Lactate concentration gradient from right atrium to pulmonary artery

Introduction We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA. Methods A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, O2 saturation (SO2) and [Lac]. We defined Δ[Lac] as ([Lac]ra - [Lac]pa), ΔSO2 as (SraO2 - SpaO2) and the change in O2 consumption (ΔVO2) as the difference in systemic VO2 calculated using Fick's equation with either SraO2 or SpaO2 in place of mixed venous SO2. Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman. Results We found SraO2 > SpaO2 (74.2 ± 9.1 versus 69.0 ± 10.4%; p < 0.001) and [Lac]ra > [Lac]pa (3.9 ± 3.0 versus 3.7 ± 3.0 mmol.l-1; p < 0.001). Δ[Lac] correlated with ΔVO2 (r2 = 0.34; p < 0.001). Conclusion We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO2 and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO2 and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac].


Introduction
Pulmonary artery (PA) blood comprises the mixed venous effluent from all organs, with the notable exception of the lungs. PA O 2 saturation (S pa O 2 ) has been promoted as an index of tissue oxygenation [1,2] because it is thought to be related to the average end capillary blood PO 2 [3].
In a prior study [4], we measured the O 2 saturation (SO 2 ) of right atrial blood (S ra O 2 ) and S pa O 2  proximal and distal ports of PA catheters (PACs) placed in critically ill patients. We noted that S pa O 2 was consistently lower than S ra O 2 by approximately 5%. Others have noted a similar step-down in O 2 saturation from the right atrium (RA) to the PA [5,6], and continuous measurements in critically ill patients have shown a similar difference between S pa O 2 and central venous (CV) O 2 saturation (S cv O 2 ) of approximately 7% [7].
The RA to PA O 2 saturation gradient (defined as ∆SO 2 = S ra O 2 -S pa O 2 ) is likely the result of mixing atrial blood with highly desaturated blood entering the right heart chambers from the coronary veins. This includes blood flowing from the coronary sinus, the great cardiac vein and other major epicardial veins.
As a result of myocardial lactate extraction from the coronary circulation, the CV lactate concentration ([Lac] cv ) is the lowest of any venous blood [8,9]

Methods
This was a prospective, sequential study performed in the George Washington University Hospital intensive care unit. The George Washington University Institutional Review Board approved the study and informed consent was obtained from the patient or from the next of kin.
The data presented were culled from a subset of patients enrolled in a previous study [4]. We enrolled individuals older than 18 years of age of either sex in whom their physicians determined that a PAC was required to guide fluid therapy. Enrollment in the study occurred at the time the patient or the nearest relative consented to the introduction of the PAC. On the basis of their medical history, we excluded patients with uncorrected valvular incompetence, intra-cardiac shunting or those who required insertion of the pulmonary artery catheter through the femoral vein. A 7.5 French, 5 lumen, 110 cm length, PAC with the right atrial lumen positioned 30 cm from the tip (Edwards Lifesciences, Irvine, CA, USA) was inserted through the internal jugular vein or the subclavian vein using a percutaneous sheath introducer (8.5 French; Edwards Lifesciences). The insertion technique is described elsewhere [4]. Care was taken to place the distal port catheter in the PA and the proximal port in the RA.
Immediately after the insertion of the PA catheter, each patient had one set of paired blood samples drawn in rapid succession, and in random order, from the proximal and distal port. We took proximal port blood to be representative of RA blood, whereas distal port blood was considered to be PA blood. The first 2 ml of blood drawn for each sample were discarded to prevent contamination with flushing fluid. Blood samples were drawn with the catheter balloon deflated to avoid contamination of the distal port sample with pulmonary capillary blood. Arterial O 2 saturation was determined from a previously in vivo calibrated pulse oximeter.
Blood samples were placed on ice and taken to a central laboratory for measurement of [Lac] (Ektachem 950 IRC Chemistry Analyzer with a Vitros Products lactate slide, Ortho-Clinical Diagnostic, Inc., Rochester, NY, USA), hemoglobin concentration ([Hb]) and O 2 saturation (ABL700 Radiometer America Inc., Westlake, OH, USA). We measured cardiac output (CO) by the thermodilution method as the average of three sequential determinations.
Systemic O 2 delivery (DO 2 ), O 2 consumption (VO 2 ), O 2 extraction ratio (ERO 2 ), double product (DP; heart rate (HR) × mean arterial pressure (MAP)) and left ventricular stroke work index (LVSWI) were computed using standard formulae. We defined ∆VO 2 as the difference in systemic VO 2 calculated with Fick's equation with either S pa O 2 or S ra O 2 in place of the mixed venous SO 2 Paired Student's t-test was used to compare atrial to PA measurements.
[Lac] ra and [Lac] pa were compared by Spearman's correlation analysis [10]. The method of Bland and Altman [11] was used to investigate the effect of lactate concentration on the differences between paired observations. The relationships between ∆[Lac] and ∆SO 2 , ∆VO 2 and other hemodynamic parameters were analyzed by Spearman's correlation analysis. Data are shown as mean ± SD with p < 0.05 denoting a significant difference.

Results
We enrolled 45 patients in the study, including 18 women. The study group was composed of 31 post-operative patients (26 post-cardiac surgery), 11 patients in septic shock from various medical conditions, 2 patients with severe gastrointestinal bleeding and 1 patient in congestive heart failure. Demographic and hemodynamic parameters for the group are listed in Table 1.
The mean SO 2 and lactate concentrations for RA and PA blood samples are shown in Table 2. S ra O 2 was greater than S pa O 2 (p < 0.001), with ∆SO 2 = 5.2 ± 4.8%.

Discussion
We detected a decreasing ∆[Lac] when comparing paired blood samples drawn from the proximal and distal ports of PACs. We also noted ∆[Lac] correlated with ∆VO 2 . To our knowledge, these novel findings have not been reported elsewhere.
Only one other study in the literature has compared central venous [Lac] to [Lac] pa . This study found no differences in [Lac], although it was biased by the use of multiple blood samples (n = 50) drawn from 12 critically ill patients [12]. Our study used only one comparison per subject, which perhaps may explain the difference in results.
We used a standard clinical laboratory instrument to measure [Lac] having a 95% precision of ± 0.1 mmol.l -1 . Even assuming a worst case scenario of a systematic instrument bias of -0.1 mmol.l -1 , the difference in [Lac] between RA and PA would have remained statistically significant.
[13], a proportion that increases substantially in sepsis [14]. As a result of myocardial lactate extraction, coronary venous [Lac] is substantially lower than arterial [Lac] and is the lowest of all venous effluents [15]. The dilution of RA blood by coronary venous blood of lower [Lac] is a plausible explanation for the small but detectable difference in [Lac] from RA to PA.
Since RA blood is the mixture of superior vena cava and inferior vena cava (IVC) blood, the possibility exists that these blood streams had not thoroughly mixed at the proximal PAC sampling port. In this case, one could expect further mixing to occur between IVC and RA blood while flowing into the pulmonary artery. Our results do not support this hypothesis.

Competing interests
The authors declare that they have no competing interests.

Key messages
• Oxygen and lactate concentrations are lower in PA blood than in RA blood.
• The oxygen and lactate concentration gradients from RA to PA are likely the result of mixing atrial with coronary venous blood.
• The possibility exists that these concentration gradients may reflect changes in myocardial energy requirements.