a b s t r a c t

Objectives: Central venous oxygen saturation calculated by gasometry (Gaso-ScvO2) is more available than central venous oxygen saturation measured by co-oximetry (Co-oxy-ScvO2) in environments with less resources and underdeveloped countries. Therefore, we aimed to determine the agreement between Co-oxy-ScvO2 and Gaso-ScvO2 and between central venous oxygen tension measured by gasometry (Gaso-PcvO2) and Co-oxy-ScvO2, respectively.

Design and settings: This is a prospective study in a university hospital’s intensive care unit.

Patients: Sixteen patients were studied during the first 48 hours after diagnosis of septic shock. All patients were intubated, connected to mechanical ventilation, and resuscitated according to the standards of care. Measurements and results: One hundred eleven pairs of central venous blood measurements were analyzed both by conventional gasometry and co-oximetry. Bland and Altman analysis between Co-oxy-ScvO2 and Gaso-ScvO2 showed lack of agreement (1.7 [- 10.7, + 14.2]). A Gaso-ScvO2 less than 70% had a positive predictive value of 63% in relation to Co-oxy-ScvO2, and its negative predictive value was 90% with 20% false-positives and 5% false-negatives. The area under the receiver operator characteristic curve of Gaso-PcvO2 to discriminate a Co-oxy-ScvO2 greater than or equal to 70% was 0.87 (confidence interval, 0.80-0.93), and the best cut-off point was a Gaso-PcvO2 more than 40 mm Hg, (sensitivity, 75%; specificity, 93%).

Conclusions: The reliability of Gaso-ScvO2 determination during the resuscitation phase of septic shock is not acceptable. There is a good agreement between a Gaso-PcvO2 more than 40 mm Hg and a Co-oxy-ScvO2 greater than or equal to 70%. Our results suggest that given these limitations, Gaso-ScvO2 results should be interpreted with caution, helped by Gaso-PcvO2 measurements and in context with other perfusion parameters.

(C) 2014

Introduction

central venous oxygen saturation is nowadays widely accepted as an alternative to mixed venous oxygen saturation to assess and provide and index of potential imbalance between oxygen delivery and consumption and hence Tissue oxygenation impairment indicative of shock [1,2]. Therefore, ScvO2 has become a metabolic monitoring parameter with extraordinary value in the resuscitation of septic shock patients and a cornerstone of an outcome-oriented algorithm such as early goal-directed therapy [3-5]. In this later study, ScvO2 was continuously measured using a central line with a fiber optic monitor built into it, but there are data showing that there is good agreement between these ScvO2 measurements and the ones obtained by co-oximetry, which is the method used in most developed countries to measure ScvO2 [6].

? Competing interest: The authors declare that they have no competing interest. This study was not supported by a medical company.

* Corresponding author. Unidad de Pacientes Criticos, Departamento de Medicina, Hospital Clinico Universidad de Chile, Facultad de Medicina Universidad de Chile, Santos Dumont 999, Independencia, Santiago Norte, Chile. Fax: +56 2 29788264.

E-mail address: [email protected] (C.M. Romero).

Co-oximetry ScvO2 (Co-oxy-ScvO2) is determined clinical labora- tories measuring hemoglobin level saturation directly by photometry (criterion standard). However, this method is not always available, especially in countries in development or “third-world countries.” In some places, hemoglobin level saturation and, hence, ScvO2, are calculated by Blood gas analyzers, which use measured PO2, PCO2, and pH, combined with published regression equations based on the oxyhemoglobin dissociation curve (ScvO2 calculated by gasometry [Gaso-ScvO2]). There is little information about the variability in results obtained with these 2 different techniques and no published studies during the resuscitation phase of septic shock.

The purposes of this study were (1) to determine the agreement between Co-oxy-ScvO2 and Gaso-ScvO2, and (2) to define the best value of agreement (cut-off point) between central venous oxygen tension measured by gasometry (Gaso-PcvO2) and Co-oxy-ScvO2.

Materials and methods

This was a prospective study performed at the intensive care unit (ICU) of Hospital Clinico Universidad de Chile. The institutional ethical

http://dx.doi.org/10.1016/j.ajem.2014.07.027

0735-6757/(C) 2014

1276 C.M. Romero et al. / American Journal of Emergency Medicine 32 (2014) 1275–1277

committee approved the study and waived the necessity of informed consent.

Patients

Sixteen patients were studied during the first 48 hours after diagnosis of septic shock. All patients were intubated, connected to mechanical ventilation, and resuscitated according to the local ICU protocol [7] that fulfills the standard of care for septic shock management [8]. Demographic and clinical data as well as severity scores, Acute Physiology and Chronic Health Evaluation II [9], and Sequential Organ Failure Assessment [10] were collected.

Central venous blood measurements and analysis

One hundred eleven pairs of measurements were performed with central venous blood and analyzed both by conventional gasometry (OMNI C Gasometer; Roche, Mannheim, Germany set at 37?C) and, almost immediately, by co-oximetry (Cobas b 221Co-oxymeter; Roche). The location of the central venous catheter tip in the superior vena cava was confirmed in all patients by chest radiography. Six pairs of measurements per patient were performed in average, as part of the usual perfusion monitoring. Paired analysis were performed on the same samples, thus no additional blood was needed. The algorithm used by our blood gas analyzer was based on the Marsoner equation [11]. According to the manufacturer, the coefficient of variation for the PO2 electrode of the blood gas analyzer for the range of PO2s of central venous blood was 1.49%, and the coefficient of variation for the co-oxymeter, for hemoglobin level saturations in the range of central venous blood was 0.37%.

