This study retrospectively analyzed the prognosis of 67 RA patients after ICU admission and identified the predictive factors of mortality. We elucidated that the prognostic factors of mortality for RA patients admitted to ICU included the use of csDMARDs, elevated updated CCI, high APACHE II score, and prolonged PT-INR at ICU admission.
Previous studies have examined the risk factors and mortality of RA patients after ICU treatment [6-9, 11-15, 17, 27, 28]. The short-term fatal outcome of RD, including RA, tended to be worse in RA patients than in the general population [9, 17, 27], and the long-term (1–3 years) mortality of RA patients was significantly increased after ICU admission [8, 27]. In our institution, the 30-day, 90-day, and 1-year mortalities after ICU admission were 21%, 27%, and 37%, each. This is likely due to the tertiary nature of our hospital and because our study design excluded mild cases. Furthermore, Peschken et al. reported that the most common reasons for ICU admission were CVD and infection [8]. CVD in patients with RA is known to be associated with a higher prevalence of comorbidity and is a cause of mortality compared with that in the general population [29] [30], whereas CVD mortality has been declining due to the current strict disease control measures [31]. The percentage of patients admitted to the ICU for CVD was lower than that for serious infections because of the possibility of a favorable response to the treatment and exclusion of patients staying for less than 24 h. A French cohort study involving patients with RD demonstrated that infection and RD exacerbation were the most common causes for ICU admission [13]. Barrett et al. reported higher rates of severe sepsis and poorer prognosis in RA patients than in the general population [27]. Patients with RA have an increased a risk of infection [2-4, 15, 17], and the most frequent site of infection is the respiratory system, followed by soft tissue, bone, and joint [5, 32]. In our study, due to the critical condition of the patients that required treatment in the ICU, sepsis (8, 30%) and respiratory infection (8, 30%) were the most common infections, as shown in Table 3. Viral hepatitis was observed in three nonsurvivors, all of whom had hepatitis B virus (HBV) reactivation. Although the reported HBV-related mortality ranges from 1.9% to 4.0% in Taiwanese patients with RA [33], all three patients with HBV reactivation in our study died of liver failure, suggesting that the prevention of HBV reactivation is important. A previous study proved that the risk factors for the ICU admission of RA patients due to infection included the non-use of csDMARDs, old age, and comorbidity with COPD or CKD [15]. The current study found that the majority of the 30-day mortality group admitted to our ICU due to infection was nonsurvivors. Immunosuppressive treatments, including bDMARDs, csDMARDs, and glucocorticoids, are reportedly associated with infection [15, 34-39], whereas we found that the use of csDMARDs reduced the risk of mortality after ICU admission using the multivariate Cox proportional hazards model. Additionally, despite the lack of a significant difference in dose-related risk of glucocorticoids in the multivariate analysis, a higher glucocorticoid dose appeared to be associated with an increased risk of mortality. Based on previous reports on the risks related to infections and medications, including glucocorticoid, csDMARDs, and bDMARDs [6, 15, 17, 36, 39, 40] [35, 41], a dose-related glucocorticoid was reported to increase the risk of infection, whereas csDMARDs were reported to reduce the risk and mortality in RA [42] [15, 43]. Treatment with glucocorticoids raised the incidence and hazard of adverse effects in RA patients, such as diabetes mellitus, osteoporosis, thrombotic stroke, CVD, serious infection, and death [44-46]. Two studies previous showed that the use of glucocorticoids for RD led to poorer prognosis in short-term outcome after ICU admission [28, 47]. Conversely, increased glucocorticoid doses might have been used in patients with higher disease activity who could not be treated with csDMARDs and/or b/tsDMARDs; however, we were unable to accurately analyze the disease activity in the patients because of altered consciousness or the ICU settings. Furthermore, a short course of glucocorticoids with methotrexate could lead to a low disease activity earlier [48]. Since several studies have reported high disease activity and early presence of joint damage as poor prognostic factors for RA [49-51], treatment with csDMARDs is necessary for prompt RA control . Together with previous reports, our results suggest that RA disease activity might be controllable using csDMARDs and minimum glucocorticoid doses, which might reduce mortality after ICU admission. In our study, most of the patients with RA (79%) had been treated with glucocorticoid due to various severe complication, such as heart, liver, and renal failure, suggesting that the patients who had been hard to use csDMARDs and decrease the amount of glucocorticoid for their disease activity and severe complication might be poorer prognosis.
