Clinical impact of preoperative diaphragm dysfunction on early outcomes and ventilation function in lung transplant: a single-center retrospective study

Baseline characteristics

During the study periods, 120 patients have received lung transplantation at our center. A total of 102 patients were included in this study except for 18 patients without preoperative diaphragm sonographic results (Fig. 1). Of these, 32.4% (33/102) had preoperative DD, and 57.6% (19/33) had a unilateral DD. DD was detected in 24 patients (72.7%) on the right side and in 23 patients (69.7%) on the left side. The baseline characteristics according to preoperative DD are presented in Table 1. The baseline characteristics were not different between the two groups except for mechanical ventilator duration before LT (11 vs. 1 day, p = 0.004) and right heart dysfunction (33.3% vs. 10.1%, p = 0.004). The median diaphragm excursion during tidal breathing was significantly lower in the DD group than that in the non-DD group (right, 0.8 vs. 2 cm, p < 0.001; left, 0.5 vs. 2 cm, p < 0.001). The median diaphragm excursion with forced breathing was also significantly lower in the DD group than that in the non-DD group (right, 1.2 vs. 3.3 cm, p < 0.001; left, 1.5 vs. 3.5 cm, p < 0.001). The TFdi of the right side and left side were also significantly lower in the DD group (right 24 vs. 100%, p = 0.001; left 26 vs. 96.5%, p = 0.006).

Fig. 1figure 1

Patient enrollment. DD diaphragm dysfunction. In total, 32.4% of patients showed preoperative DD. Of those, 54.5% recovered diaphragm function 3 months after transplantation

Table 1 Clinical characteristics according to pre-operative diaphragm dysfunctionClinical outcomes

The clinical outcomes of the two groups are shown in Table 2. There was no significant difference in hospital mortality between the two groups. However, the ratio of prolonged mechanical ventilation was significantly higher in the DD group (36.4% vs. 17.4%, p = 0.035). The duration of ventilator use in the post-transplantation period was significantly higher in the DD group (15 vs. 6.5 days, p = 0.003). The lengths of intensive care unit (ICU) stays and hospital stays were significantly higher in the DD group (ICU stays, 20 vs. 11.5 days, p = 0.016; hospital stays, 86 vs. 50.5 days, p = 0.001).

Table 2 Clinical outcomesPreoperative factors associated with prolonged mechanical ventilation after transplant

Univariate regression analysis results are shown in Table 3. In the multivariate regression analysis, pre-operative DD was significantly associated with prolonged mechanical ventilation after transplant (odds ratio 2.79, 95% confidence interval 1.07–7.32, p = 0.037).

Table 3 Multivariate regression analysis for prolonged mechanical ventilation after lung transplantComparison of GI index values between the two groups

EIT was conducted in 58 patients 1 week after LT. The median GI index value was significantly higher in the DD group (0.6 [0.5–0.7] vs. 0.5 [0.4–0.5], p < 0.001, Fig. 2). In other words, the inhomogeneity of ventilation was significantly higher in the DD group.

Fig. 2figure 2

Global inhomogeneity index according to the diaphragm dysfunction. Data are presented as medians (interquartile range). DD, diaphragm dysfunction; *** p < 0.001. Electrical impedance tomography was performed in 58 patients 1 week after transplantation. The global inhomogeneity index was significantly higher in the DD group (0.5 vs. 0.6, p < 0.001)

Lung volume assessment and serial changes determined using 3D-CT volumetry and spirometry

The total lung volume in 3D-CT volumetry was significantly lower in the DD group than that in the non-DD group (1 week, 1.7 vs. 2.5 L, p = 0.002; 3 months, 2.0 vs. 3.0 L, p = 0.018, Table 2). In addition, there were significant differences in each segment’s lung volume between the two groups (Fig. 3). The FVC at 1 and 3 months after LT was significantly lower in the pre-operative DD group, respectively (1 month, 44.2% vs. 53.1%, p = 0.045, 3 months, 55.7% vs. 65.2%, = 0.041).

Fig. 3figure 3

Each lung volume segment acquired using three-dimensional computed tomography volumetry 1 week and 3 months after transplant. *p < 0.05, **p < 0.01,***p < 0.001. The data show the lung volume (L) of each segment. There were significant differences in each segment’s lung volume at 1 week and 3 months between the two groups. DD diaphragm dysfunction

In both groups, the total lung volume was significantly increased from 1 week to 3 months (DD, 1.9 vs. 2.2 L, p < 0.001; DD (−), 2.6 vs. 3.0 L, p < 0.001, Fig. 4A). The serial change in total lung volume between the two periods tended to be lower in the DD group (0.2 vs. 0.4 L, p = 0.074).

Fig. 4figure 4

Paired t test for total lung volume and forced vital capacity (FVC). A Paired t test for total lung volume using three-dimensional computed tomography (3D-CT) volumetry. The total lung volume determined by 3D-CT volumetry was significantly increased from 1 week to 3 months in both groups regardless of preoperative DD (patients with preoperative DD, p < 0.001; patients without preoperative DD, p < 0.001). B Paired t test for FVC using spirometry FVC significantly increased from 1 to 3 months in both groups regardless of preoperative DD (patients with preoperative DD, p < 0.001; patients without preoperative DD, p < 0.001). ***p < 0.001. DD diaphragm dysfunction

In both groups, the FVC was significantly increased from 1 to 3 months regardless of the presence of DD (DD, 1.7 vs. 2.1 L, p < 0.001; DD (−), 2.2 vs. 2.7 L, p < 0.001, Fig. 4B). There was no significant difference in the serial change of FVC between the two groups (0.3 vs. 0.4 L, p = 0.448).

Natural course of pre-operative DD

In the group with preoperative DD, 54.5% (18/33) recovered diaphragm function at 3 months after transplantation, and the other 45.5% (15/33) showed DD at 3 months after transplantation (Fig. 1). Among those, 12 patients showed DD in the same site as before surgery, and the remaining 3 patients had newly developed DD in the other site after surgery (Additional file 1). In patients without preoperative DD, six (8.7%) showed postoperative DD. Seven patients showed persistent DD after 1 year of LT.

The clinical outcomes were significantly different between two groups according to diaphragm function at 3 months (Table 4). The mortality rate of patients with unimproved DD at 3 months was significantly higher than patients with improved DD (p = 0.001). Although the FVC were not different between two groups, total lung volume of 3D CT volumetry were significantly different between two groups.

Table 4 Clinical outcomes of patients with pre-operative diaphragm dysfunction according to diaphragm recovery at 3 monthsRegression analysis between pre-operative DD and clinical factors

In the univariate regression analysis, regarding preoperative clinical factors, ventilator duration (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01–1.07, p = 0.015), ICU duration (OR 1.03, 95% CI 1.01–1.05, p = 0.012) and right heart failure (OR 4.43, 95% CI 1.53–12.85, p = 0.006) were significantly associated with preoperative DD. In the multivariate regression analysis, ICU duration (OR 1.02, 95% CI 1.00–1.04, p = 0.018) and right heart failure (OR 4.86, 95% CI 1.56–15.15, p = 0.006) were significantly associated with preoperative DD.

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