Our study found that both the APACHE II and SOFA scores on admission predicted short-term outcomes of adult patients with TBM in ICU. And the APACHE II scoring system was superior to SOFA in predicting 1-year outcomes. In addition, the requirement of invasive mechanical ventilation was found to be independently associated with an unfavorable outcome.
In our study, the participants’ characteristics differed significantly from those reported in previous studies conducted in other endemic areas [17, 18], but were similar to the one conducted in non-endemic area [4]. Most obviously, all the 80 patients presented with MRC stage III illness, and 58 (73 %) required invasive mechanical ventilation. These differences might be explained by selection bias of the most severe cases requiring ICU admission in this study, since the access to intensive care was low in China. Different factors such as older age, hydrocephalus, change in consciousness and higher MRC stage were reported to be associated with poor prognosis in patients with TBM [4, 19,20,21]. However, no clinical, laboratory or imaging factors were found to be associated with poor outcomes in our study cohort. This could be explained by the participants themselves, since they were the most severe cases who were more likely to develop hydrocephalus and comatose than those with MRC stage I or II illness.
Thirty-five patients in our cohort died, among whom 29 deaths were within 28 days. The 1-year overall mortality was 46 %, which was extremely high, but comparable to a previous study [5]. In that systematic review and meta-analysis, the mortality rate was 64.8 % for patients with stage III TBM [5]. The phenomenon that most deaths (29/35) occurred early was consistent with a Madagascar cohort and a meta-analysis which consisted of 5752 adult TBM patients [22, 23].
Mechanical ventilation was reported to be required by 10-20 % of adult patients with TBM in all stages [24, 25]. For those admitted to ICU, this number increased to 70 % [4, 26]. In our study, 58 (73 %) patients received invasive mechanical ventilation during their ICU stay, of whom 37 (64 %) had an unfavorable outcome. Consistent with previous studies, the requirement of mechanical ventilation was associated with an unfavorable outcome [24, 25]. Those who needed mechanical ventilation were more critically ill because of associated sepsis and TBM-related or systemic complications, and had a higher mortality rate.
Hyponatremia is the most common electrolyte abnormality observed in hospitalized individuals and is associated with increased mortality [27]. For patients with TBM, the frequency of hyponatremia was reported to be about 40–50 % in different studies [28,29,30]. The relationship between hyponatremia and death was uncertain. It was reported to be certain in a tertiary care cohort [30]. However, hyponatremia didn’t have a predictive value on the outcome of TBM in another prospective study [29]. In a study consisted of 1048 adult TBM patients, the authors used time-updated Glasgow coma score and plasma sodium measurements to dynamically predict the death, they found that plasma sodium values were higher in HIV-infected survivors, with a less clear relationship between sodium and survival in HIV-uninfected patients [31]. We didn’t observe an association of plasma sodium levels with death in our study cohort, too. So, more prospective studies need to be carried out in different patient populations to confirm the role of hyponatremia in TBM.
GCS was used to assess the mental status of patients with TBM and low GCS scores were reported to be associated with an unfavorable outcome in numerous studies [32,33,34,35]. In our study, GCS had no association with unfavorable outcomes, which might be explained by the relatively lower GCS scores of the patients with MRC stage III illness on admission. Irritability displayed a better association with favorable outcomes in univariate analysis, partially due to its relationship with a relatively higher GCS score.
APACHE II and SOFA were the most common used scoring systems to evaluate the disease severity of patients in ICU [13, 14]. To our knowledge, few studies have used APACHE II in patients with TBM [16], and none has used SOFA. In the previous study, APACHE II showed a good predictive value as GCS and superior to MRC for discharge outcomes of adult patients with TBM [16]. To obtain the greatest power in prediction based on ROC curve analysis, the cut-off points chosen for GCS, APACHE II and SOFA were 4, 23 and 8 respectively in our study. The results showed that only APACHE II had both acceptable sensitivity and specificity. In univariate and multivariate logistic regression analyses, APACHE II and SOFA were independently associated with an unfavorable outcome. APACHE II > 23 was identified as predictor of 1-year mortality by multivariate Cox regression analysis. These two scoring systems were based on physiological variables other than levels of consciousness or neurological deficits, on which the GCS was based. Therefore the use of APACHE II and SOFA would be more suitable for assessing the prognosis of patients with TBM, especially for those admitted to ICU.
Imran and collegues have derived a simple bedside score (MASH-P) including variables baseline modified Barthel index (M), age (A), stage (S), hydrocephalus (H) and papilledema (P), which can be used easily at bedside to predict 6-month mortality in tuberculous meningitis [36]. However, the model needs external validation to assess its performance in different settings. In our study cohort, a model including APACHE II, SOFA and mechanical ventilation also showed good discrimination and good calibration. However, it also needs external validation and further assessment since there were duplicate indices between the two scoring systems such as GCS scores, mean arterial pressure and creatinine. APACHE II itself had a good predictive value on the outcome of TBM (area under the ROC curve = 0.81), so we would suggest using APACHE II alone instead of the three-factor model to reduce the workload of clinicians.
Our study has some strengths. First, no study was conducted on adult patients with TBM admitted to ICU in China. Second, participants included in our study were the most severe TBM cases of MRC stage III - a group which was not previously reported separately. Moreover, we used validated guidelines and consensus definitions to include participants and report data.
Our study was limited by its retrospective design. All data were collected from a single medical center and the sample size was not large enough. Most patients only took cranial CT scans, which lack sensitivity for TBM-associated cerebrovascular or inflammatory complications. The present results may not be applied to a less severe population since we focused on the most severe TBM cases of stage III admitted to the ICU.