Results
Patient Characteristics
During the study period, 2,370 patients were hospitalized in the five ICUs. Among them, 745 were not ventilated and 891 were considered to be ventilated for less than 48 hours. Of the 734 ventilated patients, 382 had to be discarded because they did not meet the inclusion criteria (Fig. 1). Thus, 352 patients were randomized, 170 in group 1 and 182 in group 2. Two patients were early tracheotomized within 24 hours, one in each group, and 39 were extubated within 48 hours, 17 in group 1 and 22 in group 2. All 352 patients were analyzed in an "intention-to-treat" approach. Patients' characteristics are given in Table 1. No differences were observed with respect to age, sex, comorbidities as assessed by Charlson score, type of patients, cause of admission, SAPS III score, and SOFA score at admission. Almost two thirds of the patients received antibiotics the day of TIET insertion: 111 in group 1 (65.3%) and 125 in group 2 (68.7%) (p = 0.57). Distributions of patients according to the site of intubation were also comparable in both groups. Characteristics of patients regarding ventilatory support are given in Table 2. No difference was observed between the two groups. Nonetheless, for patients who were ventilated before intubation with TIET (21 in each group), the duration of prior ventilation was longer in group 2 (median, 4; IQR, 2–5 d) than in group 1 (median, 2; IQR, 1–2 d) (p = 0.017). Overall, patients were ventilated in the ICU for a median duration of 8 days in both groups, while the median ventilation duration with TIET was 7 days (IQR, 4–12) in both groups, whence representing 80% of all VDs (3,172 out of 3,969 VD).
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Figure 1.
Flow chart of patients admitted to the ICUs between January 2012 and March 2013.
Primary Endpoint
During ventilation with TIET, pneumonia developed within 48 hours in 16 patients, eight in both groups. After 48 hours of ventilation, VAP was suspected in 27 and confirmed in 15 patients (8.8%) of group 1 and suspected in 41 and confirmed in 32 patients (17.6%) of group 2 (p = 0.018). Thus, use of subglottic secretion suctioning resulted in an event reduction of 8.8%, indicating that nine VAP could be avoided for every 100 patients ventilated with TIET. When considering VAP occurrence with respect to TIET ventilation days, rates were significantly lower in the experimental than in the control group (9.6 of 1,000 VD vs 19.8 of 1,000 VD; p = 0.0076). Logistic regression analysis applied to VAP data confirmed the protective role of suctioning (OR = 0.45; 95% CI, 0.24–0.87) and showed that none of the potentially confounding covariates (e.g., ventilation duration prior to TIET intubation or duration of TIET ventilation) impacted the significant effect of suctioning. These findings were further emphasized when analyzing time-to-VAP data by Cox PH regression analysis (HR = 0.46; 95% CI, 0.25–0.85) as evidenced in Figure 2.
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Figure 2.
Cumulative rates of patients remaining free of ventilator-associated pneumonia (VAP) in group 1 with subglottic suctioning and control group (group 2) using the Kaplan-Meier method. HR = hazard ratio.
All suspected cases of VAP were reviewed by the infectious disease specialist. Considering other possible diagnoses involved in the clinical picture, he eventually diagnosed VAP in 33 cases: eight (4.7%) in the experimental group and 25 (13.7%) in the control group (p = 0.0055). The corresponding OR and HR were equal to 0.31 (95% CI, 0.14–0.71) and 0.29 (95% CI, 0.13–0.65), respectively, whence strengthening the preventive effect of subglottic secretion suctioning.
VAP occurrence increased with ventilation duration and ICU length of stay but was not related to mortality. Specifically, ventilation duration was 15 days (IQR, 10–24 d) in patients developing a VAP and 7 days (IQR, 4–12 d) in the others (p < 0.0001), while ICU length of stay in the two groups was 19 days (IQR, 13–30 d) and 11 days (IQR, 7–18 d), respectively (p < 0.0001). By contrast, hospital mortality was 53.2% for VAP patients and 48.0% for non-VAP patients (p = 0.53). For the entire ICU stay, pneumonia was treated in 37 patients (21.8%) of group 1 and in 54 patients (29.7%) of group 2 (p = 0.11). As seen in Figure 1, 352 other patients were ventilated with conventional tubes during the study period and were not randomized. These patients were actually ventilated during a total of 3,174 days and among them 59 (16.8%) developed a VAP, yielding a prevalence rate of 18.6 of 1,000 VD close to that of group 2.
Secondary Endpoints
VAC and IVAC. Five patients were treated by extracorporeal membrane oxygenation, 2 in group 1 and 3 in group 2 and were not incorporated in the VAC prevalence estimation. During ventilation with TIET, VAC occurred in 78 patients, 37 (22%) in the experimental group and 41 (22.9%) in the control group (p = 0.84). The VAC prevalence rate was also comparable in the two groups (24.9 of 1,000 VD vs 27.2 of 1,000 VD; p = 0.56). IVAC was recognized in 34 patients, 14 (8.2%) in group 1 and 20 (11%) in group 2 (p = 0.47). Among VAC cases, 25 (32%) were associated with the diagnosis of VAP, of which 24 were IVAC, hence representing 68.6% of IVAC patients. Thus, among the 47 patients with VAP, only 25 experienced VAC (58.2%) and 24 IVAC (51%). These percentages, however, were significantly higher (p < 0.0001) than those observed in the 305 patients free of VAP: 53 (17.4%) VAC and 11 (3.6%) IVAC. The 24 VAP patients with IVAC had the same distribution as all VAP together, eight being observed in the experimental group and 16 in the control. This difference however was not significant (p = 0.14). The length of ICU stay was significantly higher in patients with VAC (median, 20 d; IQR, 14–27 d) than in patients without VAC (median, 11 d; IQR, 7–17 d) (p < 0.0001). The duration of ventilatory support with TIET was also different (median, 14 d; IQR, 9–20 d vs median, 6 d; IQR, 4–10 d; p < 0.0001). There were 46 (59%) hospital deaths among the 78 VAC patients and 75 (32.9%) among the 228 patients without VAC (p < 0.0001).
Antibiotic Consumption. For the entire ICU stay, antibiotherapy was given during a median of 7 days (IQR, 3–14 d) in group 1 and 8 days (IQR, 5–13 d) in group 2 (p = 0.45). The total number of antibiotic days in group 1 was 1,696, representing 61.6% of the 2,754 ICU days, and in group 2 it was 1,965, representing 68.5% of the 2,868 ICU days (p < 0.0001). When restricting duration to TIET ventilation, the difference between the two groups was also significant: 1,064 days (68.3% of the 1,558 VD) in the experimental group and 1,222 days (75.7% of the 1,614 VD) in the control group (p = 0.0010). Among patients with TIET ventilation for at least 2 days, 25 (16.4%) were free of any antibiotic treatment during the entire ventilation period (164 VD) in the experimental group while there were 12 (7.4%) in the control group (79 VD) (p = 0.020).
Outcome. The length of ICU stay, the duration of mechanical ventilation, and the tracheostomy rate were not significantly different between the two groups (Table 2 and Table 3). ICU mortality amounted 37.1% and 40.9% in group 1 and group 2, respectively (p = 0.46) while hospital mortality was 45.9% and 51.1%, respectively (p = 0.33).