Statistical analysis

Data were summarized as incidence and percentage for categorical variables. Quantitative variables were summarized as median, 25th and 75th percentiles, or as mean and SD. For all analysis, Co-oxy-ScvO2 was the criterion standard. To asses if both techniques could be used interchangeably, the agreements between Co-oxy-ScvO2 and Gaso-ScvO2 as well as between Co-oxy-ScvO2 and Gaso-PcvO2 were evaluated by Bland and Altman analysis, calculating the differences between both methods against their mean and 95% confidence intervals [12]. This method evaluates the agreement between 2 tests, to evaluate the potential to replace a standard by another usually easier to obtain. We assessed the sensitivity (S) and specificity (E) of Co-oxy-ScvO2 against Gaso-ScvO2 using a contingency table and calculated false-positive and false-negative rates, using as cut-off a value of 70% in ScvO2 measured by both methods. The predictive value of Gaso-PcvO2 for Co-oxy-ScvO2 was calculated using receiver operator characteristic (ROC) curves, and the best cut-off points were selected with the area under the ROC curve (AUROC). All tests were 2 sided, and P b .05 was considered significant. All statistical procedures were performed using the SPSS 17.0 statistical software (SPSS, Chicago, IL) and MedCalc (Ostend, Belgium) 12.1.3.0.

Results

Mean age of patients was 63 +- 13 years (6 women and 10 men). Origin of sepsis was pulmonary (3), abdominal (6), urinary (4), and cutaneous (3). Mean Acute Physiology and Chronic Health Evaluation II was 23 +- 8, and Sepsis-related Organ Failure Assessment score day 1 was 11 +- 3.

Bland and Altman analysis between Co-oxy-ScvO2 and Gaso-ScvO2 showed lack of agreement (1.7 [-10.7, +14.2], Fig. 1).

When taking an ScvO2 of 70% as cut-off, a Gaso-ScvO2 less than 70% was in agreement with a Co-oxy-ScvO2 less than 70% in 34% of the

cases, with an S of 88% and an E of 68%. A Gaso-ScvO2 less than 70% had a positive predictive value of 63% and a negative predictive value of 90% for a Co-oxy-ScvO2 less than 70%. False-positives rate was 20% and augmented to 34% in those patients with severe septic shock (norepinephrine doses, >=0.3 ug/kg per minute). False-negative rate was 5% and did not augment with severity of septic shock.

Regarding Gaso-PcvO2, the best cut-off point to discriminate a Co-oxy-ScvO2 greater than or equal to 70% was a Gaso-PcvO2 more than 40 mm Hg. The AUROC curve was 0.87 (0.80-0.93), with S of 75% and E of 93% (Fig. 2). No significant changes were observed when comparing patients with norepinephrine doses less than or greater than or equal to 0.3 ug/kg per minute.

Discussion

We found significant differences between measured and calculat- ed ScvO2s. Bland and Altman analysis revealed a small mean difference of 1.7% points between Co-oxy-ScvO2 and Gaso-ScvO2. However, the limits of agreement (-10.7, +14.2) are wide apart. Hence, the lack of agreement must be regarded as unacceptable for clinical purposes. In addition, the positive and negative predictive values of a Gaso-ScvO2 less than 70% in relation to Co-oxy-ScvO2 were important (63% and 90%, respectively), but with a 20% of false-positives and a 5% of false-negatives results, which means almost 20% of Gaso-ScvO2, less than 70% were actually not below 70% and overestimated as shock, and 5% of those informed as more than 70% were not and were underestimated, undetected shocks. Nonetheless, a Gaso-PcvO2 more than 40 mm Hg with an AUROC of 0.87 was able to discriminate Co-oxy-ScvO2 greater than or equal to 70% with S of 75% and E of 93%. Errors of the gasometer analyzer PO2 electrode might explain the inaccuracy of ScvO2 measurements. In addition, metabolic factors that shift the oxyhemoglobin dissociation curve and P₅₀ could also be source for error. Central or mixed venous blood samples, which have lower PcvO₂ than arterial blood, have saturations that fall on the linear part of the hemoglobin level dissociation curve. Therefore, metabolic changes in the hemoglobin level environment that would have little effect on calculations concerning arterial blood, which PaO2 fall on the flat upper part of the curve, might have a greater effect

on Gaso-ScvO2 [13].

There may be statistically significant differences between the measured and calculated ScvO2s. However, the most important issue is

20

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-10,7

Bias and Precision: ScvO2C – ScvO2G (%)

15

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50 60 70 80 90 100

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Fig. 1. Bland and Altman analysis for the paired measurements comparing Co-oxy-ScvO2 and Gaso-ScvO2. The solid line represents the mean difference between both methods, whereas the dashed lines enclosing it represent the 95% confidence interval for the bias. The upper- and lowermost dashed lines represent the limits of agreement. The fifth central dashed line is the line of identity (n = 111).

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that paired measurements of the same patient are not statistically independent. Despite this, our results are in agreement with the findings of other researchers who evaluated mixed venous oxygen saturation in a different population of critically ill patients [13,16].

Conclusions

The reliability of Gaso-ScvO2 determination during the resuscita- tion phase of septic shock is not acceptable and may lead clinicians to implement therapies with potential risk for the patient or withdraw required resuscitation maneuvers. Our results suggest that given these limitations, Gaso-ScvO2 results should be interpreted with caution, helped by Gaso-PcvO2 measurements and in context with other perfusion parameters.

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   Fig. 2. Receiver operator characteristic curve analysis for predictive value of Gaso-PcvO2 for Co-oxy-ScvO2 greater than or equal to 70%. The best cut-off value was a Gaso-PcvO2 more than 40 mm Hg; AUROC 0.87 (0.80-0.93) with S of 75% and E of 93.

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