A total of 47 patients were enrolled. Patient characteristics and demographics are shown in Table 1; no statistically significant differences were found between the two groups.
Table 1
Demographic and clinical data.
| Overall n = 47 | DD n = 20 | noDD n = 27 | p |
Age, years mean ± SD | 65.5 ± 14.8 | 64.5 ± 15.3 | 66.2 ± 14.8 | 0.7 |
Gender, male % | 57.4 | 55 | 59.3 | 1 |
BMI, kg/m2 mean ± SD | 26.9 ± 3.7 | 26.6 ± 3.9 | 27.1 ± 3.7 | 0.7 |
Patient type (%): Surgical a) OLTx or hepatectomy (14.9%) b) Other (23.4%) Medical a) Heart failure (8.5%) b) Pneumonia (23.4%) c) Other (29.8%) | 38.3 61.7 | 55 45 | 25.9 74.1 | 0.068 |
Comorbidity (%): HTNa DM type II Liver cirrhosis Kidney failure Oncologic Ischemic heart disease Atrial fibrillation Hematological COPD | 42.6 31.9 17.0 29.8 19.1 14.9 12.8 12.8 10.6 | | | |
SAPS II mean ± SD | 44.0 ± 12.3 | 40.9 ± 8.1 | 46.5 ± 14.6 | 0.14 |
LEGEND: BMI, body mass index; OLTx, orthotopic liver transplantation; HTNa, arterial hypertension; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; DD, patients with diaphragm dysfunction; noDD, patients without diaphragm dysfunction. |
Post-surgical patients accounted for 38%, and the majority of them underwent hepatic surgery or orthotopic liver transplant (OLTx). The most common comorbidities were arterial hypertension (43%), type 2 diabetes mellitus (32%) and renal failure (30%).
Diaphragm dysfunction
The prevalence of DD in our patient population was 42.5% (95% CI 28,3–57,8). There were no differences in age, sex, BMI, SAPS II score (see Table 1), initial PaO2/FiO2 ratio (p = 0.98) or respiratory rate (p = 0.13) in patients with vs without DD.
Nearly 61% (95% CI 35,7–82,7) of post-surgical patients presented DD compared with 31% (CI 15,3–50,8) of medical patients. Post-surgical patients showed a higher prevalence of diaphragmatic dysfunction than medical patients, with a relative risk of 1.97 (CI 1.022–3.794, p = 0.0429).
Effect of non-invasive ventilation
NIV was generally well tolerated and efficacious, with a mean improvement in the PaO2/FiO2 ratio of 64 ± 7 points (95% CI 42,97 − 85,20, p < 0.001; Fig. 1) and a decrease of 1.5 ± 5.5 in respiratory rate (95% CI -3,153–0,08887, p = 0.06). Tins did not significantly change from before to during NIV, while Tesp increased by 0.15 sec (95% CI 0,04 − 0,26, p = 0.007), together with total respiration time, which increased by 0.23 sec (95% CI 0,08 to 0,37, p = 0.002) - see Table 2. In our study, diaphragm excursion proved to be significantly increased during NIV (+ 0.2 cm, p = 0.001) due to mechanical pressure support, as expected (Table 2).
Table 2
Oxygenation and ultrasonographic assessment of the diaphragmatic function before and after one hour of NIV.
| T0 pre-NIV | T1 intra-NIV | mean of differences (95% CI) | p |
PaO2/FiO2, | 175 ± 65 | 239 ± 78 | 64.1 42.9–85.2 | < 0.001 |
DE (cm) | 1.511 ± 0.746 | 1.714 ± 0.945 | 0.203 0.080–0.327 | 0.001 |
RR (per minute) | 21.3 ± 6.4 | 19.7 ± 6.4 | -1.5 -3.15–0.01 | 0.06 |
Tins (sec) | 0.836 ± 0.258 | 0.879 ± 0.323 | 0.033 -0.029–0.096 | 0.29 |
Texp (sec) | 0.820 ± 0.473 | 1.027 ± 0.602 | 0.151 0.041–0.262 | 0.007 |
Ttot (sec) | 1,64 ± 0.61 | 1,906 ± 0.820 | 0,227 0.083–0.370 | 0.002 |
LEGEND: DE, diaphragm excursion; RR, respiratory rate; Tins, inspiratory time; Texp, expiration time; Ttot, respiratory cycle total time. All values expressed as mean ± SD. |
NIV treatment failed in 34% of patients (NIV non-responder, 95% CI 20,8–49,3). NIV-responder patients started with lower initial PaO2/FiO2 values and, on US diaphragm examination, showed longer respiratory times (both Tins and Tesp) before NIV. There was no significant difference in age, sex, BMI, respiratory frequency, or peak pressures during NIV (Table 3).