RA patients often have several comorbidities, and previous studies have reported the risk factors for ICU admission and mortality, such as pulmonary disorder, renal dysfunction, and hypertension [6, 13, 15]. To evaluate comorbidities, we calculated the updated CCI, which can be used to predict hospital mortality [20]. Univariate analysis showed that the updated CCI, particularly the liver and renal failure scores, was higher for nonsurvivors in the 30-day mortality group than for survivors (Table 2) [6, 13, 15, 17]. In addition, a higher updated CCI was found to be associated with an elevated risk of mortality after ICU admission using the multivariate Cox proportional hazards model. Given that nearly 80% of patients with RA suffer from comorbidities [52, 53], a higher updated CCI, which was developed for the prediction of hospital mortality [19, 20], might be a helpful predictor of poor prognosis in patients with RA after ICU admission. In the current study, the majority of RA patients were treated with mechanical ventilation and vasopressor therapy after ICU admission. Similar to another study [12], there was a significantly greater use of renal replacement therapy in the nonsurvivors of the 30-day mortality group than in the survivors. Renal replacement therapy was frequently used for worsened liver failure and renal disease among comorbidities and was increased in the nonsurvivors of the 30-day mortality group. Together with the findings from previous reports [12, 54], our data indicate that ICU patients requiring renal replacement therapy showed poorer prognosis. Previous studies reported that other organ replacement therapies, including mechanical ventilation and vasopressors, were associated with a higher mortality in the ICU population [12, 17, 47, 55, 56]. By contrast, the present study did not find any difference in the 30-day mortality groups probably because our study only included RA patients and did not include those with other collagen diseases, such as systemic lupus erythematosus, dermatomyositis, Sjögren’s disease, progressive systemic sclerosis, mixed connective tissue disease, or vasculitis.
Some studies have reported that the prognostic factors of ICU mortality in patients with RD included high APACHE II and SOFA scores, serious infection, mechanical ventilation, vasopressor, renal replacement therapy, and glucocorticoid dose [6, 7, 9, 11, 12, 17, 28]. The APACHE II and SOFA scores, which were predictive factors of ICU mortality in the general population, have also predicted ICU mortality in RA patients [6, 7, 11, 12, 14, 23]. In line with previous studies [11, 57-59], our multivariate analysis also identified an elevated APACHE II score as a predictor of mortality. In fact, in our study including only patients with RA, the 30-day mortality of the nonsurvivors was significantly higher than that of the survivors (21.7 ± 9.2 vs 14.6 ± 5.6). So far, only one report [17] has investigated the APACHE II score specifically in patients with RA, and our study demonstrated that the association between APACHE II score and mortality of RA is similar to that in previous reports on RD. Considering that the APACHE II scores of RD patients were shown to be approximately equal to those of the general population due to their critical condition needed intensive care [14, 17], the results of the current study show that the APACHE II score in RA patients was also a prognostic factor of ICU mortality. Finally, laboratory tests showed that coagulation abnormalities were a prognostic biomarker associated with poor outcome in all ICU mortality [60]. The multivariate Cox proportional hazards model demonstrated that prolonged PT-INR at ICU admission could predict ICU mortality using a routine coagulation test. Therefore, PT-INR should be extended to the ICU admission of patients treated with an anticoagulation agent for their comorbidity. The DIC scores and PT-INR on the day after ICU admission were significantly elevated in the nonsurvivors of the 30-day mortality group, thus suggesting that PT-INR, as a representative of DIC, is a useful biomarker for ICU survival. Indeed, several studies have reported that the DIC score correlated with several scoring systems used in the ICU, such as APACHE II score [61, 62]. On the other hand, Awgstwurm et. al demonstrated that the DIC and APACHE II scores were independently correlated with survival time [63]. Additionally, their study revealed that the combination of the APACHE II score with the coagulation abnormality score was a better predictor of mortality than the APACHE II score alone. In our study, PT-INR had no correlation with APACHE II score (R = −0.1363, P = 0.2714), suggesting that prolonged PT-INR in combination with the APACHE II score might predict mortality in patients with RA admitted to the ICU.
This study has several limitations. First, clinical data were retrospectively analyzed. Second, this study used a small cohort from a single institution and did not include a control group. However, the characteristics of the patients treated at the ICU vary between different institutions. Our study was able to analyze an RA population with more critical comorbidities and complications because our institution treated patients with more severe disorders, such as organ transplantation, compared with other institutions around this area. Third, we did not analyze the disease activity of all RA patients, and this approach may have affected the interventions and outcomes of the patients. However, it was difficult to identify disease activity because our study included patients with impaired consciousness and/or are immobile.