BLOOD LACTATE AS A PREDICTOR OF MORTALITY IN PATIENTS WITH POLYTRAUMA Ustyantseva I.M., Khoklova O.I., Agadzhanyan V.V.
Regional Clinical Center of Miners’ Health Protection, Leninsk-Kuznetsky, Russia
Novosibirsk Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan, Novosibirsk, Russia
Lactate is a metabolite, which level depends on the balance of intensity of the processes of its formation and utilization, and, correspondingly, its increase in the blood can be associated with increasing production and decreasing consumption [1]. The main cause of excessive formation of lactate is increasing anaerobic processes in tissues in insufficient oxygen delivery. Therefore measuring the lactate in the blood is useful for diagnosis and prediction of tissue hypoxia, for example, in shock [2]. Estimation of lactatemia is recommended as one of the most proven values for estimating the blood loss degree [3]. It has been shown that increasing blood lactate is associated with increasing mortality in patients with injuries and predicts the requirement for massive transfusion [4-6]. The examination of blood lactate in combination with systolic arterial pressure (SAP) can increase the possibility for prediction of unfavorable outcomes after severe injuries [7, 8].
SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 2001 [9], Surviving Sepsis Campaign (SSC12) 2012 [10] and Sepsis-3 2016 [11] consider the high lactate level (1 mmol/l higher that the laboratory reference) as the index of tissue hypoperfusion. Lactate clearance is associated with favorable outcomes in critically ill patients (including septic ones) [12, 13]. At the same time, the small groups of trauma patients showed that long term increase in the blood lactate was accompanied by increasing risk of infection and complications [14, 15]. Previously, we showed the possibility for using the lactate for estimating the severity of systemic inflammatory response syndrome and prediction of septic complications in patients with polytrauma [16-18].
Despite of the high amount of the studies of blood lactate and its common clinical monitoring, the diagnostic significance of this metabolite for critically ill patients has not been determined yet [10, 13, 15]. Also the significance of blood lactate level as a predictor of mortality in patients with polytrauma has not been estimated.
The objective of the study – to estimate the clinical and predictive significance of lactate level in the blood as a predictor of mortality in polytrauma.
MATERIALS AND METHODS
The retrospective analysis included the period from January 1, 2003 to January 1, 2013. There were 475 patients with polytrauma who were admitted to Regional Clinical Center of Miners’ Health Protection within 2 hours after trauma. There were 29.7 % of the women and 70.3 % of the men. The mean age of the patients was 42.2 ± 2.23. The inclusion criteria were the age of 18 and older, presence of severe multiple or associated injuries.
The ethical committee of Regional Clinical Center of Miners’ Health Protection approved the study.
The demographic data (age, gender), injury mechanism, information on vital functions at admission (heart rate (HR), systolic arterial pressure (SAP)) and estimation scores (Glasgow Coma Scale (GCS), Injury Severity Score (ISS), Abbreviated Injury Scale (AIS)) were analyzed. Also the discharge status (survival or death) was considered. 439 patients survived, 36 patients died.
The death was considered early if it happened within 48 hours after admission, the late one – after 48 hours. The causes of the lethal outcomes were determined. The most common cause of death in the early period after trauma was bleeding (66 % of the cases). The main causes of late death were head injury (39.1 %) and multiple organ insufficiency (47.1 %).
The lactate in whole venous blood was estimated within the first three hours after hospital admission with the analyzer of critical states Roche Omni S (Germany). The results were collected in the electronic form from the hospital laboratory information system. The lactate level < 2.5 mmol/l was considered as low, within 2.5-3.9 mmol/l – moderately high, and ≥ 4 mmol/l as significantly high.
The statistical analysis of the results was carried out with IBM SPSS Statistics 20. Kholmogorov-Smirnov test was used for testing the distribution of the received results. Since the distribution of most data corresponded to the normal distribution law, the quantitative variables were presented as M (SD) (M – mean arithmetic, SD – standard deviation). The categorical data was described as absolute values (n) with indication of proportions (%). The differences in the quantitative variables between the groups were identified with Student’s test. The intergroup comparison of the categorical data was carried out with consideration of the sample size with χ2 test or Fisher’s exact test. The p value < 0.05 was statistically significant.
