Central Venous Oxygen Saturation as a Predictor of a Successful Spontaneous Breathing Trial from Mechanical Ventilation: A Prospective, Nested Case-Control Study

1. INTRODUCTION

Weaning patients from mechanical ventilation are one of the key elements in the course of the treatment of critically ill patients and could represent up to 40% of the time that a patient spends on mechanical ventilation [1, 2]. A prolongation of mechanical weaning is associated with increased risk of complications, such as ventilator-associated pneumonia, tracheal injury, bleeding from digestive stress ulcers and sepsis [3-5], while early extubation and re-intubation could result to nosocomial pneumonia and increased mortality [6, 7]. Thus, identifying the optimal point when a patient can sustain spontaneous breathing is essential, but could be challenging.

In order to facilitate physicians in identifying the patients who are ready to wean from mechanical ventilation after the resolution of acute disease phase, a number of criteria have been set, in a two-step procedure [8], which begins with a trial of spontaneous breathing (SBT) via a T-tube. Since no single and consistent predictor has been found to accurately predict the SBT outcome [9, 10], the decision of a successful or not trial is based on a combination of another set of criteria evaluating the hemodynamic or not stability of the patient and the change of mental status, oxygenation and ventilatory efficiency during spontaneous breathing [8]. Previous data indicate that global tissue oxygenation is an important predictor of the weaning outcome [11, 12] and is associated, especially among patients who fail to wean, with the increased oxygen cost of breathing due to the strenuous working respiratory muscles [12]. Mixed venous oxygen saturation (SvO₂), which requires invasive measurements via right heart catheterization, and the easier to obtain central venous oxygen saturation (ScvO₂), are two indices closely associated with global tissue oxygenation; Nevertheless, their routine screening is currently not recommended as part of the evaluation of the SBT outcome. Although SvO2 and ScvO2 measurements have been previously studied in regards to several outcomes and in several patient populations [2, 13, 14], data on the prognostic accuracy of SvO₂ values, ScvO₂ values and their changes on the weaning outcome, is currently limited [2, 15, 16]. Moreover, most of these studies were conducted in selected patient populations [2, 15] or aimed to investigate whether ScvO₂ and SvO₂ could predict the extubation outcome, which is the final and not the initial step of the weaning procedure [2, 16] and could be, thus, influence by several other factors not closely associated with tissue oxygenation, such as an inadequate cough or laryngeal edema [10].

To the author’s knowledge, data on the clinical significance of ScvO₂ as a potential predictor of the SBT outcome is currently scarce. Thus, we conducted a prospective study aiming to evaluate whether ScvO₂ values and their changes between the initiation and the end of a thirty-minute long SBT could independently predict the outcome of this trial, in a general surgical and medical population of mechanically ventilated patients.

2. MATERIAL AND METHODS

3. RESULTS

A total of 77 patients (69(18-86) years old; 62.3% male) constituted the study population (Table 1). The main diagnosis of ICU entry were infections (such as pneumonia or abdominal infections) (32.5%), major surgery (chest, abdominal, brain, vascular or orthopedic surgery) (39%), cardiac arrest (3.9%), trauma (9.1%), acute respiratory failure (2.5%), status epilepticus (3.9%), burns (1.3%), stroke (3.9%) and intoxication (3.9%). Overall, 49 patients (63.6%) had a successful SBT, with the rest 28 (36.4%) having a SBT failure. Patients who had a successful SBT were younger (66 (25) vs. 73.5 (11) years old; p=0.024), while no other difference was noted between the groups in demographic and rest of baseline characteristics (Table 1).

(Table 2) presents all measurements which were contacted just before and/or at the end of the SBT. Apart from Hb concentration, which was significantly lower among those who failed the SBT (8.9 (1.9) vs. 9.8 (2.2) g/dl; p=0.028), compared to those who succeeded, no difference was noted between the two groups, regarding measurements which were contacted just before the trial. On the contrary, by the end of it, the group of patients with successful SBT had higher SaO₂end (97.8 (2) vs. 97.5 (1) %; p=0.014), higher ScvO₂end (77.2 ± 7.8 vs. 71.9 ± 8.4%; p=0.007), a trend towards higher PaO₂end (104.9±32 vs. 91.3±27.7 mm Hg; p=0.063), lower O₂ERend (20.9±7.7 vs. 25.4±7.9; p=0.020) and lower f/Vt index (60±26.37 vs. 106.2±48.3; p<0.001), compared to those with SBT failure.

