RMW was present at discharge, with MIP recovering more slowly than MEP. The significant associations between respiratory muscle strength and both exercise capacity and handgrip strength suggest that RMW contributes to overall physical deconditioning. The findings support continued assessment of MIP/MEP in deconditioned post-ICU patients and suggest that targeted respiratory muscle training beyond ICU and hospital discharge warrants further investigation, particularly given that most participants (83%) were undernourished at baseline and that older age and longer hospital LOS predicted worse recovery.