Table 3
NIV non-responder and NIV responder data before starting NIV trial.
T0 (pre-NIV) | NIV non-responder | NIV responder | p |
PaO2/FiO2 | 215,4 ± 69,38 | 155,1 ± 53,65 | 0,002 |
RR (per minute) | 21,44 ± 5,85 | 21,19 ± 6,77 | 0,903 |
Tins (sec) | 0,751 ± 0,2086 | 0,8657 ± 0,2557 | 0,039 |
Tesp (sec) | 0,6382 ± 0,2889 | 0,912 ± 0,5216 | 0,01 |
Ttot (sec) | 1,389 ± 0,4382 | 1,778 ± 0,6408 | 0,004 |
Pmax (cmH2O) | 11,75 ± 2,295 | 13,35 ± 2,727 | 0,0502 |
Age (ys) | 64,63 ± 14,38 | 65,9 ± 15,34 | 0,783 |
BMI (kg/m2) | 26,4 ± 4,545 | 27,12 ± 3,312 | 0,54 |
LEGEND: RR, respiratory rate; Tins, inspiratory time; Texp, expiration time; Ttot, respiratory cycle total time; Pmax, maximal inspiratory pressure; BMI, body mass index. All values expressed as mean ± SD. |
Post-surgical patients responded to NIV in 55% of cases, while medical patients had a benefit in 72% of cases, but this difference did not reach statistical significance (p = 0.34).
Diaphragmatic dysfunction and NIV failure
The mean T0 diaphragm excursion was slightly larger in NIV-responder patients (mean DE 1.35 ± 0.78 cm) compared to non-responders (mean DE 1.21 ± 0.85 cm), but this difference was not statistically significant (p = 0.6).
Patients without DD responded positively to the NIV trial in 70.4% (95% CI 49.8–86.2%), while patients with DD responded positively to NIV in 60% (95% CI 36.0–80.9%) of cases (p = 0.54). The degree of respiratory support provided by the ventilator was similar in the two groups: the mean pressure support was 6.59 ± 2.02 cmH2O in patients without DD and 7.70 ± 2.20 cmH2O in patients with DD (p = 0.08), while the mean PEEP was 5.85 ± 1.10 cmH2O and 5.60 ± 1.39 cmH2O, respectively (p = 0.49).
Given the above differences, assuming the use of ultrasound diaphragm excursion as a potential predictor of NIV response, the corresponding ROC curve (Fig. 2) had an area under the curve (AUC-ROC) of 0.53 (95% CI 0,382–0,680) (p = 0.7227). The best balance between sensitivity (58.1%) and specificity (62.5%) was obtained with a DE cut-off of 1.37 cm (Youden index J of 0.206).
We then evaluated the predictive capacity of the slope of the curve (cm/s), as its measurement should correspond to the speed (strength) of the diaphragm contraction. There were no significant differences between responders and non-responders (1.919 ± 0.9139 vs 2.154 ± 1.511, respectively, p = 0.695). The AUC-ROC was 0.505 (95% CI 0,395 to 0,614, p = 0,947). With a cut-off of 1.64 cm/s, the sensitivity was 56.2%, and the specificity was 29.6% (Youden Index J 0.18).
Outcome
The mean length of stay in the ICU was shorter in patients with normal diaphragm function (11 ± 9 days), compared to patients with DD (14 ± 13 days), but this difference did not reach statistical significance (p = 0.297). See Fig. 3A.
After 100 days of follow-up, mortality in patients with diaphragm dysfunction was 40% (95% CI 19.1–63.9), while in patients with normal diaphragmatic function, it was 27% (95% CI 11.6–47.8), p = 0.527 (see Fig. 3B).