The final multivariate model included age, Hb, SaO₂end and ScvO₂end. O₂ERend was opted out due to high intercorrelation to ScvO₂end (r=0.982). SaO₂end, Hb concentration and ScvO₂end were positively associated, while age was negatively associated with SBT success (Table 3). (Fig. 1) presents ROC curves for ScvO₂end, SaO₂end and Hb concentration for a successful SBT outcome, with an area under curve being 0.685, 0.625 and 0.629 for ScvO₂end, SaO₂end and Hb concentration, correspondingly. Median ΔScvO₂% value for the SBT failure group was equal to -4.2%, so we rerun the multivariate regression analysis including the binary parameter ΔScvO₂% (≥4% or <4%) instead of ScvO₂end. A decrease of less than 4% in ScvO₂ values between the beginning and the end of an SBT was also independently associated with a successful outcome (OR=18.278; 95% CI=4.017-83.163, p<0.001), along with age, Hb concentration and SaO₂end. The area under the curve for ΔScvO2% in predicting a successful SBT was 0.712

4. DISCUSSION

In this prospective, nested case-control study we indicated that ScvO₂end is an independent predictor of SBT outcome, with a decrease of ScvO₂ <4% being associated with SBT success. It is well-known that the characterization of a SBT as success or failure is normally based on a combination of subjective criteria and objective indices measured at the end of the 30 minute trial, according to guidelines, which do not include the evaluation of any ScvO₂ values. However, our study confirms that ScvO₂end as a single index is independently associated with a positive outcome and although its diagnostic accuracy was moderate (68.5% for ScvO₂ and 71.5% for ΔScvO₂), it was slightly superior to that of SaO₂, which is a routinely screened parameter.

According to the Fick principle, oxygen uptake (VO₂) depends on oxygen delivery (DO₂) and O₂ER [17, 18]. This classic equation could be reformulated as a function of SvO₂, indicating that the four components which are associated with SvO₂ values are Cardiac Output (CO), Hb concentration, VO₂ values and SaO₂ values; However, the relationship between SvO₂ and its components are not equivalent and not necessarily linear [19]. In a previous study where the relationship between SvO₂ and CO was modeled using a standard population of 1000 ICU patients, the curve between CO and SvO₂ was non-linear and CO was an important but not the predominant component of SvO₂, except when very low [19]. In any case, SvO₂ seems to be a variable that passively follows the regulation of its components so that for any change in VO₂ needs, the tissue oxygenation represents the final adjustment between O₂ delivery and uptake and determines the change in SvO₂ [19]. Previously Jubran et al [11] utilized SvO₂ monitoring in order to assess cardiovascular performance and global tissue oxygenation during the weaning process; In this study the group of patients who failed weaning established a progressive decrease in SvO₂ values, compared to the rest, probably reflecting the increased O₂ER of respiratory muscles [11, 20]. According to Zakynthinos et al [12], in mechanically ventilated patients who failed to wean and presented with increased oxygen consumption, this was met by an increased tissue O₂ER and was reflected by a drop in SvO₂ values, confirming the association between SvO₂ and tissue oxygen delivery and consumption.

Previous studies have assessed the utility of SvO₂, ScvO₂ or their changes during weaning procedures. Among ten postoperative coronary artery bypass graft patients, Cason et al indicated that SvO₂ was an important predictor of weaning, since weaning failure was associated with a drop of SvO₂ of over 60% [15]. However the study size was minimal and the patient population was selected. In another selected population of postoperative coronary artery bypass graft patients, Armaganidis and Dhainaut [21] demonstrated that SvO₂ >60% was the best weaning success predictor and it depended on O₂ER measurements. More recent studies concluded that change of ScvO₂ during SBT was the only independent predictor of weaning from mechanical ventilation among patients who passed the first step of a two-step weaning procedure [16] and among difficult-to-wean patients [2]. In these studies, a drop of more than 4.5% [16] or 5% [2] in ScvO₂ values, was associated with failure to wean from mechanical ventilation. Both protocols, though, investigated not whether ScvO₂ is an index of a successful SBT, like in our study, but whether it is as a predictor of the extubation outcome within the following 48 hours. Nevertheless, laryngeal edema, low muscle endurance and inability to clear secretions are only some of the several potential causes of re-intubation, which are not directly associated to oxygen consumption and utilization, so these results may be, to an extent, difficult to explain.