The multiple logistic regression analysis was conducted for identification of the predictors of mortality in patients with polytrauma and for estimation of the independent relationship between the lactate and the mortality. The procedure of direct stepwise search was used. The results are indicated as odds ratio (OR) and 95 % confidence interval (95 % CI).
RESULTS
The table 1 shows the characteristics of the patients with polytrauma at the moment of hospital admission. The groups did not differ significantly according to the most common cause of trauma. So, road traffic accident was the most common cause in both groups. However some significant differences in the characteristics and severity of the injuries were identified. The injury severity in the patients with lethal outcome was high and extremely high almost two times more often (p < 0.0001) as compared to the survived patients (ISS > 15) (the table 1). The differences were mainly conditioned by severity of the injuries to the head, the chest and the abdomen, whereas there were not any intergroup differences in the features of superficial injuries and extremity damages. Glasgow Coma Scale was almost 1.7 times lower in the deceased patients as compared to the survived (p < 0.001).
The statistically significant differences also included the age (the deceased patients were 1.4 times older than survived ones), HR, SAP and the mean lactate level in the blood (1.5 times higher in the deceased patients, p < 0.001).
The subsequent analysis showed the relationship between the mortality and the lactate level in the patients with polytrauma. So, the blood lactate level < 2.5 mmol/l resulted in the mortality of 5.4 % (95 % CI, 4.5-6.2 %). The mortality was 6.4 % (95 % CI, 4.5-6.2 %) for lactatemia of 2.5-3.9 mmol/l, and 18.8 % (95 % CI, 15.7-19.9 %) for the level ≥ 4 mmol/l (Fig. 1).
The multiple logistic regression analysis found that the most significant predictors of mortality in the patients with polytrauma were the blood lactate, hypertension, hypotension and ISS (the table 2). The high lactate level predicted both early and late mortality. After adjustment for SAP, HR and ISS, the initial level of lactate was independently associated with increasing mortality (the corrected odds ratio – 1.0 (95 % CI 0.1-1.1), 1.5 (95 % CI 1.1-2.0) and 3.8 (95 % CI (95 % CI 2.8-5.3) for the lactate levels < 2.5, 2.5-3.9 and ≥ 4 mmol/l correspondingly) (the table 2). Also the U-shaped relationship between the mortality and SAP was found, and the possibility of lethal outcome was significantly higher in the patients with the highest and lowest quartiles of arterial pressure than in normal or moderately high SAP.
The subsequent analysis identified the relationship between arterial pressure, lactate and mortality. So, the mortality increased in the patients with progressing hypotension (SAP < 90 mm Hg) and increasing blood lactate (Fig. 2).
DISCUSSION
The presented study of the big group of the patients with polytrauma (n = 475) showed that the initial values of lactate in the blood within 3 hours after trauma provided the additional predictive information for the traditional clinical predictors of the mortality [11, 12, 15].
We identified a complex relationship between systolic arterial pressure, lactate and the mortality in the patients with hypotension (SAP < 90 mm Hg). Along with progression of hypotension severity, the increase in lactatemia is associated with increasing risk of death. The relationship between high SAP and the mortality require further investigation.
The received results correspond with the other studies, where the initial lactate level was closely associated with the mortality in the patients with trauma regardless of such factors as injury severity, the age and hemodynamics [19, 20]. The importance of measurement of lactatemia within the first hours after trauma is conditioned by the fact it is the most reliable index of hypoxia: its blood level increases earlier than other signs of oxygen insufficiency appear (particularly, changes in AP and HR) [1]. It has been shown that the study of time course of the blood lactate level can be used for estimation of adequacy of therapy and can be one of the predictive criteria of treatment results [3, 5].
The presented study has some important methodological limitations. Particularly, this is the retrospective study, i.e. it already has some disadvantages. The heterogeneity of the patients’ population with polytrauma (comorbidity, gender) is considered insufficiently. Moreover, only the initial level of the lactate was estimated, but the prehospital interventions were not considered (replacement of circulating blood volume with fluids; resuscitation measures etc.) All these factors determine the objective of future studies.
CONCLUSION
1. The lactate level in whole blood within the first three hours after trauma is the independent predictor of mortality after polytrauma.
2. The patients with lactatemia > 2.5 mmol/l need for proper examination and controlling.