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Introduction
Trauma is the third leading cause of death worldwide, notably affecting the population under 40 years of age. Of all causes, traffic accidents are responsible for the largest number of patients. Around the world every day, about 3000 people die from injuries resulting from traffic accidents. These especially affect the 15-29 year-old age group, according with WHO reports.1,2 In Colombia, trauma is a public health problem, where traumatic injuries due to violence and traffic accidents are among the top causes of morbidity and mortality.3,4 Therefore, there is a need for a biomarker that allows us to quickly and reliably assess the diagnostic process of hypoperfusion during its early stage, in order to take the pertinent steps to reduce these mortality figures.5-7 This why lactate represents an important tool within this scenario, being a widely studied biomarker.8,9
Several publications show the relationship between lactate intake, early clearance and mortality. However, beyond these 6 h, its usefulness is controversial.8,10-19 In the present article, we tried to establish the predictive capacity of serial lactate and its clearance (at admission time, 12 and 24h) when mortality occurred in patients with trauma who entered the intensive care unit.
Materials and methods
An observational longitudinal cohort study was conducted in patients admitted to the Intensive Care Unit (ICU) of the Universidad de la Sabana Clinic (located in Chía, Cundinamarca, Colombia) between January 1st, 2010 and January 1st, 2014. The clinic is located in a busy traffic area where an large number of patients suffer traffic accidents. After the approval by the institutional ethics committee, the information of all patients diagnosed with trauma who survived at least 24h was recorded concurrently. Socio-demographic, clinical and paraclinical variables, as well as APACHE II, SOFA and ISS severity indexes were taken into account.20-24 Also, measurements of serum lactate upon admission to the ICU, at 12 and 24 h were considered. All patients with incomplete measurements or data and those referred from other institutions were excluded.
Statistical analysis
For the elaboration of the database we used Microsoft Excel 2011, version 14.0 and for the processing of data we used the statistical package STATA 12.0. Descriptive statistics were performed and the association between the averages for each of the three lactate measurements with early mortality at seven days was determined. The clearance of lactate levels was evaluated, considering the percentage of lactate cleared with respect to the previous measurement, with the following equation: % Clearance = ((basal lactate - lactate control)/basal lactate) x 100.13,25
In addition, discrimination capacity was determined by calculating the area under the ROC curve and the highest discrimination cut-off point by the Liu method, which maximizes the product of the sensitivity and specificity from which the lactate measurements were dichotomized. OR estimates were obtained in relation to mortality. All calculations were performed with a significance level of <0.05.
Results
A total of 309 polytraumatized patients were admitted to the ICU during the study period. 233 patients met the inclusion criteria for information recording as shown in flow chart 1 (Fig. 1).
Of the total number of patients with polytraumatism, 184 patients (78%) were male. Early mortality, described as less than 7 days, was 21%, being higher in the male group compared to the female group (58% vs 42%, respectively).
All measurements of lactate inflow to the unit were performed within the first 28 h SD (10) of admission to the hospital. The time of admission to the UCI was considered as hour "zero". The second measurement was performed at 12 h with an average of 10.2 h and a SD of 11.8 h. The third measurement was performed at 24 h with an average of 24.4 h and a SD of 13 h. The analysis of variance for the three measurements showed differences between the three groups of measurements with a p-value< 0.001.
The variables that were associated with early mortality were APACHE II, SOFA and ISS, as well as the lactate levels in each of the measurements. See Table 1.
The average stay for living patients was 9 days whereas for those who did not survive it was 4.7 days.
Trend of lactate levels
As shown in Table 1, the value of lactate levels decreased as time progressed from admission to 12 h and 24 h, with averages and standard deviations of: 3.28 (2.46) (CI 95% (2.92-3.64)); 2.73 (2.24) (CI 95% (2.39 3.67)); 2.21(1.68) (CI 95% (1.93 2.49)), respectively. When the lactate averages between live and dead patients are compared, statistically significant differences in the mean values at admission, 12 and 24h of -2.11-1.79 and - 1.77 were found.
Regarding the lactate clearance, an association in the differences between the admission time and the 24 h and between 12 and 24 h was found, but not between admission and the first 12 h.
Discrimination capacity of lactate for early mortality in each of the three time periods
In Table 2, the values of the area under the ROC curve of the three moments of lactate measurement are recorded. A trend of greater discrimination was observed as time progresses. Additionally, cut-off point, sensitivity and specificity values were recorded for each of the moments in relation to early mortality (seven days).