In the current study, Hb was also independently associated with SBT outcome and had a similar diagnostic accuracy to ScvO₂ values. In a large retrospective study conducted by Lai YC et al. [22]. Hb concentration was positively associated with a successful weaning, among difficult-to-wean patients, while in another smaller cohort lower Hb levels were associated with extubation failure [23], confirming our findings. The oxygen-carrying capacity of the blood depends directly on the level of Hb [24], and in normal individuals, 15 g/dl of Hb carry approximately 21 ml of oxygen per 100 ml of blood [25]. In these subjects, a 3 g/dl decrease in Hb levels would result in a reduction of the total oxygen-carrying capacity by 4/100 ml; this effect might be even more intense among patients with respiratory failure since Hb saturation is usually abnormal [26]. Under this scope, the reduction in oxygen-carrying capacity might further impede the aerobic metabolism of respiratory muscles, resulting in respiratory inefficiency and weaning failure.

SaO₂ was also identified as an independent predictor of SBT success. This result comes to an agreement with previous data which indicated that an integrative index comprising SaO₂ had a higher diagnostic accuracy in predicting the weaning outcome than other traditional indices [27]. When the arterial oxygen content is low, the diffusion gradient of oxygen from the blood to the mitochondria decreases more rapidly, potentially leading respiratory muscles to early anaerobic metabolism [26]. Surprisingly, the PaO₂ end could not discriminate between the two groups in our study, neither at the beginning nor at the end of the trial, confirming the findings of similar studies in the field [2, 16]. Traditionally, the PaO₂/FiO₂ ratio has been used to identify patient populations ready to wean from mechanical ventilation [28-30]; Nevertheless, whether the diagnostic accuracy of PaO₂ as a single index is similar to that of oxygen tension as part of composite indices remains to be investigated in the future.

The current study carries its strengths and limitations. Its prospective design minimized missing data and recall bias, while the inclusion of a general medical and surgical population allows for the generalizability of the results. Moreover, the same medical team evaluated readiness to wean and the SBT outcome, using similar criteria, so methodological bias, such as the ones that could be encountered in multi-center studies have been minimized. Although the sample size is relatively small, it is comparable to other similar studies in the field [2, 23]. A limitation of the study is that several weaning indices, such as airway occlusion pressure (P0.1), the P0.1/MIP ratio [27], and the integrative weaning index (static compliance of the respiratory system-arterial oxygen saturation/f/vt index) [31] have not been tested; However, the aim of the study was to investigate whether the diagnostic accuracy of ScvO₂ in predicting the SBT outcome was similar to the one of other parameters which are routinely used for patient assessment, according to guidelines. Another limitation is that no hemodynamic measurements to assess CO were conducted in the patient cohort, nor we obtained any measurements of SvO₂, due to the limited use of right heart catheterization; However, previous studies [32-34] demonstrated adequate correlation between ScvO₂ and SvO₂, especially among patients who are not in shock, while the costs and the potential risks of right heart catheterization make this technique less feasible in every-day clinical practice. Furthermore, most of the impact of CO on SvO2 measurements is evident when CO values are low [19]; Since none of the patients was hemodynamically unstable when SBT was attempted, we could hypothesize that measuring CO would not have changed the results. Finally, VO₂ was not directly measured and, thus, increase of VO₂ due to elevated respiratory muscle activity among patients who presented with lower ScvO₂ can only be hypothesized; future studies utilizing indirect calorimetry through a mouthpiece could provide further information on this proposed association.

In summary, in this prospective nested case-control study conducted in a general ICU population, a ScvO₂ drop of at least 4% was independently associated with failure to wean from mechanical ventilation, along with Hb concentration, SaO_2, and age. Judging whether the SBT is successful or not, in order to proceed to extubation, is depended not on a single index but on a combination of several objectively measured and clinically evaluated parameters. Whether adding the routine evaluation of ScvO₂ in this algorithm might improve the ability to correctly identify those patients who could safely proceed to extubation or not, remains to be tested in large prospective trials in the future.

CONCLUSION

ScvO₂ is an independent predictor of the weaning outcome; a drop of at least 4% from its baseline values was associated with failure to wean from mechanical ventilation. More prospective studies are needed in order to investigate whether its systematic evaluation might further facilitate the accurate identification of those able to wean from mechanical ventilation.

REFERENCES