To identify qualified published studies, two independent researchers (ZLL and SL) systematically searched the Web of Science, EMBASE, and Cochrane Library, using the following keywords: “extubation,” “weaning,” “disconnect of mechanical ventilation,” “discontinuation of mechanical ventilation,” “central venous pressure,” “CVP,” “Brain natriuretic peptide,” “BNP,” and “brain natriuretic peptide”. The searches encompassed studies up to October 2021 and were limited to those published in English. In addition, we manually searched relevant reviews and references within those publications to identify potentially relevant studies. If there was a disagreement about inclusion, a third researcher (CJH) was called to discuss the decision.

The inclusion criteria were as follows: patients were adults hospitalized in the ICU for underlying cardiovascular or respiratory disease who received MV for no less than 24 h. Patients were extubated after adequate evaluation and followed for at least 24 h after weaning from MV. CVP or BNP levels were monitored before or after extubation. Extubation failure was defined as re-intubation within 48 h, spontaneous respiratory failure, noninvasive or invasive ventilation within 48 h after extubation, or death within 48 h. The exclusion criteria were as follows: potential confounding variables for CVP, such as lax measurement of CVP, potential confounding factors for BNP such as renal insufficiency, studies lacking the necessary data, duplicate studies, reviews, case reports, abstracts or letters.

Two researchers (ZLL and SL) independently screened the titles and abstracts using set keywords, and then checked the full text according to inclusion and exclusion criteria. The following information was extracted: the first author’s name, publication year, age, sex (%), country, sample size, timing of BNP and CVP measurement, methods and durations of SBT and definition of extubation failure. When there were differences in data extraction, it was discussed with the third researcher (CJH). The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies (Stang, 2010). Studies that had a score ≥6 points were considered a “high-quality study.” This study was approved by the Ethics Committee of Shanxi Provincial People's Hospital (No. 223, 2022).

The pooled analysis was analyzed by Review Manager 5.4. Standardized mean differences (SMD) and corresponding 95% confidence intervals (CIs) of the CVP and BNP levels were collected and calculated for each study. When the median and interquartile range (IQR) was provided, the mean and standard deviation (M ± SD) was estimated using Luo’s approach and Wan’s method, respectively (Wan et al., 2014; Luo et al., 2018). Heterogeneity is evaluated by calculating the I- squared (I ²) index. I ² values of 75%–100%, 50%–75%, 25%–50% and < 25% were considered as high, moderate, low heterogeneous and homogeneous, respectively. If there was significant heterogeneity (I ² > 50% or p < 0.05), a random effect model was used, otherwise, a fixed effect model was applied.

In order to identify the potential heterogeneity, we performed subgroup analysis based on the levels of CVP and BNP before and after extubation. Moreover, we deleted one study at a time and repeated the analysis, namely the leave-one-out method for sensitivity analysis. Egger’s and Begg’s tests were used to find potential publication bias. When the p value was less than 0.05, it was considered statistically significant.

Using our search strategy, a total of 1,234 potentially original studies were identified and excluding duplications, 874 studies remained. Careful screening of titles and abstracts, identified 841 studies that did not meet the inclusion and exclusion criteria, and these were also excluded. Finally, after carefully reading the main body of the remaining 33 studies, 20 studies were eventually excluded. In the end, 12 qualified studies were inclued (Chien et al., 2008; Zapata et al., 2011; Saugel et al., 2012; Soummer et al., 2012; Ma et al., 2013; Maraghi et al., 2014; Farghaly et al., 2015; Konomi et al., 2016; Tanios et al., 2016; Haji et al., 2018; Dubo et al., 2019; Zhao et al., 2021). The screening process of these studies is shown in Figure 1. Meanwhile, Table 1 listed the basic characteristics of the included studies. As NOS scores of these studies were at least 6, all were considered of high quality.

We found seven studies that described a relationship between the CVP levels and extubation outcomes. Since there was no significant heterogeneity (I ² < 50%), the fixed effect model was applied. The fixed effect pooled SMD was 0.47 (95% CI: 0.43–0.51, p < 0.00001) (Figure 2). Subgroup analysis based on extubation time showed that the results of pooled analysis were consistent with the association between elevated CVP levels and extubation failure before extubation (SMD:0.47,95% CI: 0.43–0.51, p < 0.00001). However, this association had no significant correlation after extubation (SMD: 0.63, 95% CI: −0.05–1.31, p=0.07).

Due to the limited studies included, potential publication bias was not carried out. Since none of the studies had a significant influence on the pooled results, the leave-one-out sensitivity analyses suggested robust results.

We also found eight studies that contained information about the association between the BNP levels and extubation outcomes. Since there was no significant heterogeneity (I ² < 50%), the fixed effect model was applied. The fixed effect pooled SMD was 0.68 (95% CI: 0.49–0.86, p < 0.00001) (Figure 3). Based on the subgroup analysis of extubation time, we found that the pooled results were consistent with the relationship between high BNP levels and extubation failure before extubation (SMD: 0.57, 95% CI: 0.35–0.79, p < 0.00001) and after extubation (SMD: 0.91, 95% CI: 0.59–1.23, p < 0.00001).

No potential publication bias was observed with respect to the relationship between BNP levels and extubation outcomes, according to the results of the Egger’s test (P > 0.05) and Begg’s test (P > 0.05). The leave-one-out sensitivity also showed robust results, as none of the studies had a significant effect on the overall outcomes.

The measurement of CVP levels is affected by the observer’s mode of measurement and the patient’s condition. For example, intra-thoracic pressure, intra-abdominal pressure, position, or depth of venous catheter placement can affect the results. Although we can standardize the observer’s measurement and try to avoid a patient influence on the CVP measurements, there is poor predictive value for extubation outcomes. As ICU patients often have in-dwelling central venous catheters, CVP could easily and quickly be evaluated at the bedside. BNP is a sensitive marker for monitoring cardiac insufficiency and accurately predicts extubation outcomes. However, the utility of BNP as a marker also has its limitations. The detection of BNP is affected by age, renal insufficiency, drugs and other unavoidable factors. In conclusion, although CVP is able to identify early extubation outcomes, its predictive value is poor. In contrast, BNP has high predictive value, but the detection of extubation outcomes is inferior. Finally, the accuracy of our results may be affected by the limited number of studies we included. Since we do not have access to the original data for drawing ROC curves, we cannot determine a reliable cut-off point fot the CVP and BNP tests.