Table 2 Discrimination capacity of lactate during the first 48 h for the prediction of mortality at seven days in trauma patients.
As can be seen in Table 3, the ORs for early mortality for each one of the moments were calculated from the values of the cut-off points. We found an OR of 1.4 (CI 95% (1.17-1.68)) for the lactate at admission when a lactate level is greater than 3.04 mEq/L; at 12 h, an OR of 1.35 (CI 95% (1.14-1.60)) with a lactate greater than 3.65 mEq/L; and at 24 h, an OR of 1.65 with (95% CI (1.27-2.13)) with a cut-off point of 2.35 mEq/L.
Table 3 Bivariate analysis of logistic regression: mortality at 7 days and lactate at three different moments.
Fig. 2 shows the largest area under the curve for lactate levels at 24 h after admission (0.70) denoting a greater discriminatory power for early mortality, whereas the values of the area under the curve at admission time and 12 h are lower, 0.60 and 0.54 respectively.
Source: Authors.
Discussion
Lactate levels in the blood reflect the balance between lactate production and lactate uptake in tissues, which is usually in the range of 0.5-1.8 mM/L.26 Numerous studies have established the use of lactate as a diagnostic, therapeutic and prognostic marker for tissue hypoxia. The vast majority of these studies have used 2.0 mM/L as a cut-off. This cutoff point has been established in different scenarios and different types of patients. That is how Kliegel et al. examine patients who were resuscitated from cardiac arrest and survived at least 48 h,27 concluding that sustained hyperlac-tatemia (>2.0mM/L after 48 h) is a predictor of mortality as well as of a poor neurological prognosis. Kruse et al. carried out a systematic review establishing that the cut-off point of >2 mM/L is most frequently associated with mortality in critical patients with some type of trauma. More recently, cut-off points have been classified according to their severity, into the levels low (<2.5mg/dL), moderately elevated (2.5-3.9 mg/dL) and severely elevated (>4mg/dL).26,28-30 One of the first studies that determined the association between lactate levels and mortality in trauma patients was performed by Abramson. He found that the delay in the normalization of lactate levels after 24 and 48 h was associated with increased mortality, whereas patients who normalized lactate values before 24 h had a 100% survival rate. In our study, this finding was not confirmed. Even patients with normal lactate during the first 12 h died, this probably due to the greater severity of our patients with a mean ISS of 30 whereas the one reported in Abrasom study was 22.10
When it was explored which of the measures in the time (admission, 12 and 24 h) would have the greater discrimination capacity for survival, it was observed that those patients with lactate above 2.35mEq/L at 24h presented the highest mortality rate. However, in 2012, Dr. Marie-Alix Régnier12 found that measurements of clearance within the first four h based on lactate levels at admission, had an adequate ability to discriminate between the patients who died or survived, with an area under the ROC curve (0.78, 95% CI: 0.73-0.83). We only found that lower and later clearance was associated with mortality at 24 h, with an area under the ROC curve of 0.70 (0.58-0.83)
In 2013, Stephen R. Odom13 included 4742 trauma patients in his study, finding that initial lactate was the strongest predictor of mortality in the trauma patient when the first lactate was greater than 4 mEq/L. They also performed the calculation of lactate clearance in this group of patients, with a time interval of 6 h, finding that with lower clearance came higher mortality. Our study evaluated the clearance between admission, 12 and 24 h, only finding an association with the decrease of clearance at 24 h.
In 2015, Dr Dezman Zachary's work14 with 18,304 patients with trauma is published. Lactate clearance was evaluated at 24 h in 3887 patients and only 7.8% of the population achieved a lactate clearance of below 2 mEq/L. However, an adequate discriminatory capacity of lactate levels at 24 h with an area under the curve of 0.8 was found. The severity of the population of this study was lower than ours with an average of 25 in the ISS.
Our study has the limitation of not having evaluated lac-tate clearance within the first 6 h based on lactate levels at admission. Nevertheless, it does monitor lactate in the first 24 h, showing a broader picture and demonstrating how the later worsening of lactate levels determines increased mortality.
Conclusions
Our study showed that lactate levels greater than 2.35 mEq/L at 24 h were associated with an increased risk of mortality. On the other hand, lower lactate clearance or even negative clearance led to increased mortality, especially at 24 h. It could not be established that early clearance would improve prognosis. The findings of the present study could be influenced by reverse causality in that those patients with the worse prognosis would be precisely those in which the goals of resuscitation would not be achieved.
