Association between central venous pressure measurement and outcomes in critically ill patients with severe coma

Central venous pressure (CVP) is the pressure recorded in the superior vena cava or the right atrium and, to a lesser extent, the left ventricular preload [1], reflecting venous return and right ventricular function [2]. Thus, CVP measurements could help in fluid management [3]. However, the CVP can also be influenced by thoracic, pericardial and abdominal pressures, complicating its understanding. Recently, several studies have found that the CVP cannot predict fluid responsiveness and only higher or lower CVP values may have negative or positive predictive values [4‐6]. Therefore, the application of CVP measurement has been questioned. Some researchers have suggested that although there could be some limitations to using the CVP to assist fluid resuscitation, it would be better to fully understand and address these limitations, rather than abandoning them completely [3, 7]. The CVP levels still provide significant information about patient's cardiocirculatory status.

Many clinical studies have reported that higher CVP values may be associated with patients’ poor outcomes in different conditions, such as patients undergoing cardiac surgery [11], early Fontan failure [10], acute kidney injury (AKI) [8, 9], patients undergoing cardiopulmonary bypass surgery [9], and critically ill patients [2]. A controlled lower CVP can also reduce blood loss during hepatectomy [12]. Meanwhile, CVP measurement has been reported to shorten the time to be medically fit for discharge and benefit the clinical outcomes for patients with acute respiratory distress syndrome or sepsis [13‐15]. Some researchers have suggested using the CVP as a stopping rule for fluid infusion [3, 7]. However, to our knowledge, the value of CVP measurements in patients with coma remains unclear. Fluid administration could increase cardiac output; however, it could also increase the risk of hydrostatic pressure or edema formation. Theoretically, this situation could be more complicated in critically ill comatose patients, and CVP may be beneficial in these conditions.

Therefore, the purposes of this study were to investigate 1) the association between early CVP measurement and patients’ outcomes and 2) the association between initial CVP time and all-cause mortality of intensive care unit (ICU) patients with severe coma.

The goal of current study was to investigate the application value of CVP in patients with severe coma in the ICU. We found that early CVP was independently associated with lower all-cause in-hospital mortality in severe coma patients (GCS score 3–8). We also found the association of the initial CVP time and in-hospital mortality was presented as a “U-shape” in the RCS curve. As the initial CVP time increases, the risk of all-cause in-hospital mortality increases.

Because of the standardization of advances in technologies, such as MVs, in ICU management, more and more comatose patients are surviving life-threatening diseases. However, the high mortality rate and cost for this type of patient are still among the most severe clinical and social problems [23, 24]. Any efforts that could increase the chances of reasonable functional outcomes in patients with coma are of utmost clinical and ethical significance [25].

This is the first study to investigate the association between the early CVP and clinical outcomes in patients with severe coma. The current study was a post hoc analysis. The data included in this study were from the eICU and MIMIC-III databases, which contain ICU patients across more than 200 different hospitals in the USA, with varying CVP practices. Our analysis leverages the availability of time-stamped demographic information, comorbidities, vital signs, laboratory results, etc., to investigate whether CVP could benefit patients with severe coma. The results of the study were highly consistent across different sensitivity analyses.

Conflicting evidence on the application of the CVP has been reported in previous studies. Eskesen et al. found that the application value of the CVP measurement is low in a re-analysis of 1148 patient data sets [5]. They reported that only in certain extreme cases, such as higher or lower, does CVP measurement demonstrate some of its value in liquid management. Marik et al. conducted a meta-analysis and reported that only 57% of patients were fluid responders, and the correlation between CVP level and stroke volume index was not strong; thus, the use of the CVP for fluid resuscitation should be abandoned in widespread practice due to insufficient evidence. However, many studies have reported the association between the CVP levels and patients’ clinical outcomes with various conditions. For example, Chen et al. found in a meta-analysis that a higher CVP value was associated with higher mortality (odds ratio [OR] 1.65) and a greater risk of AKI (OR, 2.09). Quail et al. found that a higher CVP is associated with a higher risk of early Fontan failure after total cavopulmonary connections [10]. Liu et al. also found that a controlled lower CVP could reduce blood loss during hepatectomy and recommended the promotion of CVP use in clinical settings [12].

Despite the conflicting evidence reported and the value of the CVP being questioned, some clinicians still recommend the use of the CVP in clinical settings [3, 7]. One recommendation is to use CVP as a stop symbol in liquid management. Weil and Henning first proposed this approach and suggested that fluid administration could be stop as the CVP increased by 5 cmH2O or more [26]. However, Hamzaoui et al. reported that changes in the stroke volume could not be reflected by the CVP levels. Therefore, the CVP levels could not represent as a criterion for predicting fluid responsiveness [6].

Whatever the approach to CVP application, some evidence also indicates that CVP use is associated with a better clinical outcome in some patients [14, 15]. Chen et al. reported the association between the CVP using and lower 28-day mortality in septic patients [14]. Tang et al. reported that the CVP could improve the clinical outcomes of patients with acute respiratory distress syndrome [15]. However, both studies were from a single-center database; thus, the generalization of the results could be hindered. In these multicenter studies, we found that severe comas patients with CVP suing have a lower in-hospital mortality than those without CVP. Moreover, we found that with the delay in the initial CVP time, the risk of in-hospital mortality is increasing. In the secondary outcomes, we found that CVP was also associated with ICU mortality, 28-day mortality, 365-day mortality, and more days without vasopressor drugs. We believe that these results confirm the application value of CVP in comatose patients.

The detailed influence of the CVP on therapeutic interventions was difficult to explore due to the retrospective design. Previous studies reported that the trigger caused by CVP, such as fluid therapy, could lower lactate levels of patients, thus could improve outcomes [14, 15]. Semler et al. found that different fluid management based on initial CVP values could influence outcomes of acute respiratory distress syndrome patients, and conservative fluid administration could lower the mortality of patients with a low initial CVP [27]. Wang et al. found that patients who have a peak CVP value more than 12 mmHg also have worse organ function, higher SOFA score and longer hospital stay [2]. These results indicate that CVP could positively impact the latter management of patients. In the current study, we found that the IVF was significantly different between patients with and -out CVP. Generally, IVF volumes in patients with CVP were higher on day 1 and lower on day 3 compared to those in the non-CVP group. Most patients (62.1%) with CVP had an initial CVP value of ≤ 12 mmH2O. It is difficult to investigate whether the difference in the IVF on the first day was influenced by the CVP. However, relatively free fluid management may be safe when the levels maintaining as low as possible [3]. Fluid management is a double-edged sword. Correction of intravascular hypovolemia is critical for preventing and managing AKI, but excessive fluid administration could also increases the risk of AKI [28, 29]. In the current study, we also discovered that the 2-day and 7-day AKI was higher in patients with CVP, which is different from that in previous studies. The causal relationship between the increased risk of AKI and the CVP requires further research and evaluation.

In critically ill patients with severe coma (GCS score 3–8), early CVP measurements is independently associated with lower in-hospital mortality. Among patients with CVP measurements, in-hospital mortality increased with a delayed initial CVP measurement.