In this study, a total of 4,949 patients throughout Japan who underwent drainage surgery for DNIs were investigated using a Japanese nationwide inpatient database. To the best of our knowledge, this is the first study to investigate the factors affecting mortality and delay in oral dietary intake in patients with DNIs, including DNM, in a nationwide clinical setting. The present study was also unique in that it compared these two outcomes by logistic regression analysis using the same clinical risk factors as independent variables. Interestingly, a few factors were associated with both in-hospital mortality and delay in oral dietary intake. Comorbid DM and sepsis were significantly associated only with in-hospital mortality. Conversely, several factors (DNM, repeated surgical interventions, ICU admission, and rehabilitation for oral dietary intake) were found to be significantly related only to delayed oral dietary intake.
Advanced age has been reported to be a risk factor for developing DNIs (25, 26). The present study showed that age ≥ 75 years was significantly associated with both mortality (adjusted OR 5.57, 95%CI 2.8–11.1) and longer recovery of oral dietary intake (adjusted OR 1.89, 95%CI 1.48–2.41). The presence of systemic disease was the most important predisposing factor for the severity of DNI. Of them, comorbid DM is a well-known risk factor. The present study showed that DM was correlated with mortality, with an adjusted OR of 2.47 (95%CI 1.69–3.62). These results are consistent with a recent systematic review and meta-analysis, showing that DM was associated with a higher prevalence of multi-space spread of infection, complications, and failure to identify pathogens, with risk ratios of 1.96, 2.42, and 1.29, respectively (22). Conversely, DM was not a significant factor related to delay in oral dietary intake, with an adjusted OR of 0.97 (95%CI 0.82–1.16). No background mechanisms have been confirmed to explain this inconsistency. One hypothesis is that this factor was adjusted by other variables, because the crude OR of this factor was 2.60 (95%CI 2.29–2.95).
Similar to sex, obesity evaluated by BMI was relatively uniform among the three groups. Specifically, the prevalence of patients with obesity (BMI ≥ 30 kg/m2) was 4–5% in all groups, and it was not a risk factor for either mortality or delay in oral dietary intake. Although the relationship between the severity of DNIs and obesity has yet to be determined, a previous report showed that obesity (BMI ≥ 30 kg/m2) was correlated with longer hospitalization (27). The DPC database has missing data for evaluating BMI in 7% (337/4949) of cases. In the DPC data, the codes corresponding to each surgery, clinical procedure, and medication are almost complete because they are compulsory items for reimbursement of healthcare costs defined in a central system in Japan to check the adequacy of the data (All-Japan Federation of the National Health Insurance Organization). However, other information submitted with claims that is not directly related to charges may be missing, such as height/weight and smoking index (28). These less accurate data may also be responsible for the failure to identify obesity and smoking as risk factors for both mortality and delay in oral dietary intake in the present study. The smoking index was missing in 15% (754/4791) of cases in the DPC data, similar to the previous study (28).
The mortality rate for all patients with DNIs was 3% (158/4949), and that for patients with DNM was 8% (46/550). The latter rate is consistent with recent meta-analyses (6, 7) demonstrating mortality of 9–10% for the combined cervical and transthoracic approach compared to mortality of 47–50% for cervical drainage only in cases of infection to the inferior mediastinum. Interestingly, comorbidity with DNM was not found to be a significant factor for mortality. These results could be attributed to the spreading of strategies in Japan for transthoracic drainage in patients with DNM with extension below the tracheal bifurcation (11, 29). In the present cohort, 22% (158/550) of the patients with DNM underwent transthoracic drainage. In contrast to the results for mortality, the present study showed that DNM was a significant factor for the delay in oral dietary intake, with an adjusted OR of 1.41 (95%CI 1.04–1.92). In addition to severe infection, systematic debridement and broad opening of the involved fascial planes are considered to contribute to limited laryngeal elevation and/or severe scar contraction specifically around the cricopharyngeal muscle (11). Therefore, patients with DNM should receive postoperative care with careful attention to the risk of delayed recovery of oral intake.
Of the systemic diseases contributing to mortality, several previous reports addressed death due to complications with sepsis (25, 30–33). In contrast to the outcome related to DNM, the present study showed that sepsis was a significant factor only for mortality, with an adjusted OR of 3.32 (95%CI 2.29–4.82), not for a delay in oral dietary intake, with an adjusted OR of 1.15 (95%CI 0.88–1.51). Therefore, sepsis, rather than DNM, should be considered a risk factor for mortality in treating DNIs and DNM.
