Serum lactate measurement is one of the most commonly used laboratory parameter in patients with hemodynamic disturbance, sepsis, severe asthma, post-operation, brain injury, liver failure, acute lung injury, and poisoning [1]. Lactate acid is an end result of metabolism and a total of 1400 mmol/L lactate acid is produced daily. Conditions increasing lactate production or declining its elimination capacity will result in hyperlactatemia. Normal lactate value in healthy individual is 1 ± 0.5 mmol/L [2].

High lactate value is correlated with decreased blood pH and led to lactate acidosis. Lactate acidosis is defined as metabolic acidosis with lactate level >2 mmol/L [3,4]. Using lactate as diagnostic adjunct takes time, approximately 72 min in emergency triage setting. This could result in treatment delay for septic patients [4-6].

Patients with metabolic acidosis compensated with deep and rapid breathing, causing decreased CO₂ alveolar pressure and CO₂ arterial pressure. End-tidal CO₂ (ETCO₂), an invasive test to indirectly measure PaCO₂, can be used to determine acidosis severity in metabolic acidosis patients [7].

A previous prospective study stated that decresed level of ETCO₂ was correlated with high lactate level. It wass mentioned in the study that lactate level >4 mmol/L was correlated with ETCO₂ of <25 mmHg [8].

This study intended to search the correlation between ETCO₂ level and hyperlactatemia in patients with hemodynamic disturbance. We expect that this study could help such patients to get earlier treatment and also predict morbidity and mortality.

This was an observational, cross sectional study conducted on January to February 2017 in Sanglah General Hospital, Bali, Indonesia. Subjects were patients aged 13-90 years old with hemodynamic disturbance (mean arterial pressure [MAP]<65 mmHg) with or without support. Exclusion criteria was patients with pulmonary diseases. Subjects was recruited by consecutive sampling method. Eligible patients was recruited as subjects until the minimum sample was accomplished. Based on sample calculation, minimal sample should be 70 subjects. Informed consents were given by the first-degree family member of the patients. In all subjects, laboratory test of lactate level and blood good analysis were done, and capnography was used to monitor ETCO₂ simultaneously. Lactate level measurement was done with Accutrend®.

The minimum sample calculation was as follow:

Statistical analysis

The data collected will be analyzed data include analysis of descriptive statistics. The descriptive statistical analysis describes the characteristics of the study subjects and all the variables studied, mean variables, deviations, minimum values, and maximal values. Categorical scale variables are displayed using relative frequency (number and percentage). The results of the descriptive statistical analysis are presented in a single distribution table.

Data analysis in this research is divided into several stages: descriptive statistical analysis, normality test, and correlation test. All stages of data analysis using of computer programs.

Descriptive statistical analysis

This analysis aims to describe the characteristics of subjects and research variables. Variables that are numerical scale data will be described using the mean and standard deviation or median values using the interquantil range. Categorical-scale variables will be described in relative frequency. The results of descriptive statistical analysis are presented using a single distribution table.

The data result from the study was analyzed for normality test by using Kolmogorov Smirnov from which based on the result analysis that shows the data is not normally distributed. Correlation test then analyzed by using Spearman Correlation.

There were 70 subjects recruited with no drop out. Subjects’ characteristic was shown in Table 1. Median age of the subjets was 55 years old, 54.2% was male and 45.8% was female. Subjects’ case was 35.7% called for resuscitation, 32.9% was septic shock with surgery, 17.1% was septic shock without surgery, and 14.3% was hypovolemic shock with surgery. Most of the patients (55.7%) used 1 kind of support (inotropic or vasopressor), 35.7% used >1 support, and 8.6% without support. Based on hemodynamic parameter, median heart rate was 110.5 beats per minute, respiratory rate was 24 breaths per minute and mean arterial pressure (MAP) 70 mmHg. In blood gas analysis (BGA), most of the patients had compensated metabolic acidosis (82.9%).

Table 1: Study Subject Characteristic.

Normality test by Kolmogorov-Smirnov test showed that ETCO₂ and lactate level data was normally distributed (p=0.005 and p=0.019, resprectively). Correlation analysis between ETCO₂ and lactate level showed significantly strong negative correlation (correlation coefficient [r]=-0.852, p=0.001), Table 2.

Table 2: Correlation Test Result Between ETCO₂ and Lactate Level.

This means that high level of lactate was associated with low level of ETCO₂. Linear regression analysis of correlation showed that an increase of 1 mmol/L lactate was associated with decrease of 3.42 mmol/L ETCO₂ (p<0.001), Table 3.

Table 3: Linier Regression Analysis Result of ETCO₂ and Lactate Correlation.

This study aimed to asses the correlation between ETCO₂ and lactate level in patient with hemodynamic disturbance. In patient with hemodynamic disturbance, there would be a darrangement of tissue perfusion that lead to anaerobic metabolism that increased lactate level. Long term tissue perfusion derangement would eventually lead to imbalance of production and elimination of lactate. Hyperlactatemia reduced blood pH, therefore lead to lactic acidosis. Lactic acidosis is metabolic acidosis with lactate level ≥ 5 mmol/L and arterial pH<0.35. Kussmaul breathing as compensation would commence academia with signs of perfusion disturbance (eg hipotensi, oligouria, sensoric disturbance, and hypothermia). These signs could be used as predictor of acidemia severity. Based on this correlation, ETCO₂ could be used to determine academia severity in patient with metabolic acidosis. It was expected that ETCO₂ measurement by capnograph could be an indirect sign of increased lactate level in patients with hemodynamic disturbance.

Our finding of significantly negative correlation between ETCO₂ and lactate level was in accordance with previous studies. This means that low ETCO₂ was correlated with high lactate level. We found that an increase of 1 mmol/L lactate was associated with decrease of 3.42 mmol/L ETCO₂ (Figure 1).

Figure 1: Scatterplot correlation between ETCO₂ and lactate level.

A previous prospective study by Christopher in 2014 showed that decresed level of ETCO₂ was correlated with high lactate level. It wass mentioned in the study that lactate level >4 mmol/L was correlated with ETCO₂ of <25 mmHg [8]. Another study using Pearson correlation calculation demonstrated that increased lactate level was correlated with decreased ETCO₂ (95% of confidence interval) [9].

It is expected that the use of ETCO₂ monitoring as non-ivasive and fast method to detect hyperlactatemia. A study by Goyal M in 2010 stated that serum lactate measurement could take time up to 72 minutes. This required time could delay initial treatment for septic patients. Althoug there were other tools to detect lactalte level in faster time, they had not been widely used [5].

This study was a cross-sectional study and could barely describe the progression of diseases precisely.

ETCO₂ was related to serum lactate level in patients with hemodynamic disturbance; a decrease of 3.42 mmol/L ETCO₂ was associated with the increase of 1 mmol/L lactate. ETCO₂ measurement by capnograph was a non-invasive and fast method to detect hyperlactatemia.