In the present study, tracheotomy contributed only to a delay in oral dietary intake, with an adjusted OR of 1.70 (95%CI 1.44-2.00), which was similar to the result for DNM. Previous reports advocated tracheotomy for DNI cases with severe airway obstruction and/or presumed difficult re-intubation specifically managed by otolaryngologists (6, 34–37). These results are consistent with our previous study and imply that a disturbance in swallowing function may be encountered after tracheotomy, presumably resulting from desensitization of the larynx after diversion of the air passage or fixation of the larynx (11, 38).
It is plausible that undergoing repeated surgery is related to a delay in oral dietary intake, with an adjusted OR of 1.70 (95%CI 1.16–2.48). Interestingly, this factor was opposite to the risk for mortality, with an adjusted OR of 0.45 (95%CI 0.23–2.07). Singhal (39) reported that CT imaging of the neck and chest should be performed with any clinical deterioration of the patient or empirically 48–72 hours after an operative drainage procedure to identify any progression of the infection. Because initial drainage is often inadequate in patients specifically with DNM, the present results suggest surgical interventions with repeat drainage. However, these patients should receive postoperative care with careful attention to the risk of delay for recovering oral intake.
Postoperative care has been reported to play a critical role in patients with DNIs and DNM (5, 31, 40). Appropriate and careful selection of patients for ICU admission is sometimes fundamental for these patients to manage severe sepsis and/or septic shock and every possible complication, both at the beginning and after surgery (31, 40). In the present study, ICU admission was not found to be a crucial factor related to mortality. One hypothesis for these results is that the above-mentioned critical care might contribute to the survival of patients with severe morbidities.
In contrast to the above-mentioned risk factor, mechanical ventilation was a significant risk factor for both mortality and delay in oral dietary intake, with adjusted ORs of 3.96 (95%CI 2.51–6.23) and 1.92 (95%CI 1.53–2.41), respectively. One background hypothesis is that the deteriorated conditions of the patients led to endotracheal intubation in the first place. According to the previous support, most cases with DNM showed whole body deterioration and received support from an artificial respirator for an extended period (2, 40). Similar to the results for mechanical ventilation, the duration of empirical antibiotic therapy (days) was also a significant risk factor for both mortality and delay in oral dietary intake, with adjusted ORs of 1.00 (95%CI 1.00-1.02) and 1.18 (95%CI 1.17–1.19), respectively. Along with surgical drainage, high-dose intravenous antibiotics are the mainstay for the management of DNIs. These results correspond to the longer intravenous antibiotic therapy in more critically ill patients with infection.
Finally, if patients can recover from their severely ill condition, rehabilitation for dysphagia might be indicated. Although only a few reports have addressed rehabilitation for DNIs or DNM because of the absence of detailed swallowing evaluation (11, 41), the present nationwide study showed that approximately 10% of patients with DNIs received rehabilitation therapy. This was a significant factor for a delay in oral dietary intake, with an adjusted OR of 2.05 (95%CI 1.44–2.92). These results correspond to the situation where the right person (suffering from dysphagia) is in the right place (undergoing rehabilitation).
Several limitations of this study need to be acknowledged. First, this study was based on a retrospective cohort study using a national Japanese database, and generalization of the results outside Japan may not be appropriate. Second, comorbidities are less accurately recorded in administrative claims databases than in planned prospective studies. Third, the absence of records on vital signs, blood tests, and blood and bacteriological cultures in the DPC database precluded a more rigorous definition of septic shock, as discussed in the previous report (13). Moreover, DPC data come from an inpatient database, and it is difficult to evaluate the delay from onset to intervention.
Within these limitations, the current study with the largest retrospective cohort using a nationwide database has several advantages. It was found that clinical risk factors differed between mortality and delay in oral dietary intake other than age ≥ 75 years, sepsis, mechanical ventilation, and duration of empirical antibiotic therapy. Other than these factors, DM contributed only to mortality. Conversely, DNM, repeated surgery, tracheostomy, and intensive care unit admission contributed to a delay in oral dietary intake, but not mortality. Further research including multicentre prospective studies of DNM and DNI is necessary to establish precise therapeutic approaches for managing DNIs and the optimal treatment for DNM.